Researcher Profile and Settings

Master

Affiliation (Master)

• Faculty of Medicine　Specialized Medicine　Neurological Disorder

Affiliation (Master)

• Faculty of Medicine　Specialized Medicine　Neurological Disorder

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Profile and Settings

Affiliation

• Hokkaido University, 教授

Profile and Settings

• Name (Japanese)

  Fujimura

• Name (Kana)

  Miki

• Name

  200901046102567011

Alternate Names

https://neurosurgery-hokudai.jp/
https://en.neurosurgery-hokudai.jp/

Affiliation

• Hokkaido University, 教授

Achievement

Research Interests

• 脳血管障害   脳卒中   脳神経外科   cerebrovascular diseases   Neurosurgery   

Research Areas

• Life sciences / Neurosurgery

Education

• 1996/04 - 2000/03  Tohoku University  Graduate School of Medicine  Department of Neurosurgery
•        - 1994  Tohoku University

Committee Memberships

• 2019 -2023   International Society of Cerebral Blood Flow and Metabolism   Director Board Member, Educational Committee Member

Awards

• 2015/01 東北大学医学部奨学賞 金賞
  
• 2015/01 宮城県医師会 医学奨励賞
  
• 2013/03 第21回日本脳卒中の外科学会賞「鈴木賞」
  
• 2007 第２８回東北脳血管障害研究会奨励賞「中村隆賞」
  

Published Papers

• Moyamoya Syndrome Associated with Late-onset Idiopathic Aqueduct Stenosis Successfully Treated with Endoscopic Third Ventriculostomy

  Taishi HONDA, Masaki ITO, Haruto UCHINO, Taku SUGIYAMA, Miki FUJIMURA

  NMC Case Report Journal 11 13 - 18 2024/12/31
• [Microsurgery for Vertebral and Posterior Inferior Cerebellar Artery Aneurysms via Lateral Suboccipital Craniotomy].

  Taku Sugiyama, Miki Fujimura

  No shinkei geka. Neurological surgery 52 (5) 974 - 984 2024/09 

  Among ruptured intracranial aneurysms, aneurysms of the vertebral artery(VA) and posterior inferior cerebellar artery(PICA) are relatively rare, and they exhibit distinct characteristics. These include: 1) a high frequency of diverse aneurysmal morphologies, such as fusiform or dissecting aneurysms; 2) proximity to the lower cranial nerves; 3) the presence of perforators to the medulla oblongata; and, 4) obstruction to the surgical approach by specific bony structures, such as the occipital condyle and jugular tubercle. Consequently, these aneurysms often require interventions that are more complex than simple clipping or coiling, which is typical for anterior circulation aneurysms. Interventions include skull base techniques such as the far-lateral approach and revascularization procedures such as occipital artery(OA)-PICA bypass. Despite these complexities, the rarity of these aneurysms and the recent advancements in endovascular procedures pose challenges for young neurosurgeons in acquiring adequate microsurgical experience. This narrative review addresses the clinical features of VA and PICA aneurysms, the history and variations in the lateral suboccipital approach for these aneurysms, and several bypass techniques for reconstructing the PICA. Lastly, we illustrate our current microsurgical practices through a case presentation accompanied by a surgical video showcasing both the far-lateral approach and the OA-PICA bypass.
• Optimal catheter selection for acute stroke patients with type III aortic arch based on magnetic resonance angiography road mapping of the para-aortic trans-femoral access route before mechanical thrombectomy.

  Satoshi Kobayashi, Toshiya Osanai, Noriyuki Fujima, Akiyoshi Hamaguchi, Taku Sugiyama, Toshitaka Nakamura, Kazutoshi Hida, Hiroyuki Itosaka, Yoshimasa Niiya, Miki Fujimura

  World neurosurgery 2024/07/16 

  BACKGROUND: Although mechanical thrombectomy for acute ischemic stroke has a high recanalization rate, procedurally challenging lesions remain in approximately 10% of the cases. Type III aortic arches, due to their anatomical configuration, are a fundamental problem impacting this procedure. This study aimed to determine whether optimal catheter selection for type III aortic arches, using magnetic resonance angiography (MRA)-based road mapping of the para-aortic transfemoral access route, reduces the time required for mechanical thrombectomy. METHODS: We retrospectively evaluated 203 consecutive patients who underwent mechanical thrombectomy at multiple centers between April 2018 and July 2022. Twenty-three patients were diagnosed with a type III aortic arch using MRA-based road mapping performed to visualize the para-aortic access route before neuro-interventional procedures. Among the 23 patients with type III aortic arches, 10 received a Simmons-type catheter (initial Simmons group) and 13 received a JB-2-type catheter® (initial JB-2 group) as their first inner catheter. The time required for mechanical thrombectomy was compared between the groups. RESULTS: Compared with the initial JB-2 group, the initial Simmons group exhibited a significantly shorter "puncture-to-recanalization time" (105 vs. 53 min, p = 0.009) and "door-to-recanalization time" (164 vs. 129 min, p = 0.032). CONCLUSIONS: Optimal catheter selection by identifying the aortic arch before mechanical thrombectomy using MRA-based road mapping effectively reduced the mechanical thrombectomy time. This suggests that even in type III aorta cases, appropriate catheter selection may shorten the mechanical thrombectomy time and improve acute ischemic stroke prognosis.
• Effective Smartphone Application Use for Postoperative Management of Moyamoya Disease.

  Haruto Uchino, Toshiya Osanai, Masaki Ito, Kota Kurisu, Taku Sugiyama, Miki Fujimura

  Neurologia medico-chirurgica 2024/06/05 

  Continuous and careful management is necessary after revascularization surgery for moyamoya disease (MMD). The postoperative information has been shared in person or by telephone and emails among doctors; however, this is not always efficient. We aimed to describe the feasibility of remote diagnosis and text chats using a smartphone application on postoperative MMD management. Twenty consecutive patients who underwent combined direct and indirect revascularization for MMD were prospectively investigated in this study. In ten patients, the operator viewed postoperative images uploaded on a smartphone screen using the Join application (Allm Inc., Tokyo, Japan). The doctors shared the radiological findings and treatment plans using the group text chat function and performed postoperative management. We evaluated the intermodality agreements of radiological findings between the smartphone screen and conventional viewer. Postoperative courses were compared between the two patient groups that used or did not use the application. All postoperative images were uploaded to the cloud server and the operator viewed them remotely on the smartphone screen without restriction of location. Detected abnormal findings were cerebral hyperperfusion (CHP), CHP-related watershed shift phenomenon, fluid-attenuated inversion recovery cortical hyperintensity, high signal intensity on diffusion-weighted imaging, CHP-related crossed cerebellar diaschisis, and hypoperfusion. Radiological agreement between the modalities was good in all cases, and additional findings were not obtained on the conventional viewer. The postoperative courses of the Join group were as good as those of the control group. Remote radiological diagnosis and text chat using a smartphone application were feasible and useful for efficient and safe postoperative MMD management.
• Visual dysfunction and neurodegeneration caused by severe inflammatory optic neuropathy after coil embolization of a paraclinoid aneurysm: illustrative case.

  Tomohiro Okuyama, Kota Kurisu, Toshiya Osanai, Masaki Ito, Taku Sugiyama, Haruto Uchino, Miki Fujimura

  Journal of neurosurgery. Case lessons 7 (20) 2024/05/13 

  BACKGROUND: Visual impairment due to delayed optic neuropathy is a rare complication of the endovascular treatment of paraclinoid aneurysms. An inflammatory response induced in the treated aneurysm wall is a known mechanism underlying this pathophysiology. The authors describe a case with severe and progressive optic neuropathy leading to neuronal degeneration and severe visual dysfunction. OBSERVATIONS: A 42-year-old female with a history of surgical clipping for a paraclinoid aneurysm presented with a recurrence. Although the patient was unaware of any visual dysfunction, a preoperative ophthalmological examination revealed mild inferior quadrantanopia in the left eye. The coil embolization procedure was uneventful; however, the following day, the patient experienced progressive visual impairment, which worsened despite the initiation of steroid therapy. Ophthalmological examination revealed a severe decrease in visual acuity and further deterioration of the visual field. Magnetic resonance imaging showed remarkable swelling and edema of the left optic nerve adjacent to the treated aneurysm. Despite continued steroid therapy, the patient's visual function did not recover well due to subsequent optic nerve degeneration. LESSONS: Optic neuropathy after endovascular procedures can lead to severe visual dysfunction. Careful management is essential, particularly when treating a symptomatic paraclinoid aneurysm, even if symptoms are only apparent on detailed examination.
• Assessment of changes in vessel area during needle manipulation in microvascular anastomosis using a deep learning-based semantic segmentation algorithm: A pilot study.

  Minghui Tang, Taku Sugiyama, Ren Takahari, Hiroyuki Sugimori, Takaaki Yoshimura, Katsuhiko Ogasawara, Kohsuke Kudo, Miki Fujimura

  Neurosurgical review 47 (1) 200 - 200 2024/05/09 

  Appropriate needle manipulation to avoid abrupt deformation of fragile vessels is a critical determinant of the success of microvascular anastomosis. However, no study has yet evaluated the area changes in surgical objects using surgical videos. The present study therefore aimed to develop a deep learning-based semantic segmentation algorithm to assess the area change of vessels during microvascular anastomosis for objective surgical skill assessment with regard to the "respect for tissue." The semantic segmentation algorithm was trained based on a ResNet-50 network using microvascular end-to-side anastomosis training videos with artificial blood vessels. Using the created model, video parameters during a single stitch completion task, including the coefficient of variation of vessel area (CV-VA), relative change in vessel area per unit time (ΔVA), and the number of tissue deformation errors (TDE), as defined by a ΔVA threshold, were compared between expert and novice surgeons. A high validation accuracy (99.1%) and Intersection over Union (0.93) were obtained for the auto-segmentation model. During the single-stitch task, the expert surgeons displayed lower values of CV-VA (p < 0.05) and ΔVA (p < 0.05). Additionally, experts committed significantly fewer TDEs than novices (p < 0.05), and completed the task in a shorter time (p < 0.01). Receiver operating curve analyses indicated relatively strong discriminative capabilities for each video parameter and task completion time, while the combined use of the task completion time and video parameters demonstrated complete discriminative power between experts and novices. In conclusion, the assessment of changes in the vessel area during microvascular anastomosis using a deep learning-based semantic segmentation algorithm is presented as a novel concept for evaluating microsurgical performance. This will be useful in future computer-aided devices to enhance surgical education and patient safety.
• Predictive value of the hemispheric magnetic resonance angiography score on the development of indirect pial synangiosis after combined revascularization surgery for adult moyamoya disease.

  Haruto Uchino, Masaki Ito, Noriyuki Fujima, Kikutaro Tokairin, Ryota Tatezawa, Taku Sugiyama, Miki Fujimura

  Acta neurochirurgica 166 (1) 181 - 181 2024/04/17 

  PURPOSE: It is difficult to precisely predict indirect bypass development in the context of combined bypass procedures in moyamoya disease (MMD). We aimed to investigate the predictive value of magnetic resonance angiography (MRA) signal intensity in the peripheral portion of the major cerebral arteries for indirect bypass development in adult patients with MMD. METHODS: We studied 93 hemispheres from 62 adult patients who underwent combined direct and indirect revascularization between 2005 and 2019 and genetic analysis for RNF213 p.R4810K. The signal intensity of the peripheral portion of the major intracranial arteries during preoperative MRA was graded as a hemispheric MRA score (0-3 in the middle cerebral artery and 0-2 in the anterior cerebral and posterior cerebral arteries, with a high score representing low visibility) according to each vessel's visibility. Postoperative bypass development was qualitatively evaluated using MRA, and we evaluated the correlation between preoperative factors, including the hemispheric MRA score and bypass development, using univariate and multivariate analyses. RESULTS: A good indirect bypass was observed in 70% of the hemispheres. Hemispheric MRA scores were significantly higher in hemispheres with good indirect bypass development than in those with poor indirect bypass development (median: 3 vs. 1; p < 0.0001). Multiple logistic regression analysis revealed hemispheric MRA score as an independent predictor of good indirect bypass development (odds ratio, 2.1; 95% confidence interval, 1.3-3.6; p < 0.01). The low hemispheric MRA score (< 2) and wild-type RNF213 predicted poor indirect bypass development with a specificity of 0.92. CONCLUSION: Hemispheric MRA score was a predictive factor for indirect bypass development in adult patients who underwent a combined bypass procedure for MMD. Predicting poor indirect bypass development may lead to future tailored bypass surgeries for MMD.
• Systemic immune-inflammation index in dural arteriovenous fistula: a feasible biomarker reflecting its clinical characteristics

  Kota Kurisu, Toshiya Osanai, Yutaka Morishima, Masaki Ito, Haruto Uchino, Taku Sugiyama, Miki Fujimura

  Acta Neurochirurgica 166 (1) 2024/04/16
• Impact of intraoperative cortical indocyanine green extravasation on local vasogenic edema immediately after direct revascularization in an adult with moyamoya disease: illustrative case.

  Maeho Yamasaki, Masaki Ito, Haruto Uchino, Taku Sugiyama, Miki Fujimura

  Journal of neurosurgery. Case lessons 7 (13) 2024/03/25 

  BACKGROUND: Local vasogenic edema induced after direct revascularization in moyamoya disease (MMD) is associated with blood-brain barrier dysfunction, potentially leading to postoperative cerebral hyperperfusion (CHP) or delayed intracerebral hemorrhage. This phenomenon allows the leakage of fluids, proteins, and other substances from the blood vessels into the extracellular compartment. Typically, such edema is observed postoperatively rather than intraoperatively. OBSERVATIONS: A 48-year-old female with ischemic-onset MMD underwent revascularization on her left hemisphere with Suzuki's angiographic stage III. Direct bypass was successfully performed, as confirmed by intravenous indocyanine green (ICG) video angiography. Subsequently, ICG extravasation was observed near the anastomosis site, despite the absence of cortical injury or bleeding under white light microscopy. Postoperative radiological imaging showed reversible pure vasogenic edema in the corresponding area, with no evidence of CHP. The patient did not exhibit neurological deterioration and was discharged home on postoperative day 16. LESSONS: ICG, characterized by low molecular weight, water solubility, and high affinity with plasma proteins, can extravasate, serving as a direct indication of local vasogenic edema induced by direct revascularization in MMD. To enhance comprehension of the vulnerability of the blood-brain barrier in MMD, it is advisable to gather cases with prolonged observations of ICG video angiography after direct revascularization.
• Intracerebral transplantation of MRI-trackable autologous bone marrow stromal cells for patients with subacute ischemic stroke.

  Masahito Kawabori, Satoshi Kuroda, Hideo Shichinohe, Kaoru Kahata, Souichi Shiratori, Satoshi Ikeda, Taisuke Harada, Kenji Hirata, Khin Khin Tha, Masato Aragaki, Shunsuke Terasaka, Yoichi M Ito, Naoki Nishimoto, Shunsuke Ohnishi, Ichiro Yabe, Kohsuke Kudo, Kiyohiro Houkin, Miki Fujimura

  Med (New York, N.Y.) 2024/03/18 

  BACKGROUND: Ischemic stroke is one of the leading causes of death and neurological disability worldwide, and stem cell therapy is highly expected to reverse the sequelae. This phase 1/2, first-in-human study evaluated the safety, feasibility, and monitoring of an intracerebral-transplanted magnetic resonance imaging (MRI)-trackable autologous bone marrow stromal cell (HUNS001-01) for patients with subacute ischemic stroke. METHODS: The study included adults with severe disability due to ischemic stroke. HUNS001-01 cultured with human platelet lysates and labeled with superparamagnetic iron oxide was stereotactically transplanted into the peri-infarct area 47-64 days after ischemic stroke onset (dose: 2 or 5 × 107 cells). Neurological and radiographic evaluations were performed throughout 1 year after cell transplantation. The trial was registered at UMIN Clinical Trial Registry (number UMIN000026130). FINDINGS: All seven patients who met the inclusion criteria successfully achieved cell expansion, underwent intracerebral transplantation, and completed 1 year of follow-up. No product-related adverse events were observed. The median National Institutes of Health Stroke Scale and modified Rankin scale scores before transplantation were 13 and 4, which showed improvements of 1-8 and 0-2, respectively. Cell tracking proved that the engrafted cells migrated toward the infarction border area 1-6 months after transplantation, and the quantitative susceptibility mapping revealed that cell signals at the migrated area constantly increased throughout the follow-up period up to 34% of that of the initial transplanted site. CONCLUSIONS: Intracerebral transplantation of HUNS001-01 was safe and well tolerated. Cell tracking shed light on the therapeutic mechanisms of intracerebral transplantation. FUNDING: This work was supported by the Japan Agency for Medical Research and Development (AMED; JP17bk0104045 and JP20bk0104011).
• Differences between Acute Embolic and Atherosclerotic Middle Cerebral Artery Occlusion in Multiphase Arterial Spin-labeling Imaging.

  Yasuhiro Ito, Taku Sugiyama, Shunsuke Terasaka, Hitoshi Matsuzawa, Kuniaki Harada, Naoki Nakayama, Masaki Ito, Katsuhiko Maruichi, Miki Fujimura

  Neurologia medico-chirurgica 2024/03/04 

  Arterial spin-labeling magnetic resonance imaging (ASL-MRI) is widely used for evaluating collateral development in patients with acute ischemic stroke (AIS). This study aimed to characterize the findings of multiphase ASL-MRI between embolic and atherosclerotic large vessel occlusion (LVO) to aid in the differential diagnosis. Among 982 patients with AIS, 44 who were diagnosed with acute, symptomatic, and unilateral occlusion of the horizontal segment of the middle cerebral artery (MCA) were selected and categorized into embolic stroke (ES) and atherosclerosis (AT) groups. Using ASL-MRI (postlabeling delay [PLD] of 1.5, 2.0, and 2.5 s) at admission, the ipsilateral to contralateral ratio (ICR) of the signal intensity and its time-course increasing rate (from PLD 1.5 to 2.0 and 2.5, ΔICR) were measured and compared between the two groups. The mean ICR was significantly higher in the AT group than in the ES group (AT vs. ES: 0.49 vs. 0.27 for ICR1.5, 0.73 vs. 0.32 for ICR2.0, and 0.92 vs. 0.37 for ICR2.5). The ΔICR of PLD 1.5-2.0 (ΔICR2.0) and 2.5 (ΔICR2.5) were also significantly higher in the AT group than in the ES group (AT vs. ES: 50.9% vs. 26.3% for ΔICR2.0, and 92.6% vs. 42.9% for ΔICR2.5). Receiver operating characteristic curves showed moderate-to-strong discriminative abilities of each ASL-MRI parameter in predicting MCA occlusion etiology. In conclusion, multiphase ASL-MRI parameters may aid in differentiating intracranial LVO etiology during the acute phase. Thus, it is applicable to AIS management.
• Intravenous Administration of Mesenchymal Stem Cell-Derived Exosome Alleviates Spinal Cord Injury by Regulating Neutrophil Extracellular Trap Formation through Exosomal miR-125a-3p.

  Yutaka Morishima, Masahito Kawabori, Kazuyoshi Yamazaki, Soichiro Takamiya, Sho Yamaguchi, Yo Nakahara, Hajime Senjo, Daigo Hashimoto, Sakiko Masuda, Yoichiro Fujioka, Yusuke Ohba, Yuki Mizuno, Yuji Kuge, Miki Fujimura

  International journal of molecular sciences 25 (4) 2024/02/18 

  Spinal cord injury (SCI) leads to devastating sequelae, demanding effective treatments. Recent advancements have unveiled the role of neutrophil extracellular traps (NETs) produced by infiltrated neutrophils in exacerbating secondary inflammation after SCI, making it a potential target for treatment intervention. Previous research has established that intravenous administration of stem cell-derived exosomes can mitigate injuries. While stem cell-derived exosomes have demonstrated the ability to modulate microglial reactions and enhance blood-brain barrier integrity, their impact on neutrophil deactivation, especially in the context of NETs, remains poorly understood. This study aims to investigate the effects of intravenous administration of MSC-derived exosomes, with a specific focus on NET formation, and to elucidate the associated molecular mechanisms. Exosomes were isolated from the cell supernatants of amnion-derived mesenchymal stem cells using the ultracentrifugation method. Spinal cord injuries were induced in Sprague-Dawley rats (9 weeks old) using a clip injury model, and 100 μg of exosomes in 1 mL of PBS or PBS alone were intravenously administered 24 h post-injury. Motor function was assessed serially for up to 28 days following the injury. On Day 3 and Day 28, spinal cord specimens were analyzed to evaluate the extent of injury and the formation of NETs. Flow cytometry was employed to examine the formation of circulating neutrophil NETs. Exogenous miRNA was electroporated into neutrophil to evaluate the effect of inflammatory NET formation. Finally, the biodistribution of exosomes was assessed using 64Cu-labeled exosomes in animal positron emission tomography (PET). Rats treated with exosomes exhibited a substantial improvement in motor function recovery and a reduction in injury size. Notably, there was a significant decrease in neutrophil infiltration and NET formation within the spinal cord, as well as a reduction in neutrophils forming NETs in the circulation. In vitro investigations indicated that exosomes accumulated in the vicinity of the nuclei of activated neutrophils, and neutrophils electroporated with the miR-125a-3p mimic exhibited a significantly diminished NET formation, while miR-125a-3p inhibitor reversed the effect. PET studies revealed that, although the majority of the transplanted exosomes were sequestered in the liver and spleen, a notably high quantity of exosomes was detected in the damaged spinal cord when compared to normal rats. MSC-derived exosomes play a pivotal role in alleviating spinal cord injury, in part through the deactivation of NET formation via miR-125a-3p.
• The prognostic values of plasma desmosines, crosslinking molecules of elastic fibers, in the disease progression of Moyamoya disease.

  Ryosuke Tashiro, Riki Anzawa, Tomoo Inoue, Ayame Mikagi, Dan Ozaki, Keita Tominaga, Takashi Inoue, Tomohisa Ishida, Miki Fujimura, Toyonobu Usuki, Hidenori Endo, Kuniyasu Niizuma, Teiji Tominaga

  Bioorganic & medicinal chemistry 100 117602 - 117602 2024/02/01 

  Moyamoya disease (MMD) is a cerebrovascular disease which is characterized by the chronic progression of steno-occlusive changes at the terminal portion of internal carotid arteries and the development of "moyamoya vessels." Dysregulation of the extracellular matrix is regarded as a key pathophysiology underlying unique vascular remodeling. Here, we measured the concentration of elastin crosslinkers desmosine and isodesmosine in the plasma of MMD patients. We aimed to reveal its diagnostic values of desmosines in the progression of steno-occlusive lesions. The concentrations of plasma desmosines were determined by liquid chromatography-tandem mass spectrometry. The temporal profiles of steno-occlusive lesions on magnetic resonance angiography were retrospectively evaluated, and the correlation between the progression of steno-occlusive changes in intracranial arteries and plasma desmosines concentrations was further analyzed. Plasma desmosines were significantly higher in MMD patients with disease progression compared to MMD patients without disease progression. Also, the incidence of disease progression was higher in MMD patients with plasma desmosines levels over limit of quantitation (LOQ) than those with plasma desmosines levels below LOQ. In conclusion, plasma desmosines could be potential biomarkers to predict the progression of steno-occlusive changes in MMD patients.
• Ommaya reservoir placement using ultrasound guidance via anterior fontanelle combined with frameless electromagnetic neuronavigation in patients with mucopolysaccharidosis type 2: Case reports and review of the literature.

  Makoto Mizushima, Masahito Kawabori, Kazuyoshi Yamazaki, Kiyoshi Egawa, Miki Fujimura

  Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery 2024/01/02 

  Mucopolysaccharidosis type II (MPS II) results from the genetic deficiency of a lysosomal enzyme and is associated with central nervous system (CNS) dysfunction. In Japan, in addition to intravenous enzyme administration, intracerebroventricular enzyme delivery through the Ommaya reservoir has recently gained approval. Nevertheless, the ideal approach for safely implanting the reservoir into the narrow ventricles of infantile MPS II patients remains uncertain. In this report, we present two cases of successful reservoir placement in infantile MPS II patients using ultrasound guidance via the anterior fontanelle, coupled with flameless electromagnetic neuronavigation.
• Long-term Outcomes of Combined Revascularization Surgery for Moyamoya Disease in the Elderly: A Single Institute Experience

  Kota KURISU, Masaki ITO, Haruto UCHINO, Taku SUGIYAMA, Miki FUJIMURA

  Neurologia medico-chirurgica 0470-8105 2024
• Preservation of Enlarged Mastoid Emissary Vein during Microvascular Decompression for Trigeminal Neuralgia Accompanied by Abnormal Venous Drainage: A Technical Case Report

  Taku SUGIYAMA, Miki FUJIMURA

  NMC Case Report Journal 10 139 - 143 2023/12/31
• 大型動脈瘤に対するFlow Diverterによる治療成績 vessel wall imagingによる難治例の予測は可能か

  新保 大輔, 坂田 洋之, 眞野 唯, 鹿毛 淳史, 内田 浩喜, 松本 康史, 藤村 幹, 遠藤 英徳

  脳血管内治療 (NPO)日本脳神経血管内治療学会 8 (Suppl.) S334 - S334 2423-9119 2023/11
• CAS中の徐脈・低血圧に対するカテコラミン投与にてたこつぼ型心筋症と血栓性のステント閉塞を来たした1例

  舘澤 諒大, 栗栖 宏太, 長内 俊也, 大前 敬介, 伊東 雅基, 杉山 拓, 石井 伸明, 藤村 幹

  脳血管内治療 (NPO)日本脳神経血管内治療学会 8 (Suppl.) S776 - S776 2423-9119 2023/11
• もやもや病血行再建術後合併症予測におけるsystemic immune-inflammation indexの有用性

  内野 晴登, 山本 大慈, 伊東 雅基, 杉山 拓, 栗栖 宏多, 藤村 幹

  脳循環代謝 (一社)日本脳循環代謝学会 35 (1) 86 - 86 0915-9401 2023/11
• 硬膜動静脈瘻におけるSystemic immune-inflammation indexの動態に関する検討

  栗栖 宏多, 長内 俊也, 森島 穣, 伊東 雅基, 内野 晴登, 杉山 拓, 藤村 幹

  脳循環代謝 (一社)日本脳循環代謝学会 35 (1) 102 - 102 0915-9401 2023/11
• Possible Delayed Foreign Body Reactions against Titanium Clips and Coating Materials after Unruptured Cerebral Aneurysm Surgery.

  Ryota Tatezawa, Taku Sugiyama, Shuho Gotoh, Takafumi Shindo, Hiroshi Ikeda, Masaaki Hokari, Katsumi Takizawa, Naoki Nakayama, Miki Fujimura

  Neurologia medico-chirurgica 2023/08/30 

  Delayed foreign body reactions to either or both clipping and coating materials have been reported in several small series; however, studies in the titanium clip era are scarce. This study aims to survey the contemporary status of such reactions to titanium clips and coating materials. Among patients who received a total of 2327 unruptured cerebral aneurysmal surgeries, 12 developed delayed intraparenchymal reactions during outpatient magnetic resonance imaging (MRI) follow-up. A retrospective investigation was conducted. The patients' average age was 58.6 (45-73) years, and 11 were women. The aneurysms were located in the middle cerebral artery (n = 7), internal carotid artery (n = 4), or anterior communicating artery (AComA, n = 1). In 10 patients, additional coating with tiny cotton fragments was applied to the residual neck after clipping with titanium clips; however, only the clipping with titanium clips was performed in the remaining two. The median time from surgery to diagnosis was 4.5 (0.3-60) months. Seven (58.3%) patients were asymptomatic, and three developed neurological deficits. MRI findings were characterized by a solid- or rim-enhancing lobulated mass adjacent to the clip with surrounding parenchymal edema. In 11 patients, the lesions reduced in size or disappeared; however, in one patient, an AComA aneurysm was exacerbated, necessitating its removal along with optic nerve decompression. In conclusion, cotton material is a strongly suspected cause of delayed foreign body reactions, and although extremely rare, titanium clips alone may also induce such a reaction. The prognosis is relatively good with steroid therapy; however, caution is required when the aneurysm is close to the optic nerve, as in AComA aneurysms.
• Tissue Acceleration as a Novel Metric for Surgical Performance During Carotid Endarterectomy.

  Taku Sugiyama, Masaki Ito, Hiroyuki Sugimori, Minghui Tang, Toshitaka Nakamura, Katsuhiko Ogasawara, Hitoshi Matsuzawa, Naoki Nakayama, Sanju Lama, Garnette R Sutherland, Miki Fujimura

  Operative neurosurgery (Hagerstown, Md.) 2023/07/04 

  BACKGROUND AND OBJECTIVES: Gentle tissue handling to avoid excessive motion of affected fragile vessels during surgical dissection is essential for both surgeon proficiency and patient safety during carotid endarterectomy (CEA). However, a void remains in the quantification of these aspects during surgery. The video-based measurement of tissue acceleration is presented as a novel metric for the objective assessment of surgical performance. This study aimed to evaluate whether such metrics correlate with both surgeons' skill proficiency and adverse events during CEA. METHODS: In a retrospective study including 117 patients who underwent CEA, acceleration of the carotid artery was measured during exposure through a video-based analysis. Tissue acceleration values and threshold violation error frequencies were analyzed and compared among the surgeon groups with different surgical experience (3 groups: novice, intermediate, and expert). Multiple patient-related variables, surgeon groups, and video-based surgical performance parameters were compared between the patients with and without adverse events during CEA. RESULTS: Eleven patients (9.4%) experienced adverse events after CEA, and the rate of adverse events significantly correlated with the surgeon group. The mean maximum tissue acceleration and number of errors during surgical tasks significantly decreased from novice, to intermediate, to expert surgeons, and stepwise discriminant analysis showed that the combined use of surgical performance factors could accurately discriminate between surgeon groups. The multivariate logistic regression analysis revealed that the number of errors and vulnerable carotid plaques were associated with adverse events. CONCLUSION: Tissue acceleration profiles can be a novel metric for the objective assessment of surgical performance and the prediction of adverse events during surgery. Thus, this concept can be introduced into futuristic computer-aided surgeries for both surgical education and patient safety.
• Five-Year Stroke Risk and Its Predictors in Asymptomatic Moyamoya Disease: Asymptomatic Moyamoya Registry (AMORE).

  Satoshi Kuroda, Shusuke Yamamoto, Takeshi Funaki, Miki Fujimura, Hiroharu Kataoka, Tomohito Hishikawa, Jun Takahashi, Hidenori Endo, Tadashi Nariai, Toshiaki Osato, Nobuhito Saito, Norihiro Sato, Emiko Hori, Yoichi M Ito, Susumu Miyamoto

  Stroke 54 (6) 1494 - 1504 2023/06 

  BACKGROUND: Long-term outcomes are unknown in patients with asymptomatic moyamoya disease. In this report, we aimed to clarify their 5-year risk of stroke and its predictors. METHODS: We are conducting a multicenter, prospective cohort study (Asymptomatic Moyamoya Registry) in Japan. Participants were eligible if they were 20 to 70 years, had bilateral or unilateral moyamoya disease, experienced no episodes suggestive of TIA and stroke; and were functionally independent (modified Rankin Scale score 0-1). Demographic and radiological information was collected at enrollment. In this study, they are still followed up for 10 years. In this interim analysis, we defined the primary end point as a stroke occurring during a 5-year follow-up period. Independent predictors for stroke were also determined, using a stratification analysis method. RESULTS: Between 2012 and 2015, we enrolled 109 patients, of whom 103 patients with 182 involved hemispheres completed the 5-year follow-up. According to the findings on DSA and MRA, 143 hemispheres were judged as moyamoya disease and 39 hemispheres as questionable manifestations (isolated middle cerebral artery stenosis). The patients with questionable hemispheres were significantly older, more often male, and more frequently had hypertension than those with moyamoya hemisphere. Moyamoya hemispheres developed 7 strokes, including 6 hemorrhagic and 1 ischemic stroke, during the first 5 years. The annual risk of stroke was 1.4% per person, 0.8% per hemisphere, and 1.0% per moyamoya hemisphere. Independent predictor for stroke was Grade-2 choroidal anastomosis (hazard ratio, 5.05 [95% CI, 1.24-20.6]; P=0.023). Furthermore, microbleeds (hazard ratio, 4.89 [95% CI, 1.13-21.3]; P=0.0342) and Grade-2 choroidal anastomosis (hazard ratio, 7.05 [95% CI, 1.62-30.7]; P=0.0093) significantly predicted hemorrhagic stroke. No questionable hemispheres developed any stroke. CONCLUSIONS: The hemispheres with asymptomatic moyamoya disease may carry a 1.0% annual risk of stroke during the first 5 years, the majority of which are hemorrhagic stroke. Grade-2 choroidal anastomosis may predict stroke, and the microbleeds and Grade-2 choroidal anastomosis may carry the risk for hemorrhagic stroke. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: UMIN000006640.
• Association of RNF213 polymorphism and cortical hyperintensity sign on fluid-attenuated inversion recovery images after revascularization surgery for moyamoya disease: possible involvement of intrinsic vascular vulnerability.

  Haruto Uchino, Masaki Ito, Kikutaro Tokairin, Ryota Tatezawa, Taku Sugiyama, Ken Kazumata, Miki Fujimura

  Neurosurgical review 46 (1) 119 - 119 2023/05/11 

  A cortical hyperintensity on fluid-attenuated inversion recovery images (FLAIR cortical hyperintensity (FCH)) is an abnormal finding after revascularization surgery for moyamoya disease. This study aimed to investigate the pathophysiology of FCH through genetic analyses of RNF213 p.R4810K polymorphism and perioperative hemodynamic studies using single-photon emission computed tomography. We studied 96 hemispheres in 65 adults and 47 hemispheres in 27 children, who underwent combined direct and indirect revascularization. Early or late FCH was defined when it was observed on postoperative days 0-2 and 6-9, respectively. FCH scores (range: 0-6) were evaluated according to the extent of FCH in the operated hemisphere. FCHs were significantly more prevalent in adult patients than pediatric patients (early: 94% vs. 78%; late: 97% vs. 59%). In pediatric patients, FCH scores were significantly improved from the early to late phase regardless of the RNF213 genotype (mutant median [IQR]: 2 [1-5] vs. 1 [0-2]; wild-type median: 4 [0.5-6] vs. 0.5 [0-1.75]). In adults, FCH scores were significantly improved in patients with the wild-type RNF213 allele (median: 4 [2-5.25] vs. 2 [2, 3]); however, they showed no significant improvement in patients with the RNF213 mutation. FCH scores were significantly higher in patients with symptomatic cerebral hyperperfusion than those without it (early median: 5 [4, 5] vs. 4 [2-5]; late median: 4 [3-5] vs. 3 [2-4]). In conclusion, the RNF213 p.R4810K polymorphism was associated with prolonged FCH, and extensive FCH was associated with symptomatic cerebral hyperperfusion in adult patients with moyamoya disease.
• Evaluation of cholesterol crystals in carotid plaque by dual energy computed tomography

  Takuya Saito, Hidenori Endo, Daisuke Ando, Itsuki Miyagi, Yuichi Kawabata, Mika Watanabe, Atsushi Saito, Miki Fujimura, Yukako Yazawa

  Neuroradiology 65 (5) 979 - 982 0028-3940 2023/05 

  Cholesterol crystals (CCs) in carotid plaques might be an indicator of vulnerability, although they have not been fully investigated and non-invasive methods of assessment have not been established. This study examines the validity of assessing CCs using dual-energy computed tomography (DECT) that uses X-rays with different tube voltages for imaging, allowing material discrimination. We retrospectively evaluated patients who had undergone preoperative cervical computed tomography angiography and carotid endarterectomy between December 2019 and July 2020. We developed CC-based material decomposition images (MDIs) by scanning CCs crystallized in the laboratory using DECT. We compared the percentage of CCs in stained slides defined by cholesterol clefts with the percentage of CCs displayed by CC-based MDIs. Thirty-seven pathological sections were obtained from 12 patients. Thirty-two sections had CCs; of these, 30 had CCs on CC-based MDIs. CC-based MDIs and pathological specimens showed a strong correlation. Thus, DECT allows the evaluation of CCs in carotid artery plaques.
• Chronological Volume Changes of the Temporal Muscle Pedicle Used for Encephalo-myo-synangiosis in Combined Revascularization for Moyamoya Disease: A Prospective Observational Study.

  Makoto Mizushima, Masaki Ito, Noriyuki Fujima, Haruto Uchino, Taku Sugiyama, Miki Fujimura

  Neurologia medico-chirurgica 63 (7) 304 - 312 2023/04/20 

  Although postoperative neurological events due to brain compression by the swollen temporal muscle are a rare complication, the chronological volume changes of the temporal muscle pedicle and their clinical impact have not yet been documented. This prospective observational study aimed to investigate the chronological volume changes in the temporal muscle pedicle in Moyamoya disease (MMD). Eighteen consecutive combined revascularization procedures using the temporal muscle were performed for symptomatic MMD in 2021. The postoperative pedicle volume was quantified using repeated computed tomography images on postoperative days (PODs) 0, 1, 7, 14, and 30. Postoperative neurological events with radiological evaluations and collateral development evaluated using magnetic resonance angiography obtained 6 months after surgery were studied. On average, the postoperative temporal muscle pedicle volume was most significantly increased by as much as 112% ± 9.6% on POD 7 (P < 0.001) and decreased by as little as 52% ± 21% on POD 30 (P < 0.0001) relative to POD 0. One exceptional patient (overall incidence, 5.6%) demonstrated postoperative transient neurological events due to brain compression by the swollen temporal muscle with decreased focal cerebral blood flow in the adjacent cortical area. The postoperative collateral development via direct and indirect revascularizations was confirmed in 16 (89%) and 12 (67%) hemispheres, respectively. All patients, except for one rebleeding case, showed independent outcomes at the mean latest follow-up period on 290 ± 96 days after surgery. Our observations confirmed the temporal profile of muscle pedicle volume changes after combined revascularization. Through routine attempts to avoid the unfavorable effects of temporal muscle swelling, combined revascularization can provide favorable outcomes in symptomatic MMD.
• Comparison of Access Route for Endovascular Treatment by Time-Spatial Labeling Inversion Pulse (Time-SLIP) MRA and Contrast-Enhanced MRA

  Satoshi Kobayashi, Toshiya Osanai, Taku Sugiyama, Noriyuki Fujima, Ryo Takagi, Isao Yokota, Akiyoshi Hamaguchi, Toshitaka Nakamura, Kazutoshi Hida, Miki Fujimura

  Journal of Neuroendovascular Therapy 1882-4072 2023
• Retiform endothelial hyperplasia mimicking cavernous malformation as a late complication of Gamma Knife radiosurgery.

  Jun Kawagishi, Hidefumi Jokura, Mika Watanabe, Miki Fujimura, Kuniyasu Niizuma, Hidenori Endo, Hiroyoshi Suzuki, Teiji Tominaga

  Journal of neurosurgery 139 (1) 1 - 11 2022/12/23 

  OBJECTIVE: Gamma Knife radiosurgery (GKRS) is a powerful tool for the management of arteriovenous malformations; however, newly formed mass lesions resembling cavernous malformations are a rare late complication of GKRS. In this retrospective study, the authors tried to clarify the unique histological features of these mass lesions. METHODS: The authors retrospectively reviewed the clinical course of 889 patients who had undergone GKRS for arteriovenous malformations at their institute from 1991 to 2021. Among the 848 patients who had been followed up periodically with neuroradiological imaging, 37 developed a mass lesion mimicking a cavernous malformation and underwent surgical removal of the lesion. The median volume of the original nidus was 3.7 cm3 (range 0.07-30.5 cm3), and the median prescription dose was 21 Gy (range 12-25 Gy). The histological characteristics and radiological and clinical features of the 37 patients were investigated. RESULTS: Histological examination showed an organized hematoma and a structure termed "retiform endothelial hyperplasia" (RFEH) consisting of endothelium forming multiple lumen-like vascular channels mimicking cavernous malformations but lacking the subendothelial connective tissue that forms the typical vascular wall structure found in cavernous angioma and capillary telangiectasia. RFEH was detected a median of 10.8 years (range 3.2-27.4 years) after GKRS. Neuroimaging showed hematoma surrounded by massive brain edema in all 37 patients. Symptoms caused by mass effect of the lesion and perifocal edema worsened relatively rapidly but completely disappeared after surgery. No recurrence or morbidity occurred after the surgery. CONCLUSIONS: The delayed formation of RFEH that is mimicking a cavernous malformation neuroradiologically but is histologically distinct from a vascular malformation is a potential complication of GKRS. Its progressive clinical course suggests that surgical removal should be considered for symptomatic patients and/or patients with an apparent radiological mass sign.
• 脳血管内治療術者指導においてのTelementoringの有用性についての検討

  長内 俊也, 大川原 舞, 前田 拓真, 山口 裕之, 藤村 幹

  脳血管内治療 (NPO)日本脳神経血管内治療学会 7 (Suppl.) S162 - S162 2423-9119 2022/11
• 血行再建術後も再出血を繰り返す側副血行路末梢性動脈瘤を伴う成人出血型もやもや病の治療

  伊東 雅基, 内野 晴登, 杉山 拓, 長内 俊也, 川堀 真人, 藤村 幹

  脳循環代謝 (一社)日本脳循環代謝学会 34 (1) 124 - 124 0915-9401 2022/10
• 亜急性期〜慢性期脳虚血病態の治療 脳血管動脈硬化性疾患に対する亜急性/慢性期EC-ICバイパスの現代的適応

  杉山 拓, 伊東 雅基, 内野 晴登, 長内 俊也, 川堀 真人, 藤村 幹

  脳循環代謝 (一社)日本脳循環代謝学会 34 (1) 74 - 74 0915-9401 2022/10
• 成人もやもや病の術前MRA末梢動脈描出と間接血行発達度との関連

  内野 晴登, 伊東 雅基, 杉山 拓, 川堀 真人, 藤村 幹

  脳循環代謝 (一社)日本脳循環代謝学会 34 (1) 122 - 122 0915-9401 2022/10
• 血行再建術後も再出血を繰り返す側副血行路末梢性動脈瘤を伴う成人出血型もやもや病の治療

  伊東 雅基, 内野 晴登, 杉山 拓, 長内 俊也, 川堀 真人, 藤村 幹

  脳循環代謝 (一社)日本脳循環代謝学会 34 (1) 124 - 124 0915-9401 2022/10
• Impact of RNF213 c.14576G>A Variant on the Development of Direct and Indirect Revascularization in Pediatric Moyamoya Disease

  Masahito Kawabori, Masaki Ito, Ken Kazumata, Kikutaro Tokairin, Kanako C. Hatanaka, Susumu Ishikawa, Kiyohiro Houkin, Miki Fujimura

  Cerebrovascular Diseases 52 (2) 171 - 176 1015-9770 2022/09/05 

  Background: Superficial temporal artery (direct) and encephalomyosynangiosis (indirect) revascularization may develop after combined bypass surgery in pediatric patients with moyamoya disease (MMD). However, arterial development varies widely among patients, and the underlying mechanisms remain unknown. Objectives: We evaluated the relationship between the development of donor arteries after bypass surgery in pediatric patients with MMD and the MMD-susceptibility gene variant c.14576G>A of ring finger protein (RNF) 213. Methods: The data of pediatric patients with MMD (age <16 years at the time of surgery) treated with combined bypass surgery between September 2013 and April 2019 were consecutively analyzed. Quantitative measurements of the superficial temporal artery (STA), deep temporal artery (DTA), and middle meningeal artery (MMA) diameters with magnetic resonance angiography (MRA) source imaging were performed preoperatively and at 6–12 months postoperatively. The postoperative caliber change ratios (CCRs) were calculated. The relationship between CCRs and RNF213 c.14576G>A status was examined. Results: Forty-eight hemispheres from 28 pediatric patients with MMD were examined. Three hemispheres belonged to patients with the AA genotype; 33 to patients with the AG genotype (AA/AG group); and 12 to patients with the GG genotype (GG group; wild type). The CCRs for the DTA were significantly higher in patients with RNF213 variant (AA/AG group; 2.5 ± 0.1) than in the GG group (2.0 ± 0.2) (p = 0.03), whereas the CCRs for the STA were significantly higher in the GG (1.6 ± 0.1) than in the AA/AG group (1.3 ± 0.6) (p = 0.02). There was no significant difference in the CCRs for the MMA and basilar artery between the groups. Other factors, including sex, age, and MRA grading, were not associated with the development of specific bypass development. Conclusions: The extent of collateral development associated with direct or indirect bypass was found to differ between the genotypes of the RNF213 c.14576G>A associated with pediatric MMD. This genetic variant correlates with the development of the disease and affects revascularization after bypass surgery in pediatric patients with MMD.
• 【グローカル脳神経外科-1】もやもや病 治療の現状と研究課題について

  藤村 幹, 伊東 雅基, 杉山 拓, 川堀 真人, 長内 俊也

  脳神経外科ジャーナル (一社)日本脳神経外科コングレス 31 (9) 579 - 585 0917-950X 2022/09 

  もやもや病は東アジアに多い原因不明の頭蓋内動脈狭窄症で、小児と若年成人の脳卒中の原因として重要である。疾患感受性遺伝子RNF213の多型は発症年齢、臨床的重症度、血管病変進行との関連が知られており重要である。またRNF213遺伝子多型は血管外径狭小化、壁菲薄化を特徴とするnegative remodelingとの関連も報告され、病態解明が進んでいる。外科治療においては虚血例に加えて出血例に対するバイパス術の効果が明らかとなり、もやもや病に対する手術適応は拡大傾向にある。局所過灌流やwatershed shift現象など本疾患に特徴的な術後脳循環の診断と適切な術後管理による合併症回避が重要である。(著者抄録)
• Intracerebral Transplantation of Mesenchymal Stromal Cell Compounded with Recombinant Peptide Scaffold against Chronic Intracerebral Hemorrhage Model

  Soichiro Takamiya, Masahito Kawabori, Tsukasa Kitahashi, Kentaro Nakamura, Yuki Mizuno, Hironobu Yasui, Yuji Kuge, Aki Tanimori, Yasuyuki Takamatsu, Kohei Yuyama, Hideo Shichinohe, Miki Fujimura

  Stem Cells International 2022 1 - 10 1687-966X 2022/07/31 

  Background. Due to the lack of effective therapies, stem cell transplantation is an anticipated treatment for chronic intracerebral hemorrhage (ICH), and higher cell survival and engraftment are considered to be the key for recovery. Mesenchymal stromal cells (MSCs) compounded with recombinant human collagen type I scaffolds (CellSaics) have a higher potential for cell survival and engraftment compared with solo-MSCs, and we investigated the validity of intracerebral transplantation of CellSaic in a chronic ICH model. Methods. Rat CellSaics (rCellSaics) were produced by rat bone marrow-derived MSC (rBMSCs). The secretion potential of neurotrophic factors and the cell proliferation rate were compared under oxygen-glucose deprivation (OGD) conditions. rCellSaics, rBMSCs, or saline were transplanted into the hollow cavity of a rat chronic ICH model. Functional and histological analyses were evaluated, and single-photon emission computed tomography for benzodiazepine receptors was performed to monitor sequential changes in neuronal integrity. Furthermore, human CellSaics (hCellSaics) were transplanted into a chronic ICH model in immunodeficient rats. Antibodies neutralizing brain-derived neurotrophic factor (BDNF) were used to elucidate its mode of action. Results. rCellSaics demonstrated a higher secretion potential of trophic factors and showed better cell proliferation in the OGD condition. Animals receiving rCellSaics displayed better neurological recovery, higher intracerebral BDNF, and better cell engraftment; they also showed a tendency for less brain atrophy and higher benzodiazepine receptor preservation. hCellSaics also promoted significant functional recovery, which was reversed by BDNF neutralization. Conclusion. Intracerebral transplantation of CellSaics enabled neurological recovery in a chronic ICH model and may be a good option for clinical application.
• Late-onset obstructive hydrocephalus associated with occipital encephalocele with large skull defect successfully treated by endoscopic third ventriculostomy

  Yuki Munekata, Taku Sugiyama, Yuki Ueda, Makoto Mizushima, Hiroaki Motegi, Miki Fujimura

  Child's Nervous System 0256-7040 2022/07/29
• RNF213特集 RNF213遺伝子多型c.14576G>A(p.R4810K,rs112735431)を有する成人もやもや病患者におけるSTA-MCAバイパス術後遅発性・遷延性過灌流

  田代 亮介, 藤村 幹, 西澤 威人, 遠又 靖丈, 新妻 邦泰, 冨永 悌二

  The Mt. Fuji Workshop on CVD The Mt. Fuji Workshop on CVD事務局 39 159,169 - 162,169 0289-8438 2022/07
• Outcomes of combined revascularization surgery for moyamoya disease without preoperative cerebral angiography.

  Tomohiro Okuyama, Masahito Kawabori, Masaki Ito, Taku Sugiyama, Ken Kazumata, Miki Fujimura

  World neurosurgery 2022/06/21 

  OBJECTIVE: Cerebral angiography is the gold standard for diagnosing moyamoya disease (MMD), whereas magnetic resonance (MR) imaging/angiography is becoming more popular in the field of cerebrovascular disease due to its low invasiveness. Although there are concerns about using only MR imaging/angiography for preoperative analysis of MMD, considering the underestimation of pre-existing transdural collateral circulations and dangerous collaterals related to the risk of hemorrhage, we retrospectively reviewed our 10-year experience of MRI-first diagnosis and analyzed the perioperative outcomes. METHODS: We analyzed 160 consecutive direct/indirect combined revascularization procedures for MMD preoperatively assessed using MR imaging/angiography alone. Perioperative complications were assessed for up to 2 weeks after surgery. Locations of the lesions responsible for complications were further classified into the surgical field, the ipsilateral hemisphere outside the surgical field, and the contralateral hemisphere. RESULTS: Sixty-four revascularization procedures were performed in 38 children, and 96 procedures were performed in 68 adults. There was no difference in the incidence of perioperative ischemic complications between adults (6.3%) and pediatric patients (4.7%), but hemorrhagic complications were more frequently observed in adults (7.3%) than in children (0%) (P<0.05). There was no specific lesion deviation for ischemic complications; however, hemorrhagic complications predominantly occurred in the surgical field. CONCLUSIONS: Direct/indirect combined revascularization surgery based on our preoperative diagnostic protocol with the MR-first strategy resulted in favorable outcomes in pediatric MMD patients with relatively low complication rates. However, the validity of the MR-first diagnostic protocol should be further evaluated in adult patients with MMD.
• Moyamoya Disease Associated with a Deficiency of Complement Component 6.

  Masaru Kato, Yuki Kudo, Masanao Hatase, Naohisa Tsuchida, Shuhei Takeyama, Taku Sugiyama, Miki Fujimura, Ichiro Yabe, Hiroshi Tsujimoto, Yasuo Fukumori, Norimitsu Inoue, Tatsuya Atsumi

  Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 31 (8) 106601 - 106601 2022/06/16 

  OBJECTIVES: Complement component 6 (C6) deficiency is a very rare genetic defect that leads to significantly diminished synthesis, secretion, or function of C6. In the current report, we demonstrate a previously undescribed, homozygous missense mutation in exon 17 of the C6 gene (c.2545A>G p.Arg849Gly) in a 35-year-old Japanese woman with moyamoya disease and extremely low levels of CH50 (<7.0 U/mL). MATERIALS AND METHODS: The complement gene analysis using hybridization capture-based next generation sequencing was performed. CH50 was determined in patient's plasma mixed with plasma from a healthy donor or purified human C6 protein. Western blot was performed on patient's plasma using polyclonal antibodies against C6, with healthy donor's plasma and purified human C6 protein as positive controls while C6-depleted human serum as a negative control. The carriage of ring finger protein 213 variant (c.14576G>A p.Arg4859Lys), a susceptibility gene for moyamoya disease, was examined by direct sequencing. RESULTS: CH50 mixing test clearly showed a deficiency pattern, being rescued by addition of only 1% healthy donor's plasma or 1 μg/mL purified human C6 protein (1/50-1/100 of physiological concentration). Western blot revealed the absence of C6 protein in the patient's plasma, confirming a quantitative deficiency of C6. The ring finger protein 213 variant was not detected. CONCLUSIONS: Our data implies that unrecognized complement deficiencies would be harbored in cerebrovascular diseases with unknown etiologies.
• Spontaneous Obliteration of a Dissecting Aneurysm of Recurrent Artery of Heubner Monitored by Serial Magnetic Resonance Vessel Wall Imaging.

  Asuka Nakazaki, Masaki Ito, Masanori Isobe, Takeshi Takahashi, Taichi Nomura, Fumiaki Fujihara, Toyohiko Isu, Taku Sugiyama, Toshiya Osanai, Miki Fujimura

  Asian journal of neurosurgery 17 (2) 331 - 336 2022/06 

  Aneurysms of the recurrent artery of Heubner (RAH) are known to be one of the uncommon cerebral aneurysms, predominantly presenting with bleeding symptoms. Previously, nine cases of the RAH aneurysms have been reported, all of which were treated surgically or endovascularly and most cases developed postoperative cerebral infarct in the ipsilateral caudate nucleus. Herein, we report a man presenting with transient ischemic attack due to diffuse cerebral vasospasm from a minor non-disabling subarachnoid hemorrhage (SAH) from an RAH aneurysm. He visited our hospital 7 days after the first experience of a thunderclap headache complaining with transient unilateral motor weakness and thin SAH in the right sylvian fissure. Diagnostic catheter angiography revealed a dissecting fusiform aneurysm (8 mm in size) originating from the left RAH contralateral to the thin SAH. Contrast-enhanced magnetic resonance vessel wall imaging (MR-VWI) helped to identify the ruptured nature of the RAH aneurysm. Owing to his delayed ischemic condition after minor SAH, he was conservatively treated with serial MR-VWI monitoring. The aneurysm was spontaneously obliterated with an asymptomatic lacunar infarct in the ipsilateral caudate nucleus in a month. Together, this case was considered as the dissecting aneurysm of RAH with a favorable outcome after the conservative management. Although long-term follow-up is mandatory because the disappearance of the vessel wall enhancement does not necessarily secure the permanent cure of the lesion, serial MR-VWI is helpful to diagnose the ruptured nature and monitor its chronological change in combination with conventional radiological imaging techniques.
• Diagnostic Value of Vessel Wall Imaging to Determine the Timing of Extracranial-Intracranial Bypass for Moyamoya Syndrome Associated with Active Sjögren's Syndrome: A Case Report.

  Takafumi Shindo, Masaki Ito, Taku Sugiyama, Tomohiro Okuyama, Michihito Kono, Tatsuya Atsumi, Miki Fujimura

  Journal of neurological surgery. Part A, Central European neurosurgery 2022/04/22 

  BACKGROUND: Sjögren's syndrome is a chronic autoimmune disorder that predominantly affects exocrine organs. It is characterized by an organ-specific infiltration of lymphocytes. The involvement of the major cerebral arteries in Sjögren's syndrome has rarely been reported. A recent study reported a case of successful extracranial‒intracranial (EC‒IC) bypass without complications, even in the active inflammatory state, although the optimal timing of such a bypass remains unclear. CASE DESCRIPTION: We here report the case of a 43-year-old woman presenting with acute ischemic stroke due to progressive middle cerebral artery (MCA) occlusion and signs of primary Sjögren's syndrome. During intensive immunosuppressive therapy for active Sjögren's syndrome, the patient was monitored using contrast-enhanced magnetic resonance vessel wall imaging (MR-VWI). A couple of intravenous cyclophosphamide injections combined with a methylprednisolone pulse and antiplatelet therapy, resulted in clear resolution of vessel wall enhancement, which suggested remission of inflammatory vasculitis. Nevertheless, she still experienced a transient ischemic attack due to decreased regional cerebral blood flow by MCA occlusion, as demonstrated by the conventional time-of-flight MR angiography and single-photon emission computed tomography. Considering the increased risk of further stroke, the decision was made to perform EC-IC bypass as a treatment of hemodynamic impairment medically uncontrollable. Her postoperative course was uneventful without further repeated TIAs, and continued immunosuppressive therapy for Sjögren's syndrome provided effective management. CONCLUSIONS: Our findings emphasize the diagnostic value of contrast-enhanced MR-VWI in monitoring the effect of immunosuppressive therapy for the major cerebral artery vasculitis and in determining the timing of EC‒IC bypass as a 'rescue' treatment for Moyamoya syndrome associated with active Sjögren's syndrome.
• 2021 Japanese Guidelines for the Management of Moyamoya Disease: Guidelines from the Research Committee on Moyamoya Disease and Japan Stroke Society.

  Miki Fujimura, Teiji Tominaga, Satoshi Kuroda, Jun C Takahashi, Hidenori Endo, Kuniaki Ogasawara, Susumu Miyamoto

  Neurologia medico-chirurgica 62 (4) 165 - 170 2022/04/15
• 脳幹部海綿状血管腫に対する第四脳室経由摘出術

  遠藤 俊毅, 藤村 幹, 遠藤 英徳, 村上 謙介, 冨永 悌二

  脳卒中の外科 (一社)日本脳卒中の外科学会 50 (2) 130 - 135 0914-5508 2022/03 

  当院にて第四脳室経由で摘出術を行った脳幹部海綿状血管腫7例の治療成績について検討した。その結果、平均年齢は53.8歳、男性1例、女性6例であった。海綿状血管腫の部位は橋背側4例、延髄背側3例であった。全例で術前なんらかの神経症候を呈していた。6例は病変を全摘出し、すべて症状が改善した。一方、部分摘出となった1例は症状の一部が残存したが、その後は神経症状の悪化なく経過した。術後追跡期間は平均74ヵ月で、最終時のmRSは全例0-2であった。
• 脳幹部海綿状血管腫に対する第四脳室経由摘出術

  遠藤 俊毅, 藤村 幹, 遠藤 英徳, 村上 謙介, 冨永 悌二

  脳卒中の外科 (一社)日本脳卒中の外科学会 50 (2) 130 - 135 0914-5508 2022/03
• Rescue extracranial-intracranial bypass for ischemic stroke secondary to progressive human immunodeficiency virus-associated vasculopathy

  Makoto Mizushima, Taku Sugiyama, Katsuki Eguchi, Monami Tarisawa, Kikutaro Tokairin, Masaki Ito, Daigo Hashimoto, Ichiro Yabe, Miki Fujimura

  Journal of Neurological Surgery Part A: Central European Neurosurgery 2022/02/22 [Refereed][Not invited]
   

  BACKGROUND: Human immunodeficiency virus (HIV) associated vasculopathy can cause ischemic cerebral stroke; however, there is limited evidence on optimal management. Herein, we report a case of acute ischemic stroke due to progressive internal carotid artery (ICA) stenosis in an HIV-positive patient. Superficial temporal artery to middle cerebral artery (STA-MCA) bypass, in addition to the best medical treatments, prevented stroke progression. CLINICAL DESCRIPTION: A 39-year-old man with HIV infection presented with a sudden onset of aphasia and right hemiparesis. Magnetic resonance imaging revealed an ischemic lesion in the left basal ganglia and concentric thickening of the vessel wall in the terminal portion of the bilateral ICAs. Despite maximal medical treatments for HIV-associated vasculopathy and possible opportunistic infections, bilateral ICA stenoses progressed, leading to a second hemodynamic stroke event. Because tissue plasminogen activator treatment failed, we performed STA-MCA bypass. A significant improvement in neurologic symptoms and cerebral blood flow was observed after surgery. No further stroke events occurred during the continuation of medical treatments. CONCLUSION: This is the first case of STA-MCA bypass performed in a patient with recurrent ischemic stroke caused by HIV-associated vasculopathy. Although further evidence is needed, such treatment options can shed new light on the management of progressive HIV-associated vasculopathy, which is refractory to maximal medical treatment.
• Analysis of induced pluripotent stem cell clones derived from a patient with mosaic neurofibromatosis type 2.

  Yukitomo Ishi, Takumi Era, Sayaka Yuzawa, Michinari Okamoto, Ryosuke Sawaya, Hiroaki Motegi, Shigeru Yamaguchi, Shunsuke Terasaka, Kiyohiro Houkin, Miki Fujimura

  American journal of medical genetics. Part A 2022/02/18 

  The diagnosis of mosaicism is challenging in patients with neurofibromatosis type 2 (NF2) subset due to low variant allele frequency. In this study, we generated induced pluripotent stem cells (iPSCs) were generated from a patient clinically diagnosed with NF2 based on multiple schwannomas, including bilateral vestibular schwannomas and meningiomas. Genetic analysis of the patient's mononuclear cells (MNCs) from peripheral blood failed to detect NF2 alteration but successfully found p.Q65X (c.193C>T) mutation in all separate tumors with three intracranial meningiomas and one intraorbital schwannoma, and confirming mosaicism diagnosis in NF2 alteration using deep sequencing. Five different clones with patient-derived iPSCs were established from MNCs in peripheral blood, which showed sufficient expression of pluripotent markers. Genetic analysis showed that one of five generated iPSC lines from MNCs had the same p.Q65X mutation as that found in NF2. There was no significant difference in the expression of genes related to NF2 between iPSC clones with the wild-type and mutant NF2. In this case, clonal expansion of mononuclear bone marrow-derived stem cells recapitulated mosaicism's genetic alteration in NF2. Patient-derived iPSCs from mosaic NF2 would contribute to further functional research of NF2 alteration.
• Impact of RNF213 founder polymorphism (p.R4810K) on the postoperative development of indirect pial synangiosis after direct/indirect combined revascularization surgery for adult Moyamoya disease.

  Masaki Ito, Masahito Kawabori, Taku Sugiyama, Kikutaro Tokairin, Ryota Tatezawa, Haruto Uchino, Ken Kazumata, Kiyohiro Houkin, Miki Fujimura

  Neurosurgical review 45 (3) 2305 - 2313 2022/02/07 

  Direct superficial temporal artery (STA) to middle cerebral artery (MCA) anastomosis combined with indirect pial synangiosis provides favorable surgical collaterals for Moyamoya disease (MMD), especially in adults; however, factors leading to the development of each direct and indirect collateral are not well documented.We aimed to investigate the association between RNF213 founder polymorphism (p.R4810K) and each direct and indirect collateral development. By qualitative and quantitative evaluations of direct and indirect surgical collaterals using time-of-flight MR angiography, postoperative development of each type of bypass was evaluated independently into two categories. Multivariate logistic regression analysis was performed to study the contributing factors for the development of each surgical collateral. Excellent development of postoperative direct and indirect bypass was observed in 65 hemispheres (70%) by qualitative evaluation, which was confirmed by quantitative evaluation. Multivariate logistic regression analysis of excellent indirect bypass development revealed a significant positive correlation with the p.R4810K (odds ratio, OR4.0; 95%-confidence interval, CI 1.2-16), advanced MR angiographic stage (OR9.5; 95%CI 1.7-73), and preoperative middle meningeal artery caliber (OR6.8; 95%CI 1.8-35), but a significant negative correlation was found with the excellent direct bypass development (OR0.17; 95%CI 0.03-0.75). No significant correlation was observed between excellent direct bypass development and the p.R4810K (OR0.95; 95%CI 0.37-2.4).In conclusion, excellent development of indirect collaterals after STA-MCA anastomosis combined with indirect pial synangiosis occurs more frequently in adult MMD with the RNF213 founder polymorphism, suggesting a role of the p.R4810K variant for marked in-growth of indirect collaterals and the utility of preoperative genetic analysis.
• 【最新臨床脳卒中学(第2版)下-最新の診断と治療-】脳梗塞総論 慢性期治療 EC-ICバイパス術

  杉山 拓, 藤村 幹

  日本臨床 (株)日本臨床社 80 (増刊2 最新臨床脳卒中学(下)) 109 - 113 0047-1852 2022/02
• 【脳動脈瘤】脳動脈瘤診断におけるvessel wall imagingの役割

  面高 俊介, 遠藤 英徳, 藤村 幹, 冨永 悌二

  脳神経外科ジャーナル (一社)日本脳神経外科コングレス 31 (2) 81 - 86 0917-950X 2022/02 

  未破裂脳動脈瘤診断に伴う治療方針決定の際には破裂高リスク状態の動脈瘤をいかに捉えるかが重要となるが、動脈瘤の発生から破裂までの経時変化は多岐にわたり予測が難しい。近年MRIを用いた血管壁イメージング(VWI)が普及し瘤壁造影効果の評価が可能となりその役割に注目が集まっている。VWIにおける瘤壁造影効果は2013年に破裂瘤の、2014年には破裂リスクを伴う未破裂動脈瘤の特徴として初期の報告がなされ、その後これらを支持する多くの報告があり現在に至っている。VWIは瘤壁の炎症を画像化する新たなmodalityとして動脈瘤診断における有用性が期待されておりさらなるエビデンスの蓄積が求められる。(著者抄録)
• 【最新臨床脳卒中学(第2版)下-最新の診断と治療-】脳梗塞総論 慢性期治療 EC-ICバイパス術

  杉山 拓, 藤村 幹

  日本臨床 (株)日本臨床社 80 (増刊2 最新臨床脳卒中学(下)) 109 - 113 0047-1852 2022/02
• Transient Global Cerebral Hypoperfusion as a Characteristic Cerebral Hemodynamic Pattern in the Acute Stage after Combined Revascularization Surgery for Pediatric Moyamoya Disease: N-Isopropyl-P-[123I] Iodoamphetamine Single-Photon Emission Computed Tomography Study.

  Atsushi Kanoke, Miki Fujimura, Ryosuke Tashiro, Dan Ozaki, Teiji Tominaga

  Cerebrovascular diseases (Basel, Switzerland) 51 (4) 453 - 460 2022 

  INTRODUCTION: Surgical revascularization prevents cerebral ischemic attack by improving cerebral blood flow (CBF) in both adult and pediatric patients with moyamoya disease (MMD). Uneven hemodynamic changes, including local cerebral hyperperfusion and remote ischemia, can cause delayed intracerebral hemorrhage and perioperative infarctions in adult MMD patients, but the characteristic hemodynamic pattern among pediatric MMD patients after revascularization surgery is poorly understood. METHODS: This study included 16 consecutive pediatric MMD patients (age, 6-16 years; mean age, 11.3) undergoing superficial temporal artery-middle cerebral artery anastomosis combined with encephalo-duro-myo-synangiosis on 21 affected hemispheres. Perioperative management was conducted by aspirin administration and strict blood pressure control (110-130 mm Hg). We prospectively performed N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography on postoperative days (POD) 1 and 7 and analyzed the temporal changes in perioperative hemodynamics. RESULTS: Four patients (19.0%, 4/21) exhibited immediate CBF improvement from POD 1, which was classified as "immediate redistribution pattern." In contrast, 9 (42.9%, 9/21) demonstrated transient hemispheric global hypoperfusion at POD 1 and subsequent CBF improvement at POD 7, which was defined as "transient hypoperfusion pattern." Although 8 patients, including 4 with "transient hypoperfusion pattern" (44.4, 4/9), developed mild transient neurological deterioration in the acute stage, it resolved in all 21 patients, and there were no permanent neurological deficits. DISCUSSION/CONCLUSIONS: This study revealed that the "transient hypoperfusion pattern" after revascularization surgery is relatively common among pediatric MMD patients, and its outcome is favorable under strict perioperative management.
• Moyamoya Disease : Current Status of Surgical Revascularization and Research Update

  Miki Fujimura, Masaki Ito, Taku Sugiyama, Masahiro Kawabori, Toshiya Osanai

  Japanese Journal of Neurosurgery 31 (9) 579 - 585 0917-950X 2022
• 血管修復術を要した頸部穿通性外傷の2例

  杉山 拓, 月花 正幸, 数又 研, 藤村 幹

  日本脳神経外傷学会プログラム・抄録集 (一社)日本脳神経外傷学会 45回 228 - 228 2022/01
• Intravenous transplantation of amnion-derived mesenchymal stem cells promotes functional recovery and alleviates intestinal dysfunction after spinal cord injury.

  Soichiro Takamiya, Masahito Kawabori, Kazuyoshi Yamazaki, Sho Yamaguchi, Aki Tanimori, Koji Yamamoto, Shunsuke Ohnishi, Toshitaka Seki, Kotaro Konno, Khin Khin Tha, Daigo Hashimoto, Masahiko Watanabe, Kiyohiro Houkin, Miki Fujimura

  PloS one 17 (7) e0270606  2022 

  Spinal cord injury (SCI) is often accompanied by gastrointestinal dysfunction due to the disconnection of the spinal autonomic nervous system. Gastrointestinal dysfunction reportedly upregulates intestinal permeability, leading to bacterial translocation of the gut microbiome to the systemic circulation, which further activates systemic inflammation, exacerbating neuronal damage. Mesenchymal stem cells (MSC) reportedly ameliorate SCI. Here, we aimed to investigate their effect on the associated gastrointestinal dysfunction. Human amnion-derived MSC (AMSCs) were intravenously transplanted one day after a rat model of midthoracic SCI. Biodistribution of transplanted cells, behavioral assessment, and histological evaluations of the spinal cord and intestine were conducted to elucidate the therapeutic effect of AMSCs. Bacterial translocation of the gut microbiome was examined by in situ hybridization and bacterial culture of the liver. Systemic inflammations were examined by blood cytokines, infiltrating immune cells in the spinal cord, and the size of the peripheral immune tissue. AMSCs released various neurotrophic factors and were mainly distributed in the liver and lung after transplantation. AMSC-transplanted animals showed smaller spinal damage and better neurological recovery with preserved neuronal tract. AMSCs transplantation ameliorated intestinal dysfunction both morphologically and functionally, which prevented translocation of the gut microbiome to the systemic circulation. Systemic inflammations were decreased in animals receiving AMSCs in the chronic phase. Intravenous AMSC administration during the acute phase of SCI rescues both spinal damage and intestinal dysfunction. Reducing bacterial translocation may contribute to decreasing systemic inflammation.
• Efficacy of the MRA-Based Road Mapping of the Para-Aortic Access Route before Mechanical Thrombectomy in Patients with Acute Ischemic Stroke.

  Satoshi Kobayashi, Toshiya Osanai, Noriyuki Fujima, Akiyoshi Hamaguchi, Taku Sugiyama, Toshitaka Nakamura, Kazutoshi Hida, Miki Fujimura

  Cerebrovascular diseases extra 12 (1) 47 - 52 2022 

  INTRODUCTION: The aim of this study was to clarify whether magnetic resonance angiography (MRA)-based road mapping of the para-aortic transfemoral access route can reduce the procedural time of mechanical thrombectomy in patients with acute ischemic stroke. We further investigated the role of pre-procedural MRA-based road mapping in optimal initial catheter selection for rapid mechanical thrombectomy. MATERIALS AND METHODS: We retrospectively reviewed 57 consecutive patients with acute ischemic stroke who underwent mechanical thrombectomy at our hospital between April 2018 and May 2021. Twenty-nine patients underwent MRA-based road mapping to visualize the para-aortic access route, whereas 28 patients only underwent routine head magnetic resonance imaging/angiography without MRA-based road mapping before neuro-interventional procedures. We then compared the basic procedural times required for mechanical thrombectomy, such as the time from femoral artery puncture to recanalization ("puncture to recanalization time") and the time from the admission to recanalization ("door to recanalization time"), between the groups. RESULTS: MRA-based road mapping significantly reduced the "puncture to recanalization time" (52.0 min vs. 70.0 min; p = 0.019) and the "door to recanalization time" (146 min vs. 183 min; p = 0.013). CONCLUSION: MRA-based road mapping of the para-aortic access route is useful to reduce the procedural time of mechanical thrombectomy in acute stroke patients, possibly by enabling optimal initial catheter selection during the procedure.
• Association between RNF213 c.14576G>A Variant (rs112735431) and Peripheral Pulmonary Artery Stenosis in Moyamoya Disease.

  Dan Ozaki, Hidenori Endo, Ryosuke Tashiro, Koichiro Sugimura, Shunsuke Tatebe, Satoshi Yasuda, Yasutake Tomata, Toshiki Endo, Keita Tominaga, Kuniyasu Niizuma, Miki Fujimura, Teiji Tominaga

  Cerebrovascular diseases (Basel, Switzerland) 51 (3) 282 - 287 2022 

  BACKGROUND: Moyamoya disease (MMD) and peripheral pulmonary artery stenosis (PPAS) are relatively rare and demonstrate steno-occlusive vascular lesions in different organs. Genetic studies identified RNF213 polymorphism c.14576G>A (rs112735431) as a susceptibility variant for East Asian MMD. RNF213 polymorphism c.14576G>A is further associated with various vascular lesions of other organs. In this study, we aimed to clarify the incidence and clinical manifestations of PPAS in MMD patients and analyze the correlation between RNF213 genotype and PPAS. METHODS: This retrospective case-control study investigated the association between RNF213 polymorphism and PPAS in 306 MMD/quasi-MMD patients, reviewing the medical charts and imaging records of consecutive patients with MMD admitted from January 2015 to December 2020. RESULTS: PPAS was observed in 3 MMD/quasi-MMD patients (0.98%, 3/306). RNF213 polymorphism c.14576G>A was determined for all 306 MMD/quasi-MMD patients. The incidence of PPAS in RNF213-wildtype, RNF213-heterozygote, and RNF213-homozygote MMD/quasi-MMD patients was 0% (0/101), 0.5% (1/200), and 40% (2/5), respectively. The association between PPAS and homozygote polymorphism of RNF213 c.14576G>A was statistically significant in MMD/quasi-MMD patients (p = 0.0018). In all cases, pulmonary artery hypertension due to PPAS was evident during their childhood and young adolescent stages. Surgical indications for MMD were discouraged in 1 case due to her severe cardiopulmonary dysfunction. CONCLUSIONS: The homozygote variant of RNF213 polymorphism c.14576G>A can be a potential predisposing factor for PPAS in MMD/quasi-MMD patients. Despite the relatively rare entity, PPAS should be noted to determine surgical indications for MMD/quasi-MMD patients.
• 新規塞栓物質としてのカチオンパイゲルの基礎的実験

  金 芝萍, 長内 俊也, 山崎 和義, 藤村 幹, 野々山 貴之, 黒川 孝幸

  脳血管内治療 (NPO)日本脳神経血管内治療学会 6 (Suppl.) S133 - S133 2423-9119 2021/11
• 脳梗塞:急性期治療 進行性虚血性脳卒中に対するEC-ICバイパス術

  杉山 拓, 伊東 雅基, 長内 俊也, 藤村 幹

  脳循環代謝 (一社)日本脳循環代謝学会 33 (1) 73 - 73 0915-9401 2021/11
• 破裂脳動脈瘤コイル塞栓術後に遅発性のコイル突出を認めた1例

  舘澤 諒大, 長内 俊也, 東海林 菊太郎, 伊東 雅基, 進藤 崇史, 中崎 明日香, 杉山 拓, 藤村 幹

  脳血管内治療 (NPO)日本脳神経血管内治療学会 6 (Suppl.) S248 - S248 2423-9119 2021/11
• びまん性脳血管攣縮による一過性脳虚血発作で発症したHeubner動脈瘤破裂の自然消失 症例報告

  中崎 明日香, 伊東 雅基, 磯部 正則, 藤原 史明, 井須 豊彦, 野村 太一, 数又 研, 長内 俊也, 杉山 拓, 藤村 幹

  脳血管内治療 (NPO)日本脳神経血管内治療学会 6 (Suppl.) S249 - S249 2423-9119 2021/11
• 本学会助成研究の報告 Dual energy CTによる頸動脈プラーク内コレステロール結晶の評価

  齋藤 拓也, 矢澤 由加子, 内田 和孝, 宮城 樹, 川端 雄一, 遠藤 英徳, 斉藤 敦志, 渡辺 みか, 森本 剛, 藤村 幹

  脳循環代謝 (一社)日本脳循環代謝学会 33 (1) 77 - 77 0915-9401 2021/11
• 脳血管障害の病態評価における脳画像の有用性 もやもや病の周術期画像マーカーとRNF213遺伝子多型の関連

  内野 晴登, 伊東 雅樹, 東海林 菊太郎, 舘澤 諒大, 川堀 真人, 数又 研, 宝金 清博, 藤村 幹

  脳循環代謝 (一社)日本脳循環代謝学会 33 (1) 70 - 70 0915-9401 2021/11
• RNF213創始者変異は成人もやもや病複合血行再建術後の間接バイパス路発達に寄与する

  伊東 雅基, 川堀 真人, 杉山 拓, 東海林 菊太郎, 舘澤 諒大, 内野 晴登, 数又 研, 寳金 清博, 藤村 幹

  脳循環代謝 (一社)日本脳循環代謝学会 33 (1) 94 - 94 0915-9401 2021/11
• 破裂脳動脈瘤コイル塞栓術後に遅発性のコイル突出を認めた1例

  舘澤 諒大, 長内 俊也, 東海林 菊太郎, 伊東 雅基, 進藤 崇史, 中崎 明日香, 杉山 拓, 藤村 幹

  脳血管内治療 (NPO)日本脳神経血管内治療学会 6 (Suppl.) S248 - S248 2423-9119 2021/11
• びまん性脳血管攣縮による一過性脳虚血発作で発症したHeubner動脈瘤破裂の自然消失 症例報告

  中崎 明日香, 伊東 雅基, 磯部 正則, 藤原 史明, 井須 豊彦, 野村 太一, 数又 研, 長内 俊也, 杉山 拓, 藤村 幹

  脳血管内治療 (NPO)日本脳神経血管内治療学会 6 (Suppl.) S249 - S249 2423-9119 2021/11
• 脳梗塞:急性期治療 進行性虚血性脳卒中に対するEC-ICバイパス術

  杉山 拓, 伊東 雅基, 長内 俊也, 藤村 幹

  脳循環代謝 (一社)日本脳循環代謝学会 33 (1) 73 - 73 0915-9401 2021/11
• RNF213創始者変異は成人もやもや病複合血行再建術後の間接バイパス路発達に寄与する

  伊東 雅基, 川堀 真人, 杉山 拓, 東海林 菊太郎, 舘澤 諒大, 内野 晴登, 数又 研, 寳金 清博, 藤村 幹

  脳循環代謝 (一社)日本脳循環代謝学会 33 (1) 94 - 94 0915-9401 2021/11
• Prediction of atherosclerotic changes in cavernous carotid aneurysms based on computational fluid dynamics analysis: a proof-of-concept study.

  Shintaro Nakajima, Shinichiro Sugiyama, Hidenori Oishi, Kenichi Sato, Yasushi Matsumoto, Kuniyasu Niizuma, Miki Fujimura, Teiji Tominaga

  Neuroradiology 64 (3) 575 - 585 2021/09/09 

  PURPOSE: Recent computational fluid dynamics (CFD) studies have demonstrated the concurrence of atherosclerotic changes in regions exposed to prolonged blood residence. In this proof-of-concept study, we investigated a small but homogeneous cohort of large, cavernous carotid aneurysms (CCAs) to establish the clinical feasibility of CFD analysis in treatment planning, based on the association between pathophysiology and hemodynamics. METHODS: This study included 15 patients with individual large CCAs. We identified calcifications, which indicated atherosclerotic changes, using the masking data of digital subtraction angiography. We conducted a CFD simulation under patient-specific inlet flow rates measured using magnetic resonance (MR) velocimetry. In the post-CFD analysis, we calculated the blood residence time ([Formula: see text]) and segmented the surface exposed to blood residence time over 1 s ([Formula: see text]). We measured the decrease in volume after flow diversion using the original time-of-flight MR angiography data. RESULTS: Calcifications were observed in the region with [Formula: see text]. In addition, the ratio of [Formula: see text] to the surface of the aneurysmal domain exhibited a negative relationship with the rate of volume reduction at the 6- and 12-month follow-ups. Post-CFD visualization demonstrated that intra-aneurysmal swirling flow prolonged blood residence time under the condition of a small inlet flow rate, when compared to the aneurysmal volume. CONCLUSION: The results of this study suggest the usefulness of CFD analysis for the diagnosis of atherosclerotic changes in large CCAs that may affect the therapeutic response after flow diversion.
• Efficacy of Carotid Artery Stenting Performed under General Anesthesia with Somatosensory Evoked Potential Monitoring.

  Masayuki Gekka, Toshiya Osanai, Takeshi Aoki, Naoki Nakayama, Ken Kazumata, Kiyohiro Houkin, Miki Fujimura

  Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 30 (10) 106007 - 106007 2021/08/15 

  OBJECTIVES: During carotid artery stenting (CAS), hemodynamics may be affected by the carotid sinus reflex in some cases. Although general anesthesia has been reported to stabilize intraoperative hemodynamics, the patient's neurological condition must be assessed indirectly. Therefore, we investigated the changes in intraoperative hemodynamics and perioperative complications of CAS under general anesthesia and evaluated the efficacy of somatosensory evoked potential (SEP) monitoring in detecting a reduction in perfusion during CAS. MATERIALS AND METHODS: From April 2011 to August 2016,57 consecutive patients who underwent CAS under general anesthesia were evaluated. The follow-up period ranged from 3 to 8 years. During CAS, anesthesiologists monitored and managed the hemodynamics. SEP monitoring was performed during the CAS procedure in all patients. RESULTS: Intraoperative hypotension (systolic blood pressure ≤ 100 mmHg) was evident in 16 patients (28.1%), and 13 patients (22.8%) experienced intraoperative bradycardia; however, all of these cases were promptly managed under general anesthesia. None of the patients showed systolic blood pressure < 50 mmHg from baseline. Regarding perioperative complications, none of the patients exhibited myocardial infarction or postoperative hyperperfusion symptoms, and there was no mortality. Among 21 patients (36.8%) with a decrease in the intraoperative SEP, 3 (5.3%) exhibited transient ischemic symptoms and 1 (1.8%) had postoperative infarction. CONCLUSIONS: CAS under general anesthesia is a safe and effective management option in terms of intraoperative hemodynamic stability. In addition, our findings indicate that SEP monitoring could be helpful in evaluating transient postoperative cerebral ischemia or cerebral infarction after CAS.
• Pre-operative higher hematocrit and lower total protein levels are independent risk factors for cerebral hyperperfusion syndrome after superficial temporal artery-middle cerebral artery anastomosis with pial synangiosis in adult moyamoya disease patients-case-control study.

  Masahito Katsuki, Miki Fujimura, Ryosuke Tashiro, Yasutake Tomata, Taketo Nishizawa, Teiji Tominaga

  Neurosurgical review 44 (4) 2191 - 2200 2021/08 

  Superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis is a standard treatment for adult moyamoya disease (MMD) patients. Cerebral hyperperfusion (CHP) syndrome is one of the most serious complications of this procedure that can result in deleterious outcomes, but predicting CHP before revascularization surgery remains challenging. Furthermore, the hematological/serological factors associated with CHP syndrome are unknown. To investigate the correlation between pre-operative hematological/serological factors and the development of CHP syndrome after STA-MCA anastomosis with encephalo-duro-myo-synangiosis (EDMS) for MMD., a pre-operative peripheral blood test was performed within 5 days before surgery. Local cerebral blood flow (CBF) at the site of anastomosis was quantified by N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography 1 and 7 days after surgery, and the pre-operative CBF value at the corresponding area was measured. We defined CHP syndrome as a local CBF increase over 150% compared with the pre-operative value, which was responsible for delayed intracranial hemorrhage, transient focal neurological deterioration, and/or seizure. Then, we retrospectively investigated the correlation between peripheral blood test results and the development of CHP syndrome. CHP syndrome 1 day after STA-MCA anastomosis with EDMS was observed in nine patients (9/114 hemispheres; 7.9%). Multivariate analysis with multiple imputation revealed that higher hematocrit value and lower total protein level were significantly associated with the development of CHP syndrome (p value: 0.028 and 0.043, respectively). Higher pre-operative hematocrit levels and lower pre-operative total protein levels are novel risk factors for CHP syndrome after direct revascularization surgery in adult MMD patients.
• Current concepts and perspectives on brain arteriovenous malformations: A review of pathogenesis and multidisciplinary treatment.

  Taku Sugiyama, Giovanni Grasso, Fabio Torregrossa, Miki Fujimura

  World neurosurgery 2021/07/30 

  Brain arteriovenous malformations (bAVMs) are unusual vascular pathologies characterized by the abnormal aggregation of dilated arteries and veins in the brain parenchyma and for which the absence of a normal vascular structure and capillary bed leads to direct connections between arteries and veins. Although bAVMs have long been believed to be congenital anomalies that develop during the prenatal period, current studies show that inflammation is associated with AVM genesis, growth, and rupture. Interventional treatment options include microsurgery, stereotactic radiosurgery, and endovascular embolization, and management often comprises a multidisciplinary combination of these modalities. The appropriate selection of patients with brain arteriovenous malformations for interventional treatment requires balancing the risk of treatment complications against the risk of hemorrhaging during the natural course of the pathology; however, no definitive guidelines have been established for the management of brain arteriovenous malformations. In this paper, we comprehensively review the current basic and clinical studies on bAVMs and discuss the contemporary status of multidisciplinary management of bAVMs.
• Intraoperative Identification of the Shunt Point of Spinal Arteriovenous Malformations by a Selective Arterial Injection of Saline to Subtract Signals of Indocyanine Green: Technical Note.

  Soichiro Takamiya, Kazuyoshi Yamazaki, Kikutaro Tokairin, Toshiya Osanai, Takashi Shindo, Toshitaka Seki, Miki Fujimura

  World neurosurgery 151 132 - 137 2021/07 

  BACKGROUND: It is crucial to identify a shunt point for spinal arteriovenous malformation (AVM) treatment. For this purpose, some intraoperative supports have been reported-intravenous injection of indocyanine green (ICG), selective arterial injection of ICG, and selective arterial injection of saline with a high frame rate digital camera. However, there are difficulties in accurately identifying the shunt point, especially if the lesion has multiple feeders. The aim of this technical note was to report a novel method, selective arterial injection of saline to subtract signals of ICG, to precisely identify perimedullary arteriovenous fistula shunt points having multiple feeding arteries. METHODS: After exposing the lesion, a 4-F catheter was cannulated into the origins of the segmental artery. ICG was injected intravenously as a first step, and then heparinized saline solution was flushed from the catheter. RESULTS: Compared with other methods, this method could identify the exact shunt point and was effective for certain shunt point obliterations. CONCLUSIONS: Despite having similar invasiveness, selective arterial injection of saline to subtract signals of ICG is superior to previously described techniques, such as selective arterial injection of ICG. Therefore, it will be useful in spinal arteriovenous malformation surgical treatment.
• Flow-augmentation bypass for moyamoya disease.

  Miki Fujimura, Teiji Tominaga

  Journal of neurosurgical sciences 65 (3) 277 - 286 2021/06 

  Moyamoya disease (MMD) is a chronic, occlusive cerebrovascular disease with unknown etiology, which is characterized by progressive steno-occlusive changes at the terminal portion of the internal carotid artery and an abnormal vascular network formation at the base of the brain. MMD has an intrinsic temporal nature to attempt a gradual conversion of the vascular supply for the brain from intracranial/internal carotid (IC) system to extracranial/external carotid (EC) system, so called "IC-EC conversion." Compatible cerebrovascular angio-architecture could be found in association with a variety of conditions such as neuro-fibromatosis type-1, Down's syndrome and cranial irradiation, which is called as moyamoya syndrome, akin/quasi MMD, or secondary MMD. Diagnosis of moyamoya vasculopathy, either idiopathic or secondary, is clinically important because flow-augmentation bypass is markedly beneficial for this entity to prevent cerebral ischemic attack by improving cerebral blood flow. Moreover, recent evidence indicated that flow-augmentation bypass could prevent re-bleeding in hemorrhagic MMD patients. Based on these backgrounds, there is a worldwide increase in the number of MMD patients undergoing bypass surgery. We sought to demonstrate our standard surgical procedure of superficial temporal artery-middle cerebral artery bypass with indirect pial synangiosis for MMD and its technical pitfall. We also discuss the intrinsic peri-operative hemodynamics of MMD after bypass surgery, including local cerebral hyper-perfusion and characteristic hemodynamic ischemia caused by watershed shift phenomenon. The aim of this review article is to understand the basic pathology of MMD, which is essential for complication avoidance while conducting flow-augmentation bypass for MMD.
• Dysregulation of Rnf 213 gene contributes to T cell response via antigen uptake, processing, and presentation.

  Ryosuke Tashiro, Kuniyasu Niizuma, Jun Kasamatsu, Yuko Okuyama, Sherif Rashad, Atsuo Kikuchi, Miki Fujimura, Shigeo Kure, Naoto Ishii, Teiji Tominaga

  Journal of cellular physiology 236 (11) 7554 - 7564 2021/05/10 

  Growing evidence suggest the association between Moyamoya disease (MMD) and immune systems, such as antigen presenting cells in particular. Rnf213 gene, a susceptibility gene for MMD, is highly expressed in immune tissues, however, its function remains unclear. In addition, the physiological role of RNF213 gene polymorphism c.14576G > A (rs112735431), susceptibility variant for MMD, is also poorly understood. By studying Rnf213-knockout (Rnf213-KO) mice with deletion of largest exon32 and Rnf213-knockin (Rnf213-KI) mice with insertion of single-nucleotide polymorphism corresponding to c.14576G > A mutation in MMD patients, we aimed to investigate the role of RNF213 in dendritic cell development, and antigen processing and presentation. First, we found a high level of Rnf213 gene expression in conventional DCs and monocytes. Second, flow cytometric and confocal microscopic analysis revealed ovalbumin protein-pulsed Rnf213-KO and Rnf213-KI DCs showed impaired antigen uptake, proteolysis and reduced numbers of endosomes and lysosomes, and thereby failed to activate and proliferate antigen-specific T cells efficiently. In addition, Rnf213-KI DCs showed a similar phenotype to that of Rnf213-KO BMDCs. In conclusion, our findings suggest the critical role of RNF213 in antigen uptake, processing and presentation.
• Real-world treatment results for ruptured blood-blister aneurysm of the internal carotid artery: analysis of a Japanese nationwide multicenter study.

  Yusuke Egashira, Yukiko Enomoto, Noriyuki Nakayama, Miki Fujimura, Yuichiro Kikkawa, Masanori Aihara, Takatoshi Sorimachi, Takayuki Mizunari, Toru Iwama

  Neurosurgical review 44 (6) 3539 - 3546 2021/04/13 

  Ruptured blood-blister aneurysm (BBA) of the internal carotid artery (ICA) remains a challenging lesion, even in the age of modern neurosurgery and endovascular treatment. This retrospective multicenter study aimed to investigate the real-world treatment choice and treatment results. We included 182 ruptured BBAs of the ICA treated at 51 neurosurgical centers in Japan between 2013 and 2017. The baseline patient characteristics, radiological features of the aneurysm, treatment modality, details of treatment, complications of treatment, and treatment results were retrospectively collected. The treatment strategy was divided into deconstructive and reconstructive procedures. Primary clinical outcomes were evaluated using the modified Rankin scale (mRS) at final follow-up. Direct surgery was performed in 144 (79%) cases, and the remaining 38 (21%) cases received endovascular treatment. The majority of treatment selections were deconstructive and reconstructive procedures in the direct surgery group and endovascular treatment group, respectively. Overall, favorable clinical outcomes (mRS 0 to 2) were achieved in 66% of cases, and the mortality rate was 15% at the final follow-up (mean 23 months). There was no significant difference in clinical outcome between direct and endovascular treatment groups. Our large nationwide study compared the real-world treatment options for ruptured BBAs and their results. Our findings may offer beneficial information for treatment decision and for future studies investigating ruptured BBAs.
• 拡散テンソル画像を用いた急性期脳卒中片麻痺者における皮質網様体路の損傷度と歩行予後との関連

  神 将文, 阿部 浩明, 遠藤 英徳, 藤村 幹

  理学療法学 (公社)日本理学療法士協会 48 (2) 163 - 172 0289-3770 2021/04 

  【目的】本研究の目的は、皮質脊髄路(以下、CST)近傍に病変を有する脳卒中片麻痺者におけるCSTおよび皮質網様体路(以下、CRT)損傷の程度と急性期病院転院時の歩行自立度の予後との関連について明らかにすることである。【方法】対象は、拡散テンソル画像(以下、DTI)の撮像がなされた脳卒中片麻痺者41名であった。急性期病院退(転)院時のFACから歩行可能/介助の2群に分類した。初回評価時のSIASの各項目と撮像したDTIパラメータからCSTおよびCRT損傷の程度を測定し、歩行可能/介助を予測する因子をロジスティック回帰分析にて検討した。【結果】初回評価時のSIAS股関節運動機能が急性期病院転院時の歩行可能/介助を予測する有意な因子であった。一方、歩行能力にかかわるとされているCRTは歩行予後を予測する有意な因子とはならなかった。【結論】急性期病院転院時の歩行予後を予測するうえで、下肢運動機能はCRT損傷の程度よりも重要な因子であると考えられる。(著者抄録)
• Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic.

  Thanh N Nguyen, Diogo C Haussen, Muhammad M Qureshi, Hiroshi Yamagami, Toshiyuki Fujinaka, Ossama Y Mansour, Mohamad Abdalkader, Michael Frankel, Zhongming Qiu, Allan Taylor, Pedro Lylyk, Omer F Eker, Laura Mechtouff, Michel Piotin, Fabricio Oliveira Lima, Francisco Mont'Alverne, Wazim Izzath, Nobuyuki Sakai, Mahmoud Mohammaden, Alhamza R Al-Bayati, Leonardo Renieri, Salvatore Mangiafico, David Ozretic, Vanessa Chalumeau, Saima Ahmad, Umair Rashid, Syed Irteza Hussain, Seby John, Emma Griffin, John Thornton, Jose Antonio Fiorot, Rodrigo Rivera, Nadia Hammami, Anna M Cervantes-Arslanian, Hormuzdiyar H Dasenbrock, Huynh Le Vu, Viet Quy Nguyen, Steven Hetts, Romain Bourcier, Romain Guile, Melanie Walker, Malveeka Sharma, Don Frei, Pascal Jabbour, Nabeel Herial, Fawaz Al-Mufti, Atilla Ozcan Ozdemir, Ozlem Aykac, Dheeraj Gandhi, Chandril Chugh, Charles Matouk, Pascale Lavoie, Randall Edgell, Andre Beer-Furlan, Michael Chen, Monika Killer-Oberpfalzer, Vitor Mendes Pereira, Patrick Nicholson, Vikram Huded, Nobuyuki Ohara, Daisuke Watanabe, Dong Hun Shin, Pedro Sc Magalhaes, Raghid Kikano, Santiago Ortega-Gutierrez, Mudassir Farooqui, Amal Abou-Hamden, Tatsuo Amano, Ryoo Yamamoto, Adrienne Weeks, Elena A Cora, Rotem Sivan-Hoffmann, Roberto Crosa, Markus Möhlenbruch, Simon Nagel, Hosam Al-Jehani, Sunil A Sheth, Victor S Lopez Rivera, James E Siegler, Achmad Fidaus Sani, Ajit S Puri, Anna Luisa Kuhn, Gianmarco Bernava, Paolo Machi, Daniel G Abud, Octavio M Pontes-Neto, Ajay K Wakhloo, Barbara Voetsch, Eytan Raz, Shadi Yaghi, Brijesh P Mehta, Naoto Kimura, Mamoru Murakami, Jin Soo Lee, Ji Man Hong, Robert Fahed, Gregory Walker, Eiji Hagashi, Steve M Cordina, Hong Gee Roh, Ken Wong, Juan F Arenillas, Mario Martinez-Galdamez, Jordi Blasco, Alejandro Rodriguez Vasquez, Luisa Fonseca, M Luis Silva, Teddy Y Wu, Simon John, Alex Brehm, Marios Psychogios, William J Mack, Matthew Tenser, Tatemi Todaka, Miki Fujimura, Roberta Novakovic, Jun Deguchi, Yuri Sugiura, Hiroshi Tokimura, Rakesh Khatri, Michael Kelly, Lissa Peeling, Yuichi Murayama, Hugh Stephen Winters, Johnny Wong, Mohamed Teleb, Jeremy Payne, Hiroki Fukuda, Kosuke Miyake, Junsuke Shimbo, Yusuke Sugimura, Masaaki Uno, Yohei Takenobu, Yuji Matsumaru, Satoshi Yamada, Ryuhei Kono, Takuya Kanamaru, Masafumi Morimoto, Junichi Iida, Vasu Saini, Dileep Yavagal, Saif Bushnaq, Wenguo Huang, Italo Linfante, Jawad Kirmani, David S Liebeskind, Viktor Szeder, Ruchir Shah, Thomas G Devlin, Lee Birnbaum, Jun Luo, Anchalee Churojana, Hesham E Masoud, Carlos Ynigo Lopez, Brendan Steinfort, Alice Ma, Ameer E Hassan, Amal Al Hashmi, Mollie McDermott, Maxim Mokin, Alex Chebl, Odysseas Kargiotis, Georgios Tsivgoulis, Jane G Morris, Clifford J Eskey, Jesse Thon, Leticia Rebello, Dorothea Altschul, Oriana Cornett, Varsha Singh, Jeyaraj Pandian, Anirudh Kulkarni, Pablo M Lavados, Veronica V Olavarria, Kenichi Todo, Yuki Yamamoto, Gisele Sampaio Silva, Serdar Geyik, Jasmine Johann, Sumeet Multani, Artem Kaliaev, Kazutaka Sonoda, Hiroyuki Hashimoto, Adel Alhazzani, David Y Chung, Stephan A Mayer, Johanna T Fifi, Michael D Hill, Hao Zhang, Zhengzhou Yuan, Xianjin Shang, Alicia C Castonguay, Rishi Gupta, Tudor G Jovin, Jean Raymond, Osama O Zaidat, Raul G Nogueira

  Stroke and vascular neurology 2021/03/26 

  BACKGROUND: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study's objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines. METHODS: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation. FINDINGS: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p<0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p<0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile. INTERPRETATION: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction.
• 【脳神経画像Critical Findings-おさえておきたい症状とCT/MRI画像所見】CT/MRIで見落とし・誤認してはいけない疾患 CT isoattenuated/MRI isointense lesions くも膜下出血

  遠藤 英徳, 藤村 幹, 冨永 悌二

  Neurological Surgery (株)医学書院 49 (2) 220 - 228 0301-2603 2021/03 

  ＜文献概要＞Point ・くも膜下出血(SAH)の検出において,CTに加えてMRI FLAIR像やSWIが時として有効である.信号強度のみならず,シルビウス裂の左右差や側脳室下角の拡大にも注意する必要がある.・多発瘤を合併したSAHや微小動脈瘤の破裂部位診断において,vessel wall imaging(VWI)が有効である.・脳動脈解離の画像診断において,basi-parallel anatomical scanning(BPAS)は血管外径の拡張,VWIはintramural hematomaの検出や壁不安定性の評価に有効である.
• Efficacy of arterial spin labeling magnetic resonance imaging with multiple post-labeling delays to predict postoperative cerebral hyperperfusion in carotid endarterectomy.

  Hidenori Endo, Miki Fujimura, Atsushi Saito, Toshiki Endo, Kazumasa Ootomo, Teiji Tominaga

  Neurological research 43 (3) 252 - 258 2021/03 

  Introduction: Cerebral hyperperfusion (CHP) syndrome is one of the most deleterious complications after carotid endarterectomy (CEA). Arterial spin labeling (ASL) is a promising non-invasive method to evaluate various hemodynamic parameters in cerebrovascular diseases. The aim of this study was to clarify whether ASL with multiple post-labeling delays (PLDs) can predict postoperative CHP after CEA. Methods: Sixty-one patients with carotid artery stenosis treated by CEA were retrospectively analyzed. The asymmetry index of the preoperative CBF was obtained from ASL using 3 PLDs (1525 ms, 2025 ms, and 2525 ms) and single-photon emission computed tomography (SPECT). Cerebrovascular reactivity (CVR) was measured from SPECT with acetazolamide challenge. The slope of the regression line obtained from the asymmetry index of three PLDs was defined as the slope index. Results: The CHP phenomenon was observed in seven patients (11.5%), one of whom developed CHP syndrome (1.6%). Using the CHP phenomenon as a reference standard, the area under the receiver operating characteristics (ROC) was 0.68 for the asymmetry index of the preoperative SPECT, 0.71 for the asymmetry index of the preoperative ASL,0.73 for CVR, and 0.78 for the slope index. Using the cutoff value obtained by ROC analysis, the slope index demonstrated a sensitivity of 85%, specificity of 74%, positive predictive value of 30% and the negative predictive value of 98% for predicting CHP. Conclusions: The slope index calculated by ASL with multiple PLDs is a useful screening tool to predict postoperative CHP after CEA.
• [Subarachnoid Hemorrhage].

  Hidenori Endo, Miki Fujimura, Teiji Tominaga

  No shinkei geka. Neurological surgery 49 (2) 220 - 228 2021/03 

  Intracranial aneurysms or arterial dissections are major causes of subarachnoid hemorrhage(SAH). Early surgical or endovascular repair of the bleeding source is crucial because rebleeding mostly occurs within a few days after the initial attack. Radiological examination is an initial step for the appropriate diagnosis of ruptured intracranial aneurysms and arterial dissections. However, misdiagnosis may occur, especially in patients with minor bleeding or multiple aneurysms. In addition to computed tomography, magnetic resonance imaging, including FLAIR and SWI, and T2*WI are useful for detecting minor SAH. Vessel-wall imaging has recently been applied to diagnosing the site of rupture in patients with multiple cerebral aneurysms or microaneurysms, but not to assessing the instability of unruptured cerebral aneurysms or intracranial arterial dissections. In this article, we discuss the current radiological modalities and their usefulness for diagnosing SAH.
• Y-Configuration Stenting for Coil Embolization of Complex Intracranial Aneurysms: Distinguishing Between Use of Crossing-Y and Kissing-Y.

  Kenichi Sato, Yasushi Matsumoto, Atsushi Kanoke, Akira Ito, Miki Fujimura, Teiji Tominaga

  World neurosurgery 146 e1054-e1062  2021/02 

  OBJECTIVE: Coil embolization with Y stenting is recognized as a suitable treatment for complex wide-necked aneurysms. Y stenting comprises crossing-Y stenting, in which a stent is passed through the interstices of another stent, and kissing-Y stenting, in which 2 stents are arranged in parallel. The purpose of this study was to elucidate how to distinguish between use of the 2 Y-stenting techniques. METHODS: Clinical and angiographic data of patients who underwent coil embolization with Y stenting at our department from 2015 to 2019 were retrospectively analyzed. Basic characteristics, endovascular procedure, complications, and outcomes were compared between kissing-Y and crossing-Y stenting groups. RESULTS: Thirty-eight intracranial aneurysms in 38 consecutive patients were included in this study. Nineteen patients (50%) were treated with coil embolization with kissing-Y stenting and 19 (50%) with crossing-Y. Endovascular procedures were successfully performed in all but 1 patient, in the kissing-Y group, who had stent migration. One hemorrhage (2.6%) recurred 12 months after coiling with kissing-Y stenting. Angiographic follow-up (mean, 15.8 months) was available in 35 patients. Adequate occlusion was shown in 14 patients (77.8%) and 13 patients (76.5%) in the kissing-Y and crossing-Y groups, respectively. Larger, wider-necked, and more proximal aneurysms were treated with kissing-Y stenting than with crossing-Y stenting, although there were no significant differences between the groups in complication rates or clinical outcomes. CONCLUSIONS: Kissing-Y and crossing-Y stenting of intracranial aneurysms were both feasible and yielded reasonable angiographic and clinical results. The choice between the kissing-Y or crossing-Y-stenting technique should be decided according to the angioarchitecture of targeted aneurysms.
• Brain Temperature Measured by Magnetic Resonance Spectroscopy to Predict Clinical Outcome in Patients with Infarction.

  Tomohisa Ishida, Takashi Inoue, Tomoo Inoue, Toshiki Endo, Miki Fujimura, Kuniyasu Niizuma, Hidenori Endo, Teiji Tominaga

  Sensors (Basel, Switzerland) 21 (2) 2021/01/12 

  Acute ischemic stroke is characterized by dynamic changes in metabolism and hemodynamics, which can affect brain temperature. We used proton magnetic resonance (MR) spectroscopy under everyday clinical settings to measure brain temperature in seven patients with internal carotid artery occlusion to explore the relationship between lesion temperature and clinical course. Regions of interest were selected in the infarct area and the corresponding contralateral region. Single-voxel MR spectroscopy was performed using the following parameters: 2000-ms repetition time, 144-ms echo time, and 128 excitations. Brain temperature was calculated from the chemical shift between water and N-acetyl aspartate, choline-containing compounds, or creatine phosphate. Within 48 h of onset, compared with the contralateral region temperature, brain temperature in the ischemic lesion was lower in five patients and higher in two patients. Severe brain swelling occurred subsequently in three of the five patients with lower lesion temperatures, but in neither of the two patients with higher lesion temperatures. The use of proton MR spectroscopy to measure brain temperature in patients with internal carotid artery occlusion may predict brain swelling and subsequent motor deficits, allowing for more effective early surgical intervention. Moreover, our methodology allows for MR spectroscopy to be used in everyday clinical settings.
• Intraoperative Early Venous Filling Phenomenon as an Intrinsic Sign of the Local Hemodynamic Change after Revascularization Surgery in a Patient with Adult Moyamoya Disease: Implications of a Potential Arteriovenous Shunt.

  Kikutaro Tokairin, Taku Sugiyama, Masaki Ito, Miki Fujimura

  NMC case report journal 8 (1) 755 - 760 2021 

  After revascularization surgery for patients with moyamoya disease (MMD), local and global hemodynamic changes occur intraoperatively and in the early postoperative period. Local cerebral hyperperfusion and watershed shift ischemia are well-known perioperative pathologies after revascularization for MMD, but early venous filling phenomenon is markedly rare. We report the case of a 19-year-old woman with hemorrhagic-onset MMD who presented with grand mal seizure and subarachnoid hemorrhage. She underwent superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis combined with indirect pial synangiosis on the affected hemisphere. Intraoperatively, notable early arterial blood filling in the fine cortical vein was observed around the site of anastomosis right after the STA-MCA anastomosis under the surgical microscope and fluorescence indocyanine green video angiography. Recovery of consciousness after general anesthesia was normal, although she exhibited a focal seizure 1 hour later. Postoperative magnetic resonance imaging was not remarkable, and cerebral hemodynamics significantly improved in the acute stage after surgical revascularization. Considering the intrinsic vulnerability of the microvascular anatomy of MMD, the present case is notable because early venous filling was observed intraoperatively. This phenomenon suggests the existence of a potential arteriovenous shunt as an underlying pathology of MMD, but its implications in the early postoperative course should be further verified in a larger number of MMD patients undergoing surgical revascularization.
• Stroke Care during the COVID-19 Pandemic: International Expert Panel Review.

  Narayanaswamy Venketasubramanian, Craig Anderson, Hakan Ay, Selma Aybek, Waleed Brinjikji, Gabriel R de Freitas, Oscar H Del Brutto, Klaus Fassbender, Miki Fujimura, Larry B Goldstein, Roman L Haberl, Graeme J Hankey, Wolf-Dieter Heiss, Isabel Lestro Henriques, Carlos S Kase, Jong S Kim, Masatoshi Koga, Yoshihiro Kokubo, Satoshi Kuroda, Kiwon Lee, Tsong-Hai Lee, David S Liebeskind, Gregory Y H Lip, Stephen Meairs, Roman Medvedev, Man Mohan Mehndiratta, Jay P Mohr, Masao Nagayama, Leonardo Pantoni, Panagiotis Papanagiotou, Guillermo Parrilla, Daniele Pastori, Sarah T Pendlebury, Luther Creed Pettigrew, Pushpendra N Renjen, Tatjana Rundek, Ulf Schminke, Yukito Shinohara, Wai Kwong Tang, Kazunori Toyoda, Katja E Wartenberg, Mohammad Wasay, Michael G Hennerici

  Cerebrovascular diseases (Basel, Switzerland) 50 (3) 245 - 261 2021 

  BACKGROUND: Coronavirus disease 2019 (COVID-19) has placed a tremendous strain on healthcare services. This study, prepared by a large international panel of stroke experts, assesses the rapidly growing research and personal experience with COVID-19 stroke and offers recommendations for stroke management in this challenging new setting: modifications needed for prehospital emergency rescue and hyperacute care; inpatient intensive or stroke units; posthospitalization rehabilitation; follow-up including at-risk family and community; and multispecialty departmental developments in the allied professions. SUMMARY: The severe acute respiratory syndrome coronavirus 2 uses spike proteins binding to tissue angiotensin-converting enzyme (ACE)-2 receptors, most often through the respiratory system by virus inhalation and thence to other susceptible organ systems, leading to COVID-19. Clinicians facing the many etiologies for stroke have been sobered by the unusual incidence of combined etiologies and presentations, prominent among them are vasculitis, cardiomyopathy, hypercoagulable state, and endothelial dysfunction. International standards of acute stroke management remain in force, but COVID-19 adds the burdens of personal protections for the patient, rescue, and hospital staff and for some even into the postdischarge phase. For pending COVID-19 determination and also for those shown to be COVID-19 affected, strict infection control is needed at all times to reduce spread of infection and to protect healthcare staff, using the wealth of well-described methods. For COVID-19 patients with stroke, thrombolysis and thrombectomy should be continued, and the usual early management of hypertension applies, save that recent work suggests continuing ACE inhibitors and ARBs. Prothrombotic states, some acute and severe, encourage prophylactic LMWH unless bleeding risk is high. COVID-19-related cardiomyopathy adds risk of cardioembolic stroke, where heparin or warfarin may be preferable, with experience accumulating with DOACs. As ever, arteritis can prove a difficult diagnosis, especially if not obvious on the acute angiogram done for clot extraction. This field is under rapid development and may generate management recommendations which are as yet unsettled, even undiscovered. Beyond the acute management phase, COVID-19-related stroke also forces rehabilitation services to use protective precautions. As with all stroke patients, health workers should be aware of symptoms of depression, anxiety, insomnia, and/or distress developing in their patients and caregivers. Postdischarge outpatient care currently includes continued secondary prevention measures. Although hoping a COVID-19 stroke patient can be considered cured of the virus, those concerned for contact safety can take comfort in the increasing use of telemedicine, which is itself a growing source of patient-physician contacts. Many online resources are available to patients and physicians. Like prior challenges, stroke care teams will also overcome this one. Key Messages: Evidence-based stroke management should continue to be provided throughout the patient care journey, while strict infection control measures are enforced.
• Characteristic Pattern of the Cerebral Hemodynamic Changes in the Acute Stage After Combined Revascularization Surgery for Adult Moyamoya Disease: N-isopropyl-p-[123I] iodoamphetamine Single-Photon Emission Computed Tomography Study.

  Miki Fujimura, Teiji Tominaga

  Acta neurochirurgica. Supplement 132 57 - 61 2021 

  OBJECTIVE: Surgical revascularization for moyamoya disease (MMD) prevents cerebral ischemic attack by improving cerebral blood flow (CBF) and could also reduce the risk of re-bleeding in hemorrhagic-onset patients. We sought to clarify the cerebral hemodynamic changes in the acute stage after revascularization surgery for adult MMD. MATERIALS AND METHODS: The present study includes 54 consecutive adult patients with MMD (21-76 years old, 43.1 average), undergoing superficial temporal artery-middle cerebral artery anastomosis with indirect pial synangiosis on 65 affected hemispheres. We prospectively performed single-photon emission computed tomography (SPECT) at postoperative day (POD) 1 and 7 of 65 surgeries. Perioperative management was conducted with strict blood pressure control (100-130 mmHg) and minocycline hydrochloride administration. RESULTS: The outcome of 65 surgeries was favorable except for one (1.5%), which manifested as delayed intracerebral hemorrhage due to local hyperperfusion. The postoperative SPECT revealed the characteristic CBF improvement pattern with transient local hyperperfusion (POD1) and subsequent distribution of CBF in wider vascular territory (POD7) on 37 hemispheres (56.9%, 37/65). CONCLUSION: The revascularization surgery is a safe and effective treatment for adult MMD, while transient local hyperperfusion should be strictly managed by intensive perioperative care.
• Mesenchymal Stem Cell Sheet Promotes Functional Recovery and Palliates Neuropathic Pain in a Subacute Spinal Cord Injury Model.

  Kazuyoshi Yamazaki, Masahito Kawabori, Toshitaka Seki, Soichiro Takamiya, Kotaro Konno, Masahiko Watanabe, Kiyohiro Houkin, Miki Fujimura

  Stem cells international 2021 9964877 - 9964877 2021 

  Stem cell therapy has been shown to reverse the sequelae of spinal cord injury (SCI). Although the ideal treatment route remains unknown, providing a large number of stem cells to the injured site using less invasive techniques is critical to achieving maximal recovery. This study was conducted to determine whether administration of bone marrow stem cell (BMSC) sheet made on its own without a scaffold is superior to intramedullary cell transplantation in a rat subacute SCI model. Adult female Sprague-Dawley rats were subjected to SCI by 30 g clip compression at the level of Th6 and Th7 and were administered BMSC cell sheet (7 × 104 cells, subdural), cell suspension (7 × 104 cells, intramedullary), or control seven days after the injury. Motor and sensory assessments, as well as histological evaluation, were performed to determine the efficacy of the different cell transplantation procedures. While both the cell sheet and cell intramedullary injection groups showed significant motor recovery compared to the control group, the cell sheet group showed better results. Furthermore, the cell sheet group displayed a significant sensory recovery compared to the other groups. A histological evaluation revealed that the cell sheet group showed smaller injury lesion volume, less inflammation, and gliosis compared to other groups. Sensory-related fibers of μ-opioid receptors (MOR, interneuron) and hydroxytryptamine transporters (HTT, descending pain inhibitory pathway), located around the dorsal horn of the spinal cord at the caudal side of the SCI, were preserved only in the cell sheet group. Stem cells could also be found inside the peri-injured spinal cord in the cell sheet group. BMSC cell sheets were able to promote functional recovery and palliate neuropathic pain more effectively than intramedullary injections, thus serving as a good treatment option for SCI.
• Unilateral chronic subdural hematoma due to spontaneous intracranial hypotension: a report of four cases.

  Yoshinari Osada, Ichiyo Shibahara, Atsuhiro Nakagawa, Hiroyuki Sakata, Kuniyasu Niizuma, Ryuta Saito, Masayuki Kanamori, Miki Fujimura, Shinsuke Suzuki, Teiji Tominaga

  British journal of neurosurgery 34 (6) 632 - 637 2020/12 [Refereed][Not invited]
   

  Background: Chronic subdural hematoma (CSDH) is a common neurosurgical disease. A subset of patients with CSDH may exhibit underlying spontaneous intracranial hypotension (SIH). Bilateral CSDH has a causal relationship with SIH, but there is no known causal relationship between unilateral CSDH and SIH.Case description: We encountered four cases of unilateral CSDH due to SIH. The patients' age ranged between 44 and 64 years; there were three males and one female. All patients presented with headache as their initial symptom, and then became comatose. Computed tomography demonstrated unilateral CSDH and transtentorial herniation in all patients. Treatments were emergency epidural blood patch (EBP) and evacuation of CSDH. The site of cerebrospinal fluid leak could not be identified in three patients; therefore, EBP was performed at upper and lower spine. All patients recovered from SIH; however, one patient experienced poor outcome due to Duret hemorrhage and ischemic complications of transtentorial herniation. Cranial asymmetry was present in all four patients, and unilateral CSDH was located on the side of the most curved cranial convexity.Conclusions: Unilateral CSDH, asymmetric cranial morphology, and transtentorial herniation in relatively young patients may indicate underlying SIH.
• Multiple Post-Labeling DelayによるASLを用いたCEA周術期脳循環動態評価

  遠藤 英徳, 藤村 幹, 斉藤 敦志, 遠藤 俊毅, 大友 一匡, 井上 敬, 江面 正幸, 上之原 広司, 冨永 悌二

  脳循環代謝 (一社)日本脳循環代謝学会 32 (1) 104 - 104 0915-9401 2020/11
• 3D ASL法と123I-IMP SPECT併用による脳血流予備能評価と可能性について

  大友 一匡, 遠藤 英徳, 杉山 慎一郎, 藤村 幹, 冨永 悌二

  脳循環代謝 (一社)日本脳循環代謝学会 32 (1) 106 - 106 0915-9401 2020/11
• Vessel wall MRIによる脳動脈瘤の瘤壁造影効果 脳動脈瘤壁の質的診断

  遠藤 英徳, 面高 俊介, 新妻 邦泰, 藤村 幹, 佐藤 健一, 井上 敬, 江面 正幸, 上之原 広司, 冨永 悌二

  脳血管内治療 (NPO)日本脳神経血管内治療学会 5 (Suppl.) 21 - 21 2423-9119 2020/11
• もやもや病の最新研究・治療 成人もやもや病に対するバイパス術後の遅発性過灌流とRNF213遺伝子c.14576G>A多型の関連についての検討

  藤村 幹, 田代 亮介, 勝木 将人, 西澤 威人, 遠又 靖丈, 新妻 邦泰, 冨永 悌二

  脳循環代謝 (一社)日本脳循環代謝学会 32 (1) 70 - 70 0915-9401 2020/11
• 3D time-of-flight MRAを用いた成人もやもや病に対する頭蓋外内バイパス術後過灌流症候群の予測

  西澤 威人, 藤村 幹, 勝木 将人, 田代 亮介, 佐藤 健一, 麦倉 俊司, 冨永 悌二

  脳循環代謝 (一社)日本脳循環代謝学会 32 (1) 112 - 112 0915-9401 2020/11
• Multiple Post-Labeling DelayによるASLを用いたCEA周術期脳循環動態評価

  遠藤 英徳, 藤村 幹, 斉藤 敦志, 遠藤 俊毅, 大友 一匡, 井上 敬, 江面 正幸, 上之原 広司, 冨永 悌二

  脳循環代謝 (一社)日本脳循環代謝学会 32 (1) 104 - 104 0915-9401 2020/11
• 3D ASL法と123I-IMP SPECT併用による脳血流予備能評価と可能性について

  大友 一匡, 遠藤 英徳, 杉山 慎一郎, 藤村 幹, 冨永 悌二

  脳循環代謝 (一社)日本脳循環代謝学会 32 (1) 106 - 106 0915-9401 2020/11
• Prolonged/delayed cerebral hyperperfusion in adult patients with moyamoya disease with RNF213 gene polymorphism c.14576G>A (rs112735431) after superficial temporal artery-middle cerebral artery anastomosis.

  Ryosuke Tashiro, Miki Fujimura, Masahito Katsuki, Taketo Nishizawa, Yasutake Tomata, Kuniyasu Niizuma, Teiji Tominaga

  Journal of neurosurgery 1 - 8 2020/10/23 

  OBJECTIVE: Superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis is the standard surgical management for moyamoya disease (MMD), whereas cerebral hyperperfusion (CHP) is one of the potential complications of this procedure that can result in delayed intracerebral hemorrhage and/or neurological deterioration. Recent advances in perioperative management in the early postoperative period have significantly reduced the risk of CHP syndrome, but delayed intracerebral hemorrhage and prolonged/delayed CHP are still major clinical issues. The clinical implication of RNF213 gene polymorphism c.14576G>A (rs112735431), a susceptibility variant for MMD, includes early disease onset and a more severe form of MMD, but its significance in perioperative pathology is unknown. Thus, the authors investigated the role of RNF213 polymorphism in perioperative hemodynamics after STA-MCA anastomosis for MMD. METHODS: Among 96 consecutive adult patients with MMD comprising 105 hemispheres who underwent serial quantitative cerebral blood flow (CBF) analysis by N-isopropyl-p-[123I]iodoamphetamine SPECT after STA-MCA anastomosis, 66 patients consented to genetic analysis of RNF213. Patients were routinely maintained under strict blood pressure control during and after surgery. The local CBF values were quantified at the vascular territory supplied by the bypass on postoperative days (PODs) 1 and 7. The authors defined the radiological CHP phenomenon as a local CBF increase of more than 150% compared with the preoperative values, and then they investigated the correlation between RNF213 polymorphism and the development of CHP. RESULTS: CHP at POD 1 was observed in 23 hemispheres (23/73 hemispheres [31.5%]), and its incidence was not statistically different between groups (15/41 [36.6%] in RNF213-mutant group vs 8/32 [25.0%] in RNF213-wild type (WT) group; p = 0.321). CHP on POD 7, which is a relatively late period of the CHP phenomenon in MMD, was evident in 9 patients (9/73 hemispheres [12.3%]) after STA-MCA anastomosis. This prolonged/delayed CHP was exclusively observed in the RNF213-mutant group (9/41 [22.0%] in the RNF213-mutant group vs 0/32 [0.0%] in the RNF213-WT group; p = 0.004). Multivariate analysis revealed that RNF213 polymorphism was significantly associated with CBF increase on POD 7 (OR 5.47, 95% CI 1.06-28.35; p = 0.043). CONCLUSIONS: Prolonged/delayed CHP after revascularization surgery was exclusively found in the RNF213-mutant group. Although the exact mechanism underlying the contribution of RNF213 polymorphism to the prolonged/delayed CBF increase in patients with MMD is unclear, the current study suggests that genetic analysis of RNF213 is useful for predicting the perioperative pathology of patients with MMD.
• 3D ASLとI-IMP SPECTによる脳血流予備能評価と可能性について

  大友 一匡, 遠藤 英徳, 杉山 慎一郎, 遠藤 俊毅, 藤村 幹

  核医学 (一社)日本核医学会 57 (Suppl.) S163 - S163 0022-7854 2020/10
• Carotid web leads to new thrombus formation: computational fluid dynamic analysis coupled with histological evidence.

  Dan Ozaki, Toshiki Endo, Hiroyoshi Suzuki, Shin-Ichiro Sugiyama, Kaoru Endo, Ryo Itabashi, Miki Fujimura, Teiji Tominaga

  Acta neurochirurgica 162 (10) 2583 - 2588 2020/10 

  Carotid web has been recognized as a rare cause of ischemic stroke with high recurrence rate. We describe a 48-year-old woman with carotid web who developed embolic stroke. We obtained a fresh thrombus from the internal carotid artery when carotid endarterectomy was performed. A preoperative computational fluid dynamics (CFD) study showed stagnation of blood around the web structure as well as the low wall shear stress. The rheological analysis newly disclosed mechanisms of thrombus formation related to the carotid web. CFD study in the carotid web may determine indication and timing of surgical interventions with further accumulation of clinical evidence.
• Slowly progressive cerebral amyloid angiopathy-related inflammation: Characteristic findings of sequential magnetic resonance imaging.

  Keita Tominaga, Tomohiro Kawaguchi, Miki Fujimura, Atsushi Saito, Mika Watanabe, Teiji Tominaga

  Clinical neurology and neurosurgery 197 106198 - 106198 2020/10
• Supraclinoid Internal Carotid Artery Fenestration with Associated Aneurysm: Case Report and Literature Review.

  Shinya Haryu, Kenichi Sato, Yasushi Matsumoto, Toshiki Endo, Miki Fujimura, Teiji Tominaga

  NMC case report journal 7 (4) 183 - 187 2020/09 

  Fenestration of the supraclinoid internal carotid artery (ICA) is extremely rare and may occasionally be associated with saccular aneurysms; nevertheless, the natural history remains unclear. The authors reviewed the cases of fenestration of the supraclinoid ICA and evaluated the clinical characteristics and angioarchitecture with particular focus on the incidence for aneurysm development and rupture. Previously reported 24 cases and 1 new case from our institute were examined for the presence of aneurysms (including size and presence of bleb) leading to subsequent subarachnoid hemorrhage (SAH). Furthermore, 16 cases with sufficient information were classified into one of the three types according to the developmental condition of fenestration and fusion site: Type A (developed fenestration in which the ICA appears to duplicate [two cases]); Type B (hypoplastic fenestration fused to the ICA at the origin of the posterior communicating artery [Pcom] [six cases]); and Type C (hypoplastic fenestration fused to the Pcom itself or appeared to be a duplicated Pcom [eight cases]). In type A, the two cases had an aneurysm (100%), one of which caused SAH (50%). In type B, all six cases had an aneurysm (100%), and one of five led to SAH (20%) (one case lacked information regarding SAH). In type C, five of the eight cases had an aneurysm (62.5%), with no SAH (0%). The result suggested that the extent of development of fenestration and the location of fusion are related to the incidence of aneurysms and risk for rupture.
• Direct Inspection with Dual Endoscope Technique via Bilateral Transforaminal Approach Leading to Complete Resection of Recurrent Colloid Cyst of the Third Ventricle.

  Atsushi Nakayashiki, Tomohiro Kawaguchi, Kuniyasu Niizuma, Mika Watanabe, Miki Fujimura, Teiji Tominaga

  World neurosurgery 141 272 - 277 2020/09 [Refereed][Not invited]
   

  BACKGROUND: Although endoscopic approaches are widely used for resection of colloid cysts because of the lower invasiveness, removal of the recurrent colloid cyst is still challenging. Total removal is sometimes difficult to achieve with single-port endoscopy because of the restricted access and working space. To compensate for these limitations, the dual endoscope technique via the bilateral transforaminal approach was chosen. CASE DESCRIPTION: A 34-year-old woman with recurrent colloid cyst of the third ventricle was admitted to our department. She had a history of endoscopic subtotal removal at another institution. Reoperation was scheduled and the endoscopic bilateral transforaminal approach was chosen to ensure total removal with minimum complication risk. After decompression, the cyst was retracted toward the third ventricle floor via the right foramen of Monro. Under direct inspection with an angled scope via the right foramen of Monro, the cyst attachment on the third ventricle roof was sharply dissected via the left foramen of Monro, resulting in total removal. CONCLUSIONS: The dual endoscope technique via the bilateral transforaminal approach can achieve better surgical outcome by obtaining direct visualization of the cyst attachment. Although the indication should be limited, this approach can be considered especially for patients with recurrent lesions involving possible adhesion to vital structures.
• Focal Cerebellar Hyperperfusion After Bypass Surgery for Vertebrobasilar Ischemia: Effect of Cerebrovascular Reactivity as a Potential Predictor of Hyperperfusion.

  Hidenori Endo, Miki Fujimura, Taketo Nishizawa, Atsushi Saito, Teiji Tominaga

  World neurosurgery 140 101 - 106 2020/08 [Refereed][Not invited]
   

  BACKGROUND: Hyperperfusion in the posterior circulation is a rare complication after surgical revascularization for vertebrobasilar steno-occlusive diseases. We report a case of symptomatic cerebellar hyperperfusion after superficial temporal artery-superior cerebellar artery bypass for vertebrobasilar ischemia. CASE DESCRIPTION: A 59-year-old man was admitted with brainstem infarction. Angiography showed bilateral vertebral artery occlusion with poor collateral circulation. Preoperative single-photon emission computed tomography revealed that bilateral cerebellar blood flow was markedly decreased. The cerebrovascular reactivity of the bilateral cerebellum, as measured by single-photon emission computed tomography with acetazolamide challenge, showed steal phenomenon. Superficial temporal artery-superior cerebellar artery anastomosis on the right side was performed through a subtemporal approach. The day after surgery, the patient exhibited temporary disorientation and the local cerebellar blood flow increased up to 182% on the right side of the cerebellum from preoperative levels. We considered that the disorientation was caused by the hyperperfusion, and the blood pressure was strictly controlled. The cerebellar blood flow then gradually decreased to 133% over preoperative levels by 1 week after surgery. The patient did not show further neurologic worsening. CONCLUSIONS: Serial hemodynamic study is useful for early detection of hyperperfusion. Steal phenomenon in the preoperative hemodynamic study could be one of the risk factors for postoperative hyperperfusion even in the posterior circulation.
• Frequent Clinical and Radiological Progression of Optic Pathway/Hypothalamic Pilocytic Astrocytoma in Adolescents and Young Adults.

  Takuhiro Shoji, Masayuki Kanamori, Ryuta Saito, Yuko Watanabe, Mika Watanabe, Miki Fujimura, Yoshikazu Ogawa, Yukihiko Sonoda, Toshihiro Kumabe, Shigeo Kure, Teiji Tominaga

  Neurologia medico-chirurgica 60 (6) 277 - 285 2020/06/15 [Refereed][Not invited]
   

  Most cases of optic hypothalamic pilocytic astrocytoma (OHPA) develop during childhood, so few cases of histologically verified OHPA have been described in adolescents and young adults (AYA). To elucidate the clinical features of OHPA with histological verification in AYA, we reviewed the clinical and radiological finding of OHPA treated at our institute from January 1997 and July 2017. AYA are aged between 15 and 39 years. The clinical courses of 11 AYA patients with optic hypothalamic glioma (OHG) without neurofibromatosis type 1 were retrospectively reviewed. About six patients were diagnosed in childhood and followed up after 15 years of age, and five patients developed OHPA during AYA. Histological diagnosis, verified at initial presentation or recurrence, was pilocytic astrocytoma in 10 and pilomyxoid astrocytoma in one. After initial treatment including debulking surgery and/or chemotherapy, tumor progression occurred 16 times in seven patients as cyst formation, tumor growth, and intratumoral hemorrhage. Five of 10 patients suffered deterioration of visual function during AYA. One of 10 cases had endocrinopathies requiring hormone replacement at last follow-up examination. In conclusion, histological diagnoses of OHG before and in AYA were pilocytic astrocytoma or pilomyxoid astrocytoma. Both pediatric and AYA-onset OHPA demonstrate high incidences of tumor progression and visual dysfunctions in AYA, so that long-term follow up is essential after the completion of treatment for pediatric and AYA-onset OHPA. The optimal timing of debulking surgery and radiation therapy should be established to achieve the long-term tumor control and to preserve the visual function.
• Symptomatic Cerebral Hyperperfusion After Cerebral Vasospasm Associated with Aneurysmal Subarachnoid Hemorrhage.

  Hiroyuki Sakata, Hidenori Endo, Miki Fujimura, Kuniyasu Niizuma, Teiji Tominaga

  World neurosurgery 137 379 - 383 2020/05 [Refereed][Not invited]
   

  BACKGROUND: Cerebral hyperperfusion syndrome, which carries a potential risk of intracranial hemorrhage, is a rare and overlooked condition in the setting of subarachnoid hemorrhage (SAH). CASE DESCRIPTION: A 72-year-old female presenting with SAH underwent clipping of a ruptured aneurysm of the left middle cerebral artery. On post-SAH day 7, the patient exhibited motor aphasia due to cerebral vasospasm of the left middle cerebral artery. After recovery from symptomatic cerebral vasospasm, the patient became restless and suffered from right hemiparesis on post-SAH day 12. Initially, recurrence of cerebral vasospasm was suspected; however, cerebral blood flow measurement using single-photon emission computed tomography revealed apparently increased perfusion in the same territory of the left middle cerebral artery. Hypertensive therapy was not induced during the postoperative period. Her neurologic symptoms and signs of cerebral hyperperfusion gradually improved with intensive blood pressure lowering. CONCLUSIONS: This is the first report to describe postischemic cerebral hyperperfusion syndrome after symptomatic vasospasm detected using sequential single-photon emission computed tomography during the acute stage of SAH. Early diagnosis of this rare phenomenon is crucial given the necessity to lower blood pressure for preventing hemorrhagic complications, which is contrary to the usual management of patients with vasospasm.
• Author Correction: The hemodynamic complexities underlying transient ischemic attacks in early-stage Moyamoya disease: an exploratory CFD study.

  Sherif Rashad, Khalid M Saqr, Miki Fujimura, Kuniyasu Niizuma, Teiji Tominaga

  Scientific reports 10 (1) 6217 - 6217 2020/04/07 [Refereed][Not invited]
   

  An amendment to this paper has been published and can be accessed via a link at the top of the paper.
• Persistent Local Vasogenic Edema with Dynamic Change in the Regional Cerebral Blood Flow after STA-MCA Bypass for Adult Moyamoya Disease.

  Kokoro Kawamura, Miki Fujimura, Ryosuke Tashiro, Atsushi Kanoke, Atsushi Saito, Teiji Tominaga

  Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 29 (4) 104625 - 104625 2020/04 

  We report an adult moyamoya disease (MMD) patient who developed persistent local vasogenic edema with dynamic change in the regional cerebral blood flow after left superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis. A 49-year-old woman with ischemic-onset MMD underwent left STA-MCA anastomosis. Magnetic resonance (MR) imaging of fluid-attenuated inversion recovery 1 day after surgery revealed an asymptomatic local high-signal-intensity lesion at the site of anastomosis, and MR angiography demonstrated apparently patent STA-MCA bypass. Due to the increased apparent diffusion coefficient value, we diagnosed the lesion as vasogenic edema. A significant increase in focal cerebral blood flow (CBF) at the site of the anastomosis was observed on N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography (123I-IMP-SPECT) (139.8%; compared with the preoperative value). Under strict blood pressure control (systolic blood pressure under 130 mmHg), the patient remained asymptomatic during the entire peri-operative period, but the 123I-IMP-SPECT 7 days after surgery suggested paradoxical CBF decrease (72.9%). Based on this finding, we allow the patient to be maintained under normotensive condition (∼160 mmHg), which recovered the CBF (115.0%) 14 days after surgery. Vasogenic edema remained during the entire peri-operative period, but completely disappeared 83 days after surgery. Local vasogenic edema formation due to cerebral hyperperfusion is not uncommon after STA-MCA anastomosis for adult MMD, but dynamic CBF change at the site of persistent local vasogenic edema after STA-MCA anastomosis is extremely rare. We recommend serial CBF measurement in the acute stage after revascularization surgery for MMD, especially when MR imaging demonstrates local signal intensity change.
• Iatrogenic Pseudoaneurysm at the Deep Temporal Artery after Fronto-temporal Craniotomy Manifesting as Repeated Subcutaneous Hemorrhage -Case Report.

  Masahito Katsuki, Miki Fujimura, Kenichi Sato, Yasushi Matsumoto, Teiji Tominaga

  NMC case report journal 7 (2) 67 - 70 2020/04 

  Iatrogenic pseudoaneurysm formation at the deep temporal artery (DTA) is a rare complication after neurosurgical intervention by craniotomy, and its management strategy has yet to be determined. We report a patient who developed iatrogenic pseudoaneurysm at the DTA after fronto-temporal craniotomy manifesting as repeated subcutaneous hemorrhage. A 44-year-old man underwent standard fronto-temporal craniotomy for the microsurgical clipping of a ruptured anterior communicating artery aneurysm in the acute stage. The initial postoperative course was uneventful, but he developed a massive subcutaneous hematoma that penetrated the surgical wound, leading to hypovolemic shock 23 days after the aneurysm surgery. Due to the continuous hemorrhage after temporary hemostasis by ligation of the superficial temporal artery, he underwent catheter angiography, which revealed a newly-formed pseudoaneurysm at the DTA that was 16 mm in diameter. Neuroendovascular obliteration of the pseudoaneurysm was successfully performed using liquid embolization material, n-butyl-2-cyanoacrylate, under local anesthesia. Pseudoaneurysm at the DTA is a rare but possible complication after fronto-temporal craniotomy, which can be fatal due to marked hemorrhage. Due to the anatomically deep location of the DTA under the temporal muscle, we recommend accurate diagnosis of the pseudoaneurysm by catheter angiography and prompt obliteration of the affected vessel by a neuroendovascular procedure under local anesthesia, especially when the hemodynamic status is unstable.
• Optimal Timing of Extracranial-Intracranial Bypass with Microsurgical Trapping for Ruptured Blister Aneurysms of the Internal Carotid Artery.

  Hidenori Endo, Miki Fujimura, Hiroaki Shimizu, Toshiki Endo, Shunsuke Omodaka, Takashi Inoue, Kenichi Sato, Kuniyasu Niizuma, Teiji Tominaga

  World neurosurgery 136 e567-e577  2020/04 [Refereed][Not invited]
   

  OBJECTIVE: Ruptured blister aneurysms of the internal carotid artery are challenging to treat because of their difficult diagnosis and the fragility of the wall structure. Here, we sought to clarify the efficacy of extracranial-intracranial bypass followed by trapping (bypass/trapping) for ruptured blister aneurysms. METHODS: A retrospective study identified 45 patients with ruptured blister aneurysms between 1998 and 2017. Our principle was to attempt bypass/trapping as early as possible after diagnosis (early surgery). If early diagnosis was difficult, patients underwent elective surgery in the later stage when aneurysms were detected (elective surgery). Patient characteristics, radiologic findings, clinical course, and outcomes were analyzed. RESULTS: Forty-three patients were treated by bypass/trapping. Twenty-eight patients were classified as early surgery and 15 as elective surgery. Two patients experienced fatal rebleeding and did not undergo surgery. All 15 patients in the elective surgery group showed rebleeding and/or aneurysmal growth while awaiting surgery. In the elective surgery group, 10 aneurysms were missed initially by catheter angiography. In the early surgery group, 9 patients were assessed by vessel wall magnetic resonance imaging, which showed circumferential enhancement along the aneurysm wall, most of which was shown as only a small bulge in the angiography. Postoperative rebleeding did not occur in any of the patients. CONCLUSIONS: Bypass/trapping is effective to prevent rebleeding. Early surgery may be beneficial, because most patients in the elective surgery group showed rebleeding or aneurysmal growth. Vessel wall magnetic resonance imaging is a useful adjunct for early diagnosis and may contribute to prompt early surgery.
• Impact of cortical hemodynamic failure on both subsequent hemorrhagic stroke and effect of bypass surgery in hemorrhagic moyamoya disease: a supplementary analysis of the Japan Adult Moyamoya Trial.

  Jun C Takahashi, Takeshi Funaki, Kiyohiro Houkin, Satoshi Kuroda, Miki Fujimura, Yasutake Tomata, Susumu Miyamoto

  Journal of neurosurgery 134 (3) 940 - 945 2020/03/13 [Refereed][Not invited]
   

  OBJECTIVE: Here, the authors aimed to determine whether the presence of cerebral hemodynamic failure predicts subsequent bleeding attacks and how it correlates with the effect of direct bypass surgery in hemorrhagic moyamoya disease. METHODS: Data from the Japanese Adult Moyamoya (JAM) Trial were used in this study: 158 hemispheres in 79 patients. A newly formed expert panel evaluated the SPECT results submitted at trial enrollment and classified the cortical hemodynamic state of the middle cerebral artery territory of each hemisphere into one of the following three groups: SPECT stage (SS) 0 as normal, SS1 as decreased cerebrovascular reserve (CVR), and SS2 as decreased CVR with decreased baseline blood flow. In the nonsurgical cohort of the JAM Trial, the subsequent hemorrhage rate during the 5-year follow-up was compared between the SS0 (hemodynamic failure negative) and SS1+2 (hemodynamic failure positive) groups. The effect of direct or combined direct/indirect bypass surgery on hemorrhage prevention was examined in each subgroup. RESULTS: The hemodynamic grade was SS0 in 59 (37.3%) hemispheres, SS1 in 87 (55.1%), and SS2 in 12 (7.6%). In the nonsurgical cohort, subsequent hemorrhage rates in the SS0 and SS1+2 groups were 12 cases per 1000 person-years and 67 cases per 1000 person-years, respectively. Kaplan-Meier analysis revealed that hemorrhagic events were significantly more common in the SS1+2 group (p = 0.019, log-rank test). Cox regression analysis showed that hemodynamic failure was an independent risk factor for subsequent hemorrhage (HR 5.37, 95% CI 1.07-27.02). In the SS1+2 subgroup, bypass surgery significantly suppressed hemorrhagic events during 5 years (p = 0.001, HR 0.16, 95% CI 0.04-0.57), with no significant effect in the SS0 group (p = 0.655, HR 1.56, 95% CI 0.22-11.10). Examination of effect modification revealed that the effect of surgery tended to differ nonsignificantly between these two subgroups (p = 0.056). CONCLUSIONS: Hemodynamic failure is an independent risk factor for subsequent hemorrhage in hemorrhagic moyamoya disease. Direct bypass surgery showed a significant preventive effect in the hemodynamically impaired hemispheres. Thus, hemodynamic failure, as well as previously proposed factors such as choroidal anastomosis, should be considered for the surgical indication in hemorrhagic moyamoya disease.Clinical trial registration no.: C000000166 (umin.ac.jp).
• The hemodynamic complexities underlying transient ischemic attacks in early-stage Moyamoya disease: an exploratory CFD study.

  Sherif Rashad, Khalid M Saqr, Miki Fujimura, Kuniyasu Niizuma, Teiji Tominaga

  Scientific reports 10 (1) 3700 - 3700 2020/02/28 [Refereed][Not invited]
   

  Moyamoya disease (MMD) is a rare cerebro-occlusive disease with unknown etiology that can cause both ischemic and hemorrhagic stroke. MMD is characterized by progressive stenosis of the terminal internal carotid artery (ICA) and development of basal brain collaterals. Early-stage MMD is known to cause hemodynamic insufficiency despite mild or moderate stenosis of the intracranial arteries, but the exact mechanism underlying this pathophysiological condition is undetermined. We used high-resolution Large Eddy Simulations to investigate multiple complex hemodynamic phenomena that led to cerebral ischemia in five patients with early-stage MMD. The effects of transitional flow, coherent flow structures and blood shear-thinning properties through regions of tortuous and stenosed arteries were explored and linked to symptomatology. It is evidently shown that in some cases complex vortex structures, such as Rankine-type vortices, redirects blood flow away from some arteries causing significant reduction in blood flow. Moreover, partial blood hammer (PBH) phenomenon was detected in some cases and led to significant hemodynamic insufficiency. PBH events were attributed to the interaction between shear-thinning properties, transitional flow structures and loss of upstream pressure-velocity phase lag. We clearly show that the hemodynamic complexities in early-stage MMD could induce ischemia and explain the non-responsiveness to antiplatelet therapy.
• Successful endoscopic identification of the bleeding source in the ventral dura of the cervical spine in a case of superficial siderosis.

  Yoshimichi Sato, Toshiki Endo, Tomoo Inoue, Miki Fujimura, Teiji Tominaga

  Journal of neurosurgery. Spine 1 - 4 2020/02/21 

  The authors report on the case of a 65-year-old man suffering progressive gait disturbance and hearing impairment due to superficial siderosis (SS). According to the literature, repeated hemorrhage into the subarachnoid space causes SS; however, the bleeding source remains unknown in half of SS patients. In the presented case, preoperative MRI revealed a fluid-filled intraspinal cavity extending from C2 to T8 with a dural defect at the ventral C7 level. During surgery, the dural defect was seen to connect to the intraspinal cavity filled with xanthochromic fluid. Importantly, endoscopic observation verified that the rupture of fragile bridging veins in the cavity was the definite bleeding source. Postoperative MRI confirmed disappearance of the intraspinal cavity, and the patient's symptoms gradually improved. The use of endoscopy helped to establish the diagnosis and led to definite treatment. Fragile bridging veins in the fluid-filled interdural layers were novelly verified as a bleeding source in SS. Recognizing this phenomenon is important since it can establish closure of the dural defect as a definite treatment in SS with an intraspinal cavity.
• 【脳動脈瘤】脳動脈瘤手術の今後の可能性

  遠藤 英徳, 佐藤 健一, 杉山 慎一郎, 藤村 幹, 冨永 悌二

  脳神経外科ジャーナル 日本脳神経外科コングレス 29 (2) 86 - 93 0917-950X 2020/02 

  脳動脈瘤手術は、顕微鏡の導入、内視鏡や各種モニタリング技術の発展とともに進化を遂げ、確立した治療手段として普及した。しかし近年、血管内治療の目覚ましい発展に伴い、脳動脈瘤手術を取り巻く環境は混沌としている。これまで、International Subarachnoid Aneurysm Trial(ISAT)をはじめ、治療の優越に関する議論が中心であったが、hybrid surgeonが登場した最近では、治療の協働・分担・補完に関する考え方も重要となりつつある。今後は、イメージング、流体解析、分子生物学を駆使し、病態理解を深めたうえで、個々の症例に合わせて治療の最適化を目指すべきであると考える。(著者抄録)
• Enlargement of a Middle Cerebral Artery Aneurysm after Intra-Aneurysmal Embolization with Parent Artery Preservation for an Ipsilateral Large Internal Carotid Artery Aneurysm: A Case Report.

  Varadaraya Satyanarayan Shenoy, Miki Fujimura, Atsushi Saito, Kenichi Sato, Yasushi Matsumoto, Shin-Ichiro Sugiyama, Hidenori Endo, Teiji Tominaga

  Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 29 (2) 104550 - 104550 1052-3057 2020/02 [Refereed][Not invited]
   

  We report a 77-year-old woman with marked enlargement of a middle cerebral artery (MCA) aneurysm 4 years after the successful intra-aneurysmal embolization of an ipsilateral large internal carotid artery (ICA) aneurysm. She intially presented with right third cranial nerve palsy due to a large ICA aneurysm, 20.8 mm in diameter. Initial magnetic resonance angiography (MRA) revealed a signal decrease in the right MCA, suggesting hemodynamic disturbance based on the contrast pooling in the right large ICA aneurysm exhibiting "Windkessel phenomenon". The large ICA aneurysm was successfully managed by intra-aneurysmal embolization with parent artery preservation, and immediate post-treatment MRA demonstrated significant signal recovery in the right MCA. Meticulous follow-up by MRA identified sudden growth in the aneurysmal height within 1 week after embolization, with further growth over the following 4 years, necessitating microsurgical clipping. Enlargement of the ipsilateral distal aneurysm following the treatment of proximal large aneurysm could be altered by marked distal hemodynamic change in view of the sudden amelioration of the "Windkessel phenomenon". Thus, we recommend meticulous follow-up of the associated distal aneurysm after the management of proximal large or giant aneurysms with parent artery preservation.
• Future potential and challenges of aneurysm surgery

  Hidenori Endo, Kenichi Sato, Shin‒Ichiro Sugiyama, Miki Fujimura, Teiji Tominaga

  Japanese Journal of Neurosurgery 29 (2) 86 - 93 0917-950X 2020 

  Cerebral aneurysm surgery became well‒established after the introduction and widespread use of the surgical microscope, endoscopy, and monitoring techniques. However, recent advancements in endovascular techniques have changed the treatment environment. In the past, superiority or inferiority of surgery compared to endovascular treatment was the main issue in determining management strategies for cerebral aneurysms, as shown by the International Subarachnoid Aneurysm Trial or the Barrow Ruptured Aneurysm Trial. Today, however, this competition is transforming into a more collaborative relationship as hybrid surgeons who are familiar with both open surgery and endovascular treatment are increasing in number. It will be crucial to individualize the treatment strategy for each aneurysm patient using modern imaging techniques, computational flow dynamics, and molecular biology.
• Prediction of Cerebral Hyperperfusion after Superficial Temporal Artery-Middle Cerebral Artery Anastomosis by Three-Dimensional-Time-of-Flight Magnetic Resonance Angiography in Adult Patients with Moyamoya Disease.

  Taketo Nishizawa, Miki Fujimura, Masahito Katsuki, Shunji Mugikura, Ryosuke Tashiro, Kenichi Sato, Teiji Tominaga

  Cerebrovascular diseases (Basel, Switzerland) 49 (4) 396 - 403 2020 

  INTRODUCTION: Superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis is an effective surgical procedure for adult patients with moyamoya disease (MMD) and is known to have the potential to prevent cerebral ischemia and/or hemorrhagic stroke. Cerebral hyperperfusion (CHP) syndrome is one of the serious complications of this procedure that can result in deleterious outcomes, such as delayed intracerebral hemorrhage, but the prediction of CHP before revascularization surgery remains challenging. The present study evaluated the diagnostic value of preoperative three-dimensional (3D)-time-of-flight (TOF) magnetic resonance angiography (MRA) for predicting CHP after STA-MCA anastomosis for MMD. MATERIALS AND METHODS: The signal intensity of the peripheral portion of the intracranial major arteries, such as the anterior cerebral artery (ACA), MCA, and posterior cerebral artery (PCA) ipsilateral to STA-MCA anastomosis, on preoperative MRA was graded (0-2 in each vessel) according to the ability to visualize each vessel on 97 affected hemispheres in 83 adult MMD patients. Local cerebral blood flow (CBF) at the site of anastomosis was quantitatively measured by N-isopropyl-p-[123I]-iodoamphetamine single-photon emission computed tomography 1 and 7 days after surgery, in addition to the preoperative CBF value at the corresponding area. Then, we investigated the correlation between the preoperative MRA score and the development of CHP. RESULTS: The CHP phenomenon 1 day after STA-MCA anastomosis (local CBF increase over 150% compared with the preoperative value) was evident in 27 patients (27/97 hemispheres; 28%). Among them, 8 (8 hemispheres) developed CHP syndrome. Multivariate analysis revealed that the hemispheric MRA score (0-6), the summed ACA, MCA, and PCA scores for the affected hemisphere, was significantly associated with the development of CHP syndrome (p = 0.011). The hemispheric MRA score was also significantly correlated with the CHP phenomenon, either symptomatic or asymptomatic (p < 0.001). CONCLUSION: The signal intensity of the intracranial major arteries, including the ACA, MCA, and PCA, on preoperative 3D-TOF MRA may identify adult MMD patients at higher risk for CHP after direct revascularization surgery.
• Efficacy of intra-arterial indocyanine green angiography for the microsurgical treatment of dural arteriovenous fistula: A case report.

  Keisuke Sasaki, Hidenori Endo, Kuniyasu Niizuma, Yasuo Nishijima, Shinichiro Osawa, Miki Fujimura, Teiji Tominaga

  Surgical neurology international 11 46 - 46 2020 [Refereed][Not invited]
   

  Background: In this study, we report a case of dural arteriovenous fistula (dAVF) that was successfully treated using intra-arterial indocyanine green (IA-ICG) videoangiography during open surgery. Moreover, the findings of IA-ICG videoangiography were compared with those of intraoperative digital subtraction angiography (DSA). Case Description: A 72-year-old male patient with a history of hypertension, hyperlipidemia, and thrombocytosis presented with generalized seizure. DSA revealed Cognard Type III dAVF in the superior wall of the left transverse sinus, which was fed by a single artery (the left occipital artery [OA]) and drained into a single vein (the left temporal cortical vein), without drainage into a venous sinus. Since transarterial embolization was considered challenging due to the tortuosity of the left OA, surgical interruption of the shunt was performed by craniotomy. After excising the feeding artery, we were unable to observed dAVF on intraoperative DSA. However, IA-ICG videoangiography revealed the remaining shunt, which was fed by the collateral route from the feeding artery. The shunting point and draining vein were then surgically resected to eliminate the shunt. The shunt was not observed during the second IA-ICG videoangiography conducted after resection. Conclusion: ICG videoangiography is a better method compared with DSA in terms of visualizing fine vascular lesions. In contrast to the typical intravenous administration, selective IA-ICG can be repeatedly injected at a minimal dose. IA-ICG is a useful intraoperative tool that can be used to evaluate the elimination of the dAVF.
• Hemodynamic analysis of the recipient parasylvian cortical arteries for predicting postoperative hyperperfusion during STA-MCA bypass in adult patients with moyamoya disease.

  Jianjian Zhang, Sirui Li, Miki Fujimura, Tsz Yeung Lau, Xiaolin Wu, Miao Hu, Hanpei Zheng, Haibo Xu, Wenyuan Zhao, Xiang Li, Jincao Chen

  Journal of neurosurgery 1 - 8 2019/12/27 

  OBJECTIVE: Superficial temporal artery-middle cerebral artery (STA-MCA) bypass is a common approach for treating moyamoya disease (MMD); however, the selection of recipient vessels is still controversial, and its relationship with postoperative cerebral hyperperfusion (CHP) has not been revealed. The aim of the study was to investigate the relationship between the hemodynamic sources of the recipient parasylvian cortical arteries (PSCAs) and the occurrence of postoperative CHP. METHODS: The authors retrospectively analyzed the clinical data from 68 adult patients (75 hemispheres) with MMD who underwent STA-MCA bypass. Based on their hemodynamic sources from the MCA and non-MCAs, the PSCAs were classified as M-PSCAs and non-M-PSCAs, and their distributional characteristics were studied. Moreover, the patients' demographics, incidence of postoperative CHP, and post- and preoperative relative cerebral blood flow values were examined. RESULTS: The digital subtraction angiography analysis demonstrated that 40% (30/75) of the recipient PSCAs had no hemodynamic relationship with the MCA. The post- and preoperative relative cerebral blood flow values of the M-PSCA group were significantly higher than those of the non-M-PSCA group (p < 0.001). Multivariate analysis revealed that the hemodynamic source of PSCAs from the MCA was significantly associated with the development of focal (p = 0.003) and symptomatic (p = 0.021) CHP. Twelve (85.7%) of the 14 patients with symptomatic CHP and all 4 (100%) patients with postoperative hemorrhage were from the M-PSCA group. CONCLUSIONS: This study revealed that direct anastomoses of PSCAs with anterograde hemodynamic sources from the MCA had a high risk of postoperative CHP during STA-MCA bypass in adult patients with MMD.
• Neuro-endoscopic management of hemorrhagic moyamoya disease in the acute stage: single institute experience.

  Masaki Mino, Miki Fujimura, Hidenori Endo, Toshiki Endo, Kenichi Sato, Teiji Tominaga

  Neurological research 41 (12) 1097 - 1103 0161-6412 2019/12 [Refereed][Not invited]
   

  Background: Management of hemorrhagic moyamoya disease (MMD) is one of the most challenging issues in neurosurgical practice. Recently, surgical revascularization by superficial temporal artery-middle cerebral artery anastomosis was reported to significantly reduce the risk of re-bleeding in hemorrhagic-onset MMD patients in the chronic state, but the optimal treatment strategy in the acute phase of hemorrhagic MMD is undetermined. Thus, we retrospectively analyzed our surgical results for hemorrhagic MMD in the acute stage, focusing on the efficacy of neuro-endoscopic management for hematoma removal. Materials and methods: Among 26 consecutive hemorrhagic MMD patients who were managed at our institution in the acute stage, 8 patients with intracerebral hemorrhage underwent surgical evacuation of the hematoma. All patients were diagnosed with MMD before surgery by magnetic resonance angiography and/or catheter angiography. Results: The initial surgical procedure was neuro-endoscopic hematoma removal in seven patients and microsurgical hematoma removal by craniotomy in one patient. One patient treated by the neuro-endoscopic procedure required subsequent small craniotomy due to difficulty in hemostasis. Satisfactory hematoma evacuation was achieved in all eight patients, as demonstrated by post-operative computed tomography, although one patient who was deeply comatose before surgery died in the early post-operative period. Conclusion: Neuro-endoscopic hematoma removal may be the optimal management method for hemorrhagic MMD in the acute stage in terms of the maximum preservation of pre-existing collateral anastomosis without affecting the potential donor vessels used for future revascularization surgery. Abbreviations: MMD: Moyamoya disease; STA: Superficial temporal artery; MCA: Middle cerebral artery; JAM: Japan Adult Moyamoya; ICH: Intracerebral hemorrhage; IVH: Intraventricular hemorrhage; SAH: Subarachnoid hemorrhage; CT: Computed tomography; TE: Total evacuation; PE: Partial evacuation; SMR: Light mass reduction; MR: Magnetic resonance; mRS: Modified Rankin scale; GCS: Glasgow Coma Scale; ICP: Intracranial pressure.
• Development of Hemorrhage-prone Anastomoses in Asymptomatic Moyamoya Disease-A Comparative Study with Japan Adult Moyamoya Trial.

  Shusuke Yamamoto, Takeshi Funaki, Miki Fujimura, Jun C Takahashi, Haruto Uchino, Kiyohiro Houkin, Teiji Tominaga, Susumu Miyamoto, Satoshi Kuroda

  Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 28 (11) 104328 - 104328 1052-3057 2019/11 [Refereed][Not invited]
   

  OBJECTIVE: Present study was aimed to precisely evaluate the angio-architectures in patients with asymptomatic moyamoya disease (MMD) by comparing with those with hemorrhagic stroke. METHODS: This study used the data set of cerebral angiography in Asymptomatic Moyamoya Registry (AMORE) Study and Japan Adult Moyamoya (JAM) Trial at enrollment. The development of 3 subtypes of collateral vessels, including lenticulostriate, thalamic, and choroidal anastomosis, was evaluated on cerebral angiography. Suzuki's angiographical stage and posterior cerebral artery (PCA) involvement were also assessed. These findings were compared between asymptomatic (AMORE) and hemorrhagic (JAM) groups. RESULTS: This study included 55 hemispheres of 35 patients in asymptomatic group and 75 hemispheres of 75 patients in hemorrhagic group. In asymptomatic group, thalamic anastomosis was less developed than in hemorrhagic group (P = .011), but there were no significant differences in the development of lenticulostriate and choroidal anastomosis between the 2 groups (P = .077 and P = .26, respectively). Suzuki's stage was more progressed and the prevalence of PCA involvement was significantly higher in hemorrhagic group than in asymptomatic group (P = .0033 and P = .016, respectively). CONCLUSIONS: This study reveals no significant differences in the development of choroidal anastomoses between asymptomatic and hemorrhagic-onset MMD. On the other hand, disease stage and PCA involvement were less advanced in asymptomatic MMD than in hemorrhagic-onset MMD. These findings strongly suggest a certain subgroup of asymptomatic patients with MMD is at potential risk for hemorrhagic stroke.
• A novel model of cerebral hyperperfusion with blood-brain barrier breakdown, white matter injury, and cognitive dysfunction.

  Ahmed Mansour, Sherif Rashad, Kuniyasu Niizuma, Miki Fujimura, Teiji Tominaga

  Journal of neurosurgery 1 - 13 0022-3085 2019/10/18 [Refereed][Not invited]
   

  OBJECTIVE: Cerebral hyperperfusion (CHP) is associated with considerable morbidity. Its pathophysiology involves disruption of the blood-brain barrier (BBB) with subsequent events such as vasogenic brain edema and ischemic and/or hemorrhagic complications. Researchers are trying to mimic the condition of CHP; however, a proper animal model is still lacking. In this paper the authors report a novel surgically induced CHP model that mimics the reported pathophysiology of clinical CHP including BBB breakdown, white matter (WM) injury, inflammation, and cognitive impairment. METHODS: Male Sprague-Dawley rats were subjected to unilateral common carotid artery (CCA) occlusion and contralateral CCA stenosis. Three days after the initial surgery, the stenosis of CCA was released to induce CHP. Cortical regional cerebral blood flow was measured using laser speckle flowmetry. BBB breakdown was assessed by Evans blue dye extravasation and matrix metalloproteinase-9 levels. WM injury was investigated with Luxol fast blue staining. Cognitive function was assessed using the Barnes circular maze. Other changes pertaining to inflammation were also assessed. Sham-operated animals were prepared and used as controls. RESULTS: Cerebral blood flow was significantly raised in the cerebral cortex after CHP induction. CHP induced BBB breakdown evident by Evans blue dye extravasation, and matrix metalloproteinase-9 was identified as a possible culprit. WM degeneration was evident in the corpus callosum and corpus striatum. Immunohistochemistry revealed macrophage activation and glial cell upregulation as an inflammatory response to CHP in the striatum and cerebral cortex. CHP also caused significant impairments in spatial learning and memory compared with the sham-operated animals. CONCLUSIONS: The authors report a novel CHP model in rats that represents the pathophysiology of CHP observed in various clinical scenarios. This model was produced without the use of pharmacological agents; therefore, it is ideal to study the pathology of CHP as well as to perform preclinical drug trials.
• Circumferential wall enhancement in evolving intracranial aneurysms on magnetic resonance vessel wall imaging.

  Omodaka S, Endo H, Niizuma K, Fujimura M, Inoue T, Endo T, Sato K, Sugiyama SI, Tominaga T

  Journal of neurosurgery 131 1262 - 1268 0022-3085 2019/10 [Refereed][Not invited]
  
• Genetic analysis of ring finger protein 213 (RNF213) c.14576G>A polymorphism in patients with vertebral artery dissection: a comparative study with moyamoya disease.

  Ryosuke Tashiro, Miki Fujimura, Hiroyuki Sakata, Hidenori Endo, Yasutake Tomata, Mika Sato-Maeda, Kuniyasu Niizuma, Teiji Tominaga

  Neurological research 41 (9) 811 - 816 0161-6412 2019/09 [Refereed][Not invited]
   

  Background: Intracranial vertebral artery dissection (VAD) and moyamoya disease (MMD) are rare cerebrovascular diseases, both of which have an ethnic predominance in the East Asian population. Disruption of the internal elastic lamina and subsequent rupture of the medial layer result in intracranial VAD. MMD is a chronic occlusive cerebrovascular disease of unknown etiology, in which the medial layer and internal elastic lamina of the intracranial arteries are significantly compromised. Recent genetic studies found ring finger protein 213 (RNF213) to be an important susceptibility gene for MMD in East Asian patients, but the association between VAD and RNF213 has not been investigated. . Methods: We investigated polymorphism of the RNF213 gene (c.14576G>A) in genomic DNA of 24 patients with intracranial VAD in comparison with 58 patients with definitive MMD and 48 healthy controls. Results: Although RNF213 gene polymorphism (c.14576G>A) was evident in 69% of the MMD patients (40/58), none of the patients with intracranial VAD had this characteristic polymorphism (0/24, p < 0.001). The incidence of RNF213 c.14576G>A polymorphism was 4.2% in healthy controls (2/48). After adjustment by age and sex, the incidence of RNF213 c.14576G>A was significantly lower in intracranial VAD patients (p = 0.021) than that in MMD patients. Conclusions: In contrast to MMD patients, the prevalence of RNF213 c.14576G>A polymorphism was significantly lower in patients with intracranial VAD. The RNF213 gene polymorphism may preferentially affect the cerebrovascular lesion in the anterior circulation, which is originated from the primitive internal carotid arteries. The genetic background underlying intracranial VAD should be elucidated in future studies. Abbreviations: VAD: vertebral artery dissection; MMD: moyamoya disease; RNF213: ring finger protein 213; CAD: carotid artery dissection.
• Massive Intramedullary Hemorrhage After Subarachnoid Hemorrhage in Patient with Vertebrovertebral Arteriovenous Fistula.

  Inoue T, Endo T, Sato K, Fesli R, Ogawa Y, Fujimura M, Matsumoto Y, Tominaga T

  World neurosurgery 129 432 - 436 1878-8750 2019/09 [Refereed][Not invited]
  
• Coexistence of Intracranial Germ Cell Tumor with Growing Arteriovenous Fistula.

  Ishida T, Endo H, Saito R, Kanamori M, Sato K, Matsumoto Y, Endo T, Fujimura M, Tominaga T

  World neurosurgery 127 126 - 130 1878-8750 2019/07 [Refereed][Not invited]
   

  BACKGROUND: A 26-year-old man was admitted with complaints of progressive depressive mood and general fatigue. Magnetic resonance imaging revealed diffuse enhanced lesions in the neurohypophyseal, pineal, and paraventricular regions and ventricular wall. CASE DESCRIPTION: Endoscopic biopsy confirmed the presence of germ cell tumor, and chemoradiation therapy (CRT) was then performed. Most of the tumors disappeared after CRT except for the right paraventricular lesion. Follow-up magnetic resonance imaging performed 14 months after CRT showed enlargement of this residual lesion. In addition to tumor growth, coexistent flow void signals within the tumor increased. Angiographically, this vascular lesion mimicked arteriovenous malformation, which was mainly fed by the lenticulostriate artery and drained into the internal cerebral vein. Transarterial embolization was performed, resulting in effective flow reduction. Subsequently, the tumor was resected without complications. It was histopathologically diagnosed as a mature teratoma with an arteriovenous fistula (AVF). Arterial components were observed to directly connect to venous components within the tumor without any intermediate nidal components. CONCLUSIONS: To the best of our knowledge, this is the first reported case of an intracranial germ cell tumor coexistent with a growing AVF. AVF developed within a CRT-refractory teratomatous component, which was successfully treated with embolization followed by surgical resection.
• Tailor-Made Branch Reconstruction by Intracranial to Intracranial Bypass During Clipping Surgery for Middle Cerebral Artery Aneurysms.

  Sato K, Endo H, Fujimura M, Endo T, Shimizu H, Tominaga T

  World neurosurgery 127 e1152 - e1158 1878-8750 2019/07 [Refereed][Not invited]
  
• Intrinsic development of choroidal and thalamic collaterals in hemorrhagic-onset moyamoya disease: case-control study of the Japan Adult Moyamoya Trial.

  Miki Fujimura, Takeshi Funaki, Kiyohiro Houkin, Jun C Takahashi, Satoshi Kuroda, Yasutake Tomata, Teiji Tominaga, Susumu Miyamoto

  Journal of neurosurgery 130 (5) 1453 - 1459 0022-3085 2019/05/01 [Refereed][Not invited]
   

  OBJECTIVE: This study was performed to identify the angiographic features of hemorrhagic-onset moyamoya disease (MMD) in comparison with those of patients with ischemic-onset MMD. METHODS: This case-control study compared the data set of the Japan Adult Moyamoya (JAM) Trial with the angiographic data of adult patients with ischemic-onset MMD. The authors analyzed angiograms obtained at onset, classifying the collaterals into 3 subtypes: lenticulostriate anastomosis, thalamic anastomosis, and choroidal anastomosis. They then compared the extent of these collaterals, as indicated by the collateral development grade from 0 to 2 in each subtype, between the JAM Trial group and the ischemic-onset group. They also compared the involvement of the posterior cerebral artery (PCA) and Suzuki's angiographic staging between each group. RESULTS: Among 89 ischemic-onset patients, 103 symptomatic hemispheres in 80 patients were analyzed and compared with 75 hemorrhagic hemispheres from the JAM Trial. The hemorrhagic-onset patients showed a significantly higher proportion of thalamic anastomosis (p = 0.043) and choroidal anastomosis (< 0.001), as indicated by grade 2 in each subtype, compared with ischemic-onset patients. Suzuki's angiographic staging was significantly higher in the hemorrhagic group (< 0.038). There was no difference in the extent of lenticulostriate anastomosis and PCA involvement between the groups. CONCLUSIONS: In adult MMD, the characteristic pattern of the abnormal vascular networks at the base of the brain is different between each onset type. In light of the more prominent development of thalamic and choroidal anastomosis in the JAM Trial group in the present study, development of these collaterals, especially the choroidal collateral extending beyond the lateral ventricle, may play a critical role in hemorrhagic presentation in MMD.Clinical trial registration no. C000000166 (http://www.umin.ac.jp/ctr/index.htm).
• Efficacy of Direct Revascularization Surgery for Hemorrhagic Moyamoya Syndrome As a Late Complication of Cranial Irradiation for Childhood Craniopharyngioma.

  Kato Y, Fujimura M, Sato K, Endo H, Tominaga T

  Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 28 (5) e46 - e50 1052-3057 2019/05 [Refereed][Not invited]
  
• Clipping of an anterior spinal artery aneurysm using an endoscopic fluorescence imaging system for craniocervical junction epidural arteriovenous fistula: technical note.

  Mansour A, Endo T, Inoue T, Sato K, Endo H, Fujimura M, Tominaga T

  Journal of neurosurgery. Spine 1 - 6 1547-5654 2019/04 [Refereed][Not invited]
  
• Application of neuro-endoscopic target aspiration of the necrotic core for cerebral contusion with delayed progression: technical note

  Masaki Mino, Miki Fujimura, Masahiro Yoshida, Shinya Sonobe, Teiji Tominaga

  Acta Neurochirurgica 161 (2) 225 - 230 0942-0940 2019/02/13 

  Background: The optimal management strategy for cerebral contusion remains controversial, especially when standard craniotomy could not be used. We performed neuro-endoscopic target lesionectomy for the delayed progression of cerebral contusion in order to aspirate the necrotic core, which is the primal source of contusional edema. Methods: The present study included 10 consecutive patients (2 women and 8 men, with a mean age of 67 years old) with traumatic brain injury presenting with delayed deterioration of cerebral contusion where standard craniotomy could not be used. Neuro-endoscopic aspiration of the necrotic core was prospectively performed for all patients. We assessed the computed tomography findings after surgery to evaluate the efficacy of this procedure. Results: Endoscopic surgery was performed promptly after neurological deterioration, with a mean interval between trauma and surgery of 7 days, ranging from 2 to 16 days. During the operation, the centers of contusions comprised serous liquid components in all 10 patients and were easily aspirated by endoscopy. Contusional edemas were markedly decreased in all within 3 days after surgery. Conclusions: Progression of contusional edema can be caused by the accumulation of water into the necrotic core due to the rapid increase in osmolality. In light of the highly liquefied demarcated characteristics of the necrotic core, neuro-endoscopic aspiration could be an optional treatment strategy for cerebral contusion with delayed progression in a minimally invasive manner.
• Effect of choroidal collateral vessels on de novo hemorrhage in moyamoya disease: analysis of nonhemorrhagic hemispheres in the Japan Adult Moyamoya Trial.

  Takeshi Funaki, Jun C Takahashi, Kiyohiro Houkin, Satoshi Kuroda, Miki Fujimura, Yasutake Tomata, Susumu Miyamoto

  Journal of neurosurgery 132 (2) 408 - 414 2019/02/08 [Refereed][Not invited]
   

  OBJECTIVE: Following hemorrhagic stroke in moyamoya disease, de novo intracranial hemorrhage can occur in the previously unaffected nonhemorrhagic hemisphere. In the present analysis the authors intended to determine whether the presence in the nonhemorrhagic hemisphere of choroidal collateral vessels, which have been the focus of attention as a source of bleeding, affects the risk of de novo hemorrhage. METHODS: The subject of focus of the present cohort study was the nonhemorrhagic hemispheres of adult patients with hemorrhagic moyamoya disease enrolled in the Japan Adult Moyamoya Trial and allocated to the nonsurgical arm. The variable of interest was the presence of choroidal collaterals (also termed choroidal anastomoses), identified with baseline angiography and represented by a connection (anastomosis) between the anterior or posterior choroidal arteries and the medullary arteries. The outcome measure was de novo hemorrhage during the 5-year follow-up period, assessed in all nonhemorrhagic hemispheres. The incidence of de novo hemorrhage in the collateral-positive and -negative groups was compared. RESULTS: Choroidal collaterals were present in 15 of 36 (41.7%) nonhemorrhagic hemispheres analyzed. The overall annual risk of de novo hemorrhage was 2.0%. Three de novo hemorrhages occurred in the collateral-positive group, whereas no hemorrhage occurred in the collateral-negative group. The annual risk of de novo hemorrhage was significantly higher in the collateral-positive group than in the collateral-negative group (5.8% per year vs 0% per year; p = 0.017). All hemorrhage sites corresponded to the distribution of choroidal collaterals. CONCLUSIONS: The present preliminary results suggest that the presence of choroidal collaterals affects the risk of de novo hemorrhage in the nonhemorrhagic hemisphere, subject to verification in larger studies. Further studies are needed to determine the optimal treatment strategy for nonhemorrhagic hemispheres and asymptomatic patients.
• High rebleeding risk associated with choroidal collateral vessels in hemorrhagic moyamoya disease: analysis of a nonsurgical cohort in the Japan Adult Moyamoya Trial.

  Takeshi Funaki, Jun C Takahashi, Kiyohiro Houkin, Satoshi Kuroda, Shigekazu Takeuchi, Miki Fujimura, Yasutake Tomata, Susumu Miyamoto

  Journal of neurosurgery 130 (2) 337 - 673 2019/02/01 [Refereed][Not invited]
   

  OBJECTIVEChoroidal collateral vessels typical of moyamoya disease have received attention as a potential bleeding source. The authors' previous angiographic cross-sectional analysis suggested a possible association between choroidal collaterals and posterior hemorrhage, indicating a high risk for rebleeding. The present longitudinal analysis is intended to determine whether choroidal collaterals are a predictor of rebleeding in hemorrhagic moyamoya disease.METHODSThe Japan Adult Moyamoya Trial group designed an ancillary cohort study using 5-year follow-up data on 37 patients included in the nonsurgical arm of the original randomized controlled trial and compared the rebleeding rate of those with and those without choroidal collaterals, represented by the connection between the anterior or posterior choroidal arteries and the medullary arteries. An expert panel determined whether a choroidal collateral was present in each patient through the measurement of baseline angiography studies. The rebleeding rate comparison was adjusted for age, diagnosis of hypertension, and involvement of the posterior cerebral artery.RESULTSChoroidal collaterals were present in 21 patients (56.8%). The rebleeding rate was 13.1% per year in the collateral-positive group as compared with 1.3% in the negative group (p = 0.008, log-rank test). The adjusted hazard ratio for rebleeding in the collateral-positive group relative to the negative group remained statistically significant (HR 11.10, 95% CI 1.37-89.91). Radiographic assessment of the collateral-positive group revealed good correspondence between the distribution of collaterals and rebleeding sites.CONCLUSIONSResults of this study suggest that choroidal collaterals are a bleeding source with a high risk for hemorrhagic recurrence and a predictor of rebleeding in hemorrhagic moyamoya disease.
• Moyamoya disease： Modern diagnostic criteria and current status revascularization surgery

  Miki Fujimura, Teiji Tominaga

  Japanese Journal of Neurosurgery 28 (12) 789 - 795 0917-950X 2019 

  Moyamoya disease (MMD) is a progressive cerebrovascular disease with unknown etiology, characterized by steno‒occlusive changes at the terminal portion of the internal carotid artery and an abnormal vascular network formation at the base of the brain. The diagnostic criteria for MMD were updated in 2015 and included not only typical MMD patients with bilateral involvement but also patients with unilateral involvement and/or with atherosclerosis into definitive MMD. Surgical interventions including revascularization surgery comprising direct bypass has been known to prevent cerebral ischemic attack by improving cerebral blood flow and, as more recently shown, could reduce the potential risk of re‒bleeding in MMD patients with posterior hemorrhage, who have regular and extremely high re‒bleeding rate. Based on modern diagnostic criteria and increasing evidence for revascularization surgery, more MMD patients have lately undergone bypass surgery. We therefore aimed to review modern diagnostic criteria and indication of surgical revascularization for MMD.
• Identification of HLA-DRB1*04:10 allele as risk allele for Japanese moyamoya disease and its association with autoimmune thyroid disease: A case-control study.

  Ryosuke Tashiro, Kuniyasu Niizuma, Seik-Soon Khor, Katsushi Tokunaga, Miki Fujimura, Hiroyuki Sakata, Hidenori Endo, Hidetoshi Inoko, Koetsu Ogasawara, Teiji Tominaga

  PloS one 14 (8) e0220858  2019 [Refereed][Not invited]
   

  BACKGROUND AND PURPOSE: Moyamoya disease (MMD) is a progressive cerebrovascular disease with unknown etiology. Growing evidence suggest its involvement of autoimmune and genetic mechanisms in the pathogenesis of MMD. This study aims to clarify the association between HLA allele and MMD. METHODS: Case-control study: the DNA of 136 MMD patients in Japan was extracted and the genotype of human leukocyte antigen (HLA) from this DNA was determined by super-high-resolution single-molecule sequence-based typing using next-generation sequencing. Next, the frequency of each HLA allele (HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1, and HLA-DPB1) was compared with those in the Japanese control database. In addition, haplotype estimation was performed using the expectation maximization algorithm. RESULTS: The frequencies of the HLA-DRB1*04:10 allele (4.77% vs. 1.47% in the control group; P = 1.7 × 10-3; odds ratio [OR] = 3.35) and of the HLA-DRB1*04:10-HLA-DQB1*04:02 haplotype (haplotype frequency 4.41% vs. 1.35% in the control group; P = 2.0 × 10-3; OR = 3.37) significantly increased. The frequency of thyroid diseases, such as Graves' disease and Hashimoto thyroiditis, increased in HLA-DRB1*04:10-positive MMD patients compared with that in HLA-DRB1*04:10-negative MMD patients. CONCLUSIONS: HLA-DRB1*04:10 is a risk allele and HLA-DRB1*04:10-HLA-DQB1*04:02 a risk haplotype for MMD. In addition, HLA-DRB1*04:10 is associated with thyroid disease in MMD patients.
• Diagnostic Value of Contrast-Enhanced Magnetic Resonance Vessel Wall Imaging on the Onset Type of Vertebral Artery Dissection.

  Atsushi Saito, Miki Fujimura, Hidenori Endo, Shunsuke Omodaka, Atsushi Kanoke, Kenichi Sato, Teiji Tominaga

  Cerebrovascular diseases (Basel, Switzerland) 48 (3-6) 124 - 131 1015-9770 2019 [Refereed][Not invited]
   

  BACKGROUND: Circumferential enhancement along the aneurysm wall (CEAW) by magnetic resonance (MR) vessel wall imaging has been reported to be a useful indicator for the biological activity of intracranial aneurysms such as growth and rupture. However, the significance of CEAW in vertebral artery dissection (VAD) has not been examined in detail. We quantitatively analyzed CEAW on VAD focusing on the differences in the clinical onset type. METHODS: The subjects were 37 patients diagnosed with VAD who were evaluated by MR imaging in the acute phase of onset between January 2014 and May 2019. The clinical onset of VAD was categorized into 3 subtypes: (1) incidentally detected (incidental group), (2) sudden headache without cerebral ischemia and/or intracranial hemorrhage (headache group), and (3) hemorrhagic onset (hemorrhage group). Three-dimensional T1-weighted fast spin echo sequences were obtained before and after contrast material injection, and the contrast ratio (CR) of the aneurysm wall against the pituitary stalk was calculated as the indicator of CEAW. RESULTS: The CR values of VAD in the hemorrhage group were significantly higher than those in the headache group (0.95 vs. 0.65, p < 0.05), and the headache group had significantly higher CR values than the incidental group (0.65 vs. 0.56, p < 0.05). On receiver operating characteristic curve analysis, the optimal cutoff value of CR to distinguish the hemorrhage group from the headache group was 0.83 and that to distinguish the headache group from the incidental group was 0.61. CONCLUSION: The extent of CEAW precisely reflected the deleterious impact of VAD in the acute stage, including hemorrhagic presentation. The predictive value of CEAW for the prognosis of unruptured VAD should be evaluated in future studies.
• Significance of Quantitative Cerebral Blood Flow Measurement in the Acute Stage after Revascularization Surgery for Adult Moyamoya Disease: Implication for the Pathological Threshold of Local Cerebral Hyperperfusion.

  Masayuki Kameyama, Miki Fujimura, Ryosuke Tashiro, Kenichi Sato, Hidenori Endo, Kuniyasu Niizuma, Shunji Mugikura, Teiji Tominaga

  Cerebrovascular diseases (Basel, Switzerland) 48 (3-6) 217 - 225 1015-9770 2019 [Refereed][Not invited]
   

  OBJECTIVE: Superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis is a standard surgical procedure for adult patients with moyamoya disease (MMD) and plays a role in preventing ischemic and/or hemorrhagic stroke. Cerebral hyperperfusion (CHP) syndrome is a potential complication of this procedure that can result in deleterious outcomes, such as delayed intracerebral hemorrhage, but the exact threshold of the pathological increase in postoperative cerebral blood flow (CBF) is unclear. Thus, we analyzed local CBF in the acute stage after revascularization surgery for adult MMD to predict CHP syndrome under modern perioperative management. MATERIALS AND METHODS: Fifty-nine consecutive adult MMD patients, aged 17-66 years old (mean 43.1), underwent STA-MCA anastomosis with indirect pial synangiosis for 65 affected hemispheres. All patients were perioperatively managed by strict blood pressure control (systolic pressure of 110-130 mm Hg) to prevent CHP syndrome. Local CBF at the site of anastomosis was quantitatively measured using the autoradiographic method by N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography 1 and 7 days after surgery, in addition to the preoperative CBF value at the corresponding area. We defined CHP phenomenon as a local CBF increase over 150% compared to the preoperative value. Then, we investigated the correlation between local hemodynamic change and the development of CHP syndrome. RESULTS: After 65 surgeries, 5 patients developed CHP syndrome, including 2 patients with delayed intracerebral hemorrhage (3.0%), 1 with symptomatic subarachnoid hemorrhage (1.5%), and 2 with focal neurological deterioration without hemorrhage. The CBF increase ratio was significantly higher in patients with CHP syndrome (270.7%) than in patients without CHP syndrome (135.2%, p = 0.003). Based on receiver operating characteristic analysis, the cutoff value for the pathological postoperative CBF increase ratio was 184.5% for CHP syndrome (sensitivity = 83.3%, specificity =  94.2%, area under the curve [AUC] value  =  0.825) and 241.3% for hemorrhagic CHP syndrome (sensitivity =  75.0%, specificity =  97.2%, AUC value  =  0.742). CONCLUSION: Quantitative measurement of the local CBF value in the early postoperative period provides essential information to predict CHP syndrome after STA-MCA anastomosis in patients with adult MMD. The pathological threshold of hemorrhagic CHP syndrome was as high as 241.3% by the local CBF increase ratio, but 2 patients (3.0%) developed delayed intracerebral hemorrhage in this series that were managed following the intensive perioperative management protocol. Thus, we recommend routine CBF measurement in the acute stage after direct revascularization surgery for adult MMD and satisfactory blood pressure control to avoid the deleterious effects of CHP.
• Incidence and Risk Factors of the Watershed Shift Phenomenon after Superficial Temporal Artery-Middle Cerebral Artery Anastomosis for Adult Moyamoya Disease.

  Ryosuke Tashiro, Miki Fujimura, Masayuki Kameyama, Shunji Mugikura, Hidenori Endo, Yohei Takeuchi, Yasutake Tomata, Kuniyasu Niizuma, Teiji Tominaga

  Cerebrovascular diseases (Basel, Switzerland) 47 (3-4) 178 - 187 1015-9770 2019 [Refereed][Not invited]
   

  OBJECTIVE: Superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis is the standard surgical management for adult moyamoya disease (MMD) patients, but local cerebral hyperperfusion (CHP) and cerebral ischemia are potential complications of this procedure. Recent hemodynamic analysis of the acute stage after revascularization surgery for MMD revealed a more complex and unique pathophysiological condition, the so-called "watershed shift (WS) phenomenon," which is defined as a paradoxical decrease in the cerebral blood flow (CBF) at the adjacent cortex near the site of local CHP. The objective of this study was to clarify the exact incidence, clinical presentation, and risk factors of the WS phenomenon after direct revascularization surgery for adult MMD. PATIENTS AND METHODS: Among 74 patients with MMD undergoing STA-MCA anastomosis for 78 affected hemispheres, 60 adult patients comprising 64 hemispheres underwent serial quantitative CBF analysis by N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography after revascularization surgery. The local CBF was quantitatively measured at the site of anastomosis and the adjacent cortex before surgery, as well as on 1 and 7 days after surgery. Then, we investigated the incidence, clinical presentation, and risk factors of the WS phenomenon. RESULTS: The WS phenomenon was evident in 7 patients (7/64 hemispheres; 10.9%) after STA-MCA anastomosis for adult MMD. None of the patients developed neurological deterioration due to the WS phenomenon, but 1 patient developed reversible ischemic change on diffusion-weighted imaging at the site of the WS phenomenon. Multivariate analysis revealed that a lower preoperative CBF value was significantly associated with the occurrence of the WS phenomenon (20.3 ± 7.70 mL/100 g/min in WS-positive group vs. 31.7 ± 8.81 mL/100 g/min in WS-negative group, p= 1.1 × 10-2). CONCLUSIONS: The incidence of the WS phenomenon was as high as 10.9% after STA-MCA anastomosis for adult MMD. The clinical outcome of the WS phenomenon is generally favorable, but there is a potential risk for perioperative cerebral infarction. Thus, we recommend routine CBF measurement in the acute stage after revascularization surgery for adult MMD to avoid surgical complications, such as local CHP and cerebral ischemia, caused by the WS phenomenon. Concomitant detection of the WS phenomenon with local CHP is clinically important because blood pressure reduction to counteract local CHP may have to be avoided in the presence of the WS phenomenon.
• Low frequency of cervicocranial artery involvement in Japanese with renal artery fibromuscular dysplasia compared with that of Caucasians.

  Eikan Mishima, Shu Umezawa, Takehiro Suzuki, Miki Fujimura, Michiaki Abe, Junichiro Hashimoto, Takaaki Abe, Sadayoshi Ito

  Clinical and experimental nephrology 22 (6) 1294 - 1299 1342-1751 2018/12 [Refereed][Not invited]
   

  BACKGROUND: Fibromuscular dysplasia (FMD), which usually affects the renal artery, also affects the carotid, vertebral, and intracranial arteries. Previous studies have shown a high prevalence of concomitant renal artery and cervicocranial lesions in FMD patients. However, the analyzed subjects were mostly Caucasians in Western countries. METHOD: We performed a retrospective analysis to examine the prevalence of cervicocranial vascular lesions in Japanese FMD patients with renal artery involvement at a single institution. The presence of cervicocranial lesions was evaluated by Doppler echography and magnetic resonance angiography. We compared this prevalence with that reported in the literature. RESULT: Thirty-one Japanese FMD patients with renal artery lesions were studied. The mean age was 30 ± 12 years, 71% were women, and 16% were smokers; all patients were Asians and had hypertension. Multifocal, tubular, and unifocal types of renal lesions were found in 52, 35, and 13% of patients, respectively. Bilateral renal lesions were found in 13% of patients. None of the patients had a cervical vascular lesion associated with FMD. Only two patients (8%) had a lesion in the intracranial artery, of which one was a known case of moyamoya disease. CONCLUSION: These findings suggest that cervical artery involvement and intracranial artery involvement are not common in renal FMD patients in Japan, which is in contrast to the data reported for Caucasian patients in Western countries. Ethnic differences could influence the occurrence of cervicocranial lesions. A study with a larger sample size should be performed to validate these findings.
• Growth of Thrombosed Cerebral Venous Varix Following Resection of Cerebral Arteriovenous Malformation: Case Report with Pathologic Consideration.

  Haryu S, Endo H, Endo T, Sato K, Fujimura M, Tominaga T

  World neurosurgery 119 274 - 277 1878-8750 2018/11 [Refereed][Not invited]
  
• Hemorrhagic Moyamoya Disease : A Recent Update.

  Fujimura M, Tominaga T

  Journal of Korean Neurosurgical Society 2005-3711 2018/11 [Refereed][Not invited]
  
• Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Levels as a Biomarker of Acute Intracerebral Hemorrhage.

  Inoue T, Ishida T, Inoue T, Saito A, Ezura M, Uenohara H, Fujimura M, Sato K, Endo T, Omodaka S, Endo H, Niizuma K, Tominaga T

  Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 28 (2) 490 - 494 1052-3057 2018/11 [Refereed][Not invited]
  
• Stress-induced tRNA cleavage and tiRNA generation in rat neuronal PC12 cells.

  Alaa Elkordy, Eikan Mishima, Kuniyasu Niizuma, Yasutoshi Akiyama, Miki Fujimura, Teiji Tominaga, Takaaki Abe

  Journal of neurochemistry 146 (5) 560 - 569 0022-3042 2018/09 [Refereed][Not invited]
   

  Transfer RNA (tRNA) plays a role in stress response programs involved in various pathological conditions including neurological diseases. Under cell stress conditions, intracellular tRNA is cleaved by a specific ribonuclease, angiogenin, generating tRNA-derived fragments or tRNA-derived stress-induced RNA (tiRNA). Generated tiRNA contributes to the cell stress response and has potential cell protective effects. However, tiRNA generation under stress conditions in neuronal cells has not been fully elucidated. To examine angiogenin-mediated tiRNA generation in neuronal cells, we used the rat neuronal cell line, PC12, in combination with analysis of SYBR staining and immuno-northern blotting using anti-1-methyladenosine antibody, which specifically and sensitively detects tiRNA. Oxidative stress induced by arsenite and hydrogen peroxide caused tRNA cleavage and tiRNA generation in PC12 cells. We also demonstrated that oxygen-glucose deprivation, which is an in vitro model of ischemic-reperfusion injury, induced tRNA cleavage and tiRNA generation. In these stress conditions, the amount of generated tiRNA was associated with the degree of morphological cell damage. Time course analysis indicated that generation of tiRNA was prior to severe cell damage and cell death. Angiogenin over-expression did not influence the amount of tiRNA in normal culture conditions; however, it significantly increased tiRNA generation induced by cell stress conditions. Our findings show that angiogenin-mediated tiRNA generation can be induced in neuronal cells by different cell stressors, including ischemia-reperfusion. Additionally, detection of tiRNA could be used as a potential cell damage marker in neuronal cells. Cover Image for this issue: doi: 10.1111/jnc.14191.
• Metabolomic Analysis of Mouse Brain after a Transient Middle Cerebral Artery Occlusion by Mass Spectrometry Imaging.

  Abe T, Niizuma K, Kanoke A, Saigusa D, Saito R, Uruno A, Fujimura M, Yamamoto M, Tominaga T

  Neurologia medico-chirurgica 58 (9) 384 - 392 0470-8105 2018/09 [Refereed][Not invited]
   

  We performed metabolomic analyses of mouse brain using a transient middle cerebral artery occlusion (tMCAO) model with Matrix Assisted Laser Desorption/Ionization (MALDI)-mass spectrometry imaging (MSI) to reveal metabolite changes after cerebral ischemia. We selected and analyzed three metabolites, namely creatine (Cr), phosphocreatine (P-Cr), and ceramides (Cer), because these metabolites contribute to cell life and death. Eight-week-old male C57BL/6J mice were subjected to tMCAO via the intraluminal blockade of the middle cerebral artery (MCA) and reperfusion 60 min after the induction of ischemia. Each mouse was randomly assigned to one of the three groups; the groups were defined by the survival period after reperfusion: control, 1 h, and 24 h. Corrected samples were analyzed using MALDI-MSI. Results of MSI analysis showed the presence of several ionized substances and revealed spatial changes in some metabolites identified as precise substances, including Cr, P-Cr, Cer d18:1/18:0, phosphatidylcholine, L-glutamine, and L-histidine. Cr, P-Cr, and Cer d18:1/18:0 were changed after tMCAO, and P-Cr and Cer d18:1/18:0 accumulated over time in ischemic cores and surrounding areas following ischemia onset. The upregulation of P-Cr and Cer d18:1/18:0 was detected 1 h after tMCAO when no changes were evident on hematoxylin and eosin staining and immunofluorescence assay. P-Cr and Cer d18:1/18:0 can serve as neuroprotective therapies because they are biomarker candidates for cerebral ischemia.
• Continuous Minor Bleeding from Tumor Surface in Patients with Craniopharyngiomas: Case Series of Nonobstructive Hydrocephalus.

  Shoji T, Kawaguchi T, Ogawa Y, Watanabe M, Fujimura M, Tominaga T

  Journal of neurological surgery. Part A, Central European neurosurgery 79 (5) 436 - 441 2193-6315 2018/09 [Refereed][Not invited]
  
• Intracellular S1P Levels Dictate Fate of Different Regions of the Hippocampus following Transient Global Cerebral Ischemia

  Sherif Rashad, Kuniyasu Niizuma, Daisuke Saigusa, Xiaobo Han, Mika Sato-Maeda, Ritsumi Saito, Akira Uruno, Miki Fujimura, Shuntaro Ikawa, Masayuki Yamamoto, Teiji Tominaga

  Neuroscience 384 188 - 202 1873-7544 2018/08/01 [Refereed][Not invited]
   

  Sphingosine-1-phosphate (S1P) is a sphingolipid molecule produced by the action of sphingosine kinases (SphK) on sphingosine. It possesses various intracellular functions through its interactions with intracellular proteins or via its action on five G-protein-coupled cell membrane receptors. Following transient global cerebral ischemia (tGCI), only the CA1 subregion of the hippocampus undergoes apoptosis. In this study, we evaluated S1P levels and S1P-processing enzyme expression in different hippocampal areas following tGCI in rats. We found that S1P was upregulated earlier in CA3 than in CA1. This was associated with upregulation of SphK1 in both regions however, SphK2 was downregulated quickly in CA3. S1P lyase was also downregulated in CA3, but not in CA1. Spinster 2, the S1P exporter, was upregulated early in both regions, but was quickly downregulated in CA3. Together, these effects explain the variable levels of S1P in the CA1 and CA3 areas and indicate that S1P levels play a role in the preferential resistance of the CA3 subregion to tGCI-induced ischemia. FTY720 did not improve neuronal survival in the CA1 subregion, indicating that these effects were due to intracellular S1P accumulation. In conclusion, the findings suggest that intracellular S1P levels affect neuronal cell fate following tGCI.
• Biphasic Development of Focal Cerebral Hyperperfusion After Revascularization Surgery for Adult Moyamoya Disease Associated With Autosomal Dominant Polycystic Kidney Disease.

  Tashiro R, Fujimura M, Endo H, Endo T, Niizuma K, Tominaga T

  Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 27 (11) 3256 - 3260 1052-3057 2018/08 [Refereed][Not invited]
   

  BACKGROUND: Cerebral hyperperfusion (CHP) syndrome is a potential complication of superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis for moyamoya disease (MMD), but its biphasic and delayed development is extremely rare. CASE REPORT: A 47-year-old woman with autosomal dominant kidney disease (ADPKD) presented with transient ischemic attacks due to MMD, and underwent left STA-MCA anastomosis. N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography (123IMP-SPECT) 1 day after surgery revealed asymptomatic CHP at the site of anastomosis. Strict blood pressure control and minocycline hydrochloride relieved CHP at postoperative day 7. However, 2 days later, the patient complained of sensory aphasia, and 123IMP-SPECT demonstrated significant focal CHP at the site of anastomosis accompanying high-intensity signal on magnetic resonance (MR) imaging of fluid attenuated inversion recovery (FLAIR) in her left temporal lobe near the site of anastomosis. We continued strict blood pressure control and additionally administered free radical scavenger (Edaravone) and antiepileptic agents, which gradually improved sensory aphasia. MR imaging and 123IMP-SPECT also confirmed the amelioration of the FLAIR-high lesion and focal CHP in her left temporal lobe. Two months later, the patient underwent right STA-MCA anastomosis without complications. CONCLUSIONS: Although the underlying mechanism is unknown, biphasic development of focal CHP after revascularization surgery in an MMD patient with ADPKD is unique. Due to the potential vulnerability of the systemic vessels in ADPKD, it is conceivable that intrinsic vascular wall fragility in MMD could be enhanced by ADPKD and have partly led to this rare complication.
• Paradoxical Association of Symptomatic Local Vasogenic Edema with Global Cerebral Hypoperfusion after Direct Revascularization Surgery for Adult Moyamoya Disease.

  Tashiro R, Fujimura M, Mugikura S, Niizuma K, Endo H, Endo T, Tominaga T

  Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 27 (8) e172 - e176 1052-3057 2018/08 [Refereed][Not invited]
   

  BACKGROUND: Superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis is the standard treatment for Moyamoya disease (MMD). Cerebral hyperperfusion syndrome is a potential complication of this procedure and can cause local vasogenic edema and/or delayed intracerebral hemorrhage. Cerebral hypoperfusion is a contradictory postoperative pathophysiological condition implicated in MMD, but its association with symptomatic local vasogenic edema has not been reported. CASE REPORT: A 31-year-old woman with MMD underwent left STA-MCA anastomosis 3 months after a minor completed stroke in bilateral hemispheres. Eight hours after the operation, the patient developed neurological deterioration of dysarthria and mono-paresis in her right hand. Magnetic resonance (MR) angiography showed apparently patent STA-MCA bypass, whereas MR imaging of fluid-attenuated inversion recovery demonstrated a local high-signal-intensity lesion at the vascular territory supplied by the bypass. The apparent diffusion coefficient value was significantly increased in this lesion, suggesting local vasogenic edema formation. N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography revealed global hypoperfusion in the left hemisphere. The administration of a free-radical scavenger and antiepileptic agent gradually relieved her symptoms, and MR imaging 1 month after surgery confirmed the complete disappearance of local vasogenic edema. CONCLUSIONS: Vasogenic edema may be associated not only with cerebral hyperperfusion but also with hypoperfusion after STA-MCA anastomosis for MMD. Although the exact mechanism of this rare association is unknown, the intrinsic vulnerability of intracranial vascular wall structures and the increased vascular permeability in MMD may partly explain the paradoxical association of hypoperfusion and local vasogenic edema.
• Early BBB breakdown and subacute inflammasome activation and pyroptosis as a result of cerebral venous thrombosis.

  Rashad S, Niizuma K, Sato-Maeda M, Fujimura M, Mansour A, Endo H, Ikawa S, Tominaga T

  Brain research 1699 54 - 68 0006-8993 2018/07 [Refereed][Not invited]
  
• Relationship Between Perforator Infarction and Patient Outcomes After Surgical Treatment of Ruptured Anterior Communicating Artery Aneurysms.

  Mugikura S, Fujimura M, Takahashi S, Takase K

  World neurosurgery 113 390 - 391 1878-8750 2018/05 [Refereed][Not invited]
  
• Endovascular Treatments in Combination with Extracranial-Intracranial Bypass for Complex Intracranial Aneurysms

  Kenichi Sato, Hidenori Endo, Miki Fujimura, Toshiki Endo, Yasushi Matsumoto, Hiroaki Shimizu, Teiji Tominaga

  World Neurosurgery 113 e747 - e760 1878-8769 2018/05/01 [Refereed][Not invited]
   

  Background: Although most intracranial aneurysms can be treated with microsurgery or endovascular procedure alone, a subset of aneurysms may require a combined approach. The purpose of this study was to assess the efficacy of endovascular interventions combined with bypass surgery for the treatment of complex intracranial aneurysms. Methods: We retrospectively reviewed medical records from a prospectively maintained patient database to identify patients who underwent endovascular treatment of an intracranial aneurysm at our institutes between 2007 and 2017. We recruited patients who received a preplanned combination of endovascular treatment and extracranial-intracranial bypass surgery. Results: Forty-four patients (44 aneurysms) were treated with a combined approach. Twenty-four patients presented with subarachnoid hemorrhage. Treatment strategies included endovascular parent artery occlusion with the bypass surgery to restore cerebral blood flow (n = 12), endovascular trapping with bypass surgery to isolate incorporated branches (n = 12), and intra-aneurysmal coil embolization with bypass surgery to isolate incorporated branches (n = 20). During a mean period of 35.6 months, follow-up catheter angiography was performed in 35 of 44 patients (79.5%) and demonstrated complete aneurysm obliteration in 29 patients (82.9%) and bypass patency in 33 (94.3%). The postoperative aneurysm-related mortality and morbidity rates were 6.8% and 13.6%, respectively. Conclusions: Combined endovascular and surgical bypass procedures are useful for the treatment of complex intracranial aneurysms when conventional surgical or endovascular techniques are not feasible and show acceptable rates of morbidity and mortality.
• Angiographic features of hemorrhagic moyamoya disease with high recurrence risk: a supplementary analysis of the Japan Adult Moyamoya Trial.

  Takeshi Funaki, Jun C Takahashi, Kiyohiro Houkin, Satoshi Kuroda, Shigekazu Takeuchi, Miki Fujimura, Yasutake Tomata, Susumu Miyamoto

  Journal of neurosurgery 128 (3) 777 - 784 2018/03 [Refereed][Not invited]
   

  OBJECTIVE In this paper, the authors set out to identify the angiographic features of moyamoya disease with posterior hemorrhage, which is a strong predictor of rebleeding. METHODS This cross-sectional study used the data set of the Japan Adult Moyamoya Trial (clinical trial registration no.: C000000166 [ www.umin.ac.jp/ctr/index.htm ]). The panel designed the ancillary measurement of angiography at onset, classifying the collateral vessels into 3 subtypes: lenticulostriate anastomosis, thalamic anastomosis, and choroidal anastomosis. The association between each collateral and the hemorrhage site (anterior vs posterior) was assessed in the hemorrhagic hemisphere by using multivariate adjustment for potential confounders, including age, sex, and involvement of the posterior cerebral artery (PCA). The association was confirmed through topographical analysis of bleeding points. RESULTS Among the 80 participants, 75 hemorrhagic hemispheres of 75 patients were analyzed. Lenticulostriate anastomosis was detected in 21 (28.0%) hemorrhagic hemispheres, thalamic anastomosis in 22 (29.3%), and choroidal anastomosis in 35 (46.7%). Choroidal anastomosis was a factor associated with posterior hemorrhage (OR 2.77 [95% CI 1.08-7.10], p = 0.034) and remained statistically significant after the multivariate adjustment (OR 2.66 [95% CI 1.00-7.07], p = 0.049). PCA involvement was also associated with posterior hemorrhage in both univariate and multivariate analyses. Topographical analysis revealed good correspondence between bleeding points associated with positive choroidal anastomosis and the anatomical distribution of the choroidal arteries, including the thalamus and the wall of the atrium. CONCLUSIONS Choroidal anastomosis and PCA involvement are characteristic of posterior hemorrhage in moyamoya disease. Choroidal anastomosis might be considered a potential source of posterior hemorrhage at high risk of rebleeding.
• Impact of bifurcation angle and inflow coefficient on the rupture risk of bifurcation type basilar artery tip aneurysms

  Sherif Rashad, Shin-Ichiro Sugiyama, Kuniyasu Niizuma, Kenichi Sato, Hidenori Endo, Shunsuke Omodaka, Yasushi Matsumoto, Miki Fujimura, Teiji Tominaga

  Journal of Neurosurgery 128 (3) 723 - 730 1933-0693 2018/03/01 [Refereed][Not invited]
   

  OBJECTIVE: Risk factors for aneurysm rupture have been extensively studied, with several factors showing significant correlations with rupture status. Several studies have shown that aneurysm shape and hemodynamics change after rupture. In the present study the authors investigated a static factor, the bifurcation angle, which does not change after rupture, to understand its effect on aneurysm rupture risk and hemodynamics. METHODS: A hospital database was retrospectively reviewed to identify patients with cerebral aneurysms treated surgically or endovascularly in the period between 2008 and 2015. After acquiring 3D rotational angiographic data, 3D stereolithography models were created and computational fluid dynamic analysis was performed using commercially available software. Patient data (age and sex), morphometric factors (aneurysm volume and maximum height, aspect ratio, bifurcation angle, bottleneck ratio, and neck/parent artery ratio), and hemodynamic factors (inflow coefficient and wall shear stress) were statistically compared between ruptured and unruptured groups. RESULTS: Seventy-one basilar tip aneurysms were included in this study, 22 ruptured and 49 unruptured. Univariate analysis showed aspect ratio, bifurcation angle, bottleneck ratio, and inflow coefficient were significantly correlated with a ruptured status. Logistic regression analysis showed that aspect ratio and bifurcation angle were significant predictors of a ruptured status. Bifurcation angle was inversely correlated with inflow coefficient (p < 0.0005), which in turn correlated directly with mean (p = 0.028) and maximum (p = 0.014) wall shear stress (WSS) using Pearson's correlation coefficient, whereas aspect ratio was inversely correlated with mean (0.012) and minimum (p = 0.018) WSS. CONCLUSIONS: Bifurcation angle and aspect ratio are independent predictors for aneurysm rupture. Bifurcation angle, which does not change after rupture, is correlated with hemodynamic factors including inflow coefficient and WSS, as well as rupture status. Aneurysms with the hands-up bifurcation configuration are more prone to rupture than aneurysms with other bifurcation configurations.
• Subcallosal and Heubner artery infarcts following surgical repair of an anterior communicating artery aneurysm: a causal relationship with postoperative amnesia and long-term outcome

  Shunji Mugikura, Hirokazu Kikuchi, Miki Fujimura, Etsuro Mori, Shoki Takahashi, Kei Takase

  Japanese Journal of Radiology 36 (2) 81 - 89 1867-108X 2018/02/01 [Refereed][Not invited]
   

  Since the 1950s, amnesia or memory impairment has been repeatedly reported in patients following surgical repair of anterior communicating artery (ACoA) aneurysms. Postoperative infarctions following surgical repair of ACoA aneurysms are classified as involvement of the subcallosal artery (the largest unpaired perforator of the ACoA), the recurrent artery of Heubner (RAH), or a combination of both. Postoperative amnesia can seriously affect the patient’s quality of life, thus prompting physicians to discuss the symptomatology of the three infarction patterns. We made the following speculations regarding the causal relationship between the infarction pattern and postoperative amnesia. First, postoperative amnesia is most likely caused by an infarction in the territory of the subcallosal artery, particularly in the column of the fornix, a constituent of the Papez neuronal circuit. Second, infarction in the RAH territory alone is unlikely to cause significant amnesia. Third, infarcted foci in the RAH territory, when associated with a subcallosal artery infarction, can cause considerable frontal dysfunction due to impaired frontostriatal circuits in patients with postoperative amnesia, with resultant worsening of the long-term outcome or quality of life.
• Increased serum production of soluble CD163 and CXCL5 in patients with moyamoya disease: Involvement of intrinsic immune reaction in its pathogenesis.

  Miki Fujimura, Taku Fujimura, Aya Kakizaki, Mika Sato-Maeda, Kuniyasu Niizuma, Yasutake Tomata, Setsuya Aiba, Teiji Tominaga

  Brain research 1679 39 - 44 0006-8993 2018/01/15 [Refereed][Not invited]
   

  Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by a progressive stenosis at the terminal portion of the internal carotid artery and an abnormal vascular network at the base of the brain. Although its etiology is still unknown, intrinsic immune reactions such as autoimmune response has been implicated in the pathogenesis of MMD. Recently, the RING finger protein 213 (RNF213) was found to be an important risk gene for MMD, and is predominantly expressed in blood cells and the spleen. Thus, we hypothesized that patients with MMD represent an intrinsic autoimmune status mediated by M2-polarized macrophages, which play an important role in tissue remodeling and angiogenesis. We compared the serum level of soluble (s)CD163, an activating marker for CD163+ M2-polarized macrophages that has been implicated in a variety of autoimmune disorders, between MMD patients and healthy controls. We also analyzed serum levels of CXCL5, an augmented cytokines that has been correlated with the severity of autoimmune diseases. As a result, the serum sCD163 levels of MMD patients (281,465 pg/ml) were significantly higher than those of healthy controls (174,842 pg/ml) (p = .004). The serum CXCL5 levels of MMD patients (679.02 pg/ml) were significantly higher than those of healthy controls (401.79 pg/ml) (p = .046). There were no differences in the serum sCD163 and CXCL5 levels between each genotype of the RNF213 polymorphism (wild-type or variant) among MMD patients. Although this is a pilot study and further validation with larger number of samples is necessary, our results indicate that patients with MMD may have increased autoimmune activity, and our results shed light on the pathogenesis of MMD via CD163+ M2-polarized macrophages.
• もやもや病(ウイリス動脈輪閉塞症)診断・治療ガイドライン(改訂版)

  寶金 清博, 冨永 悌二, 宮本 享, 鈴木 則宏, 黒田 敏, 小泉 昭夫, 高橋 淳, 佐藤 典宏, 数又 研, 高木 康志, 大木 宏一, 舟木 健史, 藤村 幹, 厚生労働科学研究費補助金難治性疾患克服事業ウイリス動脈輪閉塞症における病態・治療に関する研究班

  脳卒中の外科 (一社)日本脳卒中の外科学会 46 (1) 1 - 24 0914-5508 2018/01 [Refereed][Not invited]
  
• Patient with Recurrent Anterior Cerebral Artery Dissecting Aneurysm After Stent-Assisted Coil Embolization Successfully Treated with A3-A3 Anastomosis

  Yoshiharu Takahashi, Hidenori Endo, Toshiki Endo, Miki Fujimura, Kuniyasu Niizuma, Teiji Tominaga

  World Neurosurgery 109 77 - 81 1878-8769 2018/01/01 [Refereed][Not invited]
   

  Background With recent advances in endovascular devices and techniques, the use of endovascular treatment has been reported for intracranial dissecting aneurysms. However, the efficacy of this endovascular approach for intracranial dissection is still unknown. We report the case of a patient with a recurrent anterior cerebral artery (ACA) dissecting aneurysm after endovascular treatment. Case Description A 67-year-old woman underwent stent-assisted coil embolization for a ruptured ACA dissecting aneurysm of the left A2 segment. Aneurysmal dilatation was completely occluded after embolization. However, follow-up angiography 40 days after treatment showed compaction of the coil mass and reenlargement of the aneurysm. Open surgery was performed, considering the risk of rebleeding from the recurrent dissecting aneurysm. A3-A3 anastomosis followed by trapping of the coiled aneurysm along with the stent was successfully performed through the interhemispheric approach. The postoperative course was uneventful, and angiography 6 months after surgery revealed disappearance of the aneurysm and patency of the A3-A3 anastomosis. Conclusions Stent-assisted coil embolization for an ACA dissecting aneurysm may not be curative, and the coiled aneurysm may recur within a short time period. Microsurgical bypass trapping can be considered as the alterative or salvage treatment because of curability. Revascularization surgery, such as A3-A3 anastomosis, should be performed before trapping to avoid ischemic complications.
• Embolization of ruptured arteriovenous malformations in the cerebellopontine angle cistern

  Hidenori Endo, Shin-ichiro Osawa, Yasushi Matsumoto, Toshiki Endo, Kenichi Sato, Kuniyasu Niizuma, Miki Fujimura, Teiji Tominaga

  Neurosurgical Review 41 (1) 173 - 182 1437-2320 2018/01/01 [Refereed][Not invited]
   

  Among brainstem arteriovenous malformations (AVMs), there exist small AVMs predominantly located in the cerebellopontine angle cistern (CPAC) with minimal extension into the pial surface of the brainstem. However, previous studies of CPAC AVMs did not particularly discuss the role of embolization in the treatment of these lesions. This study was conducted to clarify the effectiveness and validity of embolization in the treatment of CPAC AVMs. We retrospectively reviewed five patients with CPAC AVMs who underwent endovascular treatment. These patients were treated with embolization followed by open surgery or gamma knife (GK) radiosurgery. Radiological findings and clinical course for these patients were then assessed. All five patients presented with a hemorrhage. Angiography revealed that the main feeder contained a dilated pontine perforating artery in all cases. Embolization through the dilated pontine perforating artery effectively reduced shunt flow within the nidus or obliterated associated aneurysms. Magnetic resonance imaging showed infarction on the lateral pons in four patients, one of which developed transient mild dizziness and mild ataxia of the right side. Subsequent open surgery was performed in three patients, and GK radiosurgery was performed in two patients without complications. At the end of the follow-up period, all patients demonstrated favorable outcomes. Postoperative rebleeding did not occur in any of the patients. Disappearance of the AVM was confirmed in four patients, except in the one patient treated with GK. Although ischemic complications should be noted, embolization of CPAC AVMs may be an appropriate treatment option to reduce the risk of subsequent surgery or radiosurgery.
• Successful presurgical endovascular management of venous sinus thrombosis associated with high-grade cerebral arteriovenous malformation: A case report

  Yoshinari Osada, Hidenori Endo, Kenichi Sato, Yasushi Matsumoto, Toshiki Endo, Miki Fujimura, Teiji Tominaga

  Interventional Neuroradiology 23 (6) 656 - 660 1591-0199 2017/12/01 [Refereed][Not invited]
   

  We report a case of a 39-year-old man presenting with a high-grade left parieto-occipital arteriovenous malformation (AVM) complicated by superior sagittal sinus (SSS) stenosis, seven years after the first presentation. Magnetic resonance imaging revealed a newly developed perilesional edema. Venous sinus stenosis acutely progressed to occlusion and induced multiple intracerebral hemorrhages. An emergent balloon venoplasty of the SSS successfully recanalized the thrombosed sinus. Further, multistage transarterial nidus embolization was performed followed by surgical resection, resulting in a complete eradication of the large AVM. The emergence of perilesional edema is a key radiological feature for the early recognition of a newly developed venous drainage route disturbance, which would result in hemorrhagic events. Venous sinus thrombosis is a rare cause of drainage route disturbance in cerebral AVMs. For such cases, the recanalization of venous drainage concomitant with flow reduction by performing transarterial embolization is effective in preventing further hemorrhage, which enables a safe performance of subsequent radical surgery.
• Revascularization of the anterior cerebral artery by Y-shaped superficial temporal artery interposition graft for the treatment of a de novo aneurysm arising at the site of A₃-A₃ bypass: technical case report.

  Endo H, Sugiyama SI, Endo T, Fujimura M, Shimizu H, Tominaga T

  Journal of neurosurgery 1 - 5 0022-3085 2017/12 [Refereed][Not invited]
  
• 神経アポトーシスにおけるS1Pシグナル伝達 虚血性細胞死に対する抵抗性と脆弱性への関連(S1P signaling in neuronal apoptosis: links to resistance and vulnerability to ischemic cell death)

  Rashad Sherif, 新妻 邦泰, 三枝 大輔, 韓 笑波, 前田 美香, 藤村 幹, 井川 俊太郎, 冨永 悌二

  脳循環代謝 29 (1) 215 - 215 0915-9401 2017/11
• Intra-operative hemorrhage due to hyperperfusion during direct revascularization surgery in an adult patient with moyamoya disease: a case report

  Hiroki Uchida, Hidenori Endo, Miki Fujimura, Toshiki Endo, Kuniyasu Niizuma, Teiji Tominaga

  Neurosurgical Review 40 (4) 679 - 684 1437-2320 2017/10/01 [Refereed][Not invited]
   

  Hemorrhagic complication is one of the notable surgical complications of the revascularization surgery for moyamoya disease (MMD). Cerebral hyperperfusion (CHP) has been considered as the underlying cause of this complication. It mostly occurs several days after surgery, but the intra-operative hemorrhage immediately after bypass has not been reported previously. A 21-year-old woman presented right thalamic hemorrhage and was diagnosed as having MMD by cerebral angiography. In light of the location of the hemorrhage at the vascular territory of posterior circulation and the manifestation of transient ischemic attack during the follow-up period, she underwent revascularization surgery to prevent future ischemic attack and rebleeding. Superficial temporal artery (STA) was uneventfully anastomosed to the temporal M4 branch of the middle cerebral artery in an end-to-side manner. A few minutes after the completion of the anastomosis, hemorrhage occurred in the fissure adjacent to the site of anastomosis. Indocyanine green (ICG) video angiography just before hemorrhage showed focal early filling through the STA graft with early venous filling around the site of the anastomosis. The bleeding was controlled by immediate hypotensive therapy (systolic blood pressure 117 to 91 mmHg). The mean blood flows of the STA graft measured by ultrasonic flowmetry before and after hypotensive therapy were 52.8 and 24.2 ml/min, respectively. Single-photon emission computed tomography (SPECT) on the next day after surgery showed focal hyperperfusion in the surgical side. Intra-operative ultrasonic flowmetry, ICG, and postoperative SPECT would explain that CHP was the potential cause of the hemorrhagic complication. This is the first case describing intra-operative hemorrhagic complication during revascularization surgery for MMD. Surgeons need to be aware of this rare complication and its management method.
• Temporal and Spatial Changes in Cerebral Blood Flow during Management for Preventing Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage: Serial Semiquantitative Analysis

  Kenichi Sato, Hiroaki Shimizu, Takashi Inoue, Miki Fujimura, Hidenori Endo, Teiji Tominaga

  Journal of Stroke and Cerebrovascular Diseases 26 (9) 2027 - 2037 1532-8511 2017/09/01 [Refereed][Not invited]
   

  Background Delayed cerebral ischemia is a major cause of morbidity after aneurysmal subarachnoid hemorrhage. The management for preventing the delayed cerebral ischemia is clinically difficult because of its multifactorial nature. We tested the hypothesis that spatial and temporal changes of regional cerebral blood flow after subarachnoid hemorrhage might relate to the incidence of the delayed cerebral ischemia and the clinical outcome. Methods Eighty-eight patients who underwent single-photon emission computed tomography twice during 14 days after the onset of aneurysmal subarachnoid hemorrhage were retrospectively analyzed. Regional cerebral blood flow was automatically analyzed in statistical imaging analyses using 3-dimensional stereotaxic region of interest template and 3-dimensional stereotaxic surface projection. Ratios were calculated by dividing the regional cerebral blood flow of patients by that of normal volunteers. We assessed the relation of changes in regional cerebral blood flow with the development of the delayed cerebral ischemia and the clinical outcome at 3 months. Results The regional cerebral blood flow of areas that eventually contained infarction significantly decreased, whereas those with significant increase were associated with transient neurological symptoms during the management for the delayed cerebral ischemia. Patients with both areas of regional cerebral blood flow increasing and decreasing during this period had worse outcomes than patients with a unidirectional change. Conclusions Cerebral perfusion may change temporally and spatially during the management for preventing the delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Regional hypoperfusion refractory to the management might exist, which could impact on the clinical outcome. An additional therapeutic approach targeting on such regions may be required.
• Transient Global Cerebral Ischemia Induces RNF213, a Moyamoya Disease Susceptibility Gene, in Vulnerable Neurons of the Rat Hippocampus CA1 Subregion and Ischemic Cortex

  Mika Sato-Maeda, Miki Fujimura, Sherif Rashad, Yuiko Morita-Fujimura, Kuniyasu Niizuma, Hiroyuki Sakata, Shuntaro Ikawa, Teiji Tominaga

  Journal of Stroke and Cerebrovascular Diseases 26 (9) 1904 - 1911 1532-8511 2017/09/01 [Refereed][Not invited]
   

  The RING finger protein 213 (RNF213) is an important susceptibility gene for moyamoya disease (MMD) and is also implicated in other types of intracranial major artery stenosis/occlusion (ICAS) however, the role of RNF213 in the development of ICAS including MMD is unclear. The constitutive expression of the RNF213 gene is relatively weak in brain tissue, while information regarding the expression patterns of the RNF213 gene under cerebral ischemia, which is one of characteristic pathologies associated with ICAS, is currently limited. Our objective was to address this critical issue, and we investigated Rnf213 mRNA expression in rat brains after 5 minutes of transient global cerebral ischemia (tGCI) by occluding the common carotid arteries coupled with severe hypotension. Rnf213 gene expression patterns were investigated with in situ RNA hybridization and a real-time polymerase chain reaction (PCR) from 1 to 72 hours after tGCI. In situ RNA hybridization revealed a significant increase in Rnf213 mRNA levels in the hippocampus CA1 sub-region 48 hours after tGCI. The significant induction of the Rnf213 gene was also evident in the ischemic cortex. Double staining of Rnf213 mRNA with NeuN immunohistochemistry revealed Rnf213 hybridization signal expression exclusively in neurons. The real-time PCR analysis confirmed the induction of the Rnf213 gene after tGCI. The up-regulation of the Rnf213 gene in vulnerable neurons in the hippocampus CA1 after tGCI suggests its involvement in forebrain ischemia, which is an underlying pathology of MMD. Further investigations are needed to elucidate its exact role in the pathophysiology of ICAS including MMD.
• Endovascular Treatment for carotid blowout syndrome after radiation for esophageal cancer: A case report

  Shigefumi Takahashi, Tomohiro Kawaguchi, Kuniyasu Nhzuma, Atsuhiro Nakagawa, Miki Fujimura, Takenori Ogawa, Yukio Katori, Teiji Tominaga

  Neurological Surgery 45 (9) 791 - 798 1882-1251 2017/09/01 [Refereed][Not invited]
   

  Here, we discuss a case of carotid blowout syndrome successfully treated with endovascular parent artery occlusion. A 71-year-old woman underwent treatment for esophageal cancer resection, followed by 50-Gy radiotherapy. 19 years prior. Due to local recurrence, she underwent 66- and 72-Gy radiation treatments at 2 and 4 years after the initial treatment, respectively. Afterward, tracheostomy and enterostomy were performed. This time, she was transported to our emergency department because of acute eruptive bleeding from the tracheal tube. As her vitals indicated shock, emergency endovascular treatment was performed. Digital subtraction angiography revealed that the common carotid artery in the left-sided of the neck had a pseudoaneurysm extruding to the pharyngeal cavity, which was considered to be the lesion responsible for the acute rupture. She was diagnosed as having carotid blowout syndrome. Balloon test occlusion showed that the cross flow via the anterior and posterior communicating arteries was sufficient, so parent artery occlusion was chosen for bleeding control. Carotid bifurcation was preserved to keep the collateral circulation via the external carotid artery. The patient was discharged 22 days after treatment, without any neurological deficits. Although injured vessel removal with high-flow bypass was an ideal treatment to achieve bleeding control without ischemic complication, endovascular treatment can be an efficient second-best treatment. To minimize the risk of late ischemic complications, flow preservation via carotid bifurcation might be important.
• Endoscopic third ventriculostomy for hydrocephalus in a patient with Klippel-Feil syndrome: a case report.

  Ishida T, Inoue T, Fujimura M, Shimoda Y, Ezura M, Uenohara H, Tominaga T

  Clinical case reports 5 (8) 1344 - 1347 2017/08 [Refereed][Not invited]
   

  A patient with Klippel-Feil syndrome presented with hydrocephalus secondary to intraventricular hemorrhage. Fusion of the cervical vertebrae may have impeded cerebrospinal fluid flow. Change in the properties of cerebrospinal fluid flow after hemorrhage may have induced noncommunicating hydrocephalus. Endoscopic third ventriculostomy was effective for the treatment of hydrocephalus associated with Klippel-Feil syndrome.
• Navigation-guided clipping of a de novo aneurysm associated with superficial temporal artery-middle cerebral artery bypass combined with indirect pial synangiosis in a patient with moyamoya disease

  Daiki Aburakawa, Miki Fujimura, Kuniyasu Niizuma, Hiroyuki Sakata, Hidenori Endo, Teiji Tominaga

  Neurosurgical Review 40 (3) 517 - 521 1437-2320 2017/07/01 [Refereed][Not invited]
   

  De novo aneurysms associated with superficial temporal artery (STA)-middle cerebral artery (MCA) bypass are an extremely rare complication of direct revascularization surgery for moyamoya disease (MMD). The basic pathology of MMD includes fragility of the intracranial arterial wall characterized by medial layer thinness and waving of the internal elastic lamina. However, the incidence of newly formed aneurysms at the site of anastomosis currently remains unknown. Among 317 consecutive direct/indirect combined revascularization surgeries performed for MMD, we encountered a 52-year-old woman manifesting a de novo aneurysm adjacent to the site of anastomosis 11 years after successful STA-MCA bypass with encephalo-duro-myo-synangiosis (EDMS). Although the patient remained asymptomatic, the aneurysm gradually increased in diameter to more than 6 mm with the formation of a daughter sac, and a computational fluid dynamic study revealed low wall shear stress at the aneurysm dome. The patient underwent microsurgical clipping of the aneurysm using a neuro-navigation system that permitted the minimally invasive dissection of the temporal muscle flap used for EDMS at the site of the aneurysm without affecting pial synangiosis. The aneurysm was successfully occluded using a titanium clip without complications. The postoperative course was uneventful, and the patient was discharged without neurological deficits. De novo aneurysms associated with STA-MCA bypass for MMD may be safely treated with microsurgical clipping, even in cases initially managed by a combined revascularization procedure that includes complex pial synangiosis. We recommend the application of the neuro-navigation system for the maximum preservation of pial synangiosis during this procedure.
• Uneven cerebral hemodynamic change as a cause of neurological deterioration in the acute stage after direct revascularization for moyamoya disease: cerebral hyperperfusion and remote ischemia caused by the ‘watershed shift’

  Xian-kun Tu, Miki Fujimura, Sherif Rashad, Shunji Mugikura, Hiroyuki Sakata, Kuniyasu Niizuma, Teiji Tominaga

  Neurosurgical Review 40 (3) 507 - 512 1437-2320 2017/07/01 [Refereed][Not invited]
   

  Superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis is the standard surgical treatment for moyamoya disease (MMD). The main potential complications of this treatment are cerebral hyperperfusion (CHP) syndrome and ischemia, and their managements are contradictory to each other. We retrospectively investigated the incidence of the simultaneous manifestation of CHP and infarction after surgery for MMD. Of the 162 consecutive direct revascularization surgeries performed for MMD, we encountered two adult cases (1.2%) manifesting the simultaneous occurrence of symptomatic CHP and remote infarction in the acute stage. A 47-year-old man initially presenting with infarction developed CHP syndrome (aphasia) 2 days after left STA-MCA anastomosis, as assessed by quantitative single-photon emission computed tomography (SPECT). Although lowering blood pressure ameliorated his symptoms, he developed cerebral infarction at a remote area in the acute stage. Another 63-year-old man, who initially had progressing stroke, presented with aphasia due to focal CHP in the left temporal lobe associated with acute infarction at the tip of the left frontal lobe 1 day after left STA-MCA anastomosis, when SPECT showed a paradoxical decrease in cerebral blood flow (CBF) in the left frontal lobe despite a marked increase in CBF at the site of anastomosis. Symptoms were ameliorated in both patients with the normalization of CBF, and there were no further cerebrovascular events during the follow-up period. CHP and cerebral infarction may occur simultaneously not only due to blood pressure lowering against CHP, but also to the ‘watershed shift’ phenomenon, which needs to be elucidated in future studies.
• Application of actuator-driven pulsed water jet in aneurysmal subarachnoid hemorrhage surgery: its effectiveness for dissection around ruptured aneurysmal walls and subarachnoid clot removal

  Hidenori Endo, Toshiki Endo, Atsuhiro Nakagawa, Miki Fujimura, Teiji Tominaga

  Neurosurgical Review 40 (3) 485 - 493 1437-2320 2017/07/01 [Refereed][Not invited]
   

  In clipping surgery for aneurysmal subarachnoid hemorrhage (aSAH), critical steps include clot removal and dissection of aneurysms without premature rupture or brain injuries. To pursue this goal, a piezo actuator-driven pulsed water jet (ADPJ) system was introduced in this study. This study included 42 patients, who suffered aSAH and underwent clipping surgery. Eleven patients underwent surgery with the assistance of the ADPJ system (ADPJ group). In the other 31 patients, surgery was performed without the ADPJ system (Control group). The ADPJ system was used for clot removal and aneurysmal dissection. The clinical impact of the ADPJ system was judged by comparing the rate of premature rupture, degree of clot removal, and clinical outcomes. Intraoperatively, a premature rupture was encountered in 18.2 and 25.8% of cases in the ADPJ and control groups, respectively. Although the differences were not statistically significant, intraoperative observation suggested that the ADPJ system was effective in clot removal and dissection of aneurysms in a safe manner. Computed tomography scans indicated the achievement of higher degrees of clot removal, especially when the ADPJ system was used for cases with preoperative clot volumes of more than 25 ml (p = 0.047, Mann–Whitney U test). Clinical outcomes, including incidence of postoperative brain injury or symptomatic vasospasm, were similar in both groups. We described our preliminary surgical results using the ADPJ system for aSAH. Although further study is needed, the ADPJ system was considered a safe and effective tool for clot removal and dissection of aneurysms.
• Circumferential Wall Enhancement on Magnetic Resonance Imaging is Useful to Identify Rupture Site in Patients with Multiple Cerebral Aneurysms

  Shunsuke Omodaka, Hidenori Endo, Kuniyasu Niizuma, Miki Fujimura, Toshiki Endo, Kenichi Sato, Shin-ichiro Sugiyama, Takashi Inoue, Teiji Tominaga

  Neurosurgery 2017/06/06 [Refereed][Not invited]
  
• Embolization of the choroidal artery in the treatment of cerebral arteriovenous malformations

  Alaa Elkordy, Hidenori Endo, Kenichi Sato, Yasushi Matsumoto, Ryushi Kondo, Kuniyasu Niizuma, Toshiki Endo, Miki Fujimura, Teiji Tominaga

  Journal of Neurosurgery 126 (4) 1114 - 1122 1933-0693 2017/04/01 [Refereed][Not invited]
   

  OBJECTIVE: The anterior and posterior choroidal arteries are often recruited to supply arteriovenous malformations (AVMs) involving important paraventricular structures, such as the basal ganglia, internal capsule, optic radiation, lateral geniculate body, and medial temporal lobe. Endovascular embolization through these arteries is theoretically dangerous because they supply eloquent territories, are of small caliber, and lack collaterals. This study aimed to investigate the safety and efficacy of embolization through these arteries. METHODS: This study retrospectively reviewed 13 patients with cerebral AVMs who underwent endovascular embolization through the choroidal arteries between 2006 and 2014. Embolization was performed as a palliative procedure before open surgery or Gamma Knife radiosurgery. Computed tomography and MRI were performed the day after embolization to assess any surgical complications. The incidence and type of complications and their association with clinical outcomes were analyzed. RESULTS: Decreased blood flow was achieved in all patients after embolization. Postoperative CT detected no hemorrhagic complications. In contrast, postoperative MRI detected that 4 of the 13 patients (30.7%) developed infarctions: 3 patients after embolization through the anterior choroidal artery, and 1 patient after embolization through the lateral posterior choroidal artery. Two of the 4 patients in whom embolization was from the cisternal segment of the anterior choroidal artery (proximal to the plexal point) developed symptomatic infarction of the posterior limb of the internal capsule, 1 of whom developed morbidity (7.7%). The treatment-related mortality rate was 0%. Additional treatment was performed in 12 patients: open surgery in 9 and Gamma Knife radiosurgery in 3 patients. Complete obliteration was confrmed by angiography at the last follow-up in 10 patients. Recurrent bleeding from the AVMs did not occur in any of the cases during the follow-up period. CONCLUSIONS: Ischemic complications are possible following the embolization of cerebral AVMs through the choroidal artery, even with modern neurointerventional devices and techniques. Although further study is needed, embolization through the choroidal artery may be an appropriate treatment option when the risk of surgery or radiosurgery is considered to outweigh the risk of embolization.
• Efficacy of Revascularization Surgery for the Adult Patients with Hemorrhagic-onset Moyamoya Disease

  Miki Fujimura, Hidenori Endo, Kuniyasu Niizuma, Teiji Tominaga

  Japanese Journal of Neurosurgery 日本脳神経外科コングレス 26 (2) 112 - 116 2017/02 [Refereed][Not invited]
   

    Moyamoya disease is a chronic cerebrovascular disease with unknown etiology characterized by steno-occlusive changes at the terminal portion of the internal carotid artery and an abnormal vascular network at the base of the brain. Increasing evidence suggests that surgical revascularization such as direct extracranial-intracranial bypass has potential roles not only for preventing ischemic stroke, but also for reducing the risk of re-bleeding in adult patients with hemorrhagic-onset. Based on these observations, we performed direct/indirect combined revascularization surgery for eleven affected hemispheres of ten adult patients presenting with intracranial hemorrhage. The results of revascularization surgeries were favorable in all patients, and no patient suffered cerebrovascular event during the follow-up period.

• Preventive Effect of Clazosentan against Cerebral Vasospasm after Clipping Surgery for Aneurysmal Subarachnoid Hemorrhage in Japanese and Korean Patients

  Miki Fujimura, Jin-Yang Joo, Jong-Soo Kim, Motonori Hatta, Yoshinari Yokoyama, Teiji Tominaga

  CEREBROVASCULAR DISEASES 44 (1-2) 59 - 67 1015-9770 2017 [Refereed][Not invited]
   

  Background: Clazosentan has been explored worldwide for the prophylaxis of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). In a dose-finding trial (CONSCIOUS-1) conducted in Israel, Europe, and North America, clazosentan (1, 5, and 15 mg/h) significantly reduced the incidence of cerebral vasospasm, but its efficacy in Japanese and Korean patients was unknown. We conducted a double-blind comparative study to evaluate the occurrence of cerebral vasospasm in Japanese and Korean patients with aSAH. Methods: The aim of this multicenter, double-blind, randomized, placebo-controlled, dose-finding phase 2 clinical trial, was to evaluate the efficacy, pharmacokinetics, and safety of clazosentan (5 and 10 mg/h) against cerebral vasospasm after clipping surgery in Japanese and Korean patients with aSAH. Patients aged between 20 and 75 years were administered the study drug within 56 h after the aneurysm rupture and up to day 14 post-aSAH. The incidence of vasospasm, defined as an inner artery diameter reduction of major intracranial arteries >= 34% based on catheter angiography, was compared between each treatment group. Cerebral infarction due to vasospasm at 6 weeks and patients' outcome at 3 months was also compared. Results: Among 181 enrolled patients, 158 completed the study and were analyzed. The incidence of vasospasm up to day 14 after aSAH onset was 80.0% in the placebo group (95% CI 67.0-89.6), 38.5% in the 5 mg/h clazosentan group (95% CI 25.3-53.0), and 35.3% in the 10 mg/h clazosentan group (95% CI 22.4-49.9), indicating that the incidence of vasospasm was significantly reduced by clazosentan treatment (placebo vs. 5 mg/h clazosentan, p < 0.0001; placebo vs. 10 mg/h clazosentan, p < 0.0001). The occurrence of cerebral infarction due to vasospasm was 20.8% in the placebo group (95% CI 10.8-34.1), 3.8% in the 5 mg/h clazosentan group (95% CI 0.5-13.2), and 4.2% in the 10 mg/h clazosentan group (95% CI 0.5-14.3), indicating that clazosentan significantly reduced the occurrence of cerebral infarctions caused by vasospasm (placebo vs. 5 mg/h clazosentan, p = 0.0151; placebo vs. 10 mg/h clazosentan, p = 0.0165). The overall incidence of allcause death and/or vasospasm-related morbidity/mortality was significantly reduced in the 10 mg/h clazosentan group compared with the placebo group (p = 0.0003). Conclusion: These results suggest that clazosentan prevents cerebral vasospasm and subsequent cerebral infarction, and could thereby improve outcomes after performing a clipping surgery for aSAH in Japanese and Korean patients. (C) 2017 The Author(s) Published by S. Karger AG, Basel
• De Novo Development of Moyamoya Disease in an Adult Female with a Genetic Variant of the RNF-213 Gene: Case Report

  Ryosuke Tashiro, Miki Fujimura, Kuniyasu Niizuma, Hidenori Endo, Hiroyuki Sakata, Mika Sato-Maeda, Teiji Tominaga

  Journal of Stroke and Cerebrovascular Diseases 26 (1) e8 - e11 1532-8511 2017/01/01 [Refereed][Not invited]
   

  Background The de novo development of moyamoya disease (MMD) in adults is extremely rare, with only 2 cases being previously reported. Furthermore, the mechanisms underlying the progression of adult MMD have not been elucidated yet. Case report A transient ischemic attack occurred in a 46-year-old woman, owing to progressive MMD. Magnetic resonance (MR) angiography performed 7 years before the diagnosis of MMD did not detect any steno-occlusive changes in the major intracranial vessels, including the internal carotid artery (ICA) and the middle cerebral artery (MCA). However, during the last 2 years, serial MR angiography revealed the gradual progression of left MCA stenosis and ultimately showed apparent stenosis of the bilateral terminal ICA to proximal MCA. Catheter angiography confirmed the definitive diagnosis of MMD. A genetic analysis of RING-finger protein (RNF)-213, an MMD susceptibility gene, revealed that not only the patient, but also her sister, brother, and daughter had the heterozygous variant of the RNF-213 gene. Because of hemodynamic compromise with ischemic symptoms, the patient underwent revascularization surgery on the affected hemisphere, without complications. She had no cerebrovascular event in the postoperative follow-up period of 8 months, and there was no evidence of the further progression of MMD. Conclusion We herein present the entire clinical course of the de novo development of MMD in a female adult. Newly developed MMD in an adult patient with a characteristic variant of the RNF-213 gene appears to be unique.
• Development of Abnormal Hemispheric Vascular Networks Mimicking Cerebral Proliferative Angiopathy in a Child Originally Diagnosed with Deep-Seated Arteriovenous Fistula

  Hiroyuki Sakata, Miki Fujimura, Kenichi Sato, Kuniyasu Niizuma, Hidenori Endo, Teiji Tominaga

  Journal of Stroke and Cerebrovascular Diseases 25 (10) e200 - e204 1532-8511 2016/10/01 [Refereed][Not invited]
   

  Cerebral proliferative angiopathy (CPA), which is characterized by diffuse vascular abnormalities with intermingled normal brain parenchyma, is a rare clinical entity distinct from classical cerebral arteriovenous malformations. Its pathology at initial state and subsequent course of progression has totally been undetermined. We herein presented a case of a child who was initially diagnosed with deep-seated arteriovenous fistula (AVF), and ultimately developed symptomatic CPA-like vascular lesion over a long period of clinical follow-up. A 7-month-old boy was incidentally found to have an AVF in the right basal ganglia and conservatively followed up. Serial magnetic resonance angiograms revealed the gradual proliferation and enlargement of pial and medullary vessels surrounding the AVF. Seven years later, he had a transient ischemic attack followed by intraventricular hemorrhage. A catheter angiogram showed a diffuse large vascular malformation composed of 2 distinct structures, including AVF in the right basal ganglia and the surrounding proliferated pial and medullary arteries in the right hemisphere. Single-photon emission computed tomography with N-isopropyl[123I]-p-iodoamphetamine revealed apparent hemodynamic compromise on the right hemisphere. Targeted embolization of the pseudoaneurysm originating from the right A1 perforator was performed to prevent rebleeding without complications. The patient had no further cerebrovascular events. Perinidal hypoperfusion induced by a deep-seated AVF could be one of the underlying pathologies of progressive angiogenic activity. This is the first case showing the development of abnormal hemispheric vascular networks mimicking CPA, which offers insight into the pathogenesis of this new entity.
• Long-term follow-up of pediatric moyamoya disease treated by combined direct–indirect revascularization surgery: single institute experience with surgical and perioperative management

  Sherif Rashad, Miki Fujimura, Kuniyasu Niizuma, Hidenori Endo, Teiji Tominaga

  Neurosurgical Review 39 (4) 615 - 623 1437-2320 2016/10/01 [Refereed][Not invited]
   

  Moyamoya disease (MMD) is a rare occlusive cerebrovascular disease that mainly presents in children as cerebral ischemia. Prompt treatment with either a direct or indirect revascularization procedure is necessary for children with MMD in order to prevent repeated ischemic events. We herein present our experience with combined direct and indirect bypass surgery for the treatment of pediatric MMD as well as our uniquely designed perioperative protocol. Twenty-three patients with MMD, aged between 2 and 16 years old (mean 9.36), underwent 38 combined bypass procedures between 2008 and 2015. All patients underwent single superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis combined with encephalo-duro-myo-synangiosis (EDMS). The perioperative management protocol was stratified into two unique eras: the first era with normotensive care and the second era with strict blood pressure control (systolic 100–130 mmHg) and routine aspirin administration. Patients were followed after surgery for a period ranging between 3 and 131 months (mean 77 months) in yearly clinical and radiological follow-ups. Three postoperative complications were observed: two cases of cerebral hyperperfusion (2/38, 5.3 %) and one case of perioperative minor stroke (1/38, 2.6 %), two of which were in the first era. No strokes, either ischemic or hemorrhagic, were observed in the follow-up period, and the activity of daily living as shown by the modified Rankin Scale improved in 20 patients, with no deterioration being observed in any of our patients. STA-MCA bypass with EDMS is safe and effective for the management of pediatric MMD and provides long-term favorable outcomes. Perioperative care with blood pressure control combined with the administration of aspirin may reduce the potential risk of surgical complications.
• A study of prognostic factors in 45 cases of atypical meningioma.

  Toshiki Endo, Ayumi Narisawa, Hosam Shata Mohamed Ali, Kensuke Murakami, Takashi Watanabe, Mika Watanabe, Hidefumi Jokura, Hidenori Endo, Miki Fujimura, Yukihiko Sonoda, Teiji Tominaga

  Acta neurochirurgica 158 (9) 1661 - 7 0001-6268 2016/09 [Refereed][Not invited]
   

  BACKGROUND: Atypical meningioma differs from Grade I meningioma in terms of high recurrence rate and short life expectancy. We evaluated the clinical course of atypical meningioma and investigated prognostic factors affecting its outcomes. METHOD: We reviewed 45 patients with atypical meningioma who underwent surgical intervention between January 2000 and December 2013. The mean age of the patients and mean follow-up period was 58.7 years and 81.0 months, respectively. Analyses included factors such as patient age, gender, location and size of tumor, extent of surgical resection (Simpson Grading System), and MIB-1 labeling index (LI). Univariate analysis was used to detect prognostic factors associated with recurrence and survival. RESULTS: The 5-year recurrence-free rate for all 45 patients was 58.4 %; 5- and 10-year survival rates were 83.2 % and 79.9 %, respectively. In univariate analyses, age >60 years, and MIB-1 LI correlated with disease recurrence, whereas age >60 years, subtotal surgical resection, MIB-1 LI, and indication for radiotherapy correlated with death. MIB-1 LI levels higher than 12.8 % and 19.7 % predicted recurrence and death, respectively. In our cohort, 26 patients received postoperative radiotherapy including conventional radiation (n = 21) or gamma knife radiosurgery (n = 5). Postoperative radiotherapy did not decrease recurrence rates in our cohort (p = 0.63). Six and two patients who died during the study period underwent conventional radiation and radiosurgery, respectively. CONCLUSIONS: Age, male gender, extent of surgical resection, and higher MIB-1 LI influenced the outcome of atypical meningioma. In our cohort, postoperative radiotherapy failed to provide long-term tumor control. Following incomplete surgical resection of atypical meningioma in elderly patients, adjuvant postoperative radiotherapy may not be an ideal treatment option, particularly when MIB-1 LI is higher than 19.7 %.
• A case of hydrocephalus in listeria meningitis treated by endoscopic third ventriculostomy

  Takatsugu Abe, Tomohiro Kawaguchi, Miki Fujimura, Teiji Tominaga

  Neurological Surgery 44 (9) 761 - 766 1882-1251 2016/09/01 [Refereed][Not invited]
   

  A 69-year-old woman presented with anorexia, fever, and vomiting. The patient was not a compromised host. She was finally diagnosed with Listeria meningitis and treated with ampicillin and gentamicin. However, her condition worsened over time. Non-contrast head CT showed ventricular dilatation. As a result, continuous nght ventricular drainage was performed. Non-contrast MRI revealed hydrocephalus due to stenosis of the fourth ventricle. She underwent endoscopic third ventriculostomy (ETV) to improve cerebrospinal fluid circulation. This procedure achieved a good result. The efficacy of ETV for post-infectious hydrocephalus has not been proven, but previous cases suggest that ETV would be effective in non-communicating hydrocephalus, even if it were a result of neuroinfection.
• Quantitative assessment of circumferential enhancement along the wall of cerebral aneurysms using mr imaging

  S. Omodaka, H. Endo, K. Niizuma, M. Fujimura, T. Inoue, K. Sato, S. I. Sugiyama, T. Tominaga

  American Journal of Neuroradiology 37 (7) 1262 - 1266 1936-959X 2016/07/01 [Refereed][Not invited]
   

  BACKGROUND AND PURPOSE: The incidence of wall enhancement of cerebral aneurysms on vessel wall MR imaging has been described as higher in ruptured intracranial aneurysms than in unruptured intracranial aneurysms, but the difference in the degree of enhancement between ruptured and unruptured aneurysms is unknown. We compared the degree of enhancement between ruptured and unruptured intracranial aneurysms by using quantitative MR imaging measures. MATERIALS AND METHODS: We performed quantitative analyses of circumferential enhancement along the wall of cerebral aneurysms in 28 ruptured and 76 unruptured consecutive cases by using vessel wall MR imaging. A 3D-T1-weighted fast spin-echo sequence was obtained before and after contrast media injection, and the wall enhancement index was calculated. We then compared characteristics between ruptured and unruptured aneurysms. RESULTS: The wall enhancement index was significantly higher in ruptured than in unruptured aneurysms (1.70 1.06 versus 0.89 0.88, respectively P=.0001). The receiver operating characteristic curve analysis found that the most reliable cutoff value of the wall enhancement index to differentiate ruptured from unruptured aneurysms was 0.53 (sensitivity, 0.96 specificity, 0.47). The wall enhancement index remained significant in the multivariate logistic regression analysis (P< .0001). CONCLUSIONS: Greater circumferential enhancement along the wall of cerebral aneurysms correlates with the ruptured state. A quantitative evaluation of circumferential enhancement by using vessel wall MR imaging could be useful in differentiating ruptured from unruptured intracranial aneurysms.
• Temporal profile of magnetic resonance angiography and decreased ratio of regulatory T cells after immunological adjuvant administration to mice lacking RNF213, a susceptibility gene for moyamoya disease

  Atsushi Kanoke, Miki Fujimura, Kuniyasu Niizuma, Taku Fujimura, Aya Kakizaki, Akira Ito, Hiroyuki Sakata, Mika Sato-Maeda, Shigeo Kure, Teiji Tominaga

  Brain Research 1642 1 - 9 1872-6240 2016/07/01 [Refereed][Not invited]
   

  Moyamoya disease (MMD) is a chronic, occlusive cerebrovascular disease with an unknown etiology and is characterized by an abnormal vascular network at the base of the brain. Recent studies identified the RNF213 gene (RNF213) as an important susceptibility gene for MMD however, the mechanisms underlying the RNF213 abnormality related to MMD have not yet been elucidated. We previously reported that Rnf213-deficient mice and Rnf213 p. R4828K knock-in mice did not spontaneously develop MMD, indicating the importance of secondary insults in addition to genetic factors in the pathogenesis of MMD. The most influential secondary insult is considered to be an immunological reaction because RNF213 is predominantly expressed in immunological tissues. Therefore, we herein attempted to evaluate the role of an immunological stimulation as a supplementary insult to the target disruption of RNF213 in the pathophysiology of MMD. Rnf213-deficient mice were treated with strong immunological adjuvants including muramyl dipeptide (MDP)-Lys (L18), and then underwent time-sequential magnetic resonance angiography (MRA) up to 40 weeks of age. The results obtained did not reveal any characteristic finding of MMD, and no significant difference was observed in MRA findings or the anatomy of the circle of Willis between Rnf213-deficient mice and wild-type mice after the administration of MDP-Lys (L18). The ratio of regulatory T cells after the administration of MDP-Lys (L18) was significantly decreased in Rnf213-deficient mice (p< 0.01), suggesting the potential role of the RNF213 abnormality in the differentiation of regulatory T cells. Although the mechanisms underlying the development of MMD currently remain unclear, the RNF213 abnormality may compromise immunological self-tolerance, thereby contributing to the development of MMD.
• Brain stem infarction due to basilar artery dissection in a patient with moyamoya disease four years after successful bilateral revascularization surgeries

  Takatsugu Abe, Miki Fujimura, Shunji Mugikura, Hidenori Endo, Teiji Tominaga

  Journal of Stroke and Cerebrovascular Diseases 25 (6) e79 - e82 1532-8511 2016/06/01 [Refereed][Not invited]
   

  Moyamoya disease (MMD) is a rare cerebrovascular disease with an unknown etiology and is characterized by intrinsic fragility in the intracranial vascular walls such as the affected internal elastic lamina and thinning medial layer. The association of MMD with intracranial arterial dissection is extremely rare, whereas that with basilar artery dissection (BAD) has not been reported previously. A 46-year-old woman developed brain stem infarction due to BAD 4 years after successful bilateral superficial temporal artery-middle cerebral artery anastomosis with indirect pial synangiosis for ischemic-onset MMD. She presented with sudden occipitalgia and subsequently developed transient dysarthria and mild hemiparesis. Although a transient ischemic attack was initially suspected, her condition deteriorated in a manner that was consistent with left hemiplegia with severe dysarthria. Magnetic resonance (MR) imaging revealed brain stem infarction, and MR angiography delineated a double-lumen sign in the basilar artery, indicating BAD. She was treated conservatively and brain stem infarction did not expand. One year after the onset of brain stem infarction, her activity of daily living is still dependent (modified Rankin Scale of 4), and there were no morphological changes associated with BAD or recurrent cerebrovascular events during the follow-up period. The association of MMD with BAD is extremely rare. While considering the common underlying pathology such as an affected internal elastic lamina and fragile medial layer, the occurrence of BAD in a patient with MMD in a stable hemodynamic state is apparently unique.
• Nonaneurysmal subarachnoid hemorrhage due to unfused or twiglike middle cerebral artery rupture: Two case reports

  Ryosuke Tashiro, Takashi Inoue, Ichiyo Shibahara, Masayuki Ezura, Hiroshi Uenohara, Miki Fujimura, Teiji Tominaga

  Journal of Stroke and Cerebrovascular Diseases 25 (6) e77 - e78 1532-8511 2016/06/01 [Refereed][Not invited]
   

  Background An unfused or twiglike middle cerebral artery (MCA) is a congenital anomaly related to the abnormal development of the MCA. An unfused or twiglike MCA can cause both ischemic and hemorrhagic strokes. Previous reports have shown that an unfused or twiglike MCA with coexisting aneurysms can cause subarachnoid hemorrhage (SAH). Cases Two patients presented with nonaneurysmal SAH due to an unfused or twiglike MCA. Both patients had stenosis of the proximal M1 segment of the left MCA and abnormal vascular nets distal to the stenotic lesion. Vasculature distal to the abnormal vascular nets remained grossly normal. These findings were not evident in computed tomography or magnetic resonance angiography. Conclusion An unfused or twiglike MCA can cause nonaneurysmal SAH. Digital subtraction angiography is necessary for accurate diagnosis.
• Implications of Off-Label Use of Acetazolamide in the Management of Moyamoya Disease in Japan

  Shunji Mugikura, Miki Fujimura, Shoki Takahashi

  RADIOLOGY 279 (2) 652 - 653 0033-8419 2016/05 [Refereed][Not invited]
  
• Clinical features of subarachnoid hemorrhage in patients with positive cancer history

  Ichiyo Shibahara, Takashi Watanabe, Masayuki Ezura, Takashi Inoue, Miki Fujimura, Naoto Kimura, Tomoo Inoue, Ichiro Suzuki, Akiko Nishino, Shinjitsu Nishimura, Hiroshi Uenohara, Teiji Tominaga

  JOURNAL OF NEURO-ONCOLOGY 128 (1) 129 - 136 0167-594X 2016/05 [Refereed][Not invited]
   

  Advances in cancer treatment have dramatically increased long-term survivors. Prolonged survival increases comorbidity risk, but there is a paucity of studies on how cancer history alters clinical outcomes from subsequent diseases. This study aims to investigate whether positive cancer history influences clinical outcome following subarachnoid hemorrhage (SAH). We retrospectively reviewed consecutive SAH patients admitted between January 2008 and March 2014. Medical histories, known SAH risk factors, and outcome were compared between SAH patients with and without cancer history. Out of the 498 SAH patients, 55 cases had cancer history, 438 cases had no cancer history and 5 cases had an unknown cancer history. Compared with SAH patients without cancer history, those with cancer history had poorer Hunt & Hess grade at SAH presentation (P = 0.021), and poorer modified Rankin Scale (mRS) score at discharge (P < 0.001). After adjustment for age, sex, modified Fisher, previous SAH, history of hypertension, current smoking status, and current alcohol consumption, positive cancer history remained an independent risk factor for poorer mRS0-6 [odds ratio (OR) = 2.25, 95 % confidence interval (CI) 1.28-3.94] and mRS6 (OR = 2.74, 95 % CI 1.40-5.37). Furthermore, stratified analysis by Hunt & Hess grade adjusted by age, sex, and modified Fisher scale, OR of poorer mRS0-6 was 2.12 (95 % CI 0.89-5.05) and OR of mRS6 was 3.68 (95 % CI 1.35-10.04). After adjustment of patients for demographic factors, classical risk factors for SAH and Hunt & Hess grade, previous cancer history is a risk factor for the poor functional outcome of SAH.
• Ventricle wall dissection and vascular preservation with the pulsed water jet device: novel tissue dissector for flexible neuroendoscopic surgery.

  Tomohiro Kawaguchi, Atsuhiro Nakagawa, Toshiki Endo, Miki Fujimura, Yukihiko Sonoda, Teiji Tominaga

  Journal of neurosurgery 124 (3) 817 - 22 2016/03 [Refereed][Not invited]
   

  OBJECTIVE: Neuroendoscopic surgery allows minimally invasive surgery, but lacks effective methods to control bleeding. Water jet dissection with continuous flow has been used in liver and kidney surgery since the 1980s, and is effective for tissue manipulation with vascular preservation, but involves some potential risks, such as elevation of intracranial pressure during application in the ventricles. The authors previously reported the efficacy of the actuator-driven pulsed water jet device (ADPJ) to dissect soft tissue with vascular preservation in microscopic neurosurgery. This feasibility study investigated the use of the ADPJ to reduce the amount of water usage, leading to more safety with sustained efficacy. METHODS: A small-diameter pulsed water jet device was developed for use with the flexible neuroendoscope. To identify the optimal conditions for the water jet, the flow rate, water pressure, and distance between the nozzle and target were analyzed in an in vitro study by using a gelatin brain phantom. A ventricle model was used to monitor the internal pressure and temperature. For ex vivo experiments the porcine brain was harvested and ventricle walls were exposed, and subsequently immersed into physiological saline. For in vivo experiments the cortex was microsurgically resected to make the small cortico-ventricle window, and then the endoscope was introduced to dissect ventricle walls. RESULTS: In the in vitro experiments, water pressure was approximately 6.5 bar at 0.5 mm from the ADPJ nozzle and was maintained at 1 mm, but dropped rapidly toward 50% at 2 mm, and became 10% at 3.5 mm. The ADPJ required less water to achieve the same dissection depth compared with the continuous-flow water jet. With the ventricle model, the internal pressure and temperature were well controlled at the baseline, with open water drainage. These results indicated that the ADPJ can be safely applied within the ventricles. The ADPJ was introduced into a flexible endoscope and the ventricle walls were dissected in both the ex vivo and in vivo conditions. The ventricle wall was dissected without obscuring the view, and the vascular structures were anatomically preserved under direct application. Histological examination revealed that both the vessels on the ventricle wall and the fine vessels in the parenchyma were preserved. CONCLUSIONS: The ADPJ can safely and effectively dissect the ventricle wall, with vascular preservation in immersed conditions. To achieve the optimal result of tissue dissection with minimal surgical risk, the ADPJ is a potential device for neuroendoscopic surgery of the ventricles.
• Moyamoya Disease

  Miki Fujimura, Oh Young Bang, Jong S. Kim

  Frontiers of Neurology and Neuroscience 40 204 - 220 1662-2804 2016 [Refereed][Not invited]
   

  Moyamoya disease (MMD) is a chronic occlusive cerebrovascular disease characterized by progressive stenosis at the terminal portion of the internal carotid artery and an abnormal vascular network at the base of the brain. Although its etiology is unknown, recent genetic studies have identified RNF213 in the 17q25-ter region as an important susceptibility gene of MMD among East Asian populations. A c.14576G> A polymorphism in RNF213 was identified in 95% of MMD patients with a family history and in 79% of sporadic cases, and patients carrying this polymorphism exhibited significantly earlier disease onset and a more-severe form of MMD. Due possibly to genetic differences, the prevalence of MMD is higher in East Asia (e.g., Korea and Japan) than in Western countries. The MMD prevalence peaks at two ages with different clinical presentations: around 10 years and at 30-45 years. Ischemic symptoms, including transient ischemic attacks, are the most important clinical manifestation in both children and adults. Intracranial hemorrhages are more frequent in adults than in children. Catheter angiography is a diagnostic method of choice. Magnetic resonance angiography and computed tomography angiography are noninvasive diagnostic methods. High-resolution vessel-wall magnetic resonance imaging also helps in diagnosing MMD by revealing concentric vessel-wall narrowing with basal collaterals. Surgical revascularization such as extracranial-intracranial bypass is the preferred procedure for MMD patients presenting with ischemic stroke. Surgical therapy may also be effective in patients with hemorrhages, based on recent observations in the Japan Adult Moyamoya trial. Procedure-related cerebral infarction and hyperperfusion syndrome are potential complications that can lead to neurological deterioration.
• A case of ruptured infectious anterior cerebral artery aneurysm treated by interposition graft bypass using the superficial temporal artery.

  Abe T, Endo H, Shimizu H, Fujimura M, Endo T, Sakata H, Watanabe M, Tominaga T

  Surgical neurology international 7 5  2229-5097 2016 [Refereed][Not invited]
  
• Grossly calcified choroid plexus concealing foramen of Monro meningiomas as an unusual cause of obstructive hydrocephalus.

  Kawaguchi T, Fujimura M, Tominaga T

  Asian journal of neurosurgery 11 (1) 74  1793-5482 2016/01 [Refereed][Not invited]
  
• Transient middle cerebral artery occlusion in mice induces neuronal expression of RNF213, a susceptibility gene for moyamoya disease

  Mika Sato-Maeda, Miki Fujimura, Atsushi Kanoke, Yuiko Morita-Fujimura, Kuniyasu Niizuma, Teiji Tominaga

  Brain Research 1630 50 - 55 1872-6240 2016 [Refereed][Not invited]
   

  Although recent genome-wide and locus-specific association studies revealed that the RING finger protein 213 (RNF213) gene is an important susceptibility gene for moyamoya disease (MMD), the exact mechanism by which the genetic alteration of RNF213 contributes to the development of MMD has not yet been elucidated. A quantitative reverse transcription polymerase chain reaction (PCR) analysis revealed that the constitutive expression of the RNF213 gene was very low in adult and embryonic brain tissue. However, information regarding the temporal and spatial expression patterns of the RNF213 gene under the condition of cerebral ischemia, which is one of characteristic pathologies associated with MMD, is currently limited. In order to address this critical issue, Rnf213 mRNA expression was investigated in mouse brains subjected to 60 min of transient middle cerebral artery occlusion (tMCAO). Male C57BL6/j mice underwent tMCAO through the intraluminal blockade of MCA. Expression of the Rnf213 gene in the tMCAO brain was investigated with in situ RNA hybridization and a real-time PCR analysis from 1 to 72 h after tMCAO. In situ RNA hybridization revealed a significant increase in Rnf213 mRNA levels in the cerebral cortex supplied by the affected MCA, especially at the penumbra area, as early as 6 h after tMCAO, and these levels had increased further by 24 h. Rnf213 gene expression remained unchanged in the non-ischemic hemisphere or control specimens. Double staining of Rnf213 mRNA with NeuN immunohistochemistry revealed Rnf213 hybridization signal expression mostly in neurons. The real-time PCR analysis confirmed induction of the Rnf213 gene after tMCAO. Therefore, the Rnf213 gene was up-regulated in the ischemic brain, especially at the penumbra area, 6 h after tMCAO. Early increases in RNF213 gene expression in neurons after tMCAO indicate its involvement in cerebral ischemia, which is an underlying pathology of MMD. Further investigation is required to clarify its exact role in the pathophysiology of MMD.
• Difference in Transcranial Doppler Velocity and Patient Age between Proximal and Distal Middle Cerebral Artery Vasospasms after Aneurysmal Subarachnoid Hemorrhage.

  Misaki Kohama, Shinichiro Sugiyama, Kenichi Sato, Hidenori Endo, Kuniyasu Niizuma, Toshiki Endo, Makoto Ohta, Yasushi Matsumoto, Miki Fujimura, Teiji Tominaga

  Cerebrovascular diseases extra 6 (2) 32 - 9 2016 [Refereed][Not invited]
   

  BACKGROUND: Transcranial Doppler (TCD) is used to monitor cerebral vasospasm after subarachnoid hemorrhage (SAH), but its diagnostic ability is reported to be limited. Therefore, the purpose of this study was to investigate the relationship between the diagnosability of TCD and the localization of the vasospasm. METHODS: This retrospective study included 20 patients who presented with symptomatic vasospasm after SAH. All 20 patients underwent daily TCD examinations and cerebral angiography after the onset of delayed cerebral ischemia. We defined positive findings on TCD as a maximum flow velocity >200 cm/s or as a mean flow velocity >120 cm/s at the horizontal part of the middle cerebral artery (MCA). We also examined the site of vasospasm on cerebral angiography. RESULTS: Fourteen patients had true-positive findings on TCD examination, and cerebral angiography showed diffuse vasospasm involving the horizontal segment of the MCA. However, 6 patients had false-negative findings on TCD examination, and cerebral angiography showed vasospasm localized at the distal part of the MCA (the insular and/or cortical segments). The patients with proximal vasospasm were significantly younger than those with distal vasospasm. Blood flow velocity at initial TCD and the increase in velocity at the onset of vasospasm were lower and smaller, respectively, in the distal vasospasm group. CONCLUSIONS: In patients with cerebral vasospasm localized at the distal part of the MCA, flow velocity at the horizontal segment of the MCA did not increase to the level we defined as positive. To avoid such false negatives, a slight increase in velocity on TCD should be considered as positive in distal vasospasm cases, especially in older patients.
• Risk factors for meningitis after craniotomy in patients with subarachnoid hemorrhage due to anterior circulation aneurysms rupture

  Takashi Inoue, Hiroaki Shimizu, Miki Fujimura, Kenichi Sato, Hidenori Endo, Kuniyasu Niizuma, Hiroyuki Sakata, Teiji Tominaga

  CLINICAL NEUROLOGY AND NEUROSURGERY 139 302 - 306 0303-8467 2015/12 [Refereed][Not invited]
   

  Objectives: Postoperative meningitis is a serious complication occurring after neurosurgical interventions. However, few investigations have focused specifically on the risk factors that predispose patients to meningitis after major craniotomy. This study identified the risk factors for postoperative meningitis after neurovascular surgery, and investigated the relationship between postoperative meningitis and clinical outcome. Patients and methods: A total of 148 consecutive patients with subarachnoid hemorrhage (SAH) who underwent clipping surgery through a pterional approach within 72 h between January 2007 and September 2011 were retrospectively analyzed. The treatment strategy of our hospital for patients with SAH was based on the findings of digital subtraction angiography in the acute phase. Coil embolization was firstly considered, and clipping through craniotomy if indicated was performed as soon as possible. Prophylactic antibiotics were administered before beginning craniotomy and for at least 3 days after. Hydrocortisone was used to prevent hyponatremia if allowed by the medical condition of the patient. Intrathecal administration of nicardipine hydrochloride was given if required for vasospasm treatment. Meningitis was clinically diagnosed from the blood samplings and cerebrospinal fluid (CSF) examinations. Data were collected from the electronic and paper charts. The status of modified Rankin scale (mRS) 0-2 at discharge was defined as favorable outcome. Results: A total of 14 patients (9.5%) had meningitis during this study period. Symptomatic vasospasm was detected in 33 patients (22.3%), and 12 patients (8.1%) had permanent neurological deficits caused by vasospasm. Overall, 109 patients (73.6%) had favorable outcome. The longer duration of drainage placement, presence of CSF leakage, and intrathecal administration of vasodilatory agent showed significantly higher incidence of postoperative meningitis in univariate analysis (p = 0.0093, 0.0017, and 0.0090, respectively). The proportion of favorable outcome patients at discharge (mRS 0-2) was significantly lower in patients with postoperative meningitis (35.7%) than in patients without it (77.6%) (p = 0.0004). The duration of in-hospital stay was significantly longer in patients with postoperative meningitis (median 58.5, range 28-115 days) than in patients without it (median 38.5, range 19-149 days) (p < 0.001). Multivariate logistic regression analysis showed that only presence of CSF leakage was associated with postoperative meningitis (p = 0.0299). Conclusion: Meningitis after surgery is still a serious complication that requires preventative intervention. The clinical outcome of patients with postoperative meningitis after neurovascular surgery is not still satisfactory. (C) 2015 Elsevier B.V. All rights reserved.
• A Case of Small Middle Cerebral Artery (M1) Aneurysm with Rapid Enlargement

  Miki Fujimura, Kuniyasu Niizuma, Teiji Tominaga

  Japanese Journal of Neurosurgery 24 (12) 878 - 882 2015/12 [Refereed][Not invited]
  
• Experimental model of small subcortical infarcts in mice with long-lasting functional disabilities

  Hiroki Uchida, Hiroyuki Sakata, Miki Fujimura, Kuniyasu Niizuma, Yoshihiro Kushida, Mari Dezawa, Teiji Tominaga

  BRAIN RESEARCH 1629 318 - 328 0006-8993 2015/12 [Refereed][Not invited]
   

  Small subcortical infarcts account for 25% of all ischemic strokes. Although once considered to be a small vessel disease with a favorable outcome, recent studies have reported relatively poor long-term prognoses following small subcortical infarcts. Limited pre-clinical modeling has hampered understanding of the etiology and development of treatments for this disease. Therefore, we attempted to develop a new experimental model of small subcortical infarcts in mice to investigate pathophysiological changes in the corticospinal tract and assess long-term behavioral performance. The vasoconstrictor peptide, endothlin-1 (ET-1), in combination with the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), were injected into the internal capsule of mice. Histological and behavioral tests were performed 0-8 weeks after the injection. The ET-1/L-NAME injection resulted in severe neurological deficits that continued for up to 8 weeks. The loss of axons and myelin surrounded by reactive gliosis was identified in the region of the injection, in which the vasoconstriction of microvessels was also observed. Moreover, a tract-tracing study revealed an interruption in axonal flow at the internal capsule. The present model of small subcortical infarcts is unique and novel due to the reproduction of neurological deficits that continue for a long period, up to 8 weeks, as well as the use of mice as experimental animals. The reproducibility, simplicity, and easy adoptability make the present model highly appealing for use in further pre-clinical studies on small subcortical infarcts. (C) 2015 Elsevier B.V. All rights reserved.
• Cerebral Blood Flow after Acute Bypass with Parent Artery Trapping in Patients with Ruptured Supraclinoid Internal Carotid Artery Aneurysms

  Hidenori Endo, Miki Fujimura, Hiroaki Shimizu, Takashi Inoue, Kenichi Sato, Kuniyasu Niizuma, Teiji Tominaga

  JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 24 (10) 2358 - 2368 1052-3057 2015/10 [Refereed][Not invited]
   

  Background: Bypass with parent artery trapping is an alternative treatment method for ruptured internal carotid artery (ICA) aneurysms when clipping or coiling is contraindicated. However, the efficacy and safety of this strategy during the acute stage of subarachnoid hemorrhage (SAH) is undetermined. Methods: A retrospective review of 955 consecutive patients presenting SAH between 2006 and 2014 identified 17 patients with ruptured ICA aneurysms treated by bypass with parent artery trapping within 72 hours after the bleeding (bypass group). The 26 cases with ruptured posterior communicating artery aneurysms treated with clipping during the same period were defined as a control group (clipping group). Postoperative cerebral blood flow (CBF) was evaluated by single photon emission computed tomography (SPECT). We analyzed the postoperative hemodynamic status, surgical complications, and the clinical outcomes. Results: Postoperative rebleeding did not occur in any of the cases. CBF in the first postoperative week in the bypass group was lower than that in the clipping group (P = .0165). This CBF decrease improved in the second postoperative week and did not differ from that of the clipping group. The incidence of acute ischemic complications was significantly higher in the bypass group (P = .0284), but the incidence of delayed cerebral ischemia did not differ between the 2 groups. The incidence of favorable outcomes at 6 months was 82.4% in the bypass group and 81% in the clipping group. Conclusions: Although the transient CBF decrease with acute ischemic complications should be noted, acute bypass with parent artery trapping is safe and effective for unclippable/uncoilable ruptured ICA aneurysms.
• Temporal profile of the vascular anatomy evaluated by 9.4-tesla magnetic resonance angiography and histological analysis in mice with the R4859K mutation of RNF213, the susceptibility gene for moyamoya disease

  Atsushi Kanoke, Miki Fujimura, Kuniyasu Niizuma, Akira Ito, Hiroyuki Sakata, Mika Sato-Maeda, Yuiko Morita-Fujimura, Shigeo Kure, Teiji Tominaga

  BRAIN RESEARCH 1624 497 - 505 0006-8993 2015/10 [Refereed][Not invited]
   

  Moyamoya disease (MMD) is a chronic, occlusive cerebrovascular disease with an unknown etiology. Recent genome-wide and locus-specific association studies identified the RNF213 gene (RNF213) as an important susceptibility gene of MMD among East Asian populations; however, the mechanism by which an abnormality in RNF213 leads to MMD has not yet been elucidated. Therefore, we herein generated Rnf213-knock-in mice (RNF213-KI) expressing a missense mutation in mouse Rnf213, p. R4828K, on Exon 61, corresponding to human RNF213, p. R4859K, on Exon 60, in MMD patients, and investigated whether they developed MMD. We assessed the temporal profile of intracranial arteries by 9.4-T magnetic resonance angiography (MRA) continuously in the same mouse up to 64 weeks of age. The ratios of the outer diameter of the internal carotid artery (ICA)/basilar artery (BA) and middle cerebral artery (MCA)/BA were evaluated histopathologically. The common carotid arteries (CCA) were sectioned and arterial wall thickness/thinness was evaluated by Elastica-Masson staining before and after CCA ligation, which selectively induced vascular hyperplasia. The results obtained showed that RNF213-KI grew normally, with no significant difference being observed in MBA findings or the anatomy of the circle of Willis between homozygous RNF213-KI and wild-type (Wt) littermates. Furthermore, no significant difference was noted in the diameter of the intracranial vasculature (ICA/BA; p= 0.82, MCA/BA; p =0.27) or in vascular remodeling after CCA ligation. Therefore, RNF213-KI did not spontaneously develop MMD. Multiple secondary insults such as environmental factors may contribute to the onset of MMD in addition to genetic factors. (c) 2015 Elsevier B.V. All rights reserved.
• Use of actuator-driven pulsed water jet in brain and spinal cord cavernous malformations resection

  Toshiki Endo, Yoko Takahashi, Atsuhiro Nakagawa, Kuniyasu Niizuma, Miki Fujimura, Teiji Tominaga

  Clinical Neurosurgery 11 394 - 403 0148-396X 2015/09/01 [Refereed][Not invited]
   

  Background: A piezo actuator-driven pulsed water jet (ADPJ) system is a novel surgical instrument that enables dissection of tissue without thermal damage. It can potentially resect intra-axial lesions while preserving neurological function. OBJECTIVE: To report our first experience of applying an ADPJ system to brain and spinal cord cavernous malformations. METHODS: Four patients (2 women and 2 men, mean age 44.5 years) with brain (n = 3) and spinal cord (n = 1) cavernous malformations were enrolled in the study. All surgeries were performed with the aid of the ADPJ system. Postoperative neurological function and radiological findings were evaluated. RESULTS: The ADPJ system was useful in dissecting boundaries between the lesion and surrounding brain/spinal cord tissues. The pulsed water jet provided a clear surgical view and helped surgeons follow the margins. Water jet dissection peeled off the brain and spinal cord tissues from the lesion wall. Surrounding gliotic tissue was preserved. As a consequence, the cavernous malformations were successfully removed. Postoperative magnetic resonance imaging confirmed total removal of lesions in all cases. Preoperative neurological symptoms completely resolved in 2 patients. The others experienced partial recovery. No patients developed new postoperative neurological deficits facial palsy temporarily worsened in 1 patient who underwent a suprafacial colliculus approach for the brainstem lesion. CONCLUSION: The ADPJ provided a clear surgical field and enabled surgeons to dissect boundaries between lesions and surrounding brain and spinal cord gliotic tissue. The ADPJ system is a feasible option for cavernous malformation surgery, enabling successful tumor removal and preservation of neurological function.
• Significance of Cerebral Blood Flow Analysis in the Acute Stage after Revascularization Surgery for Moyamoya Disease

  Miki Fujimura, Teiji Tominaga

  NEUROLOGIA MEDICO-CHIRURGICA 55 (10) 775 - 781 0470-8105 2015/09 [Refereed][Not invited]
   

  Moyamoya disease is a chronic, occlusive cerebrovascular disease with unknown etiology characterized by steno-occlusive changes at the terminal portion of the internal carotid artery, either bilaterally or unilaterally, and an abnormal vascular network at the base of the brain. Surgical revascularization such as extracranial-intracranial (EC-IC) bypass is the preferred procedure for moyamoya disease. Despite the favorable long-term outcome, cerebral infarction and hyperperfusion syndrome are potential complications of this procedure, which can lead to neurological deterioration in the acute stage. In light of the similar clinical presentations between perioperative ischemia and hyperperfusion, it is essential to attempt a prompt cerebral blood flow (CBF) measurement in the acute stage after EC-IC bypass for moyamoya disease to differentiate these distinct pathologies, because the management of cerebral ischemia and hyperperfusion is contradictory to each other. Routine CBF analysis by single-photon emission computed tomography and/or magnetic resonance imaging not only facilitated a safer perioperative management but also provided important information about dynamic pathology of the hemodynamic conversion in the acute stage after revascularization surgery for moyamoya disease. We represent the current status of CBF analysis during the perioperative period of revascularization surgery for moyamoya disease, and sought to discuss its significance and efficacy to avoid surgical complications.
• High-grade Cerebral Arteriovenous Malformation Treated with Targeted Embolization of a Ruptured Site: Wall Enhancement of an Intranidal Aneurysm as a Sign of Ruptured Site

  Shunsuke Omodaka, Hidenori Endo, Miki Fujimura, Kuniyasu Niizuma, Kenichi Sato, Yasushi Matsumoto, Teiji Tominaga

  NEUROLOGIA MEDICO-CHIRURGICA 55 (10) 813 - 817 0470-8105 2015/09 [Refereed][Not invited]
   

  Partial targeted embolization of the ruptured site of cerebral arteriovenous malformations (AVMs) is considered effective to prevent rebleeding. The site of rupture is usually determined by morphological features, such as an intranidal aneurysm or a venous varix; however, the site can be difficult to identify in high-grade AVM with complicated angioarchitecture. The authors present a case of a 36-year-old woman with high-grade AVM presented with repeated hemorrhage. Cerebral angiography showed intranidal aneurysm, which was considered the ruptured site. The T-1-weighted imaging with gadolinium enhancement demonstrated linear enhancement along the outer surface of the thickened wall of the intranidal aneurysm, which could be supplementary information to identify the ruptured site. Obliteration of the intranidal aneurysm was successfully achieved by emergent targeted embolization using N-butyl cyanoacrylate. The patient recovered and regained an independent status. The patient underwent volume-staged radiosurgery and experienced no further hemorrhage during the 26 months follow-up. Targeted embolization of the ruptured site is considered effective to prevent rebleeding in high-grade cerebral AVMs. Wall enhancement of the intranidal aneurysm, in addition to the structural characteristics, could be helpful in identifying the site of rupture embedded in the complicated angioarchitecture.
• Use of Actuator-Driven Pulsed Water Jet in Brain and Spinal Cord Cavernous Malformations Resection

  Toshiki Endo, Yoko Takahashi, Atsuhiro Nakagawa, Kuniyasu Niizuma, Miki Fujimura, Teiji Tominaga

  OPERATIVE NEUROSURGERY 11 (3) 394 - 403 2332-4252 2015/09 [Refereed][Not invited]
   

  BACKGROUND: A piezo actuator-driven pulsed water jet (ADPJ) system is a novel surgical instrument that enables dissection of tissue without thermal damage. It can potentially resect intra-axial lesions while preserving neurological function. OBJECTIVE: To report our first experience of applying an ADPJ system to brain and spinal cord cavernous malformations. METHODS: Four patients (2 women and 2 men, mean age 44.5 years) with brain (n = 3) and spinal cord (n = 1) cavernous malformations were enrolled in the study. All surgeries were performed with the aid of the ADPJ system. Postoperative neurological function and radiological findings were evaluated. RESULTS: The ADPJ system was useful in dissecting boundaries between the lesion and surrounding brain/spinal cord tissues. The pulsed water jet provided a clear surgical view and helped surgeons follow the margins. Water jet dissection peeled off the brain and spinal cord tissues from the lesion wall. Surrounding gliotic tissue was preserved. As a consequence, the cavernous malformations were successfully removed. Postoperative magnetic resonance imaging confirmed total removal of lesions in all cases. Preoperative neurological symptoms completely resolved in 2 patients. The others experienced partial recovery. No patients developed new postoperative neurological deficits; facial palsy temporarily worsened in 1 patient who underwent a suprafacial colliculus approach for the brainstem lesion. CONCLUSION: The ADPJ provided a clear surgical field and enabled surgeons to dissect boundaries between lesions and surrounding brain and spinal cord gliotic tissue. The ADPJ system is a feasible option for cavernous malformation surgery, enabling successful tumor removal and preservation of neurological function.
• Outflow Occlusion with Occipital Artery-Posterior Inferior Cerebellar Artery Bypass for Growing Vertebral Artery Fusiform Aneurysm with Ischemic Onset: A Case Report

  Ryuzaburo Kochi, Hidenori Endo, Miki Fujimura, Kenichi Sato, Shin-ichiro Sugiyama, Shin-ichiro Osawa, Teiji Tominaga

  JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 24 (8) E223 - E226 1052-3057 2015/08 [Refereed][Not invited]
   

  Surgical treatments should be considered for vertebral artery fusiform aneurysms, which become symptomatic due to cerebral ischemia or mass effect. Ischemic complication is one of the major problems after surgical or endovascular trapping, which is associated with unfavorable outcomes. The authors present a case with growing vertebral artery (VA) fusiform aneurysm with ischemic onset successfully treated with outflow occlusion with occipital artery-posterior inferior cerebellar artery (OA-PICA) bypass. A 50-year-old woman presented with left PICA territory infarction. Left vertebral angiography (VAG) showed occlusion of the left VA at the proximal V4 segment. Right VAG revealed that the distal part of the left V4 segment with fusiform aneurysmal dilatation was reconstituted through vertebrobasilar junction, and the left PICA was the outlet of the blood flow from the fusiform aneurysm. Although the patient was treated conservatively, enlargement of the left VA fusiform aneurysm was observed 8 months after the initial presentation. Considering the potential risks for future stroke or bleeding, we performed clip occlusion of the origin of the left PICA, which could achieve outflow occlusion of the fusiform aneurysm with preservation of the perforators arising around the aneurysm. We created OA-PICA anastomosis for revascularization of the distal PICA. The postoperative course was uneventful, and the postoperative right VAG revealed occlusion of the fusiform aneurysm. Outflow occlusion instead of trapping is an effective surgical option for VA fusiform aneurysm to achieve obliterate the aneurysm with preservation of the perforator at the blind end.
• Therapeutic Clip Occlusion of the Anterior Choroidal Artery Involved with Partially Thrombosed Fusiform Aneurysm: A Case Report

  Sherif Rashad, Hidenori Endo, Ahmed Elsayed Sultan, Hiroaki Shimizu, Miki Fujimura, Kenichi Sato, Yasushi Matsumoto, Teiji Tominaga

  JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 24 (8) E227 - E230 1052-3057 2015/08 [Refereed][Not invited]
   

  Background: We describe a rare case with partially thrombosed fusiform anterior choroidal artery (AchA) aneurysm successfully treated with therapeutic occlusion of the AchA. Clinical presentation: A 58-year-old man presented with transient mild hemiparesis of the right side. Magnetic resonance imaging (MRI) showed an ischemic lesion in the posterior limb of the left internal capsule. Digital subtraction angiography (DSA) revealed a left internal carotid artery saccular aneurysm (14.5-mm diameter) arising from the supraclinoid segment. The left AchA was not detected in the initial DSA, and MRI showed the aneurysm to be partially thrombosed. The second DSA performed 2 weeks after the onset showed recanalization of the thrombosed portion of the aneurysm with the left AchA apparently arising from its tip. The aneurysm was diagnosed as a partially thrombosed fusiform AchA aneurysm. Results: Open surgery was performed and a titanium clip was applied to the base of the fusiform aneurysm under motor evoked potential monitoring, which remained unchanged after clipping. Occlusion of the aneurysm was confirmed by Doppler ultrasound and intraoperative fluorescence angiography. Furthermore, Doppler ultrasound and fluorescence angiography showed that the blood flow supplying the pyramidal tract was reconstituted by the retrograde collateral flow from the choroidal segment. The aneurysm was completely obliterated in postoperative DSA, which demonstrated retrograde filling of the AchA through the posterior circulation. The patient manifested transient weakness of the right side postoperatively, which was completely recovered after short-term rehabilitation. Conclusions: This case illustrates the unique clinical course of a rare partially thrombosed fusiform AchA aneurysm, successfully treated with therapeutic clip occlusion of the AchA under the multimodal monitoring.
• Ruptured Cerebral Microaneurysm Diagnosed by 3-Dimensional Fast Spin-Echo T1 Imaging with Variable Flip Angles

  Hidenori Endo, Kuniyasu Niizuma, Miki Fujimura, Kenichi Sato, Takashi Inoue, Shin-ichiro Osawa, Teiji Tominaga

  JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 24 (8) E231 - E235 1052-3057 2015/08 [Refereed][Not invited]
   

  Cerebral microaneurysms, which are 2 mm or small in size, are a rare cause of subarachnoid hemorrhage (SAH). The authors present 2 cases with ruptured microaneurysms, in which 3-dimensional (3D) fast spin-echo T1 imaging with variable flip angles (CUBE T1) using gadolinium-diethylenetriaminepentaacetic acid (Gd) enhancement was useful in diagnosing the microaneurysms as the source of bleeding. Case 1 was a 61-year-old woman who had an SAH localized to the left Sylvian fissure. A small bulge (1.4 mm) at the bifurcation of left middle cerebral artery (MCA), which was detected by 3D angiography, was well enhanced by CUBE T1 with Gd enhancement. The patient was successfully treated by trapping of the lower division of the left M2 segment with superficial temporal artery-M3 bypass. The intraoperative findings indicated that the microaneurysm at the bifurcation of the left MCA was the ruptured site. Case 2 was a 41-year-old man who had a diffuse SAH. A small bulge (1.5 mm) at the inferolateral wall of the left internal carotid artery (ICA), which was detected by 3D angiography, was well enhanced by CUBE T1 with Gd enhancement. The patient was treated by trapping of the left ICA with external carotid artery-saphenous vein graft-M2 bypass without complications. The intraoperative findings indicated that the microaneurysm at the inferolateral wall of the left ICA was the ruptured site. CUBE T1 with Gd enhancement was useful as an adjunctive tool for the diagnosis of ruptured cerebral microaneurysms. This sequence might enable neurosurgeons to perform curative surgery with certainty for ruptured microaneurysms.
• Local Vasogenic Edema without Cerebral Hyperperfusion after Direct Revascularization Surgery for Moyamoya Disease

  Hiroyuki Sakata, Miki Fujimura, Shunji Mugikura, Kenichi Sato, Teiji Tominaga

  JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 24 (7) E179 - E184 1052-3057 2015/07 [Refereed][Not invited]
   

  Superficial temporal artery-middle cerebral artery anastomosis is generally used as the standard surgical treatment for moyamoya disease to prevent cerebral ischemic attacks. Although the main potential complications associated with this treatment are cerebral hyperperfusion and ischemia, the adverse impacts of revascularization surgery remain unclear. Of the 142 consecutive surgeries for moyamoya disease at our hospital from 2008, we herein presented 2 cases of adult-onset moyamoya disease that manifested local vasogenic edema at the site of anastomosis without cerebral hyperperfusion; 1 in a 31-year-old woman presented with transient ischemic attack and the other in a 22-year-old man manifested as minor completed stroke. Both patients underwent superficial temporal artery-middle cerebral artery anastomosis, resulting in the formation of a reversible high-signal-intensity lesion at the site of anastomosis on T2-weighted images along with an increase in apparent diffusion coefficient values, whereas diffusion-weighted images showed no changes. Neither hyperperfusion nor hypoperfusion, as assessed by single-photon emission computed tomography with N-isopropyl[123I]-p-iodoamphetamine, was observed postoperatively. In light of the increased risk of the further progression of vasogenic edema to intracerebral hemorrhage, these patients were treated with prophylactic blood pressure lowering and the intravenous infusion of a free radical scavenger. They did not have any further cerebrovascular events during the follow-up period. Regional vasogenic edema without cerebral hyperperfusion, possibly due to cerebral ischemia/reperfusion injury, may be another novel entity that needs to be considered as a potential complication after extracranial-intracranial bypass for moyamoya disease. Strict postoperative management should be used to avoid hemorrhagic transformation. (C) 2015 by National Stroke Association
• Consistent delayed unilateral neuronal death after modified transient focal cerebral ischemia in mice that mimics neuronal injury after transient global cerebral ischemia

  Yasuo Nishijima, Kuniyasu Niizuma, Miki Fujimura, Yosuke Akamatsu, Hiroaki Shimizu, Teiji Tominaga

  JOURNAL OF NEUROSURGERY 123 (1) 243 - 253 0022-3085 2015/07 [Refereed][Not invited]
   

  OBJECT Numerous studies have attempted to reveal the pathophysiology of ischemic neuronal injury using a representative transient global cerebral ischemia (tGCI) model in rodents; however, most of them have used gerbil or rat models. Recent advances in transgene and gene-knockout technology have enabled the precise molecular mechanisms of ischemic brain injury to be investigated. Because the predominant species for the study of genetic mutations is the mouse, a representative mouse model of tGCI is of particular importance. However, simple mouse models of tGC1 are less reproducible; therefore, a more complex process or longer duration of ischemia, which causes a high mortality rate, has been used in previous tGCI models in mice. In this study, the authors aimed to overcome these problems and attempted to produce consistent unilateral delayed hippocampal CA1 neuronal death in mice. METHODS C57BL/6 mice were subjected to short-term unilateral cerebral ischemia using a 4-mm silicone-coated intraluminal suture to obstruct the origin of the posterior cerebral artery (PCA), and regional cerebral blood flow (rCBF) of the PCA territory was measured using laser speckle flowmetry. The mice were randomly assigned to groups of different ischemic durations and histologically evaluated at different time points after ischemia. The survival rate and neurological score of the group that experienced 15 minutes of ischemia were also evaluated. RESULTS Consistent neuronal death was observed in the medial CA1 subregion 4 days after 15 minutes of ischemia in the group of mice with a reduction in rCBF of < 65% in the PCA territory during ischemia. Morphologically degenerated cells were mostly positive for terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick-end labeling and cleaved caspase 3 staining 4 days after ischemia. The survival rates of the mice 24 hours (n = 24), 4 days (n = 15), and 7 days (n = 7) after being subjected to 15 minutes of ischemia were 95.8%, 100%, and 100%, respectively, and the mice had slight motor deficits. CONCLUSIONS The authors established a model of delayed unilateral hippocampal neuronal death in C57BL16 Mice by inducing ischemia in the PCA territory using an intraluminal suture method and established inclusion criteria for PCA-territory rCBF monitored by laser speckle flowmetry. This model may be useful for investigating the precise molecular mechanisms of ischemic brain injury.
• Required knowledge for stroke specialists (11) management of moyamoya disease

  Miki Fujimura, Teiji Tominaga

  Neurological Surgery 43 (6) 557 - 565 1882-1251 2015/06/01 [Refereed][Not invited]
  
• Current Status of Revascularization Surgery for Moyamoya Disease: Special Consideration for Its 'Internal Carotid-External Carotid (IC-EC) Conversion' as the Physiological Reorganization System

  Miki Fujimura, Teiji Tominaga

  TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE 236 (1) 45 - 53 0040-8727 2015/05 [Refereed][Not invited]
   

  Moyamoya disease is a chronic cerebrovascular disease with unknown etiology, which is characterized by bilateral steno-occlusive changes at the terminal portion of the internal carotid artery and an abnormal vascular network formation at the base of the brain. Moyamoya disease is known to have unique and dynamic nature to convert the vascular supply for the brain from internal carotid (IC) system to the external carotid (EC) system, as indicated by Suzuki's angiographic staging established in 1969. Insufficiency of this 'IC-EC conversion system' may result in cerebral ischemia, as well as in intracranial hemorrhage from inadequate collateral vascular network, both of which represent the clinical presentation of moyamoya disease. Therefore, surgical revascularization by extracranial-intracranial bypass is the preferred procedure for moyamoya disease to complement 'IC-EC conversion' and thus to avoid cerebral infarction and/or intracranial hemorrhage. Long-term outcome of revascularization surgery for moyamoya disease is favorable, but rapid increase in cerebral blood flow on the affected hemisphere could temporarily cause unfavorable phenomenon such as cerebral hyperperfusion syndrome. We would review the current status of revascularization surgery for moyamoya disease based on its basic pathology, and sought to discuss the significance of measuring cerebral blood flow in the acute stage and intensive perioperative management. (C) 2015 Tohoku University Medical Press
• [A case of atherothrombotic embolization developing with slowly progressive symptoms and requiring differential diagnosis from metastatic tumor recurrence].

  Sho Umegaki, Ryuta Saito, Yosuke Akamatsu, Hiroyuki Sakata, Ken-Ichi Sato, Miki Fujimura, Yukihiko Sonoda, Teiji Tominaga

  No shinkei geka. Neurological surgery 43 (4) 339 - 43 0301-2603 2015/04 [Refereed][Not invited]
   

  We report a case of atherothrombotic embolization that developed with slowly progressive symptoms and required differential diagnosis from metastatic tumor recurrence. A 64-year-old man with a history of lung cancer and metastatic brain tumor was carefully followed at our outpatient department for tumor recurrence. Five years after surgery for brain metastasis and whole brain radiation therapy, he had no recurrence and systemic disease was well controlled. At a routine follow up in October 2013, he complained of slight right arm dysesthesia. Follow up brain magnetic resonance (MR) imaging revealed no lesion. Two months later, he developed right hemiparesthesia and gait disturbance. Spinal MR imaging was unremarkable. However, at a routine follow up in January 2014, multiple enhancements were detected near the resection cavity and regions delineating the sulci. At first, this was diagnosed as tumor recurrence. However, 3 days later, additional MR imaging detected new multiple small infarctions after worsening right hemiparesis and dysarthria. With the diagnosis of embolic stroke, we searched for an embolic source. Cardiogenic embolization and carotid bifurcation stenosis studies were negative, but severe stenosis and thrombosis were detected near the left common carotid artery origin. This site was in the field of radiation the patient received as treatment for primary lung cancer.
• A case of akin moyamoya disease associated with type-I diabetes mellitus managed by extracranial-intracranial bypass

  Yosuke Akamatsu, Miki Fujimura, Hiroyuki Sakata, Hidenori Endo, Ryo Itabashi, Teiji Tominaga

  Neurological Surgery 43 (3) 227 - 233 1882-1251 2015/03/01 [Refereed][Not invited]
   

  Moyamoya disease is characterized by idiopathic steno-occlusion at the terminal portion of the internal carotid artery with concomitant abnormal vascular networks that can lead to transient ischemic attacks and hemorrhagic stroke with symptoms of headache, confusion, dizziness, ataxia, seizure, and cognitive and personality changes. Because these symptoms also occur in patients with type 1 diabetes mellitus (T1DM), patients with both diseases might go unnoticed and without the less common diagnosis of akin moyamoya disease, accurate diagnosis and treatment could be delayed. Here, we report the case of a 32-year-old woman with past history of T1 DM for 26 years presenting with right amaurosis, which was diagnosed as akin moyamoya disease even though she had suffered right incomplete hemiparesis 2 years ago. She underwent superficial temporal artery-middle cerebral artery anastomosis with pial synangiosis in the left hemisphere without complication. She had no cerebrovascular events postoperatively. Although akin moyamoya disease associated with T1 DM is rare in Japan, we recommend that clinicians consider the coexistence of both diseases when evaluating patients with T1DM who have neurologic signs or symptoms and not overlook the possibility of cerebrovascular diseases, such as akin moyamoya disease.
• Diagnosis of Moyamoya Disease: International Standard and Regional Differences

  Miki Fujimura, Teiji Tominaga

  NEUROLOGIA MEDICO-CHIRURGICA 55 (3) 189 - 193 0470-8105 2015/03 [Refereed][Not invited]
   

  Moyamoya disease is a chronic, occlusive cerebrovascular disease with unknown etiology characterized by bilateral steno-occlusive changes at the terminal portion of the internal carotid artery and an abnormal vascular network at the base of the brain. These diagnostic criteria of the moyamoya disease, stated by the Research Committee on Spontaneous Occlusion of the Circle of Willis (moyamoya disease) in Japan, are well established and generally accepted as the definition of this rare entity. On the contrary to the diagnosis of definitive moyamoya disease, there is some confusion in the terminology and understanding of quasi-moyamoya disease; moyamoya disease in association with various disease entities, such as atherosclerosis, autoimmune diseases, Down syndrome, etc. Although the clinical management is not affected by these semantic distinctions, terminological confusion may interfere with the international collaboration of the clinical investigation of these rare conditions. In this article, we sought to review the international standard and regional differences in the diagnosis of moyamoya disease and quasi-moyamoya disease.
• Blood Pressure Lowering and Minocycline Administration as Secure and Effective Postoperative Management after Revascularization Surgery for Moyamoya Disease

  Miki FUJIMURA, Kuniyasu NIIZUMA, Hidenori ENDO, Kenichi SATO, Takashi INOUE, Teiji TOMINAGA

  Surgery for Cerebral Stroke (一社)日本脳卒中の外科学会 43 (2) 136 - 140 0914-5508 2015/03 [Refereed][Not invited]
   

  もやもや病に対して直接血行再建術を行い、脳保護作用を持つミノサイクリン塩酸塩を用いて周術期管理を行った連続75例89手術の治療成績、周術期合併症の頻度を検証した。全例、浅側頭動脈-中大脳動脈吻合術を施行し、過灌流予防を目的とした血圧管理とミノサイクリン塩酸塩投与を行った結果、過灌流による血圧依存性に変動する出血を伴わない局所神経脱落症状を認めた症例はなかった。しかし、無症候性ではあったものの過灌流による遅発性頭蓋内出血を6例6側に認め、高年齢と男性が遅発性頭蓋内出血の正の関連因子であることが示唆された。
• Quantitative analysis of early postoperative cerebral blood flow contributes to the prediction and diagnosis of cerebral hyperperfusion syndrome after revascularization surgery for moyamoya disease

  Miki Fujimura, Kuniyasu Niizuma, Hidenori Endo, Kenichi Sato, Takashi Inoue, Hiroaki Shimizu, Teiji Tominaga

  NEUROLOGICAL RESEARCH 37 (2) 131 - 138 0161-6412 2015/02 [Refereed][Not invited]
   

  Objective: Cerebral hyperperfusion syndrome (HPS) is a potential complication of extracranial-intracranial (EC-IC) bypass for moyamoya disease; however, the pathological threshold of the early cerebral blood flow (CBF) increases after EC-IC bypass has yet to be determined. The purpose of this study is to evaluate the predictive and diagnostic values of early quantitative CBF analysis for the detection of HPS after EC-IC bypass for moyamoya disease. Methods: We quantitatively evaluated regional CBF at the site of the anastomosis in 23 patients with moyamoya disease aged between 18 and 66 years (mean, 39.6) before and 1 day after superficial temporal artery-middle cerebral artery anastomosis by an auto-radiographic method using N-isopropyl-p-[I-123] iodoamphetamine single-photon emission computed tomography. Results: Regional CBF 1 day after surgery was significantly higher in patients with HPS (n = 5; mean, 54.6 ml/100 g/minutes) than in patients without HPS (n = 18; mean, 40.5 ml/100 g/minutes) (P = 0.038). The postoperative/preoperative CBF ratio was significantly higher in patients with HPS (1.84) than in patients without HPS (1.34) (P = 0.044). Multivariate analyses showed that the regional CBF value 1 day after surgery (P = 0.036) and operating on the left hemisphere (P = 0.026) significantly correlated with HPS. All patients with HPS developed symptoms and/or intracerebral hemorrhage more than 2 days after EC-IC bypass. Receiver operating characteristic analysis indicated that the cutoff value of pathological postoperative CBF increase was 46.1 ml/100 g/minutes (sensitivity = 80%, specificity = 77.8%, AUC value = 0.81). Conclusion: Quantitative analysis of early postoperative CBF is useful for predicting and diagnosing HPS after revascularization surgery for moyamoya disease.
• Combined open and endovascular surgery for complex cerebral aneurysms

  Hiroaki Shimizu, Yasushi Matsumoto, Hidenori Endo, Takashi Inoue, Miki Fujimura, Teiji Tominaga

  Japanese Journal of Neurosurgery 24 (3) 165 - 172 0917-950X 2015 [Refereed][Not invited]
   

  In the treatment of cerebral aneurysms, a combination of open and endovascular surgeries may be necessary when simple clipping or coiling are difficult. The authors retrospectively analyzed such patients to clarify the current status and issues to be overcome. Between 2003 and 2012, clipping was selected as the first choice until 2007 and coiling thereafter. Five representative cases with the combination therapy are presented. Case 1:A giant internal carotid artery (IC) aneurysm at the cavernous portion was treated with a high flow bypass and parent artery occlusion, based on the finding of the preoperative balloon test occlusion which revealed severe reduction of cerebral blood flow upon IC occlusion. Case 2: A ruptured vertebral artery dissection involving the posterior inferior cerebellar artery (PICA) was treated with the occipital artery (OA) - PICA bypass followed by internal trapping of the dissection and the parent artery with a coil. Wallenberg syndrome developed, but the patient became independent. Case 3: A giant basilar artery- superior cerebellar artery (SCA) aneurysm was treated with a superficial temporal artery- SCA bypass followed by coil embolization of the aneurysm sac, because the SCA originated from the dome of the aneurysm. Case 4: Clipping was intended for so-called kissing aneurysms, comprising IC-posterior communicating artery (Pcom) and anterior choroidal aneurysms however, adhesion between the aneurysms and with the Pcom itself was too tight to dissect. After discussion with the endovascular surgeons, the clipping was abandoned and coil embolization was successfully performed one month later. Case 5: A case of a subarachnoid hemorrhage with IC-PC and basilar tip aneurysms. Coiling was intended for both aneurysms in the acute stage. It was revealed during the coiling procedure for the basilar tip aneurysm that one of the two humps of the aneurysm was difficult to occlude completely. A perforating artery of the basilar tip was shown by microcatheter angiography. The surgical team was consulted and the basilar tip aneurysm was clipped successfully after coiling of the IC-PC aneurysm. For aneurysms which are difficult to treat with simple clipping or coiling, a combination of open and endovascular surgeries may play a valuable role after effective communication between the neurosurgeons and endovascular surgeons. There remain certain limitations in terms of completeness of the aneurysm occlusion and perforators which still need to be overcome.
• Cortical Microvascularization and Leptomeningeal Collaterals in Moyamoya Disease

  Shunji Mugikura, Miki Fujimura, Shoki Takahashi

  EUROPEAN NEUROLOGY 73 (5-6) 351 - 352 0014-3022 2015 [Refereed][Not invited]
  
• Enhanced post-ischemic angiogenesis in mice lacking RNF213; a susceptibility gene for moyamoya disease

  Akira Ito, Miki Fujimura, Kuniyasu Niizuma, Atsushi Kanoke, Hiroyuki Sakata, Yuiko Morita-Fujimura, Atsuo Kikuchi, Shigeo Kure, Teiji Tominaga

  BRAIN RESEARCH 1594 310 - 320 0006-8993 2015/01 [Refereed][Not invited]
   

  Moyamoya disease (MMD) is a chronic occlusive cerebrovascular disease with unknown etiology that is characterized by the development of abnormal vascular networks at the base of the brain. Recent genome-wide studies identified RNF213 as an important MMD susceptibility gene. However, the exact mechanism by which the RNF213 abnormality leads to MMD remains unknown. Thus, we sought to clarify the role of RNF213 in angiogenesis under ischemic conditions using conventional RNF213 knockout mice. We assessed the infarction volume, cerebral edema, and vascular density in the ischemic brain after transient middle cerebral artery occlusion (tMCAO). To further evaluate systemic angiogenesis following chronic ischemia, we investigated blood flow recovery using laser speckle flowmetry, the severity of ambulatory impairments, and vascular density in the hind-limb after permanent femoral artery ligation. Results were compared between homozygous RNF213 knockout mice (RNF213 -/-) and wild-type littermates (Wt). No significant differences were observed in infarction volume or the formation of edema following tMCAO, or in vascular density 28 days after tMCAO between RNF213 -/- and Wt. Blood flow recovery was significantly improved in RNF213 -/- from 3 to 28 days after femoral artery ligation, and angiogenesis as shown by vascular density in the hind-limb was significantly enhanced in RNF213 -/- at 28 days. The amelioration of ambulatory impairments was also evident in RNF213 -/-. Angiogenesis was enhanced in mice lacking RNF213 after chronic hind-limb ischemia, which suggested the potential role of the RNF213 abnormality in the development of pathological vascular networks in chronic ischemia. (C) 2014 Elsevier B.V. All rights reserved.
• Increased vascular MMP-9 in mice lacking RNF213: Moyamoya disease susceptibility gene

  Shinya Sonobe, Miki Fujimura, Kuniyasu Niizuma, Taku Fujimura, Sadanori Furudate, Yasuo Nishijima, Shigeo Kure, Teiji Tominaga

  NeuroReport 25 (18) 1442 - 1446 1473-558X 2014/12/17 [Refereed][Not invited]
   

  Moyamoya disease (MMD) is a chronic occlusive cerebrovascular disease with unknown etiology. Recent genetic studies have identified RNF213 as an important susceptibility gene for MMD. To evaluate the role of RNF213 in vascular remodeling, RNF213 knockout mice (RNF213-/-) and their wild-type littermates (WT) were subjected to common carotid artery ligation to induce vascular hyperplasia. We examined the vascular expression of matrix metalloproteinase (MMP)-9, known to be increased in MMD. MMP-9 expression was significantly higher in RNF213-/- mice than in wild-type mice 1 and 7 days after common carotid artery ligation. The vascular wall was significantly thinner in RNF213-/- mice at 14 days. The increased vascular expression of MMP-9 and subsequent vascular wall thinning in RNF213-/- mice could reflect the early characteristic of MMD, consistent with the recently proposed constrictive remodeling theory.
• スパズム期に来院したくも膜下出血の治療

  木村 尚人, 大沢 伸一郎, 江面 正幸, 藤村 幹, 井上 敬, 上之原 広司, 冨永 悌二

  東北脳血管障害研究会学術集会記録集 サノフィ(株)仙台オフィス 36回 232 - 248 1880-9278 2014/12
• パルスジェットメスを用いた蝶形骨縁髄膜腫摘出手術- 血管温存能を活用して - Usefulness of Water Pulsed Jet in dissecting Sphenoid ridge meningioma and preserving arteries．

  遠藤俊毅, 中川敦寛, 藤村幹, 清水宏明, 園田順彦, 冨永悌二

  脳神経外科 42 (11) 1019 - 1025 2014/11 [Refereed][Not invited]
  
• A case of bilateral giant internal carotid artery aneurysms at the cavernous portion managed by 2-stage extracranial-intracranial bypass with parent artery occlusion: Consideration for bypass selection and timing of surgeries

  Miki Fujimura, Kenichi Sato, Naoto Kimura, Takashi Inoue, Hiroaki Shimizu, Teiji Tominaga

  Journal of Stroke and Cerebrovascular Diseases 23 (8) e393 - e398 1532-8511 2014/09/01 [Refereed][Not invited]
   

  Bilateral giant internal carotid artery (ICA) aneurysms at the cavernous portion with bilateral cranial nerve symptoms are extremely rare. Extracranial-intracranial (EC-IC) bypass with parent artery occlusion (PAO) is one of the preferred procedures for giant ICA aneurysm at the cavernous portion with cranial nerve palsy however, optimal bypass selection and the timing of surgery are controversial, particularly in bilateral cases. A 28-year-old woman developed left third nerve palsy with giant ICA aneurysms at the bilateral cavernous portion. Because only the left aneurysm was symptomatic, she initially underwent left EC-IC bypass using a saphenous vein graft with PAO without complications, which relieved her symptoms. However, she developed right third/fifth nerve palsy 10 months later, at which time magnetic resonance (MR) imaging and MR angiography revealed an enlarged right ICA aneurysm and shrunken left ICA aneurysm. Balloon test occlusion of the right ICA identified sufficient ischemic tolerance therefore, she underwent right superficial temporal artery-middle cerebral artery bypass with PAO. Both bypasses were confirmed by MR angiography to be patent after surgery. Cranial nerve palsy gradually improved postoperatively, and single-photon emission computed tomography confirmed static cerebral hemodynamics. In conclusion, high-flow EC-IC bypass with PAO is recommended in the first stage of surgery on a unilaterally symptomatic side to minimize postoperative hemodynamic stress to the contralateral aneurysm. Once the contralateral side becomes symptomatic, second stage EC-IC bypass with PAO, either low-flow or high-flow bypass, is recommended based on the results of balloon test occlusion.
• Efficacy of extracranial-intracranial bypass for progressive middle cerebral artery occlusion associated with active Sjögren's syndrome: Case report

  Hiroyuki Sakata, Miki Fujimura, Kenichi Sato, Hiroaki Shimizu, Teiji Tominaga

  Journal of Stroke and Cerebrovascular Diseases 23 (8) e399 - e402 1532-8511 2014/09/01 [Refereed][Not invited]
   

  Sjögren syndrome affecting the major cerebral arteries is rare, and an optimal therapeutic strategy to counteract such a lesion has not yet been established. We herein report a case of a 39-year-old woman with a history of primary Sjögren syndrome, which had previously been treated with immunosuppressive therapy, manifesting with a crescendo transient ischemic attack because of left middle cerebral artery stenosis. Despite the administration of high doses of prednisolone and azathioprine for active Sjögren syndrome, the frequency of crescendo transient ischemic attacks increased with the progression of stenosis and magnetic resonance imaging showed the development of subacute cerebral infarction. Single-photon emission computed tomography with N-isopropyl[123I]-p-iodoamphetamine revealed apparent hemodynamic compromise in the affected cerebral hemisphere. In light of the increased risk of further progression of cerebral infarction, we decided to perform surgical revascularization in spite of her active inflammatory condition. The patient underwent extracranial-intracranial bypass without complications and was treated with intensive immunosuppressive therapy during the perioperative period. Based on our findings, we recommend surgical revascularization for occlusive cerebrovascular disease with hemodynamic compromise in combination with intensive immunosuppressive therapy, even in the active inflammatory state of autoimmune diseases, if ischemic symptoms are medically uncontrollable.
• Moyamoya syndrome associated with Basal meningioma successfully treated by the modified transsphenoidal approach: case report.

  Ogawa Y, Fujimura M, Tominaga T

  Journal of neurological surgery reports 75 (1) e77 - 80 2193-6358 2014/08 [Refereed][Not invited]
  
• Temporal profile of the vascular anatomy evaluated by 9.4-T magnetic resonance angiography and histopathological analysis in mice lacking RNF213: A susceptibility gene for moyamoya disease

  Shinya Sonobe, Miki Fujimura, Kuniyasu Niizuma, Yasuo Nishijima, Akira Ito, Hiroaki Shimizu, Atsuo Kikuchi, Natsuko Arai-Ichinoi, Shigeo Kure, Teiji Tominaga

  Brain Research 1552 64 - 71 0006-8993 2014/03/13 [Refereed][Not invited]
   

  Moyamoya disease (MMD) is a chronic occlusive cerebrovascular disease with unknown etiology. Recent genome-wide and locus-specific association studies identified RNF213 as an important MMD susceptibility gene. However, the exact mechanism by which an abnormality in RNF213 leads to MMD is unknown. To evaluate the role of RNF213 in the etiology of MMD, we generated RNF213-deficient mice (RNF213-/-) by deleting exon 32 of RNF213 by the Cre-lox system, and investigated whether they developed MMD. The temporal profile of cervical/intracranial arteries was evaluated by 9.4-T magnetic resonance angiography (MRA). The anatomy of the circle of Willis was analyzed by a trans-cardiac injection of carbon black dye. The common carotid arteries (CCA) were sectioned and the arterial wall thickness/thinness was evaluated by Elastica-Masson staining before and after CCA ligation, which selectively induced vascular hyperplasia. As a result, RNF213-/- grew normally, and no significant difference was observed in MRA findings, the anatomy of the circle of Willis, or vascular wall thickness/thinness between RNF-/- and wild-type littermates (Wt.) under normal conditions until 64 weeks of age. However, Elastica-Masson staining demonstrated that both the intima and medial layer were significantly thinner after CCA ligation in RNF213-/- than in Wt. after 14 days (P< 0.01). In conclusion, mice lacking the RNF213 gene did not spontaneously develop MMD, indicating that a functional loss of RNF213 did not sufficiently induce MMD. Suppression of vascular remodeling in RNF213-/- requires further examination to clarify the role of RNF213. © 2014 Elsevier B.V.
• Combined use of bio-absorbable polymer system with titanium plate in revascularization surgery for moyamoya disease

  Miki Fujimura, Hiroshi Uenohara, Teiji Tominaga

  Japanese Journal of Neurosurgery 23 (5) 418 - 422 0917-950X 2014 [Refereed][Not invited]
   

  Moyamoya disease is a chronic occlusive cerebrovascular disease with unknown etiology that is common in children and young adults with a female predominance. Wound trouble is a potential complication of revascularization surgery for moyamoya disease, while the optimal procedure of the cranioplasty and skin closure is undetermined. To minimize the postoperative physical stress to the typically thin scalp with poorer blood supply found in most moyamoya patients, we used a bio-absorbable polymer system (80% poly-L lactic acid and 18% poly-glycolic acid LactoSorb®) adjacent to the incision in combination with a titanium plate for cranium fixation in 48 surgeries for 43 patients aged from 10 to 62 years (mean 38.9). There was no wound trouble during the mean follow-up period of 13.8 months. None of the 43 patients suffered from wound infection, subcutaneous cerebrospinal fluid collection, nor the delayed wound healing that frequently affects a patient’s admission schedule. There was no adverse effect from the bio-absorbable polymer system itself including delayed inflammation around the site of fixation. Combined use of a bio-absorbable polymer system with a titanium plate is a safe and effective procedure for treating moyamoya disease that can also avoid surgical complications on the scalp.
• Hyponatremia caused by siadh following endoscopic third ventriculostomy: A case report

  Ryota Shigeeda, Hidenori Endo, Miki Fujimura, Yoshikazu Ogawa, Hiroaki Shimizu, Teiji Tominaga

  Neurological Surgery 42 (4) 335 - 339 1882-1251 2014 [Refereed][Not invited]
   

  A 25-year-old man complained of disorientation and gait disturbance during the past 2 weeks. The patient had been treated for cerebellar astrocytoma by open surgery thrice, at ages 3, 5, and 11. Ventriculo-peritoneal shunt was performed for postoperative hydrocephalus at the age of 11. Magnetic resonance imaging (MRI) showed enlargement of both lateral ventricles, ballooning of the third ventricle, and obstruction of the aqueduct of Sylvius. The patient was diagnosed with recurrent hydrocephalus due to shunt malfunction, and treated by endoscopic third ventriculostomy (ETV) using a flexible endoscopic system. He was relieved of the symptoms immediately after surgery, and postoperative MRI showed reduced hydrocephalus. However, the symptoms reoccurred 6 days after surgery. Computed tomography did not show recurrence of hydrocephalus. Laboratory tests revealed hyponatremia (117 mEq/L) and low serum osmolality (240 mOsm/kg). The patient gained 2.4 kg over the preoperative body weight. The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was considered to be the cause of the hyponatremia, which was successfully treated with 3 days of fluid restriction. The patient was discharged 24 days after surgery. Hyponatremia is a relatively rare complication of ETV. When a patient shows recurrence of hydrocephalus-related symptoms during the early postoperative period after ETV, hyponatremia caused by SIADH should be considered.
• Angiographic circulation time and cerebral blood flow during balloon test occlusion of the internal carotid artery.

  Kenichi Sato, Hiroaki Shimizu, Takashi Inoue, Miki Fujimura, Yasushi Matsumoto, Ryushi Kondo, Hidenori Endo, Yukihiko Sonoda, Teiji Tominaga

  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 34 (1) 136 - 43 0271-678X 2014/01 [Refereed][Not invited]
   

  Angiography-based balloon test occlusion (BTO) has been empirically used to predict tolerance to permanent carotid artery occlusion. We tested the hypothesis that the laterality of the hemispheric circulation time (HCT) of the contrast medium at cerebral angiography would reflect bilateral asymmetry of the cerebral blood flow (CBF) during BTO. Thirty-one consecutive patients who underwent BTO of the internal carotid artery were retrospectively analyzed. HCT was defined as the interval between the time-to-peak in the middle cerebral artery and the cortical veins calculated using time-density curve. The difference in HCT between the occluded and nonoccluded side was calculated at the carotid or dominant vertebral angiograms obtained during BTO. We estimated the correlation between the difference in HCT and bilateral asymmetry of the CBF, which was quantitatively determined by single-photon emission computed tomography. The HCT was 5.3±1.5 seconds and regional CBF was 41.3±11.3 mL/100 g per minute in the occluded side, compared with 3.6±0.9 seconds and 48.4±14.9 mL/100 g per minute in the nonoccluded side, respectively. The difference in HCT was strongly correlated with the asymmetry ratio of the CBF (r(2)=0.89, P<0.0001). Angiographically based measurement of the cerebral circulation time can provide valuable information concerning cerebral hemodynamics.
• Recurrent extracranial internal carotid artery vasospasm diagnosed by serial magnetic resonance angiography and superselective transarterial injection of a calcium channel blocker

  Yoshiteru Shimoda, Miki Fujimura, Naoto Kimura, Masayuki Ezura, Hiroshi Uenohara, Teiji Tominaga

  Journal of Stroke and Cerebrovascular Diseases 23 (5) e383 - e387 1532-8511 2014 [Refereed][Not invited]
   

  Recurrent vasospasm of the extracranial internal carotid artery (ICA) is extremely rare, and optimal management is unclear. A 25-year-old woman developed transient dysarthria and left-sided hemiparesis. Initial magnetic resonance (MR) imaging showed spotty acute infarction in the right temporal lobe, and MR angiography revealed right ICA occlusion. ICA occlusion was spontaneously resolved within 6 days of its onset, whereas transient left ICA narrowing was evident at 12 days. Because recurrent occlusion of the right ICA occurred at 14 days when the contralateral ICA was still narrowed, we attempted a local intra-arterial injection of a calcium channel blocker based on the diagnosis of recurrent extracranial ICA vasospasm. The local injection of 1 mg of nicardipine partially dilated the affected ICA, which confirmed the diagnosis of vasospasm. After the introduction of oral medication with benidipine hydrochloride, bilateral ICA vasospasm was completely resolved 23 days after its onset, as shown by MR angiography. In conclusion, we recommend intensive radiologic follow-up at the acute stage and therapeutic catheter angiography when the bilateral lesion is evident because bilateral occlusion of the ICA could lead to a catastrophic condition. © 2014 by National Stroke Association.
• Cardiopulmonary complication as a pitfall of the perioperative management of moyamoya syndrome with atherosclerosis: Conflict to counteract with cerebral hyperperfusion

  Hiroyuki Sakata, Miki Fujimura, Kenichi Sato, Hiroaki Shimizu, Teiji Tominaga

  Neurological Surgery 42 (8) 737 - 743 1882-1251 2014 [Refereed][Not invited]
   

  A 42-year-old man with a history of hypertension and obesity presented with transient dysesthesia in his left upper and lower extremities and was found to have moyamoya syndrome associated with atherosclerosis. He underwent superficial temporal artery-middle cerebral artery anastomosis with pial synangiosis in the right hemisphere 1 month after the onset of symptoms. Prophylactic blood pressure lowering (< 130 mmHg) as well as minocycline administration was introduced immediately after surgery to prevent symptomatic cerebral hyperperfusion, but he developed pulmonary edema due to congestive heart failure several hours after surgery. We subsequently allowed his systolic blood pressure to be under 140 mmHg, which dramatically improved his cardiopulmonary condition. The neurologic status of the patient was unremarkable, but 123I-IMP-SPECT the day after surgery demonstrated an intense increase in the cerebral blood flow at the site of the anastomosis. Moreover, postoperative magnetic resonance angiography demonstrated the bypass as thick, high signal. Together, these results led us to the diagnosis of cerebral hyperperfusion. The patient did not demonstrate any neurological sign during the entire perioperative period, but CT scan performed 7 days after surgery revealed a delayed intra-cerebral hemorrhage in the right temporal lobe due to the cerebral hyperperfusion. We continued to mildly lower his blood pressure, and neither ischemic nor hemorrhagic events were subsequently observed he was discharged without neurological deficit 2 weeks after surgery. In conclusion, congestive heart failure and pulmonary edema are potential complications of the perioperative management of moyamoya syndrome with atherosclerotic background. Moreover, cardiopulmonary complications should be mentioned as a potential pitfall of the intensive perioperative management of moyamoya disease to counteract with cerebral hyperperfusion.
• Usefulness of laser speckle flowgraphy for the assessment of ocular blood flow in extracranial-intracranial bypass

  Shunsuke Omodaka, Hidenori Endo, Hiroshi Doi, Hiroaki Shimizu, Miki Fujimura, Naoko Aizawa, Toru Nakazawa, Teiji Tominaga

  Journal of Stroke and Cerebrovascular Diseases 23 (10) e445 - e448 1532-8511 2014 [Refereed][Not invited]
   

  Laser speckle flowgraphy (LSFG) is a noninvasive technique that can measure relative blood flow velocity in the optic fundus. The authors present a case of symptomatic internal carotid artery occlusion treated with superficial temporal artery (STA)- middle cerebral artery (MCA) bypass in which an improvement of ocular circulation was confirmed by LSFG. A 47-year-old man presented with a 1-month history of repeated left blurred vision and motor weakness of the right leg. Diffusionweighted magnetic resonance imaging revealed a small infarction in the left frontal lobe. Carotid angiography revealed that the left internal carotid artery was occluded at the C4 portion. Single-photon emission computed tomography indicated that the cerebral blood flow in the left MCA territory was markedly impaired. Ophthalmologic examination revealed ischemic change of the left optic fundi, and LSFG revealed decreased blood flow around the left optic disc. Left STA-MCA bypass was successfully performed. Both ischemic ocular symptoms and the ischemic symptoms of the right leg were completely recovered after surgery. Postoperative ophthalmologic examination revealed improvement of both ischemic changes of the left optic fundi. Moreover, LSFG revealed improvement of the blood flow around the left optic disc. LSFG can be a promising clinical tool for the assessment of ocular circulation before and after bypass surgery for occlusive cerebrovascular disease.
• Development of moyamoya disease in pregnancy and puerperium: Case report

  Yosuke Akamatsu, Miki Fujimura, Hiroshi Uenohara, Hiroaki Shimizu, Teiji Tominaga

  Neurologia Medico-Chirurgica 54 (10) 824 - 826 1349-8029 2014 [Refereed][Not invited]
   

  Progressive moyamoya disease in pregnancy and puerperium has not been reported previously. Here, we present a 39-year-old woman who had been found to have moderate stenosis of right middle cerebral artery (MCA) 4 years prior to her pregnancy, finally suffering minor completed stroke due to progressive moyamoya disease at the early postpartum period. Three days after cesarean section without any complication, she developed cerebral infraction at right hemisphere, when magnetic resonance angiography indicated apparent progression of the proximal MCA stenosis. Catheter angiography demonstrated nearly occlusion of the right terminal internal carotid artery (ICA) and the development of an abnormal vascular network at the base of the brain as well as MCA stenosis, indicating a definitive diagnosis of moyamoya disease with unilateral involvement. The patient underwent superficial temporal artery-middle cerebral artery anastomosis 1 month after the onset of stroke, and she did not manifest as further neurological events during the follow-up period of 2 years. Moyamoya disease could newly develop in pregnancy and puerperium, which should be noted as a pitfall of the management of moyamoya disease with pregnancy.
• Issues in Revascularization Surgery for Elderly Patients with Moyamoya Disease

  Miki FUJIMURA, Hiroaki SHIMIZU, Takashi INOUE, Kuniyasu NIIZUMA, Teiji TOMINAGA

  Surgery for Cerebral Stroke 42 (1) 37 - 41 0914-5508 2014/01 [Refereed][Not invited]
  
• Minocycline prevents focal neurological deterioration due to cerebral hyperperfusion after extracranial-intracranial bypass for moyamoya disease

  Miki Fujimura, Kuniyasu Niizuma, Takashi Inoue, Kenichi Sato, Hidenori Endo, Hiroaki Shimizu, Teiji Tominaga

  Neurosurgery 74 (2) 163 - 170 0148-396X 2014 [Refereed][Not invited]
   

  Background: Cerebral hyperperfusion (CHP) is a potential complication of superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis for moyamoya disease (MMD), and optimal postoperative management has not yet been established. Minocycline, a neuroprotective antibiotic agent, plays a role in blocking matrix metalloproteinase 9 (MMP-9), which contributes to edema formation and hemorrhagic conversion after cerebral ischemia-reperfusion. Patients with MMD have been shown to have increased serum MMP-9 levels. Objective: To examine the effect of minocycline on the prevention of postoperative CHP after STA-MCA anastomosis for MMD. Methods: N-isopropyl-p-[123I]iodoamphetamine single-photon emission computed tomography was performed 1 and 7 days after STA-MCA anastomosis on 109 hemispheres in 86 consecutive patients with MMD (ages, 9-69 years mean, 37.2 years). Postoperative systolic blood pressure was strictly maintained at lower than 130 mm Hg in all 109 surgeries. The most 60 recent hemispheres were managed by the intraoperative and postoperative intravenous administration of minocycline hydrochloride (200 mg/d). The incidence of focal neurological deterioration (FND) due to CHP was then compared with that in 36 patients undergoing 49 surgeries managed without minocycline. Results: FND due to CHP was observed in 4 operated hemispheres in patients treated without minocycline (4/49, 8.16%), and in none in the minocycline-treated group (0/60) (P =.0241). Multivariate analysis revealed that minocycline administration (P < .001), surgery on the left hemisphere (P =.031), and a smaller recipient artery diameter (P < .001) significantly correlated with FND due to CHP. Conclusion: The administration of minocycline with strict blood pressure control may represent secure and effective postoperative management to prevent symptomatic CHP after STA-MCA anastomosis for MMD. Copyright © 2013 by the Congress of Neurological Surgeons.
• Development of a de novo arteriovenous malformation after bilateral revascularization surgery in a child with moyamoya disease: Case report

  Miki Fujimura, Naoto Kimura, Masayuki Ezura, Kuniyasu Niizuma, Hiroshi Uenohara, Teiji Tominaga

  Journal of Neurosurgery: Pediatrics 13 (6) 647 - 649 1933-0715 2014 [Refereed][Not invited]
   

  The development of a de novo arteriovenous malformation (AVM) in patients with moyamoya disease is extremely rare. A 14-year-old girl developed an AVM in the right occipital lobe during the 4-year postoperative period following successful bilateral revascularization surgeries. She suffered a transient ischemic attack with hemodynamic compromise of the bilateral hemispheres at the age of 10 years. Results of an initial examination by 1.5-T MRI and MR angiography satisfied the diagnostic criteria of moyamoya disease but failed to detect any vascular malformation. Bilateral direct and indirect revascularization surgeries in the anterior circulation relieved her symptoms, and she underwent MRI and MR angiography follow-up every year after surgery. Serial T2-weighted MRI revealed the gradual appearance of flow voids in the right occipital lobe during the follow-up period. Magnetic resonance angiography ultimately indicated the development of an AVM 4 years after these surgeries when catheter angiography confirmed the diagnosis of an AVM in the right occipital lobe. The AVM remained asymptomatic, and the patient remained free of cerebrovascular events during the time she was observed by the authors. Acquired AVM in moyamoya disease is extremely rare, with only 3 pediatric cases including the present case being reported in the literature. The development of a de novo AVM in a postoperative patient with moyamoya disease appears to be unique, and this case may provide insight into the dynamic pathology of AVMs.
• SMTP-7, a new thrombolytic agent, decreases hemorrhagic transformation after transient middle cerebral artery occlusion under warfarin anticoagulation in mice

  Akira Ito, Kuniyasu Niizuma, Hiroaki Shimizu, Miki Fujimura, Keiji Hasumi, Teiji Tominaga

  Brain Research 1578 38 - 48 1872-6240 2014 [Refereed][Not invited]
   

  Stachybotrys microspora triprenyl phenol-7 (SMTP-7) is a new thrombolytic agent that exhibits anti-inflammatory effects. We previously demonstrated that the hemorrhagic transformation was fewer with SMTP-7 than with recombinant tissue plasminogen activator (rt-PA) following ischemia-reperfusion in animal models. We hypothesized that SMTP-7 may decrease hemorrhagic transformation after ischemia-reperfusion under the warfarin-treated condition. Transient middle cerebral artery occlusion (MCAO) was induced for 3 h using an intraluminal suture in warfarin-treated mice to produce hemorrhagic transformation. Warfarin was administered orally for a 24-h feeding period before MCAO through bottled drinking water (5 mg in 375 ml tap water), resulting in a mean INR of 5.6×0.2. Mice were treated with vehicle, rt-PA, or SMTP-7 5h before reperfusion. Twenty percent of vehicle-treated and 50.0% of rt-PA-treated mice died 24 h after reperfusion, while all SMTP-7-treated mice survived. Hemorrhagic severity in SMTP-7-treated mice was significantly lower than that in rt-PA-treated mice. Neurological deficit was significantly lower in SMTP-7-treated mice than vehicle- and rt-PA-treated mice. These results indicate that SMTP-7 decreases mortality, hemorrhagic transformation, and neurological deficits, and can be a safe thrombolytic agent following MCAO under the warfarin-treated condition.
• 静脈採血による脳血流定量法 SPECTによる検討

  井上 敬, 藤村 幹, 清水 宏明, 藤原 悟, 冨永 悌二

  東北脳血管障害研究会学術集会記録集 サノフィ(株)仙台オフィス 35回 46 - 63 1880-9278 2013/12
• Signal changes on T2*-weighted magnetic resonance imaging from the acute to chronic phases in patients with subarachnoid hemorrhage

  Takashi Inoue, Shihomi Takada, Hiroaki Shimizu, Kuniyasu Niizuma, Miki Fujimura, Kenichi Sato, Hidenori Endo, Teiji Tominaga

  Cerebrovascular Diseases 36 (5-6) 421 - 429 1015-9770 2013/12 [Refereed][Not invited]
   

  Background: Timing of the onset of subarachnoid hemorrhage (SAH) is important for treatment decision-making, especially as some patients visit hospital several weeks after the onset of SAH. T2*-weighted (T2*W) magnetic resonance (MR) imaging is regarded as a sensitive method for the detection of deoxyhemoglobin or hemosiderin deposits. This study investigated the characteristics of the abnormal low intensity changes on T2*W imaging in patients with SAH, how long the abnormal low intensity persisted, and whether the day of onset could be predicted based on the T2*W imaging changes. Methods: The study included patients treated for SAH associated with ruptured cerebral aneurysms, or who had previously suffered such SAH and were followed up at our hospital, between 2006 and 2007. MR imaging was performed using a whole-body 3.0-tesla MR scanner. All patients underwent gradient recalled echo (GRE) and echo planar (EP) T2*W imaging. The strength of the low intensity areas was evaluated as the following 5 grades: grade 0, no abnormal low intensity on both GRE and EP T2*W images grade 1, no abnormal intensity on GRE T2*W images and low intensity on EP T2*W images grade 2, spotty abnormal low intensity on both GRE and EP T2*W images grade 3, medium abnormal low intensity (< 5 mm) on both GRE and EP T2*W images, and grade 4, large abnormal low intensity (≥5 mm) on both GRE and EP T2*W images. Results: A total of 50 patients with 74 MR images were included during the study period. Abnormal low intensity on T2*W imaging was observed in all patients. The T2* score gradually decreased from the onset of SAH until day 90, showing a significant negative linear correlation (R2 = 0.25, p = 0.0002). On the other hand, the T2* score did not change after 1 year. The square correlation coefficient between the recorded and calculated days from the onset of SAH was 0.29 (p = 0.0107). The pure error was ±10 days. Conclusion: The T2* score gradually decreased until 90 days from the onset of SAH, but persisted for 16 years after the onset. We could predict the day of onset with pure error ±10 days in patients with SAH within 90 days of onset using our grading system for T2*W images. © 2013 S. Karger AG, Basel.
• Relative Residence Time Prolongation in Intracranial Aneurysms: A Possible Association With Atherosclerosis

  Shin-ichiro Sugiyama, Kuniyasu Niizuma, Toshio Nakayama, Hiroaki Shimizu, Hidenori Endo, Takashi Inoue, Miki Fujimura, Makoto Ohta, Akira Takahashi, Teiji Tominaga

  NEUROSURGERY 73 (5) 767 - 776 0148-396X 2013/11 [Refereed][Not invited]
   

  BACKGROUND: Intracranial aneurysms can have atherosclerotic wall properties that may be important in predicting aneurysm history or estimating the potential risks of surgical treatments. OBJECTIVE: To investigate hemodynamic characteristics of atherosclerotic lesions in intracranial aneurysms using computational fluid dynamics. METHODS: Intraoperative video recordings of 30 consecutive patients with an unruptured middle cerebral artery aneurysm were examined to identify atherosclerotic lesions on an aneurysm wall. For computational fluid dynamics analyses, geometries of aneurysms and adjacent arteries were reconstructed from 3-dimensional rotational angiography. Transient simulations were conducted under patient-specific pulsatile inlet conditions measured by phase-contrast magnetic resonance velocimetry. Three hemodynamic wall parameters were calculated: time-averaged wall shear stress, oscillatory shear index, and relative residence time (RRT). Statistical analyses were performed to discriminate the risk factors of atherosclerotic lesion formation. RESULTS: Among 30 aneurysms, 7 atherosclerotic lesions with remarkable yellow lipid deposition were identified in 5 aneurysms. All 7 atherosclerotic lesions spatially agreed with the area with prolonged RRT. Univariate analysis revealed that male sex (P = .03), cigarette smoking (P = .047), and maximum RRT (P = .02) are significantly related to atherosclerotic lesion on the intracranial aneurysmal wall. Of those variables that influenced atherosclerotic lesion of the intracranial aneurysmal wall, male sex (P = .005) and maximum RRT (P = .004) remained significant in the multivariate regression model. CONCLUSION: The area with prolonged RRT colocalized with atherosclerotic change on the aneurysm wall. Male sex and maximum RRT were independent risk factors for atherogenesis in intracranial aneurysms.
• Issues in moyamoya disease: Consideration for its intrinsic physiologi-cal reorganization system

  Miki Fujimura, Teiji Tominaga

  Japanese Journal of Neurosurgery 22 (9) 695 - 698 0917-950X 2013/09/25 [Refereed][Not invited]
   

  Moyamoya disease is a chronic occlusive cerebrovascular disease with unknown etiology characterized by bilateral steno-occlusive changes at the terminal portion of the internal carotid artery (ICA), associated with abnormal vascular networks at the base of the brain. Recent genetic research suggests that the RNF213 gene located at chromosome 17q25 may be the susceptibility gene for moyamoya disease. RNF213 mutation predicts both early-onset and the severe form of moyamoya disease. As secondary insults in addition to the genetic abnor-mality, autoimmune response, inflammation/infection, radiation, and endothelial progenitor cells may together be implicated in the etiology of moyamoya disease. Finally, the dynamic nature of moyamoya disease, which is the self- compensatory reorganization system demonstrating the conversion of the blood flow supply from ICA system to the external carotid artery system, should be clarified to understand the pathophysiology of moyamoya disease.
• Moyamoya Disease in Pregnancy: A Single Institute Experience

  Miki Fujimura, Kozo Akagi, Hiroshi Uenohara, Teiji Tominaga

  NEUROLOGIA MEDICO-CHIRURGICA 53 (8) 561 - 564 0470-8105 2013/08 [Refereed][Not invited]
   

  Moyamoya disease is a rare chronic, occlusive cerebrovascular disease characterized by bilateral stenoocclusive changes at the terminal portion of the internal carotid artery and an abnormal vascular network at the base of the brain. Moyamoya disease particularly affects children and young adults with female predominance, thus pregnant patients with moyamoya disease are not uncommon. Among 4,400 patients with consecutive deliveries in our hospital, 6 patients (0.14%) aged from 24 to 40 years (mean 32.7 years) were found to have moyamoya disease, all of whom underwent cesarean section. Four patients who had been diagnosed with moyamoya disease before pregnancy did not show neurological events in pregnancy and puerperium, but two patients who were newly diagnosed or progressed during the perinatal period suffered neurological deterioration due to ischemic stroke. Surgical revascularization at the subacute stage relieved their symptoms and they did not suffer permanent neurological deficit. We recommend that pregnant patients with moyamoya disease should be carefully managed under the collaboration of obstetricians and neurosurgeons, and that the procedure of the delivery should selected, by the obstetricians to avoid unfavorable sequelae caused by hyperventilation and/or blood pressure elevation.
• Quantitative assessment of cerebral hemodynamics using single photon emission computed tomography with venous blood sampling

  Takashi Inoue, Miki Fujimura, Hiroaki Shimizu, Yoshitake Takahashi, Teiji Tominaga

  CLINICAL NEUROLOGY AND NEUROSURGERY 115 (6) 684 - 689 0303-8467 2013/06 [Refereed][Not invited]
   

  Objective: Quantitative cerebral blood flow (CBF) measured by single photon emission computed tomography (SPECT) with arterial blood sampling is one of the most reliable methods to assess the hemodynamics in individual patients. SPECT with venous blood sampling is less invasive. The present study compared the measurement of CBF using N-isopropyl-p-(iodine-123)-iodoamphetamine SPECT with venous blood sampling and with arterial blood sampling in patients with major cerebral artery occlusive disease. Methods: Two normal subjects and 14 patients with major cerebral artery occlusive disease underwent SPECT with arterial and venous blood sampling. The microsphere method was used for quantitative SPECT imaging. Whole brain radioactivity was corrected when the detectors rotated in the forward direction (F-1-F-7). Venous sampling was performed 30 min after radiotracer injection. Arterial blood radioactivity was estimated by multiple regression analysis from these parameters. The cerebrovascular reactivity to acetazolamide was also measured. Results: Multiple regression analysis established the following formula: Ca-10 = -1.099F(1) + 1.629F(2) - 2.143F(3) - 2.766F(4) - 1.208F(5) + 2.113F(6) + 3.259F(7) + 1.241Cv(30) + 94.958 (where Ca-10 is the arterial blood radioactivity at 10 min, F-1-F-7 are the whole brain radioactivity in the forward direction, Cv(30) is the venous blood radioactivity at 30 min). Mean CBF values were 32.2 +/- 6.6 ml/100 g/min for measured arterial radioactivity and 42.2 +/- 7.8 ml/100 g/min for calculated arterial radioactivity based on venous radioactivity. Conclusions: The present modified method of calculating quantitative CBF from whole brain and venous blood radioactivities correlated well with values determined with arterial blood radioactivity. (C) 2012 Elsevier B.V. All rights reserved.
• Noninvasive measurement of human brain temperature adjacent to arteriovenous malformation using 3.0 T magnetic resonance spectroscopy

  Takashi Inoue, Hiroaki Shimizu, Miki Fujimura, Atsushi Saito, Yoshichika Yoshioka, Tsuyoshi Matsuda, Teiji Tominaga

  CLINICAL NEUROLOGY AND NEUROSURGERY 115 (4) 445 - 449 0303-8467 2013/04 [Refereed][Not invited]
   

  Object: The brain temperature at rest is determined by the balance between heat produced by cerebral energy turnover, which is identical to cerebral metabolism, and heat that is removed, primarily by cerebral blood flow. The present study investigated whether brain temperature measured by proton magnetic resonance (MR) spectroscopy can detect cerebral hemodynamic impairment in patients with arteriovenous malformations (AVMs) as shown by single photon emission computed tomography (SPECT). Methods: Brain temperature, cerebral blood flow, and cerebrovascular reactivity were measured using proton MR spectroscopy and SPECT in five healthy volunteers and six patients with AVMs. Regions of interest were selected adjacent to the AVMs and in the corresponding contralateral region. Results: Brain temperature around AVMs was calculated in all subjects using MR spectroscopy. The mean brain temperature in volunteers was 37.1 +/- 0.41 degrees C. A significant correlation was observed between brain temperature ratio (affected side/contralateral side) and cerebrovascular reactivity ratio (affected side/contralateral side) (r = -0.82, p = 0.0480). Conclusion: Brain temperature measured by proton MR spectroscopy can detect cerebral hemodynamic impairment in patients with AVMs. Further investigations regarding the relationships between brain temperature and clinical feature in patients with AVMs are needed. (c) 2012 Elsevier B.V. All rights reserved.
• Concurrent dural and perimedullary arteriovenous fistulas at the craniocervical junction: Case series with special reference to angioarchitecture ; Clinical article

  Kenichi Sato, Toshiki Endo, Kuniyasu Niizuma, Miki Fujimura, Takashi Inoue, Hiroaki Shimizu, Teiji Tominaga

  Journal of Neurosurgery 118 (2) 451 - 459 0022-3085 2013/02 [Refereed][Not invited]
   

  Object. Dural arteriovenous fistulas (DAVFs) and perimedullary arteriovenous fistulas (PAVFs) are uncommonly associated in the craniocervical junction. The purpose of this study was to describe the clinical and angiographic characteristics of such concurrent lesions. Methods. Authors reviewed 9 cases with a coexistent DAVF and PAVF at the craniocervical junction. Clinical presentation, angiographic characteristics, intraoperative findings, and treatment outcomes were assessed. Results. All patients (male/female ratio 5:4 mean age 66.3 years) presented with subarachnoid hemorrhage. Angiography revealed that 8 patients had both a DAVF and PAVF on the same side, whereas 1 patient had 3 arteriovenous fistulas, 1 DAVF, and 1 PAVF on the right side and 1 DAVF on the left side. All of the fistulas shared dilated perimedullary veins (anterior spinal vein, 7 cases anterolateral spinal vein, 2 cases) as a main drainage route. The shared drainage route was rostrally directed in 8 of 9 cases. Eight patients exhibited an arterial aneurysm on the distal side of the feeding arteries to the PAVF, and the aneurysm in each case was intraoperatively confirmed as a bleeding point. One patient had ruptured venous ectasia at the perimedullary fistulous point. All patients underwent direct surgery via a posterolateral approach. No recurrence was observed in the 4 patients who underwent postoperative angiography, and no rebleeding event was recorded among any of the 9 patients during the follow-up period (mean 38.4 months). Conclusions. The similarity of the angioarchitecture and the close anatomical relationship between DAVF and PAVF at the craniocervical junction suggested that these lesions are pathogenetically linked. The pathophysiological mechanism and anatomical features of these lesions represent a unique vascular anomaly that should be recognized angiographically to plan a therapeutic strategy. © AANS, 2013.
• Medullary infarction as a poor prognostic factor after internal coil trapping of a ruptured vertebral artery dissection Clinical article

  Hidenori Endo, Yasushi Matsumoto, Ryushi Kondo, Kenichi Sato, Miki Fujimura, Takashi Inoue, Hiroaki Shimizu, Akira Takahashi, Teiji Tominaga

  NEUROSURGICAL FOCUS 34 (1) 131 - 139 1092-0684 2013/01 [Refereed][Not invited]
   

  Object. Internal coil trapping is a treatment method used to prevent rebleeding from a ruptured intracranial vertebral artery dissection (VAD). Postoperative medullary infarctions have been reported as a complication of this treatment strategy. The aim of this study was to determine the relationship between a postoperative medullary infarction and the clinical outcomes for patients with ruptured VADs treated with internal coil trapping during the acute stage of a subarachnoid hemorrhage (SAH). Methods. A retrospective study identified 38 patients who presented between 2006 and 2011 with ruptured VADs and underwent internal coil trapping during the acute stage of SAH. The SAH was identified on CT scanning, and the diagnosis for VAD was rendered by cerebral angiography. Under general anesthesia, the dissection was packed with coils, beginning at the distal end and proceeding proximally. When VAD involved the origin of the posterior inferior cerebellar artery (PICA) with a large cerebellar territory, an occipital artery (OA)-PICA anastomosis was created prior to internal coil trapping. The pre- and postoperative radiological findings, clinical course, and outcomes were analyzed. Results. The internal coil trapping was completed within 24 hours after admission. An OA-PICA anastomosis followed by internal coil trapping was performed in 5 patients. Postoperative rebleeding did not occur in any patient during a mean follow-up period of 16 months. The postoperative MRI studies showed medullary infarctions in 18 patients (47%). The mean length of the trapped VAD for the infarction group (15.7 +/- 6.0 mm) was significantly longer than that of the non-infarction group (11.5 +/- 4.3 mm) (p = 0.019). Three of the 5 patients treated with OA-PICA anastomosis had postoperative medullary infarction. The clinical outcomes at 6 months were favorable (modified Rankin Scale Scores 0-2) for 23 patients (60.5%) and unfavorable (modified Rankin Scale Scores 3-6) for 15 patients (39.5%). Of the 18 patients with postoperative medullary infarctions, the outcomes were favorable for 6 patients (33.3%) and unfavorable for 12 patients (66.7%). A logistic regression analysis predicted the following independent risk factors for unfavorable outcomes: postoperative medullary infarctions (OR 21.287 [95% CI 2.622-498.242], p = 0.003); preoperative rebleeding episodes (OR 7.450 [95% CI 1.140-71.138], p = 0.036); and a history of diabetes mellitus (OR 45.456 [95% CI 1.993-5287.595], p = 0.013). Conclusions. A postoperative medullary infarction was associated with unfavorable outcomes after internal coil trapping for ruptured VADs. Coil occlusion of the long segment of the VA led to medullary infarction, and an OA-PICA bypass did not prevent medullary infarction. A VA-sparing procedure, such as flow diversion by stenting, is an alternative treatment in the future, if this approach is demonstrated to effectively prevent rebleeding. (http://thejns.org/doi/abs/10.3171/2012.9.JNS12566)
• Medullary infarction as a poor prognostic factor after internal coil trapping of a ruptured vertebral artery dissection Clinical article

  Hidenori Endo, Yasushi Matsumoto, Ryushi Kondo, Kenichi Sato, Miki Fujimura, Takashi Inoue, Hiroaki Shimizu, Akira Takahashi, Teiji Tominaga

  JOURNAL OF NEUROSURGERY 118 (1) 131 - 139 0022-3085 2013/01 [Refereed][Not invited]
   

  Object. Internal coil trapping is a treatment method used to prevent rebleeding from a ruptured intracranial vertebral artery dissection (VAD). Postoperative medullary infarctions have been reported as a complication of this treatment strategy. The aim of this study was to determine the relationship between a postoperative medullary infarction and the clinical outcomes for patients with ruptured VADs treated with internal coil trapping during the acute stage of a subarachnoid hemorrhage (SAH). Methods. A retrospective study identified 38 patients who presented between 2006 and 2011 with ruptured VADs and underwent internal coil trapping during the acute stage of SAH. The SAH was identified on CT scanning, and the diagnosis for VAD was rendered by cerebral angiography. Under general anesthesia, the dissection was packed with coils, beginning at the distal end and proceeding proximally. When VAD involved the origin of the posterior inferior cerebellar artery (PICA) with a large cerebellar territory, an occipital artery (OA)-PICA anastomosis was created prior to internal coil trapping. The pre- and postoperative radiological findings, clinical course, and outcomes were analyzed. Results. The internal coil trapping was completed within 24 hours after admission. An OA-PICA anastomosis followed by internal coil trapping was performed in 5 patients. Postoperative rebleeding did not occur in any patient during a mean follow-up period of 16 months. The postoperative MRI studies showed medullary infarctions in 18 patients (47%). The mean length of the trapped VAD for the infarction group (15.7 +/- 6.0 mm) was significantly longer than that of the non-infarction group (11.5 +/- 4.3 mm) (p = 0.019). Three of the 5 patients treated with OA-PICA anastomosis had postoperative medullary infarction. The clinical outcomes at 6 months were favorable (modified Rankin Scale Scores 0-2) for 23 patients (60.5%) and unfavorable (modified Rankin Scale Scores 3-6) for 15 patients (39.5%). Of the 18 patients with postoperative medullary infarctions, the outcomes were favorable for 6 patients (33.3%) and unfavorable for 12 patients (66.7%). A logistic regression analysis predicted the following independent risk factors for unfavorable outcomes: postoperative medullary infarctions (OR 21.287 [95% CI 2.622-498.242], p = 0.003); preoperative rebleeding episodes (OR 7.450 [95% CI 1.140-71.138], p = 0.036); and a history of diabetes mellitus (OR 45.456 [95% CI 1.993-5287.595], p = 0.013). Conclusions. A postoperative medullary infarction was associated with unfavorable outcomes after internal coil trapping for ruptured VADs. Coil occlusion of the long segment of the VA led to medullary infarction, and an OA-PICA bypass did not prevent medullary infarction. A VA-sparing procedure, such as flow diversion by stenting, is an alternative treatment in the future, if this approach is demonstrated to effectively prevent rebleeding. (http://thejns.org/doi/abs/10.3171/2012.9.JNS12566)
• A case of moyamoya disease presenting with progressive stroke during the late perinatal period successfully managed by bilateral revascularization surgeries

  Takashi Sasaki, Miki Fujimura, Yosuke Akamatsu, Naoto Kimura, Masayuki Ezura, Hiroshi Uenohara, Kozo Akagi, Teiji Tominaga

  Neurological Surgery 40 (12) 1095 - 1099 0301-2603 2012/12 [Refereed][Not invited]
   

  We report a case of moyamoya disease presenting with progressive stroke during the late perinatal period, which was successfully managed by emergency caesarean section and subsequent bilateral revascularization surgeries. A 27-year-old woman at 33 weeks of pregnancy suffered from progressive monoparesis on her left hand. Magnetic resonance (MR) imaging/angiography revealed definitive moyamoya disease presenting with acute spotty cerebral infarctions on the right cerebral hemisphere. At 34 weeks of pregnancy, she was transferred to our hospital, where both neurosurgeons and obstetricians were involved in her management. She underwent emergency caesarean section on the day of admission without deterioration of her neurological status, while MRI demonstrated newly-formed spotty infarction on the left hemisphere. Then she was managed by antithrombotic therapy for 4 weeks, and then underwent right superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis, followed by left STA-MCA anastomosis one month later without complications. Postoperative course was uneventful, and MRI after surgeries showed no expansion of ischemic lesion. The MRA showed apparently patent STA-MCA bypasses bilaterally. She was discharged without complication, and her symptom significantly improved two weeks after the left revascularization surgery.
• Hemodynamic analysis of growing intracranial aneurysms arising from a posterior inferior cerebellar artery

  Shin-Ichiro Sugiyama, Hui Meng, Kenichi Funamoto, Takashi Inoue, Miki Fujimura, Toshio Nakayama, Shunsuke Omodaka, Hiroaki Shimizu, Akira Takahashi, Teiji Tominaga

  World Neurosurgery 78 (5) 462 - 468 1878-8750 2012/11 [Refereed][Not invited]
   

  Objective: The role of hemodynamics in the growth of intracranial aneurysms is not completely clear. We present a hemodynamic study with two adjacent unruptured aneurysms arising from one parent artery but growing in different ways. This study aimed to investigate whether there were differences in hemodynamic characteristics between the two growing aneurysms. Methods: A 62-year-old female patient presented with six unruptured intracranial aneurysms. Catheter angiography at 6-month intervals revealed that two aneurysms located adjacently at the right posterior inferior cerebellar artery were growing over a 1-year period. Three-dimensional aneurysm geometries were acquired via rotational angiography. Computational fluid dynamic simulations were conducted on the 3D aneurysm geometries under patient-specific pulsatile flow conditions that were measured by magnetic resonance velocimetry. Results: The proximal multilobular aneurysm demonstrated high flow and physiological levels of wall shear stress (WSS) in the region of growth, whereas the distal rounded aneurysm had low flow and low WSS in the growing sac. Conclusion: Growing aneurysms can have heterogeneous hemodynamic and morphologic characteristics and different growing patterns. Growing regions of an aneurysm could be exposed to either high WSS at the inflow zone or low WSS and high oscillatory shear in the aneurysm sac. © 2012 Elsevier Inc.
• Local hemodynamics at the rupture point of cerebral aneurysms determined by computational fluid dynamics analysis

  Shunsuke Omodaka, Shin-Ichirou Sugiyama, Takashi Inoue, Kenichi Funamoto, Miki Fujimura, Hiroaki Shimizu, Toshiyuki Hayase, Akira Takahashi, Teiji Tominaga

  Cerebrovascular Diseases 34 (2) 121 - 129 1015-9770 2012/09 [Refereed][Not invited]
   

  Background: Cerebral aneurysms carry a high risk of rupture and so present a major threat to the patient's life. Accurate criteria for predicting aneurysm rupture are important for therapeutic decision-making, and some clinical and morphological factors may help to predict the risk for rupture of unruptured aneurysms, such as sex, size and location. Hemodynamic forces are considered to be key in the natural history of cerebral aneurysms, but the effect on aneurysm rupture is uncertain, and whether low or high wall shear stress (WSS) is the most critical in promoting rupture remains extremely controversial. This study investigated the local hemodynamic features at the aneurysm rupture point. Methods: Computational models of 6 ruptured middle cerebral artery aneurysms with intraoperative confirmation of rupture point were constructed from 3-dimensional rotational angiography images. Computational fluid dynamics (CFD) simulations were performed under pulsatile flows using patient-specific inlet flow conditions. Time-averaged WSS (TAWSS) and oscillatory shear index (OSI) were calculated, and compared at the rupture point and at the aneurysm wall without the rupture point. We performed an additional CFD simulation of a bleb-removed model for a peculiar case in which bleb formation could be confirmed by magnetic resonance angiography. Results: All rupture points were located at the body or dome of the aneurysm. The TAWSS at the rupture point was significantly lower than that at the aneurysm wall without the rupture point (1.10 vs. 4.96 Pa, p = 0.031). The OSI at the rupture point tended to be higher than at the aneurysm wall without the rupture point, although the difference was not significant (0.0148 vs. 0.0059, p = 0.156). In a bleb-removed simulation, the TAWSS at the bleb-removed area was 6.31 Pa, which was relatively higher than at the aneurysm wall (1.94 Pa). Conclusion: The hemodynamics of 6 ruptured cerebral aneurysms of the middle cerebral artery were examined using retrospective CFD analysis. We could confirm the rupture points in all cases. With those findings, local hemodynamics of ruptured aneurysms were quanti-tatively investigated. The rupture point is located in a low WSS region of the aneurysm wall. Bleb-removed simulation showed increased WSS of the bleb-removed area, associated with the flow impaction area. Although the number of subjects in this study was relatively small, our findings suggest that the location of the rupture point is related to a low WSS at the aneurysm wall. Further investigations will elucidate the detailed hemodynamic effects on aneurysm rupture. © 2012 S. Karger AG, Basel.
• Annual rupture risk of growing unruptured cerebral aneurysms detected by magnetic resonance angiography: Clinical article

  Takashi Inoue, Hiroaki Shimizu, Miki Fujimura, Atsushi Saito, Teiji Tominaga

  Journal of Neurosurgery 117 (1) 20 - 25 0022-3085 2012/07 [Refereed][Not invited]
   

  Object. In this paper, the authors' goals were to clarify the characteristics of growing unruptured cerebral aneurysms detected by serial MR angiography and to establish the recommended follow-up interval. Methods. A total of 1002 patients with 1325 unruptured cerebral aneurysms were retrospectively identified. These patients had undergone follow-up evaluation at least twice. Aneurysm growth was defined as an increase in maximum aneurysm diameter by 1.5 times or the appearance of a bleb. Results. Aneurysm growth was observed in 18 patients during the period of this study (1.8%/person-year). The annual rupture risk after growth was 18.5%/person-year. The proportion of females among patients with growing aneurysms was significantly larger than those without growing aneurysms (p = 0.0281). The aneurysm wall was reddish, thin, and fragile on intraoperative findings. Frequent follow-up examination is recommended to detect aneurysm growth before rupture. Conclusions. Despite the relatively short period, the annual rupture risk of growing unruptured cerebral aneurysms detected by MR angiography was not as low as previously reported. Surgical or endovascular treatment can be considered if aneurysm growth is detected during the follow-up period.
• Efficacy of prophylactic blood pressure lowering according to a standardized postoperative management protocol to prevent symptomatic cerebral hyperperfusion after direct revascularization surgery for moyamoya disease

  Miki Fujimura, Takashi Inoue, Hiroaki Shimizu, Atsushi Saito, Shunji Mugikura, Teiji Tominaga

  Cerebrovascular Diseases 33 (5) 436 - 445 1015-9770 2012/05 [Refereed][Not invited]
   

  Background: Cerebral hyperperfusion is a potential complication of superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis for moyamoya disease, but the optimal postoperative management has not been determined. Aggressive blood pressure lowering is controversial because of the risk of ischemic complications. Objective: To establish the optimal postoperative management protocol to prevent symptomatic cerebral hyperperfusion in moyamoya disease. Methods: N-isopropyl-p-[ 123I]-iodoamphetamine single-photon emission computed tomography was performed 1 and 7 days after STA-MCA anastomosis on 152 hemispheres from 108 consecutive patients with moyamoya disease (2-69, mean 33.3 years). Between 2004 and 2007 (period 1), 65 patients were maintained under normotensive conditions after 93 operations, and only patients with cerebral hyperperfusion underwent blood pressure lowering. Between 2008 and 2010 (period 2), all 43 patients were prospectively subjected to intensive blood pressure lowering (< 130 mm Hg of systolic blood pressure) immediately after 59 operations. Then the incidence of symptomatic cerebral hyperperfusion was compared between the two groups. Results: Systolic blood pressure the day after surgery was significantly lower in period 2 (mean, 120.9 mm Hg) than in period 1 (133.9 mm Hg) (p < 0.0001). Symptomatic cerebral hyperperfusion was seen in 22 patients during period 1 (23 hemispheres, 24.7%), but only in 4 patients during period 2 (6.7%, p = 0.0047). Multivariate analysis revealed that prophylactic blood pressure lowering was significantly associated with the prevention of symptomatic cerebral hyperperfusion (p = 0.015). Symptomatic cerebral hyperperfusion was relieved in all patients without developing a permanent neurological deficit due to cerebral hyperperfusion. Conclusion: Prophylactic blood pressure lowering prevents symptomatic cerebral hyperperfusion after STA-MCA anastomosis in patients with moyamoya disease. Accurate diagnosis of cerebral hyperperfusion and blood pressure lowering, and considering the severity of hemodynamic compromise in the contralateral and/or remote areas are essential for postoperative management of moyamoya disease. Copyright © 2012 S. Karger AG, Basel.
• Consistent focal cerebral ischemia without posterior cerebral artery occlusion and its real-time monitoring in an intraluminal suture model in mice: Laboratory investigation

  Yosuke Akamatsu, Hiroaki Shimizu, Atsushi Saito, Miki Fujimura, Teiji Tominaga

  Journal of Neurosurgery 116 (3) 657 - 664 0022-3085 2012/03 [Refereed][Not invited]
   

  Object. In the intraluminal suture model of middle cerebral artery occlusion (MCAO) in the mouse, disturbance of blood flow from the internal carotid artery to the posterior cerebral artery (PCA) may affect the size of the infarction. In this study, PCA involvement in the model was investigated and modified for consistent MCAO without involving the PCA territory. Methods. Thirty-seven C57Bl/6 mice were randomly divided into 4 groups according to the length of coating over the tip of the suture (1, 2, 3, or 4 mm) and subjected to transient MCAO for 2 hours. Real-time topographical cerebral blood flow was monitored over both hemispheres by laser speckle flowmetry. After 24 hours of reperfusion, the infarct territories and volumes were evaluated. Results. The 1- and 2-mm coating groups showed all lesions in the MCA territory. In the 3- and 4-mm coating groups, 62.5% and 75% of mice, respectively, showed lesions in both the MCA and the PCA territories and other lesions in the MCA territory. Mice in the 1- and 2-mm coating groups had significantly smaller infarct volumes than the 3- and 4-mm groups. Laser speckle flowmetry was useful to distinguish whether the PCA territory would undergo infarction. Conclusions. Small changes in the coating length of the intraluminal suture may be critical, and 1-2 mm of coating appeared to be optimal to produce consistent MCAO without involving the PCA territory. Laser speckle flowmetry could predict the territory of infarction and improve the consistency of the infarct size.
• Lessons learned from moyamoya disease: Outcome of direct/indirect revascularization surgery for 150 affected hemispheres

  Miki Fujimura, Teiji Tominaga

  Neurologia Medico-Chirurgica 52 (5) 327 - 332 1349-8029 2012 [Refereed][Not invited]
   

  Moyamoya disease is a chronic, occlusive cerebrovascular disease with unknown etiology characterized by bilateral steno-occlusive changes at the terminal portion of the internal carotid artery and an abnormal vascular network at the base of the brain. Recent advances in molecular biology and genetic research have provided better understanding of the pathophysiology of moyamoya disease, but surgical revascularization still remains the preferred treatment for this entity. The present study investigated the clinical course of 106 consecutive patients with moyamoya disease who underwent superficial temporal artery-middle cerebral artery anastomosis with indirect pial synangiosis in 150 hemispheres. The outcomes of surgery on the operated hemisphere were favorable, with no cerebrovascular event during the outpatient follow-up period (mean 58.4 months) in 89.3% (134/150). Two patients suffered hemor-rhagic events on the operated hemisphere during the follow-up period (2/150, 1.33%), one of whom suffered deteriorated neurological status after hemorrhage. Despite the favorable long-term outcome, the incidence of temporary neurological deterioration due to cerebral hyperperfusion was 18.0% (27/150), but no patients suffered permanent neurological deterioration directly caused by hyperperfu-sion. In conclusion, direct/indirect revascularization surgery is a safe and effective treatment for moyamoya disease, although the issue of bleeding/re-bleeding remains to be solved. Postoperative cerebral hyperperfusion and peri-operative infarction are potential complications of this procedure, so we recommend intensive postoperative care and cerebral blood flow measurement in the acute stage, because the management of hyperperfusion is contradictory to that of ischemia.
• Temporal profile of de novo development of moyamoya vasculopathy in an adult

  Yoshiteru Shimoda, Miki Fujimura, Takashi Inoue, Hiroaki Shimizu, Teiji Tominaga

  Neurologia Medico-Chirurgica 52 (5) 339 - 342 1349-8029 2012 [Refereed][Not invited]
   

  A 46-year-old woman developed transient ischemic attack (TIA) caused by progressive moyamoya vas-culopathy in the right hemisphere. She had presented with minor cerebellar infarction due to left vertebral artery dissection 7 years prior to the onset of TIA. Initial carotid angiography at the onset of vertebral artery dissection demonstrated absence of steno-occlusive changes in the anterior circulation. During the next 7 years, she had been strictly followed up with magnetic resonance angiography every 6 months, which demonstrated the asymptomatic development of steno-occlusive change in the proximal right middle cerebral artery, finally involving the terminal internal carotid artery. Carotid angiography at the onset of TIA showed terminal internal carotid artery stenosis with abnormal vascular network at the right base of the brain, indicating a definitive diagnosis of moyamoya vasculopathy with unilateral involvement. She underwent right superficial temporal artery-middle cerebral artery anastomosis without complication one month later. TIA completely disappeared after surgery, and no cerebrovascu-lar events occurred during the follow-up period of 6 months. De novo formation of moyamoya vas-culopathy is extremely rare in adulthood. The present case demonstrated the entire temporal profile of the development of this rare entity in adulthood. The previous presentation of vertebral artery dissection before the development of moyamoya vasculopathy as well as the initiation of steno-occlusive change at the middle cerebral artery is apparently unique.
• Occipital artery-anterior inferior cerebellar artery bypass with microsurgical trapping for exclusively intra-meatal anterior inferior cerebellar artery aneurysm manifesting as subarachnoid hemorrhage

  Miki Fujimura, Takashi Inoue, Hiroaki Shimizu, Teiji Tominaga

  Neurologia Medico-Chirurgica 52 (6) 435 - 438 1349-8029 2012 [Refereed][Not invited]
   

  A 77-year-old woman presented with an extremely rare exclusively intra-meatal anterior inferior cerebellar artery (AICA) aneurysm manifesting as subarachnoid hemorrhage. The aneurysm was located at a non-branching site of its meatal loop, deeply inside the internal auditory canal. The ipsilateral posterior inferior cerebellar artery was hypoplastic and the affected AICA supplied a wide vascular territory in the right cerebellum. The patient underwent microsurgical trapping of the distal AICA aneurysm in the acute stage. Collateral back flow to the parent artery was poor, so right occipital artery (OA)-AICA anastomosis was performed prior to aneurysm trapping. The postoperative course was uneventful, and magnetic resonance imaging after surgery did not demonstrate any ischemic change. Postoperative angiography showed complete disappearance of the AICA aneurysm and the apparently patent OA-AICA bypass. She did not suffer neurological deficit except for right incomplete hearing disturbance, and postoperative single photon emission computed tomography demonstrated absence of hemodynamic compromise in the cerebellum. OA-AICA anastomosis with aneurysm trapping could be the optimal surgical management of the AICA aneurysm located exclusively inside the internal auditory canal, especially if the parent artery supplies a wide vascular territory.
• Ruptured aneurysm of a posterior inferior cerebellar artery communicating artery

  Shin-Ichiro Sugiyama, Miki Fujimura, Takashi Inoue, Hiroaki Shimizu, Mika Watanabe, Teiji Tominaga

  Neurologia Medico-Chirurgica 52 (2) 81 - 83 0470-8105 2012 [Refereed][Not invited]
   

  A hypertensive 60-year-old man presented with a rare aneurysm arising from the posterior inferior cerebellar artery (PICA) communicating artery, manifesting as subarachnoid hemorrhage with intraventricular hemorrhage. Angiography showed a small aneurysm arising from a fine and tortuous artery interconnecting the bilateral vermian branches of distal PICAs. The right PICA was absent and its vermian territory was supplied by the left PICA through this communicating artery. The right anterior inferior cerebellar artery was also connected to the vermian branch of the right PICA. At surgery, a reddish and apparent fusiform aneurysm was noted at the top of the arterial loop under the cerebellar vermis. Microsurgical trapping and removal of the aneurysm was performed without complication. Histological examination demonstrated typical findings of a true aneurysm. Only four previous cases of aneurysm of the communicating artery between the bilateral distal PICAs have been reported. In all five reported cases including ours, the PICA communicating artery contributed to the collateral blood supply of the contralateral vermian territory based on vascular anomalies. Hemodynamic stress and congenital vulnerability may have caused this aneurysm. Trapping is suitable to treat this precarious aneurysm if other collateral vessels supply the contralateral vermian territory.
• Subarachnoid hemorrhage due to ruptured posterior cerebral artery aneurysm simultaneously associated with multiple remote intracerebral hemorrhages

  Shinya Sonobe, Miki Fujimura, Hidenori Endo, Takashi Inoue, Hiroaki Shimizu, Teiji Tominaga

  Neurologia Medico-Chirurgica 51 (12) 836 - 838 0470-8105 2011/12/25 [Refereed][Not invited]
   

  A 61-year-old woman presented with aneurysmal subarachnoid hemorrhage (SAH) associated with multiple remote intracerebral hemorrhages (ICHs). She had undergone microsurgical neck clipping for ruptured right middle cerebral artery aneurysm and ventriculo-peritoneal shunting 16 years previously. Computed tomography revealed SAH predominantly in the basal cistern and ambient cistern, in association with multiple ICHs in the bilateral tegmentum of the brain stem and right caudate nucleus. Digital subtraction angiography revealed an aneurysm at the P1 segment of the left posterior cerebral artery. The ruptured aneurysm was microsurgically clipped via a left subtemporal approach without complications. Simultaneous occurrence of aneurysmal SAH and multiple remote ICHs is rare. The spatial pattern of the ICHs in the present case is apparently unique.
• Flow Analysis of Rupture Point in Cerebral Aneurysms: Computational Fluid Dynamics Study

  S. Omodaka, T. Inoue, K. Funamoto, S. Sugiyama, M. Fujimura, H. Shimizu, T. Hayase, A. Takahashi, T. Tominaga

  Proceedings on the 5th East Asian Pacific Student Workshop on Nano-Biomedical Engineering 68 - 69 2011/12/13 [Not refereed][Not invited]
  
• Predictive role of modified clinical diffusion mismatch in early neurological deterioration due to atherothrombotic ischemia in the anterior circulation

  Atsushi Saito, Hiroaki Shimizu, Miki Fujimura, Takashi Inoue, Teiji Tominaga

  Acta Neurochirurgica 153 (11) 2205 - 2210 0001-6268 2011/11 [Refereed][Not invited]
   

  Background: Atherothrombotic ischemia is the most frequent cause of cerebral ischemia however, few reports have addressed the prognostic factors predicting early neurological deterioration (END) when the occlusive lesion is limited to the anterior main trunk, middle cerebral artery (MCA) or internal cerebral artery (ICA). Method: Between 2006 and 2008, 122 atherothrombotic ischemia patients were diagnosed with MCA or ICA occlusive disease on magnetic resonance angiography. The National Institutes of Health Stroke Scale (NIHSS) score and the modified Alberta Stroke Program Early CT Score on diffusion-weighted imaging [ASPECTS-DW (modified)] were calculated. Clinical-DWI mismatch (CDM) was evaluated using NIHSS and the ASPECTS-DW (modified) to examine the predictive efficacy for early neurological deterioration. Results: Eighteen of 122 (14.8%) patients fulfilled the definition of CDM. END was observed in 24 patients (19.7%) within 15 days after admission. CDM was observed in 14 cases in the END (+) group (14 of 24 cases, 58.3%) and 4 cases in the END (-) group (4 of 98 cases, 4.1%) (p=0.001). Multivariate logistic regression analysis demonstrated that CDM was a significant predictive factor of END (odds ratio 26.68, p=0.0001). Conclusions: CDM based on NIHSS and ASPECTS-DW (modified) could be a significant predictive factor for END of atherothrombotic ischemia in MCA/ICA. © 2011 Springer-Verlag.
• Stachybotrys microspora triprenyl phenol-7, a novel fibrinolytic agent, suppresses superoxide production, matrix metalloproteinase-9 expression, and thereby attenuates ischemia/reperfusion injury in rat brain

  Yosuke Akamatsu, Atsushi Saito, Miki Fujimura, Hiroaki Shimizu, Moataz Mekawy, Keiji Hasumi, Teiji Tominaga

  NEUROSCIENCE LETTERS 503 (2) 110 - 114 0304-3940 2011/10 [Refereed][Not invited]
   

  Stachybotrys microspora triprenyl phenol-7 (SMTP-7) is a novel fibrinolytic agent with anti-inflammatory effect. Previous study demonstrated that SMTP-7 further ameliorated infarction volume in a mouse embolic stroke model compared with tissue type plasminogen activator (tPA), but the reason SMTP-7 has more beneficial effect than tPA has not yet been determined. In the present study, we investigated whether SMTP-7 has an intrinsic neuroprotective effect against transient focal cerebral ischemia (tFCI). Sprague-Dawley rats were subjected to tFCI by intraluminal middle cerebral artery occlusion for 2 h. Following induction of tFCI, rats were randomized into two groups based on the agent administered: SMTP-7 group and vehicle group. We examined cerebral infarction volume 24 h after reperfusion, and evaluated superoxide production, the expressions of nitrotyrosine and matrix metalloproteinase-9 (MMP-9), which play major roles in secondary brain injury and hemorrhagic transformation. The findings showed that SMTP-7 significantly suppressed superoxide production, the expression of nitrotyrosine and MMP-9 after tFCI, and consequently attenuated ischemic neuronal damage. These results suggest that SMTP-7 has an intrinsic neuroprotective effect on ischemia/reperfusion injury through the suppression of oxidative stress and MMP-9 activation. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
• Immunoliposomal drug-delivery system targeting lectin-like oxidized low-density lipoprotein receptor-1 for carotid plaque lesions in rats: Laboratory investigation

  Atsushi Saito, Hiroaki Shimizu, Yusuke Doi, Tatsuhiro Ishida, Miki Fujimura, Takashi Inoue, Hiroshi Kiwada, Teiji Tominaga

  Journal of Neurosurgery 115 (4) 720 - 727 0022-3085 2011/10 [Refereed][Not invited]
   

  Object. Targeted drug delivery with immunoliposomes has been applied to various in vivo animal models and is newly focused as a novel therapeutic target. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX1) is a potent regulator of systemic atherosclerosis, and the authors focused on its effect on carotid plaques. The authors developed a LOX1-targeted liposomal rho-kinase inhibitor and examined the therapeutic effect on carotid intimal hypertrophy in rats. Methods. LOX1-targeted rho-kinase inhibitor fasudil-containing liposomes, composed of hydrogenated soy phosphatidylcholine/ cholesterol/PEG2000-DSPE, were prepared by conjugating anti-LOX1 antibodies on the surface and by remote loading of fasudil. Carotid intimal hypertrophy was induced by balloon injury, and the drugs were intravenously administered on Day 3 postinjury. The rats were divided into 4 groups: nontreatment, treatment with intravenous fasudil (2 mg), treatment with liposomal fasudil (2 mg), and treatment with LOX1-targeted liposomal fasudil (2 mg). The authors compared intimal hypertrophy, atherosclerotic factor, and matrix metalloproteinase-9 expression among groups. Results. DiI-labeled LOX1-targeted liposomes were prominently observed in the lesions on Day 7 after the surgery. The intimal thickness was significantly reduced in the LOX1-targeted liposomal fasudil-treated group (mean 81.6 ± 13.9 mm) compared with the other groups (no treatment 105.4 ± 16.8 μm fasudil treatment 102.4 ± 20.0 μm and liposomal fasudil treatment 102.8 ± 22.2 μm p = 0.046). Matrix metalloproteinase-9 expression was also significantly reduced in the LOX1-targeted liposomal fasudil group. Conclusions. Liposomes conjugated with anti-LOX1 antibody effectively reached carotid artery lesions, and liposomal rho-kinase significantly inhibited intimal hypertrophy. The new liposomal drug delivery system targeting LOX1 may become a therapeutic strategy for atherosclerotic diseases.
• Cerebral blood flow after surgery for unruptured cerebral aneurysms: Effects of surgical manipulation and irrigation fluid

  Hiroaki Shimizu, Takashi Inoue, Miki Fujimura, Atsushi Saito, Teiji Tominaga

  Neurosurgery 69 (3) 677 - 688 0148-396X 2011/09 [Refereed][Not invited]
   

  Background: Cerebral blood flow (CBF) is important in the management of cerebrovascular diseases. Surgical manipulation may compromise the appropriate interpretation of postoperative CBF changes, but the effects are not well understood. Objective: To investigate the effect of surgical manipulation on postoperative CBF in a setting of prospective randomized comparison of 2 irrigation fluids during surgery. Methods: Twenty patients undergoing the clipping of unruptured cerebral aneurysms through the pterional approach were randomly assigned to use of Artcereb, an artificial cerebrospinal fluid, or physiological saline as irrigation fluid. Postoperative CBF and clinical conditions were evaluated 3 times in the first 7 to 10 postoperative days. Results: Postoperative CBF decreased by 10 to 15% on the first postoperative day in the ipsilateral inferior frontal gyrus, where surgical manipulation may be greatest. CBF reduction was less in regions remote from the surgical site and later in the follow-up periods. Selection of irrigation fluid did not influence postoperative CBF significantly, although postoperative clinical conditions may be better using Artcereb. Conclusion: Postoperative CBF changes due to surgical manipulation should be considered in patients whose hemodynamic conditions are important for appropriate management. Copyright © 2011 by the Congress of Neurological Surgeons.
• Ruptured aneurysm at the anterior wall of the internal carotid artery in a patient with systemic lupus erythematosus and secondary antiphospholipid syndrome

  Masashi Chonan, Miki Fujimura, Takashi Inoue, Teiji Tominaga

  Neurological Surgery 39 (7) 675 - 680 0301-2603 2011/07/10 [Refereed][Not invited]
   

  A 60 year-old woman, who had a 45-year history of systemic lupus erythematosus (SLE) and secondary antiphospholipid syndrome, presented with subarachnoid hemorrhage due to a ruptured aneurysm at the anterior wall of the non-branching site of the right internal carotid artery. She underwent radical surgery on the day of onset. In light of the possibility of arterial dissection, we performed extracranial-intracranial bypass prior to careful exploration of the aneurysm. Based on the finding of saccular aneurysm, she ultimately underwent neck clipping of the aneurysm without complication. Postoperative course was uneventful, and she did not suffer from cerebral vasospasm. We recommend early surgical intervention in patients with aneurysmal SAH associated with SLE, while intrinsic pathologies of SLE such as fragile vascular structure and the risk for ischemic complication should be considered.
• Asymptomatic intracerebral hemorrhage under strict blood pressure control due to postoperative cerebral hyperperfusion in a patient with moyamoya disease

  Akira Ito, Miki Fujimura, Takashi Inoue, Teiji Tominaga

  Neurological Surgery 39 (7) 681 - 686 0301-2603 2011/07/10 [Refereed][Not invited]
   

  We report a case of moyamoya disease manifesting as asymptomatic intracerebral hemorrhage due to postoperative cerebral hyperperfusion, despite the prophylactic intensive blood pressure control. This 35-year-old man initially suffered from right upper quadrantanopsia and was found to have cerebral infarction in the left occipital lobe due to moyamoya disease. He also manifested preoperatively a small intracerebral hemorrhage at the left caudate nucleus. The left cerebral hemisphere showed apparent hemodynamic compromise, thus he underwent left superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis with indirect pial synangiosis. He was subjected to prophylactic strict blood pressure control postoperatively to avoid hyperperfusion syndrome. The N-isopropyl-p-123I-lodoamphetamine SPECT (123I-IMP-SPECT) 1 day after surgery showed intense increase in cerebral blood flow (CBF) at the site of the anastomosis, and further blood pressure lowering was attempted. He did not suffer from neurologic deterioration during the postoperative period, while computed tomography (CT) 7 days after surgery revealed asymptomatic intracerebral hematoma (ICH) at the subcortex under the site of the anastomosis. Cerebral hyperperfusion is a potential complication of revascularization surgery for moyamoya disease. Accurate diagnosis and proper management of hyperperfusion are essential to avoid deleterious neurologic event due to hyperperfusion.
• Significance of focal cerebral hyperperfusion as a cause of transient neurologic deterioration after extracranial-intracranial bypass for moyamoya disease: Comparative study with non-moyamoya patients using n-isopropyl-p-[ 123I]iodoamphetamine single-photon emission computed tomography

  Miki Fujimura, Hiroaki Shimizu, Takashi Inoue, Shunji Mugikura, Atsushi Saito, Teiji Tominaga

  Neurosurgery 68 (4) 957 - 965 0148-396X 2011/04 [Refereed][Not invited]
   

  BACKGROUND: Superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis prevents cerebral ischemic attack by improving cerebral blood flow in patients with occlusive cerebrovascular disease and hemodynamic compromise. Recent evidence suggests that focal cerebral hyperperfusion is a potential complication of this procedure for moyamoya disease. OBJECTIVE: To clarify the exact differences in the incidence and clinical manifestations of this phenomenon between patients with and without moyamoya disease. METHODS: N-isopropyl-p-[I]iodoamphetamine single-photon emission computed tomography was performed 1 and 7 days after STA-MCA anastomosis on 121 hemispheres from 86 consecutive patients with moyamoya disease (2-67 years of age mean, 34.3 years) and on 28 hemispheres from 28 non-moyamoya patients (12-67 years of age mean, 56.5 years). The incidence of symptomatic hyperperfusion, defined as a significant focal increase in cerebral blood flow at the site of the anastomosis that is responsible for the apparent neurological signs, was compared between groups. RESULTS: Symptomatic cerebral hyperperfusion including mild focal neurological signs was seen in 25 patients with moyamoya disease (26 hemispheres, 21.5%) but in none of the patients without moyamoya disease (P = .0069). Multivariate analysis revealed that moyamoya disease was significantly associated with the development of symptomatic cerebral hyperperfusion (P = .0008). All patients with symptomatic hyperperfusion were relieved by intensive blood pressure control, and no patients suffered from permanent neurological deficit caused by hyperperfusion. CONCLUSION: Symptomatic cerebral hyperperfusion is a potential complication of STA-MCA anastomosis, especially in patients with moyamoya disease. Accurate diagnosis and adequate management of hyperperfusion are recommended, especially in patients with moyamoya disease. © 2011 by the Congress of Neurological Surgeons.
• Compromise of brain tissue caused by cortical venous reflux of intracranial dural arteriovenous fistulas: Assessment with diffusion-weighted magnetic resonance imaging

  Kenichi Sato, Hiroaki Shimizu, Miki Fujimura, Takashi Inoue, Yasushi Matsumoto, Teiji Tominaga

  Stroke 42 (4) 998 - 1003 0039-2499 2011/04 [Refereed][Not invited]
   

  Background and Purpose- Cortical venous reflux (CVR) is a high risk factor for aggressive behavior of intracranial dural arteriovenous fistulas (DAVF). The pathological conditions in brain tissue affected by CVR were investigated by diffusion-weighted magnetic resonance imaging. Methods- A retrospective review identified 56 patients with DAVFs who underwent diffusion-weighted imaging before treatment. Twenty patients had neurological symptoms corresponding to the brain area affected by CVR (Group I), 21 patients with CVR had no focal brain dysfunctions (Group II), and 15 patients had no CVR (Group III). Apparent diffusion coefficient (ADC) was measured for 11 brain areas predefined based on normal venous drainage patterns in the 56 patients and in 21 normal volunteers. The mean ADC ratio was calculated for each area by dividing the ADC value of patients by that of normal volunteers. Results- Areas affected by CVR in Group I showed a mean ADC-to-control ratio of 0.72, which was significantly lower than that of Group II (0.96, P< 0.01). Follow-up studies demonstrated significantly increased ADC ratios in brain areas affected by CVR after the DAVFs were treated successfully. The mean ADC ratio of an affected area remained low, with persistent symptoms in 1 patient who underwent palliative treatment. Conclusions- Decreased ADC was observed in the brain parenchyma affected by CVR and was associated with regional brain dysfunction. Successful treatment of the DAVF increased the ADC toward normal levels. The ADC may be a useful indicator of the severity of CVR. © 2011 American Heart Association. All rights reserved.
• Simultaneous occurrence of subarachnoid hemorrhage and epistaxis due to ruptured petrous internal carotid artery aneurysm: Association with transsphenoidal surgery and radiation therapy: Case report

  Hidenori Endo, Miki Fujimura, Takashi Inoue, Yasushi Matsumoto, Yshikazu Ogawa, Jun Kawagishi, Hidefumi Jokura, Hiroaki Shimizu, Teiji Tominaga

  Neurologia Medico-Chirurgica 51 (3) 226 - 229 0470-8105 2011 [Refereed][Not invited]
   

  A 62-year-old woman presented with simultaneous subarachnoid hemorrhage (SAH) and massive epistaxis. The patient had been treated for pituitary prolactinoma by two transsphenoidal surgeries, gamma knife radiosurgery, and conventional radiation therapy since age 43 years. Cerebral angiography showed left petrous internal carotid artery (ICA) aneurysm with slight stenosis on the adjacent left petrous ICA. She underwent superficial temporal artery-middle cerebral artery (STA-MCA) double anastomosis with endovascular internal trapping without complication the day after onset. Postoperative course was uneventful the patient did not develop symptomatic vasospasm, recurrent epistaxis, or cerebrospinal fluid rhinorrhea. Postoperative angiography demonstrated complete disappearance of the aneurysm with patent STA-MCA anastomosis. The patient was discharged 2 months after surgery without neurological deficit. The present case is extremely rare with simultaneous onset of SAH and epistaxis caused by ruptured petrous ICA aneurysm. The transsphenoidal surgeries and radiation therapies might have been critical in the formation of the petrous ICA aneurysm.
• A genome-wide association study identifies RNF213 as the first Moyamoya disease gene.

  Fumiaki Kamada, Yoko Aoki, Ayumi Narisawa, Yu Abe, Shoko Komatsuzaki, Atsuo Kikuchi, Junko Kanno, Tetsuya Niihori, Masao Ono, Naoto Ishii, Yuji Owada, Miki Fujimura, Yoichi Mashimo, Yoichi Suzuki, Akira Hata, Shigeru Tsuchiya, Teiji Tominaga, Yoichi Matsubara, Shigeo Kure

  Journal of human genetics 56 (1) 34 - 40 1434-5161 2011/01 [Refereed][Not invited]
   

  Moyamoya disease (MMD) shows progressive cerebral angiopathy characterized by bilateral internal carotid artery stenosis and abnormal collateral vessels. Although ∼ 15% of MMD cases are familial, the MMD gene(s) remain unknown. A genome-wide association study of 785,720 single-nucleotide polymorphisms (SNPs) was performed, comparing 72 Japanese MMD patients with 45 Japanese controls and resulting in a strong association of chromosome 17q25-ter with MMD risk. This result was further confirmed by a locus-specific association study using 335 SNPs in the 17q25-ter region. A single haplotype consisting of seven SNPs at the RNF213 locus was tightly associated with MMD (P = 5.3 × 10(-10)). RNF213 encodes a really interesting new gene finger protein with an AAA ATPase domain and is abundantly expressed in spleen and leukocytes. An RNA in situ hybridization analysis of mouse tissues indicated that mature lymphocytes express higher levels of Rnf213 mRNA than their immature counterparts. Mutational analysis of RNF213 revealed a founder mutation, p.R4859K, in 95% of MMD families, 73% of non-familial MMD cases and 1.4% of controls; this mutation greatly increases the risk of MMD (P = 1.2 × 10(-43), odds ratio = 190.8, 95% confidence interval = 71.7-507.9). Three additional missense mutations were identified in the p.R4859K-negative patients. These results indicate that RNF213 is the first identified susceptibility gene for MMD.
• Paradoxical Association of Moyamoya Syndrome With Large Middle Cerebral Artery Aneurysm and Subarachnoid Hemorrhage -Case Report

  Hidenori Endo, Miki Fujimura, Takashi Inoue, Hiroaki Shimizu, Teiji Tominaga

  NEUROLOGIA MEDICO-CHIRURGICA 50 (12) 1088 - 1091 0470-8105 2010/12 [Refereed][Not invited]
   

  A 60-year-old woman was admitted to our hospital because of fluctuating dysarthria during the past 2 months. Magnetic resonance imaging revealed old cerebral infarction of the left cerebral hemisphere with acute subarachnoid hemorrhage in the left sylvian fissure. Cerebral angiography showed a large saccular aneurysm, 14 mm in diameter, at the bifurcation of the left middle cerebral artery (MCA) in association with moyamoya vasculopathy with atherosclerosis, including steno-occlusive changes at the bilateral terminal internal carotid arteries and abnormal net-like vessels at the base of the brain. She underwent microsurgical neck clipping of the large aneurysm followed by superficial temporal artery-MCA anastomosis without complication. Intraoperative findings showed no evidence of aneurysm rupture, suggesting that the subarachnoid hemorrhage was due to the intrinsic pathology of moyamoya vasculopathy. The postoperative course was uneventful, and the patient was discharged without neurological deficit. Association of moyamoya syndrome with large MCA aneurysm is extremely rare, and formation of large aneurysm at the vascular territory of an occluded vessel is apparently unique.
• 各種画像の三次元融合画像を用いた術前検討の有用性

  新妻 邦泰, 井上 敬, 藤村 幹, 藤原 悟, 清水 宏明, 冨永 悌二

  東北脳血管障害研究会学術集会記録集 32回 11 - 15 2010/12 [Refereed][Not invited]
  
• もやもや病治療における脳外科術中高感度赤外線モニタリングシステム．

  荒船龍彦, 鷲尾利克, 鎮西清行, 佐久間一郎, 金田道寛, 中川敦寛, 藤村幹, 冨永悌二

  J Jpn Comput Assist Surgery 12 238 - 239 2010/12 [Refereed][Not invited]
  
• Efficacy of Revascularization Surgery for Moyamoya Syndrome Associated With Graves' Disease

  Hidenori Endo, Miki Fujimura, Kuniyasu Niizuma, Hiroaki Shimizu, Teiji Tominaga

  NEUROLOGIA MEDICO-CHIRURGICA 50 (11) 977 - 983 0470-8105 2010/11 [Refereed][Not invited]
   

  Appropriate management of moyamoya syndrome associated with Graves' disease is undetermined because of the rarity of this combination Patients tend to present with cerebrovascular events such as transient ischemic attack (TIA) in a thyrotoxic state, which is relieved by proper antithyroid therapy Four patients with moyamoya syndrome associated with Graves' disease were successfully treated with revascularization surgery on 5 hemispheres among 58 consecutive patients (2-62 years old, mean 34 4 years) with moyamoya disease in 80 hemispheres treated from March 2004 to May 2007 Three patients presented with TIA, and one patient presented with intracerebral hemorrhage Three patients were thyrotoxic at the onset of the cerebrovascular events All patients underwent revascularization surgery after normalization of thyroid function Euthyroid state was strictly maintained perioperatively One patient developed symptomatic cerebral hyperperfusion, which was resolved by blood pressure control Postoperative courses of the other patients were uneventful, and all 4 patients have remained neurologically stable after discharge Cerebrovascular reconstruction surgery is a successful treatment option for moyamoya syndrome associated with Graves' disease Timing of surgery during the euthyroid state and perioperative management considering the thyroid function and the cerebral hemodynamic change are the keys to successful surgical treatment
• Lectin-like oxidized low-density lipoprotein receptor 1 and matrix metalloproteinase expression in ruptured and unruptured multiple dissections of distal middle cerebral artery: case report

  Atsushi Saito, Miki Fujimura, Takashi Inoue, Hiroaki Shimizu, Teiji Tominaga

  ACTA NEUROCHIRURGICA 152 (7) 1235 - 1240 0001-6268 2010/07 [Refereed][Not invited]
   

  Oxidized low-density lipoprotein receptor 1 (LOX1) is a critical factor for atherosclerosis in a variety of vascular diseases; however, its major role in cerebral arterial dissecting aneurysm is unclear. We present a case of remarkable contrast of LOX1 expression in ruptured and unruptured multiple middle cerebral artery dissections and discuss the correlation of LOX1 with matrix metalloproteinases (MMPs). A 59-year-old woman presented with subarachnoid hemorrhage associated with left temporal subcortical hematoma. Emergent cerebral angiography demonstrated aneurysmal dilatation at the origin of the left anterior temporal artery (ATA) and occlusion on the distal side of ATA. Infectious aneurysm was excluded. Intraoperative findings showed ruptured dissection of the left ATA and unruptured aneurysmal dilatation of another temporal branch of the left M1 portion. Both lesions were trapped by clips and resected. Histopathological examination confirmed that both ruptured and unruptured aneurysmal dilatations were diagnosed as arterial dissections. Immunohistochemical examination demonstrated remarkable expressions of LOX1, MMP-2, and MMP-9 in hypertrophic media outside the intima in ruptured dissection, on the other hand, those expressions in the intima and inside hypertrophic media in the unruptured dissection. This is the first report to reveal immunohistochemical findings of LOX1 and MMPs in multiple dissections of MCA. The contrast localization of LOX1 and MMPs might contribute to the fragility of the arterial wall layer of ruptured/unruptured arterial dissections.
• Postoperative neurological deterioration in pediatric moyamoya disease: watershed shift and hyperperfusion Clinical article

  Toshiaki Hayashi, Reizo Shirane, Miki Fujimura, Teiji Tominaga

  JOURNAL OF NEUROSURGERY-PEDIATRICS 6 (1) 73 - 81 1933-0707 2010/07 [Refereed][Not invited]
   

  Object. Young patients with moyamoya disease frequently exhibit extensive cerebral infarction at the time of initial presentation, and even in the early postoperative period. To investigate clinical characteristics in the early postoperative period, the authors prospectively analyzed findings of MR imaging, MR angiography, and SPECT before and after surgery. The authors focused in particular on how postoperative neurological deterioration occurred. Methods. Between August 2005 and June 2009, 22 patients younger than 18 years of age with moyamoya disease were treated at Miyagi Children's Hospital. The mean patient age (+/- SD) was 8.58 +/- 4.55 years (range 2-17 years). Superficial temporal artery middle cerebral artery bypass and indirect bypass of encephalosynangiosis between the brain surface and the temporal muscle, galea, and dura mater were performed in 35 hemispheres. Magnetic resonance imaging and MR angiography were performed before surgery, at 7 days postoperatively, and 3-6 months after surgery. A (123)I-isopropyl iodoamphetamine SPECT scan was also obtained pre- and postoperatively. Results. During the postoperative period, neurological deterioration was observed after 15 operations (10 cases of motor paresis, I of aphasia, and 4 of sensory disturbance) in 13 patients. All symptoms had resolved by the time of discharge, except in 2 patients who suffered cerebral infarction. All patients exhibited disappearance (94.3%) or reduction (5.7%) of transient ischemic attacks (TIAs) during the follow-up period. Perioperative studies revealed 2 different types of radiological findings, focal uptake decrease on SPECT indicative of cerebral ischemia due to dynamic change in cerebral hemodynamics caused by bypass flow, the so-called watershed shift, and perioperative edematous lesions on MR imaging due to cerebral hyperperfusion. The frequent occurrence of preoperative TIAs was significantly associated with watershed shift, whereas preoperative MR imaging findings and preoperative SPECT findings were not. Age at operation was the only factor significantly associated with postoperative hyperperfusion. Conclusions. In young patients, moyamoya disease exhibits rapid progression, resulting in poor clinical outcome. The risk of postoperative neurological deterioration in very young moyamoya patients with frequent TIAs should be noted. The findings in this study showed that direct bypass is not completely safe in patients with moyamoya disease because it causes dynamic change in postoperative cerebral hemodynamics. (DOI: 10.3171/2010.4.PEDS09478)
• Simultaneous Occurrence of Subarachnoid Hemorrhage and Cerebral Infarction Caused by Anterior Cerebral Artery Dissection Treated by Endovascular Trapping -Case Report

  Tomoo Inoue, Miki Fujimura, Yasushi Matsumoto, Ryushi Kondo, Takashi Inoue, Hiroaki Shimizu, Teiji Tominaga

  NEUROLOGIA MEDICO-CHIRURGICA 50 (7) 574 - 577 0470-8105 2010/07 [Refereed][Not invited]
   

  A 48-year-old man presented with a rare dissection of the anterior cerebral artery (ACA) causing simultaneous subarachnoid hemorrhage (SAH) and cerebral infarction manifesting as sudden onset of headache and left hemiparesis. Computed tomography and magnetic resonance imaging showed SAH localized in the interhemispheric fissure and cerebral infarction in the territory of the right ACA. Digital subtraction angiography (DSA) demonstrated segmental narrowing and dilatation at the right A(1) and A(2) portions of the ACA, leading to a diagnosis of ACA dissection. Fourteen days after the onset, DSA confirmed the enlarged fusiform dilatation of the right A(2) portion with distal narrowing, suggesting the risk of rerupture of the dissection. Endovascular obliteration of the aneurysm with parent artery occlusion was performed without anastomosis on day 16. The aneurysm was catheterized and obliterated with detachable coils. Postoperative DSA revealed complete obliteration of the dissection and parent artery. The patient was doing well without recurrence of the dissection 8 months after the intervention. The simultaneous occurrence of SAH and cerebral infarction in patients with ACA dissection is extremely rare, and the optimal treatment has not yet been established. Endovascular treatment is safe and effective for the treatment of ACA dissection.
• Acute-stage diffusion-weighted magnetic resonance imaging for predicting outcome of poor-grade aneurysmal subarachnoid hemorrhage

  Kenichi Sato, Hiroaki Shimizu, Miki Fujimura, Takashi Inoue, Yasushi Matsumoto, Teiji Tominaga

  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM 30 (6) 1110 - 1120 0271-678X 2010/06 [Refereed][Not invited]
   

  We investigated the role of acute-stage diffusion-weighted images (DWIs) for predicting outcome of poor-grade subarachnoid hemorrhage (SAH). This study included 38 patients with poor-grade SAH who underwent DWI within 24 h after onset. DWI findings were divided into three groups on the basis of lesion area: none (N), spotty (S, <= 10 mm(2)), or areal (A, > 10 mm(2)). We evaluated the correlation between preoperative DWI findings and clinical outcome, and the characteristics of DWI abnormalities. DWI abnormalities were revealed in 81.6% of cases (group S 34.2%; group A 47.3%). All patients in groups N and S and 73.3% of patients in group A were treated radically. For those patients without rerupture, favorable outcomes were achieved in 100% of group N, 53.8% of group S, and 0% of group A. Abnormal lesions on initial DWI, which resulted in permanent lesions, showed a mean apparent diffusion coefficient ratio to the control value of 0.71, which was significantly lower than 0.95 observed in reversible lesions (P< 0.01). We recommend radical treatment for even poor-grade SAH as long as the preoperative DWI shows no or only spotty lesions. DWI may provide an objective means to estimate the outcome of poor-grade SAH. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 1110-1120; doi: 10.1038/jcbfm.2009.264; published online 6 January 2010
• Unilateral moyamoya syndrome involving the ipsilateral anterior and posterior circulation associated with paroxysmal nocturnal hemoglobinuria

  Shunji Mugikura, Shuichi Higano, Miki Fujimura, Hiroaki Shimizu, Shoki Takahashi

  JAPANESE JOURNAL OF RADIOLOGY 28 (3) 243 - 246 1867-108X 2010/04 [Refereed][Not invited]
   

  Moyamoya refers to a phenomenon of stenoocclusive changes at or around the terminal part of the internal carotid artery (ICA). Moyamoya vessels develop in patients with (moyamoya syndrome) or without (moyamoya disease) various underlying diseases or conditions. Recent evidence shows that stenoocclusive lesions tend to involve the ipsilateral ICA system and posterior cerebral artery (PCA) predominantly in moyamoya disease. A 53-year-old Japanese woman with paroxysmal nocturnal hemoglobinuria presented with cerebral infarction from stenoocclusive involvement in the ipsilateral ICA and PCA associated with moyamoya vessels; she had no contralateral vascular lesion. Although predominant involvement of the ipsilateral ICA and PCA was associated with underlying disease (moyamoya syndrome) in the present case, it is a characteristic finding of moyamoya disease. We discuss the possible pathogenesis of the vascular changes of this case.
• Unilateral moyamoya syndrome involving the ipsilateral anterior and posterior circulation associated with paroxysmal nocturnal hemoglobinuria

  Shunji Mugikura, Shuichi Higano, Miki Fujimura, Hiroaki Shimizu, Shoki Takahashi

  Japanese Journal of Radiology 28 (3) 243 - 246 1867-1071 2010/04 [Refereed][Not invited]
   

  Moyamoya refers to a phenomenon of stenoocclusive changes at or around the terminal part of the internal carotid artery (ICA). Moyamoya vessels develop in patients with (moyamoya syndrome) or without (moyamoya disease) various underlying diseases or conditions. Recent evidence shows that stenoocclusive lesions tend to involve the ipsilateral ICA system and posterior cerebral artery (PCA) predominantly in moyamoya disease. A 53-year-old Japanese woman with paroxysmal nocturnal hemoglobinuria presented with cerebral infarction from stenoocclusive involvement in the ipsilateral ICA and PCA associated with moyamoya vessels she had no contralateral vascular lesion. Although predominant involvement of the ipsilateral ICA and PCA was associated with underlying disease (moyamoya syndrome) in the present case, it is a characteristic fi nding of moyamoya disease. We discuss the possible pathogenesis of the vascular changes of this case. © Japan Radiological Society 2010.
• Relationship between lectin-like oxidized low-density lipoprotein receptor 1 expression and preoperative echogenic findings of vulnerable carotid plaque

  Atsushi Saito, Miki Fujimura, Takashi Inoue, Hiroaki Shimizu, Teiji Tominaga

  ACTA NEUROCHIRURGICA 152 (4) 589 - 595 0001-6268 2010/04 [Refereed][Not invited]
   

  Lectin-like oxidized low-density lipoprotein 1 (LOX1) is an important cell surface receptor for the progression of atherosclerosis. Our purpose is to clarify the relationships of LOX1 and atherosclerotic factors for the vulnerability of carotid plaque and preoperative echogenic findings. We examined LOX1 expression, matrix metalloproteinase (MMP)-2,9, and tissue inhibitor of MMP (TIMP)-2 by immunohistochemical analysis using carotid endarterectomy specimens obtained from 14 patients. Groups were divided into stable plaque group A and vulnerable plaque group B by preoperative echogenic findings of carotid plaques. Endothelial immunoreactivity was calculated, and the immunohistochemical findings were compared. LOX1 was remarkably expressed, especially in smooth muscle cells in vulnerable plaque and colocalized in MMP-9 positive cells and apoptotic cells. All LOX1, MMP-2,9, and TIMP2 were remarkably expressed in the subendothelial layer in group B compared with group A. The endothelial LOX1 index was 63.75 +/- 4.92 in group A and 83.0 +/- 5.02 in group B (p = 0.02). The endothelial MMP-2 index was 24.38 +/- 5.50 in group A and 32.83 +/- 6.79 in group B (p = 0.01). The endothelial MMP-9 index was 46.13 +/- 6.31 in group A and 59.17 +/- 2.14 in group B (p = 0.002). The endothelial TIMP-2 index had no significant difference between two groups (p = 0.14). LOX-1 may play an important role in the progression of vulnerable carotid plaque and might regulate vulnerable plaque formation in cooperation with MMPs and TIMP-2. Endothelial MMP-2 might suppress TIMP-2 activation in vulnerable plaques.
• Asymptomatic Moyamoya Disease Subsequently Manifesting as Transient Ischemic Attack, Intra cerebral Hemorrhage, and Subarachnoid Hemorrhage in a Short Period-Case Report

  Miki Fujimura, Shunji Mugikura, Hiroaki Shimizu, Teiji Tominaga

  NEUROLOGIA MEDICO-CHIRURGICA 50 (4) 316 - 319 0470-8105 2010/04 [Refereed][Not invited]
   

  A 59-year-old man, who had incidentally been found to have asymptomatic moyamoya disease 4 months previously, suffered transient ischemic attack (TIA) in the left extremities. Three weeks later, he again suffered TIA, and neuroimaging examination revealed fresh subarachnoid hemorrhage in the interhemispheric cistern as well as an asymptomatic thalamic hemorrhage in the contralateral hemisphere, which was not evident at the first onset of TIA. Digital subtraction angiography confirmed the diagnosis of moyamoya disease, and single-photon emission computed tomography demonstrated significant hemodynamic compromise in the right hemisphere. He underwent superficial temporal artery-middle cerebral artery anastomosis with indirect pial synangiosis without complication one month later. The TIA completely disappeared after surgery, and no further cerebrovascular event occurred during the follow-up period of 2 years. Asymptomatic moyamoya disease may manifest with a dynamic course, so careful follow up is necessary. Simultaneous manifestation of ischemic attack, subarachnoid hemorrhage, and intracerebral hemorrhage in a short period in the present case may indicate the underlying mechanism of the cerebrovascular events in this rare entity.
• De Novo Formation of Orbital Cavernous Malformation 9 Years After Surgical Management of Dural Arteriovenous Fistula in the Anterior Middle Fossa-Case Report

  Shunsuke Omodaka, Miki Fujimura, Toshiki Endo, Takashi Inoue, Hiroaki Shimizu, Teiji Tominaga

  NEUROLOGIA MEDICO-CHIRURGICA 50 (4) 324 - 327 0470-8105 2010/04 [Refereed][Not invited]
   

  A 30-year-old man presented with recurrent dural arteriovenous fistula (dAVF) associated with de nova orbital cavernous malformation (CM), manifesting as progressive left visual disturbance. He had undergone transarterial embolization and subsequent surgical management for a left anterior middle fossa dAVF 9 years previously. External carotid angiography showed recurrence of the dAVF. Magnetic resonance imaging revealed a well delineated intraorbital mass lesion with hypointense signal rim by T(2)-weighted imaging, adjacent to the shunting point of the recurrent dAVF. Transcranial subtotal removal of the intraorbital mass lesion through the orbitopterional approach revealed continuity between the mass lesion and the draining vein of the recurrent dAVF. The histological diagnosis was CM. His symptom was relieved postoperatively, and no regrowth was seen during the follow-up period of one year. The coexistence of recurrent dAVF with newly formed orbital CM is extremely rare, but may indicate the underlying mechanism of the formation of CMs and recurrent dAVF.
• Associated neurosurgical diseases

  Miki Fujimura, Teiji Tominaga

  Moyamoya Disease Update 132 - 138 2010 [Refereed][Not invited]
   

  Moyamoya disease is a chronic, occlusive cerebrovascular disease with unknown etiology, characterized by bilateral steno-occlusive changes at the terminal portion of the internal carotid artery and an abnormal vascular network at the base of the brain [1]. The association of moyamoya disease with further neurosurgical diseases, such as cerebral aneurysms [2-5], brain tumors, cervical carotid artery stenosis, and cerebrovascular malformations, has been described previously [6-11]. It is well known that moyamoya disease is frequently associated with intracranial aneurysms located within the abnormal basal network or the circle of Willis, which are explained by the intrinsic pathology of moyamoya disease, such as hemodynamic stress and fragile structure of the collateral vessels [2-5]. On the other hand, the association with atherosclerotic cervical carotid artery stenosis or with brain tumors leads to the diagnosis of akin moyamoya disease (quasi-moyamoya disease) according to the diagnostic criteria of the Research Committee on Spontaneous Occlusion of the Circle of Willis, of the Ministry of Health, Labor, and Welfare, Tokyo, Japan. The coincidence of moyamoya disease with cerebral vascular malformations including arteriovenous malformation [6, 7], cerebral cavernous malformation [8-10], and venous malformation [10] has been reported in the literature. A rare association of with dural arteriovenous fistula is also demonstrated [11]. In this chapter, we especially focus on the association of moyamoya disease with further cerebrovascular disease based on our experience. © 2010 Springer-Verlag Tokyo.
• Risk factors for complication

  Miki Fujimura, Teiji Tominaga

  Moyamoya Disease Update 275 - 280 2010 [Refereed][Not invited]
   

  Surgical revascularization for moyamoya disease prevents cerebral ischemic attacks by improving cerebral blood flow (CBF), and superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis and/or indirect pial synangiosis such as encephalo-myo-synangiosis (EMS) are generally accepted as the optimal surgical treatment for moyamoya disease [1-3]. Despite their favorable long-term outcome, perioperative cerebral ischemia and cerebral hyper-perfusion are potential complications of these procedures [1, 4-6]. Patients with moyamoya disease are known to suffer from transient neurological deterioration in the acute stage after surgical revascularization at a substantial rate, and cerebral ischemia has been considered as the major reason for this deterioration [7]. Recent investigations of the time-sequential cerebral hemodynamics in the acute stage after revascularization surgery for moyamoya disease, however, revealed that cerebral hyperperfusion as well as cerebral ischemia could result in transient neurologic deterioration after surgical revascularization [4-6]. In this chapter, the author seeks to focus on perioperative cerebral ischemia and cerebral hyperperfusion as potential complications, and discuss their risk factors. Prediction and accurate diagnosis of these pathologies is clinically important because the management of each of these conditions is contradictory. © 2010 Springer-Verlag Tokyo.
• Overview: Issues in young children and adults

  Teiji Tominaga, Miki Fujimura

  Moyamoya Disease Update 287 - 293 2010 [Refereed][Not invited]
   

  Moyamoya disease is a chronic, occlusive cerebrovascular disease with unknown etiology which has two peaks in age distribution, a first peak in children and the second peak in young adults [1]. The most recent epidemiological national survey in Japan estimates that the annual number of the patients with moyamoya disease is 7,700 with the incidence rate of 5.4 per million populations, with the female/male ratio of 1.8:1 [2]. The peaks in age distribution of moyamoya disease consist of a first peak in children and the second peak in young adults. The incidence of patients with family history was 12.1% among definitive moyamoya patients [2]. In this chapter, the authors seek to overview the characteristics of moyamoya disease in children and young adults. © 2010 Springer-Verlag Tokyo.
• Headache in moyamoya disease

  Reizo Shirane, Miki Fujimura

  Moyamoya Disease Update 110 - 113 2010 [Refereed][Not invited]
   

  Moyamoya disease is a chronic, occlusive cerebrovascular disease with unknown etiology characterized by bilateral steno-occlusive changes at the terminal portion of the internal carotid artery and an abnormal vascular network at the base of the brain [1]. Clinical presentation of moyamoya disease includes transient ischemic attack (TIA), cerebral infarction, intracerebral hemorrhage, and seizure [2]. TIA is one of the most common clinical presentations of moyamoya disease both in pediatric and adult cases [2], while intracerebral hemorrhage is mostly seen among adult cases [3]. Recently, headache is also considered to be one of the common clinical presentations of moyamoya disease. Patients with moyamoya disease may complain of headache before and after revascularization surgery. In this chapter, the authors focus on headache as the clinical presentation of moyamoya disease, and discuss the incidence and mechanism of this symptom. We further discuss the efficacy of revascularization surgery for the improvement of headache. © 2010 Springer-Verlag Tokyo.
• Bench top animal model for blast-induced traumatic brain injury using microexplosives: Difference of pathology by the presence of the skull

  Nakagawa A, Arafune T, Fujimura M, Ohtani K, Yamamoto H, Matsunaga T, Washio T, Tsukamoto A, Nakano T, Yamada M, Sato C, Goda K, Ogawa Y, Miyazaki S, Sun M, Kumabe T, Jalali B, Haga Y, Ushida T, Takayama K, Nishino S, Niinomi M, Sakum I, Tominaga T

  IFS Collaborative Research Forum, Book of Proceedings 82 - 83 2010 [Refereed][Not invited]
  
• Clinical implications of intraoperative infrared brain surface monitoring during superficial temporal artery-middle cerebral artery anastomosis in patients with moyamoya disease Clinical article

  Atsuhiro Nakagawa, Miki Fujimura, Tatsuhiko Arafune, Ichiro Sakuma, Teiji Tominaga

  JOURNAL OF NEUROSURGERY 111 (6) 1158 - 1164 0022-3085 2009/12 [Refereed][Not invited]
   

  Object. Surgical revascularization for moyamoya disease prevents cerebral ischemic attacks by improving cerebral blood flow (CBF). Symptomatic cerebral hyperperfusion is a potential complication of this procedure, but its treatment is contradictory to that for ischemia. Because intraoperative techniques to detect hyperperfusion are still lacking, the authors performed intraoperative infrared monitoring in moyamoya disease using a novel infrared imaging system. Methods. During superficial temporal artery-middle cerebral artery anastomosis in 25 patients (26 hemispheres) with moyamoya disease, the authors monitored the brain surface temperature intraoperatively with the IRIS-V infrared imaging system. The average gradation value change (indicating temperature change) was calculated using commercial software. Magnetic resonance imaging, MR angiography, and N-isopropyl-p-[(123)I] iodoamphetamine SPECT studies were performed routinely before and within 10 days after surgery. Results. Patency of bypass, detailed local hemodynamics, and changes in cortical surface temperature around the anastomosis site were well recognized by the IRIS-V infrared imaging system in all cases. In the present study, 10 patients suffered transient neurological symptoms accompanied by an increase in CBF around the anastomosis site, recognized as symptomatic hyperperfusion. The increase in temperature was significantly higher in these patients. Intensive blood pressure control was undertaken, and free-radical scavengers were administered. No patient in the present study suffered a permanent neurological deficit. Conclusions. Although the present method does not directly monitor surface CBF, temperature rise around the anastomosis site during surgery might be an indicator of postoperative hyperperfusion. Prospective evaluation with a larger number of patients is necessary to validate this technique. (DOI: 10.3171/2009.4.JNS08585)
• Neuroendoscopic Management of Symptomatic Septum Pellucidum Cavum Vergae Cyst Using a High-Definition Flexible Endoscopic System -Case Report

  Yasuo Nishijima, Miki Fujimura, Ken-ichi Nagamatsu, Misaki Kohama, Teiji Tominaga

  NEUROLOGIA MEDICO-CHIRURGICA 49 (11) 549 - 552 0470-8105 2009/11 [Refereed][Not invited]
   

  A 24-year-old man, who had an asymptomatic septum pellucidum cyst incidentally found one year previously, presented with severe headache and right abducens nerve palsy caused by expansion of the midline cyst. Preoperative magnetic resonance (MR) imaging revealed obstructive hydrocephalus due to the enlarged midline cyst. Neuroendoscopic fenestration of the septum pellucidum cyst was successfully performed via a right frontal approach using a high-resolution flexible neuroendoscopic system without complication. Communication between the cyst cavity and bilateral lateral ventricles was constructed via a single trajectory. The entire inner cyst wall could be inspected from the cyst cavity by manipulating the flexible neuroendoscopic system, which excluded the presence of neoplasm. His symptoms were completely relieved after surgery, and postoperative MR imaging showed significant improvement of hydrocephalus and shrinkage of the midline cyst. Septum pellucidum cavum vergae cyst may expand and become symptomatic, so fenestration using a flexible neuroendoscope system may be the optimal method for constructing communication to the bilateral lateral ventricles with minimal invasion.
• Increased expression of serum matrix metalloproteinase-9 in patients with moyamoya disease

  Miki Fujimura, Mika Watanabe, Ayumi Narisawa, Hiroaki Shimizu, Teiji Tominaga

  SURGICAL NEUROLOGY 72 (5) 476 - 480 0090-3019 2009/11 [Refereed][Not invited]
   

  Background: Moyamoya disease is a chronic occlusive cerebrovascular disease with unknown etiology characterized by an abnormal vascular network at the base of the brain, which can manifest both as ischemic stroke and as cerebral hemorrhage. It was also reported that the patients with moyamoya disease are more vulnerable to cerebral hyperperfusion such as postoperative hemorrhagic complication after extracranial-intracranial bypass surgery despite its low flow revascularization. However, the underlying mechanisms of its pathologic angiogenesis and the occurrence of hemorrhage are undetermined. Excessive degradation of the vascular matrix by MMPs, proteolytic enzymes that degrade all the components of extracellular matrix, can lead to instability of the vascular structure and can thereby cause bleeding. The MMPs also play an important role in tissue remodeling including angiogenesis in both physiologic and pathologic condition. Methods: We examined the serum levels of MMP-2 and MMP-9 in 16 cases with definitive moyamoya disease by enzyme-linked immunosorbent assay and compared them with those from healthy controls. Results: The serum MMP-9 level was significantly higher in moyamoya disease (40.18 ng/mL) than in healthy controls (13.75 ng/mL, P=.0372). There was no difference in serum MMP-2 level between moyamoya disease (646.65 ng/mL) and healthy control (677.60 ng/mL). Immunohistochemistry on the surgical specimens showed significant increase in MMP-9 expression within the arachnoid membrane of moyamoya disease. Conclusion: The increased expression of MMP-9 may contribute to pathologic angiogenesis and/or to the instability of the vascular structure and could thereby cause hemorrhage in moyamoya disease. (C) 2009 Elsevier Inc. All rights reserved.
• Incidence and risk factors for symptomatic cerebral hyperperfusion after superficial temporal artery-middle cerebral artery anastomosis in patients with moyamoya disease

  Miki Fujimura, Shun Mugikura, Tomohiro Kaneta, Hiroaki Shimizu, Teiji Tominaga

  SURGICAL NEUROLOGY 71 (4) 442 - 447 0090-3019 2009/04 [Refereed][Not invited]
   

  Background: Superficial temporal artery-middle cerebral artery anastomosis for moyamoya disease prevents cerebral ischemic attack by improving CBE, whereas recent evidence suggests that the temporary neurologic deterioration because of postoperative cerebral hyperfusion could occur despite its low-flow revascularization. The present study investigates the incidence and the risk factors for symptomatic hyperfusion after STA-MCA anastomosis in patients with moyamoya disease. Methods: We prospectively performed N-isopropyl-p-(sic) iodoamphetamine single-photon emission computed tomography 1 and 7 days after STA-MCA anastomosis on 80 hemispheres of 58 consecutive patients with moyamoya disease (approximately 2-62 years old, 34.4 years old in average). Mean follow-up period was 22.7 months. Symptomatic cerebral hyperperfusion was defined as the presence of the significant increase in CBF at the site of the anastomosis that is responsible for the apparent neurologic sign. Results: Twenty-one patients (22 sides, 27.5%) temporarily had symptomatic cerebral hyperfusion, who were subjected of intensive blood pressure control. Postoperative magnetic resonance imaging/angiography showed the thiek high signal of bypass without ischemic changes in all 21 patients. Adult-onset (P = .013) or hemorrhagic-onset patients (P = .027) had significantly higher risk for symptomatic hyperfusion. There was no difference in intraoperative temporary occlusion time between each group. No patients had permanent neurologic deficit because of hyperperfusion. Conclusion: The STA-MCA anastomosis is a safe and effective treatment of moyamoya disease, although adult-onset and/or hemorrhagic-onset patients had higher risk for symptomatic hyperperfusion. We recommend routine CBF measurement especially for these patients because the management of hyperperfusion is contradictory to that of ischemia. (c) 2009 Elsevier Inc. All rights reserved.
• Cerebral ischemia owing to compression of the brain by swollen temporal muscle used for encephalo-myo-synangiosis in moyamoya disease

  Miki Fujimura, Tomohiro Kaneta, Hiroaki Shimizu, Teiji Tominaga

  NEUROSURGICAL REVIEW 32 (2) 245 - 249 0344-5607 2009/04 [Refereed][Not invited]
   

  Compression of the brain by swollen temporal muscle used for indirect pial synangiosis is a rare complication after the revascularization surgery for moyamoya disease, and its mechanism and clinical presentation are undetermined. A 26-year-old woman, who had been suffering transient ischemic attack (TIA), underwent superficial temporal artery-middle cerebral artery anastomosis with encephalo-myo-synangiosis (EMS) on the affected hemisphere. The (123)I-IMP-SPECT 1 day after surgery demonstrated an improvement of cerebral blood flow (CBF) on the operated hemisphere. Two days later, however, she suffered fluctuating aphasia when computed tomography scan revealed marked swelling of the temporal muscle used for EMS. The (123)I-IMP-SPECT 4 days after surgery showed significant decrease in CBF by the compression of the brain. Then, we performed revision of EMS. The base of the temporal muscle was markedly compressed by the edge of the free bone flap, which resulted in swelling of the entire temporal muscle used for EMS. We drilled out the edge of the free bone flap for decompression. Her aphasia disappeared postoperatively, and CBF normalized 7 days after the initial surgery. Her TIA disappeared, and there was no deterioration during the follow-up period. The STA-MCA bypass has been patent since the initial surgery. Surgical revascularization including EMS has a substantial risk for cerebral ischemia owing to compression of the brain by temporal muscle swelling. Relative wide bone window for temporal muscle insertion is necessary to avoid this rare complication. Once the flow compromise is confirmed, we recommend early decompression by the revision of EMS.
• Syringomyelia with obstructive hydrocephalus at the foramens of Luschka and Magendie successfully treated by endoscopic third ventriculostomy

  Tomohiro Kawaguchi, Miki Fujimura, Teiji Tominaga

  SURGICAL NEUROLOGY 71 (3) 349 - 352 0090-3019 2009/03 [Refereed][Not invited]
   

  Background: Syringomyelia rarely accompanies hydrocephalus except for the cases with Chiari malformation, and the efficacy of endoscopic third ventriculostomy for this entity is undetermined. Case Report: A 55-year-old man developed sensory disturbance and discrete movement disturbance on the bilateral upper limb during the past 3 years. On admission, he presented with slight tetraparesis and hyperreflection on his lower limbs with rectovesical dysfunction. Preoperative MR imaging demonstrated marked enlargement of the lateral ventricles as well as the third and fourth ventricle due to obstruction of the foramens of Luschka and Magendie. Spine MR imaging showed longitudinal dilatation of the central canal from the cerebrospinal junction toward the thoracic level with communication to the fourth ventricle, whereas Chiari malformation and tight cisterna magna were absent. He was successfully treated by ETV. The patient significantly recovered from his symptoms postoperatively, and MR imaging after surgery showed apparent shrinkage of the syrinx as well as the ventricles. Conclusion: The efficacy of the normalization of cerebrospinal fluid circulation and subsequent improvement of the syringomyelia in the present case may suggest that ETV could be a therapeutic choice for syringomyelia associated with hydrocephalus due to the obstruction of the foramens of Luschka and Magendie, especially when the connection between the ventricular system and the dilated central canal is evident, and may give a clue to the explanation for Gardner's hydrodynamic theory. (c) 2009 Elsevier Inc. All rights reserved.
• Neuroendoscopic Management of a Colloid Cyst at the Third Ventricle Using the High-definition Flexible Neuroendoscopic System: Report of Two Cases

  Misaki Kohama, Miki Fujimura, Kenichi Nagamatsu, Kensuke Murakami, Teiji Tominaga

  NEUROLOGICAL SURGERY 37 (3) 261 - 267 0301-2603 2009/03 [Refereed][Not invited]
   

  Colloid cysts are benign intracranial lesions located at the anterior roof of the third ventricle, which can result in the obstruction of the foramen of Monro and subsequent hydrocephalus or sudden death. Colloid cysts have been treated by microsurgical resection or by stereotactic aspiration. More recently, the use of rigid neuroendoscopy for colloid cysts has been attempted, but the efficacy of the flexible neuroendoscopic system is undetermined except for limited reports. A 40-year-old man and a 52-year-old man were presented with obstructive hydrocephalus owing to colloid cysts in the third ventricle, who were diagnosed by the typical findings of pre-operative CT scan and MRI. In the first case, endoscopic resection of the cyst was attempted using a high-definition flexible neuroendoscopic system with a CCD camera at the tip of the endoscope. The procedure relieved his symptoms. Hydrocephalus was improved after surgery. and postoperative MRI revealed the disappearance of the third ventricle lesion. Histological examination confirmed the diagnosis of colloid cyst. In the second case, endoscopic removal of the cyst wall and the evacuation of the cyst content were attempted using a high-definition flexible endoscopic system which resulted in the improvement of hydrocephalus and marked shrinkage of the third ventricle lesion observed in postoperative MRI. There was no recurrence in either patient. We recommend endoscopic treatment for colloid cysts using the high-definition neuroendoscopic system, which enables safe and thorough manipulation of the lesion and surrounding structures.
• Delayed intracerebral hemorrhage after superficial temporal artery-middle cerebral artery anastomosis in a patient with moyamoya disease: possible involvement of cerebral hyperperfusion and increased vascular permeability

  Miki Fujimura, Hiroaki Shimizu, Shunji Mugikura, Teiji Tominaga

  SURGICAL NEUROLOGY 71 (2) 223 - 227 0090-3019 2009/02 [Refereed][Not invited]
   

  Background: Postoperative intracerebral hemorrhage is a rare complication after surgical revascularization for moyamoya disease, and its mechanism is totally undetermined. Case Description: A 47-year-old woman with moyamoya disease, experiencing crescendo transient ischemic attack on her tell hand, underwent STA-MCA anastomosis on the right hemisphere. Postoperative MR imaging 1 day after Surgery demonstrated asymptomatic vasogenic edema without ischemic change at the subcortex under the site of the anastomosis that expanded the next day, and STA-MCA bypass was apparently patent with the strong high signal by MR angiography. N-isopropyl-p-[(123)I]iodo-amphetamine single-photon emission CT showed marked increase in the CBF on the hemisphere operated oil. Four days after surgery, the patient complained of sudden headache and experienced severe monoparesis in her left hand due to the intracerebral hemorrhage at the corresponding lesion to the prior vasogenic edema. Edema around hematoma was prolonged for as long as a month; while intensive blood pressure control and the use of adrenocorticosteroid gradually relieved her symptoms, The patient completely recovered from her symptoms 2 months later, and she was discharged without neurologic deficit. tier transient ischemic attacks completely disappeared postoperatively. Conclusion: Early increase in CBF associated with vasogenic edema formation at the site of the anastomosis could be the warning sign for subsequent hemorrhagic complication, and intensive blood pressure control is warranted in Such patients. Alternatively, it would be necessary to elucidate the biochemical mechanism of the deleterious cascade during reperfusion in moyamoya disease to avoid this rare complication. (C) 2009 Elsevier Inc. All rights reserved.
• Efficacy of the revascularization surgery for adult-onset moyamoya disease with the progression of cerebrovascular lesions

  Ayumi Narisawa, Miki Fujimura, Teiji Tominaga

  CLINICAL NEUROLOGY AND NEUROSURGERY 111 (2) 123 - 126 0303-8467 2009/02 [Refereed][Not invited]
   

  Object: In moyamoya disease, despite its progressive nature of the occlusive lesions in pediatric patients, the prevalence of the progression in adult patients is undetermined. Furthermore, the optimal timing of the revascularization surgery for progressive cases is controversial. To address these issues, we retrospectively investigate four cases with the adult-onset moyamoya disease manifesting as progression before revascularization surgery. Methods: From March 2004 to May 2007, 49 patients with adult-onset moyamoya disease aged from 19 to 62 years old (mean 40.5) underwent superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis on 63 hemispheres. All patients were strictly followed up by magnetic resonance (MR) imaging/angiography postoperatively. Twenty-seven hemispheres of 15 adult patients without surgery were also followed up at outpatient service during the same period. If the patients manifest as the progression of the steno-occlusive lesion on the hemisphere without surgery, they undergo revascularization surgery after the confirmation of hemodynamic compromise. Results: During this period, 47 hemispheres including those of outpatient cases were conservatively followed up after initial diagnosis. Among them, six hemispheres (12.8%) of four patients had been proven to show apparent progression of steno-occlusive lesion and were subjected to revascularization surgery. Postoperative courses were uneventful in all four cases, and no patient suffered cerebrovascular event on the operated hemisphere after surgery. Conclusion: Adult-onset moyamoya disease, either bilateral or unilateral, has a substantial risk for progression, and careful follow-up is necessary for asymptomatic hemisphere. Once the patient manifests as the progression of cerebrovascular occlusive lesions or ischemic symptoms, we recommend revascularization surgery after the confirmation of the hemodynamic compromise. (c) 2008 Elsevier B.V. All rights reserved.
• Intraoperative infrared brain surface blood flow monitoring during superficial temporal artery-middle cerebral artery anastomosis in patients with childhood moyamoya disease

  Atsuhiro Nakagawa, Miki Fujimura, Tatsuhiko Arafune, Ichiro Sakuma, Teiji Tominaga

  CHILDS NERVOUS SYSTEM 24 (11) 1299 - 1305 0256-7040 2008/11 [Refereed][Not invited]
   

  Objective To monitor patency of the bypass and to accomplish comprehensive visualized evaluation of brain surface hemodynamics in childhood moyamoya patients, we performed intraoperative monitoring using novel infrared imaging system. Materials and methods Intraoperative monitoring of brain surface blood flow by IRIS V infrared imaging system has been conducted during superficial temporal artery-middle cerebral artery anastomosis on seven sides of five pediatric patients with moyamoya disease (man/woman=2:3, 7-8 years old). The range of recipient artery was 0.7-0.8 mm (average 0.75 mm). Magnetic resonance imaging and magnetic resonance angiography were performed routinely before and after surgery. Conclusions In all cases, patency of bypass, as well as detailed local hemodynamics and changes of brain surface temperature distribution could be evaluated. Intraoperative infrared system will be a feasible monitoring not only for noninvasive intraoperative evaluation of bypass patency but also for local hemodynamics even in patients with childhood moyamoya disease.
• Cerebral cavernous malformation - Its genetic and biological background

  Miki Fujimura, Teiji Tominaga

  Brain and Nerve 60 (11) 1271 - 1274 1881-6096 2008/11 [Refereed][Not invited]
   

  Cerebral cavernous malformations (CCMs) are vascular lesions of the central nervous system that consisit of enlarged vascular channels without intervening normal parenchyma. The CCMs can occur as sporadic or autosomal-dominant inherited condition. Linkage analysis of the familial CCMs has identified three different loci at 7q21.2 (CCM1), 7q13 (CCM2), and 3q25.2-q27 (CCM3). The genes at these loci have been identified as Krev1 Interaction Trapped 1 KRIT1 (CCM1), MGC4607 malcavernin (CCM2), and PDCD10 (CCM3), respectively. Recent investigations on these genes suggest that there are interactions between each gene, although the exact pathway of the formation of CCMs is still undetermined. In this review, the authors summarize the currently available knowledge on the molecular events associated with CCMs.
• Temporal change of 3-T magnetic resonance imaging/angiography during symptomatic cerebral hyperperfusion following superficial temporal artery-middle cerebral artery anastomosis in a patient with adult-onset moyamoya disease

  Misaki Kohama, Miki Fujimura, Shunji Mugikura, Teiji Tominaga

  NEUROSURGICAL REVIEW 31 (4) 451 - 455 0344-5607 2008/10 [Refereed][Not invited]
   

  Superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis is a safe and effective treatment for moyamoya disease, although recent evidence suggests its substantial risk for symptomatic cerebral hyperperfusion. The diagnostic value of single-photon emission computed tomography (SPECT) for postoperative hyperperfusion in moyamoya patients is well established, but that of magnetic resonance (MR) imaging/angiography is undetermined. A 22-year-old woman with hemorrhagic-onset moyamoya disease underwent STA-MCA anastomosis on the right hemisphere, but she suffered from transient left hemiparesis and facial paresis owing to cerebral hyperperfusion from 3 to 11 days after surgery as delineated by SPECT. The time-sequential 3-T MR angiography revealed intense high signal of donor STA and dilated branches of MCA around the site of the anastomosis. These findings were most prominent at 8 days after surgery, when her neurologic signs were most apparent. Intensive blood pressure control relieved her symptom and she was discharged without neurologic deficit. MR findings normalized 3 months later. The characteristic findings of 3-T MR angiography, which was not evident by 1.5-T MR angiography in the previous studies, may reflect intrinsic pathology of postoperative cerebral hyperperfusion. It could be a useful diagnostic tool after revascularization surgery for moyamoya disease.
• Efficacy of superficial temporal artery-middle cerebral artery anastomosis with routine postoperative cerebral blood flow measurement during the acute stage in childhood moyamoya disease

  Miki Fujimura, Tomohiro Kaneta, Teiji Tominaga

  CHILDS NERVOUS SYSTEM 24 (7) 827 - 832 0256-7040 2008/07 [Refereed][Not invited]
   

  Object Surgical revascularization for moyamoya disease prevents cerebral ischemic attacks by improving cerebral blood flow (CBF). It is undetermined, however, how rapid increase in CBF affects chronic ischemic brain during the acute stage in childhood moyamoya disease. Materials and methods The present study includes nine consecutive cases of patients with childhood moyamoya disease (2 similar to 8 years old, 6.2 in average), who underwent superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis on 17 hemispheres. We prospectively performed single-photon emission computed tomography 1 and 7 days after 17 surgeries. The follow-up period ranged from 12 to 37 months (24.9 in average). Results The outcome of 17 surgeries was excellent (disappearance of transient ischemic attack) in 14 hemispheres (82.4%) and good (reduction of transient ischemic attack) in three hemispheres (17.6%). No patient suffered peri-operative infarction, except for one (5.9%) manifesting as pseudolaminar necrosis in a part of the cerebral cortex supplied by STA-MCA bypass at the subacute stage, which did not affect his long-term neurological status. One patient (5.9%) presented with transient facial palsy due to hyperperfusion, which resolved within several days. No patient manifested permanent neurological deterioration during the follow-up period. Conclusion The STA-MCA anastomosis is a safe and effective treatment for childhood moyamoya disease. We recommend routine CBF measurement for avoiding surgical complications including both cerebral ischemia and hyperperfusion.
• Surgical treatment for choroid plexus tumors in the fourth ventricle: brain stem infiltration hinders total extirpation

  Toshihiro Kumabe, Miki Fujimura, Hidefumi Jokura, Teiji Tominaga

  NEUROSURGICAL REVIEW 31 (2) 165 - 172 0344-5607 2008/04 [Refereed][Not invited]
   

  The significance of surgery for choroid plexus tumors is well established, but surgical resection of those in the fourth ventricle has not been evaluated. This study reviewed five consecutive patients with choroid plexus tumors in the fourth ventricle treated in our institute between 1996 and 2005, focusing on the factors that hindered total extirpation. Two cases were choroid plexus papillomas, and three cases were choroid plexus carcinomas. Preoperative T2-weighted magnetic resonance imaging showed a diffuse high-intensity lesion in the brain stem in four patients. Infiltration into the fourth ventricle floor was apparent in all five patients during surgery, which hindered total resection of the tumors without neurological deterioration. Intraoperative bleeding was well controlled in all five patients by cauterizing the feeding arteries at the early stage of surgery through the telovelar approach. Performance status was improved in all patients postoperatively. All patients with choroid plexus carcinomas underwent radiation therapy after the surgical removal. No patient suffered tumor progression within the follow-up of 24-129 months (mean 64 months). Total resection of choroid plexus tumors in the fourth ventricle is difficult because of invasion into the fourth ventricle floor. Adjuvant therapy for choroid plexus tumors with brain stem infiltration must be established.
• Surgical treatment for choroid plexus tumors in the fourth ventricle: brain stem infiltration hinders total extirpation.

  Kumabe T, Fujimura M, Jokura H, Tominaga T

  Neurosurgical review 31 (2) 165 - 72; discussion 172 0344-5607 2008/04 [Refereed][Not invited]
  
• Progressive moyamoya syndrome associated with de novo formation of the ipsilateral venous and contralateral cavernous malformations: case report

  Elke Januschek, Miki Fujimura, Shunji Mugikura, Teiji Tominaga

  SURGICAL NEUROLOGY 69 (4) 423 - 427 0090-3019 2008/04 [Refereed][Not invited]
   

  Background: Association of moyamoya disease with multiple vascular malformations is extremely rare. Case Presentation: A 33-year-old man, who had been affected with moyamoya syndrome with TIA during the past 3 years, was admitted to our hospital because of crescendo TlAs with numbness in his right hand and dysarthria. Magnetic resonance angiography showed apparent progression of the steno-occlusive changes bilaterally. We then planned surgical revascularization on the symptomatic side. At the time of readmission for surgery, an asymptomatic small intracerebral hemorrhage in the right frontal cortex was found, which presented on MRI as a CCM. Cerebral angiogram showed avascular lesion corresponding to the location of CCM as well as a newly formed venous malformation on the left side. One month later, STA-MCA anastomosis with pial synangiosis was performed without complications. Significant improvement in CBF on the left hemisphere was confirmed by postoperative single-photon emission CT. There were no ischemic changes on a postoperative MRI, and STA-MCA bypass was apparently patent by MRA. The TIA completely disappeared after surgery, and the patient was discharged without neurologic deficit. Persistence of the CCM and venous malformation were confirmed by T2*-weighted image and 3-dimensional contrast-enhanced gradient echo/SWI 4 months after surgery, respectively. Conclusion: The association of moyamoya syndrome with CCM and venous malformation is extremely rare. The coincidence of the progressive moyamoya syndrome with these newly formed vascular malformations may give a clue to the underlying mechanism of the progression of this rare entity. (C) 2008 Elsevier Inc. All rights reserved.
• A case of masticatory disturbance incidental to trigeminal schwannoma: changes in occlusal force and masticatory sensation before and after radiosurgery.

  M. Iikubo, M. Sakamoto, T. Furuuchi, M. Fujimura, T. Tominaga, S. Takahashi, I. Kojima, T. Sasano

  The British journal of radiology 81 (963) e84 - 7 2008/03 [Refereed][Not invited]
   

  We report here a case of masticatory disturbance evoked by trigeminal schwannoma, in which we have evaluated the changes in occlusal force and masticatory sensation before and after treatment for the tumour. The patient was a 43-year-old woman and her chief complaint was a loss of masticatory sensation on her left side. MR imaging revealed an enhanced tumour in the left cavernous sinus/Meckel's cave. The left masseter muscle function and occlusal force showed remarkable decreases before treatment; however, the sensory thresholds of her facial skin and dental pulp were not significantly different from the control side, indicating that her loss of masticatory sensation was not due to sensory disturbance but to occlusal force weakness. Gamma-knife radiosurgery resulted in a significant improvement in masticatory sensation following an increase in occlusal force.
• Neuro-endoscopic management of mesencephalic intraparenchymal cyst: a case report.

  Endo H, Fujimura M, Watanabe M, Tominaga T

  Surg Neurol 832  2008/02/19 [Refereed][Not invited]
  
• Neurenteric cyst of the craniocervical junction in an infant

  Hiroyuki Sakata, Miki Fujimura, Masaki Iwasaki, Teiji Tominaga

  NEUROLOGIA MEDICO-CHIRURGICA 48 (2) 86 - 89 0470-8105 2008/02 [Refereed][Not invited]
   

  A 1-year-old boy presented with an extremely rare neurenteric cyst of the craniocervical junction manifesting as weakness in all extremities, slowly progressing over 2 months with rapid deterioration during the last few days. Neurological examination on admission showed tetraparesis with hyper-reflexia in the extremities. Magnetic resonance imaging demonstrated an intradural extramedullary cystic lesion located ventrally to the cord, extending from the craniocervical junction to the C3 level. The cyst wall was not enhanced with contrast medium, and the cyst content was isointense to the cerebrospinal fluid. He underwent total removal of the cyst through a left suboccipital craniectomy with C1 hemilaminectomy. The lesion had not adhered to the surrounding structures except for attachment to the left C2 nerve root outlet. Histological examination of the surgical specimen revealed typical neurenteric cyst with single layer epithelium. His symptoms improved significantly after the surgery, and he suffered no recurrence during the 2-year follow-up period. Neurenteric cyst should be considered in the differential diagnosis of intradural extramedullary cystic lesion located ventrally to the cord at the craniocervical junction in infants. Early surgical removal is recommended.
• Application of high-definition flexible neuroendoscopic system to the treatment of primary pineal malignant B-cell lymphoma.

  Endo H, Fujimura M, Kumabe T, Kanamori M, Watanabe M, Tominaga T

  Surg Neurol 979  2008/01/18 [Refereed][Not invited]
  
• Shock wave-induced brain injury in rat: Novel traumatic brain injury animal model

  Atsuhiro Nakagawa, Miki Fujimura, Kaoruko Kato, Hironobu Okuyama, Tokitada Hashimoto, Kazuyoshi Takayama, Teiji Tominaga

  INTRACRANIAL PRESSURE AND BRAIN MONITORING XIII: MECHANISMS AND TREATMENT 102 421 - + 0065-1419 2008 [Refereed][Not invited]
   

  Background In blast wave injury and high-energy traumatic brain injury, shock waves (SW) play an important role along with cavitation phenomena. However, due to lack of reliable and reproducible technical approaches, extensive study of this type of injury has not yet been reported. The present study aims to develop reliable SW-induced brain injury model by focusing micro-explosion generated SW in the rat brain. Methods Adult male rats were exposed to single SW focusing created by detonation of microgram order of silver azide crystals with laser irradiation at a focal point of a truncated ellipsoidal cavity of 20 mm minor diameter and the major to minor diameter ratio of 1.41 after craniotomy. The pressure profile was recorded using polyvinylidene fluoride needle hydrophone. Animals were divided into three groups according to the given overpressure: Group 1: Control, Group II:12.5 +/- 2.5 MPa (high pressure), and Group III: 1.0 +/- 0.2 MPa (low pressure). Histological changes were evaluated over time by hematoxylin-eosin staining. Finding: Group II SW injuries resulted in contusional hemorrhage in reproducible manner. Group III exposure resulted in spindle-shaped changes of neurons and elongation of nucleus without marked neuronal injury. Conclusions The use of SW loading by micro-explosion is useful to provide a reliable and reproducible SW-induced brain injury model in rats.
• Prevalence and clinicoepidemiological features of moyamoya disease in Japan - Findings from a nationwide epidemiological survey

  Shinichi Kuriyama, Yasuko Kusaka, Miki Fujimura, Kenji Wakai, Akiko Tamakoshi, Shuji Hashimoto, Ichiro Tsuji, Yutaka Inaba, Takashi Yoshimoto

  STROKE 39 (1) 42 - 47 0039-2499 2008/01 [Refereed][Not invited]
   

  Background and Purpose-The objectives of the present study were to estimate an annual number of patients with moyamoya disease in Japan and to describe the clinicoepidemiological features of the disease. Methods-The study consisted of 2 questionnaire surveys, which were distributed to randomly selected departments of neurosurgery, internal medicine, neurology, cerebrovascular medicine, and pediatrics in hospitals throughout Japan. The first survey inquired about the number of the patients treated in 2003, and the second requested additional detailed clinicoepidemiological information about each patient identified in the first survey. Results-In 2003, the total number of patients treated in Japan was estimated at 7700 (95% confidence interval, 6300 to 9300). Sex ratio (women to men) of the patients was 1.8. For men, the peak of moyamoya disease was observed in patients aged 10 to 14 years and for women aged 20 to 24 years. Annual rate of newly diagnosed cases in 2003 was 0.54 per 100 000 population. Family history of moyamoya disease was found in 12.1% of the patients. The majority (77.9%) were treated as outpatients. Conclusions-Although the clinicoepidemiological features of the patients in the present study were almost similar to those obtained in previous ones, the estimated prevalence of moyamoya disease in Japan has almost doubled during the recent decade (3900 in 1994 and 7700 in 2003). The increase could partly be explained by the increase in newly diagnosed cases (0.35 in 1994 and 0.54 in 2003 per 100 000 population).
• Intraoperative infrared brain surface blood flow monitoring during superficial temporal artery-middle cerebral artery anastomosis in a patient with moyamoya disease: clinical implication of the gradation value in postoperative clinical course - A case report

  Atsuhiro Nakagawa, Miki Fujimura, Tatsuhiko Arafune, Hideaki Suzuki, Ichiro Sakuma, Teiji Tominaga

  INTRACRANIAL PRESSURE AND BRAIN MONITORING XIII: MECHANISMS AND TREATMENT 102 159 - + 0065-1419 2008 [Refereed][Not invited]
   

  Background Superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis is a safe and effective treatment for moyamoya disease. Symptomatic cerebral hyperperfusion is a potential complication of this procedure, especially in adult cases. Accurate diagnosis of postoperative hyperperfusion is important because its treatment is contradictory to that for ischemia. Intraoperative techniques to detect hyperperfusion are still lacking. Methods We performed intraoperative infrared (IR) brain surface monitoring in a 36-year-old man who underwent left STA-MCA anastomosis. Findings IR monitoring not only detected the patency of bypass, as also confirmed by conventional Doppler sonography and postoperative magnetic resonance angiography, but also delineated the local brain surface hemodynamics after revascularization. Analysis of gradation value disclosed an abnormal increase in brain surface cerebral blood flow (indirectly indicated as a temperature change) after removal of the temporary clip. The patient suffered from transient right upper extremity numbness and dysarthria due to focal hyperperfusion from postoperative days2 through 6. Intensive blood pressure control completely relieved his symptoms, and he was discharged without neurologic deficit. Conclusions Intraoperative brain surface monitoring by IR imaging may be useful to predict cerebral hyperperfusion after revascularization surgery for moyamoya disease. Further evaluation with a larger number of patients is necessary to validate this technique.
• PUMA is involved in acute brain injury after subarachnoid hemorrhage in rats

  Kuniyasu Niizuma, Hidenori Endo, Miki Fujimura, Teiji Tominaga, Pak H. Chan

  Journal of Cerebral Blood Flow and Metabolism 27 (1) BP55 - 01 0271-678X 2007/11/13 

  Background and aims: Subarachnoid hemorrhage (SAH) results in a high mortality rate, despite sophisticated medical management and neurosurgical techniques. Recent studies have emphasized the importance of acute brain injury after SAH, in which apoptosis is involved as one of the major mechanisms. We have reported the involvement of mitochondrial cytochrome c release in apoptotic cell death after SAH. However, the molecular mechanism of this cytochrome c release remains unresolved. PUMA (p53-upregulated modulator of apoptosis), which is one of the BH3-only proteins, was shown to localize to mitochondria and to function to induce cytochrome c release in several recent in vitro studies. These reports inspired us to investigate the role of PUMA in the mechanisms of acute brain injury after SAH. Methods: To examine the relationship between acute brain injury and the PUMA pathway following SAH, we used a perforation SAH model in rats. One, 6 and 24 hours after SAH, samples were taken from the cerebral cortex and used for Western blot, coimmunoprecipitation or immunohistochemistry. Protein extraction of the mitochondrial fraction was performed using a multiple centrifugation method for Western blot and coimmunoprecipitation. To investigate apoptotic cell death after SAH, DNA fragmentation was analyzed with a commercial enzyme immunoassay. Finally, we intravenously administered an inhibitor against p53, pifithrin-α (PFT), to examine the role of PUMA as a downstream target of p53 and the relationship between PUMA inhibition and acute brain injury. Results: Western blot analysis showed that the expression of PUMA significantly increased in the mitochondrial fraction 6 hours after SAH. Double immunofluorescence for PUMA and COX demonstrated that PUMA colocalized with COX (which was used as a mitochondrial marker) in the cerebral cortex 6 hours after SAH. PUMA expression precipitated by Bcl-XL in the mitochondrial fraction increased time dependently and a significant increase was observed at 1 and 6 hours. Western blot analysis showed a significant increase in cytosolic cytochrome c 24 hours after SAH compared with sham-operated brains. Double immunofluorescence showed that some cortical cells with strong PUMA immunoreactivity colocalized with cytochrome c-positive cells at 24 hours. Western blot analysis showed that mitochondrial localization of PUMA, which was transcriptionally controlled by p53, and cytosolic cytochrome c release were significantly inhibited by PFT 6 hours after SAH. Moreover, DNA fragmentation at 24 hours was significantly decreased in the PFT-treated animals compared with vehicle-treated animals. Conclusions: We found that PUMA is upregulated in mitochondria and directly binds to Bcl-XL after SAH. Mitochondrial localization of PUMA and protein interaction between PUMA and Bcl-XL might induce release of cytochrome c to the cytosol, resulting in acute brain injury following SAH.
• Reduction in oxidative stress by SOD1 overexpression attenuates acute brain injury after subarachnoid hemorrhage via activation of Akt/GSK3b survival signaling

  Hidenori Endo, Kuniyasu Niizuma, Miki Fujimura, Teiji Tominaga, Pak H. Chan

  Journal of Cerebral Blood Flow and Metabolism 27 (1) BP51 - 01 0271-678X 2007/11/13 

  Introduction: Subarachnoid hemorrhage (SAH) results in a high mortality rate, despite sophisticated medical management and neurosurgical techniques. Recent studies have emphasized the importance of acute brain injury after SAH. Oxidative stress plays important roles in the pathogenesis of acute brain injury after SAH. We have reported that copper/zincsuperoxide dismutase (SOD1) is a crucial endogenous enzyme responsible for eliminating superoxide, and that overexpression of SOD1 reduces cell injury after SAH. In cerebral ischemia, SOD1 overexpression decreased ischemic neuronal death through activation of the Akt/GSK3b survival pathway. In this study, we investigate the relationship between SOD1 and the Akt/GSK3b pathway in acute brain injury after SAH. We address this issue by examining apoptotic cell death, superoxide production, and phosphorylation of Akt/GSK3b after SAH, using both wild-type (Wt) and SOD1 transgenic (Tg) rats. Materials and methods: To examine the relationship between SOD1 and the Akt/GSK3b pathway following SAH, we used a perforation SAH model in both Wt and SOD1 Tg rats. One, 6 and 24 hours after SAH, samples were taken from the cerebral cortex, and used for Western blot analysis and immunohistochemical analysis. To investigate apoptotic cell death in acute brain injury after SAH, DNA fragmentation was analyzed with a commercial enzyme immunoassay. Early production of superoxide anions (O2?) during SAH was investigated with the use of hydroethidine (HEt). Results: The mortality rate at 24 hours for the SOD1 Tg rats (7.69%) was significantly decreased compared with the Wt rats (31.4%). DNA fragmentation in the SOD1 Tg rats was significantly decreased at 24 hours compared with the Wt rats at the same time point. O2? production shown by oxidized HEt signals was observed in the cerebral cortex at 1 hour in the Wt rats, and was markedly decreased in the SOD1 Tg rats. Western blot analysis showed that immunoreactivity of phospho-Akt and phospho-GSK3b was significantly increased at 6 hours compared with the control brain samples in the Wt rats. In the SOD1 Tg rats, the increase in phospho-Akt and phospho-GSK3b levels was more prominent and persistent. In a comparison between the two groups, phospho-Akt and phospho-GSK3b were significantly increased at 24 hours in the SOD1 Tg rats. An immunohistochemistry study showed slight immunoreactivity of phospho-Akt and phospho-GSK3b in the cerebral cortex of the control brains. This immunoreactivity became stronger at 24 hours in both groups. In the SOD1 Tg rats, phospho-Akt and phospho-GSK3b expression at 24 hours was more prominent than in the Wt rats. A double immunofluorescent study demonstrated that phospho-Akt-positive cells colocalized with phospho-GSK3b-positive cells in the cerebral cortex 6 hours after SAH. Moreover, phospho-GSK3b-positive cells colocalized with neurons at the same time point. Conclusions: This study suggests that oxidative stress plays a significant role in acute brain injury after SAH, and that the neuroprotection of SOD1 is partly mediated by activation of the Akt/GSK3b survival pathway. Reducing oxidative stress, thereby activating the survival pathway, could be a therapeutic target for acute brain injury after SAH in a clinical situation.
• Seizure following superficial temporal-middle cerebral artery anastomosis in patients with Moyamoya disease: possible contribution of postoperative cerebral hyperperfusion

  Ayumi Narisawa, Miki Fujimura, Hiroaki Shimizu, Teiji Tominaga

  NEUROLOGICAL SURGERY 35 (5) 467 - 474 0301-2603 2007/05 [Refereed][Not invited]
   

  Surgical revascularization for moyamoya disease prevents cerebral ischemic attacks by improvirig.cerebral blood flown (CBF). Seizure is known as a rare complication after revascularization for moyamoya disease, although its underlying mechanism is undetermined. We investigated the relationship between seizure attack,and postoperative alteration in CBF in patients with moyamoya disease. CBF was routinely measured by N-isopropyl-p-[I-123] iodpamphetamine (I-123-IMP-SPECT)1 and 7 days after; superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis on 64 sides of the 44 consecative patients. (male female=13: 31, 2-62 years old) with moyamoya disease Three patients (male: female=1: 2 40 5,5 years old) suffered from seizure attack at 1 to 10 days after surgery Two-of the three patients manifested as seizures at 8-10 days after surgery and:presented transient neurologic deteriolation before seizure. Postoperative SPECT revealed significant increase in CBF at the sites of the anastomosis in all three patients. Postoperative magnetic resonance imaging showed no ischemic changes, and magnetic resonance angipgraphy showed the apparently patent STA-MCA anastomosis as thick high signal intensity sigh in all three patients. The anatomical location and the temporal profile of hyperfusion were completely in accordance with the focus of seizure attack. Intensive blood pressure control and the use of antiepileptic agents were instituted. The neurologic deficits were resolved and no seizure attack recurred in three patients. Seizure following STA MCA anastomosis can be caused by hyperfusion in patients with moyamoya disease. When seizure attacks occur, routine CBF measurement is recommended to differentiate hyperfusion and ischemia, since the treatments for these conditions are contradictory.
• [Delayed ischemic neurological deficit in patients with aneurysmal subarachnoid hemorrhage: its pathogenesis, prevention and treatment].

  Tominaga T, Fujimura M

  Nihon rinsho. Japanese journal of clinical medicine 64 Suppl 8 650 - 653 0047-1852 2006/11 [Refereed][Not invited]
  
• [Cerebral cavernous malformation].

  Fujimura M, Tominaga T

  Nihon rinsho. Japanese journal of clinical medicine 64 Suppl 8 691 - 694 0047-1852 2006/11 [Refereed][Not invited]
  
• Intraoperative brain surface blood flow monitoring using IRIS V thermographic imaging system in patients with Moyamoya disease

  Atsuhiro Nakagawa, Miki Fujimura, Tomohiro Ohki, Hideaki Suzuki, Kazuyoshi Takayama, Teiji Tominaga

  NEUROLOGICAL SURGERY 34 (10) 1017 - 1025 0301-2603 2006/10 [Refereed][Not invited]
   

  Surgical revascularization for moyamoya disease prevents cerebral ischemic attacks by improving CBF. But little is known about the changes of intraoperative cerebral hemodynamics and its effect on postoperative neurological status including symptomatic cerebral hyperperfusion. To address this issue, we applied a novel infrared camera system (IRIS-V thermographic system) for real-time, visual monitoring of surface CBF during surgery in patients with moyamoya disease. Seven patients (8 sides, male:female= 3:4, 7-62 years old) with moyamoya disease were included in the study. After STA-MCA anastomosis, STA were occluded transiently and recanalized, and whole sequence was recorded by IRIS-V system. Correlation between clinical, radiological findings and infrared imaging were investigated. Patency of bypass was confirmed by this camera during surgery in all cases. The intraoperative imaging patterns were divided into two groups. Group A: Change of brain surface color (++) (3 cases). Group B: Change of brain surface color (-) (4 cases). Transient symptomatic hyperperfusion occurred in all patients in Group A, whereas all patients in Group B showed non-symptomatic transient focal hyperperfusion on SPECT. No patient suffered permanent neurological deterioration compared to preoperative status. Characteristic pattern of the intraoperative cerebral hemodynamics as delineated by IRIS-V could be the optimal predictor for postoperative transient symptomatic hyperperfusion after direct bypass in patients with moyamoya disease.
• Diagnostic value of perfusion-weighted MRI for evaluating postoperative alteration of cerebral hemodynamics following STA-MCA anastomosis in patients with moyamoya disease

  Miki Fujimura, Shunji Mugikura, Hiroaki Shimizu, Teiji Tominaga

  NEUROLOGICAL SURGERY 34 (8) 801 - 809 0301-2603 2006/08 [Refereed][Not invited]
   

  Objective Surgical revascularization for moyamoya disease prevents cerebral ischemic attacks by improving cerebral blood flow (CBF). But little is known about the changes of CBF and its effect on neurological status during the acute stage after direct bypass for moyamoya disease. Methods and Results Perfusion-weighted magnetic resonance imaging (PWI) by the SE-EPI method was performed 4 and 10 days after superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis on 11 sides of 9 patients (male:female = 2:7, 24-61 years old) with moyamoya disease. All patients underwent single-photon emission computed tomography (SPECT) 1 and 7 days after surgery. The time-to-peak (TTP) by PWI showed focal decrease at the site of the anastomosis 4 days after STA-MCA anastomosis compared to preoperative TTP, and was further decreased in larger territory 10 days after surgery in all patients. Postoperative cerebral blood volume (CBV) by PWI showed significant increase compared to preoperative CBV in four patients who suffered symptomatic cerebral hyperperfusion after surgery. Postoperative SPECT revealed apparent increase of CBF in all patients and the patency of the STA-MCA bypass was confirmed by MRA. All patients were discharged without neurological deterioration compared to preoperative neurological status, and none of them suffered ischemic attack after surgery. Conclusion Postoperative decrease in TTP by PWI could be a sensitive parameter for the normalization of CBF after STA-MCA anastomosis in patients with moyamoya disease. Postoperative increase in CBV may suggest cerebral hyperperfusion and could be the optimal predictor for hyperperfusion syndrome after STA-MCA anastomosis in patients with moyamoya disease.
• Precocious puberty caused by hCG-producing germinoma involving the bilateral basal ganglia and cerebral white matter without typical radiologic findings: Case report

  Shinichiro Sugiyama, Toshihiro Kumabe, Masaki Mino, Miki Fujimura, Ikuma Fujiwara, Teiji Tominaga

  NEUROLOGICAL SURGERY 34 (6) 619 - 624 0301-2603 2006/06 [Refereed][Not invited]
   

  An 8-year-old boy presented with a rare case of germinoma involving the bilateral basal ganglia and cerebral white matter manifesting as precocious puberty. Magnetic resonance (MR) imaging at the initial presentation demonstrated mild hyperintense areas in the bilateral basal ganglia and corpus callosum on T1-weighted images, and a small hyperintense spot in the right internal capsule on T2-weighted images. Human chorionic gonadotropin (hGG) level was elevated in the cerebrospinal fluid (CSF), so we strongly suspected that threre was a hGG-producing germinoma originating in the bilateral basal ganglia. Stereotactic biopsy was performed. Histological examination revealed two-cell pattern germinoma. After three cycles of combination chemotherapy consisting of ifosfamide, cisplatin, and etoposide, followed by whole brain irradiation with a total dose of 24 Gy, the CSF hCG level fell below the detection limit, but MR imaging demonstrated no significant change. Intracranial hGG-producing germinoma should be suspected in patients presenting with precocious puberty and elevated CSF hCG level. Moreover, slight intensity change on MR imaging is important to identify germinoma arising from the basal ganglia in the early stage.
• Biological effect of shock waves: Brain damage by shock waves in rats - Pressure dependence

  Kaoruko Kato, Miki Fujimura, Atsuhiro Nakagawa, Atsushi Saito, Teiji Tominaga

  FUTURE MEDICAL ENGINEERING BASED ON BIONANOTECHNOLOGY, PROCEEDINGS 11 (1) 949 - + 2006 [Refereed][Not invited]
   

  To introduce shock waves (SW) as treatment modality in the vicinity of brain, it is necessary to understand the threshold of brain damage. In this study, we have evaluated pressure dependent SW induced brain damage. Brain of Sprague-Dawley rat (8 week old) was exposed to single shot of SW produced by AgN3, and were divided into 7 groups according to the exposed overpressure of shock wave, and time of sacrifice. Group A served as control. Estimated overpressure of applied SW was over 10 MPa in group B, C, D, and nearly 1 MPa in group E, F, G. The rat was sacrificed at 4, 24, 72 hours, respectively. The specimen were evaluated morphologically (hematoxykin and eosin stain) and biochemically (heat shock protein 72 and TUNEL stain). Subcortical hematoma and contusion were common findings in group B, C, D. In goup C and D, marked necrosis, and TUNEL positive cells could be observed. Heat shock protein 72 was positive in the cells around these necrotic area. In group D, E, and F, fusiform changes in nucleus were observed in some specimen. Present results show that two type of neuronal death, i.e. necrosis and apoptosis, can be induced by SW beyond 1 MPa.
• 膠芽腫におけるマトリックスメタロプロテアーゼ(MMP)の発現と浸潤能に関する検討

  渡辺みか, 隈部俊宏, 藤村幹, 遠藤希之, 三浦弘守, 安達友津, 森谷卓也, 冨永悌二, 笹野公伸

  日本病理学会会誌 93 (1) 348 - 348 2004/05 [Refereed][Not invited]
  
• 膠芽腫と有鉤嚢虫症を合併したTurcot症候群の一例

  新妻邦泰, 隈部俊宏, 藤村幹, 渡辺みか, 冨永悌二, 嘉山孝正

  Brain Tumor Pathology 21 (Suppl.) 52 - 52 2004/05 [Refereed][Not invited]
  
• 海綿状血管種・脳動静脈奇形におけるマトリックス分解酵素発現の免疫組織学的検討

  藤村幹, 渡辺みか, 冨永悌二

  脳卒中 26 (1) 280 - 280 2004/03 [Refereed][Not invited]
  
• Interhemispheric cyst causing leg monoparesis in the elderly: Case report

  Toshiaki Hayashi, Michiharu Nishijima, Kunihiko Umezawa, Miki Fujimura, Mitumori Kaimori

  Neurologia Medico-Chirurgica 41 (9) 463 - 465 0470-8105 2001 [Refereed][Not invited]
   

  A 64-year-old female presented with a rare case of interhemispheric cerebral cyst manifesting as progressive monoparesis in the right lower extremity for 2 years. Surgical excision of the cyst wall was performed and communication to the subdural space was created. Postoperatively, the cyst was greatly reduced in size, and the neurological signs and symptoms were markedly improved. Interhemispheric cyst often presents with motor disturbances such as hemiparesis or paraparesis. These symptoms tend to progress slowly and sometimes years are required for a proper diagnosis. Interhemispheric cyst can also cause slowly progressive monoparesis in the lower extremity.
• Coating of Cerebral Arteries with Fibrin Glue in Patients with Aneurysmal Subarachnoid Hemorrhage:Frequency of Chronic Hydrocephalus

  FUJIMURA Miki, SUGAWARA Takayuki, SEKI Hirofumi, OKU Tatsuya, NIIMURA Kaku, HIGUCHI Hiroshi

  Surgery for Cerebral Stroke 一般社団法人 日本脳卒中の外科学会 23 (6) 455 - 458 0914-5508 1995 

  We studied the clinical records of 21 patients from 35 to 80 years old (average 57.8) who were radically operated for subarachnoid hemorrhage (SAH) due to ruptured intracranial aneurysms and followed at least 3 months. In all cases, blood clots were removed as widely as possible, and fibrin glue coating therapy was carried out to prevent cerebral vasospasm by protecting the main arteries (C1 portion of the internal carotid artery, M1-M2 portion of the middle cerebral artery, and A1-A2 portion of the anterior cerebral artery) from blood clots. Aneurysm locations were as follows: middle cerebral artery (MCA): 10 cases, anterior communicating artery (Acom A): 6 cases, and internal carotid artery (ICA): 5 cases. All cases were beyond grade 2 in Hunt and Kosnik classification of SAH and belong to group 3 or 4 in Fisher's grading system.
  As a result, four cases (19%) presented symptomatic chronic hydrocephalus, and needed ventriculo-peritoneal shunt. Three cases had the location in Acom A (3/6, 50%), and one in ICA (1/5, 20%), respectively. All belonged to grade 3 in Hunt and Kosnik classification and represented diffuse symmetrical high density area in all cisterns in computed tomography. Our result did not represent the high frequency of chronic hydrocephalus compared with the former reports.
  In conclusion, fibrin glue coating therapy did not raise the frequency of chronic hydrocephalus in SAH patients. This seems to suggest that intrathecal injection of fibrin glue can be used for various purposes in the field of clinical neurosurgery.

MISC

• 高齢もやもや病患者に対する血行再建術:長期治療成績の検討

  藤村幹, 栗栖宏多, 伊東雅基, 内野晴登, 杉山拓  日本老年脳神経外科学会プログラム・抄録集  37th-  2024
• もやもや病におけるRNF213変異の血管negative remodeling促進効果

  内野晴登, 伊東雅基, 杉山拓, 栗栖宏多, 藤村幹  日本脳神経CI学会総会プログラム・抄録集  47th-  2024
• もやもや病STA-MCA吻合直後ICG色素血管外漏出-術直後から局所血管原性浮腫を呈した1成人例-

  伊東雅基, 山崎前穂, 内野晴登, 杉山拓, 藤村幹  日本脳神経CI学会総会プログラム・抄録集  47th-  2024
• Comprehensive validation of circulating microRNA signatures for Moyamoya disease

  伊東雅基, 内野晴登, 東海林菊太郎, 杉山拓, 川堀真人, 岩田育子, 矢部一郎, 寶金清博, 藤村幹  月刊メディカル・サイエンス・ダイジェスト  50-  (6)  2024
• CAS中の徐脈・低血圧に対するカテコラミン投与にてたこつぼ型心筋症と血栓性のステント閉塞を来たした1例

  舘澤諒大, 栗栖宏太, 長内俊也, 大前敬介, 大前敬介, 伊東雅基, 杉山拓, 石井伸明, 藤村幹  脳血管内治療(Web)  8-  (Supplement)  2023
• 特殊な血管性病変とその治療 解離性脳動脈瘤

  杉山拓, 藤村幹  Clinical Neuroscience  41-  (10)  2023
• 高齢者における頚動脈内膜剥離術の臨床的特徴および治療成績の検討

  池田寛, 杉山拓, 伊東雅基, 内野晴登, 長内俊也, 藤村幹  日本老年脳神経外科学会プログラム・抄録集  36th-  2023
• 地域医療と脳血管外科:高齢患者に対する血行再建術に着目して

  藤村幹, 伊東雅基, 内野晴登, 杉山拓  日本老年脳神経外科学会プログラム・抄録集  36th-  2023
• 成人もやもや病のMRA末梢動脈信号強度と間接血行発達度の関連

  内野晴登, 伊東雅基, 杉山拓, 川堀真人, 長内俊也, 藤村幹  日本脳神経CI学会総会プログラム・抄録集  46th-  2023
• 成人もやもや病複合血行再建術後バイパス路発達におけるRNF213創始者変異の意義

  伊東雅基, 川堀真人, 杉山拓, 東海林菊太郎, 舘澤諒大, 内野晴登, 数又研, 寳金清博, 藤村幹  Mt. Fuji Workshop on CVD  39th-  2022
• A Pilot study of the Usefulness of Telementoring in Teaching Endovascular Therapy

  長内俊也, 大川原舞, 前田拓真, 山口裕之, 藤村幹  脳血管内治療(Web)  7-  (Supplement)  2022
• 三次元融合画像による術前シミュレーションが有効であった脳幹部海綿状血管腫の一例

  大木聡悟, 茂木洋晃, 澤谷亮佑, 岡本迪成, 越前谷すみれ, 杉山拓, 山口秀, 藤村幹  日本脳腫瘍の外科学会プログラム・抄録集  27th-  2022
• 成人もやもや病に対する直接・間接複合血行再建術後のバイパス路発達の術前要因

  伊東雅基, 内野晴登, 川堀真人, 杉山拓, 数又研, 宝金清博, 藤村幹  日本分子脳神経外科学会プログラム・抄録集  22nd-  2022
• 高齢者虚血型もやもや病の疫学と治療

  藤村幹, 伊東雅基, 杉山拓, 遠藤英徳, 冨永悌二  日本老年脳神経外科学会プログラム・抄録集  35th (CD-ROM)-  2022
• 基本をマスター 脳神経外科手術のスタンダード 内頸動脈瘤に対するhigh flow bypass

  遠藤 英徳, 藤村 幹, 冨永 悌二  脳神経外科速報  30-  (3)  258  -265  2020/03  [Not refereed][Not invited]
   

  ＜POINT 1＞手順:施設ごとの術式と手順を十分に理解し、安全確実な手技を心がけることが重要である。＜POINT 2＞手術適応:クリッピング術で根治困難な、傍前床突起部大型・巨大動脈瘤、部分血栓化動脈瘤、血豆状動脈瘤、海綿静脈洞部動脈瘤などが良い適応である。＜POINT 3＞周術期管理:画像による周術期脳循環動態の把握、graft開存を意識した抗血栓療法など、きめ細かい周術期管理が治療成績向上に必要である。(著者抄録)
• 成人もやもや病に対するバイパス術後の遅発性過灌流とRNF213遺伝子c.14576G>A多型の関連についての検討

  藤村幹, 田代亮介, 勝木将人, 西澤威人, 遠又靖丈, 新妻邦泰, 冨永悌二  脳循環代謝(Web)  32-  (1)  2020
• 三叉神経根近傍の脳幹脳動静脈奇形に対する塞栓術の治療成績

  遠藤 英徳, 松本 康史, 佐藤 健一, 大沢 伸一郎, 藤村 幹, 新妻 邦泰, 冨永 悌二  脳血管内治療  4-  (Suppl.)  S199  -S199  2019/11  [Not refereed][Not invited]
  
• 外科的血行再建と脳循環 成人もやもや病に対するSTA-MCAバイパス術後急性期の脳循環動態と臨床像についての検討

  藤村 幹, 田代 亮介, 亀山 昌幸, 佐藤 健一, 遠藤 英徳, 新妻 邦泰, 冨永 悌二  脳循環代謝  31-  (1)  87  -87  2019/11  [Not refereed][Not invited]
  
• 外科的血行再建と脳循環 術中ICGによるCEA術後過灌流予測

  井上 敬, 坂田 洋之, 井上 智夫, 江面 正幸, 上之原 広司, 斉藤 敦志, 藤村 幹, 遠藤 英徳, 新妻 邦泰, 冨永 悌二  脳循環代謝  31-  (1)  88  -88  2019/11  [Not refereed][Not invited]
  
• 成人もやもや病に対するSTA-MCAバイパス術後の特異な脳循環動態 watershed shift現象の臨床像に関する検討

  田代 亮介, 藤村 幹, 亀山 昌幸, 麦倉 俊司, 遠藤 英徳, 新妻 邦泰, 冨永 悌二  脳循環代謝  31-  (1)  112  -112  2019/11  [Not refereed][Not invited]
  
• 側副血行発達の異なる系統マウスにおける微小循環の検討

  鹿毛 淳史, 西嶌 泰生, 藤村 幹, 新妻 邦泰, 遠藤 英徳, Liu Jialing, 冨永 悌二  脳循環代謝  31-  (1)  120  -120  2019/11  [Not refereed][Not invited]
  
• 専門医に求められる最新の知識 脳血管障害 脳底動脈瘤に対するバイパスと血管内治療を併用したハイブリッド治療戦略

  遠藤 英徳, 佐藤 健一, 藤村 幹, 杉山 慎一郎, 千葉 朋浩, 冨永 悌二  脳神経外科速報  29-  (9)  960  -966  2019/09  [Not refereed][Not invited]
   

  開頭術や脳血管内治療の進歩により、脳動脈瘤の治療成績は向上している。しかし、大型・巨大脳底動脈瘤はいまだに治療困難であり、治療に伴う合併症も多い。これらの動脈瘤の多くは後大脳動脈や上小脳動脈などの分枝、もしくはそれらに起始する穿通枝が動脈瘤に巻き込まれ、かつ血栓化や石灰化、脳幹への癒着を伴っていることが治療を困難なものにしている。本稿では、同疾患に対する直達手術と脳血管内治療を組み合わせたhybrid strategyについて、症例報告を提示して解説する。Hybrid strategyでは、2つの治療方法を組み合わせることでそれぞれの長所を生かして合併症を回避し、良好な治療成績を得られる可能性がある。(著者抄録)
• 脳動脈瘤の出血源診断における造影MRIの有用性

  面高 俊介, 遠藤 英徳, 新妻 邦泰, 遠藤 俊毅, 佐藤 健一, 藤村 幹, 松本 康史, 井上 敬, 冨永 悌二  東北脳血管障害研究会学術集会記録集  40回-  0076  -0091  2018/12  [Not refereed][Not invited]
  
• バイオマーカーによる脳卒中診断

  井上 敬, 石田 邦久, 新妻 邦泰, 井上 智夫, 齋藤 敦志, 江面 正幸, 遠藤 英徳, 藤村 幹, 冨永 悌二  脳循環代謝  30-  (1)  119  -119  2018/10  [Not refereed][Not invited]
  
• 小児もやもや病に対する直接間接複合バイパス術―長期治療成績と課題―

  藤村幹, 遠藤英徳, 新妻邦泰, 冨永悌二  Mt. Fuji Workshop on CVD  36-  1  -4  2018/07  [Not refereed][Not invited]
  
• 脳血管障害の基礎知識 脳卒中専門医に知っておいてほしいキーワード外科系(第13回) 頭蓋内内頸動脈系の動脈解離

  遠藤 英徳, 冨永 悌二, 藤村 幹, 松本 康史  分子脳血管病  17-  (1)  62  -65  2018/01  [Not refereed][Not invited]
   

  脳動脈解離は、画像診断技術の発展によりその診断機会が増え、従来考えられていたほどまれではないことが明らかとなった。出血または虚血で発症するほか、軽微な頭痛で発見されることもあり、その自然経過は完全にはわかっていない。多くは椎骨脳底動脈領域に生じるが、とくに若年者では内頸動脈系にも発生することがあり、若年性脳卒中の原因としても近年注目されている。また、くも膜下出血で発症する"チマメ状動脈瘤"も内頸動脈解離の亜型と報告されている。脳梗塞に対しては内科治療、出血に対しては外科治療の対象となることが多く、治療に際して、解離の部位や形状、周囲血管の状態などの正確な画像診断が求められる。(著者抄録)
• Current Indications and Problems of CEA and CAS

  遠藤英徳, 藤村幹, 松本康史, 遠藤俊毅, 佐藤健一, 新妻邦泰, 井上敬, 冨永悌二  脳神経外科ジャーナル  27-  (7)  514‐521(J‐STAGE)  2018  [Not refereed][Not invited]
  
• 治療困難な脳動脈瘤に対するバイパス術併用血管内治療

  佐藤 健一, 藤村 幹, 遠藤 英徳, 松本 康史, 冨永 悌二  脳血管内治療  2-  (Suppl.)  S121  -S121  2017/11  [Not refereed][Not invited]
  
• もやもや病を究める もやもや病の脳循環研究 SPECTを用いた術後急性期病態の解明

  藤村 幹, 麦倉 俊司, 遠藤 英徳, 新妻 邦泰, 藤原 悟, 冨永 悌二  脳循環代謝  29-  (1)  144  -144  2017/11  [Not refereed][Not invited]
  
• 頭蓋外内バイパス術後急性期に低灌流にもかかわらず症候性血管原性浮腫を生じた成人もやもや病の1例

  田代 亮介, 藤村 幹, 麦倉 俊司, 新妻 邦泰, 遠藤 英徳, 冨永 悌二  脳循環代謝  29-  (1)  193  -193  2017/11  [Not refereed][Not invited]
  
• Multi-delay ASLによるCEA周術期脳循環動態評価

  遠藤 英徳, 藤村 幹, 遠藤 俊毅, 面高 俊介, 大友 一匡, 新妻 邦泰, 冨永 悌二  脳循環代謝  29-  (1)  180  -180  2017/11  [Not refereed][Not invited]
  
• Choroidal arteryを標的としたAVM塞栓術の治療成績

  遠藤 英徳, 松本 康史, 佐藤 健一, 新妻 邦泰, 遠藤 俊毅, 藤村 幹, 冨永 悌二  脳血管内治療  2-  (Suppl.)  S32  -S32  2017/11  [Not refereed][Not invited]
  
• 仙骨部脊髄動静脈シャント疾患に対する外科治療

  遠藤 俊毅, 佐藤 健一, 藤村 幹, 面高 俊介, 遠藤 英徳, 松本 康史, 冨永 悌二  脳血管内治療  2-  (Suppl.)  S110  -S110  2017/11  [Not refereed][Not invited]
  
• 造影MRIを用いた多発脳動脈瘤の出血源診断

  面高 俊介, 遠藤 英徳, 新妻 邦泰, 遠藤 俊毅, 藤村 幹, 佐藤 健一, 松本 康史, 冨永 悌二  脳血管内治療  2-  (Suppl.)  S269  -S269  2017/11  [Not refereed][Not invited]
  
• Further Implications of Off-Label Use of Acetazolamide in the Management of Moyamoya Disease in Japan

  Shunji Mugikura, Miki Fujimura, Shoki Takahashi, Kei Takase  RADIOLOGY  284-  (1)  301  -302  2017/07  [Not refereed][Not invited]
  
• 脳動脈瘤治療の標準化と最適化 脳動脈瘤塞栓術の標準化と最適化

  松本 康史, 佐藤 健一, 遠藤 俊毅, 遠藤 英徳, 藤村 幹, 冨永 悌二  The Mt. Fuji Workshop on CVD  35-  72  -77  2017/07  [Not refereed][Not invited]
  
• Can Combined Bypass Surgery at Middle Cerebral Artery Territory Save Anterior Cerebral Artery Territory in Adult Moyamoya Disease? COMMENT

  Miki Fujimura, Teiji Tominaga  NEUROSURGERY  80-  (3)  438  -438  2017/03  [Not refereed][Not invited]
  
• 10分で速習! スライドでわかる脳神経外科手術のポイント VA-PICA ANに対する手術のコツとピットフォール

  遠藤 英徳, 藤村 幹, 遠藤 俊毅, 冨永 悌二  脳神経外科速報  27-  (3)  265  -272  2017/03  [Not refereed][Not invited]
  
• 新規脳梗塞治療薬SMTP-7の開発

  新妻邦泰, 藤村幹, 清水宏明, 冨永悌二  脳循環代謝(Web)  29-  (1)  2017
• 内頚動脈前壁チマメ状動脈瘤の病態と治療戦略

  遠藤英徳, 藤村幹, 清水宏明, 遠藤俊毅, 藤原悟, 冨永悌二  日本臨床脳神経外科学会プログラム・抄録集  20th-  2017
• 下垂体腺腫治療後の内頸動脈瘤形成 その成因と治療

  坂田 洋之, 遠藤 英徳, 藤村 幹, 小川 欣一, 城倉 英史, 川岸 潤, 佐藤 健一, 松本 康史, 遠藤 俊毅, 冨永 悌二  東北脳血管障害研究会学術集会記録集  38回-  0271  -0283  2016/12  [Not refereed][Not invited]
  
• 成人もやもや病に対する直接間接複合バイパス術 脳循環画像に基づいた周術期管理の効果とpitfall

  藤村 幹, 坂田 洋之, 新妻 邦泰, 遠藤 英徳, 井上 敬, 冨永 悌二  脳循環代謝  28-  (1)  182  -182  2016/11  [Not refereed][Not invited]
  
• CEA術前脳循環予備能測定は必要か?

  井上 敬, 江面 正幸, 上之原 広司, 遠藤 英徳, 藤村 幹, 冨永 悌二  脳循環代謝  28-  (1)  218  -218  2016/11  [Not refereed][Not invited]
  
• Arterial Spin Labelingを使用したCEA周術期脳循環動態評価

  遠藤 英徳, 藤村 幹, 遠藤 俊毅, 井上 敬, 清水 宏明, 冨永 悌二  脳循環代謝  28-  (1)  208  -208  2016/11  [Not refereed][Not invited]
  
• 後方循環血行力学的脳虚血に対して血行再建を行った2例

  長田 佳整, 遠藤 英徳, 遠藤 俊毅, 佐藤 健一, 松本 康史, 藤村 幹, 冨永 悌二  脳循環代謝  28-  (1)  216  -216  2016/11  [Not refereed][Not invited]
  
• Choroidal arteryを標的としたAVM塞栓術の治療成績

  遠藤 英徳, 松本 康史, 佐藤 健一, 近藤 竜史, 新妻 邦泰, 遠藤 俊毅, 藤村 幹, 冨永 悌二  脳血管内治療  1-  (Suppl.)  S98  -S98  2016/11  [Not refereed][Not invited]
  
• 待機手術を施行した脊髄軟膜動静脈瘻の1治療例

  新妻 邦泰, 佐藤 健一, 遠藤 俊毅, 眞野 唯, 赤松 洋祐, 藤村 幹, 冨永 悌二  脳血管内治療  1-  (Suppl.)  S130  -S130  2016/11  [Not refereed][Not invited]
  
• 食道癌・咽頭癌に関連する感染性仮性総頸動脈破裂の一治療例

  新妻 邦泰, 川口 奉洋, 佐々木 貴史, 藤村 幹, 小川 武則, 香取 幸夫, 松本 康史, 冨永 悌二  脳血管内治療  1-  (Suppl.)  S208  -S208  2016/11  [Not refereed][Not invited]
  
• OUTCOME AND RISK FACTORS FOR MENINGITIS AFTER CRANIOTOMY IN PATIENTS WITH SUBARACHNOID HEMORRHAGE

  T. Inoue, M. Fujimura, H. Endo, T. Tominaga  INTERNATIONAL JOURNAL OF STROKE  11-  (SUPP 3)  66  -66  2016/10  [Not refereed][Not invited]
  
• 脳主幹動脈閉塞に対する緊急EC-IC bypassの治療成績

  遠藤 英徳, 藤村 幹, 清水 宏明, 井上 敬, 藤原 悟, 冨永 悌二  The Mt. Fuji Workshop on CVD  34-  196  -200  2016/08  [Not refereed][Not invited]
   

  脳主幹動脈閉塞に対する緊急extracranial-intracranial(EC-IC) bypassの治療成績について検討した。前方循環の脳主幹動脈閉塞に対して緊急EC-IC bypass術を施行した11例を対象とした。閉塞部位は内頸動脈が7例、中大脳動脈(M1)が4例で、閉塞機転の原因は、動脈硬化7例、動脈解離3例、放射線治療後1例であった。症状出現から手術開始までの時間は6.5〜96時間であった。Single bypassを9例、double bypassを2例に行い、M4の遮断時間は18〜54分であった。Modified NIHSSは9例で術後改善し、中央値の推移は術直前6、術翌日5、術後7日目3であった。術後7日目のmodified NIHSSは術直前と比較して有意に改善した。腎不全に起因する全身状態悪化をきたした1例で梗塞増大による症状悪化を認めた。6ヵ月後に画像追跡を行った9例全例でbypassの開存を確認した。6ヵ月後の転帰は、良好(mRS 0-2)が8例(73%)であった。
• EDARAVONE (MCI-186) ALLEVIATES ACUTE BRAIN INJURY AFTER SUBARACHNOID HEMORRHAGE IN RATS

  K. Niizuma, A. Ito, T. Sasaki, M. Fujimura, P. H. Chan, T. Tominaga  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM  36-  359  -360  2016/06  [Not refereed][Not invited]
  
• MOUSE MODEL OF LACUNAR INFARCTS WITH LONG-LASTING FUNCTIONAL DISABILITIES

  H. Uchida, K. Niizuma, H. Sakata, M. Fujimura, M. Dezawa, T. Tominaga  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM  36-  215  -215  2016/06  [Not refereed][Not invited]
  
• QUANTITATIVE MEASUREMENT OF CEREBRAL BLOOD FLOW USING SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY WITH VENOUS BLOOD SAMPLING

  T. Inoue, H. Shimizu, M. Fujimura, K. Sato, H. Endo, K. Niizuma, H. Sakata, T. Tominaga  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM  36-  402  -402  2016/06  [Not refereed][Not invited]
  
• Arterial Spin Labelingを使用したCEA周術期脳循環動態評価

  遠藤英徳, 藤村幹, 遠藤俊毅, 井上敬, 清水宏明, 冨永悌二  脳循環代謝(Web)  28-  (1)  2016
• Current status of the revascularization surgery for moyamoya disease

  Miki Fujimura, Teiji Tominaga  Japanese Journal of Neurosurgery  25-  (10)  844  -850  2016  [Not refereed][Not invited]
   

  Moyamoya disease is a chronic cerebrovascular disease with unknown etiology characterized by steno-occlusive changes at the terminal portion of the internal carotid artery and an abnormal vascular network at the base of the brain. Moyamoya disease has unique and dynamic nature to convert the vascular supply for the brain from internal carotid(IC) system to the external carotid(EC) system. Malfunction of this‘IC-EC conversion system’leads to cerebral ischemia,as well as to intracranial hemorrhage from inadequate collateral vascular network,both of which represent the clinical presentation of moyamoya disease. Therefore,surgical revascularization by extracranial-intracranial bypass is the optimal procedure to complement‘IC-EC conversion’,thereby preventing cerebral infarction and/or intracranial hemorrhage. Long term outcome of revascularization surgery is favorable,and the recent randomized control trial,such as the Japan Adult Moyamoya trial,further supports the validity of this procedure for moyamoya disease. Cerebral ischemia and hyperperfusion syndrome are potential complications of this procedure,which should be carefully managed by intensive perioperative care. We sought to review the current status of revascularization surgery for moyamoya disease,especially focusing on pre-operative diagnosis,surgical indication/procedure,and peri-operative management.
• The pathophysiology of moyamoya disease: An update

  Oh Young Bang, Miki Fujimura, Seung-Ki Kim  Journal of Stroke  18-  (1)  12  -20  2016  [Not refereed][Not invited]
   

  Moyamoya disease (MMD) is a unique cerebrovascular disease characterized by the progressive stenosis of large intracranial arteries and a hazy network of basal collaterals called moyamoya vessels. Because the etiology of MMD is unknown, its diagnosis is based on characteristic angiographic findings. Re-vascularization techniques (e.g., bypass surgery) are used to restore perfusion, and are the primary treatment for MMD. There is no specific treatment to prevent MMD progression. This review summarizes the recent advances in MMD pathophysiology, including the genetic and circulating factors related to disease development. Genetic and environmental factors may play important roles in the development of the vascular stenosis and aberrant angiogenesis in complex ways. These factors include the related changes in circulating endothelial/smooth muscle progenitor cells, cytokines related to vascular remodeling and angiogenesis, and endothelium, such as caveolin which is a plasma membrane protein. With a better understanding of MMD pathophysiology, nonsurgical approaches targeting MMD pathogenesis may be available to stop or slow the progression of this disease. The possible strategies include targeting growth factors, retinoic acid, caveolin-1, and stem cells.
• A case of ruptured infectious anterior cerebral artery aneurysm treated by interposition graft bypass using the superficial temporal artery

  Takatsugu Abe, Hidenori Endo, Hiroaki Shimizu, Miki Fujimura, Toshiki Endo, Hiroyuki Sakata, Mika Watanabe, Teiji Tominaga  Surgical Neurology International  7-  (1)  2016/01/01  [Not refereed][Not invited]
   

  Background: To describe the application of an interposition graft bypass using superficial temporal artery (STA) for the treatment of a ruptured anterior cerebral artery (ACA) infectious aneurysm. Case Description: A 30-year-old male suffered from severe headache with high fever. The patient's diagnosis was ruptured infectious ACA aneurysm at the A3 segment with a maximum diameter of 4.5 mm, caused by infectious endocarditis. The patient was initially treated with high-dose intravenous antibiotics. Follow-up digital subtraction angiography (DSA) revealed that the fusiform aneurysm had enlarged to a maximum diameter of 14.0 mm. A left paracentral artery, supplying the motor area of the left lower extremity, originated from the body of this aneurysm. Because the angiographic findings suggested a risk of recurrent bleeding, the patient underwent open surgery. Interposition graft bypass using the STA was performed to reconstruct the left A3 segment in an end-to-side manner (left proximal callosomarginal artery - STA graft - left distal pericallosal artery). Then, the origin of the left paracentral artery was cut and anastomosed to the STA graft in an end-to-side manner. The affected parent artery was trapped, and the aneurysm was resected. Postoperative magnetic resonance imaging showed no ischemic or hemorrhagic complications, and postoperative DSA revealed the patency of the interposition graft. Pathological diagnosis of the resected aneurysm revealed features corresponding to infectious cerebral aneurysm. The postoperative course was uneventful, and the patient was discharged without any neurological deficits. Conclusion: In the treatment of infectious cerebral aneurysms, revascularization should be considered when the affected artery supplies the eloquent area. Interposition graft bypass using the STA is one of the options for revascularization surgery for the treatment of infectious ACA aneurysms.
• 三叉神経根近傍の脳幹脳動静脈奇形 臨床的特徴と治療成績

  遠藤 英徳, 佐藤 健一, 大沢 伸一郎, 松本 康史, 藤村 幹, 藤原 悟, 冨永 悌二  東北脳血管障害研究会学術集会記録集  37回-  248  -266  2015/12  [Not refereed][Not invited]
  
• ONYXはAVMの治療成績を向上させたか? 脳動静脈奇形に対する集学的治療における血管内治療

  新妻 邦泰, 佐藤 健一, 松本 康史, 遠藤 英徳, 藤村 幹, 近藤 竜史, 川岸 潤, 冨永 悌二  JNET: Journal of Neuroendovascular Therapy  9-  (6)  S191  -S191  2015/11  [Not refereed][Not invited]
  
• 脳動静脈奇形に対する集学的治療における血管内治療

  佐藤 健一, 松本 康史, 遠藤 英徳, 藤村 幹, 近藤 竜史, 川岸 潤, 冨永 悌二  JNET: Journal of Neuroendovascular Therapy  9-  (6)  228  -228  2015/11  [Not refereed][Not invited]
  
• 小児もやもや病に対する直接間接複合バイパス術 長期治療成績の検討

  藤村 幹, ラシャド・シェリフ, 遠藤 英徳, 新妻 邦泰, 坂田 洋之, 佐藤 健一, 冨永 悌二  脳循環代謝  27-  (1)  139  -139  2015/10  [Not refereed][Not invited]
  
• 破裂内頸動脈瘤に対するEC-IC bypassの治療成績

  遠藤 英徳, 藤村 幹, 清水 宏明, 井上 敬, 佐藤 健一, 藤原 悟, 冨永 悌二  脳循環代謝  27-  (1)  142  -142  2015/10  [Not refereed][Not invited]
  
• CEA術後過灌流予測における脳循環予備能測定の意義

  井上 敬, 江面 正幸, 上之原 広司, 遠藤 英徳, 藤村 幹, 藤原 悟, 富永 悌二  脳循環代謝  27-  (1)  152  -152  2015/10  [Not refereed][Not invited]
  
• 深部脳動静脈奇形周囲にcerebral proliferative angiopathyの2次的形成を認めた小児例

  坂田 洋之, 藤村 幹, 佐藤 健一, 新妻 邦泰, 遠藤 英徳, 冨永 悌二  脳循環代謝  27-  (1)  190  -190  2015/10  [Not refereed][Not invited]
  
• クモ膜下出血後急性期脳血流の時間的・空間的変化と臨床転帰との相関についての検討

  佐藤 健一, 遠藤 英徳, 藤村 幹, 井上 敬, 清水 宏明, 冨永 悌二  脳循環代謝  27-  (1)  190  -190  2015/10  [Not refereed][Not invited]
  
• 【脳卒中における脳循環代謝画像のすべて-初心者からエキスパートまで-】脳卒中の各病態における脳循環代謝画像の意義 くも膜下出血後脳血流の時間的・空間的変化 3-D SRT softwareを用いたSPECT解析

  佐藤 健一, 清水 宏明, 井上 敬, 藤村 幹, 遠藤 英徳, 冨永 悌二  The Mt. Fuji Workshop on CVD  33-  98,108  -102,108  2015/07  [Not refereed][Not invited]
   

  脳動脈瘤破裂によるくも膜下出血(SAH)後、遅発性脳虚血(DCI)予防治療中の88例(男27例、女61例、平均年齢61.2歳)を対象に、SPECT検査を急性期に2回施行し3次元SRTソフトウェアを用いて脳血流量を評価し、局所脳血流量の変化と対応領域の脳梗塞出現の有無および臨床転帰について後方視的に検討した。88症例の脳全体1936領域中40領域でDCIによる脳梗塞巣を認めた。各領域のradio-signal countを両側小脳半球のradio-signal countの平均で除したrCBF比が、正常ボランティア10例の平均と比較して1回目も2回目もhypoperfusion(90%未満)であった領域の13.0%、1回目がnormoperfusion(90%〜110%未満)で2回目がhypoperfusionであった領域の19.1%に脳梗塞巣を認めた。またSAH急性期治療中にrCBFが増加する領域と減少する領域が混在する42例ではそれ以外の群と比較して3ヵ月後の臨床転帰が有意に不良で、転帰不良の原因の50%はDCIによるものであった。
• 開頭術または血管内塞栓術後の残存・再発脳動脈瘤に対する開頭術

  清水 宏明, 柳澤 俊晴, 遠藤 英徳, 井上 敬, 藤村 幹, 松本 康史, 冨永 悌二  脳卒中の外科  43-  (3)  212  -217  2015/05  [Not refereed][Not invited]
   

  2001年以降に開頭術またはコイル塞栓術を施行し、術後に動脈瘤の残存、再発または破裂を呈して開頭術を施行した14名(男3、女11、平均年齢58歳)を対象に、臨床症状や再手術の成績について再調査した。初回発症形式は、くも膜下出血8名、未破裂動脈瘤6名で、開頭術を8名(クリッピング術7、ラッピング術1)、コイル塞栓術を6名に施行した。再手術前の症状は、破裂1名、動脈瘤頸部残存2名、動脈瘤の増大11名であった。どちらの術式でも、初回手術で不完全閉塞の場合に再発リスクが上昇し、コイル塞栓術の場合は10mm以上の大きさも再発リスクになることが示された。
• 1型糖尿病に合併した成人・類もやもや病の1手術例

  赤松 洋祐, 藤村 幹, 坂田 洋之, 遠藤 英徳, 板橋 亮, 冨永 悌二  Neurological Surgery  43-  (3)  227  -233  2015/03  [Not refereed][Not invited]
   

  32歳女。6歳時に1型糖尿病を発症しインスリン自己注射を行っていた。右眼前暗黒感で受診し、MRIで頭蓋内虚血性病変を指摘された。123I-IMP SPECTでは、左前頭葉・頭頂葉において左前頭葉の梗塞巣周囲に広がる安静時血流低下を認めた。左大脳半球に直接・間接血行再建術を施行した。周術期の血糖コントロールは持続皮下インスリン注入療法にボーラスインスリン療法を併用した。過灌流症候群の予防を目的として、術直後より予防的降圧とミノサイクリン塩酸塩投与を開始した。術翌日、7日目のSPECT上も明らかな過灌流はみられなかった。術後MRAでは良好なSTAの開通性を確認し、拡散強調像でも新たな虚血性病変はなく、術後2週間で神経学的欠損症状もなく自宅退院した。術後3ヵ月間、脳血管イベントはなく経過している。
• 【脳動脈瘤と脳動静脈奇形の最新治療】開頭・血管内手術を利用した複合脳動脈瘤手術

  清水 宏明, 松本 康史, 遠藤 英徳, 井上 敬, 藤村 幹, 冨永 悌二  脳神経外科ジャーナル  24-  (3)  165  -172  2015/03  [Not refereed][Not invited]
   

  クリップやコイルで治療困難な脳動脈瘤に、開頭・血管内複合手術が行われる場合がある。症例提示:1)海綿静脈洞部巨大内頸動脈瘤に術前バルーンテスト閉塞の所見をもとにバイパス術+親動脈閉塞、2)破裂椎骨動脈解離の血管内親動脈閉塞術に先立ち閉塞される後下小脳動脈にバイパスを施行、3)巨大脳底-上小脳動脈瘤の瘤壁から起始する上小脳動脈にバイパス作成後、瘤内コイル塞栓術、4)内頸動脈kissing aneurysmsに対するクリッピング術中に断念し瘤内コイル塞栓術、5)脳底動脈先端部瘤のコイル塞栓術中に不完全閉塞になることが判明し断念、クリッピング施行。複合手術では両治療チームの協働が重要である。(著者抄録)
• クモ膜下出血後脳血流の時間的・空間的変化 3DSRT softwareを用いたSPECT解析

  佐藤 健一, 清水 宏明, 井上 敬, 藤村 幹, 遠藤 英徳, 冨永 悌二  脳血管攣縮  30-  56  -56  2015/03  [Not refereed][Not invited]
  
• Cerebral blood flow measurement using single photon emission computed tomography with venous blood sampling

  T. Inoue, S. Fujiwara, M. Ezura, H. Uenohara, M. Fujimura, T. Tominaga  CEREBROVASCULAR DISEASES  39-  18  -18  2015  [Not refereed][Not invited]
  
• 出血発症した三叉神経根近傍の脳幹部動静脈奇形4例の治療経験

  大沢 伸一郎, 遠藤 英徳, 佐藤 健一, 松本 康史, 藤村 幹, 藤原 悟, 冨永 悌二  JNET: Journal of Neuroendovascular Therapy  8-  (6)  368  -368  2014/12  [Not refereed][Not invited]
  
• Laser speckle flowgraphyを用いてバイパス術前後の眼循環評価を行った内頸動脈閉塞症の一例

  面高 俊介, 遠藤 英徳, 藤村 幹, 清水 宏明, 藤原 悟, 冨永 悌二  東北脳血管障害研究会学術集会記録集  36回-  138  -150  2014/12  [Not refereed][Not invited]
  
• 非出血性脳動脈解離の外科治療

  遠藤 英徳, 清水 宏明, 鈴木 一郎, 近藤 竜史, 松本 康史, 藤村 幹, 井上 敬, 佐藤 健一, 藤原 悟, 冨永 悌二  東北脳血管障害研究会学術集会記録集  36回-  290  -314  2014/12  [Not refereed][Not invited]
  
• 頸椎脱臼骨折整復術前の予防的椎骨動脈塞栓術の二例

  新妻 邦泰, 川口 奉洋, 佐藤 健一, 藤村 幹, 遠藤 俊毅, 笹治 達郎, 松本 康史, 冨永 悌二  JNET: Journal of Neuroendovascular Therapy  8-  (6)  382  -382  2014/12  [Not refereed][Not invited]
  
• [Usefulness of pulsed water jet in dissecting sphenoid ridge meningioma while preserving arteries].

  Toshiki Endo, Atsuhiro Nakagawa, Miki Fujimura, Yukihiko Sonoda, Hiroaki Shimizu, Teiji Tominaga  No shinkei geka. Neurological surgery  42-  (11)  1019  -25  2014/11  [Not refereed][Not invited]
   

  We report the utility of a pulsed water jet device in meningioma surgery. The presented case is that of a 61-year-old woman with left visual disturbance. MRI demonstrated heterogeneously enhanced mass with intratumoral hemorrhage, indicating sphenoid ridge meningioma on her left side. The tumor invaded the cavernous sinus and left optic canal, engulfing the internal carotid artery in the carotid cistern and encased middle cerebral arteries. During the operation, the pulsed water jet device was useful for dissecting the tumor away from the arteries since it was safe in light of preserving parent arteries. The jet did not cause any vascular injury and did not induce vasospasm as shown by postoperative symptomatology and MRIs. With the aid of pulsed water jet, we could achieve total resection of the tumor except for the piece within the cavernous sinus. The patient had no new neurological deficits after the operation. We consider the pulsed water jet as a useful device, especially when the need to dissect meningioma from parent arteries exists. The jet can help neurosurgeons simultaneously achieve tumor resection and preservation of blood vessels.
• 破裂瘤の治療後早期に破裂した前交通動脈瘤の一例 血行力学的変化の検討

  新妻 邦泰, 杉山 慎一郎, 遠藤 英徳, 佐藤 健一, 松本 康史, 藤村 幹, 冨永 悌二  脳循環代謝  26-  (1)  166  -166  2014/11  [Not refereed][Not invited]
  
• 破裂内頸動脈瘤に対するEC-IC bypass術後急性期の脳循環動態

  遠藤 英徳, 藤村 幹, 佐藤 健一, 清水 宏明, 藤原 悟, 冨永 悌二  脳循環代謝  26-  (1)  176  -176  2014/11  [Not refereed][Not invited]
  
• CEA術前後にSPECTは必須か?

  井上 敬, 藤村 幹, 佐藤 健一, 遠藤 英徳, 新妻 邦泰, 坂田 洋之, 江面 正幸, 上之原 広司, 藤原 悟, 冨永 悌二  脳循環代謝  26-  (1)  200  -200  2014/11  [Not refereed][Not invited]
  
• もやもや病疾患感受性遺伝子RNF213 R4859K変異マウスにおける経時的頭部MRA所見に関する検討

  鹿毛 淳史, 藤村 幹, 新妻 邦泰, 坂田 洋之, 伊藤 明, 前田 美香, 呉 繁夫, 冨永 悌二  脳循環代謝  26-  (1)  180  -180  2014/11  [Not refereed][Not invited]
  
• もやもや病疾患感受性遺伝子RNF213ノックアウトマウスの一過性局所脳虚血への反応性の検討

  伊藤 明, 藤村 幹, 新妻 邦泰, 坂田 洋之, 鹿毛 淳史, 呉 繁夫, 冨永 悌二  脳循環代謝  26-  (1)  208  -208  2014/11  [Not refereed][Not invited]
  
• Experimental Model of Lacunar Infarcts in Mice with Long-Lasting Functional Disabilities

  Hiroki Uchida, Hiroyuki Sakata, Miki Fujimura, Kuniyasu Niizuma, Mari Dezawa, Teiji Tominaga  CEREBROVASCULAR DISEASES  38-  9  -9  2014/09  [Not refereed][Not invited]
  
• A Case of Anterior Communicating Artery Aneurysm Ruptured after the Treatment of Another Ruptured Aneurysm

  Kuniyasu Niizuma, Shin-ichiro Sugiyama, Hidenori Endo, Kenichi Sato, Yasushi Matsumoto, Miki Fujimura, Teiji Tominaga  CEREBROVASCULAR DISEASES  38-  46  -47  2014/09  [Not refereed][Not invited]
  
• 【脳動脈瘤の最新知識-成因・病態から最先端治療まで-】Clippingとparent artery occlusion/flow alterationの使い分けを要する内頸動脈瘤の治療

  清水 宏明, 遠藤 英徳, 井上 敬, 藤村 幹, 松本 康史, 冨永 悌二  脳神経外科ジャーナル  23-  (9)  721  -728  2014/09  [Not refereed][Not invited]
   

  内頸動脈のチマメ様動脈瘤や動脈解離(A群)あるいは大型瘤(B群)の手術ではclippingと親動脈閉塞手術の選択が問題になり得る。われわれはA群では再破裂回避が重要と考え、急性期にバイパス術を併用して頭蓋内trappingを行っている。B群では動脈瘤の状況に応じて、clipping、trapping、blind-alley formation、flow alterationのいずれかに適宜バイパス術を併用している。成績は比較的良好であったが、バイパス閉塞、穿通枝障害、コイル塞栓部での血栓形成などの合併症も経験した。バイパス術選択と確実な実施、親動脈閉塞の方法、抗血栓剤の選択などが留意点と考える。(著者抄録)
• Actuator-driven pulsed water jet surgery system: Initial clinical experience

  Atsuhiro Nakagawa, Toshiki Endo, Yukihiko Sonoda, Ryuta Saito, Masaki Iwasaki, Miki Fujimura, Tomohiro Kawaguchi, Hidenori Endo, Yoshikazu Ogawa, Teiji Tominaga  Transactions of Japanese Society for Medical and Biological Engineering  52-  (0)  63  -O-64  2014/08/17  [Not refereed][Not invited]
   

  Object. The purpose of present study is to report the safety and efficacy of piezo actuator-driven pulsed water jet (ADPJ) system in neurosurgery and spinal cord surgery. Methods. The ADPJ system have been used as a part of standard procedure for brain and spinal cord pathologies after approval from internal review board of Tohoku University Hospital. Results. The system have been used in 5 malignant glioma, 6 meningioma, 1 callosotomy for intractable epilepsy, 1 cerebrovascular disease, and 5 spinal cord tumor. There was no complication related to the use of the system. Tissue could be dissected under preservation of fine arteries (diameter 200 microns). The present power was not enough for certain pathologies, especially for hard lesions. Conclusion. Although additional effort to enhance efficacy is necessary, present study indicated that the ADPJ have possibility to become novel surgical tools to assist maximal lesion removal and preserving postoperative function.
• 脳血管内治療における数値流体力学 CFD(Computational Fluid Dynamics)の最前線 初心者のための脳動脈瘤CFD解析のパラダイムシフト

  木村 尚人, 高尾 洋之, 中山 敏男, 面高 俊介, 杉山 伸一郎, 新妻 邦泰, 藤村 幹, 井上 敬, 江面 正幸, 山本 誠, 村山 雄一, 冨永 悌二  脳神経外科速報  24-  (7)  758  -762  2014/07  [Not refereed][Not invited]
  
• Genetics and Biomarkers of Moyamoya Disease: Significance of RNF213 as a Susceptibility Gene

  Miki Fujimura, Shinya Sonobe, Yasuo Nishijima, Kuniyasu Niizuma, Hiroyuki Sakata, Shigeo Kure, Teiji Tominaga  J Stroke  16-  (2)  65  -72  2014/05  [Not refereed][Not invited]
   

  Published online: May 30, 2014
• もやもや病合併妊娠:移行期医療の現状と問題点

  藤村幹, 林俊哲, 白根礼造, 上之原広司, 冨永悌二  小児の脳神経  39-  (1)  112  2014/04/30  [Not refereed][Not invited]
  
• 第三脳室開窓術後にSIADHによる低ナトリウム血症を呈した1例

  重枝 諒太, 遠藤 英徳, 藤村 幹, 小川 欣一, 清水 宏明, 冨永 悌二  Neurological Surgery  42-  (4)  335  -339  2014/04  [Not refereed][Not invited]
   

  症例は25歳男性で、意識障害、歩行障害を主訴に当院入院となった。入院時、臨床経過および頭部MRI所見より、Shunt不全による水頭症再発と診断し、内視鏡的第三脳室開窓術を施行した。術後、意識レベルは改善し、独歩可能となったが、術後6日目より再び意識レベルの悪化、独歩不可能となり、血液検査所見、体重の推移から、SIADHによる低ナトリウム血症と診断した。水制限を開始したところ、意識レベルは改善し、独歩可能な状態となった。水制限は3日間で終了したが、術後10日目に血清Naは改善し、術後24日目に自宅退院となった。
• 当施設における症候性脳血管攣縮 当院でのくも膜下出血治療方針の転換および開頭術転帰不良因子の検討

  井上 敬, 清水 宏明, 藤村 幹, 遠藤 英徳, 冨永 悌二  脳血管攣縮  29-  1  -3  2014/02  [Not refereed][Not invited]
   

  2003年〜2012年に破裂動脈瘤によるクモ膜下出血に対し、発症72時間以内に開頭クリッピング術またはコイル塞栓術を施行した1066例の成績を報告した。内訳はクリッピング術575例、塞栓術491例で、2007年以降はコイル塞栓術を第一選択とする方針に変更しており、クリッピング術の占める割合は変更前67%、変更後44%であった。転帰良好例(mRS 0〜2)が占める割合は2007年以前71%、以降76%であった。2007年以降の開頭クリッピング術において、転帰良好例は87%であった。症候性脳血管攣縮を来たした症例は22.3%で、永続的神経脱落症状は8.1%に認めた。髄膜炎は9.5%に発症した。入院時WFNS重症例および髄膜炎の発症が転帰不良と関係しており、脳血管攣縮の発症そのものは関連がなかった。
• モヤモヤ病におけるMRAによる前方・後方循環病期分類

  麦倉 俊司, 村田 隆紀, 高橋 昭喜, 藤村 幹  Japanese Journal of Radiology  32-  (Suppl.)  8  -8  2014/02  [Not refereed][Not invited]
  
• クモ膜下出血後脳血流の時間的・空間的変化-3DSRT softwareを用いたSPECT解析

  佐藤健一, 清水宏明, 井上敬, 藤村幹, 冨永悌二  日本脳循環代謝学会総会プログラム・抄録号  26th-  2014
• 外科治療と循環代謝 もやもや病に対する頭蓋外内血行再建術前後の吻合部局所CBF変化と過灌流症候群の関連についての検討

  藤村 幹, 新妻 邦泰, 遠藤 英徳, 井上 敬, 清水 宏明, 冨永 悌二  脳循環代謝  25-  (1)  114  -114  2013/11  [Not refereed][Not invited]
  
• 内頸動脈遮断時の脳血液循環時間と脳血流量の関係について

  佐藤 健一, 清水 宏明, 井上 敬, 藤村 幹, 遠藤 英徳, 冨永 悌二  脳循環代謝  25-  (1)  128  -128  2013/11  [Not refereed][Not invited]
  
• 各種バイパス術における術後急性期の脳循環 手術侵襲による影響との鑑別を含めて

  清水 宏明, 遠藤 英徳, 藤村 幹, 井上 敬, 佐藤 健一, 冨永 悌二  脳循環代謝  25-  (1)  156  -156  2013/11  [Not refereed][Not invited]
  
• 内頸動脈遮断時の脳血液循環時間と脳血流量の関係

  佐藤 健一, 清水 宏明, 藤村 幹, 井上 敬, 松本 康史, 遠藤 英徳, 冨永 悌二  JNET: Journal of Neuroendovascular Therapy  7-  (6)  178  -178  2013/11  [Not refereed][Not invited]
  
• Cerebral Hyperperfusion Syndrome After Superficial Temporal Artery- middle Cerebral Artery Bypass for Severe Intracranial Steno-occlusive Disease: A Case Control Study COMMENT

  Miki Fujimura  NEUROSURGERY  72-  (6)  942  -943  2013/06  [Not refereed][Not invited]
  
• High Flow EC-IC Bypass and Aneurysmal Trapping for Ruptured IC Anterior Wall Aneurysm: Postoperative Evaluation of SPECT and MRI/MRA Findings in the Acute Stage

  藤村幹, 藤村幹, 清水宏明, 井上敬, 木村尚人, 江面正幸, 上之原広司, 冨永悌二  脳卒中の外科  41-  (3)  2013
• 増大した未破裂脳動脈瘤破裂率の検討

  井上敬, 清水宏明, 藤原悟, 上之原広司, 藤村幹, 冨永悌二  日本脳ドック学会総会プログラム・抄録集  22nd-  2013
• 動脈血放射性カウント推定法:定量SPECTへの応用

  井上敬, 藤村幹, 清水宏明, 江面正幸, 上之原広司, 藤原悟, 冨永悌二  脳循環代謝  25-  (1)  2013
• ワルファリン内服下マウス中大脳動脈閉塞モデルにおける,新規血栓溶解薬SMTP-7の治療効果

  伊藤明, 新妻邦泰, 清水宏明, 藤村幹, 冨永悌二  脳循環代謝  25-  (1)  2013
• 出血性椎骨動脈解離に対するinternal coil trappingにおける術後延髄梗塞の転帰への影響

  遠藤 英徳, 松本 康史, 近藤 竜史, 佐藤 健一, 藤村 幹, 井上 敬, 清水 宏明, 藤原 悟, 高橋 明, 冨永 悌二  JNET: Journal of Neuroendovascular Therapy  6-  (5)  207  -207  2012/11  [Not refereed][Not invited]
  
• けいれん発作後経時的イオマゼニール結合能評価

  井上 敬, 清水 宏明, 藤村 幹, 遠藤 英徳, 荻田 庄吾, 藤原 悟, 冨永 悌二  脳循環代謝  24-  (1)  170  -170  2012/11  [Not refereed][Not invited]
  
• CFD解析による脳動脈瘤壁硬化病変予測の可能性

  新妻 邦泰, 杉山 慎一郎, 井上 敬, 遠藤 英徳, 藤村 幹, 佐藤 健一, 清水 宏明, 高橋 明, 冨永 悌二  脳循環代謝  24-  (1)  195  -195  2012/11  [Not refereed][Not invited]
  
• 5. もやもや病の研究課題 : 生理的代償機構とその破綻の解明(PS3-2 虚血性疾患の課題と展望,プレナリーセッション,脳神経外科学の課題,第32回日本脳神経外科コングレス総会)

  藤村 幹, 冨永 悌二  脳神経外科ジャーナル  21-  87  -87  2012/04/20
• Efficacy and Limitation of Prophylactic Blood Pressure Lowering to Avoid Hyperperfusion Syndrome after Revascularization Surgery for Moyamoya Disease

  藤村幹, 清水宏明, 井上敬, 斉藤敦志, 冨永悌二  脳卒中の外科  40-  (2)  2012
• マウス中大脳動脈閉塞モデルにおける梗塞領域再現性向上の工夫と2次元的脳血流リアルタイムモニタリング

  赤松洋祐, 清水宏明, 斉藤敦志, 藤村幹, 冨永悌二  脳循環代謝  24-  (1)  2012
• 60歳以上の高齢発症もやもや病に対する頭蓋外内バイパス術の治療成績

  藤村幹, 清水宏明, 井上敬, 木村尚人, 江面正幸, 上之原広司, 冨永悌二  脳循環代謝  24-  (1)  2012
• Usefulness of Rapid Saturation of Cropidogrel to Non-Cardiogenic Cerebral Infarction - Pilot Study

  Naoto Kimura, Masayuki Ezura, Miki Fujimura, Akira Ito, Misaki Aizawa, Kenichi Tsukita, Koichi Narikawa, Yasushi Suzuki, Hiroshi Uenohara  CEREBROVASCULAR DISEASES  34-  75  -76  2012  [Not refereed][Not invited]
  
• 脳外科術中高感度赤外モニタリングシステム

  荒船龍彦, 鷲尾利克, 鎮西清行, 佐久間一郎, 中川敦寛, 藤村幹, 冨永悌二  第51回日本生体医工学会大会 プログラム・抄録集  177  -178  2012  [Not refereed][Not invited]
  
• Revascularization Surgery for Pediatric Moyamoya Disease : Significance of Peri-operative Management to avoid Surgical Complication

  FUJIMURA Miki, TOMINAGA Teiji  No Shinkei Geka Journal  20-  (11)  802  -808  2011/11/20  

  Background: Moyamoya disease is a chronic occlusive cerebrovascular disease with unknown etiology, which is one of the most common causes of child-onset stroke in Japan. Surgical revascularizations, both direct and indirect procedures, prevent cerebral ischemic attack by improving cerebral blood flow, while neurological deterioration during the acute stage after revascularization is not rare. The objective of this study was to clarify the concept of revascularization surgery for pediatric moyamoya disease while considering the risk of surgical complications in the acute stage. Patients and methods: The present study includes 19 consecutive patients with moyamoya disease aged from 2 to 14 years old (mean 8.5), who underwent superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis with indirect pial synangiosis for 32 affected hemispheres. Single-photon emission computed tomography (SPECT) was performed 1 and 7 days after surgery in all cases to evaluate hemodynamic alteration after surgery. Long-term outcome was evaluated by the neurological status 3 months after surgery, and the underlying pathology of surgical complications in the acute stage was diagnosed based on SPECT and magnetic resonance findings. Results: In 28 of 32 hemispheres (87.5%), patients showed a complete disappearance of ischemic attack, 4 of 32 hemispheres (12.5%) showed a reduction of ischemic attack, while none showed deterioration of their symptoms (0%). Transient focal neurologic deterioration due to cerebral hyperperfusion was evident in 2 patients (6.3%), and was resolved by blood pressure lowering. One patient developed pseudo-laminar necrosis probably due to a thrombosis one week after surgery (3.1%), which did not affect his long-term outcome. Conclusion: STA-MCA anastomosis with pial synangiosis is a safe and effective treatment for pediatric moyamoya disease. Routine cerebral blood flow measurement in the acute stage is essential to avoid surgical complications including both cerebral ischemia and hyperperfusion.
• 亜急性期のPTAが奏功した内頸動脈閉塞症の2例

  高木 英誠, 江面 正幸, 木村 尚人, 藤村 幹, 上之原 広司  JNET: Journal of Neuroendovascular Therapy  5-  (4)  234  -234  2011/11  [Not refereed][Not invited]
  
• ラットくも膜下出血後のacute brain injuryに対するedaravoneの治療効果

  新妻 邦泰, 藤村 幹, 遠藤 英徳, 清水 宏明, Chan Pak H, 冨永 悌二  脳循環代謝  23-  (1)  167  -167  2011/11  [Not refereed][Not invited]
  
• 全ゲノム関連解析による最初のもやもや病遺伝子 RNF213の同定

  鎌田 文顕, 青木 洋子, 成澤 あゆみ, 阿部 裕, 小松崎 匠子, 菅野 潤子, 新堀 哲也, 松原 洋一, 呉 繁夫, 菊池 敦生, 土屋 滋, 藤村 幹, 冨永 悌二, 小野 栄夫, 石井 直人, 大和田 祐二, 真下 陽一, 鈴木 洋一, 羽田 明  日本小児科学会雑誌  115-  (9)  1478  -1478  2011/09  [Not refereed][Not invited]
  
• 【脳血管バイパス術】内頸動脈系閉塞性脳血管病変に対するSTA-MCA bypass術後の急性期画像評価

  遠藤 英徳, 藤村 幹, 井上 敬, 清水 宏明, 冨永 悌二  脳卒中の外科  39-  (3)  163  -168  2011/05  [Not refereed][Not invited]
   

  2008年4月〜2009年12月に浅側頭動脈・中大脳動脈(STA-MCA)吻合術を施行した閉塞性脳血管病変8例(男性7例、女性1例、平均62.3歳)を対象に、内頸動脈系閉塞性脳血管病変に対する術後急性期画像評価の有用性を検討した。全例で術前にXe-SPECTを撮影し、発症急性期に血行再建術を行った1例を除く7例で術前にDiamox負荷Xe-SPECTを施行した。安静時脳血流は8例中6例で低下し、脳循環予備能は7例全例で低下していた。内頸動脈系閉塞性脳血管病変に対するSTA-MCA吻合術は安全かつ有効な治療と考えられた。術後急性期の画像評価により、過灌流の有無、バイパス開存性、虚血性・出血性合併症の有無が早期から把握され、病態把握に基づいた安全な周術期管理が可能になると思われた。
• 3. Revascularization Surgery for Child-onset Moyamoya Disease : Significance of Perioperative Management to Avoid Surgical Complication in the Acute Stage(PS2-3 Problems in Pediatric Neurosurgery,Plenary Session,Professional Spirit and Research Mind of Neurosurgeons,The 31st Annual Meeting of The Japanese Congress of Neurological Surgeons)

  Fujimura Miki  Japanese journal of neurosurgery  20-  76  -76  2011/04/10
• 術後過還流により無症候性脳出血を呈した梗塞・出血混合発症型もやもや病の1例

  伊藤明, 藤村幹, 井上敬, 清水宏明, 冨永悌二  東北脳血管障害研究会学術集会記録集  33rd-  2011
• マウス中大脳動脈閉塞モデルにおける梗塞領域再現性向上の工夫と脳血流リアルタイムモニタリング

  赤松洋祐, 清水宏明, 斉藤敦志, 藤村幹, 冨永悌二  脳循環代謝  23-  (1)  2011
• くも膜下出血発症15日以降の症候性脳血管攣縮16例の検討

  斉藤敦志, 井上敬, 清水宏明, 藤村幹, 冨永悌二  脳循環代謝  23-  (1)  2011
• 脳動脈瘤破裂点の流体力学的特徴:コンピュータ流体解析による検討

  面高俊介, 井上敬, 船本健一, 杉山慎一郎, 藤村幹, 清水宏明, 早瀬敏幸, 高橋明, 冨永悌二  脳循環代謝  23-  (1)  2011
• Posterior Circulation and High Prevalence of Ischemic Stroke among Young Pediatric Patients with Moyamoya Disease: Evidence of Angiography-Based Differences by Age at Diagnosis

  S. Mugikura, S. Higano, R. Shirane, M. Fujimura, Y. Shimanuki, S. Takahashi  AMERICAN JOURNAL OF NEURORADIOLOGY  32-  (1)  192  -198  2011/01  [Not refereed][Not invited]
   

  BACKGROUND AND PURPOSE: At diagnosis, the primary clinical manifestations of pediatric Moyamoya disease are TIA or CSs. CSs are reported to be more prevalent in younger than in older children. We sought to determine whether age-related differences in clinical manifestations are associated with age-related angiographic differences. MATERIALS AND METHODS: We divided 78 patients diagnosed with Moyamoya disease before 16 years of age into four 4-year age groups and examined the relationships between age at diagnosis and clinical manifestations and angiographic and MR imaging findings. RESULTS: Among the 4 diagnostic age groups, in those younger than 4 years of age, the prevalence of CSs and of infarctions on MR images was highest, and along with severity of steno-occlusive lesions of the PCA, the prevalence was significantly higher than that in the next diagnostic age group (4-7 years), though the severity of steno-occlusive lesions in the (CA and the degree of transdural collaterals did not differ significantly. The prevalence of CSs and infarctions did not differ significantly in the 3 oldest diagnostic age groups, whereas ICA and PCA lesions and transdural collaterals correlated positively with diagnostic age. CONCLUSIONS: The high prevalence of CSs and infarctions in patients diagnosed before 4 years of age is associated with advanced steno-occlusive lesions of the PCA. In patients 4 years of age and older at diagnosis, transdural collaterals develop in parallel with advancement of ICA and RCA lesions, which may contribute to the nearly constant prevalence of CSs.
• 類もやもや病に合併した大型中大脳動脈瘤の一手術例

  遠藤 英徳, 藤村 幹, 井上 敬, 藤原 悟, 清水 宏明, 冨永 悌二  東北脳血管障害研究会学術集会記録集  32回-  51  -54  2010/12  [Not refereed][Not invited]
   

  症例は69歳女性で、一過性構音障害で近医にてMRI上異常所見を指摘され当院に入院した。FLAIR及びT2WIで基底槽と左シルビウス裂に沿ったクモ膜下出血と左大脳半球に陳旧性脳梗塞、脳血管撮影では両側内頸動脈終末部近傍に閉塞・狭窄性変化と周囲にもやもや血管の増生、左中大脳動脈分岐部にblebを伴う径14mmの大型嚢状動脈瘤とその近位のM1に高度狭窄、SPECTで左大脳半球の著明な循環予備能低下を認めた。類もやもや病と診断し開頭手術を行った。左前頭側頭開頭で脳表のクモ膜下出血を除去し、シルビウス裂を剥離してM1を遠位に辿り、動脈瘤をclippingした。脳虚血防止にsuperficial temporal artery-middle cerebral artery bypassを行って終了した。術翌日のMRI・MRAで出血性・虚血性合併症は認めず、IMP-SPECTで脳血流量の著明な増加を認め、過灌流予防に厳重な血圧管理を行った。術後3週間で神経脱落症状なく自宅退院した。
• もやもや病における脳血流量の検討

  酒見 紀久子, 小田桐 逸人, 佐藤 多智雄, 児玉 裕康, 南部 武幸, 藤村 幹, 富永 悌二, 梁川 功, 岡田 賢, 福田 寛  核医学技術  30-  (2)  145  -148  2010/04  [Refereed]
   

  もやもや病疾患の初回安静時Diamox負荷時の123I-IMP脳血流SPECT画像を解析ソフトiSSP/SEEを用いて比較検討した。もやもや病と診断した12例を対象とした。初回安静時検査からDiamox負荷検査時までの検査間隔は2〜4日以内で、血行再建術後の1日および7日目にも123I-IMP SPECT撮像を行った。脳血流量値は初回安静時とDiamox負荷時とも対照側に比べて病巣側が有意に低値を示した。Diamox負荷による脳血流量上昇は、病巣側と対照側の脳血流量に差があり、病巣側において上昇が少なかった。再建術後1日目の脳血流量は初回安静時より高値を示したが、7日目では病巣側と対照側の脳血流量は差が認められず、正常状態に戻った。
• 小児もやもや病の治療戦略 小児もやもや病に対するSTA-MCA吻合術の治療成績について 術後急性期脳血流評価による周術期合併症の回避

  藤村 幹, 井上 敬, 遠藤 英徳, 斎藤 敦志, 清水 宏明, 冨永 悌二  小児の脳神経  35-  (2)  181  -181  2010/04  [Not refereed][Not invited]
  
• Untitled Commentary

  Miki Fujimura, Teiji Tominaga  WORLD NEUROSURGERY  73-  (2)  2010/02  [Not refereed][Not invited]
  
• 静脈血採血による定量スペクト

  井上敬, 藤村幹, 清水宏明, 藤原悟, 冨永悌二  脳循環代謝  22-  (1)  2010
• 皮質静脈逆流を伴う硬膜動静脈瘻における脳実質侵襲の評価:拡散強調画像による検討

  佐藤健一, 清水宏明, 藤村幹, 井上敬, 松本康史, 冨永悌二  脳循環代謝  22-  (1)  2010
• 高磁場MRIにより血管形態の変化を詳細に観察し得た前大脳動脈解離による脳梗塞の1例

  佐藤祥一郎, 板橋亮, 矢澤由加子, 古井英介, 藤村幹, 井上敬, 藤原悟  東北脳血管障害研究会学術集会記録集  31st-  63  -66  2009/12/05  [Not refereed][Not invited]
  
• ラット全脳虚血後の遅発性海馬CA1神経細胞死におけるPUMAの役割について

  新妻 邦泰, 藤村 幹, 遠藤 英徳, 斉藤 敦志, 清水 宏明, チャン・パク・フー, 冨永 悌二  脳循環代謝  21-  (1)  115  -115  2009/11  [Not refereed][Not invited]
  
• もやもや病に対するEC-IC bypass術後急性期3D-TOF MRAを用いた症候性過灌流の診断と予測についての検討

  藤村 幹, 麦倉 俊司, 新妻 邦泰, 清水 宏明, 冨永 悌二  脳循環代謝  21-  (1)  138  -138  2009/11  [Not refereed][Not invited]
  
• Comparison between lectin-like oxidized low density lipoprotein receptor 1 expression and preoperative echogenic findings of vulnerable carotid plaque

  A. Saito, M. Fujimura, T. Inoue, H. Shimizu, T. Tominaga  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM  29-  S502  -S503  2009/10  [Not refereed][Not invited]
  
• Mechanism of Primary Blast Injury: Insight from Microexplosive Generated Shock Wave-Induced Brain Injury Animal Model and Engineering Experiments

  Atsuhiro Nakagawa, Miki Fujimura, Hironobu Okuyama, Tokitada Hashimoto, Kaoruko Kato, Mika Watanabe, Kazuyoshi Takayama, Teiji Tominaga  NEUROSURGERY  65-  (2)  413  -414  2009/08  [Not refereed][Not invited]
  
• The Leptomeningeal "Ivy Sign" on Fluid-Attenuated Inversion Recovery MR Imaging in Moyamoya Disease: A Sign of Decreased Cerebral Vascular Reserve?

  N. Mori, S. Mugikura, S. Higano, T. Kaneta, M. Fujimura, A. Umetsu, T. Murata, S. Takahashi  AMERICAN JOURNAL OF NEURORADIOLOGY  30-  (5)  930  -935  2009/05  [Not refereed][Not invited]
   

  BACKGROUND AND PURPOSE: Moyamoya disease is an idiopathic occlusive cerebrovascular disorder with abnormal microvascular proliferation. We investigated the clinical utility of leptomeningeal high signal intensity (ivy sign) sometimes seen on fluid-attenuated inversion recovery images in Moyamoya disease. MATERIALS AND METHODS: We examined the relationship between the degree of the ivy sign and the severity of the ischemic symptoms in 96 hemispheres of 48 patients with Moyamoya disease. We classified each cerebral hemisphere into 4 regions from anterior to posterior. In 192 regions of 24 patients, we examined the relationship between the degree of the ivy sign and findings of single-photon emission CT, including the resting cerebral blood flow (CBF) and cerebral vascular reserve (CVR). RESULTS: The degree of the ivy sign showed a significant positive relationship with the severity of the ischemic symptoms (P < .001). Of the 4 regions, the ivy sign was most frequently and prominently seen in the anterior part of the middle cerebral artery region. The degree of the ivy sign showed a negative relationship with the resting CBF (P < .0034) and a more prominent negative relationship with the CVR (P < .001). CONCLUSIONS: The leptomeningeal ivy sign indicates decreased CVR in Moyamoya disease.
• colloid cystの2例

  李 麗, 麦倉 俊司, 日向野 修一, 梅津 篤司, 村田 隆紀, 高橋 昭喜, 藤村 幹, 冨永 悌二  Japanese Journal of Radiology  27-  (Suppl.)  15  -15  2009/04  [Not refereed][Not invited]
  
• 硬膜動静脈奇形の病態と治療成績:multimodality treatmentにおける外科的治療の役割

  清水宏明, 佐藤健一, 松本康史, 近藤竜史, 井上敬, 藤村幹, 冨永悌二  Journal of Neuroendovascular Therapy  3-  (4)  2009
• 重症くも膜下出血の予後予測における急性期拡散強調画像の有用性

  佐藤健一, 清水宏明, 藤村幹, 井上敬, 松本康史, 冨永悌二  脳循環代謝  21-  (1)  2009
• 重症くも膜下出血の予後予測における急性期拡散強調画像の有用性

  佐藤健一, 清水宏明, 井上敬, 藤村幹, 松本康史, 冨永悌二  日本脳神経外科学会総会抄録集(CD-ROM)  68th-  2009
• 虚血発症頭蓋内内頚動脈解離の診断と治療

  清水宏明, 松本康史, 近藤竜史, 井上敬, 藤村幹, 斉藤敦志, 高橋明, 冨永悌二  日本脳神経外科学会総会抄録集(CD-ROM)  68th-  2009
• 頚動脈プラークに対する新たなdrug delivery systemの試み

  斉藤敦志, 石井竜弘, 清水宏明, 藤村幹, 冨永悌二  日本脳神経外科学会総会抄録集(CD-ROM)  68th-  2009
• ラット全脳虚血後の遅発性海馬CA1神経細胞死におけるPIDDosomeの役割について

  新妻邦泰, 藤村幹, 遠藤英徳, 斉藤敦志, 清水宏明, CHAN PH, 冨永悌二  日本脳神経外科学会総会抄録集(CD-ROM)  68th-  2009
• もやもや病ならびに他の閉塞性脳血管障害に対するEC-IC bypass術後の過灌流と予後についての比較検討

  藤村幹, 清水宏明, 井上敬, 斎藤敦志, 藤原悟, 冨永悌二  日本脳神経外科学会総会抄録集(CD-ROM)  68th-  2009
• Immunoliposomeを用いた頚動脈プラークに対するdrug delivery system

  斉藤敦志, 藤村幹, 清水宏明, 冨永悌二  脳循環代謝  21-  (1)  2009
• 脊髄損傷後の脳機能局在変化とNogo受容体 機能MRIによる検討

  遠藤 俊毅, 藤村 幹, Olson Lars, 冨永 悌二  脊髄外科  22-  (2)  122  -125  2008/12  [Not refereed][Not invited]
  
• もやもや病術後過灌流評価における3D‐SSPの有用性について

  金田朋洋, 高浪健太郎, 吉田さやか, 阿部恵子, 高橋昭喜, 藤村幹, 三田村篤, 細貝良行, 丸岡伸, 福田寛  核医学  45-  (4)  377  -377  2008/11  [Not refereed][Not invited]
  
• チマメないし解離性破裂内頸動脈瘤の治療戦略

  遠藤 英徳, 清水 宏明, 藤村 幹, 井上 敬, 冨永 悌二  日本脳神経外科学会総会CD-ROM抄録集  67回-  2H  -O33  2008/10  [Not refereed][Not invited]
  
• 脳脊髄機能MRIをもちいた脊髄損傷後の脳脊髄可塑性の描出とその意義

  遠藤 俊毅, 藤村 幹, Olson Lars, 冨永 悌二  日本脳神経外科学会総会CD-ROM抄録集  67回-  3J  -10  2008/10  [Not refereed][Not invited]
  
• colloid cystの二例

  李 麗, 麦倉 俊司, 日向野 修一, 梅津 篤司, 村田 隆紀, 高橋 昭喜, 藤村 幹, 冨永 悌二  核医学  45-  (2)  143  -143  2008/05  [Not refereed][Not invited]
  
• モヤモヤ病におけるleptomeningeal ivy signの臨床的意義

  森 菜緒子, 麦倉 俊司, 日向野 修一, 梅津 篤司, 高橋 昭喜, 藤村 幹  Radiation Medicine  26-  (Suppl.I)  9  -9  2008/04  [Not refereed][Not invited]
  
• 脳動脈瘤治療の施設内paradigm shift:短期結果と今後の展望

  清水宏明, 藤村幹, 井上敬, 松本康史, 近藤竜史, 高橋明, 冨永悌二  日本脳神経外科学会総会抄録集(CD-ROM)  67th-  2008
• もやもや病に対するSTA-MCA吻合術の治療成績:急性期合併症と長期成績について

  藤村幹, 清水宏明, 冨永悌二  日本脳神経外科学会総会抄録集(CD-ROM)  67th-  2008
• Medullary streaksを観察し得た急性期脳梗塞の一例

  中川敦寛, 藤村幹, 冨永悌二, 麦倉俊司, 黒田宙, 野村亮介, 篠澤洋太郎  第30回東北脳血管障害研究会学術集会記録集  57  -60  2008  [Not refereed][Not invited]
  
• Commentary

  Teiji Tominaga, Miki Fujimura  Surgical Neurology  68-  (6)  682  2007/12  [Not refereed][Not invited]
  
• くも膜下出血急性期脳損傷 SOD1過剰発現による酸化ストレス減少とAkt/GSK3β生存シグナル活性化の影響

  遠藤 英徳, 藤村 幹, Pak H. Chan, 冨永 悌二  神経外傷  30-  (2)  102  -108  2007/12  [Not refereed][Not invited]
   

  くも膜下出血(SAH)後の急性期脳損傷と酸化ストレスとの関係を解明するため、copper/zinc-superoxide dismutase(SOD1)過剰発現ラットを用いAkt/GSK3β生存シグナル経路に着目して研究を行った。その結果、SOD1過剰発現によってSAH後のスーパーオキシド増加に伴う酸化型ハイドロエチジンの増加と大脳皮質でのアポトーシスが抑制され、SAH 24時間後の死亡率は有意に減少した。また、SAH後の大脳皮質の神経細胞においてAktとGSK3βのリン酸化が促進し、これらはSOD1過剰発現下で持続的に増加した。SOD1の過剰発現は酸化ストレスを軽減し、Akt/GSK3β生存シグナル経路の活性化を介して神経保護作用を発揮することが示された。
• Association of cavernous malformation within vestibular schwannoma: Immunohistochemical analysis of matrix metalloproteinase-2 and-9 - Case report

  Hiroyuki Sakata, Miki Fujimura, Mika Watanabe, Teiji Tominaga  NEUROLOGIA MEDICO-CHIRURGICA  47-  (11)  509  -512  2007/11  [Not refereed][Not invited]
   

  A 65-year-old man presented with a rare case of cavernous malformation with hemorrhage located within vestibular schwannoma. He had suffered hearing impairment for 20 years, and was admitted to our hospital with vertigo and ataxic gait. Neurological examination revealed hearing loss, facial nerve paresis, and left cerebellar ataxia. Magnetic resonance imaging demonstrated a left vestibular schwannoma 35 mm in diameter, as well as a heterogeneous area associated with hypointense rim within the tumor, indicating intraturnoral hemorrhage. Subtotal removal of the tumor together with the fibrously encapsulated hematoma was performed through a left retrosigmoid craniotomy. Histological examination of the surgical specimen revealed cavernous malformation within vestibular schwannoma. Immunohistochernistry for matrix metalloproteinase (MMP)-2 and -9, and tissue inhibitors of metalloproteinase-2 showed strong expression in the endothelial cells of the cavernous malformation, but not in the interstitial structures. His symptoms significantly improved after surgery and he underwent gamma-knife therapy for the residual tumor. Cavernous malformations may show dynamic characteristics such as repeated hemorrhage and de novo formation. MMP-2 and -9, which are implicated in angiogenesis and hemorrhage, may be upregulated in such tumors.
• 甲状腺機能亢進症を合併した(類)もやもや病手術例の検討 周術期管理と術後急性期脳循環動態について

  遠藤 英徳, 藤村 幹, 冨永 悌二  日本脳神経外科学会総会CD-ROM抄録集  66回-  3K  -P55  2007/10  [Not refereed][Not invited]
  
• もやもや病に対する直接血行再建術後急性期の病態について 3-Tesla MRIを用いた検討

  小濱 みさき, 藤村 幹, 麦倉 俊司, 冨永 悌二  日本脳神経外科学会総会CD-ROM抄録集  66回-  3K  -P55  2007/10  [Not refereed][Not invited]
  
• Symptomatic hyperperfusion after superficial temporal artery-middle cerebral artery anastomosis in a child with moyamoya disease

  Miki Fujimura, Tomohiro Kaneta, Hiroaki Shimizu, Teiji Tominaga  CHILDS NERVOUS SYSTEM  23-  (10)  1195  -1198  2007/10  [Not refereed][Not invited]
   

  Object Surgical revascularization for moyamoya disease prevents cerebral ischemic attacks by improving cerebral blood flow (CBF). It is undetermined, however, how rapid increase in CBF affects ischemic brain at acute stage, especially in children. Case report A 4-year-old girl with moyamoya disease underwent right superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis. She suffered temporary left facial palsy 5 days after surgery. Postoperative N-isopropyl-p-[I-123]iodoamphetamine single-photon emission computed tomography (I-123-IMP-SPECT) revealed focal intense increase in CBF at the sites of anastomosis. Magnetic resonance imaging/angiography showed the apparently patent STA-MCA anastomosis as a thick high signal without ischemic changes. Her symptom improved 9 days after surgery, and single-photon emission computed tomography (SPECT) 2 months later showed normalization of CBF. Surgical revascularization completely relieved the transient ischemic attack on her left hand that was seen before surgery. Conclusion We demonstrated, for the first time, that delayed focal neurological deficit after STA-MCA anastomosis can be caused by focal hyperperfusion in childhood moyamoya disease.
• Symptomatic hyperperfusion after superficial temporal artery-middle cerebral artery anastomosis in a child with moyamoya disease

  Miki Fujimura, Tomohiro Kaneta, Hiroaki Shimizu, Teiji Tominaga  CHILDS NERVOUS SYSTEM  23-  (10)  1195  -1198  2007/10  [Not refereed][Not invited]
   

  Object Surgical revascularization for moyamoya disease prevents cerebral ischemic attacks by improving cerebral blood flow (CBF). It is undetermined, however, how rapid increase in CBF affects ischemic brain at acute stage, especially in children. Case report A 4-year-old girl with moyamoya disease underwent right superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis. She suffered temporary left facial palsy 5 days after surgery. Postoperative N-isopropyl-p-[I-123]iodoamphetamine single-photon emission computed tomography (I-123-IMP-SPECT) revealed focal intense increase in CBF at the sites of anastomosis. Magnetic resonance imaging/angiography showed the apparently patent STA-MCA anastomosis as a thick high signal without ischemic changes. Her symptom improved 9 days after surgery, and single-photon emission computed tomography (SPECT) 2 months later showed normalization of CBF. Surgical revascularization completely relieved the transient ischemic attack on her left hand that was seen before surgery. Conclusion We demonstrated, for the first time, that delayed focal neurological deficit after STA-MCA anastomosis can be caused by focal hyperperfusion in childhood moyamoya disease.
• 36 幼児期に発症した頭蓋頚椎移行部のNeuroenteric cystの1手術例(北日本脳神経外科連合会第30回学術集会)

  坂田 洋之, 藤村 幹, 岩崎 真樹, 冨永 悌二  新潟医学会雑誌  121-  (4)  224  -225  2007/04
• Pressure-dependent effect of shock waves on rat brain: induction of neuronal apoptosis mediated by a caspase-dependent pathway

  Kaoruko Kato, Miki Fujimura, Atsuhiro Nakagawa, Atsushi Saito, Tomohiro Ohki, Kazuyoshi Takayama, Teiji Tominaga  JOURNAL OF NEUROSURGERY  106-  (4)  667  -676  2007/04  [Not refereed][Not invited]
   

  Object. Shock waves have been experimentally applied to various neurosurgical treatments including fragmentation of cerebral emboli, perforation of cyst walls or tissue, and delivery of drugs into cells. Nevertheless, the application of shock waves to clinical neurosurgery remains challenging because the threshold for shock wave-induced brain injury has not been determined. The authors investigated the pressure-dependent effect of shock waves on histological changes of rat brain, focusing especially on apoptosis. Methods. Adult male rats were exposed to a single shot of shock waves (produced by silver azide explosion) at over-pressures of 1 or 10 MPa after craniotomy. Histological changes were evaluated sequentially by H & E staining and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL). The expression of active caspase-3 and the effect of the nonselective caspase inhibitor N-benzyloxyc irbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK) were examined to evaluate the contribution of a caspase-dependent pathway to shock wave-induced brain injury. High-overpressure (> 10 MPa) shock wave exposure resulted in contusional hemorrhage associated with a significant increase in TUNEL-positive neurons exhibiting chromatin condensation, nuclear segmentation, and apoptotic bodies. The maximum increase was seen at 24 hours after shock wave application. Low-overpressure (I MPa) shock wave exposure resulted in spindle-shaped changes in neurons and elongation of nuclei without marked neuronal injury. The administration of Z-VAD-PAK significantly reduced the number of TUNEL-positive cells observed 24 hours after high-overpressure shock wave exposure (p < 0.01). A significant increase in the cytosolic expression of active caspase-3 was evident 24 hours after high-overpressure shock wave application; this increase was prevented by Z-VAD-FMK administration. Double immunofluorescence staining showed that TUNEL-positive cells were exclusively neurons. Conclusions. The threshold for shock wave-induced brain injury is speculated to be under 1 MPa, a level that is lower than the threshold for other organs. High-overpressure shock wave exposure results in brain injury, including neuronal apoptosis mediated by a caspase-dependent pathway. This is the first report in which the pressure-dependent effect of shock wave on the histological characteristics of brain tissue is demonstrated.
• Pressure-dependent effect of shock waves on rat brain: induction of neuronal apoptosis mediated by a caspase-dependent pathway

  Kaoruko Kato, Miki Fujimura, Atsuhiro Nakagawa, Atsushi Saito, Tomohiro Ohki, Kazuyoshi Takayama, Teiji Tominaga  JOURNAL OF NEUROSURGERY  106-  (4)  667  -676  2007/04  [Not refereed][Not invited]
   

  Object. Shock waves have been experimentally applied to various neurosurgical treatments including fragmentation of cerebral emboli, perforation of cyst walls or tissue, and delivery of drugs into cells. Nevertheless, the application of shock waves to clinical neurosurgery remains challenging because the threshold for shock wave-induced brain injury has not been determined. The authors investigated the pressure-dependent effect of shock waves on histological changes of rat brain, focusing especially on apoptosis. Methods. Adult male rats were exposed to a single shot of shock waves (produced by silver azide explosion) at over-pressures of 1 or 10 MPa after craniotomy. Histological changes were evaluated sequentially by H & E staining and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL). The expression of active caspase-3 and the effect of the nonselective caspase inhibitor N-benzyloxyc irbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK) were examined to evaluate the contribution of a caspase-dependent pathway to shock wave-induced brain injury. High-overpressure (> 10 MPa) shock wave exposure resulted in contusional hemorrhage associated with a significant increase in TUNEL-positive neurons exhibiting chromatin condensation, nuclear segmentation, and apoptotic bodies. The maximum increase was seen at 24 hours after shock wave application. Low-overpressure (I MPa) shock wave exposure resulted in spindle-shaped changes in neurons and elongation of nuclei without marked neuronal injury. The administration of Z-VAD-PAK significantly reduced the number of TUNEL-positive cells observed 24 hours after high-overpressure shock wave exposure (p < 0.01). A significant increase in the cytosolic expression of active caspase-3 was evident 24 hours after high-overpressure shock wave application; this increase was prevented by Z-VAD-FMK administration. Double immunofluorescence staining showed that TUNEL-positive cells were exclusively neurons. Conclusions. The threshold for shock wave-induced brain injury is speculated to be under 1 MPa, a level that is lower than the threshold for other organs. High-overpressure shock wave exposure results in brain injury, including neuronal apoptosis mediated by a caspase-dependent pathway. This is the first report in which the pressure-dependent effect of shock wave on the histological characteristics of brain tissue is demonstrated.
• くも膜下出血急性期脳損傷 SOD1過剰発現による酸化ストレス減少とAkt/GSK3β生存シグナル活性化の影響

  遠藤 英徳, 藤村 幹, チャン・パク, 冨永 悌二  日本神経外傷学会プログラム・抄録集  30回-  67  -67  2007/03  [Not refereed][Not invited]
  
• Temporary neurologic deterioration due to cerebral hyperperfusion after superficial temporal artery-middle cerebral artery anastomosis in patients with adult-onset moyamoya disease

  Miki Fujimura, Tomohiro Kaneta, Shunji Mugikura, Hiroaki Shimizu, Teiji Tominaga  SURGICAL NEUROLOGY  67-  (3)  273  -282  2007/03  [Not refereed][Not invited]
   

  Background: Surgical revascularization for moyamoya disease prevents cerebral ischemic attacks by improving CBF, but little is known about the change in CBF and its effect on neurologic status during the acute stage after revascularization. Methods: I-123-IMP-SPECT was performed 1 and 7 days after STA-MCA anastomosis on 34 sides of 27 consecutive patients with adult-onset moyamoya disease (6 men, 21 women; 22-62 years old). The follow-up period ranged from 5 to 28 months (mean, 17.6 months). Results: Thirteen patients (13 sides, 38.2%) suffered temporary neurologic deterioration due to hyperperfusion several days after surgery, which was sustained for several days (7.4 days in average). Postoperative magnetic resonance imaging/angiography showed the STA as a higher intensity signal than the preoperative finding without ischemic changes in all 13 patients. Postoperative SPECT revealed focal intense increase in CBF at the sites of anastomosis in all 13 patients. Eleven patients (32.4%) had transient focal neurologic deficit mimicking ischemic attack. Two patients (5.9%) had cerebral hyperperfusion syndrome associated with subarachnoid hemorrhage extending to the ipsilateral sylvian cistern. Symptoms were relieved by intensive blood pressure control, and no patients had permanent neurologic deficit or delayed neurologic deterioration during the follow-up period. Conclusions: Surgical revascularization including STA-MCA anastomosis is a safe and effective treatment for moyamoya disease, although temporary neurologic deterioration due to hyperperfusion could occur at a substantial rate. Routine CBF measurement is recommended for accurate diagnosis of postoperative hyperperfusion in moyamoya disease because its treatment is contradictory to that for ischemia. (c) 2007 Elsevier Inc. All rights reserved.
• Temporary neurologic deterioration due to cerebral hyperperfusion after superficial temporal artery-middle cerebral artery anastomosis in patients with adult-onset moyamoya disease

  Miki Fujimura, Tomohiro Kaneta, Shunji Mugikura, Hiroaki Shimizu, Teiji Tominaga  SURGICAL NEUROLOGY  67-  (3)  273  -282  2007/03  [Not refereed][Not invited]
   

  Background: Surgical revascularization for moyamoya disease prevents cerebral ischemic attacks by improving CBF, but little is known about the change in CBF and its effect on neurologic status during the acute stage after revascularization. Methods: I-123-IMP-SPECT was performed 1 and 7 days after STA-MCA anastomosis on 34 sides of 27 consecutive patients with adult-onset moyamoya disease (6 men, 21 women; 22-62 years old). The follow-up period ranged from 5 to 28 months (mean, 17.6 months). Results: Thirteen patients (13 sides, 38.2%) suffered temporary neurologic deterioration due to hyperperfusion several days after surgery, which was sustained for several days (7.4 days in average). Postoperative magnetic resonance imaging/angiography showed the STA as a higher intensity signal than the preoperative finding without ischemic changes in all 13 patients. Postoperative SPECT revealed focal intense increase in CBF at the sites of anastomosis in all 13 patients. Eleven patients (32.4%) had transient focal neurologic deficit mimicking ischemic attack. Two patients (5.9%) had cerebral hyperperfusion syndrome associated with subarachnoid hemorrhage extending to the ipsilateral sylvian cistern. Symptoms were relieved by intensive blood pressure control, and no patients had permanent neurologic deficit or delayed neurologic deterioration during the follow-up period. Conclusions: Surgical revascularization including STA-MCA anastomosis is a safe and effective treatment for moyamoya disease, although temporary neurologic deterioration due to hyperperfusion could occur at a substantial rate. Routine CBF measurement is recommended for accurate diagnosis of postoperative hyperperfusion in moyamoya disease because its treatment is contradictory to that for ischemia. (c) 2007 Elsevier Inc. All rights reserved.
• Expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) in cerebral cavernous malformations: immunohistochemical analysis of MMP-2,-9 and TIMP-2

  M. Fujimura, M. Watanabe, H. Shimizu, T. Tominaga  ACTA NEUROCHIRURGICA  149-  (2)  179  -183  2007/02  [Not refereed][Not invited]
   

  Object. Hemorrhage from cerebral vascular malformations such as cerebral cavernous malformation (CCM) can result in significant mortality and morbidity, but its underlying mechanism is undetermined. Excessive degradation of the vascular matrix by matrix metalloproteinases (MMPs), proteolytic enzymes that degrade all the components of extracellular matrix, can lead to instability of the vascular structure and can thereby cause bleeding. Thus we examined the expression of MMPs and tissue inhibitors of metalloproteinase (TIMP) in CCM. Patients and methods. We performed immunohistochemistry for MMP-2, -9, and TIMP-2 using Paraffin-embedded sections of the surgical specimens obtained from seven patients with CCM. All patients had a history of hemorrhage from CCM. Findings. In all patients (7/7, 100%), MMP-2 and -9 were strongly expressed in endothelial cells of CCMs. Endothelial expression of TIMP-2 was also evident in all seven patients. In contrast, MMP-2, -9 and TIMP-2 were not identified in adjacent normal brain tissue. Conclusion. We found that CCM showed the increased endothelial expression of MMP-2, -9, and TIMP-2. Endothelial expression of MMPs and/or TIMP may affect the vascular matrix stability, and thus can contribute to hemorrhage from CCM.
• Expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) in cerebral cavernous malformations: immunohistochemical analysis of MMP-2,-9 and TIMP-2

  M. Fujimura, M. Watanabe, H. Shimizu, T. Tominaga  ACTA NEUROCHIRURGICA  149-  (2)  179  -183  2007/02  [Not refereed][Not invited]
   

  Object. Hemorrhage from cerebral vascular malformations such as cerebral cavernous malformation (CCM) can result in significant mortality and morbidity, but its underlying mechanism is undetermined. Excessive degradation of the vascular matrix by matrix metalloproteinases (MMPs), proteolytic enzymes that degrade all the components of extracellular matrix, can lead to instability of the vascular structure and can thereby cause bleeding. Thus we examined the expression of MMPs and tissue inhibitors of metalloproteinase (TIMP) in CCM. Patients and methods. We performed immunohistochemistry for MMP-2, -9, and TIMP-2 using Paraffin-embedded sections of the surgical specimens obtained from seven patients with CCM. All patients had a history of hemorrhage from CCM. Findings. In all patients (7/7, 100%), MMP-2 and -9 were strongly expressed in endothelial cells of CCMs. Endothelial expression of TIMP-2 was also evident in all seven patients. In contrast, MMP-2, -9 and TIMP-2 were not identified in adjacent normal brain tissue. Conclusion. We found that CCM showed the increased endothelial expression of MMP-2, -9, and TIMP-2. Endothelial expression of MMPs and/or TIMP may affect the vascular matrix stability, and thus can contribute to hemorrhage from CCM.
• 感度波長域7-14μmの赤外線画像開頭術中モニタリング:適応と術中~術後急性期管理における臨床的意義

  中川敦寛, 藤村幹, 荒船龍彦, 山口喬弘, 清水宏明, 佐久間一郎, 冨永悌二  日本脳神経外科学会総会抄録集(CD-ROM)  66th-  2007
• もやもや病に対するSTA-MCA吻合術後・症候性過灌流とその関連因子についての検討

  藤村幹, 清水宏明, 冨永悌二  脳循環代謝  19-  (2)  2007
• もやもや病に対するSTA-MCA吻合術後・症候性過灌流とその関連因子についての検討

  藤村幹, 清水宏明, 冨永悌二  日本脳神経外科学会総会抄録集(CD-ROM)  66th-  2007
• 赤外線画像システムIRIS Vを用いたもやもや病血行再建術中脳表モニタリング:術後経過との相関に関する検討

  中川敦寛, 藤村幹, 清水宏明, 高山和喜, 冨永悌二  新潟医学会雑誌  121-  (4)  2007
• Malignant transformation of high-grade astrocytoma associated with neurocysticercosis in a patient with Turcot syndrome

  Kuniyasu Niizuma, Miki Fujimura, Toshihiro Kumabe, Tominaga Tominaga  JOURNAL OF CLINICAL NEUROSCIENCE  14-  (1)  53  -55  2007/01  [Not refereed][Not invited]
   

  A 45-year-old woman with anaplastic astrocytoma was clinically diagnosed with Turcot syndrome, and subsequently developed simultaneous neurocysticercosis and malignant transformation to glioblastoma. The parasitic cysts and glioblastoma were microsurgically removed. Histological examination of surgical specimens revealed neurocysticercosis between the normal brain tissue and glioblastoma. The clinical course and histological findings suggest that the parasitic infection and/or genetic changes contributed to the malignant transformation of the astrocytic tumour. (C) 2006 Published by Elsevier Ltd.
• Prediction of Postoperative Cerebral Hyperperfusion in Patients with Moyamoya Disease by Intraoperative Monitoring of Cerebral Hemodynamics Using IRIS-V Infrared Imaging System: Two Case Report

  NAKAGAWA Atsuhiro, FUJIMURA Miki, SUZUKI Hideaki, OHKI Tomohiro, TAKAYAMA Kazuyoshi, TOMINAGA Teiji  Nosotchu no Geka Kenkyukai koenshu  35-  (2)  136  -141  2007  [Not refereed][Not invited]
   

  Surgical revascularization for moyamoya disease prevents cerebral ischemic attacks by improving cerebral blood flow (CBF). But little is known about the change in intraoperative cerebral hemodynamics and its effect on postoperative neurological status, including symptomatic cerebral hyperperfusion. To address this issue, we applied a novel infrared imaging system (IRIS-V infrared imaging system) for intraoperative monitoring of surface hemodynamics in 2 patients with moyamoya disease. We investigated the correlation between clinical, radiological findings, and changes of the gradation value in infrared imaging using imaging software. The camera showed apparent revascularization during surgery in both cases. In case 1, a 36-year-old male who presented with transient ischemic attack (TIA) underwent superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis with pial synangiosis. His cerebrovascular reactivity was significantly compromised as shown by preoperative IMP-SPECT. Intraoperative infrared imaging disclosed an increase in brain surface temperature due to increase in blood flow around the anastomosis. The gradation value gradually increased after recanalization of bypass during several minutes. Postoperative IMP-SPECT showed a focal increase in CBF around the site of anastomosis 1 day after surgery. Beginning on the next day, he suffered fluctuated aphasia, numbness and fine movement disturbance on his right hand for 7 days. Intensive blood pressure control relieved his symptoms, and he was discharged without neurological deficit. The anatomical location and the temporal profile of hyperperfusion accorded with the neurological deficits.
  In case 2, a 29-year-old female who presented with TIA had already undergone surgical revascularization on the symptomatic right side. Then she underwent left STA-MCA anastomosis on the asymptomatic side with decreased cerebrovascular reserve capacity. Intraoperative infrared imaging disclosed no significant increase in brain surface color around the site of anastomosis except for the apparent revascularization through STA-MCA bypass. The gradation value did change significantly before or after recanalization of bypass. Postoperative IMP-SPECT showed a mild increase in CBF on the entire MCA territory without focal intense accumulation. Her postoperative course was uneventful, and she was discharged without neurological deterioration.
  Characteristic patterns of the intraoperative cerebral hemodynamics as delineated by IRIS-V may be the optimal predictor for postoperative transient symptomatic hyperperfusion after direct bypass in patients with moyamoya disease.
  
• 脳虚血後の遅発性海馬CA1神経細胞死におけるp53の役割について

  遠藤英徳, 藤村幹, チャンパク, 冨永悌二  脳卒中  29-  (2)  385  -385  2007  [Not refereed][Not invited]
  
• もやもや病周術期における痙攣と血行再建術後急性期の脳循環動態との関連について

  成澤あゆみ, 藤村幹, 清水宏明, 冨永悌二  Neurological Surgery  35-  (5)  467  -474  2007  [Not refereed][Not invited]
  
• Malignant transformation of high-grade astrocytoma associated with neurocysticercosis in a patient with Turcot syndrome

  Kuniyasu Niizuma, Miki Fujimura, Toshihiro Kumabe, Tominaga Tominaga  JOURNAL OF CLINICAL NEUROSCIENCE  14-  (1)  53  -55  2007/01  [Not refereed][Not invited]
   

  A 45-year-old woman with anaplastic astrocytoma was clinically diagnosed with Turcot syndrome, and subsequently developed simultaneous neurocysticercosis and malignant transformation to glioblastoma. The parasitic cysts and glioblastoma were microsurgically removed. Histological examination of surgical specimens revealed neurocysticercosis between the normal brain tissue and glioblastoma. The clinical course and histological findings suggest that the parasitic infection and/or genetic changes contributed to the malignant transformation of the astrocytic tumour. (C) 2006 Published by Elsevier Ltd.
• 高感度赤外線画像システムIRIS-Vを用いたもやもや病術中血行動態モニタリングによる術後過灌流の予測 2症例の検討

  中川敦寛, 藤村幹, 鈴木秀明, 大木友博, 高山和喜, 冨永悌二  脳卒中の外科  35-  (2)  136  -141  2007  [Not refereed][Not invited]
   

  Surgical revascularization for moyamoya disease prevents cerebral ischemic attacks by improving cerebral blood flow (CBF). But little is known about the change in intraoperative cerebral hemodynamics and its effect on postoperative neurological status, including symptomatic cerebral hyperperfusion. To address this issue, we applied a novel infrared imaging system (IRIS-V infrared imaging system) for intraoperative monitoring of surface hemodynamics in 2 patients with moyamoya disease. We investigated the correlation between clinical, radiological findings, and changes of the gradation value in infrared imaging using imaging software. The camera showed apparent revascularization during surgery in both cases. In case 1, a 36-year-old male who presented with transient ischemic attack (TIA) underwent superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis with pial synangiosis. His cerebrovascular reactivity was significantly compromised as shown by preoperative IMP-SPECT. Intraoperative infrared imaging disclosed an increase in brain surface temperature due to increase in blood flow around the anastomosis. The gradation value gradually increased after recanalization of bypass during several minutes. Postoperative IMP-SPECT showed a focal increase in CBF around the site of anastomosis 1 day after surgery. Beginning on the next day, he suffered fluctuated aphasia, numbness and fine movement disturbance on his right hand for 7 days. Intensive blood pressure control relieved his symptoms, and he was discharged without neurological deficit. The anatomical location and the temporal profile of hyperperfusion accorded with the neurological deficits.
  In case 2, a 29-year-old female who presented with TIA had already undergone surgical revascularization on the symptomatic right side. Then she underwent left STA-MCA anastomosis on the asymptomatic side with decreased cerebrovascular reserve capacity. Intraoperative infrared imaging disclosed no significant increase in brain surface color around the site of anastomosis except for the apparent revascularization through STA-MCA bypass. The gradation value did change significantly before or after recanalization of bypass. Postoperative IMP-SPECT showed a mild increase in CBF on the entire MCA territory without focal intense accumulation. Her postoperative course was uneventful, and she was discharged without neurological deterioration.
  Characteristic patterns of the intraoperative cerebral hemodynamics as delineated by IRIS-V may be the optimal predictor for postoperative transient symptomatic hyperperfusion after direct bypass in patients with moyamoya disease.
  
• 脳虚血後の遅発性海馬CA1神経細胞死におけるp53の役割について

  遠藤英徳, 藤村幹, チャンパク, 冨永悌二  脳卒中  29-  (2)  385  -385  2007  [Not refereed][Not invited]
  
• もやもや病周術期における痙攣と血行再建術後急性期の脳循環動態との関連について

  成澤あゆみ, 藤村幹, 清水宏明, 冨永悌二  Neurological Surgery  35-  (5)  467  -474  2007  [Not refereed][Not invited]
  
• Association of cavernous malformation within vestibular schwannoma: immunohistochemical analysis of matrix metalloproteinase-2 and -9.

  Sakata Hiroyuki, Fujimura Miki, Watanabe Mika, Tominaga Teiji  Neurol Med Chir (Tokyo)  47-  (11)  509  -512  2007  [Not refereed][Not invited]
  
• Surgical treatment of paraventricular cavernous angioma: Fibre tracking for visualizing the corticospinal tract and determining surgical approach

  Kuniyasu Niizuma, Miki Fujimura, Toshihiro Kumabe, Shuichi Higano, Teiji Tominaga  JOURNAL OF CLINICAL NEUROSCIENCE  13-  (10)  1028  -1032  2006/12  [Not refereed][Not invited]
   

  Surgical treatment of deep-seated lesions involving the corticospinal tract is one of the most challenging areas of contemporary neurosurgery, even given the recent development of radiological methods including three-dimensional anisotropy contrast magnetic resonance imaging (MRI) axonography. Fibre tracking using diffusion tensor imaging is another MRI technique that can be used to visualize anisotropy and the orientation of white matter tracts in the brain. We report herein a patient with a paraventricular cavernous angioma manifesting as hemiparesis caused by haemorrhage. Preoperative conventional MRI failed to determine the anatomical relationship between the paraventricular lesion and the corticospinal tract, whereas fibre tracking using free software (dTV for MR-DTI analysis) indicated that the corticospinal tract was displaced anterolaterally from the medial side. The paraventricular lesion was completely removed without damaging the corticospinal tract using a transcortical transventricular approach. Preoperative fibre tracking is useful in surgical planning for procedures involving deep-seated lesions adjacent to the corticospinal tract, and may avoid postoperative morbidity due to corticospinal tract injury. (c) 2006 Elsevier Ltd. All rights reserved.
• くも膜下出血急性期脳損傷 SOD1過剰発現による酸化ストレス減少とAkt/GSK3β生存シグナル活性化の影響

  遠藤 英徳, 藤村 幹, チャン・パク, 冨永 悌二  脳循環代謝  18-  (3)  110  -110  2006/11  [Not refereed][Not invited]
  
• もやもや病に対する血行再建術前後の脳循環と臨床像:SPECT・脳灌流MRIと術中赤外線画像装置による検討

  藤村幹, 成澤あゆみ, 中川敦寛, 清水宏明, 冨永悌二  脳循環代謝  18-  (3)  2006
• モヤモヤ病血行再建術後の痙攣:術後局所過灌流との関連について

  成澤あゆみ, 藤村幹, 清水宏明, 冨永悌二  日本脳神経外科学会総会抄録集(CD-ROM)  65th-  2006
• モヤモヤ病に対する血行再建術前後の脳循環と臨床像:SPECT・PWIと術中赤外線画像装置による検討

  藤村幹, 麦倉俊司, 金田朋洋, 中川敦寛, 清水宏明, 冨永悌二  日本脳神経外科学会総会抄録集(CD-ROM)  65th-  2006
• もやもや病に対するSTA-MCA吻合術後・過灌流と一過性神経脱落症状について：IMP SPECTを用いた検討

  藤村幹, 清水宏明, 冨永悌二  脳卒中の外科  34-  (1)  37  -41  2006  [Not refereed][Not invited]
  
• 脳虚血後の細胞死調節因子IAP family proteinの反応経路について

  斉藤敦志, 藤村幹, 冨永悌二  脳循環代謝  18-  (1)  26  -26  2006  [Not refereed][Not invited]
  
• 定型的画像所見を呈さなかった両側基底核部および大脳半球白質に浸潤する中枢神経系hCG産生胚腫による思春期早発症の1例

  杉山慎一郎, 隈部俊宏, 三野正樹, 藤村幹, 藤原幾磨, 冨永悌二  Neurological Surgery  34-  (6)  619  -624  2006  [Not refereed][Not invited]
  
• もやもや病に対する血行再建術後急性期の臨床像と脳循環動態 脳灌流MRIを用いた検討

  藤村幹, 麦倉俊司, 清水宏明, 冨永悌二  Neurological Surgery  34-  (8)  801  -809  2006  [Not refereed][Not invited]
  
• 高感度赤外線画像システムIRIS Vを用いたもやもや病術中血行動態モニタリング

  中川敦寛, 藤村幹, 大木友博, 鈴木秀明, 高山和喜, 冨永悌二  Neurological Surgery  34-  (10)  1017  -1025  2006  [Not refereed][Not invited]
  
• 【インターベンション時代の脳卒中学(改訂第2版) 超急性期から再発予防まで】 脳血管障害各論 脳血管奇形 海綿状血管腫 (日本臨床)

  藤村幹, 冨永悌二  日本臨床  64-  (増刊8 インターベンション時代の脳卒中学(下))  691  -694  2006  [Not refereed][Not invited]
  
• 【インターベンション時代の脳卒中学(改訂第2版) 超急性期から再発予防まで】 脳血管障害各論 くも膜下出血と脳動脈瘤 脳血管攣縮 DINDの発生機序と予防および治療 (日本臨床)

  冨永悌二, 藤村幹  日本臨床  64-  (増刊8 インターベンション時代の脳卒中学(下))  650  -653  2006  [Not refereed][Not invited]
  
• Transient focal neurological deficit due to hyperperfusion after superficial temporal middle cerebral artery anastomosis in patients with moyamoya disease

  Miki Fujimura, Hiroaki Shimizu, Teiji, Tominaga  Surgery for Cerebral Stroke  34-  (1)  37  -41  2006  [Not refereed][Not invited]
  
• 脳虚血後の細胞死調節因子IAP family proteinの反応経路について

  斉藤敦志, 藤村幹, 冨永悌二  脳循環代謝  18-  (1)  26  -26  2006  [Not refereed][Not invited]
  
• 定型的画像所見を呈さなかった両側基底核部および大脳半球白質に浸潤する中枢神経系hCG産生胚腫による思春期早発症の1例

  杉山慎一郎, 隈部俊宏, 三野正樹, 藤村幹, 藤原幾磨, 冨永悌二  Neurological Surgery  34-  (6)  619  -624  2006  [Not refereed][Not invited]
  
• もやもや病に対する血行再建術後急性期の臨床像と脳循環動態 脳灌流MRIを用いた検討

  藤村幹, 麦倉俊司, 清水宏明, 冨永悌二  Neurological Surgery  34-  (8)  801  -809  2006  [Not refereed][Not invited]
  
• 高感度赤外線画像システムIRIS Vを用いたもやもや病術中血行動態モニタリング

  中川敦寛, 藤村幹, 大木友博, 鈴木秀明, 高山和喜, 冨永悌二  Neurological Surgery  34-  (10)  1017  -1025  2006  [Not refereed][Not invited]
  
• 【インターベンション時代の脳卒中学(改訂第2版) 超急性期から再発予防まで】 脳血管障害各論 脳血管奇形 海綿状血管腫 (日本臨床)

  藤村幹, 冨永悌二  日本臨床  64-  (増刊8 インターベンション時代の脳卒中学(下))  691  -694  2006  [Not refereed][Not invited]
  
• 【インターベンション時代の脳卒中学(改訂第2版) 超急性期から再発予防まで】 脳血管障害各論 くも膜下出血と脳動脈瘤 脳血管攣縮 DINDの発生機序と予防および治療 (日本臨床)

  冨永悌二, 藤村幹  日本臨床  64-  (増刊8 インターベンション時代の脳卒中学(下))  650  -653  2006  [Not refereed][Not invited]
  
• Surgical treatment of paraventricular cavernous angioma: fibre tracking for visualizing the corticospinal tract and determining surgical approach.

  Niizuma Kuniyasu, Fujimura Miki, Kumabe Toshihiro, Higano Shuichi, Tominaga Teiji  J Clin Neurosci  13-  (10)  1028  -1032  2006  [Not refereed][Not invited]
  
• Delayed lymphocytic infundibuloneurohypo-physitis following successful transsphenoidal treatment of Cushing's disease

  T Kawaguchi, H Ikeda, M Fujimura, T Yoshimoto, T Tominaga  JOURNAL OF CLINICAL NEUROSCIENCE  12-  (3)  320  -323  2005/04  [Not refereed][Not invited]
   

  Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan Lymphocytic infundibuloneurohypophysitis is a rare disorder in which neurohypophyseal function is impaired by an autoimmune process. Although several etiologies for this rare entity have been suggested, its occurrence following transsphenoidal adenomectomy has not been reported. A 20-year-old man presented with diabetes insipidus - seven years after successful transsphenoidal microadenomectomy for Cushing's disease, first diagnosed at the age of 13. Seven years later, he developed fairly rapid onset of polydipsia and polyuria. Magnetic resonance imaging demonstrated swelling of the posterior pituitary gland with thickening of the pituitary stalk. Endocrinological evaluation revealed neurohypophyseal dysfunction without the adenohypophysis being affected. On the basis of these findings, a diagnosis of lymphocytic infundibuloneurohypophysitis was made. The mass lesion of the posterior pituitary resolved after the administration of corticosteroids for two months and no operation was required. Lymphocytic infundibuloneurohypophysitis should be considered in the differential diagnosis of pituitary mass lesions following transsphenoidal surgery, especially when the mass is confined to the posterior pituitary gland with neurohypophyseal function being compromised. (c) 2004 Elsevier Ltd. All rights reserved.
• Ectopic recurrence of craniopharyngioma

  T Kawaguchi, M Fujimura, R Shirane, T Shoji, M Watanabe, T Tominaga  JOURNAL OF CLINICAL NEUROSCIENCE  12-  (3)  307  -309  2005/04  [Not refereed][Not invited]
   

  50-year-old woman first presented with recurrent craniopharyngioma in the suprasellar region. The recurrent tumor was removed via the frontobasal interhemispheric approach. Two years later, magnetic resonance imaging revealed a further recurrence in the primary suprasellar region and a cystic mass with ring enhancement on the surface of the left frontal lobe. Both lesions were removed via the frontobasal interhemispheric approach. Histological examination showed the left frontal lesion was an ectopic recurrence of craniopharyngioma. Ectopic recurrence of craniopharyngioma is extremely rare. (c) 2004 Elsevier Ltd. All rights reserved.
• Delayed lymphocytic infundibuloneurohypo-physitis following successful transsphenoidal treatment of Cushing's disease

  T Kawaguchi, H Ikeda, M Fujimura, T Yoshimoto, T Tominaga  JOURNAL OF CLINICAL NEUROSCIENCE  12-  (3)  320  -323  2005/04  [Not refereed][Not invited]
   

  Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan Lymphocytic infundibuloneurohypophysitis is a rare disorder in which neurohypophyseal function is impaired by an autoimmune process. Although several etiologies for this rare entity have been suggested, its occurrence following transsphenoidal adenomectomy has not been reported. A 20-year-old man presented with diabetes insipidus - seven years after successful transsphenoidal microadenomectomy for Cushing's disease, first diagnosed at the age of 13. Seven years later, he developed fairly rapid onset of polydipsia and polyuria. Magnetic resonance imaging demonstrated swelling of the posterior pituitary gland with thickening of the pituitary stalk. Endocrinological evaluation revealed neurohypophyseal dysfunction without the adenohypophysis being affected. On the basis of these findings, a diagnosis of lymphocytic infundibuloneurohypophysitis was made. The mass lesion of the posterior pituitary resolved after the administration of corticosteroids for two months and no operation was required. Lymphocytic infundibuloneurohypophysitis should be considered in the differential diagnosis of pituitary mass lesions following transsphenoidal surgery, especially when the mass is confined to the posterior pituitary gland with neurohypophyseal function being compromised. (c) 2004 Elsevier Ltd. All rights reserved.
• Ectopic recurrence of craniopharyngioma

  T Kawaguchi, M Fujimura, R Shirane, T Shoji, M Watanabe, T Tominaga  JOURNAL OF CLINICAL NEUROSCIENCE  12-  (3)  307  -309  2005/04  [Not refereed][Not invited]
   

  50-year-old woman first presented with recurrent craniopharyngioma in the suprasellar region. The recurrent tumor was removed via the frontobasal interhemispheric approach. Two years later, magnetic resonance imaging revealed a further recurrence in the primary suprasellar region and a cystic mass with ring enhancement on the surface of the left frontal lobe. Both lesions were removed via the frontobasal interhemispheric approach. Histological examination showed the left frontal lesion was an ectopic recurrence of craniopharyngioma. Ectopic recurrence of craniopharyngioma is extremely rare. (c) 2004 Elsevier Ltd. All rights reserved.
• A case of cellular blue naevus with intracranial invasion and malignant transformation

  N Noshita, M Fujimura, T Kumabe, R Shirane, M Watanabe, T Tominaga  ACTA NEUROCHIRURGICA  147-  (2)  211  -213  2005/02  [Not refereed][Not invited]
  
• Thrombosed vertebral artery aneurysm presenting with hemorrhage and bulbar compression: report of two cases

  S Shiraishi, M Fujimura, H Kon, O Motohashi, M Kameyama, K Ishii, T Onuma  CLINICAL NEUROLOGY AND NEUROSURGERY  107-  (2)  123  -127  2005/02  [Not refereed][Not invited]
   

  Bulbar compression by vertebral artery (VA) aneurysm is extremely rare and only reported in a few cases. We report two cases with thrombosed VA aneurysm compressing medulla oblongata; one presented with bulbar apoplexy hemorrhage and the other with subarachnoid hemorrhage (SAH). A 61-year-old male (case 1) presented with consciousness disturbances, left hemiplegia, and subsequent respiratory arrest. He was subjected to controlled ventilation, and computed tomography (CT) scan showed bulbar hemorrhage. Magnetic resonance imaging (MRI) and digital subtraction angiogram (DSA) revealed fusiform right VA aneurysm with partial thrombosis and bulbar compression. Intra-aneurysmal embolization with Guglielmi detachable coils (GDCs) relieved his clinical symptom including respiratory disturbance. Three months after the onset, he remained moderately disabled. A 76-year-old male (case 2) presented with severe headache and subsequent respiratory disturbance. CT scan on admission showed subarachnoid hemorrhage with acute hydrocephalus. Ventricular drainage rapidly improved consciousness while respiratory disturbance persisted over several days. MRI and DSA suggested spontaneous thrombosis of the right VA dissection with bulbar compression. He showed gradual recovery of his respiration over a week. After ventriculo-peritoneal shunting, he was transferred with moderate disability. These results suggest that the elimination of the pulsatile effect of VA aneurysm adjacent to medulla oblongata can improve symptoms caused by aneurysm-related compression. Early diagnosis and appropriate treatment such as intra-aneurysmal embolization for ameliorating the blood flow inside the aneurysm can relieve mass effect and clinical symptoms. (C) 2004 Elsevier B.V. All rights reserved.
• A case of cellular blue naevus with intracranial invasion and malignant transformation

  N Noshita, M Fujimura, T Kumabe, R Shirane, M Watanabe, T Tominaga  ACTA NEUROCHIRURGICA  147-  (2)  211  -213  2005/02  [Not refereed][Not invited]
  
• Thrombosed vertebral artery aneurysm presenting with hemorrhage and bulbar compression: report of two cases

  S Shiraishi, M Fujimura, H Kon, O Motohashi, M Kameyama, K Ishii, T Onuma  CLINICAL NEUROLOGY AND NEUROSURGERY  107-  (2)  123  -127  2005/02  [Not refereed][Not invited]
   

  Bulbar compression by vertebral artery (VA) aneurysm is extremely rare and only reported in a few cases. We report two cases with thrombosed VA aneurysm compressing medulla oblongata; one presented with bulbar apoplexy hemorrhage and the other with subarachnoid hemorrhage (SAH). A 61-year-old male (case 1) presented with consciousness disturbances, left hemiplegia, and subsequent respiratory arrest. He was subjected to controlled ventilation, and computed tomography (CT) scan showed bulbar hemorrhage. Magnetic resonance imaging (MRI) and digital subtraction angiogram (DSA) revealed fusiform right VA aneurysm with partial thrombosis and bulbar compression. Intra-aneurysmal embolization with Guglielmi detachable coils (GDCs) relieved his clinical symptom including respiratory disturbance. Three months after the onset, he remained moderately disabled. A 76-year-old male (case 2) presented with severe headache and subsequent respiratory disturbance. CT scan on admission showed subarachnoid hemorrhage with acute hydrocephalus. Ventricular drainage rapidly improved consciousness while respiratory disturbance persisted over several days. MRI and DSA suggested spontaneous thrombosis of the right VA dissection with bulbar compression. He showed gradual recovery of his respiration over a week. After ventriculo-peritoneal shunting, he was transferred with moderate disability. These results suggest that the elimination of the pulsatile effect of VA aneurysm adjacent to medulla oblongata can improve symptoms caused by aneurysm-related compression. Early diagnosis and appropriate treatment such as intra-aneurysmal embolization for ameliorating the blood flow inside the aneurysm can relieve mass effect and clinical symptoms. (C) 2004 Elsevier B.V. All rights reserved.
• もやもや病に対する血行再建術後急性期の臨床像と脳循環動態・放射線学的変化の検討:術後過潅流について

  藤村幹, 清水宏明, 冨永悌二  日本脳神経外科学会総会抄録集(CD-ROM)  64th-  2005
• ラット大脳への衝撃波照射による神経細胞死の検討

  加藤薫子, 中川敦寛, 藤村幹, 斉藤敦志, 大木友博, 平野孝幸, 高山和喜, 冨永悌二  平成17年度 衝撃波シンポジウム講演論文集  337  -339  2005  [Not refereed][Not invited]
  
• Diagnostic value of super-selective bilateral cavernous sinus sampling with hypothalamic stimulating hormone loading in patients with ACTH-producing pituitary adenoma

  M Fujimura, H Ikeda, A Takahashi, M Ezura, T Yoshimoto, T Tominaga  NEUROLOGICAL RESEARCH  27-  (1)  11  -15  2005/01  [Not refereed][Not invited]
   

  Aims: Early diagnosis and early treatment by transsphenoidal surgery is desirable for ACTH-producing pituitary microadenoma, but accurate localization of the functional lesion is not always possible before surgery because magnetic resonance (MR) imaging may provide false negative and/or positive findings. The diagnostic value of super-selective bilateral cavernous sinus sampling with the administration of corticotropin-releasing hormone (CRH) was assessed in patients with functioning ACTH-producing pituitary adenoma. Methods: Fifteen patients with pituitary adenoma (14 with microadenoma) aged from 23 to 74 years (mean 46.7 years) underwent cavernous sinus sampling with or without the CRH loading test and subsequent transsphenoidal surgery in our institute from October 1997 through to November 2002. MR imaging including dynamic scan failed to detect the adenomatous lesion in all patients. To eliminate the bias due to uneven blood flow in the cavernous sinuses and the multi-hormonal response to CRH administration, the ACTH/FSH ratios were evaluated. The inter-cavernous gradient (ICG) was calculated as the higher/lower ACTH venous blood levels in the right and left cavernous sinuses with or without CRH loading. The adjusted ICG was calculated using the ACTH/FSH ratios. The results were compared with the surgical findings. An ICG of 1.4 or greater was considered to indicate the localization of the responsible lesion. Results: Transsphenoidal surgery revealed the functioning lesion on the right in five cases, the left in six, the midline in three and the bilateral lateral wings (double adenoma) in one. Adjusted ICG with CRH loading had a localization accuracy of 93.3% (14/15), which was significantly higher than that of 73.3% (11/15) using ICG without hypothalamic stimulating hormone loading (p=0.0402). Conclusions: Super-selective cavernous sinus sampling or with hypothalamic stimulating hormone administration can provide accurate localization the responsible lesion in patients with ACTH-producing pituitary adenoma.
• Neuroprotective effect of an antioxidant in ischemic brain injury - Involvement of neuronal apoptosis

  M Fujimura, T Tominaga, PH Chan  NEUROCRITICAL CARE  2-  (1)  59  -66  2005  [Not refereed][Not invited]
   

  The production of reactive oxygen species (ROS) has been implicated in reperfusion injury after cerebral ischemia, and antioxidant enzymes are believed to be among the major mechanisms by which the cells counteract the deleterious effect of ROS after cerebral ischemia. ROS also mediate the mitochondrial signaling pathway that may lead to apoptosis following cerebral ischemia. The recent development and availability of transgenic and knockout mutant rodents that either overexpress or are deficient in antioxidant genes have provided powerful tools for dissecting the molecular and cellular mechanisms of signaling pathways, direct oxidative damage, or both that are involved in ischemic brain injury. This article focuses on the contribution of ROS or an antioxidant system to the molecular pathway of postischemic apoptosis following transient focal cerebral ischemia by using transgenic mice that overexpress the cytosolic antioxidant copper/zinc superoxide dismutase.
• STA-MCA吻合術後にfocal hyperperfusionを呈したもやもや病の２症例

  藤村幹, 清水宏明, 金田朋洋, 冨永悌二  東北脳SPECT研究会講演集  14-  (1)  20  -25  2005  [Not refereed][Not invited]
  
• Congestive myelopathyを呈した肋間動静脈シャントの一治験例

  斉藤敦志, 高橋敏行, 江面正幸, 藤村幹, 隈部俊宏, 冨永悌二  東北脳血管障害研究会27回学術集会記録集  81  -85  2005  [Not refereed][Not invited]
  
• Diagnostic value of super-selective bilateral cavernous sinus sampling with hypothalamic stimulating hormone loading in patients with ACTH-producing pituitary adenoma

  M Fujimura, H Ikeda, A Takahashi, M Ezura, T Yoshimoto, T Tominaga  NEUROLOGICAL RESEARCH  27-  (1)  11  -15  2005/01  [Not refereed][Not invited]
   

  Aims: Early diagnosis and early treatment by transsphenoidal surgery is desirable for ACTH-producing pituitary microadenoma, but accurate localization of the functional lesion is not always possible before surgery because magnetic resonance (MR) imaging may provide false negative and/or positive findings. The diagnostic value of super-selective bilateral cavernous sinus sampling with the administration of corticotropin-releasing hormone (CRH) was assessed in patients with functioning ACTH-producing pituitary adenoma. Methods: Fifteen patients with pituitary adenoma (14 with microadenoma) aged from 23 to 74 years (mean 46.7 years) underwent cavernous sinus sampling with or without the CRH loading test and subsequent transsphenoidal surgery in our institute from October 1997 through to November 2002. MR imaging including dynamic scan failed to detect the adenomatous lesion in all patients. To eliminate the bias due to uneven blood flow in the cavernous sinuses and the multi-hormonal response to CRH administration, the ACTH/FSH ratios were evaluated. The inter-cavernous gradient (ICG) was calculated as the higher/lower ACTH venous blood levels in the right and left cavernous sinuses with or without CRH loading. The adjusted ICG was calculated using the ACTH/FSH ratios. The results were compared with the surgical findings. An ICG of 1.4 or greater was considered to indicate the localization of the responsible lesion. Results: Transsphenoidal surgery revealed the functioning lesion on the right in five cases, the left in six, the midline in three and the bilateral lateral wings (double adenoma) in one. Adjusted ICG with CRH loading had a localization accuracy of 93.3% (14/15), which was significantly higher than that of 73.3% (11/15) using ICG without hypothalamic stimulating hormone loading (p=0.0402). Conclusions: Super-selective cavernous sinus sampling or with hypothalamic stimulating hormone administration can provide accurate localization the responsible lesion in patients with ACTH-producing pituitary adenoma.
• Neuroprotective effect of an antioxidant in ischemic brain injury - Involvement of neuronal apoptosis

  M Fujimura, T Tominaga, PH Chan  NEUROCRITICAL CARE  2-  (1)  59  -66  2005  [Not refereed][Not invited]
   

  The production of reactive oxygen species (ROS) has been implicated in reperfusion injury after cerebral ischemia, and antioxidant enzymes are believed to be among the major mechanisms by which the cells counteract the deleterious effect of ROS after cerebral ischemia. ROS also mediate the mitochondrial signaling pathway that may lead to apoptosis following cerebral ischemia. The recent development and availability of transgenic and knockout mutant rodents that either overexpress or are deficient in antioxidant genes have provided powerful tools for dissecting the molecular and cellular mechanisms of signaling pathways, direct oxidative damage, or both that are involved in ischemic brain injury. This article focuses on the contribution of ROS or an antioxidant system to the molecular pathway of postischemic apoptosis following transient focal cerebral ischemia by using transgenic mice that overexpress the cytosolic antioxidant copper/zinc superoxide dismutase.
• STA-MCA吻合術後にfocal hyperperfusionを呈したもやもや病の２症例

  藤村幹, 清水宏明, 金田朋洋, 冨永悌二  東北脳SPECT研究会講演集  14-  (1)  20  -25  2005  [Not refereed][Not invited]
  
• Congestive myelopathyを呈した肋間動静脈シャントの一治験例

  斉藤敦志, 高橋敏行, 江面正幸, 藤村幹, 隈部俊宏, 冨永悌二  東北脳血管障害研究会27回学術集会記録集  81  -85  2005  [Not refereed][Not invited]
  
• Combined three-dimensional anisotropy contrast imaging and magnetoencephalography guidance to preserve visual function in a patient with an occipital lobe tumor

  T Inoue, M Fujimura, T Kumabe, N Nakasato, S Higano, T Tominaga  MINIMALLY INVASIVE NEUROSURGERY  47-  (4)  249  -252  2004/08  [Not refereed][Not invited]
   

  Objective: Three-dimensional anisotropy contrast (3-DAC) magnetic resonance imaging and magnetoencephalography (MEG) of visually evoked magnetic fields (VEFs) were used to accurately localize the optic radiation and primary visual cortex before surgery for an occipital tumor. Patient and Methods: A 26-year-old male presented with an occipital lobe tumor located intrinsically underneath the right calcarine fissure. 3-DAC imaging showed that the right optic radiation was located along the superior and lateral surfaces of the lesion. Mapping of the VEFs demonstrated that the primary visual cortex was located superior and lateral to the lesion. The lesion was totally resected via an infero-medial cortical incision using a frameless stereotactic system. Histopathology indicated a pilocytic astrocytoma. No visual deficit was found before or after surgery. Conclusion: Combined 3-DAC imaging and MEG can provide essential information about the optic radiation and primary visual cortex for planning the surgical treatment of occipital lobe tumors.
• Combined three-dimensional anisotropy contrast imaging and magnetoencephalography guidance to preserve visual function in a patient with an occipital lobe tumor

  T Inoue, M Fujimura, T Kumabe, N Nakasato, S Higano, T Tominaga  MINIMALLY INVASIVE NEUROSURGERY  47-  (4)  249  -252  2004/08  [Not refereed][Not invited]
   

  Objective: Three-dimensional anisotropy contrast (3-DAC) magnetic resonance imaging and magnetoencephalography (MEG) of visually evoked magnetic fields (VEFs) were used to accurately localize the optic radiation and primary visual cortex before surgery for an occipital tumor. Patient and Methods: A 26-year-old male presented with an occipital lobe tumor located intrinsically underneath the right calcarine fissure. 3-DAC imaging showed that the right optic radiation was located along the superior and lateral surfaces of the lesion. Mapping of the VEFs demonstrated that the primary visual cortex was located superior and lateral to the lesion. The lesion was totally resected via an infero-medial cortical incision using a frameless stereotactic system. Histopathology indicated a pilocytic astrocytoma. No visual deficit was found before or after surgery. Conclusion: Combined 3-DAC imaging and MEG can provide essential information about the optic radiation and primary visual cortex for planning the surgical treatment of occipital lobe tumors.
• Hydrocephalus due to cerebrospinal fluid overproduction by bilateral choroid plexus papillomas

  M Fujimura, T Onuma, M Kameyama, O Motohashi, H Kon, K Yamamoto, K Ishii, T Tominaga  CHILDS NERVOUS SYSTEM  20-  (7)  485  -488  2004/07  [Not refereed][Not invited]
   

  Case report: A 10-month-old boy, with congenital deafness and blindness associated with chromosomal deletion [46XY, del(13)(q32)], presented with intractable ascites 9 months after ventriculo-peritoneal shunting for congenital hydrocephalus. Revision of the ventriculo-atrial shunt resulted in shunt failure 1 month later. External ventricular drainage revealed cerebrospinal fluid (CSF) overproduction (2,000 ml/day). Magnetic resonance imaging showed marked lobular enlargement of the bilateral choroid plexuses extending from the trigone to the body and inferior horn of the lateral ventricle. Multi-staged resection was performed via bilateral temporo-occipital transcortical approaches, and CSF production significantly decreased to 100 ml/day postoperatively. Histological assessment of the villous surface suggested villous hyperplasia of the choroid plexus and thorough evaluation including the proximal portion of the lobular lesion near the attachment revealed choroid plexus papilloma. He was discharged after ventriculo-peritoneal shunting without additional neurological deficits except for hyperreflexia of the left extremities. Conclusion: CSF overproduction caused by bilateral choroid plexus papillomas can result in hydrocephalus. Radical resection of the bilateral ventricular lesions should be considered for this entity. Thorough evaluation of the surgical specimen is recommended because histological examination of only the lobular surface of the choroid plexus lesion may fail to identify choroid plexus neoplasm.
• Hydrocephalus due to cerebrospinal fluid overproduction by bilateral choroid plexus papillomas

  M Fujimura, T Onuma, M Kameyama, O Motohashi, H Kon, K Yamamoto, K Ishii, T Tominaga  CHILDS NERVOUS SYSTEM  20-  (7)  485  -488  2004/07  [Not refereed][Not invited]
   

  Case report: A 10-month-old boy, with congenital deafness and blindness associated with chromosomal deletion [46XY, del(13)(q32)], presented with intractable ascites 9 months after ventriculo-peritoneal shunting for congenital hydrocephalus. Revision of the ventriculo-atrial shunt resulted in shunt failure 1 month later. External ventricular drainage revealed cerebrospinal fluid (CSF) overproduction (2,000 ml/day). Magnetic resonance imaging showed marked lobular enlargement of the bilateral choroid plexuses extending from the trigone to the body and inferior horn of the lateral ventricle. Multi-staged resection was performed via bilateral temporo-occipital transcortical approaches, and CSF production significantly decreased to 100 ml/day postoperatively. Histological assessment of the villous surface suggested villous hyperplasia of the choroid plexus and thorough evaluation including the proximal portion of the lobular lesion near the attachment revealed choroid plexus papilloma. He was discharged after ventriculo-peritoneal shunting without additional neurological deficits except for hyperreflexia of the left extremities. Conclusion: CSF overproduction caused by bilateral choroid plexus papillomas can result in hydrocephalus. Radical resection of the bilateral ventricular lesions should be considered for this entity. Thorough evaluation of the surgical specimen is recommended because histological examination of only the lobular surface of the choroid plexus lesion may fail to identify choroid plexus neoplasm.
• Cerebral infarction in the caudate nucleus associated with acute epidural hematoma and diffuse brain injury in a child after severe head injury

  M Fujimura, M Kameyama, O Motohashi, H Kon, K Ishii, T Onuma  CHILDS NERVOUS SYSTEM  20-  (6)  430  -433  2004/06  [Not refereed][Not invited]
   

  Case report: A 6-year-old boy was admitted to our hospital 20 min after receiving a direct impact to his head in an automobile accident. He was semi-comatose on admission and computed tomography showed acute epidural hematoma in the right supratentorial region. Three hours later, his consciousness deteriorated due to the enlargement of the hematoma. Surgical removal of hematoma relieved his consciousness disturbance. Post-operative magnetic resonance imaging revealed spotty high-intensity lesions in the corpus callosum on T2-weighted images, and a solitary high-intensity lesion in the left caudate nucleus extending to the medial globus pallidum on T2-weighted and diffusion-weighted images. Magnetic resonance angiography showed no abnormality in the main arteries. These results suggested cerebral infarction in the vascular territory supplied by the recurrent artery of Heubner in association with diffuse brain injury. Post-operative course was uneventful and he was discharged without neurological deficit. Conclusions: Post-traumatic cerebral infarction in the caudate nucleus is extremely rare, and its association with diffuse brain injury and epidural hematoma is apparently unique.
• Cerebral infarction in the caudate nucleus associated with acute epidural hematoma and diffuse brain injury in a child after severe head injury

  M Fujimura, M Kameyama, O Motohashi, H Kon, K Ishii, T Onuma  CHILDS NERVOUS SYSTEM  20-  (6)  430  -433  2004/06  [Not refereed][Not invited]
   

  Case report: A 6-year-old boy was admitted to our hospital 20 min after receiving a direct impact to his head in an automobile accident. He was semi-comatose on admission and computed tomography showed acute epidural hematoma in the right supratentorial region. Three hours later, his consciousness deteriorated due to the enlargement of the hematoma. Surgical removal of hematoma relieved his consciousness disturbance. Post-operative magnetic resonance imaging revealed spotty high-intensity lesions in the corpus callosum on T2-weighted images, and a solitary high-intensity lesion in the left caudate nucleus extending to the medial globus pallidum on T2-weighted and diffusion-weighted images. Magnetic resonance angiography showed no abnormality in the main arteries. These results suggested cerebral infarction in the vascular territory supplied by the recurrent artery of Heubner in association with diffuse brain injury. Post-operative course was uneventful and he was discharged without neurological deficit. Conclusions: Post-traumatic cerebral infarction in the caudate nucleus is extremely rare, and its association with diffuse brain injury and epidural hematoma is apparently unique.
• Exclusively extradural arteriovenous malformation with neurogenic claudication - Case illustration

  K Niizuma, M Fujimura, T Takahashi, A Takahashi, M Watanabe, T Tominaga  JOURNAL OF NEUROSURGERY  100-  (4)  397  -397  2004/04  [Not refereed][Not invited]
  
• Exclusively extradural arteriovenous malformation with neurogenic claudication - Case illustration

  K Niizuma, M Fujimura, T Takahashi, A Takahashi, M Watanabe, T Tominaga  JOURNAL OF NEUROSURGERY  100-  (4)  397  -397  2004/04  [Not refereed][Not invited]
  
• Routine clinical adoption of magnetic resonance imaging was associated with better outcome after surgery in elderly patients with a malignant astrocytic tumour: a retrospective review

  M Fujimura, T Kumabe, T Tominaga, H Jokura, R Shirane, T Yoshimoto  ACTA NEUROCHIRURGICA  146-  (3)  251  -255  2004/03  [Not refereed][Not invited]
   

  Background. There is controversy about extensive surgical treatment for a malignant astrocytic tumour in more elderly patients who may have poorer outcomes and higher complication rates. This retrospective study investigated outcome in elderly patients with malignant astrocytic tumour before and after the adoption of routine clinical use of magnetic resonance (MR) imaging. Methods. During 1982 through 1999, 88 patients with malignant astrocytic tumour aged 60 years or over were treated in our institute. Thirty-seven patients had an anaplastic astrocytoma and 51 had a glioblastoma. Thirty-seven patients treated from 1982 to 1988 did not have pre-operative evaluation by MR imaging (Group A), 26 patients treated from 1989 to 1995 had preoperative MR imaging evaluation (Group B), and 25 patients treated after 1996 underwent preoperative MR imaging with functional brain mapping and intra-operative navigation system monitoring (Group C). Findings. The median survival time was 8.8 months in Group A, 12.7 months in Group B, and 17.6 months in Group C. Patients with glioblastoma in Group B (11.7 months, n = 15) and Group C (16.0 months, n = 19) had significantly longer median survival time than in Group A (6 months. n = 17) (P = 0.0054 between Groups A and B, P = 0.0024 between Groups A and C). Better preoperative performance status, more thorough surgical resection, and better performance status after the initial treatment was obtained after the introduction of MR imaging, and patients with the optimal indicators showed significantly longer survival time compared with the patients without these factors. Interpretation. Pre-operative MR imaging may contribute to longer survival time by providing an earlier diagnosis in patients with better performance status, by allowing more thorough surgical resection, and resulting in better performance status after the treatment.
• Routine clinical adoption of magnetic resonance imaging was associated with better outcome after surgery in elderly patients with a malignant astrocytic tumour: a retrospective review

  M Fujimura, T Kumabe, T Tominaga, H Jokura, R Shirane, T Yoshimoto  ACTA NEUROCHIRURGICA  146-  (3)  251  -255  2004/03  [Not refereed][Not invited]
   

  Background. There is controversy about extensive surgical treatment for a malignant astrocytic tumour in more elderly patients who may have poorer outcomes and higher complication rates. This retrospective study investigated outcome in elderly patients with malignant astrocytic tumour before and after the adoption of routine clinical use of magnetic resonance (MR) imaging. Methods. During 1982 through 1999, 88 patients with malignant astrocytic tumour aged 60 years or over were treated in our institute. Thirty-seven patients had an anaplastic astrocytoma and 51 had a glioblastoma. Thirty-seven patients treated from 1982 to 1988 did not have pre-operative evaluation by MR imaging (Group A), 26 patients treated from 1989 to 1995 had preoperative MR imaging evaluation (Group B), and 25 patients treated after 1996 underwent preoperative MR imaging with functional brain mapping and intra-operative navigation system monitoring (Group C). Findings. The median survival time was 8.8 months in Group A, 12.7 months in Group B, and 17.6 months in Group C. Patients with glioblastoma in Group B (11.7 months, n = 15) and Group C (16.0 months, n = 19) had significantly longer median survival time than in Group A (6 months. n = 17) (P = 0.0054 between Groups A and B, P = 0.0024 between Groups A and C). Better preoperative performance status, more thorough surgical resection, and better performance status after the initial treatment was obtained after the introduction of MR imaging, and patients with the optimal indicators showed significantly longer survival time compared with the patients without these factors. Interpretation. Pre-operative MR imaging may contribute to longer survival time by providing an earlier diagnosis in patients with better performance status, by allowing more thorough surgical resection, and resulting in better performance status after the treatment.
• マウスクモ膜下出血後のneurogenesisとapoptosis

  三野正樹, 上井英之, 近藤健男, 藤村幹, 冨永悌二  脳循環代謝  16-  (1)  49  -50  2004  [Not refereed][Not invited]
  
• Neuronal death/survival signaling pathways in cerebral ischemia. (NeuroRx)

  Sugawara Taku, Fujimura Miki, Noshita Nobuo, Kim Gyung Whan, Saito Atsushi, Hayashi Takeshi, Narasimhan Purnima, Maier Carolina M, Chan Pak H  NeuroRx  1-  (1)  17  -25  2004  [Not refereed][Not invited]
  
• Intractable vomiting as an early clinical symptom of cerebrospinal fluid seeding to the fourth ventricle in patients with high-grade astrocytoma

  M Fujimura, T Kumabe, H Jokura, R Shirane, T Yoshimoto, T Tominaga  JOURNAL OF NEURO-ONCOLOGY  66-  (1-2)  209  -216  2004/01  [Not refereed][Not invited]
   

  Object. Cerebrospinal fluid (CSF) seeing of high-grade astrocytoma is common, but the early clinical symptoms are not well characterized. Here, we report five patients with disseminated high-grade astrocytoma in the fourth ventricle region who presented with intractable vomiting prior to the detection of the metastatic deposits with enhancement. Patients and methods. From 1994 to 2000, 133 patients of high-grade astrocytoma were treated in our institute and were followed up until December 2002. Follow-up magnetic resonance (MR) imaging was performed in all patients every 2-3 months. The CSF seeding was defined as leptomeningeal enhancement. Signs and symptoms of CSF seeding were checked at the monthly outpatient examination. Results. Among them, 5 patients aged from 27 to 58 years (mean 43.8 years) with one anaplastic astrocytoma and four glioblastomas showed intractable vomiting without signs of high intracranial pressure as evaluated by MR imaging or ocular fundus examination prior to the detection of the fourth ventricle dissemination. Fourth ventricle dissemination appeared 1-3 months after vomiting in five patients. One patient with glioblastoma received gamma knife radiotherapy for a fourth ventricle lesion appearing as a high intensity area on T2-weighted imaging before the appearance of the enhanced nodule, and this lesion was cured. Four patients died of progression of the fourth ventricle lesion. Conclusion. Intractable vomiting may be an early clinical symptom of CSF seeding to the fourth ventricle in patients with high-grade astrocytoma. Early detection and immediate radiotherapy for this lesion are recommended to control fourth ventricle dissemination.
• PTEN gene mutation and high MIB-4 labeling index may contribute to dissemination in patients with glioblastoma

  H Kato, M Fujimura, T Kumabe, C Ishioka, R Kanamaru, T Yoshimoto  JOURNAL OF CLINICAL NEUROSCIENCE  11-  (1)  37  -41  2004/01  [Not refereed][Not invited]
   

  Dissemination of glioblastomas is often observed, but the underlying mechanism is not well clarified especially from the genetic viewpoints. The present study examined whether PTEN gene mutations and MIB-1 labeling index (LI) correlate with the dissemination in 39 consecutive patients with glioblastomas. Dissemination was defined as leptomenigeal enhancement by magnetic resonance imaging performed in all patients every 2-3 months. We examined PTEN mutations in 26 patients using cDNA-based direct sequencing and MlB-1 LI in 38 patients. Median survival time of the 39 patients was 16.2 months. Dissemination was found in 17 of 39 patients (43.6%). PTEN mutation was significantly associated with dissemination (P=0.0140), and higher MlB-1 LI ( greater than or equal to35%) resulted in earlier dissemination (P=0.0156). Kaplan-Meier survival plots showed a significantly poorer survival for patients with PTEN mutation (P=0.0012). The results indicate that the evaluation of PTEN mutation and MlB-1 LI are useful to predict dissemination and prognosis of glioblastomas. (C) 2003 Elsevier Ltd. All rights reserved.
• The 7th Japanese and Korean Friendship Conference on Suegrery for Cerebral Stroke

  藤村幹  脳神経外科  32-  (7)  760  -761  2004  [Not refereed][Not invited]
  
• Neuronal death/survival signaling pathways in cerebral ischemia. (NeuroRx)

  Sugawara Taku, Fujimura Miki, Noshita Nobuo, Kim Gyung Whan, Saito Atsushi, Hayashi Takeshi, Narasimhan Purnima, Maier Carolina M, Chan Pak H  NeuroRx  1-  (1)  17  -25  2004  [Not refereed][Not invited]
  
• Intractable vomiting as an early clinical symptom of cerebrospinal fluid seeding to the fourth ventricle in patients with high-grade astrocytoma

  M Fujimura, T Kumabe, H Jokura, R Shirane, T Yoshimoto, T Tominaga  JOURNAL OF NEURO-ONCOLOGY  66-  (1-2)  209  -216  2004/01  [Not refereed][Not invited]
   

  Object. Cerebrospinal fluid (CSF) seeing of high-grade astrocytoma is common, but the early clinical symptoms are not well characterized. Here, we report five patients with disseminated high-grade astrocytoma in the fourth ventricle region who presented with intractable vomiting prior to the detection of the metastatic deposits with enhancement. Patients and methods. From 1994 to 2000, 133 patients of high-grade astrocytoma were treated in our institute and were followed up until December 2002. Follow-up magnetic resonance (MR) imaging was performed in all patients every 2-3 months. The CSF seeding was defined as leptomeningeal enhancement. Signs and symptoms of CSF seeding were checked at the monthly outpatient examination. Results. Among them, 5 patients aged from 27 to 58 years (mean 43.8 years) with one anaplastic astrocytoma and four glioblastomas showed intractable vomiting without signs of high intracranial pressure as evaluated by MR imaging or ocular fundus examination prior to the detection of the fourth ventricle dissemination. Fourth ventricle dissemination appeared 1-3 months after vomiting in five patients. One patient with glioblastoma received gamma knife radiotherapy for a fourth ventricle lesion appearing as a high intensity area on T2-weighted imaging before the appearance of the enhanced nodule, and this lesion was cured. Four patients died of progression of the fourth ventricle lesion. Conclusion. Intractable vomiting may be an early clinical symptom of CSF seeding to the fourth ventricle in patients with high-grade astrocytoma. Early detection and immediate radiotherapy for this lesion are recommended to control fourth ventricle dissemination.
• PTEN gene mutation and high MIB-4 labeling index may contribute to dissemination in patients with glioblastoma

  H Kato, M Fujimura, T Kumabe, C Ishioka, R Kanamaru, T Yoshimoto  JOURNAL OF CLINICAL NEUROSCIENCE  11-  (1)  37  -41  2004/01  [Not refereed][Not invited]
   

  Dissemination of glioblastomas is often observed, but the underlying mechanism is not well clarified especially from the genetic viewpoints. The present study examined whether PTEN gene mutations and MIB-1 labeling index (LI) correlate with the dissemination in 39 consecutive patients with glioblastomas. Dissemination was defined as leptomenigeal enhancement by magnetic resonance imaging performed in all patients every 2-3 months. We examined PTEN mutations in 26 patients using cDNA-based direct sequencing and MlB-1 LI in 38 patients. Median survival time of the 39 patients was 16.2 months. Dissemination was found in 17 of 39 patients (43.6%). PTEN mutation was significantly associated with dissemination (P=0.0140), and higher MlB-1 LI ( greater than or equal to35%) resulted in earlier dissemination (P=0.0156). Kaplan-Meier survival plots showed a significantly poorer survival for patients with PTEN mutation (P=0.0012). The results indicate that the evaluation of PTEN mutation and MlB-1 LI are useful to predict dissemination and prognosis of glioblastomas. (C) 2003 Elsevier Ltd. All rights reserved.
• The 7th Japanese and Korean Friendship Conference on Suegrery for Cerebral Stroke

  藤村幹  脳神経外科  32-  (7)  760  -761  2004  [Not refereed][Not invited]
  
• Temporal changes of neurogenesis in the mouse hippocampus after experimental subarachnoid hemorrhage

  M Mino, H Kamii, M Fujimura, T Kondo, S Takasawa, H Okamoto, T Yoshimoto  NEUROLOGICAL RESEARCH  25-  (8)  839  -845  2003/12  [Not refereed][Not invited]
   

  Recent studies indicate the existence of progenitor cells and their potential for neurogenesis in the subventricular zone (SVZ) and the hippocampus dentate gyrus (DG) of normal adult mammalian brain. Increased neurogenesis has been shown following cerebral ischemia and traumatic brain injury, however, the involvement of neurogenesis in subarachnoid hemorrhage (SAH) has not been examined. Adult male CD-I mice were subjected to SAH by endovascular perforation of the left anterior cerebral artery. Mice received intraperitoneal injections of the cell proliferation-specific marker 5'-bromodeoxyuridine (BrdU) after SAH induction. BrdU incorporation was examined from 1 to 30 days after SAH by immunohistochemistry. The BrdU-positive cells were detected in SVZ and DC of normal control brain, and were significantly decreased in both areas three days after SAH. The number of these cells had recovered to its control level seven days after SAH. Double staining with BrdU and NeuN indicated that the majority of the BrdU-positive cells migrating into the granular cell layer of the DG became NeuN-positive 30 days after SAH. In conclusion, temporal changes of the neurogenesis as shown in the present study suggest that neurogenesis in the hippocampus may affect functional outcome after SAH. The induction of the neurogenesis can provide therapeutic value against SAH.
• Temporal changes of neurogenesis in the mouse hippocampus after experimental subarachnoid hemorrhage

  M Mino, H Kamii, M Fujimura, T Kondo, S Takasawa, H Okamoto, T Yoshimoto  NEUROLOGICAL RESEARCH  25-  (8)  839  -845  2003/12  [Not refereed][Not invited]
   

  Recent studies indicate the existence of progenitor cells and their potential for neurogenesis in the subventricular zone (SVZ) and the hippocampus dentate gyrus (DG) of normal adult mammalian brain. Increased neurogenesis has been shown following cerebral ischemia and traumatic brain injury, however, the involvement of neurogenesis in subarachnoid hemorrhage (SAH) has not been examined. Adult male CD-I mice were subjected to SAH by endovascular perforation of the left anterior cerebral artery. Mice received intraperitoneal injections of the cell proliferation-specific marker 5'-bromodeoxyuridine (BrdU) after SAH induction. BrdU incorporation was examined from 1 to 30 days after SAH by immunohistochemistry. The BrdU-positive cells were detected in SVZ and DC of normal control brain, and were significantly decreased in both areas three days after SAH. The number of these cells had recovered to its control level seven days after SAH. Double staining with BrdU and NeuN indicated that the majority of the BrdU-positive cells migrating into the granular cell layer of the DG became NeuN-positive 30 days after SAH. In conclusion, temporal changes of the neurogenesis as shown in the present study suggest that neurogenesis in the hippocampus may affect functional outcome after SAH. The induction of the neurogenesis can provide therapeutic value against SAH.
• A case of germinoma in the septum pellucidum manifesting as amnesia and hemiparesis

  K Sato, T Nagayama, M Fujimura, K Okamoto, M Kamiya, Y Nakazato  ACTA NEUROCHIRURGICA  145-  (10)  923  -926  2003/10  [Not refereed][Not invited]
   

  Background. We report a rare case of germinoma mainly located in the septum pellucidum. Case description. A 19-year-old man presented with germinoma located in the septum pellucidum manifesting as amnesia and right hemiparesis. Magnetic resonance imaging demonstrated a heterogeneously enhanced mass in the septum pellucidum and abnormal T2-weighted signals in the left basal ganglia. An anterior transcallosal approach was performed to remove the mass in the septum pellucidum. The histological diagnosis was germinoma. Radiotherapy and chemotherapy were given. He was discharged with slight amnesia and right hemipareis. Interpretation. Intracranial germinoma can arise from the septum pellucidum.
• A case of germinoma in the septum pellucidum manifesting as amnesia and hemiparesis

  K Sato, T Nagayama, M Fujimura, K Okamoto, M Kamiya, Y Nakazato  ACTA NEUROCHIRURGICA  145-  (10)  923  -926  2003/10  [Not refereed][Not invited]
   

  Background. We report a rare case of germinoma mainly located in the septum pellucidum. Case description. A 19-year-old man presented with germinoma located in the septum pellucidum manifesting as amnesia and right hemiparesis. Magnetic resonance imaging demonstrated a heterogeneously enhanced mass in the septum pellucidum and abnormal T2-weighted signals in the left basal ganglia. An anterior transcallosal approach was performed to remove the mass in the septum pellucidum. The histological diagnosis was germinoma. Radiotherapy and chemotherapy were given. He was discharged with slight amnesia and right hemipareis. Interpretation. Intracranial germinoma can arise from the septum pellucidum.
• Two cases of impending herniation due to multiple traumatic acute subdural hematomas: Combination of burr hole evacuation and craniotomy

  O Motohashi, M Kameyama, H Kon, M Fujimura, T Onuma  NEUROLOGICAL SURGERY  31-  (5)  529  -535  2003/05  [Not refereed][Not invited]
   

  A contralateral extra-axial hematoma sometimes occurs during an operation on an acute subdural hematoma and may become fatal. Using a combined procedure of burr hole evacuation and craniotomy, we treated 2 cases of multiple traumatic acute subdural hematomas. Our policy for such cases is first to perform a burr hole evacuation for the acute subdural hematoma in the emergency room, while simultaneously preparing the operation room for a possible further operation. Next, we perform computed tomography (CT) of the brain. If the evacuation does not provide enough decompression, we either carry out a craniotomy at the same site, or, we observe the patient without resorting to craniotomy. However, if the patient's condition deteriorates, burr hole evacuation is repeated and/or craniotomy is carried out as soon as possible on the lesion at the already prepared operation room. Both of our patients received craniotomy for another subdural hematoma after the burr hole evacuation. Though his intracranial pressure was well managed during the acute stage, one of the patients died 21 days after the trauma due to an extensive brain infarction caused by vasospasm. The other regained consciousness and was able to walk 5 months after the trauma in spite of cerebral infarction from vasospasm. The possible mechanism of vasospasm in severe head injury is also discussed.
• Role of superoxide in poly(ADP-ribose) polymerase upregulation after transient cerebral ischemia

  P Narasimhan, M Fujimura, N Noshita, PH Chan  MOLECULAR BRAIN RESEARCH  113-  (1-2)  28  -36  2003/05  [Not refereed][Not invited]
   

  Creative stress plays a pivotal role in ischemic-reperfusion cell injury. Oxygen-derived free radicals trigger DNA strand damage, which is responsible for the activation of poly(ADP-ribose) polymerase (PARP). Recent studies have shown that peroxynitrite is the primary mediator of DNA damage and, hence, PARP activation after ischemia. PARP activation depletes NAD and ATP pools, ultimately resulting in necrotic cell death by loss of energy stores. Our study shows that PARP is upregulated as early as 15 min after 1 h of transient focal cerebral ischemia and remains for 8 h. We also examined the role of superoxide in PARP induction using copper/zinc-superoxide dismutase transgenic mice. Immunohistochemical and Western blotting data showed that there was no increased induction in PARP expression in these mice, suggesting that one of the mechanisms by which ischemic injury is attenuated in these mice might be by the inhibition of PARP induction. Furthermore, double staining of ischemic tissue with a PARP antibody and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling (TUNEL) indicated that most cells that are positive for TUNEL do not stain for the PARP antibody, confirming recent reports that PARP activation is involved in necrotic cell death rather than apoptosis during ischemic-reperfusion injury. (C) 2003 Elsevier Science B.V. All rights reserved.
• Two cases of impending herniation due to multiple traumatic acute subdural hematomas: Combination of burr hole evacuation and craniotomy

  O Motohashi, M Kameyama, H Kon, M Fujimura, T Onuma  NEUROLOGICAL SURGERY  31-  (5)  529  -535  2003/05  [Not refereed][Not invited]
   

  A contralateral extra-axial hematoma sometimes occurs during an operation on an acute subdural hematoma and may become fatal. Using a combined procedure of burr hole evacuation and craniotomy, we treated 2 cases of multiple traumatic acute subdural hematomas. Our policy for such cases is first to perform a burr hole evacuation for the acute subdural hematoma in the emergency room, while simultaneously preparing the operation room for a possible further operation. Next, we perform computed tomography (CT) of the brain. If the evacuation does not provide enough decompression, we either carry out a craniotomy at the same site, or, we observe the patient without resorting to craniotomy. However, if the patient's condition deteriorates, burr hole evacuation is repeated and/or craniotomy is carried out as soon as possible on the lesion at the already prepared operation room. Both of our patients received craniotomy for another subdural hematoma after the burr hole evacuation. Though his intracranial pressure was well managed during the acute stage, one of the patients died 21 days after the trauma due to an extensive brain infarction caused by vasospasm. The other regained consciousness and was able to walk 5 months after the trauma in spite of cerebral infarction from vasospasm. The possible mechanism of vasospasm in severe head injury is also discussed.
• Role of superoxide in poly(ADP-ribose) polymerase upregulation after transient cerebral ischemia

  P Narasimhan, M Fujimura, N Noshita, PH Chan  MOLECULAR BRAIN RESEARCH  113-  (1-2)  28  -36  2003/05  [Not refereed][Not invited]
   

  Creative stress plays a pivotal role in ischemic-reperfusion cell injury. Oxygen-derived free radicals trigger DNA strand damage, which is responsible for the activation of poly(ADP-ribose) polymerase (PARP). Recent studies have shown that peroxynitrite is the primary mediator of DNA damage and, hence, PARP activation after ischemia. PARP activation depletes NAD and ATP pools, ultimately resulting in necrotic cell death by loss of energy stores. Our study shows that PARP is upregulated as early as 15 min after 1 h of transient focal cerebral ischemia and remains for 8 h. We also examined the role of superoxide in PARP induction using copper/zinc-superoxide dismutase transgenic mice. Immunohistochemical and Western blotting data showed that there was no increased induction in PARP expression in these mice, suggesting that one of the mechanisms by which ischemic injury is attenuated in these mice might be by the inhibition of PARP induction. Furthermore, double staining of ischemic tissue with a PARP antibody and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling (TUNEL) indicated that most cells that are positive for TUNEL do not stain for the PARP antibody, confirming recent reports that PARP activation is involved in necrotic cell death rather than apoptosis during ischemic-reperfusion injury. (C) 2003 Elsevier Science B.V. All rights reserved.
• Fatal rupture following intra-aneurysmal embolization for the distal posterior inferior cerebellar artery aneurysm with parent artery preservation

  M Fujimura, M Nishijima, H Midorikawa, K Umezawa, T Hayashi, M Kaimori  CLINICAL NEUROLOGY AND NEUROSURGERY  105-  (2)  117  -120  2003/04  [Not refereed][Not invited]
   

  This 70-year-old female was admitted to our hospital I day after a sudden consciousness disturbance. Computed tomography (CT) showed subarachnoid hemorrhage (SAH), and angiogram revealed an irregular-shaped aneurysm at the lateral medullary segment of the left posterior inferior cerebellar artery (PICA). The patient was treated by intra-aneurysmal embolization with Guglielmi detachable coil (GDC) with parent artery preservation. Post-operative angiogram showed obliteration of the aneurysm except for the neck remnant, but she presented with rerupture 19 days after the onset and died 3 days later. Postmortem examination revealed massive hematoma around the aneurysm, which compressed medulla oblongata from behind. Histological assessment showed the 'entry' where the aneurysmal wall lacked internal elastic lamina, providing evidence of dissecting aneurysm. The present case suggests that embolization of distal PICA aneurysm with parent artery preservation should be avoided because radiological evaluation may fail to rule out the possibility of dissection, where the aneurysmal wall is affected not only at the 'entry' but also in the adjacent region. (C) 2002 Elsevier Science B.V. All rights reserved.
• A case of vertebral artery occlusion following heading play in soccer

  O Motohashi, M Kameyama, H Kon, M Fujimura, T Onuma  NEUROLOGICAL SURGERY  31-  (4)  431  -434  2003/04  [Not refereed][Not invited]
   

  A 13-year-old boar suffered from cerebeller infarction due to right vertebral artery occlusion after heading a ball during a rainy soccer game. Dissection of the vertebral artery after trivial head trauma is well known, but heading as the cause has not been reported. We speculated in this present case that excessive impact force to the young boy's neck due to the heavy rain-soaked ball might have caused right vertebral artery dissection and occlusion. High quality balls are recommended for young amateur players on rainy days.
• Spinal lipoma associated with terminal syringohydromyelia and a spinal arachnoid cyst in a patient with cloacal exstrophy

  M Fujimura, Y Kusaka, R Shirane  CHILDS NERVOUS SYSTEM  19-  (4)  254  -257  2003/04  [Not refereed][Not invited]
   

  Case report: A 2-year-old girl presented with repaired cloacal exstrophy and a subcutaneous mass at the midline of the lumbosacral region. Neurological examination revealed mild paraparesis with bilateral lower-extremity hyperreflexia and sensory disturbance below the level of L4. A CT scan showed asymmetrical spina bifida on the right side extending from L2 to L5, and symmetrical spina bifida below SI. Magnetic resonance imaging showed a low-set conus with terminal syringohydromyelia, lumbosacral lipoma, and the extradural arachnoid cysts at Th12-L4 compressing the spinal dural sac from behind. Surgical removal of the arachnoid cyst and lipoma relieved spinal dural sac compression and the tethered spinal cord. The patient showed an improvement in the lower-extremity hyperreflexia postoperatively. Conclusion: The rare association of the cloacal exstrophy with the multiple spinal cord abnormalities as shown in the present case indicates that detailed routine screening of the spinal cord is necessary for the careful planning of treatment in patients with anorectal anomalies.
• Fatal rupture following intra-aneurysmal embolization for the distal posterior inferior cerebellar artery aneurysm with parent artery preservation

  M Fujimura, M Nishijima, H Midorikawa, K Umezawa, T Hayashi, M Kaimori  CLINICAL NEUROLOGY AND NEUROSURGERY  105-  (2)  117  -120  2003/04  [Not refereed][Not invited]
   

  This 70-year-old female was admitted to our hospital I day after a sudden consciousness disturbance. Computed tomography (CT) showed subarachnoid hemorrhage (SAH), and angiogram revealed an irregular-shaped aneurysm at the lateral medullary segment of the left posterior inferior cerebellar artery (PICA). The patient was treated by intra-aneurysmal embolization with Guglielmi detachable coil (GDC) with parent artery preservation. Post-operative angiogram showed obliteration of the aneurysm except for the neck remnant, but she presented with rerupture 19 days after the onset and died 3 days later. Postmortem examination revealed massive hematoma around the aneurysm, which compressed medulla oblongata from behind. Histological assessment showed the 'entry' where the aneurysmal wall lacked internal elastic lamina, providing evidence of dissecting aneurysm. The present case suggests that embolization of distal PICA aneurysm with parent artery preservation should be avoided because radiological evaluation may fail to rule out the possibility of dissection, where the aneurysmal wall is affected not only at the 'entry' but also in the adjacent region. (C) 2002 Elsevier Science B.V. All rights reserved.
• A case of vertebral artery occlusion following heading play in soccer

  O Motohashi, M Kameyama, H Kon, M Fujimura, T Onuma  NEUROLOGICAL SURGERY  31-  (4)  431  -434  2003/04  [Not refereed][Not invited]
   

  A 13-year-old boar suffered from cerebeller infarction due to right vertebral artery occlusion after heading a ball during a rainy soccer game. Dissection of the vertebral artery after trivial head trauma is well known, but heading as the cause has not been reported. We speculated in this present case that excessive impact force to the young boy's neck due to the heavy rain-soaked ball might have caused right vertebral artery dissection and occlusion. High quality balls are recommended for young amateur players on rainy days.
• Spinal lipoma associated with terminal syringohydromyelia and a spinal arachnoid cyst in a patient with cloacal exstrophy

  M Fujimura, Y Kusaka, R Shirane  CHILDS NERVOUS SYSTEM  19-  (4)  254  -257  2003/04  [Not refereed][Not invited]
   

  Case report: A 2-year-old girl presented with repaired cloacal exstrophy and a subcutaneous mass at the midline of the lumbosacral region. Neurological examination revealed mild paraparesis with bilateral lower-extremity hyperreflexia and sensory disturbance below the level of L4. A CT scan showed asymmetrical spina bifida on the right side extending from L2 to L5, and symmetrical spina bifida below SI. Magnetic resonance imaging showed a low-set conus with terminal syringohydromyelia, lumbosacral lipoma, and the extradural arachnoid cysts at Th12-L4 compressing the spinal dural sac from behind. Surgical removal of the arachnoid cyst and lipoma relieved spinal dural sac compression and the tethered spinal cord. The patient showed an improvement in the lower-extremity hyperreflexia postoperatively. Conclusion: The rare association of the cloacal exstrophy with the multiple spinal cord abnormalities as shown in the present case indicates that detailed routine screening of the spinal cord is necessary for the careful planning of treatment in patients with anorectal anomalies.
• Optochiasmal arachnoiditis following cotton wrapping of anterior communicating artery aneurysm treated by surgical removal of granuloma

  M Fujimura, M Nishijima, K Umezawa, T Hayashi, Y Mino, T Sakuraba, H Midorikawa  JOURNAL OF CLINICAL NEUROSCIENCE  10-  (2)  254  -257  2003/03  [Not refereed][Not invited]
   

  We report the case of a 50 year old female who presented with visual disturbance due to optochiasmal arachnoiditis and foreign body granuloma 9 months after cotton wrapping for ruptured anterior communicating artery (AcomA) aneurysm. Magnetic resonance imaging (MRI) revealed enhanced mass lesion around AcomA complex and hyperintense signal on optic chiasm and right optic tract by fluid-attenuated inversion recovery image. Despite the repeated steroid pulse therapy, she deteriorated and MRI showed expansion of the granulomatous lesion over 5 months. Surgical removal of foreign body granuloma resulted in marked improvement of visual disturbance as well as of the MRI findings. We conclude that the use of cotton sheet close to the optic nerve should be avoided, and that surgical removal of the granuloma would be the optimal choice especially for the patient in whom steroid therapy fails to improve clinical symptoms. (C) 2003 Elsevier Science Ltd. All rights reserved.
• Optochiasmal arachnoiditis following cotton wrapping of anterior communicating artery aneurysm treated by surgical removal of granuloma

  M Fujimura, M Nishijima, K Umezawa, T Hayashi, Y Mino, T Sakuraba, H Midorikawa  JOURNAL OF CLINICAL NEUROSCIENCE  10-  (2)  254  -257  2003/03  [Not refereed][Not invited]
   

  We report the case of a 50 year old female who presented with visual disturbance due to optochiasmal arachnoiditis and foreign body granuloma 9 months after cotton wrapping for ruptured anterior communicating artery (AcomA) aneurysm. Magnetic resonance imaging (MRI) revealed enhanced mass lesion around AcomA complex and hyperintense signal on optic chiasm and right optic tract by fluid-attenuated inversion recovery image. Despite the repeated steroid pulse therapy, she deteriorated and MRI showed expansion of the granulomatous lesion over 5 months. Surgical removal of foreign body granuloma resulted in marked improvement of visual disturbance as well as of the MRI findings. We conclude that the use of cotton sheet close to the optic nerve should be avoided, and that surgical removal of the granuloma would be the optimal choice especially for the patient in whom steroid therapy fails to improve clinical symptoms. (C) 2003 Elsevier Science Ltd. All rights reserved.
• 脳室内における衝撃波医療応用に向けた基礎実験

  中川敦寛, 斎藤務, 日下康子, 大木友博, 神部真理子, 藤村幹, 平野孝幸, 上之原広司, 佐藤泰彦, 白根礼造, 高山和喜, 冨永悌二  平成15年度 衝撃波シンポジウム講演論文集  363  -364  2003  [Not refereed][Not invited]
  
• Mild hypothermia attenuates cytochrome C release but does not alter Bcl-2 expression or caspase activation after experimental stroke

  MA Yenari, S Iwayama, DY Cheng, GH Sun, M Fujimura, Y Morita-Fujimura, PH Chan, GK Steinberg  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM  22-  (1)  29  -38  2002/01  [Not refereed][Not invited]
   

  Mild hypothermia protects the brain from ischemia, but the underlying mechanisms of this effect are not well known. The authors previously found that hypothermia reduces the density of apoptotic cells, but it is not certain whether temperature alters associated biochemical events. Mitochondrial release of cytochrome c has recently been shown to be a key trigger in caspase activation and apoptosis via the intrinsic pathway. Using a model of transient focal cerebral ischemia, the authors determined whether mild hypothermia altered expression of Bcl-2 family proteins, mitochondrial release of cytochrome c, and caspase activation. Mild hypothermia significantly decreased the amount of cytochrome c release 5 hours after the onset of ischemia, but mitochondrial translocation of Bax was not observed until 24 hours. Mild hypothermia did not alter Bcl-2 and Bax expression, and caspase activation was not observed. The present study provides the first evidence that intraischemic mild hypothermia attenuates the release of cytochrome c in the brain, but does not appear to affect other biochemical aspects of the intrinsic apoptotic pathway. They conclude that necrotic processes may have been interrupted to prevent cytochrome c release, and that the ameliorative effect of mild hypothermia may be a result of maintaining mitochondrial integrity. Furthermore, the authors show it is unlikely that mild hypothermia alters the intrinsic apoptotic pathway.
• A case of calvarial eosinophilic granuloma with rapid expansion and wide skull invasion: immunohistochemical analysis of Ki-67

  M Fujimura, M Nishijima, K Umezawa, T Hayashi, M Kaimori  JOURNAL OF CLINICAL NEUROSCIENCE  9-  (1)  72  -76  2002/01  [Not refereed][Not invited]
   

  A 15-year-old male visited our neurological service with progressive occipitalgia. Computed tomography showed an osteolytic lesion at the occipital cranium, which grew rapidly during a month. Magnetic resonance Imaging, showed the lesion as low intensity on T1- and high intensity on T2-weighted images. The mass was soft and successfully removed with surrounding cranium. Histological examination revealed an eosinophilic granuloma with wide skull invasion. Immunohistochemical analysis on the specimen disclosed Ki-67 expression with labeling index of 6.2%. Relatively high proliferative activity in the present case indicates that the local replication of Langerhans' cells as well as inflammatory response contributes to the expansion of calvarial eosinophilic granuloma. This is the first report demonstrating the result of Ki-67 expression on calvarial eosinophilic granuloma. (C) 2002 Harcourt Publishers Ltd.
• Overexpression of copper/zinc superoxide dismutase in transgenic rats protects vulnerable neurons against ischemic damage by blocking the mitochondrial pathway of caspase activation

  T Sugawara, N Noshita, A Lewen, Y Gasche, M Ferrand-Duke, M Fujimura, Y Morita-Fujimura, PH Chan  JOURNAL OF NEUROSCIENCE  22-  (1)  209  -217  2002/01  [Not refereed][Not invited]
   

  Mitochondria are known to be involved in the early stage of apoptosis by releasing cytochrome c, caspase-9, and the second mitochondria-derived activator of caspases (Smac). We have reported that overexpression of copper/zinc superoxide dismutase (SOD1) reduced superoxide production and ameliorated neuronal injury in the hippocampal CA1 subregion after global ischemia. However, the role of oxygen free radicals produced after ischemia/reperfusion in the mitochondrial signaling pathway has not been clarified. Five minutes of global ischemia was induced in male SOD1-transgenic (Tg) and wildtype (Wt) littermate rats. Cytosolic expression of cytochrome c and Smac and activation of caspases were evaluated by immunohistochemistry, Western blot, and caspase activity assay. Apoptotic cell death was characterized by DNA nick end and single-stranded DNA labeling. In the Wt animals, early superoxide production, mitochondrial release of cytochrome c, Smac, and cleaved caspase-9 were observed after ischemia. Active caspase-3 was subsequently increased, and 85% of the hippocampal CA1 neurons showed apoptotic DNA damage 3 d after ischemia. Tg animals showed less superoxide production and cytochrome c and Smac release. Subsequent active caspase-3 expression was not evident, and only 45% of the neurons showed apoptotic DNA damage. A caspase-3 inhibitor (N-benzyloxycarbonyl-val-ala-asp-fluoromethyl ketone) reduced cell death only in Wt animals. These results suggest that overexpression of SOD1 reduced oxidative stress, thereby attenuating the mitochondrial release of cytochrome c and Smac, resulting in less caspase activation and apoptotic cell death. Oxygen free radicals may play a pivotal role in the mitochondrial signaling pathway of apoptotic cell death in hippocampal CA1 neurons after global ischemia.
• Mild hypothermia attenuates cytochrome C release but does not alter Bcl-2 expression or caspase activation after experimental stroke

  MA Yenari, S Iwayama, DY Cheng, GH Sun, M Fujimura, Y Morita-Fujimura, PH Chan, GK Steinberg  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM  22-  (1)  29  -38  2002/01  [Not refereed][Not invited]
   

  Mild hypothermia protects the brain from ischemia, but the underlying mechanisms of this effect are not well known. The authors previously found that hypothermia reduces the density of apoptotic cells, but it is not certain whether temperature alters associated biochemical events. Mitochondrial release of cytochrome c has recently been shown to be a key trigger in caspase activation and apoptosis via the intrinsic pathway. Using a model of transient focal cerebral ischemia, the authors determined whether mild hypothermia altered expression of Bcl-2 family proteins, mitochondrial release of cytochrome c, and caspase activation. Mild hypothermia significantly decreased the amount of cytochrome c release 5 hours after the onset of ischemia, but mitochondrial translocation of Bax was not observed until 24 hours. Mild hypothermia did not alter Bcl-2 and Bax expression, and caspase activation was not observed. The present study provides the first evidence that intraischemic mild hypothermia attenuates the release of cytochrome c in the brain, but does not appear to affect other biochemical aspects of the intrinsic apoptotic pathway. They conclude that necrotic processes may have been interrupted to prevent cytochrome c release, and that the ameliorative effect of mild hypothermia may be a result of maintaining mitochondrial integrity. Furthermore, the authors show it is unlikely that mild hypothermia alters the intrinsic apoptotic pathway.
• A case of calvarial eosinophilic granuloma with rapid expansion and wide skull invasion: immunohistochemical analysis of Ki-67

  M Fujimura, M Nishijima, K Umezawa, T Hayashi, M Kaimori  JOURNAL OF CLINICAL NEUROSCIENCE  9-  (1)  72  -76  2002/01  [Not refereed][Not invited]
   

  A 15-year-old male visited our neurological service with progressive occipitalgia. Computed tomography showed an osteolytic lesion at the occipital cranium, which grew rapidly during a month. Magnetic resonance Imaging, showed the lesion as low intensity on T1- and high intensity on T2-weighted images. The mass was soft and successfully removed with surrounding cranium. Histological examination revealed an eosinophilic granuloma with wide skull invasion. Immunohistochemical analysis on the specimen disclosed Ki-67 expression with labeling index of 6.2%. Relatively high proliferative activity in the present case indicates that the local replication of Langerhans' cells as well as inflammatory response contributes to the expansion of calvarial eosinophilic granuloma. This is the first report demonstrating the result of Ki-67 expression on calvarial eosinophilic granuloma. (C) 2002 Harcourt Publishers Ltd.
• Overexpression of copper/zinc superoxide dismutase in transgenic rats protects vulnerable neurons against ischemic damage by blocking the mitochondrial pathway of caspase activation

  T Sugawara, N Noshita, A Lewen, Y Gasche, M Ferrand-Duke, M Fujimura, Y Morita-Fujimura, PH Chan  JOURNAL OF NEUROSCIENCE  22-  (1)  209  -217  2002/01  [Not refereed][Not invited]
   

  Mitochondria are known to be involved in the early stage of apoptosis by releasing cytochrome c, caspase-9, and the second mitochondria-derived activator of caspases (Smac). We have reported that overexpression of copper/zinc superoxide dismutase (SOD1) reduced superoxide production and ameliorated neuronal injury in the hippocampal CA1 subregion after global ischemia. However, the role of oxygen free radicals produced after ischemia/reperfusion in the mitochondrial signaling pathway has not been clarified. Five minutes of global ischemia was induced in male SOD1-transgenic (Tg) and wildtype (Wt) littermate rats. Cytosolic expression of cytochrome c and Smac and activation of caspases were evaluated by immunohistochemistry, Western blot, and caspase activity assay. Apoptotic cell death was characterized by DNA nick end and single-stranded DNA labeling. In the Wt animals, early superoxide production, mitochondrial release of cytochrome c, Smac, and cleaved caspase-9 were observed after ischemia. Active caspase-3 was subsequently increased, and 85% of the hippocampal CA1 neurons showed apoptotic DNA damage 3 d after ischemia. Tg animals showed less superoxide production and cytochrome c and Smac release. Subsequent active caspase-3 expression was not evident, and only 45% of the neurons showed apoptotic DNA damage. A caspase-3 inhibitor (N-benzyloxycarbonyl-val-ala-asp-fluoromethyl ketone) reduced cell death only in Wt animals. These results suggest that overexpression of SOD1 reduced oxidative stress, thereby attenuating the mitochondrial release of cytochrome c and Smac, resulting in less caspase activation and apoptotic cell death. Oxygen free radicals may play a pivotal role in the mitochondrial signaling pathway of apoptotic cell death in hippocampal CA1 neurons after global ischemia.
• Matrix metalloproteinase inhibition prevents oxidative stress-associated blood-brain barrier disruption after transient focal cerebral ischemia

  Y Gasche, JC Copin, T Sugawara, M Fujimura, PH Chan  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM  21-  (12)  1393  -1400  2001/12  [Not refereed][Not invited]
   

  Oxidative stress generated during stroke is a critical event leading to blood-brain barrier (BBB) disruption with secondary vasogenic edema and hemorrhagic transformation of infarcted brain tissue, restricting the benefit of thrombolytic reperfusion. In this study, the authors demonstrate that ischemia-reperfusion-induced BBB disruption in mice deficient in copper/zinc-superoxide dismutase (SOD1) was reduced by 88% (P < 0.0001) and 73% (P < 0.01), respectively, after 3 and 7 hours of reperfusion occurring after I hour of ischemia by the inhibition of matrix metalloproteinases. Accordingly, the authors show that local metalloproteinase-generated proteolytic imbalance is more intense in ischemic regions of SOD1 mice than in wild-type litter mates. Moreover, active in situ proteolysis is, for the first time, demonstrated in ischemic leaking capillaries that produce reactive oxygen species. By showing that oxidative stress mediates BBB disruption through metalloproteinase activation in experimental ischemic stroke, this study provides a new target for future therapeutic strategies to prevent BBB disruption and potentially reperfusion-triggered intracerebral hemorrhage.
• Matrix metalloproteinase inhibition prevents oxidative stress-associated blood-brain barrier disruption after transient focal cerebral ischemia

  Y Gasche, JC Copin, T Sugawara, M Fujimura, PH Chan  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM  21-  (12)  1393  -1400  2001/12  [Not refereed][Not invited]
   

  Oxidative stress generated during stroke is a critical event leading to blood-brain barrier (BBB) disruption with secondary vasogenic edema and hemorrhagic transformation of infarcted brain tissue, restricting the benefit of thrombolytic reperfusion. In this study, the authors demonstrate that ischemia-reperfusion-induced BBB disruption in mice deficient in copper/zinc-superoxide dismutase (SOD1) was reduced by 88% (P < 0.0001) and 73% (P < 0.01), respectively, after 3 and 7 hours of reperfusion occurring after I hour of ischemia by the inhibition of matrix metalloproteinases. Accordingly, the authors show that local metalloproteinase-generated proteolytic imbalance is more intense in ischemic regions of SOD1 mice than in wild-type litter mates. Moreover, active in situ proteolysis is, for the first time, demonstrated in ischemic leaking capillaries that produce reactive oxygen species. By showing that oxidative stress mediates BBB disruption through metalloproteinase activation in experimental ischemic stroke, this study provides a new target for future therapeutic strategies to prevent BBB disruption and potentially reperfusion-triggered intracerebral hemorrhage.
• Superoxide during reperfusion contributes to caspase-8 expression and apoptosis after transient focal stroke

  Y Morita-Fujimura, M Fujimura, T Yoshimoto, PH Chan  STROKE  32-  (10)  2356  -2361  2001/10  [Not refereed][Not invited]
   

  Background and Purpose-Reactive oxygen species produced during reperfusion may play a detrimental role in focal cerebral ischemia (FCI). We examined the protein expression of caspase-8, which plays a major role in both Fas-dependent and cytochrome c-dependent apoptotic pathways after FCI with or without reperfusion. Caspase-8 expression after transient FCI was compared between wild-type and transgenic mice that overexpress the cytosolic antioxidant copper/zinc superoxide dismutase (SOD1). Methods-Adult male CD-1 mice were subjected to I hour of FCI and reperfusion or to permanent FCI by intraluminal blockade of the middle cerebral artery. DNA fragmentation was evaluated by genomic DNA gel electrophoresis. Caspase-8 expression was analyzed by Western blot. Results-Caspase-8 was significantly induced 4 hours after transient FCI and remained at an increased level until 24 hours, whereas it was not modified after permanent FCI. Genomic DNA gel electrophoresis showed DNA laddering in a pattern similar to that seen in apoptosis, with a small amount of background smear 24 hours after transient FCI, whereas 25 hours of permanent FCI resulted in less DNA laddering with a strong background smear. Caspase-8 induction was significantly reduced in SOD1 transgenic mice compared with wild-type mice 4 hours after transient FCI. Conclusions-The results suggest that increased reactive oxygen species production during reperfusion may contribute to the induction of caspase-8, thereby exacerbating apoptosis after FCI.
• Superoxide during reperfusion contributes to caspase-8 expression and apoptosis after transient focal stroke

  Y Morita-Fujimura, M Fujimura, T Yoshimoto, PH Chan  STROKE  32-  (10)  2356  -2361  2001/10  [Not refereed][Not invited]
   

  Background and Purpose-Reactive oxygen species produced during reperfusion may play a detrimental role in focal cerebral ischemia (FCI). We examined the protein expression of caspase-8, which plays a major role in both Fas-dependent and cytochrome c-dependent apoptotic pathways after FCI with or without reperfusion. Caspase-8 expression after transient FCI was compared between wild-type and transgenic mice that overexpress the cytosolic antioxidant copper/zinc superoxide dismutase (SOD1). Methods-Adult male CD-1 mice were subjected to I hour of FCI and reperfusion or to permanent FCI by intraluminal blockade of the middle cerebral artery. DNA fragmentation was evaluated by genomic DNA gel electrophoresis. Caspase-8 expression was analyzed by Western blot. Results-Caspase-8 was significantly induced 4 hours after transient FCI and remained at an increased level until 24 hours, whereas it was not modified after permanent FCI. Genomic DNA gel electrophoresis showed DNA laddering in a pattern similar to that seen in apoptosis, with a small amount of background smear 24 hours after transient FCI, whereas 25 hours of permanent FCI resulted in less DNA laddering with a strong background smear. Caspase-8 induction was significantly reduced in SOD1 transgenic mice compared with wild-type mice 4 hours after transient FCI. Conclusions-The results suggest that increased reactive oxygen species production during reperfusion may contribute to the induction of caspase-8, thereby exacerbating apoptosis after FCI.
• 術後患者管理の変遷によるクモ膜下出血症例の治療成績,及び,脳血管れん縮発生頻度の推移

  梅沢邦彦, 藤村幹, 林俊哲, 西島美知春  青森県立中央病院医誌  46-  (3)  174  -176  2001/09/20  [Not refereed][Not invited]
  
• Interhemispheric cyst causing leg monoparesis in the elderly - Case report

  T Hayashi, M Nishijima, K Umezawa, M Fujimura, M Kaimori  NEUROLOGIA MEDICO-CHIRURGICA  41-  (9)  463  -465  2001/09  [Not refereed][Not invited]
   

  A 64-year-old female presented with a rare case of interhemispheric cerebral cyst manifesting as progressive monoparesis in the right lower extremity for 2 years. Surgical excision of the cyst wall was performed and communication to the subdural space was created. Postoperatively, the cyst was greatly reduced in size, and the neurological signs and symptoms were markedly improved. Interhemispheric cyst often presents with motor disturbances such as hemiparesis or paraparesis. These symptoms tend to progress slowly and sometimes years are required for a proper diagnosis. Interhemispheric cyst can also cause slowly progressive monoparesis in the lower extremity.
• Interhemispheric cyst causing leg monoparesis in the elderly - Case report

  T Hayashi, M Nishijima, K Umezawa, M Fujimura, M Kaimori  NEUROLOGIA MEDICO-CHIRURGICA  41-  (9)  463  -465  2001/09  [Not refereed][Not invited]
   

  A 64-year-old female presented with a rare case of interhemispheric cerebral cyst manifesting as progressive monoparesis in the right lower extremity for 2 years. Surgical excision of the cyst wall was performed and communication to the subdural space was created. Postoperatively, the cyst was greatly reduced in size, and the neurological signs and symptoms were markedly improved. Interhemispheric cyst often presents with motor disturbances such as hemiparesis or paraparesis. These symptoms tend to progress slowly and sometimes years are required for a proper diagnosis. Interhemispheric cyst can also cause slowly progressive monoparesis in the lower extremity.
• Oxidative stress-dependent release of mitochondrial cytochrome c after traumatic brain injury

  A Lewen, M Fujimura, T Sugawara, P Matz, JC Copin, PH Chan  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM  21-  (8)  914  -920  2001/08  [Not refereed][Not invited]
   

  Mitochondrial cytochrome c translocation to the cytosol initiates the mitochondrial-dependent apoptotic pathway. This event has not been previously reported in traumatic; brain injury (TBI). The authors determined the expression of cytochrome c in cytosolic and mitochondrial fractions after severe TBI produced by the controlled cortical impact model in the mouse. One hour after trauma there was an increase in cytosolic cytochrome c immunoreactivity. The increases in cytosolic cytochrome c preceded DNA fragmentation, which started at 4 hours. Western blots of mitochondrial and cytosolic fractions confirmed that there was a translocation of cytochrome c from the mitochondria after TBI. Mice deficient in manganese superoxide dismutase (MnSOD) showed an increased loss of mitochondrial cytochrome c after trauma, but less apoptotic cell death 4 and 24 hours after injury compared with wild-type control mice. However, the overall cell death was increased in MnSOD mice, as illustrated by a larger cortical lesion in these animals. The results show that cytochrome c is released from the mitochondria after severe TBI partly by a free radical-dependent mechanism, and that massive mitochondrial cytochrome c release is a predictor of necrotic cell death rather than apoptosis.
• Oxidative stress-dependent release of mitochondrial cytochrome c after traumatic brain injury

  A Lewen, M Fujimura, T Sugawara, P Matz, JC Copin, PH Chan  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM  21-  (8)  914  -920  2001/08  [Not refereed][Not invited]
   

  Mitochondrial cytochrome c translocation to the cytosol initiates the mitochondrial-dependent apoptotic pathway. This event has not been previously reported in traumatic; brain injury (TBI). The authors determined the expression of cytochrome c in cytosolic and mitochondrial fractions after severe TBI produced by the controlled cortical impact model in the mouse. One hour after trauma there was an increase in cytosolic cytochrome c immunoreactivity. The increases in cytosolic cytochrome c preceded DNA fragmentation, which started at 4 hours. Western blots of mitochondrial and cytosolic fractions confirmed that there was a translocation of cytochrome c from the mitochondria after TBI. Mice deficient in manganese superoxide dismutase (MnSOD) showed an increased loss of mitochondrial cytochrome c after trauma, but less apoptotic cell death 4 and 24 hours after injury compared with wild-type control mice. However, the overall cell death was increased in MnSOD mice, as illustrated by a larger cortical lesion in these animals. The results show that cytochrome c is released from the mitochondria after severe TBI partly by a free radical-dependent mechanism, and that massive mitochondrial cytochrome c release is a predictor of necrotic cell death rather than apoptosis.
• Oxidative cellular damage and the reduction of APE/Ref-1 expression after experimental traumatic brain injury

  A Lewen, T Sugawara, Y Gasche, M Fujimura, PH Chan  NEUROBIOLOGY OF DISEASE  8-  (3)  380  -390  2001/06  [Not refereed][Not invited]
   

  The DNA repair enzyme, apurinic/apyrimidinic endonuclease (or redox effector factor-1, APE/Ref-1), is involved in base excision repair of apurinic/apyrimidinic sites after oxidative DNA damage. We investigated the expression of APE/Ref-1 and its relationship to oxidative stress after severe traumatic brain injury produced by controlled cortical impact in normal mice, and in mice over- or underexpressing copper-zinc superoxide dismutase (SOD1TG and SOD1KO, respectively). Oxygen free radical-mediated cellular injury was visualized with 8-hydroxyguanine immunoreactivity as a marker for DNA oxidation, and in situ hydroethidine oxidation as a marker for superoxide production. After trauma there was a reduced expression of APE/Ref-1 in the ipsilateral cortex and hippocampus that correlated with the gene dosage levels of cytosolic superoxide dismutase. The decrease in APE/Ref-1 expression preceded DNA fragmentation. There was also a close correlation between APE/Ref-1 protein levels 4 h after trauma and the volume of the lesion 1 week after injury. Our data have demonstrated that reduction of APE/Ref-1 protein levels correlates closely with the level of oxidative stress after traumatic brain injury. We suggest that APE/Ref-1 immunoreactivity is a sensitive marker for oxidative cellular injury. (C) 2001 Academic Press.
• Oxidative cellular damage and the reduction of APE/Ref-1 expression after experimental traumatic brain injury

  A Lewen, T Sugawara, Y Gasche, M Fujimura, PH Chan  NEUROBIOLOGY OF DISEASE  8-  (3)  380  -390  2001/06  [Not refereed][Not invited]
   

  The DNA repair enzyme, apurinic/apyrimidinic endonuclease (or redox effector factor-1, APE/Ref-1), is involved in base excision repair of apurinic/apyrimidinic sites after oxidative DNA damage. We investigated the expression of APE/Ref-1 and its relationship to oxidative stress after severe traumatic brain injury produced by controlled cortical impact in normal mice, and in mice over- or underexpressing copper-zinc superoxide dismutase (SOD1TG and SOD1KO, respectively). Oxygen free radical-mediated cellular injury was visualized with 8-hydroxyguanine immunoreactivity as a marker for DNA oxidation, and in situ hydroethidine oxidation as a marker for superoxide production. After trauma there was a reduced expression of APE/Ref-1 in the ipsilateral cortex and hippocampus that correlated with the gene dosage levels of cytosolic superoxide dismutase. The decrease in APE/Ref-1 expression preceded DNA fragmentation. There was also a close correlation between APE/Ref-1 protein levels 4 h after trauma and the volume of the lesion 1 week after injury. Our data have demonstrated that reduction of APE/Ref-1 protein levels correlates closely with the level of oxidative stress after traumatic brain injury. We suggest that APE/Ref-1 immunoreactivity is a sensitive marker for oxidative cellular injury. (C) 2001 Academic Press.
• Manganese superoxide dismutase affects cytochrome c release and caspase-9 activation after transient focal cerebral ischemia in mice

  N Noshita, T Sugawara, M Fujimura, Y Morita-Fujimura, PH Chan  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM  21-  (5)  557  -567  2001/05  [Not refereed][Not invited]
   

  Release of cytochrome c from mitochondria to cytosol is a critical step in the mitochondrial-dependent signaling pathways of apoptosis. The authors have reported that manganese superoxide dismutase (Mn-SOD) attenuated cytochrome c release and apoptotic cell death after focal cerebral ischemia (FCI). To investigate downstream to the cytochrome c-dependent pathway, the authors examined caspase-9 activation after transient FCI by immunohistochemistry and Western blotting in both wild-type and Sod2 -/+ mice. Mice were subjected to 60 minutes of middle cerebral artery occlusion followed by 1, 2, 4, or 24 hours of reperfusion. Two hours after reperfusion, cytochrome c and caspase-9 were observed in the cytosol and significantly increased in Sod2 -/+ mutants compared with wild-type mice as shown by Western blotting. Immunofluorescent double labeling for cytochrome c and caspase-9 showed cytosolic cytochrome c 1 hour after transient FCI. Cleaved caspase-9 first appeared in the cytosol at 2 hours and colocalized with cytochrome c. Terminal deoxynucleotidyl transferase-mediated uridine 5 ' -triphosphate-biotin nick and labeling (TUNEL) showed significant increase of positive cells in Sod2 -/+ mice compared with the wild-type in the cortex, but not in the caudate putamen. The current study revealed Mn-SOD might affect cytochrome L translocation and downstream caspase activation in the mitochondrial-dependent cell death pathway after transient FCI.
• Manganese superoxide dismutase affects cytochrome c release and caspase-9 activation after transient focal cerebral ischemia in mice

  N Noshita, T Sugawara, M Fujimura, Y Morita-Fujimura, PH Chan  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM  21-  (5)  557  -567  2001/05  [Not refereed][Not invited]
   

  Release of cytochrome c from mitochondria to cytosol is a critical step in the mitochondrial-dependent signaling pathways of apoptosis. The authors have reported that manganese superoxide dismutase (Mn-SOD) attenuated cytochrome c release and apoptotic cell death after focal cerebral ischemia (FCI). To investigate downstream to the cytochrome c-dependent pathway, the authors examined caspase-9 activation after transient FCI by immunohistochemistry and Western blotting in both wild-type and Sod2 -/+ mice. Mice were subjected to 60 minutes of middle cerebral artery occlusion followed by 1, 2, 4, or 24 hours of reperfusion. Two hours after reperfusion, cytochrome c and caspase-9 were observed in the cytosol and significantly increased in Sod2 -/+ mutants compared with wild-type mice as shown by Western blotting. Immunofluorescent double labeling for cytochrome c and caspase-9 showed cytosolic cytochrome c 1 hour after transient FCI. Cleaved caspase-9 first appeared in the cytosol at 2 hours and colocalized with cytochrome c. Terminal deoxynucleotidyl transferase-mediated uridine 5 ' -triphosphate-biotin nick and labeling (TUNEL) showed significant increase of positive cells in Sod2 -/+ mice compared with the wild-type in the cortex, but not in the caudate putamen. The current study revealed Mn-SOD might affect cytochrome L translocation and downstream caspase activation in the mitochondrial-dependent cell death pathway after transient FCI.
• 術後患者管理の変遷によるくも膜下出血症例の治療成績および脳血管れん縮発生頻度の推移

  梅沢邦彦, 西島美知春, 藤村幹, 林俊哲  脳血管れん縮  16-  358  -361  2001/03/20  [Not refereed][Not invited]
  
• Overexpression of copper-zinc superoxide dismutase attenuates acute activation of activator protein-1 after transient focal cerebral ischemia in mice

  CY Huang, M Fujimura, YY Chang, PH Chan  STROKE  32-  (3)  741  -747  2001/03  [Not refereed][Not invited]
   

  Background and Purpose-Reactive oxygen species (ROS) have been implicated in reperfusion injury after focal cerebral ischemia (FCI). ROS are known to regulate the activity of transcription factors such as activator protein-1 (AP-1), which is a dimer consisting of members of the Jun and Fos families. We investigated the role of ROS in AP-1 activity after FCI using transgenic mice that overexpressed copper-zinc superoxide dismutase (SOD1) and that had reduced infarction volume after FCI. Methods-The SOD1 transgenic mice and their wild-type littermates were subjected to middle cerebral artery occlusion and reperfusion by intraluminal suture blockade. After 60 minutes of middle cerebral artery occlusion, mice were allowed to recover for 1, 2, and 4 hours before euthanasia. Protein expression of c-Jun and c-Fos was examined by immunohistochemistry and Western blotting. AP-1 DNA-protein binding activity was assessed by electrophoretic mobility shirt assays. Results-In wild-type mice, immunohistochemistry demonstrated acute c-Jun and c-Fos activation in ischemic cortex and its outer boundary. Expression of both was reduced in SOD1 transgenic mice. Western blotting confirmed that SOD1 overexpression was associated with reduced c-Jun and c-Fos protein levels in ischemic brain. Electrophoretic mobility shift assays revealed that the ischemia-enhanced DNA binding activity observed in wild-type mice was reduced in SOD1 transgenic mice. Supershift assays indicated that c-Jun participated in the bound AP-1 complex. Conclusions-SOD1 overexpression prevents early activation of AP-1 after transient FCI in mice. This may block the expression of downstream target genes that are injurious, thereby reducing the infarction volume after transient FCI in mice.
• Severe subarachnoid hemorrhage with pulmonary edema successfully treated by intra-aneurysmal embolization using guglielmi detachable coils - Two case reports

  M Fujimura, M Nishijima, K Umezawa, H Kon, T Tanaka, H Midorikawa  NEUROLOGIA MEDICO-CHIRURGICA  41-  (3)  135  -139  2001/03  [Not refereed][Not invited]
   

  A 48-year-old male and a 39-year-old female presented with subarachnoid hemorrhage (SAH) due to ruptured anterior communicating artery aneurysms. Both patients were comatose on admission. Chest radiography disclosed pulmonary edema. They were conservatively treated under controlled ventilation, but cardiopulmonary dysfunction persisted over 2 days. The patients were then treated by intraaneurysmal embolization with Guglielmi detachable coils (GDCs) 2 days after the onset. The postoperative courses were uneventful, and the patients showed full recovery from pulmonary edema and were discharged without neurological deficits. Neurogenic pulmonary edema is one of the serious complications of SAH, and is a leading cause of poor clinical outcome. The favorable outcomes of the present cases suggest that intra-aneurysmal embolization with GDCs is an excellent choice for the patients with severe aneurysmal SAH complicated with pulmonary edema, in whom conventional surgical treatment under general anesthesia is difficult to perform in the acute stage.
• Overexpression of copper-zinc superoxide dismutase attenuates acute activation of activator protein-1 after transient focal cerebral ischemia in mice

  CY Huang, M Fujimura, YY Chang, PH Chan  STROKE  32-  (3)  741  -747  2001/03  [Not refereed][Not invited]
   

  Background and Purpose-Reactive oxygen species (ROS) have been implicated in reperfusion injury after focal cerebral ischemia (FCI). ROS are known to regulate the activity of transcription factors such as activator protein-1 (AP-1), which is a dimer consisting of members of the Jun and Fos families. We investigated the role of ROS in AP-1 activity after FCI using transgenic mice that overexpressed copper-zinc superoxide dismutase (SOD1) and that had reduced infarction volume after FCI. Methods-The SOD1 transgenic mice and their wild-type littermates were subjected to middle cerebral artery occlusion and reperfusion by intraluminal suture blockade. After 60 minutes of middle cerebral artery occlusion, mice were allowed to recover for 1, 2, and 4 hours before euthanasia. Protein expression of c-Jun and c-Fos was examined by immunohistochemistry and Western blotting. AP-1 DNA-protein binding activity was assessed by electrophoretic mobility shirt assays. Results-In wild-type mice, immunohistochemistry demonstrated acute c-Jun and c-Fos activation in ischemic cortex and its outer boundary. Expression of both was reduced in SOD1 transgenic mice. Western blotting confirmed that SOD1 overexpression was associated with reduced c-Jun and c-Fos protein levels in ischemic brain. Electrophoretic mobility shift assays revealed that the ischemia-enhanced DNA binding activity observed in wild-type mice was reduced in SOD1 transgenic mice. Supershift assays indicated that c-Jun participated in the bound AP-1 complex. Conclusions-SOD1 overexpression prevents early activation of AP-1 after transient FCI in mice. This may block the expression of downstream target genes that are injurious, thereby reducing the infarction volume after transient FCI in mice.
• Severe subarachnoid hemorrhage with pulmonary edema successfully treated by intra-aneurysmal embolization using guglielmi detachable coils - Two case reports

  M Fujimura, M Nishijima, K Umezawa, H Kon, T Tanaka, H Midorikawa  NEUROLOGIA MEDICO-CHIRURGICA  41-  (3)  135  -139  2001/03  [Not refereed][Not invited]
   

  A 48-year-old male and a 39-year-old female presented with subarachnoid hemorrhage (SAH) due to ruptured anterior communicating artery aneurysms. Both patients were comatose on admission. Chest radiography disclosed pulmonary edema. They were conservatively treated under controlled ventilation, but cardiopulmonary dysfunction persisted over 2 days. The patients were then treated by intraaneurysmal embolization with Guglielmi detachable coils (GDCs) 2 days after the onset. The postoperative courses were uneventful, and the patients showed full recovery from pulmonary edema and were discharged without neurological deficits. Neurogenic pulmonary edema is one of the serious complications of SAH, and is a leading cause of poor clinical outcome. The favorable outcomes of the present cases suggest that intra-aneurysmal embolization with GDCs is an excellent choice for the patients with severe aneurysmal SAH complicated with pulmonary edema, in whom conventional surgical treatment under general anesthesia is difficult to perform in the acute stage.
• SOD1 down-regulates NF-kappa B and c-mye expression in mice after transient focal cerebral ischemia

  CY Huang, M Fujimura, N Noshita, YY Chang, PH Chan  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM  21-  (2)  163  -173  2001/02  [Not refereed][Not invited]
   

  Reactive oxygen species (ROS) are implicated in reperfusion injury after focal cerebral ischemia (FCI). Reactive oxygen species regulate activity of transcription factors like NF-kappaB. The authors investigated the role of ROS in NF-kappaB activity after FCI using transgenic mice that overexpressed human coppcr/zinc-superoxide dismutase: (SODI) and that had reduced infarction volume after FCI. Superoxide dismutase transgenic and wild-type mice were subjected to 1 hour of middle cerebral artery occlusion (MCAO) and subsequent reperfusion. Immunohistochemistry showed SODI overexpression attenuated ischemia-induced NF-kappaB p65 immunoreactivity. Colocalization of NF-kappaB and the neuronal marker, microtubule-associated proteins (MAPs), showed that NF-kappaB was up-regulated in neurons after FCI. Electrophoretic mobility shift assays showed that SOD1 overexpression reduced ischemia-induced NF-kappaB DNA binding activity. Supershift assays showed that DNA-protein complexes contained p65 and p50 subunits. Immunoreactivity of c-myc, an NF-kappaB downstream gene, was increased in the ischemic cortex and colocalized with NF-KB. Western blotting showed that SOD1 overexpression reduced NF-KB and c-Myc protein levels in the ischemic brain. Colocalization of c-Myc and TUNEL staining was observed 24 hours after FCI. The current findings provide the first evidence that SOD 1 overexpression attenuates activation of NF-kappaB after transient FCI in mice and that preventing this early activation may block expression of downstream deleterious genes like c-myc, thereby reducing ischemic damage.
• Increased cytochrome c-mediated DNA fragmentation and cell death in manganese-superoxide dismutas-deficient mice after exposure to subarachnoid hemolysate

  PG Matz, M Fujimura, A Lewen, Y Morita-Fujimura, PH Chan  STROKE  32-  (2)  506  -515  2001/02  [Not refereed][Not invited]
   

  Background and Purpose-We sought to investigate the mechanisms for oxidative injury caused by subarachnoid hemolysate, a pro-oxidant. Methods-Injection of 50 muL of subarachnoid hemolysate or saline was performed in CD1 mice (n = 75), mutant mice deficient in Mn-superoxide dismutase (Sod2 +/-; n = 23), and their wild-type littermates (n = 23), Subcellular location of cytochrome c was studied by immunocytochemistry, immunofluorescence, and immunoblotting of cellular fractions. DNA fragmentation was assessed though DNA laddering and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL). Cell death was examined through basic histology Results-Cytochrome c immunoreactivity was present in the cytosol of neurons at 3 hours after hemolysate injection and increased by 4 hours compared with saline-injected animals (P<0,02), Cytosolic cytochrome c was more abundant in Sod2+/- mutants. DNA fragmentation was evident at 14 hours, but not 3 hours, after hemolysate injection as determined by DNA laddering and TUNEL staining (P<0,02). DNA fragmentation colocalized to cells with cytosolic cytochrome c and iron. In Sod2+/- mutants, the extent of fragmentation was increased as determined by TUNEL staining (52% increase; P<0.02) and DNA laddering (optical density = 0.819 versus 0.391; P<0.01), Cell death was evident on basic histology as early as 3 hours after hemolysate injection. No cell death was evident in controls. In Sod2+/- mutants, cell death was increased by 51% compared with wild-type littermates (P<0,05), Conclusions-These results demonstrate that subarachnoid blood products are associated with the presence of cytochrome c in the cytosol and subsequent cell death in neurons. It appears that Mn-superoxide dismutase plays a role in preventing cell death after exposure to subarachnoid blood products.
• SOD1 down-regulates NF-kappa B and c-mye expression in mice after transient focal cerebral ischemia

  CY Huang, M Fujimura, N Noshita, YY Chang, PH Chan  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM  21-  (2)  163  -173  2001/02  [Not refereed][Not invited]
   

  Reactive oxygen species (ROS) are implicated in reperfusion injury after focal cerebral ischemia (FCI). Reactive oxygen species regulate activity of transcription factors like NF-kappaB. The authors investigated the role of ROS in NF-kappaB activity after FCI using transgenic mice that overexpressed human coppcr/zinc-superoxide dismutase: (SODI) and that had reduced infarction volume after FCI. Superoxide dismutase transgenic and wild-type mice were subjected to 1 hour of middle cerebral artery occlusion (MCAO) and subsequent reperfusion. Immunohistochemistry showed SODI overexpression attenuated ischemia-induced NF-kappaB p65 immunoreactivity. Colocalization of NF-kappaB and the neuronal marker, microtubule-associated proteins (MAPs), showed that NF-kappaB was up-regulated in neurons after FCI. Electrophoretic mobility shift assays showed that SOD1 overexpression reduced ischemia-induced NF-kappaB DNA binding activity. Supershift assays showed that DNA-protein complexes contained p65 and p50 subunits. Immunoreactivity of c-myc, an NF-kappaB downstream gene, was increased in the ischemic cortex and colocalized with NF-KB. Western blotting showed that SOD1 overexpression reduced NF-KB and c-Myc protein levels in the ischemic brain. Colocalization of c-Myc and TUNEL staining was observed 24 hours after FCI. The current findings provide the first evidence that SOD 1 overexpression attenuates activation of NF-kappaB after transient FCI in mice and that preventing this early activation may block expression of downstream deleterious genes like c-myc, thereby reducing ischemic damage.
• Increased cytochrome c-mediated DNA fragmentation and cell death in manganese-superoxide dismutas-deficient mice after exposure to subarachnoid hemolysate

  PG Matz, M Fujimura, A Lewen, Y Morita-Fujimura, PH Chan  STROKE  32-  (2)  506  -515  2001/02  [Not refereed][Not invited]
   

  Background and Purpose-We sought to investigate the mechanisms for oxidative injury caused by subarachnoid hemolysate, a pro-oxidant. Methods-Injection of 50 muL of subarachnoid hemolysate or saline was performed in CD1 mice (n = 75), mutant mice deficient in Mn-superoxide dismutase (Sod2 +/-; n = 23), and their wild-type littermates (n = 23), Subcellular location of cytochrome c was studied by immunocytochemistry, immunofluorescence, and immunoblotting of cellular fractions. DNA fragmentation was assessed though DNA laddering and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL). Cell death was examined through basic histology Results-Cytochrome c immunoreactivity was present in the cytosol of neurons at 3 hours after hemolysate injection and increased by 4 hours compared with saline-injected animals (P<0,02), Cytosolic cytochrome c was more abundant in Sod2+/- mutants. DNA fragmentation was evident at 14 hours, but not 3 hours, after hemolysate injection as determined by DNA laddering and TUNEL staining (P<0,02). DNA fragmentation colocalized to cells with cytosolic cytochrome c and iron. In Sod2+/- mutants, the extent of fragmentation was increased as determined by TUNEL staining (52% increase; P<0.02) and DNA laddering (optical density = 0.819 versus 0.391; P<0.01), Cell death was evident on basic histology as early as 3 hours after hemolysate injection. No cell death was evident in controls. In Sod2+/- mutants, cell death was increased by 51% compared with wild-type littermates (P<0,05), Conclusions-These results demonstrate that subarachnoid blood products are associated with the presence of cytochrome c in the cytosol and subsequent cell death in neurons. It appears that Mn-superoxide dismutase plays a role in preventing cell death after exposure to subarachnoid blood products.
• Severe subarachnoid hemorrhage with pulmonary edema successfully treated by intra-aneurysmal embolization using Guglielmi detachable coils

  Miki Fujimura, Michiharu Nishijima, Kunihiko Umezawa, Hiroyuki Kon, Teruhiko Tanaka, Hiroshi Midorikawa  Neurologia Medico-Chirurgica  41-  (3)  135  -139  2001  [Not refereed][Not invited]
   

  A 48-year-old male and a 39-year-old female presented with subarachnoid hemorrhage (SAH) due to ruptured anterior communicating artery aneurysms. Both patients were comatose on admission. Chest radiography disclosed pulmonary edema. They were conservatively treated under controlled ventilation, but cardiopulmonary dysfunction persisted over 2 days. The patients were then treated by intra-aneurysmal embolization with Guglielmi detachable coils (GDCs) 2 days after the onset. The postoperative courses were uneventful, and the patients showed full recovery from pulmonary edema and were discharged without neurological deficits. Neurogenic pulmonary edema is one of the serious complications of SAH, and is a leading cause of poor clinical outcome. The favorable outcomes of the present cases suggest that intra-aneurysmal embolization with GDCs is an excellent choice for the patients with severe aneurysmal SAH complicated with pulmonary edema, in whom conventional surgical treatment under general anesthesia is difficult to perform in the acute stage.
• マウス局所脳虚血後のAP endonucleaseの発現動態とDNA障害に関する基礎的検討 Superoxideの役割について

  藤村幹, 吉本高志, 近藤健男, 森田維子, 藤村, ChanPak.H  脳循環代謝  13-  (1)  38  -39  2001  [Not refereed][Not invited]
  
• Reduction of copper,zinc-superoxide dismutase in knockout mice does not affect edema or infarction volumes and the early release of mitochondrial cytochrome c after permanent focal cerebral ischemia

  M Fujimura, Y Morita-Fujimura, JC Copin, T Yoshimoto, PH Chan  BRAIN RESEARCH  889-  (1-2)  208  -213  2001/01  [Not refereed][Not invited]
   

  Copper,zinc-superoxide dismutase (SOD1) was shown to be highly protective against ischemia/reperfusion injury in the brain. We have recently reported that SOD1 prevents the release of mitochondrial cytochrome c and subsequent apoptosis after ischemia/reperfusion in mice. To investigate its dose dependent effect on permanent focal cerebral ischemia, we examined neurological deficit scores, infarction volume, and the amount of hemisphere enlargement after 24 h of focal cerebral ischemia in both knockout mutants of SOD1 (Sod1 -/+ and Sod1 -/-) and wild-type littermates. We also examined the release of cytochrome c and subsequent DNA fragmentation after ischemia. There were no differences in the neurological deficit scores, infarction volumes and edema formation. There was also no difference of the amount cytosolic cytochrome c at 2 h and of the amount of DNA fragmentation at 24 h after focal cerebral ischemia. The results indicate that the SOD1 enzyme does not appear to affect cerebral infarction, cerebral edema nor the mitochondrial signaling pathway for apoptosis following permanent focal cerebral ischemia where there is no reperfusion injury. (C) 2001 Elsevier Science B.V. All rights reserved.
• Reduction of copper,zinc-superoxide dismutase in knockout mice does not affect edema or infarction volumes and the early release of mitochondrial cytochrome c after permanent focal cerebral ischemia

  M Fujimura, Y Morita-Fujimura, JC Copin, T Yoshimoto, PH Chan  BRAIN RESEARCH  889-  (1-2)  208  -213  2001/01  [Not refereed][Not invited]
   

  Copper,zinc-superoxide dismutase (SOD1) was shown to be highly protective against ischemia/reperfusion injury in the brain. We have recently reported that SOD1 prevents the release of mitochondrial cytochrome c and subsequent apoptosis after ischemia/reperfusion in mice. To investigate its dose dependent effect on permanent focal cerebral ischemia, we examined neurological deficit scores, infarction volume, and the amount of hemisphere enlargement after 24 h of focal cerebral ischemia in both knockout mutants of SOD1 (Sod1 -/+ and Sod1 -/-) and wild-type littermates. We also examined the release of cytochrome c and subsequent DNA fragmentation after ischemia. There were no differences in the neurological deficit scores, infarction volumes and edema formation. There was also no difference of the amount cytosolic cytochrome c at 2 h and of the amount of DNA fragmentation at 24 h after focal cerebral ischemia. The results indicate that the SOD1 enzyme does not appear to affect cerebral infarction, cerebral edema nor the mitochondrial signaling pathway for apoptosis following permanent focal cerebral ischemia where there is no reperfusion injury. (C) 2001 Elsevier Science B.V. All rights reserved.
• 急性くも膜下出血症例における血管内手術の有用性

  林俊哲, 西島美知春, 梅沢邦彦, 藤村幹, 緑川宏, 松尾国弘  日本脳神経外科学会総会抄録集  59th-  (Abstract)  327  2000/10/24  [Not refereed][Not invited]
  
• 術後治療の変遷によるクモ膜下出血症例の治療成績,及び脳血管れん縮発生頻度の推移

  梅沢邦彦, 藤村幹, 林俊哲, 西島美知春  日本脳神経外科学会総会抄録集  59th-  (Abstract)  122  2000/10/24  [Not refereed][Not invited]
  
• Effect of hypotension severity on hippocampal CA1 neurons in a rat global ischemia model

  T Sugawara, M Kawase, A Lewen, N Noshita, Y Gasche, M Fujimura, PH Chan  BRAIN RESEARCH  877-  (2)  281  -287  2000/09  [Not refereed][Not invited]
   

  Neuronal death in the hippocampal CA1 subregion has been shown to occur in a delayed manner after transient global ischemia. The 2-vessel occlusion model is one of the most frequently used global ischemia paradigms in rodents. Although researchers often fail to induce bilateral delayed CA1 neuronal death, the importance of hypotension severity has not been fully discussed. We induced 10 min of global ischemia with 2-vessel occlusion and various severities of hypotension in rats, and the subsequent neuronal damage and neurogenesis in the hippocampal CA1 pyramidal cell layer were immunohistochemically studied. Neuronal apoptosis after global ischemia was also characterized by terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling (TUNEL). The mean arterial blood pressure of 31-35 mmHg was the most appropriate range of hypotension in this model because of low mortality and consistent bilateral CA1 injury. Most of the neurons in the CA1 pyramidal cell layer lost neuron specific nuclear protein and became TUNEL-positive 3 days after ischemia. There was no evidence of apoptosis or neurogenesis at 7-28 days. There were ischemia-tolerant neurons in the CA1 pyramidal cell layer that survived delayed neurodegeneration, however, further studies are necessary to characterize the property of these neurons. (C) 2000 Elsevier Science B.V. All rights reserved.
• Effect of hypotension severity on hippocampal CA1 neurons in a rat global ischemia model

  T Sugawara, M Kawase, A Lewen, N Noshita, Y Gasche, M Fujimura, PH Chan  BRAIN RESEARCH  877-  (2)  281  -287  2000/09  [Not refereed][Not invited]
   

  Neuronal death in the hippocampal CA1 subregion has been shown to occur in a delayed manner after transient global ischemia. The 2-vessel occlusion model is one of the most frequently used global ischemia paradigms in rodents. Although researchers often fail to induce bilateral delayed CA1 neuronal death, the importance of hypotension severity has not been fully discussed. We induced 10 min of global ischemia with 2-vessel occlusion and various severities of hypotension in rats, and the subsequent neuronal damage and neurogenesis in the hippocampal CA1 pyramidal cell layer were immunohistochemically studied. Neuronal apoptosis after global ischemia was also characterized by terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling (TUNEL). The mean arterial blood pressure of 31-35 mmHg was the most appropriate range of hypotension in this model because of low mortality and consistent bilateral CA1 injury. Most of the neurons in the CA1 pyramidal cell layer lost neuron specific nuclear protein and became TUNEL-positive 3 days after ischemia. There was no evidence of apoptosis or neurogenesis at 7-28 days. There were ischemia-tolerant neurons in the CA1 pyramidal cell layer that survived delayed neurodegeneration, however, further studies are necessary to characterize the property of these neurons. (C) 2000 Elsevier Science B.V. All rights reserved.
• Reduction of the DNA base excision repair protein, XRCC1, may contribute to DNA fragmentation after cold injury-induced brain trauma in mice

  M Fujimura, Y Morita-Fujimura, N Noshita, T Yoshimoto, PH Chan  BRAIN RESEARCH  869-  (1-2)  105  -111  2000/06  [Not refereed][Not invited]
   

  The X-ray repair cross-complementing group 1 (XRCC1) protein plays a central role in the DNA base excision repair pathway by interacting with DNA ligase III and DNA polymerase beta. The present study examined the protein expression of XRCC1 and DNA fragmentation before and after cold injury-induced brain trauma (CIBT) in mice, in which apoptosis is assumed to participate. Immunohistochemistry showed the nuclear expression of XRCC1 in the entire region of the control brains. Fifteen minutes after CIBT, nuclear immunoreactivity was predominantly decreased in the inner boundary of the lesion, followed by a significant reduction of XRCC1 in the entire lesion 4 h after CIBT. A characteristic 70-kDa band was detected in the non-traumatic area, and was markedly decreased after CIBT as shown by Western blot analysis. DNA fragmentation was also observed after CIBT, and double staining with XRCC1 immunohistochemistry and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling showed a spatial relationship between XRCC1 loss and DNA fragmentation 24 h after CIBT. These data indicate that early decrease of XRCC1 and failure of the DNA repair mechanism may contribute to DNA-damaged neuronal cell death after CIBT. (C) 2000 Elsevier Science B.V. All rights reserved.
• Reduction of the DNA base excision repair protein, XRCC1, may contribute to DNA fragmentation after cold injury-induced brain trauma in mice

  M Fujimura, Y Morita-Fujimura, N Noshita, T Yoshimoto, PH Chan  BRAIN RESEARCH  869-  (1-2)  105  -111  2000/06  [Not refereed][Not invited]
   

  The X-ray repair cross-complementing group 1 (XRCC1) protein plays a central role in the DNA base excision repair pathway by interacting with DNA ligase III and DNA polymerase beta. The present study examined the protein expression of XRCC1 and DNA fragmentation before and after cold injury-induced brain trauma (CIBT) in mice, in which apoptosis is assumed to participate. Immunohistochemistry showed the nuclear expression of XRCC1 in the entire region of the control brains. Fifteen minutes after CIBT, nuclear immunoreactivity was predominantly decreased in the inner boundary of the lesion, followed by a significant reduction of XRCC1 in the entire lesion 4 h after CIBT. A characteristic 70-kDa band was detected in the non-traumatic area, and was markedly decreased after CIBT as shown by Western blot analysis. DNA fragmentation was also observed after CIBT, and double staining with XRCC1 immunohistochemistry and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling showed a spatial relationship between XRCC1 loss and DNA fragmentation 24 h after CIBT. These data indicate that early decrease of XRCC1 and failure of the DNA repair mechanism may contribute to DNA-damaged neuronal cell death after CIBT. (C) 2000 Elsevier Science B.V. All rights reserved.
• The cytosolic antioxidant copper/zinc-superoxide dismutase prevents the early release of mitochondrial cytochrome c in ischemic brain after transient focal cerebral ischemia in mice

  M Fujimura, Y Morita-Fujimura, N Noshita, T Sugawara, M Kawase, PH Chan  JOURNAL OF NEUROSCIENCE  20-  (8)  2817  -2824  2000/04  [Not refereed][Not invited]
   

  Release of mitochondrial cytochrome c into the cytosol is a critical step in apoptosis. We have reported that early release of cytochrome c in vivo occurs after permanent focal cerebral ischemia (FCI) and is mediated by the mitochondrial antioxidant manganese superoxide dismutase (SOD). However, the role of reactive oxygen species produced after ischemia-reperfusion in the mitochondrial apoptosis process is still unknown, although overexpression of copper/zinc-SOD (SOD1), a cytosolic isoenzyme, protects against ischemia-reperfusion. We now hypothesize that the overexpression of SOD1 also prevents apoptosis after FCI. To address this issue, we examined the subcellular distribution of the cytochrome c protein in both wild-type mice and in SOD1 transgenic (Tg) mice after transient FCI. Cytosolic cytochrome c was detected as early as 2 hr after reperfusion, and correspondingly, mitochondrial cytochrome c was significantly reduced after FCI. Cytosolic cytochrome c was significantly lower in the SOD1 Tg mice compared with wild types 2 (p < 0.0001) and 4 (p < 0.05) hr after FCI. Apaf-1, which interacts with cytochrome c and activates caspases, was constitutively expressed in both groups of animals, with no alteration after FCI. Double staining with cytochrome c immunohistochemistry and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling showed a spatial relationship between cytosolic cytochrome c expression and DNA fragmentation. A significant amount of DNA laddering was detected 24 hr after ischemia and was reduced in SOD1 Tg mice. These data suggest that SOD1 blocks cytosolic release of cytochrome c and could thereby reduce apoptosis after transient FCI.
• The cytosolic antioxidant copper/zinc-superoxide dismutase prevents the early release of mitochondrial cytochrome c in ischemic brain after transient focal cerebral ischemia in mice

  M Fujimura, Y Morita-Fujimura, N Noshita, T Sugawara, M Kawase, PH Chan  JOURNAL OF NEUROSCIENCE  20-  (8)  2817  -2824  2000/04  [Not refereed][Not invited]
   

  Release of mitochondrial cytochrome c into the cytosol is a critical step in apoptosis. We have reported that early release of cytochrome c in vivo occurs after permanent focal cerebral ischemia (FCI) and is mediated by the mitochondrial antioxidant manganese superoxide dismutase (SOD). However, the role of reactive oxygen species produced after ischemia-reperfusion in the mitochondrial apoptosis process is still unknown, although overexpression of copper/zinc-SOD (SOD1), a cytosolic isoenzyme, protects against ischemia-reperfusion. We now hypothesize that the overexpression of SOD1 also prevents apoptosis after FCI. To address this issue, we examined the subcellular distribution of the cytochrome c protein in both wild-type mice and in SOD1 transgenic (Tg) mice after transient FCI. Cytosolic cytochrome c was detected as early as 2 hr after reperfusion, and correspondingly, mitochondrial cytochrome c was significantly reduced after FCI. Cytosolic cytochrome c was significantly lower in the SOD1 Tg mice compared with wild types 2 (p < 0.0001) and 4 (p < 0.05) hr after FCI. Apaf-1, which interacts with cytochrome c and activates caspases, was constitutively expressed in both groups of animals, with no alteration after FCI. Double staining with cytochrome c immunohistochemistry and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling showed a spatial relationship between cytosolic cytochrome c expression and DNA fragmentation. A significant amount of DNA laddering was detected 24 hr after ischemia and was reduced in SOD1 Tg mice. These data suggest that SOD1 blocks cytosolic release of cytochrome c and could thereby reduce apoptosis after transient FCI.
• Subarachnoid hemolysate produces DNA fragmentation in a pattern similar to apoptosis in mouse brain

  PG Matz, M Fujimura, PH Chan  BRAIN RESEARCH  858-  (2)  312  -319  2000/03  [Not refereed][Not invited]
   

  Stroke and traumatic brain/spinal cord injuries are often associated with hemorrhage. Despite the relative frequency of hemorrhage in the central nervous system (CNS), little is known about what role blood and hemoglobin (Hb) play in mediating cellular injury. Since Hb and hemolysate have been associated with generation of oxidative stress and cell injury, we examined whether apoptosis was present after cortical exposure to subarachnoid hemolysate. Subarachnoid hemorrhage (SAH) was induced in CD-1 mice (n = 25) by injection of 50 mu l of autologous hemolysate over the right parietal cortex. Saline-injected mice (n. = 13) were used as controls. Subjects were sacrificed at 24 h. Transcardiac perfusion fixation was performed on a subgroup of hemolysate- (n. = 15) and saline-injected (n = 9) animals. Sections were stained for DNA fragmentation using the terminal deoxyuridine nick end-labeling (TUNEL) method and also immunostained for the hemeoxygenase-1 (HO-1) protein to assess blood distribution In the remaining animals (n = 6 SAH, n = 4 saline), DNA was extracted and precipitated from 40 mg of tissue and subjected to electrophoresis on a 1.5% agarose gel. DNA fragmentation was evident on TUNEL staining in 10/15 subjects injected with hemolysate as compared to 0/9 subjects injected with saline (p < 0.01, Fisher exact test). TUNEL-positive cells were most abundant closest to the site of cortical SAH, as evidenced by HO-1 immunoreactivity. TUNEL-positive cells were also seen remotely in the hippocampus and basal forebrain. The presence of apoptosis was suggested by DNA laddering on electrophoresis in the hemolysate-injected subjects (4/6 animals). No laddering was evident in saline-injected subjects (rt = 4). These results provide evidence that the presence of subarachnoid blood products is associated with DNA fragmentation and apoptotic cell death. (C) 2000 Elsevier Science B.V. All rights reserved.
• Subarachnoid hemolysate produces DNA fragmentation in a pattern similar to apoptosis in mouse brain

  PG Matz, M Fujimura, PH Chan  BRAIN RESEARCH  858-  (2)  312  -319  2000/03  [Not refereed][Not invited]
   

  Stroke and traumatic brain/spinal cord injuries are often associated with hemorrhage. Despite the relative frequency of hemorrhage in the central nervous system (CNS), little is known about what role blood and hemoglobin (Hb) play in mediating cellular injury. Since Hb and hemolysate have been associated with generation of oxidative stress and cell injury, we examined whether apoptosis was present after cortical exposure to subarachnoid hemolysate. Subarachnoid hemorrhage (SAH) was induced in CD-1 mice (n = 25) by injection of 50 mu l of autologous hemolysate over the right parietal cortex. Saline-injected mice (n. = 13) were used as controls. Subjects were sacrificed at 24 h. Transcardiac perfusion fixation was performed on a subgroup of hemolysate- (n. = 15) and saline-injected (n = 9) animals. Sections were stained for DNA fragmentation using the terminal deoxyuridine nick end-labeling (TUNEL) method and also immunostained for the hemeoxygenase-1 (HO-1) protein to assess blood distribution In the remaining animals (n = 6 SAH, n = 4 saline), DNA was extracted and precipitated from 40 mg of tissue and subjected to electrophoresis on a 1.5% agarose gel. DNA fragmentation was evident on TUNEL staining in 10/15 subjects injected with hemolysate as compared to 0/9 subjects injected with saline (p < 0.01, Fisher exact test). TUNEL-positive cells were most abundant closest to the site of cortical SAH, as evidenced by HO-1 immunoreactivity. TUNEL-positive cells were also seen remotely in the hippocampus and basal forebrain. The presence of apoptosis was suggested by DNA laddering on electrophoresis in the hemolysate-injected subjects (4/6 animals). No laddering was evident in saline-injected subjects (rt = 4). These results provide evidence that the presence of subarachnoid blood products is associated with DNA fragmentation and apoptotic cell death. (C) 2000 Elsevier Science B.V. All rights reserved.
• Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke

  GT Manley, M Fujimura, TH Ma, N Noshita, F Filiz, AW Bollen, P Chan, AS Verkman  NATURE MEDICINE  6-  (2)  159  -163  2000/02  [Not refereed][Not invited]
   

  Cerebral edema contributes significantly to morbidity and death associated with many common neurological disorders. However, current treatment options are limited to hyperosmolar agents and surgical decompression, therapies introduced more than 70 years ago. Here we show that mice deficient in aquaporin-4 (AQP4), a glial membrane water channel, have much better survival than wild-type mice in a model of brain edema caused by acute water intoxication. Brain tissue water content and swelling of pericapillary astrocytic foot processes in AQP4-deficient mice were significantly reduced. In another model of brain edema, focal ischemic stroke produced by middle cerebral artery occlusion, AQP4-deficient mice had improved neurological outcome. Cerebral edema, as measured by percentage of hemispheric enlargement at 24 h, was decreased by 35% in AQP4-deficient mice. These results implicate a key role for AQP4 in modulating brain water transport, and suggest that AQP4 inhibition may provide a new therapeutic option for reducing brain edema in a wide variety of cerebral disorders.
• Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke

  GT Manley, M Fujimura, TH Ma, N Noshita, F Filiz, AW Bollen, P Chan, AS Verkman  NATURE MEDICINE  6-  (2)  159  -163  2000/02  [Not refereed][Not invited]
   

  Cerebral edema contributes significantly to morbidity and death associated with many common neurological disorders. However, current treatment options are limited to hyperosmolar agents and surgical decompression, therapies introduced more than 70 years ago. Here we show that mice deficient in aquaporin-4 (AQP4), a glial membrane water channel, have much better survival than wild-type mice in a model of brain edema caused by acute water intoxication. Brain tissue water content and swelling of pericapillary astrocytic foot processes in AQP4-deficient mice were significantly reduced. In another model of brain edema, focal ischemic stroke produced by middle cerebral artery occlusion, AQP4-deficient mice had improved neurological outcome. Cerebral edema, as measured by percentage of hemispheric enlargement at 24 h, was decreased by 35% in AQP4-deficient mice. These results implicate a key role for AQP4 in modulating brain water transport, and suggest that AQP4 inhibition may provide a new therapeutic option for reducing brain edema in a wide variety of cerebral disorders.
• マウス局所脳虚血後のミトコンドリアからのcytochrome cの漏出とapoptosis;SOD-2の役割について

  藤村幹, 川瀬誠, 森田維子, 藤村, 近藤健男, ChanPak H, 吉本高志  脳卒中  22-  (1)  184  -184  2000  [Not refereed][Not invited]
  
• マウス局所脳虚血再灌流後のmatrix metalloproteinase-9の誘導と活性化 血液脳関門の破綻との関連について

  藤村幹, YvanKasche, 森田維子, 藤村, 近藤健男, ChanPak H, 吉本高志  日本脳神経外科学会59回総会抄録集  79  -79  2000  [Not refereed][Not invited]
  
• マウス局所脳虚血後のミトコンドリアからの cytochrome c 漏出とアポトーシス.

  藤村幹, 森田-藤村維子, 川瀬誠, 近藤健男, 吉本高志, PH Chan  脳卒中  22-  (3)  472  -476  2000  [Not refereed][Not invited]
  
• 一過性全脳虚血後のApurinic/Apyrimidinic Endonuclease発現動態 ApoptosisにおけるDNA修復機能

  川瀬誠, 藤村幹, 藤村維子, 近藤健男, ChanPak H, 吉本高志  脳循環代謝  11-  (4)  388  -389  2000  [Not refereed][Not invited]
  
• 局所脳虚血および凍結脳外傷後のmitochondriaからのcytochrome c漏出とapoptosis superoxide dismutasesの役割について

  藤村幹, 森田維子, 藤村, 近藤健男, ChanPak H, 吉本高志  神経免疫研究  13-  79  -84  2000  [Not refereed][Not invited]
  
• Overexpression of copper and zinc superoxide dismutase in transgenic mice prevents the induction and activation of matrix metalloproteinases after cold injury-induced brain trauma

  Y Morita-Fujimura, M Fujimura, Y Gasche, JC Copin, PH Chan  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM  20-  (1)  130  -138  2000/01  [Not refereed][Not invited]
   

  Matrix metalloproteinases (MMPs), a family of proteolytic enzymes which degrade the extracellular matrix, are implicated in blood-brain barrier disruption, which is a critical event leading to vasogenic edema. To investigate the role of reactive oxygen species (ROS) in the expression of MMPs in vasogenic edema, the authors measured gelatinase activities before and after cold injury (CI) using transgenic mice that overexpress superoxide dismutase-1. A marked induction of pro-gelatinase B (pro-MMP-9) was seen 2 hours after CI and was maximized at 12 hours in wild-type mice. The pro-MMP-9 level was significantly lower in transgenic mice 4 hours (P < 0.001) and 12 hours (P < 0.05) after CI compared to wild-type mice. The activated MMP-9 was detected from 6 to 24 hours after injury. A mild induction of pro-gelatinase a (pro-MMP-2) was seen at 6 hours and was sustained until 7 days. In contrast, the activated form of MMP-2 appeared at 24 hours, was maximized at 7 days, and was absent in transgenic mice. Western blot analysis showed that the tissue inhibitors of metalloproteinases were not modified after CI. The results suggest that ROS production after CI may contribute to the induction and/or activation of MMPs and could thereby exacerbate endothelial cell injury and the development of vasogenic edema after injury.
• Overexpression of copper and zinc superoxide dismutase in transgenic mice prevents the induction and activation of matrix metalloproteinases after cold injury-induced brain trauma

  Y Morita-Fujimura, M Fujimura, Y Gasche, JC Copin, PH Chan  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM  20-  (1)  130  -138  2000/01  [Not refereed][Not invited]
   

  Matrix metalloproteinases (MMPs), a family of proteolytic enzymes which degrade the extracellular matrix, are implicated in blood-brain barrier disruption, which is a critical event leading to vasogenic edema. To investigate the role of reactive oxygen species (ROS) in the expression of MMPs in vasogenic edema, the authors measured gelatinase activities before and after cold injury (CI) using transgenic mice that overexpress superoxide dismutase-1. A marked induction of pro-gelatinase B (pro-MMP-9) was seen 2 hours after CI and was maximized at 12 hours in wild-type mice. The pro-MMP-9 level was significantly lower in transgenic mice 4 hours (P < 0.001) and 12 hours (P < 0.05) after CI compared to wild-type mice. The activated MMP-9 was detected from 6 to 24 hours after injury. A mild induction of pro-gelatinase a (pro-MMP-2) was seen at 6 hours and was sustained until 7 days. In contrast, the activated form of MMP-2 appeared at 24 hours, was maximized at 7 days, and was absent in transgenic mice. Western blot analysis showed that the tissue inhibitors of metalloproteinases were not modified after CI. The results suggest that ROS production after CI may contribute to the induction and/or activation of MMPs and could thereby exacerbate endothelial cell injury and the development of vasogenic edema after injury.
• Neuroprotective effects of an antioxidant in cortical cerebral ischemia: prevention of early reduction of the apurinic/apyrimidinic endonuclease DNA repair enzyme

  YY Chang, M Fujimura, Y Morita-Fujimura, GW Kim, CY Huang, HS Wu, M Kawase, JC Copin, PH Chan  NEUROSCIENCE LETTERS  277-  (1)  61  -64  1999/12  [Not refereed][Not invited]
   

  We examined the effects of the free radical scavenger, 21-aminosteroid, on apurinic/apyrimidinic endonuclease (APE/Ref-1) protein expression and subsequent infarction volume after photothrombotic cortical cerebral ischemia in mice. Immunohistochemistry and Western blot analysis showed a significant reduction in APE/Ref-1 expression 6 and 24 h after ischemia in untreated animals, whereas in drug-treated animals the reduction was much less at the same time points. The administration of 21-aminosteroid significantly decreased subsequent infarction volume 3 days after ischemia. These data suggest that 21-aminosteroid prevents the early decrease of APE/Ref-1 expression, thereby reducing cortical infarction after photothrombotic cerebral ischemia. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.
• Neuroprotective effects of an antioxidant in cortical cerebral ischemia: prevention of early reduction of the apurinic/apyrimidinic endonuclease DNA repair enzyme

  YY Chang, M Fujimura, Y Morita-Fujimura, GW Kim, CY Huang, HS Wu, M Kawase, JC Copin, PH Chan  NEUROSCIENCE LETTERS  277-  (1)  61  -64  1999/12  [Not refereed][Not invited]
   

  We examined the effects of the free radical scavenger, 21-aminosteroid, on apurinic/apyrimidinic endonuclease (APE/Ref-1) protein expression and subsequent infarction volume after photothrombotic cortical cerebral ischemia in mice. Immunohistochemistry and Western blot analysis showed a significant reduction in APE/Ref-1 expression 6 and 24 h after ischemia in untreated animals, whereas in drug-treated animals the reduction was much less at the same time points. The administration of 21-aminosteroid significantly decreased subsequent infarction volume 3 days after ischemia. These data suggest that 21-aminosteroid prevents the early decrease of APE/Ref-1 expression, thereby reducing cortical infarction after photothrombotic cerebral ischemia. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.
• Early decrease of XRCC1, a DNA base excision repair protein, may contribute to DNA fragmentation after transient focal cerebral ischemia in mice

  M Fujimura, Y Morita-Fujimura, T Sugawara, PH Chan  STROKE  30-  (11)  2456  -2462  1999/11  [Not refereed][Not invited]
   

  Background and Purpose-DNA damage and the DNA repair mechanism are known to be involved in ischemia/reperfusion injury in the brain. The x-ray repair cross-complementing group 1 (XRCC1) protein plays a central role in the DNA base excision repair pathway by interacting with DNA ligase III and DNA polymerase beta. The present study examined the protein expression of XRCC1 and DNA fragmentation before and after transient focal cerebral ischemia (FCI), Methods-Adult male CD-1 mice were subjected to 60 minutes of FCI by intraluminal blockade of the middle cerebral artery. XRCC1 protein expression was analyzed by immunohistochemistry and Western blot analysis, DNA damage was evaluated by gel electrophoresis and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL). The spatial relationship between XRCC1 expression and DNA damage was examined by double staining with XRCC1 and TUNEL after FCI. Results-Immunohistochemistry showed the nuclear expression of XRCC1 in all regions of the control brains and that it was predominant in the hippocampus. The XRCC1 level was markedly reduced in the caudate putamen at 10 minutes, further decreased in the entire middle cerebral artery territory at I hour, and remained reduced until 4 and 24 hours after FCI, Western blot analysis of the normal control brain showed a characteristic band of 70 kDa, which decreased after FCI, A significant amount of DNA fragmentation was detected by DNA gel electrophoresis 24 hours but not 4 hours after FCI. Double staining showed that the neurons that lost XRCC1 immunoreacrivity became TUNEL positive, Conclusions-These results suggest that the early decrease of XRCC1 and the failure of the DNA repair mechanism may contribute, at least in part, to DNA fragmentation after FCI.
• Mitochondrial release of cytochrome c corresponds to the selective vulnerability of hippocampal CA1 neurons in rats after transient global cerebral ischemia

  T Sugawara, M Fujimura, Y Morita-Fujimura, M Kawase, PH Chan  JOURNAL OF NEUROSCIENCE  19-  (22)  art. no.  -RC39  1999/11  [Not refereed][Not invited]
   

  Release of cytochrome c from mitochondria to the cytosol is a critical step in apoptotic cell death after focal cerebral ischemia. The relationship among cytochrome c release, selective vulnerability, and delayed death of hippocampal CA1 neurons after transient global ischemia was examined. Global ischemia was induced by 10 min of bilateral common carotid artery occlusion and hypotension in rats. Cytosolic expression of cytochrome c was evaluated by immunohistochemistry and Western blotting. Apoptosis after global ischemia was also characterized by terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL) staining and DNA gel electrophoresis. Immunohistochemistry showed cytosolic cytochrome c-positive cells exclusively in the CA1 subregion of the hippocampus as early as 2 hr after ischemia. Double fluorescent immunostaining confirmed that CA1 neurons and a small number of astrocytes expressed cytochrome c. Western blot analysis revealed a band (15 kDa) of cytochrome c in the cytosolic fraction and a corresponding decrease in the mitochondrial fraction. A significant number of TUNEL-positive cells appeared only in the CA1 pyramidal cell layer of the hippocampus, and DNA gel electrophoresis showed a significant amount of DNA fragmentation 3-5 d after ischemia. Our data provide the first evidence that cytochrome c was released to the cytosol from mitochondria in CA1 neurons after global ischemia and that the release preceded DNA fragmentation. These findings suggest cytochrome c involvement in the delayed death of hippocampal CA1 neurons in rats after transient global ischemia.
• Early decrease of XRCC1, a DNA base excision repair protein, may contribute to DNA fragmentation after transient focal cerebral ischemia in mice

  M Fujimura, Y Morita-Fujimura, T Sugawara, PH Chan  STROKE  30-  (11)  2456  -2462  1999/11  [Not refereed][Not invited]
   

  Background and Purpose-DNA damage and the DNA repair mechanism are known to be involved in ischemia/reperfusion injury in the brain. The x-ray repair cross-complementing group 1 (XRCC1) protein plays a central role in the DNA base excision repair pathway by interacting with DNA ligase III and DNA polymerase beta. The present study examined the protein expression of XRCC1 and DNA fragmentation before and after transient focal cerebral ischemia (FCI), Methods-Adult male CD-1 mice were subjected to 60 minutes of FCI by intraluminal blockade of the middle cerebral artery. XRCC1 protein expression was analyzed by immunohistochemistry and Western blot analysis, DNA damage was evaluated by gel electrophoresis and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL). The spatial relationship between XRCC1 expression and DNA damage was examined by double staining with XRCC1 and TUNEL after FCI. Results-Immunohistochemistry showed the nuclear expression of XRCC1 in all regions of the control brains and that it was predominant in the hippocampus. The XRCC1 level was markedly reduced in the caudate putamen at 10 minutes, further decreased in the entire middle cerebral artery territory at I hour, and remained reduced until 4 and 24 hours after FCI, Western blot analysis of the normal control brain showed a characteristic band of 70 kDa, which decreased after FCI, A significant amount of DNA fragmentation was detected by DNA gel electrophoresis 24 hours but not 4 hours after FCI. Double staining showed that the neurons that lost XRCC1 immunoreacrivity became TUNEL positive, Conclusions-These results suggest that the early decrease of XRCC1 and the failure of the DNA repair mechanism may contribute, at least in part, to DNA fragmentation after FCI.
• Copper-zinc superoxide dismutase prevents the early decrease of apurinic/apyrimidinic endonuclease and subsequent DNA fragmentation after transient focal cerebral ischemia in mice

  M Fujimura, Y Morita-Fujimura, P Narasimhan, JC Copin, M Kawase, PH Chan  STROKE  30-  (11)  2408  -2415  1999/11  [Not refereed][Not invited]
   

  Background and Purpose-DNA damage and its repair mechanism are thought to be involved in ischemia/reperfusion injury in the brain. We have previously shown that apurinic/apyrimidinic endonuclease (APE/Ref-1), a multifunctional protein in the DNA base excision repair pathway, rapidly decreased after transient focal cerebral ischemia (FCI) before the peak of DNA fragmentation. To further investigate the role of reactive oxygen species in APE/Ref-1 expression in vivo, we examined the expression of APE/Ref-1 and DNA damage after FCI in wild-type and transgenic mice overexpressing copper-zinc superoxide dismutase, Methods-Transgenic mice overexpressing copper-zinc superoxide dismutase and wild-type littermates were subjected to 60 minutes of transient FCI by intraluminal blockade of the middle cerebral artery, APE/Ref-1 protein expression was analyzed by immunohistochemistry and Western blot analysis. DNA damage was evaluated by gel electrophoresis and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL), Results-A similar level of APE/Ref-1 was detected in the control brains from both groups. APE/Ref-1 was significantly reduced 1 hour after transient FCI in both groups, whereas the transgenic mice had less reduction than that seen in wild-type mice 1 and 4 hours after FCI, DNA laddering was detected 24 hours after FCI and was decreased in transgenic mice. Double staining with APE/Ref-1 and TUNEL showed that the neurons that lost APE/Ref-1 immunoreactivity became TUNEL positive. Conclusions-These results suggest that reactive oxygen species contribute to the early decrease of APE/Ref- I and thereby exacerbate DNA fragmentation after transient FCI in mice.
• Mitochondrial release of cytochrome c corresponds to the selective vulnerability of hippocampal CA1 neurons in rats after transient global cerebral ischemia

  T Sugawara, M Fujimura, Y Morita-Fujimura, M Kawase, PH Chan  JOURNAL OF NEUROSCIENCE  19-  (22)  art. no.  -RC39  1999/11  [Not refereed][Not invited]
   

  Release of cytochrome c from mitochondria to the cytosol is a critical step in apoptotic cell death after focal cerebral ischemia. The relationship among cytochrome c release, selective vulnerability, and delayed death of hippocampal CA1 neurons after transient global ischemia was examined. Global ischemia was induced by 10 min of bilateral common carotid artery occlusion and hypotension in rats. Cytosolic expression of cytochrome c was evaluated by immunohistochemistry and Western blotting. Apoptosis after global ischemia was also characterized by terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL) staining and DNA gel electrophoresis. Immunohistochemistry showed cytosolic cytochrome c-positive cells exclusively in the CA1 subregion of the hippocampus as early as 2 hr after ischemia. Double fluorescent immunostaining confirmed that CA1 neurons and a small number of astrocytes expressed cytochrome c. Western blot analysis revealed a band (15 kDa) of cytochrome c in the cytosolic fraction and a corresponding decrease in the mitochondrial fraction. A significant number of TUNEL-positive cells appeared only in the CA1 pyramidal cell layer of the hippocampus, and DNA gel electrophoresis showed a significant amount of DNA fragmentation 3-5 d after ischemia. Our data provide the first evidence that cytochrome c was released to the cytosol from mitochondria in CA1 neurons after global ischemia and that the release preceded DNA fragmentation. These findings suggest cytochrome c involvement in the delayed death of hippocampal CA1 neurons in rats after transient global ischemia.
• Early appearance of activated matrix metalloproteinase-9 after focal cerebral ischemia in mice: A possible role in blood-brain barrier dysfunction

  Y Gasche, M Fujimura, Y Morita-Fujimura, JC Copin, M Kawase, J Massengale, PH Chan  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM  19-  (9)  1020  -1028  1999/09  [Not refereed][Not invited]
   

  During cerebral ischemia blood-brain barrier (BBB) disruption is a critical event leading to vasogenic edema and secondary brain injury. Gelatinases A and B are matrix metalloproteinases (MMP) able to open the BBB. The current study analyzes by zymography the early gelatinases expression and activation during permanent ischemia in mice (n = 15). ProMMP-9 expression was significantly (P < 0.001) increased in ischemic regions compared with corresponding contralateral regions after 2 hours of ischemia (mean 694.7 arbitrary units [AU], SD +/- 238.4 versus mean 107.6 AU, SD +/- 15.6) and remained elevated until 24 hours (mean 745.7 AU, SD +/- 157.4). Moreover, activated MMP-9 was observed 4 hours after the initiation of ischemia. At the same time as the appearance of activated MMP-9, we detected by the Evan's blue extravasation method a clear increase of BBB permeability. Tissue inhibitor of metalloproteinase-l was not modified during permanent ischemia at any time. The ProMMP-2 was significantly (P < 0.05) increased only after 24 hours of permanent ischemia (mean 213.2 AU, SD +/- 60.6 versus mean 94.6 AU, SD +/- 13.3), and no activated form was observed. The appearance of activated MMP-9 after 4 hours of ischemia in correlation with BBB permeability alterations suggests that MMP-9 may play an active role in early vasogenic edema development after stroke.
• Exacerbation of delayed cell injury after transient global ischemia in mutant mice with CuZn superoxide dismutase deficiency

  M Kawase, K Murakami, M Fujimura, Y Morita-Fujimura, Y Gasche, T Kondo, RW Scott, PH Chan  STROKE  30-  (9)  1962  -1968  1999/09  [Not refereed][Not invited]
   

  Background and Purpose-We have demonstrated that copper-zinc superoxide dismutase (CuZn-SOD), a cytosolic isoenzyme of SODs, has a protective role in the pathogenesis of superoxide radical-mediated brain injury. Using mice bearing a disruption of the CuZn-SOD gene (Sod1), the present study was designed to clarify the role of superoxide anion in the pathogenesis of selective vulnerability after transient global ischemia. Methods-Sod1 knockout homozygous mutant mice (Sod1 -/-) with a complete absence of endogenous CuZn-SOD activity, heterozygous mutant mice (Sod1 +/-) with a 50% decrease in the activity, and littermate wild-type mice (male, 35 to 45 g) were subjected to global ischemia. Since the plasticity of the posterior communicating artery (PcomA) has been reported to influence the outcome of hippocampal injury, we assessed the relation between the plasticity of PcomAs and the decrease of regional cerebral blood flow in global ischemia. Results-The fluorescence intensity of hydroethidine oxidation, a measurement of ethidium fluorescence for superoxide radicals, was increased in mutant mice 1 day after both 5 and 10 minutes of global ischemia, compared with wild-type mice. Hippocampal injury in the PcomA hypoplastic brains showed significant exacerbation in mutant mice compared with wild-type littermates 3 days after 5 minutes of global ischemia, although a marked difference was not observed at 1 day. Conclusions-These data suggest that superoxide radicals play an important role in the pathogenesis of delayed injury in the vulnerable hippocampal CAI subregion after transient global ischemia.
• Early appearance of activated matrix metalloproteinase-9 and blood-brain barrier disruption in mice after focal cerebral ischemia and reperfusion

  M Fujimura, Y Gasche, Y Morita-Fujimura, J Massengale, M Kawase, PH Chan  BRAIN RESEARCH  842-  (1)  92  -100  1999/09  [Not refereed][Not invited]
   

  Blood-brain barrier (BBB) disruption is thought to play a critical role in the pathophysiology of ischemia/reperfusion. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that can degrade all the components of the extracellular matrix when they are activated. Gelatinase A (MMP-2) and gelatinase B (MMP-9) are able to digest the endothelial basal lamina, which plays a major role in maintaining BBB impermeability. The present study examined the expression and activation of gelatinases before and after transient focal cerebral ischemia (FCI) in mice. Adult male CD1 mice were subjected to 60 min FCI and reperfusion. Zymography was performed from 1 to 23 h after reperfusion using the protein extraction method with detergent extraction and affinity-support purification. MMP-9 expression was also examined by both immunohistochemistry and Western blot analysis, and tissue inhibitors to metalloproteinase-1 was measured by reverse zymography. The BBB opening was evaluated by the Evans blue extravasation method. The 88-kDa activated MMP-9 was absent from the control specimens, while it appeared 3 h after transient ischemia by zymography. At this time point, the BBB permeability alteration was detected in the ischemic brain. Both pro-MMP-9 (96 kDa) and pro-MMP-2 (72 kDa) were seen in the: control specimens, and were markedly increased after FCI. A significant induction of MMP-9 was confirmed by both immunohistochemistry and Western blot analysis. The early appearance of activated MMP-9, associated with evidence of BBB permeability alteration, suggests that activation of MMP-9 contributes to the early formation of vasogenic edema after transient FCI. (C) 1999 Elsevier Science B.V. All rights reserved.
• Early appearance of activated matrix metalloproteinase-9 after focal cerebral ischemia in mice: A possible role in blood-brain barrier dysfunction

  Y Gasche, M Fujimura, Y Morita-Fujimura, JC Copin, M Kawase, J Massengale, PH Chan  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM  19-  (9)  1020  -1028  1999/09  [Not refereed][Not invited]
   

  During cerebral ischemia blood-brain barrier (BBB) disruption is a critical event leading to vasogenic edema and secondary brain injury. Gelatinases A and B are matrix metalloproteinases (MMP) able to open the BBB. The current study analyzes by zymography the early gelatinases expression and activation during permanent ischemia in mice (n = 15). ProMMP-9 expression was significantly (P < 0.001) increased in ischemic regions compared with corresponding contralateral regions after 2 hours of ischemia (mean 694.7 arbitrary units [AU], SD +/- 238.4 versus mean 107.6 AU, SD +/- 15.6) and remained elevated until 24 hours (mean 745.7 AU, SD +/- 157.4). Moreover, activated MMP-9 was observed 4 hours after the initiation of ischemia. At the same time as the appearance of activated MMP-9, we detected by the Evan's blue extravasation method a clear increase of BBB permeability. Tissue inhibitor of metalloproteinase-l was not modified during permanent ischemia at any time. The ProMMP-2 was significantly (P < 0.05) increased only after 24 hours of permanent ischemia (mean 213.2 AU, SD +/- 60.6 versus mean 94.6 AU, SD +/- 13.3), and no activated form was observed. The appearance of activated MMP-9 after 4 hours of ischemia in correlation with BBB permeability alterations suggests that MMP-9 may play an active role in early vasogenic edema development after stroke.
• Exacerbation of delayed cell injury after transient global ischemia in mutant mice with CuZn superoxide dismutase deficiency

  M Kawase, K Murakami, M Fujimura, Y Morita-Fujimura, Y Gasche, T Kondo, RW Scott, PH Chan  STROKE  30-  (9)  1962  -1968  1999/09  [Not refereed][Not invited]
   

  Background and Purpose-We have demonstrated that copper-zinc superoxide dismutase (CuZn-SOD), a cytosolic isoenzyme of SODs, has a protective role in the pathogenesis of superoxide radical-mediated brain injury. Using mice bearing a disruption of the CuZn-SOD gene (Sod1), the present study was designed to clarify the role of superoxide anion in the pathogenesis of selective vulnerability after transient global ischemia. Methods-Sod1 knockout homozygous mutant mice (Sod1 -/-) with a complete absence of endogenous CuZn-SOD activity, heterozygous mutant mice (Sod1 +/-) with a 50% decrease in the activity, and littermate wild-type mice (male, 35 to 45 g) were subjected to global ischemia. Since the plasticity of the posterior communicating artery (PcomA) has been reported to influence the outcome of hippocampal injury, we assessed the relation between the plasticity of PcomAs and the decrease of regional cerebral blood flow in global ischemia. Results-The fluorescence intensity of hydroethidine oxidation, a measurement of ethidium fluorescence for superoxide radicals, was increased in mutant mice 1 day after both 5 and 10 minutes of global ischemia, compared with wild-type mice. Hippocampal injury in the PcomA hypoplastic brains showed significant exacerbation in mutant mice compared with wild-type littermates 3 days after 5 minutes of global ischemia, although a marked difference was not observed at 1 day. Conclusions-These data suggest that superoxide radicals play an important role in the pathogenesis of delayed injury in the vulnerable hippocampal CAI subregion after transient global ischemia.
• Early appearance of activated matrix metalloproteinase-9 and blood-brain barrier disruption in mice after focal cerebral ischemia and reperfusion

  M Fujimura, Y Gasche, Y Morita-Fujimura, J Massengale, M Kawase, PH Chan  BRAIN RESEARCH  842-  (1)  92  -100  1999/09  [Not refereed][Not invited]
   

  Blood-brain barrier (BBB) disruption is thought to play a critical role in the pathophysiology of ischemia/reperfusion. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that can degrade all the components of the extracellular matrix when they are activated. Gelatinase A (MMP-2) and gelatinase B (MMP-9) are able to digest the endothelial basal lamina, which plays a major role in maintaining BBB impermeability. The present study examined the expression and activation of gelatinases before and after transient focal cerebral ischemia (FCI) in mice. Adult male CD1 mice were subjected to 60 min FCI and reperfusion. Zymography was performed from 1 to 23 h after reperfusion using the protein extraction method with detergent extraction and affinity-support purification. MMP-9 expression was also examined by both immunohistochemistry and Western blot analysis, and tissue inhibitors to metalloproteinase-1 was measured by reverse zymography. The BBB opening was evaluated by the Evans blue extravasation method. The 88-kDa activated MMP-9 was absent from the control specimens, while it appeared 3 h after transient ischemia by zymography. At this time point, the BBB permeability alteration was detected in the ischemic brain. Both pro-MMP-9 (96 kDa) and pro-MMP-2 (72 kDa) were seen in the: control specimens, and were markedly increased after FCI. A significant induction of MMP-9 was confirmed by both immunohistochemistry and Western blot analysis. The early appearance of activated MMP-9, associated with evidence of BBB permeability alteration, suggests that activation of MMP-9 contributes to the early formation of vasogenic edema after transient FCI. (C) 1999 Elsevier Science B.V. All rights reserved.
• Inhibition of interleukin-1 beta converting enzyme family proteases (caspases) reduces cold injury-induced brain trauma and DNA fragmentation in mice

  Y Morita-Fujimura, M Fujimura, M Kawase, K Murakami, GW Kim, PH Chan  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM  19-  (6)  634  -642  1999/06  [Not refereed][Not invited]
   

  The authors examined the effect of z-VAD.FMK, an inhibitor that blocks caspase family proteases, on cold injury-induced brain trauma, in which apoptosis as well as necrosis is assumed to play a role. A vehicle alone or with zVAD.FMK was administered into the cerebral ventricles of mice 15 minutes before and 24 and 48 hours after cold injury. At 24 hours after cold injury, infarction volumes in the zVAD.FMK-treated animals were significantly smaller than infarction volumes in the vehicle-treated animals, and were further decreased at 72 hours (0.92 +/- 1.80 mm(3), z-VAD.FMK treated animals: 7.46 +/- 3.53 mm(3), vehicle-treated animals: mean +/- SD, n = 7 to 8). The amount of DNA fragmentation was significantly decreased in the z-VAD.FMK-treated animals compared with the vehicle-treated animals, as shown by terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling staining and DNA gel electrophoresis. By Western blot analysis, both the proform and activated form of interleukin-1 beta converting enzyme (caspase 1) were detected in the control brain, and the activated form showed moderate reduction after sold injury-induced brain trauma. These results indicate that caspase inhibitors could reduce cold injury-induced brain trauma by preventing neuronal cell death by DNA damage. The caspase family pretenses appear to contribute to the mechanisms of cell death in cold injury-induced brain trauma and to provide therapeutic targets for traumatic brain injury.
• Release of mitochondrial cytochrome c and DNA fragmentation after cold injury-induced brain trauma in mice: possible role in neuronal apoptosis

  Y Morita-Fujimura, M Fujimura, M Kawase, SF Chen, PH Chan  NEUROSCIENCE LETTERS  267-  (3)  201  -205  1999/06  [Not refereed][Not invited]
   

  Recent studies have shown that release of mitochondrial cytochrome c is a critical step in the apoptosis process. In this study, we examined the subcellular distribution of the cytochrome c protein after cold injury (Cl), in which apoptosis is assumed to participate. Western blotting and immunohistochemistry showed cytosolic cytochrome c as early as 1 h after Cl, and correspondingly, there was a reduction in mitochondrial cytochrome c after injury. Neuronal distribution of cytosolic cytochrome c was shown by double staining with a neuronal nuclear marker by immunohistochemistry. A significant amount of DNA laddering was detected 4 h after Cl, and increased in a time-dependent manner. These data suggest that early cytochrome c release from mitochondria may contribute to apoptosis induction after traumatic brain injury. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.
• Inhibition of interleukin-1 beta converting enzyme family proteases (caspases) reduces cold injury-induced brain trauma and DNA fragmentation in mice

  Y Morita-Fujimura, M Fujimura, M Kawase, K Murakami, GW Kim, PH Chan  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM  19-  (6)  634  -642  1999/06  [Not refereed][Not invited]
   

  The authors examined the effect of z-VAD.FMK, an inhibitor that blocks caspase family proteases, on cold injury-induced brain trauma, in which apoptosis as well as necrosis is assumed to play a role. A vehicle alone or with zVAD.FMK was administered into the cerebral ventricles of mice 15 minutes before and 24 and 48 hours after cold injury. At 24 hours after cold injury, infarction volumes in the zVAD.FMK-treated animals were significantly smaller than infarction volumes in the vehicle-treated animals, and were further decreased at 72 hours (0.92 +/- 1.80 mm(3), z-VAD.FMK treated animals: 7.46 +/- 3.53 mm(3), vehicle-treated animals: mean +/- SD, n = 7 to 8). The amount of DNA fragmentation was significantly decreased in the z-VAD.FMK-treated animals compared with the vehicle-treated animals, as shown by terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling staining and DNA gel electrophoresis. By Western blot analysis, both the proform and activated form of interleukin-1 beta converting enzyme (caspase 1) were detected in the control brain, and the activated form showed moderate reduction after sold injury-induced brain trauma. These results indicate that caspase inhibitors could reduce cold injury-induced brain trauma by preventing neuronal cell death by DNA damage. The caspase family pretenses appear to contribute to the mechanisms of cell death in cold injury-induced brain trauma and to provide therapeutic targets for traumatic brain injury.
• Release of mitochondrial cytochrome c and DNA fragmentation after cold injury-induced brain trauma in mice: possible role in neuronal apoptosis

  Y Morita-Fujimura, M Fujimura, M Kawase, SF Chen, PH Chan  NEUROSCIENCE LETTERS  267-  (3)  201  -205  1999/06  [Not refereed][Not invited]
   

  Recent studies have shown that release of mitochondrial cytochrome c is a critical step in the apoptosis process. In this study, we examined the subcellular distribution of the cytochrome c protein after cold injury (Cl), in which apoptosis is assumed to participate. Western blotting and immunohistochemistry showed cytosolic cytochrome c as early as 1 h after Cl, and correspondingly, there was a reduction in mitochondrial cytochrome c after injury. Neuronal distribution of cytosolic cytochrome c was shown by double staining with a neuronal nuclear marker by immunohistochemistry. A significant amount of DNA laddering was detected 4 h after Cl, and increased in a time-dependent manner. These data suggest that early cytochrome c release from mitochondria may contribute to apoptosis induction after traumatic brain injury. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.
• Early decrease of apurinic/apyrimidinic endonuclease expression after transient focal cerebral ischemia in mice

  M Fujimura, Y Morita-Fujimura, M Kawase, PH Chan  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM  19-  (5)  495  -501  1999/05  [Not refereed][Not invited]
   

  The authors examined the protein expression of apurinic/apyrimidinic endonuclease (APE/Ref-1), a multifunctional protein in the DNA base excision repair pathway, before and after transient focal ischemia in mice. Immunohistochemistry showed the nuclear expression of APE/Ref-1 in the entire region of the control brains. Nuclear immunoreactivity was decreased as early as 5 minutes after 60 minutes of ischemia in the ischemic core, which was followed by a significant reduction of APE/Ref-1-positive cells in the entire middle cerebral artery territory. Western blot analysis of the sample from the nonischemic brain showed a characteristic 37-kDa band, which was reduced after ischemia. A significant amount of DNA fragmentation was observed at 24 hours, but not at 4 hours, after ischemia. The authors' data provide the first evidence that APE/Ref-1 rapidly decreases after transient focal ischemia, and that this reduction precedes the peak of DNA fragmentation in the brain regions that are destined to show necrosis and apoptosis. Although further examination is necessary to elucidate the direct relationship between the APE/Ref-1 decrease and ischemic necrosis and apoptosis, our results suggest the possibility that rapid decrease of APE/Ref-1 and the failure of the DNA repair mechanism may contribute to necrosis or apoptosis after transient focal ischemia.
• Manganese superoxide dismutase mediates the early release of mitochondrial cytochrome C and subsequent DNA fragmentation after permanent focal cerebral ischemia in mice

  M Fujimura, Y Morita-Fujimura, M Kawase, JC Copin, B Calagui, CJ Epstein, PH Chan  JOURNAL OF NEUROSCIENCE  19-  (9)  3414  -3422  1999/05  [Not refereed][Not invited]
   

  Recent studies have shown that release of mitochondrial cytochrome c is a critical step in the apoptosis process. We have reported that cytosolic redistribution of cytochrome c in vivo occurred after transient focal cerebral ischemia (FCI) in rats and preceded the peak of DNA fragmentation. Although the involvement of reactive oxygen species in the cytosolic redistribution of cytochrome c in vitro has been suggested, the detailed mechanism by which cytochrome c release is mediated in vivo has not yet been established. Also, the role of mitochondrial oxidative stress in cytochrome c release is unknown. These issues can be addressed using knock-out mutants that are deficient in the level of the mitochondrial antioxidant manganese superoxide dismutase (Mn-SOD). In this study we examined the subcellular distribution of the cytochrome c protein in both wild-type mice and heterozygous knock-outs of the syn-SOD gene (Sod2 -/+) after permanent FCI, in which apoptosis is assumed to participate. Cytosolic cytochrome c was detected as early as 1 hr after ischemia, and correspondingly, mitochondrial cytochrome c showed a significant reduction 2 hr after ischemia (p < 0.01). Cytosolic accumulation of cytochrome c was significantly higher in Sod2 -/+ mice compared with wild-type animals (p < 0.05). N-benzyloxycarbonyl-val-ala-asp-fluoromethyl ketone (z-VAD.FMK), a nonselective caspase inhibitor, did not affect cytochrome c release after ischemia. A significant amount of DNA laddering was detected 24 hr after ischemia and increased in Sod2 -/+ mice. These data suggest that Mn-SOD blocks cytosolic release of cytochrome c and could thereby reduce apoptosis after permanent FCI.
• Manganese superoxide dismutase mediates the early release of mitochondrial cytochrome C and subsequent DNA fragmentation after permanent focal cerebral ischemia in mice

  M Fujimura, Y Morita-Fujimura, M Kawase, JC Copin, B Calagui, CJ Epstein, PH Chan  JOURNAL OF NEUROSCIENCE  19-  (9)  3414  -3422  1999/05  [Not refereed][Not invited]
   

  Recent studies have shown that release of mitochondrial cytochrome c is a critical step in the apoptosis process. We have reported that cytosolic redistribution of cytochrome c in vivo occurred after transient focal cerebral ischemia (FCI) in rats and preceded the peak of DNA fragmentation. Although the involvement of reactive oxygen species in the cytosolic redistribution of cytochrome c in vitro has been suggested, the detailed mechanism by which cytochrome c release is mediated in vivo has not yet been established. Also, the role of mitochondrial oxidative stress in cytochrome c release is unknown. These issues can be addressed using knock-out mutants that are deficient in the level of the mitochondrial antioxidant manganese superoxide dismutase (Mn-SOD). In this study we examined the subcellular distribution of the cytochrome c protein in both wild-type mice and heterozygous knock-outs of the syn-SOD gene (Sod2 -/+) after permanent FCI, in which apoptosis is assumed to participate. Cytosolic cytochrome c was detected as early as 1 hr after ischemia, and correspondingly, mitochondrial cytochrome c showed a significant reduction 2 hr after ischemia (p < 0.01). Cytosolic accumulation of cytochrome c was significantly higher in Sod2 -/+ mice compared with wild-type animals (p < 0.05). N-benzyloxycarbonyl-val-ala-asp-fluoromethyl ketone (z-VAD.FMK), a nonselective caspase inhibitor, did not affect cytochrome c release after ischemia. A significant amount of DNA laddering was detected 24 hr after ischemia and increased in Sod2 -/+ mice. These data suggest that Mn-SOD blocks cytosolic release of cytochrome c and could thereby reduce apoptosis after permanent FCI.
• Reduction of apurinic/apyrimnidinic endonuclease expression after transient global cerebral ischemia in rats - Implication of the failure of DNA repair in neuronal apoptosis

  M Kawase, M Fujimura, Y Morita-Fujimura, PH Chan  STROKE  30-  (2)  441  -448  1999/02  [Not refereed][Not invited]
   

  Background and Purpose-To clarify the relationship between apurinic/apyrimidinic endonuclease (APE/Ref-1), a multifunctional protein in the DNA base excision repair pathway, and delayed neuronal cell death associated with apoptosis, we examined the expression of APE/Ref-1 before and after transient global ischemia in rats. Methods-Global ischemia was induced by bilateral common carotid artery occlusion and hypotension. Expression of the APE/Ref-1 protein was evaluated by Western blot and immunohistochemical analyses. Apoptosis after global ischemia was observed by DNA electrophoresis and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphatebiotin nick end labeling (TUNEL) staining. Results-Immunohistochemistry showed the nuclear expression of APE/Ref-1 in the control brains. Nuclear immunoreactivity of APE/Ref-1 was significantly decreased 2 days after 10 minutes of ischemia in the hippocampal CA1 subregion. Western blot analysis of a sample from the normal brains showed a characteristic 37-kDa band, which was reduced in the hippocampal CA1 subregion after ischemia. A significant amount of DNA fragmentation was observed at 3 days but not at 1 day after ischemia. Double staining with APE/Ref-1 and TUNEL clearly showed that the neurons that lost APE/Ref-1 immunoreactivity became TUNEL positive, Conclusions-Our data provide evidence that APE/Ref-1 decreased in hippocampal CA1 neurons after transient global ischemia and that this reduction precedes DNA fragmentation, which is destined to cause apoptosis. Our results suggest the possibility that a decrease of APE/Ref-1 activity and the failure of DNA repair may underlie the mechanism of apoptosis after transient focal ischemia.
• Reduction of apurinic/apyrimnidinic endonuclease expression after transient global cerebral ischemia in rats - Implication of the failure of DNA repair in neuronal apoptosis

  M Kawase, M Fujimura, Y Morita-Fujimura, PH Chan  STROKE  30-  (2)  441  -448  1999/02  [Not refereed][Not invited]
   

  Background and Purpose-To clarify the relationship between apurinic/apyrimidinic endonuclease (APE/Ref-1), a multifunctional protein in the DNA base excision repair pathway, and delayed neuronal cell death associated with apoptosis, we examined the expression of APE/Ref-1 before and after transient global ischemia in rats. Methods-Global ischemia was induced by bilateral common carotid artery occlusion and hypotension. Expression of the APE/Ref-1 protein was evaluated by Western blot and immunohistochemical analyses. Apoptosis after global ischemia was observed by DNA electrophoresis and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphatebiotin nick end labeling (TUNEL) staining. Results-Immunohistochemistry showed the nuclear expression of APE/Ref-1 in the control brains. Nuclear immunoreactivity of APE/Ref-1 was significantly decreased 2 days after 10 minutes of ischemia in the hippocampal CA1 subregion. Western blot analysis of a sample from the normal brains showed a characteristic 37-kDa band, which was reduced in the hippocampal CA1 subregion after ischemia. A significant amount of DNA fragmentation was observed at 3 days but not at 1 day after ischemia. Double staining with APE/Ref-1 and TUNEL clearly showed that the neurons that lost APE/Ref-1 immunoreactivity became TUNEL positive, Conclusions-Our data provide evidence that APE/Ref-1 decreased in hippocampal CA1 neurons after transient global ischemia and that this reduction precedes DNA fragmentation, which is destined to cause apoptosis. Our results suggest the possibility that a decrease of APE/Ref-1 activity and the failure of DNA repair may underlie the mechanism of apoptosis after transient focal ischemia.
• CD38 disruption impairs glucose-induced increases in cyclic ADP-ribose, [Ca2+](i), and insulin secretion

  Ichiro Kato, Yasuhiko Yamamoto, Miki Fujimura, Naoya Noguchi, Shin Takasawa, Hiroshi Okamoto  Journal of Biological Chemistry  274-  (4)  1869  -1872  1999/01/22  [Not refereed][Not invited]
   

  Increases in [Ca2+](i) in pancreatic beta cells, resulting from Ca2+ mobilization from intracellular stores as well as Ca2+ influx from extracellular sources, are important in insulin secretion by glucose. Cyclic ADP-ribose (cADPR), accumulated in beta cells by glucose stimulation, has been postulated to serve as a second messenger for intracellular Ca2+ mobilization for insulin secretion, and CD38 is thought to be involved in the cADPR accumulation (Takasawa, S., Tohgo, A., Noguchi, N., Koguma, T., Nata, K., Sugimoto, T., Yonekura, H., and Okamoto, H. (1993) J. Biol. Chem. 268, 26052-26054). Here we created 'knockout' (CD38(-/-)) mice by homologous recombination. CD38(-/-) mice developed normally but showed no increase in their glucose-induced production of cADPR in pancreatic islets. The glucose- induced [Ca2+](i) rise and insulin secretion were both severely impaired in CD38(-/-) islets, whereas CD38(-/-) islets responded normally to the extracellular Ca2+ influx stimulants tolbutamide and KCl. CD38(-/-) mice showed impaired glucose tolerance, and the serum insulin level was lower than control, and these impaired phenotypes were rescued by beta cell-specific expression of CD38 cDNA. These results indicate that CD38 plays an essential role in intracellular Ca2+ mobilization by cADPR for insulin secretion.
• 一過性全脳虚血後のApurinic/Apyrimidinic Endonuclease発現低下 ApoptosisにおけるDNA修復機能

  川瀬誠, 近藤健男, 藤村幹, 藤村維子, ChanPak H, 吉本高志  日本脳神経外科学会58回総会抄録集  248  -248  1999  [Not refereed][Not invited]
  
• CD38 disruption impairs glucose-induced increases in cyclic ADP-ribose, [Ca2+](i), and insulin secretion

  Kato, I, Y Yamamoto, M Fujimura, N Noguchi, S Takasawa, H Okamoto  JOURNAL OF BIOLOGICAL CHEMISTRY  274-  (4)  1869  -1872  1999/01  [Not refereed][Not invited]
   

  Increases in [Ca2+](i) in pancreatic beta cells, resulting from Ca2+ mobilization from intracellular stores as well as Ca2+ influx from extracellular sources, are important in insulin secretion by glucose. Cyclic ADP-ribose (cADPR), accumulated in beta cells by glucose stimulation, has been postulated to serve as a second messenger for intracellular Ca2+ mobilization for insulin secretion, and CD38 is thought to be involved in the cADPR accumulation (Takasawa, S,, Tohgo, k, Noguchi, N,, Koguma, T,, Nata, K,, Sugimoto, T,, Yonekura, H.,, and Okamoto, H, (1993) J. Biol. Chem, 268, 26052-26054), Here we created "knockout" (CD38(-/-)) mice by homologous recombination, CD38(-/-) mice developed normally but showed no increase in their glucose-induced production of cADPR in pancreatic islets, The glucose-induced [Ca2+](i) rise and insulin secretion were both severely impaired in CD38(-/-) islets, whereas CD38(-/-) islets responded normally to the extracellular Ca2+ influx stimulants tolbutamide and KCl, CD38(-/-) mice showed impaired glucose tolerance, and the serum insulin level was lower than control, and these impaired phenotypes were rescued by beta cell-specific expression of CD38 cDNA These results indicate that CD38 plays an essential role in intracellular Ca2+ mobilization by cADPR for insulin secretion.
• Early decrease in apurinic/apyrimidinic endonuclease is followed by DNA fragmentation after cold injury-induced brain trauma in mice

  Y Morita-Fujimura, M Fujimura, M Kawase, PH Chan  NEUROSCIENCE  93-  (4)  1465  -1473  1999  [Not refereed][Not invited]
   

  Apurinic/apyrimidinic endonuclease, a multifunctional protein in the DNA base excision repair pathway, plays a central role in repairing DNA damage caused by reactive oxygen species. We examined protein expression of apurinic/apyrimidinic endonuclease before and after cold injury-induced brain trauma in mice, where we have previously shown reactive oxygen species to participate. Immunohistochemistry showed the nuclear expression of apurinic/apyrimidinic endonuclease in the entire region of control brains. One hour after cold injury-induced brain trauma, nuclear immunoreactivity was predominantly decreased in the inner boundary of the lesion, whereas there was a slight increase in the outer boundary area. Four hours after cold injury-induced brain trauma, nuclear immunoreactivity was almost absent in the entire lesion, and remained so until 24 h. At this time, a marked increase in apurinic/apyrimidinic endonuclease immunoreactivity was seen in the outer boundary zone. Western blot analysis of the sample from the non-ischemic area showed a characteristic 37,000 mol. wt band, which decreased markedly 24 h after cold injury-induced brain trauma. A time-dependent increase in DNA fragmentation was also observed after cold injury-induced brain trauma. Our data provide the first evidence that apurinic/apyrimidinic endonuclease decreased rapidly in the lesion after cold injury-induced brain trauma, whereas it was significantly increased at the outer boundary zone. Although further examination is necessary to elucidate the direct relationship between apurinic/apyrimidinic endonuclease alteration and the pathogenesis of cold injury-induced brain trauma, our results suggest the possibility that an early decrease in apurinic/apyrimidinic endonuclease and failure of the DNA repair mechanism may contribute to DNA-damaged neuronal cell death after cold injury-induced brain trauma. (C) 1999 IBRO. Published by Elsevier Science Ltd.
• Copper-zinc superoxide dismutase prevents the early decrease of apurinic/apyrimidinic endonuclease and subsequent DNA fragmentation after transient focal cerebral ischemia in mice

  FUJIMURA M  Stroke  30-  (11)  2408  -2415  1999  [Not refereed][Not invited]
  
• Early decrease in apurinic/apyrimidinic endonuclease is followed by DNA fragmentation after cold injury-induced brain trauma in mice

  Y Morita-Fujimura, M Fujimura, M Kawase, PH Chan  NEUROSCIENCE  93-  (4)  1465  -1473  1999  [Not refereed][Not invited]
   

  Apurinic/apyrimidinic endonuclease, a multifunctional protein in the DNA base excision repair pathway, plays a central role in repairing DNA damage caused by reactive oxygen species. We examined protein expression of apurinic/apyrimidinic endonuclease before and after cold injury-induced brain trauma in mice, where we have previously shown reactive oxygen species to participate. Immunohistochemistry showed the nuclear expression of apurinic/apyrimidinic endonuclease in the entire region of control brains. One hour after cold injury-induced brain trauma, nuclear immunoreactivity was predominantly decreased in the inner boundary of the lesion, whereas there was a slight increase in the outer boundary area. Four hours after cold injury-induced brain trauma, nuclear immunoreactivity was almost absent in the entire lesion, and remained so until 24 h. At this time, a marked increase in apurinic/apyrimidinic endonuclease immunoreactivity was seen in the outer boundary zone. Western blot analysis of the sample from the non-ischemic area showed a characteristic 37,000 mol. wt band, which decreased markedly 24 h after cold injury-induced brain trauma. A time-dependent increase in DNA fragmentation was also observed after cold injury-induced brain trauma. Our data provide the first evidence that apurinic/apyrimidinic endonuclease decreased rapidly in the lesion after cold injury-induced brain trauma, whereas it was significantly increased at the outer boundary zone. Although further examination is necessary to elucidate the direct relationship between apurinic/apyrimidinic endonuclease alteration and the pathogenesis of cold injury-induced brain trauma, our results suggest the possibility that an early decrease in apurinic/apyrimidinic endonuclease and failure of the DNA repair mechanism may contribute to DNA-damaged neuronal cell death after cold injury-induced brain trauma. (C) 1999 IBRO. Published by Elsevier Science Ltd.
• Early decrease of apurinic/apyrimidinic endonuclease expression after transient focal cerebral ischemia in mice.

  Fujimura M, Morita-Fujimura Y, Kawase M, Chan P H  J Cereb Blood Flow Metab  19-  (5)  495  -501  1999  [Not refereed][Not invited]
  
• Cytosolic redistribution of cytochrome c after transient focal cerebral ischemia in rats

  M Fujimura, Y Morita-Fujimura, K Murakami, M Kawase, PH Chan  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM  18-  (11)  1239  -1247  1998/11  [Not refereed][Not invited]
   

  Recent in vitro cell-free studies have shown that cytochrome c release from mitochondria is a critical step in the apoptotic process. The present study examined the expression of cytochrome c protein after transient focal cerebral ischemia in rats, in which apoptosis was assumed to contribute to the expansion of the ischemic lesion. In situ labeling of DNA breaks in frozen sections after 90 minutes of middle cerebral artery (MCA) occlusion showed a significant number of striatal and cortical neurons, which were maximized at 24 hours after ischemia, exhibiting chromatin condensation, nuclear segmentation, and apoptotic bodies. Cytosolic localization of cytochrome c was detected immunohistochemically in the ischemic area as early as 4 hours after 90 minutes of MCA occlusion. Western blot analysis of the cytosolic fraction revealed a strong single 15-kDa band, characteristic of cytochrome c, only in the samples from the ischemic hemisphere. Western blot analysis of the mitochondrial fraction showed a significant amount of mitochondrial cytochrome c in nonischemic brain, which was decreased in ischemic brain 24 hours after ischemia. These results provide the first evidence that cytochrome c is being released from mitochondria to the cytosol after transient focal ischemia. Although further evaluation is necessary to elucidate its correlation with DNA fragmentation, our results suggest the possibility that cytochrome c release may play a role in DNA-damaged neuronal cell death after transient focal cerebral ischemia in rats.
• Cytosolic redistribution of cytochrome c after transient focal cerebral ischemia in rats

  M Fujimura, Y Morita-Fujimura, K Murakami, M Kawase, PH Chan  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM  18-  (11)  1239  -1247  1998/11  [Not refereed][Not invited]
   

  Recent in vitro cell-free studies have shown that cytochrome c release from mitochondria is a critical step in the apoptotic process. The present study examined the expression of cytochrome c protein after transient focal cerebral ischemia in rats, in which apoptosis was assumed to contribute to the expansion of the ischemic lesion. In situ labeling of DNA breaks in frozen sections after 90 minutes of middle cerebral artery (MCA) occlusion showed a significant number of striatal and cortical neurons, which were maximized at 24 hours after ischemia, exhibiting chromatin condensation, nuclear segmentation, and apoptotic bodies. Cytosolic localization of cytochrome c was detected immunohistochemically in the ischemic area as early as 4 hours after 90 minutes of MCA occlusion. Western blot analysis of the cytosolic fraction revealed a strong single 15-kDa band, characteristic of cytochrome c, only in the samples from the ischemic hemisphere. Western blot analysis of the mitochondrial fraction showed a significant amount of mitochondrial cytochrome c in nonischemic brain, which was decreased in ischemic brain 24 hours after ischemia. These results provide the first evidence that cytochrome c is being released from mitochondria to the cytosol after transient focal ischemia. Although further evaluation is necessary to elucidate its correlation with DNA fragmentation, our results suggest the possibility that cytochrome c release may play a role in DNA-damaged neuronal cell death after transient focal cerebral ischemia in rats.
• An autopsy case of a ruptured cerebral aneurysm treated with interlocking detachable coils

  Y Otawara, T Sugawara, H Seki, M Fujimura, N Tomichi  NEUROLOGICAL SURGERY  25-  (9)  829  -833  1997/09  [Not refereed][Not invited]
   

  We described an autopsy case of a ruptured aneurysmal subarachnoid hemorrhage treated with endovascular embolization by interlocking detachable coils. An 85-year-old male presented with sudden onset of severe subarachnoid hemorrhage. Cerebral angiogram revealed a right internal carotid-posterior communicating artery aneurysm. Post-operative angiogram revealed complete obliteration of the aneurysm, except for its orifice. Following the embolization of the aneurysm, tissue plasminogen activator was intrathecally perfused for anti-vasospasm treatment. Follow-up angiogram showed stable obliteration of the aneurysm, and no particular findings of cerebral vasospasm. The patient had been recovering without any neurological deficits, but died from pneumonia on the 25th day after the embolization. Autopsy findings revealed the disappearance of subarachnoid hemorrhage, and no visible finding of cerebral infarction or edema. The inner lumen of the aneurysm was occupied by a mixture of the coils and the clots. The surface of the embolized coils was directly observed through the orifice of the aneurysm without any membranous substance from the inner lumen of the internal carotid artery. This pathological finding is different from the previously reported animal models in which the surface of the embolized coils was covered with endothelial membrane 2 weeks after embolization. Further examinations are required to clarify the pathogenesis of the endothelial regrowth.
• An autopsy case of a ruptured cerebral aneurysm treated with interlocking detachable coils

  Yasunari Otawara, Takayuki Sugawara, Hirobumi Seki, Miki Fujimura, Nobukazu Tomichi  Neurological Surgery  25-  (9)  829  -833  1997/09  [Not refereed][Not invited]
   

  We described an autopsy case of a ruptured aneurysmal subarachnoid hemorrhage treated with endovascular embolization by interlocking detachable coils. An 85-year-old male presented with sudden onset of severe subarachnoid hemorrhage. Cerebral angiogram revealed a right internal carotid-posterior communicating artery aneurysm. Post-operative angiogram revealed complete obliteration of the aneurysm, except for its orifice. Following the embolization of the aneurysm, tissue plasminogen activator was intrathecally perfused for anti-vasospasm treatment. Follow-up angiogram showed stable obliteration of the aneurysm, and no particular findings of cerebral vasospasm. The patient had been recovering without any neurological deficits, but died from pneumonia on the 25th day after the embolization. Autopsy findings revealed the disappearance of the subarachnoid hemorrhage, and no visible finding of cerebral infarction or edema. The inner lumen of the aneurysm was occupied by a mixture of the coils and the clots. The surface of the embolized coils was directly observed through the orifice of the aneurysm without any membranous substance from the inner lumen of the internal carotid artery. This pathological finding is different from the previously reported animal models in which the surface of the embolized coils was covered with endothelial membrane 2 weeks after embolization. Further examinations are required to clarify the pathogenesis of the endothelial regrowth.
• Carcinomatous change in the cranial metastasis from a metastasizing mixed tumor of the salivary gland -Case report-

  Miki Fujimura, Takayuki Sugawara, Hirobumi Seki, Yasunari Otawara, Tsutomu Sakuma, Yoshishige Nakano, Takashi Yoshimoto  Neurologia Medico-Chirurgica  37-  (7)  546  -550  1997/07  [Not refereed][Not invited]
   

  A 57-year-old female who had had a mixed tumor of the submandibular gland for 30 years presented with a cranial metastasis in the ipsilateral occipital region. Detailed histological examinations of the primary tumor failed to detect any carcinomatous component. In contrast, the metastasis contained a carcinomatous component. This histological discrepancy was confirmed by assessment of the expression of Ki-67 antigen in these tumor specimens and comparison with five typical benign mixed tumors. Cranial metastasis of a histologically benign mixed tumor is extremely rare, and a carcinomatous change in the metastatic tumor is apparently unique.
• Carcinomatous change in the cranial metastasis from a metastasizing mixed tumor of the salivary gland -Case report-

  Miki Fujimura, Takayuki Sugawara, Hirobumi Seki, Yasunari Otawara, Tsutomu Sakuma, Yoshishige Nakano, Takashi Yoshimoto  Neurologia Medico-Chirurgica  37-  (7)  546  -550  1997/07  [Not refereed][Not invited]
   

  A 57-year-old female who had had a mixed tumor of the submandibular gland for 30 years presented with a cranial metastasis in the ipsilateral occipital region. Detailed histological examinations of the primary tumor failed to detect any carcinomatous component. In contrast, the metastasis contained a carcinomatous component. This histological discrepancy was confirmed by assessment of the expression of Ki-67 antigen in these tumor specimens and comparison with five typical benign mixed tumors. Cranial metastasis of a histologically benign mixed tumor is extremely rare, and a carcinomatous change in the metastatic tumor is apparently unique.
• Nicotinamide inhibits inducible nitric oxide synthase mRNA in primary rat glial cells

  M Fujimura, T Tominaga, T Yoshimoto  NEUROSCIENCE LETTERS  228-  (2)  107  -110  1997/06  [Not refereed][Not invited]
   

  Nitric oxide (NO) exerts cytotoxic effects on various cells including neuronal cells. Glial NO production, mediated via induction of inducible NO synthase (iNOS), enhances neurotoxicity associated with the N-methyl-D-aspartate (NMDA) receptor. The present study examined whether nicotinamide, an inhibitor of poly (ADP-ribose) synthetase, inhibits NO formation in primary culture of rat glial cells. Nicotinamide (5-20 mM) suppressed iNOS mRNA expression and subsequent NO formation, which were induced by the combination of interferon-gamma and lipopolysaccharide, in a dose dependent manner. In addition, high-concentration (20 mM) nicotinamide decreased mRNA of interferon regulatory factor-1, a transcription factor which plays a major role in iNOS mRNA induction. These results suggest that nicotinamide may have protective effect on glial NO-related pathologies by preventing iNOS mRNA induction. (C) 1997 Elsevier Science Ireland Ltd.
• Attenuation of nitric oxide synthase induction in IRF-1-deficient glial cells

  M Fujimura, T Tominaga, Kato, I, S Takasawa, M Kawase, T Taniguchi, H Okamoto, T Yoshimoto  BRAIN RESEARCH  759-  (2)  247  -250  1997/06  [Not refereed][Not invited]
   

  Nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) exerts inhibitory and cytotoxic effects on various cells including neuronal cells. Glial NO production, mediated via induction of iNOS, is thought to facilitate neuronal damage during cerebral ischemia. Recently, interferon regulatory factor-1 (IRF-1) has been reported to be an essential transcription factor for iNOS mRNA induction in murine macrophages. However, expression of IRF-l and its role in the central nervous system have not been examined. In the present study, by using primary glial cell cultures from mice with targeted disruption of the IRF-1 gene, we investigated whether IRF-1 is involved in iNOS mRNA induction in glial cells. After stimulation with lipopolysaccharide and interferon-gamma, IRF-1 mRNA was strongly induced in wild-type (IRF-1 +/+) glial cells. iNOS mRNA induction and nitrite production in IRF-1 -/- glial cells were reduced as compared with those observed in IRF-l +/+ glial cells. Diethyldithiocarbamate, a selective inhibitor of nuclear transcription factor kappa B (NF-kappa B), completely inhibited iNOS mRNA induction. These results suggest that not only NF-kappa B but also IRF-1 play important roles in iNOS mRNA induction in the central nervous system.
• Nicotinamide inhibits inducible nitric oxide synthase mRNA in primary rat glial cells

  M Fujimura, T Tominaga, T Yoshimoto  NEUROSCIENCE LETTERS  228-  (2)  107  -110  1997/06  [Not refereed][Not invited]
   

  Nitric oxide (NO) exerts cytotoxic effects on various cells including neuronal cells. Glial NO production, mediated via induction of inducible NO synthase (iNOS), enhances neurotoxicity associated with the N-methyl-D-aspartate (NMDA) receptor. The present study examined whether nicotinamide, an inhibitor of poly (ADP-ribose) synthetase, inhibits NO formation in primary culture of rat glial cells. Nicotinamide (5-20 mM) suppressed iNOS mRNA expression and subsequent NO formation, which were induced by the combination of interferon-gamma and lipopolysaccharide, in a dose dependent manner. In addition, high-concentration (20 mM) nicotinamide decreased mRNA of interferon regulatory factor-1, a transcription factor which plays a major role in iNOS mRNA induction. These results suggest that nicotinamide may have protective effect on glial NO-related pathologies by preventing iNOS mRNA induction. (C) 1997 Elsevier Science Ireland Ltd.
• Attenuation of nitric oxide synthase induction in IRF-1-deficient glial cells

  M Fujimura, T Tominaga, Kato, I, S Takasawa, M Kawase, T Taniguchi, H Okamoto, T Yoshimoto  BRAIN RESEARCH  759-  (2)  247  -250  1997/06  [Not refereed][Not invited]
   

  Nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) exerts inhibitory and cytotoxic effects on various cells including neuronal cells. Glial NO production, mediated via induction of iNOS, is thought to facilitate neuronal damage during cerebral ischemia. Recently, interferon regulatory factor-1 (IRF-1) has been reported to be an essential transcription factor for iNOS mRNA induction in murine macrophages. However, expression of IRF-l and its role in the central nervous system have not been examined. In the present study, by using primary glial cell cultures from mice with targeted disruption of the IRF-1 gene, we investigated whether IRF-1 is involved in iNOS mRNA induction in glial cells. After stimulation with lipopolysaccharide and interferon-gamma, IRF-1 mRNA was strongly induced in wild-type (IRF-1 +/+) glial cells. iNOS mRNA induction and nitrite production in IRF-1 -/- glial cells were reduced as compared with those observed in IRF-l +/+ glial cells. Diethyldithiocarbamate, a selective inhibitor of nuclear transcription factor kappa B (NF-kappa B), completely inhibited iNOS mRNA induction. These results suggest that not only NF-kappa B but also IRF-1 play important roles in iNOS mRNA induction in the central nervous system.
• A ruptured aneurysm at the distal end of the basilar artery fenestration associated with multiple fenestrations of the vertebrobasilar system: Case report

  M Fujimura, T Sugawara, H Higuchi, T Oku, H Seki  SURGICAL NEUROLOGY  47-  (5)  469  -472  1997/05  [Not refereed][Not invited]
   

  BACKGROUND An aneurysm at the fenestrated basilar artery usually arises at the proximal end of the fenestration, with few exceptions. We failed to reveal any case of aneurysm at this site associated with multiple fenestrations of the vertebrobasilar system. CASE REPORT This 62-year-old male was admitted to our hospital 1 day after a sudden onset of headache. CT scan showed subarachnoid hemorrhage, and angiogram revealed an aneurysm at the distal end of the fenestrated basilar artery in association with two other fenestrations of the vertebrobasilar system. The limb of the basilar artery fenestration was trapped tightly with one clip through the transcondylar approach. Postoperative course was uneventful, and postoperative angiogram showed complete disappearance of the aneurysm. CONCLUSION An extremely rare case of an aneurysm at the distal end of the fenestrated basilar artery in association with multiple fenestrations of the vertebrobasilar system is reported. The coexistence of vertebral artery fenestration and the fenestration of the vertebrobasilar junction may give a clue to the mechanism of occurrence of basilar artery fenestration. (C) 1997 by Elsevier Science Inc.
• A ruptured aneurysm at the distal end of the basilar artery fenestration associated with multiple fenestrations of the vertebrobasilar system: Case report

  M Fujimura, T Sugawara, H Higuchi, T Oku, H Seki  SURGICAL NEUROLOGY  47-  (5)  469  -472  1997/05  [Not refereed][Not invited]
   

  BACKGROUND An aneurysm at the fenestrated basilar artery usually arises at the proximal end of the fenestration, with few exceptions. We failed to reveal any case of aneurysm at this site associated with multiple fenestrations of the vertebrobasilar system. CASE REPORT This 62-year-old male was admitted to our hospital 1 day after a sudden onset of headache. CT scan showed subarachnoid hemorrhage, and angiogram revealed an aneurysm at the distal end of the fenestrated basilar artery in association with two other fenestrations of the vertebrobasilar system. The limb of the basilar artery fenestration was trapped tightly with one clip through the transcondylar approach. Postoperative course was uneventful, and postoperative angiogram showed complete disappearance of the aneurysm. CONCLUSION An extremely rare case of an aneurysm at the distal end of the fenestrated basilar artery in association with multiple fenestrations of the vertebrobasilar system is reported. The coexistence of vertebral artery fenestration and the fenestration of the vertebrobasilar junction may give a clue to the mechanism of occurrence of basilar artery fenestration. (C) 1997 by Elsevier Science Inc.
• Giant thrombosed fusiform aneurysm at the branch of the middle cerebral artery presenting with intramural hemorrhage: A case report

  Miki Fujimura, Hirobumi Seki, Takayuki Sugawara, Tsutomu Sakuma, Yasunari Ohtawara, Norio Harata  Neurological Surgery  25-  (2)  151  -155  1997/02  [Not refereed][Not invited]
   

  We report a rare case of a giant thrombosed fusiform aneurysm at the branch of left middle cerebral artery presenting with intramural hemorrhage of the aneurysm. A twenty-year-old man with familial and past history of migraine presented sudden temporalgia on August 13, 1995. Computed tomography (CT) scan on the day of the first attack revealed a well delineated high density area at the left Sylvian fissure, 2.5cm in diameter. Angiogram showed avascular area corresponding to the lesion, but no visualization of the aneurysm. On October 18, this patient presented sudden temporalgia again. CT scan on the day of the second attack indicated new intramural hemorrhage and surgery was performed on October 31. No evidence of subarachnoid hemorrhage was shown during the operation, and the lesion was proven to be a thrombosed fusiform aneurysm at the branch of the middle cerebral artery. The parent artery was clipped at both proximal and distal sides of the aneurysm, and the aneurysm was totally removed with success. Histological finding further supported the idea that the attacks mentioned were due to intramural hemorrhage of the thrombosed aneurysm. Postoperative course was uneventful and the patient was discharged without any neurological deficit. Intramural hemorrhage of a giant fusiform aneurysm is relatively rare, only reported in several autopsy cases. Furthermore, we failed to discover any comparable cases of giant fusiform aneurysm presenting symptoms directly caused by intramural hemorrhage of the aneurysm.
• Giant thrombosed fusiform aneurysm at the branch of the middle cerebral artery presenting with intramural hemorrhage: A case report

  M Fujimura, H Seki, T Sugawara, T Sakuma, Y Ohtawara, N Harata  NEUROLOGICAL SURGERY  25-  (2)  151  -155  1997/02  [Not refereed][Not invited]
   

  We report a rare case of a giant thrombosed fusiform aneurysm at the branch of left middle cerebral artery presenting with intramural hemorrhage of the aneurysm. A twenty-year-old man with familial and past history of migraine presented sudden temporalgia on August 13, 1995. Computed tomography (CT) scan on the day of the first attack revealed a well delineated high density area at the left Sylvian fissure, 2.5cm in diameter. Angiogram showed avascular area corresponding to the lesion, but no visualization of the aneurysm. On October 18, this patient presented sudden temporalgia again. CT scan on the day of the second attack indicated new intramural hemorrhage and surgery was performed on October 31. No evidence of subarachnoid hemorrhage was shown during the operation, and the lesion was proven to be a thrombosed fusiform aneurysm al the branch of the middle cerebral artery. The parent artery was clipped at both proximal and distal sides of the aneurysm, and the aneurysm was totally removed with success. Histological finding further supported the idea that the attacks mentioned were due to intramural hemorrhage of the thrombosed aneurysm. Postoperative course was uneventful and the patient was discharged without any neurological deficit. Intramural hemorrhage of a giant fusiform aneurysm is relatively rare, only reported in several autopsy cases. Furthermore, we failed to discover any comparable cases of giant fusiform aneurysm presenting symptoms directly caused by intramural hemorrhage of the aneurysm.
• Inducible nitric oxide synthase following hypoxia in rat cultured glial cells

  M Kawase, H Kinouchi, Kato, I, A Akabane, T Kondo, S Arai, M Fujimura, H Okamoto, T Yoshimoto  BRAIN RESEARCH  738-  (2)  319  -322  1996/11  [Not refereed][Not invited]
   

  Nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) exerts inhibitory and cytotoxic effects on various cells including neuronal cells. In the present study, we examined the ability of rat glial cells to produce NO following hypoxia/reoxygenation in vitro by measuring nitrite. The levels of nitrite produced in the cultured media of glial cells significantly increased after 12-h hypoxia but not after 0- and 6-h hypoxia. The NOS inhibitor, N-G-monomethyl-L-arginine, decreased hypoxia-induced nitrite formation. In glial cells after hypoxia/reoxygenation, the iNOS mRNA and protein expressions were detected by reverse-transcription polymerase chain reaction and by immunocytochemical analysis, respectively. The present study provides the first evidence that hypoxia induces NO production from glial cells. This hypoxia-induced, glial cell-derived NO may play a critical role in the pathogenesis of cerebral ischemia in vivo.
• Inducible nitric oxide synthase following hypoxia in rat cultured glial cells

  M Kawase, H Kinouchi, Kato, I, A Akabane, T Kondo, S Arai, M Fujimura, H Okamoto, T Yoshimoto  BRAIN RESEARCH  738-  (2)  319  -322  1996/11  [Not refereed][Not invited]
   

  Nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) exerts inhibitory and cytotoxic effects on various cells including neuronal cells. In the present study, we examined the ability of rat glial cells to produce NO following hypoxia/reoxygenation in vitro by measuring nitrite. The levels of nitrite produced in the cultured media of glial cells significantly increased after 12-h hypoxia but not after 0- and 6-h hypoxia. The NOS inhibitor, N-G-monomethyl-L-arginine, decreased hypoxia-induced nitrite formation. In glial cells after hypoxia/reoxygenation, the iNOS mRNA and protein expressions were detected by reverse-transcription polymerase chain reaction and by immunocytochemical analysis, respectively. The present study provides the first evidence that hypoxia induces NO production from glial cells. This hypoxia-induced, glial cell-derived NO may play a critical role in the pathogenesis of cerebral ischemia in vivo.
• Perivascular coating with fibrin glue of cerebral arteries in patients with aneurysmal subarachnoid hemorrhage; Incidence of chronic hydrocephalus

  M Fujimura, T Sugawara, H Seki, T Oku, K Niimura, Y Otawara, H Higuchi  TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE  179-  (4)  267  -272  1996/08  [Not refereed][Not invited]
   

  The incidence of chronic hydrocephalus was studied in 39 patients with subarachnoid hemorrhage, who underwent perivascular coating with fibrin glue of cerebral arteries after clipping of aneurysm. A use was made of this procedure in order to prevent vasospasm by keeping the main cerebral arteries away from direct contact with subarachnoid clots. Most cases in this series belonged to group 3 of Fisher's CT grade (33/39, 84.6%). As a result, despite the high CT grade, the incidence of chronic hydrocephalus was as low as 17.9% (7/39), almost in agreement with those of the previous literature. In conclusion, (1) coating with fibrin glue did not increase the incidence of chronic hydrocephalus and (2) intrathecal application of fibrin glue is a promising method in the field of clinical neurosurgery.
• Perivascular coating with fibrin glue of cerebral arteries in patients with aneurysmal subarachnoid hemorrhage; Incidence of chronic hydrocephalus

  M Fujimura, T Sugawara, H Seki, T Oku, K Niimura, Y Otawara, H Higuchi  TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE  179-  (4)  267  -272  1996/08  [Not refereed][Not invited]
   

  The incidence of chronic hydrocephalus was studied in 39 patients with subarachnoid hemorrhage, who underwent perivascular coating with fibrin glue of cerebral arteries after clipping of aneurysm. A use was made of this procedure in order to prevent vasospasm by keeping the main cerebral arteries away from direct contact with subarachnoid clots. Most cases in this series belonged to group 3 of Fisher's CT grade (33/39, 84.6%). As a result, despite the high CT grade, the incidence of chronic hydrocephalus was as low as 17.9% (7/39), almost in agreement with those of the previous literature. In conclusion, (1) coating with fibrin glue did not increase the incidence of chronic hydrocephalus and (2) intrathecal application of fibrin glue is a promising method in the field of clinical neurosurgery.
• Cine-mode magnetic resonance imaging of a thoracic intradural arachnoid cyst: Case report

  M Fujimura, T Tominaga, K Koshu, H Shimizu, T Yoshimoto  SURGICAL NEUROLOGY  45-  (6)  533  -536  1996/06  [Not refereed][Not invited]
   

  We report the appearance of a thoracic intradural arachnoid cyst on cine-mode magnetic resonance imaging (MRI). Based on the operative findings, cine-mode MRI was more sensitive for identifying the intradural location of arachnoid cysts than was conventional MRI. The value of cine-mode MRI in diagnosing this rare entity is discussed.
• Anomalous Internal Carotid Artery-Anterior Cerebral Artery Anastomosis Associated with Fenestration and Cerebral Aneurysm: —Case Report—

  Miki Fujimura, Hirobumi Seki, Takayuki Sugawara, Tatsuya Oku, Hiroshi Higuchi, Nobukazu Tomichi  Neurologia medico-chirurgica  36-  (4)  229  -233  1996  [Not refereed][Not invited]
   

  A 69-year-old female presented with a ruptured aneurysm at the distal tip of a fenestrated anomalous artery which originated in the ophthalmic segment of the internal carotid artery (ICA), passed between the optic nerves, ascended along the midline, and formed the fenestration before dividing into the bilateral pericallosal arteries. The anomalous artery manifested as subarachnoid hemorrhage. Four days later, she died from severe pulmonary edema. The angiographic finding was confirmed by post mortem examination. Numerous perforating vessels from the anomalous artery and the distal ICA supplied the optic nerves and chiasm. This finding supports the idea that this anomalous vessel may be an extreme developmental variation of the prechiasmal arterial plexus. © 1996, The Japan Neurosurgical Society. All rights reserved.
• Cine-mode magnetic resonance imaging of a thoracic intradural arachnoid cyst: Case report

  Miki Fujimura, Teiji Tominaga, Keiji Koshu, Hiroaki Shimizu, Takashi Yoshimoto  Surgical Neurology  45-  (6)  533  -536  1996  [Not refereed][Not invited]
   

  We report the appearance of a thoracic intradural arachnoid cyst on cine-mode magnetic resonance imaging (MRI). Based on the operative findings, cine-mode MRI was more sensitive for identifying the intradural location of arachnoid cysts than was conventional MRI. The value of cine-mode MRI in diagnosing this rare entity is discussed.
• Anomalous Internal Carotid Artery-Anterior Cerebral Artery Anastomosis Associated with Fenestration and Cerebral Aneurysm: —Case Report—

  Miki Fujimura, Hirobumi Seki, Takayuki Sugawara, Tatsuya Oku, Hiroshi Higuchi, Nobukazu Tomichi  Neurologia medico-chirurgica  36-  (4)  229  -233  1996  [Not refereed][Not invited]
   

  A 69-year-old female presented with a ruptured aneurysm at the distal tip of a fenestrated anomalous artery which originated in the ophthalmic segment of the internal carotid artery (ICA), passed between the optic nerves, ascended along the midline, and formed the fenestration before dividing into the bilateral pericallosal arteries. The anomalous artery manifested as subarachnoid hemorrhage. Four days later, she died from severe pulmonary edema. The angiographic finding was confirmed by post mortem examination. Numerous perforating vessels from the anomalous artery and the distal ICA supplied the optic nerves and chiasm. This finding supports the idea that this anomalous vessel may be an extreme developmental variation of the prechiasmal arterial plexus. © 1996, The Japan Neurosurgical Society. All rights reserved.
• GANGLIOGLIOMA IN THE BASAL GANGLIA TOTALLY RESECTED BY A TRANS-DISTAL SYLVIAN APPROACH

  M FUJIMURA, T KAYAMA, T KUMABE, T YOSHIMOTO  TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE  175-  (3)  211  -218  1995/03  [Not refereed][Not invited]
   

  A patient with a ganglioglioma in the basal ganglia is presented. An 18-year-old man presented with involuntary movement in his right hand and right homonymous hemianopsia. Computed tomography and magnetic resonance imaging revealed a cystic tumor with an enhancing nodule in the basal ganglia extending into the thalamus. The mass was totally resected by a trans-distal Sylvian approach and was histologically proven to be a ganglioglioma. This is a rare case of midline ganglioglioma in a patient who underwent gross total resection.
• GANGLIOGLIOMA IN THE BASAL GANGLIA TOTALLY RESECTED BY A TRANS-DISTAL SYLVIAN APPROACH

  M FUJIMURA, T KAYAMA, T KUMABE, T YOSHIMOTO  TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE  175-  (3)  211  -218  1995/03  [Not refereed][Not invited]
   

  A patient with a ganglioglioma in the basal ganglia is presented. An 18-year-old man presented with involuntary movement in his right hand and right homonymous hemianopsia. Computed tomography and magnetic resonance imaging revealed a cystic tumor with an enhancing nodule in the basal ganglia extending into the thalamus. The mass was totally resected by a trans-distal Sylvian approach and was histologically proven to be a ganglioglioma. This is a rare case of midline ganglioglioma in a patient who underwent gross total resection.

Books etc

• 神経疾患最新の治療

  南江堂 2006
• 神経疾患最新の治療

  南江堂 2006
• Pharmacology of Cerebral Ischemia

  Wissenschaftliche Verlagsgesellschaft, Stuttgart 1998
• Maturation Phenomenon in Cerebral Ischemia

  Springer Verlag, Heidelberg 1998
• Pharmacology of Cerebral Ischemia

  Wissenschaftliche Verlagsgesellschaft, Stuttgart 1998
• Maturation Phenomenon in Cerebral Ischemia

  Springer Verlag, Heidelberg 1998

Presentations

• 内視鏡的第三脳室開窓術の治療成績について  [Not invited]

  第４２回日本脳神経外科学会東北地方会  2007
• モヤモヤ病に対する直接血行再建術と治療成績；術後急性期脳血流評価の有用性  [Not invited]

  第３６回日本脳卒中の外科学会総会  2007
• 軟性鏡による内視鏡的第三脳室開窓術の治療成績  [Not invited]

  第１６回脳神経外科手術と機器学会  2007
• 病期進行と多彩な血管病変の合併を認めた成人発症もやもや病の１手術例  [Not invited]

  第２２回TKNJ Conference  2007
• もやもや病患者末梢血における制御型T細胞関連マーカー（CD4/25, Foxp3)の検討  [Not invited]

  第８回日本分子脳神経外科学会  2007
• Therapeutic value of STA-MCA anastomosis with postoperative CBF measurement during the acute stage in patients with moyamoya disease  [Not invited]

  Congress of Neurological Surgeons 2007 Annual Meeting  2007
• もやもや病に対するSTA-MCA吻合術後・症候性過灌流とその関連因子についての検討  [Not invited]

  第６６回日本脳神経外科学会総会  2007
• Oxidative stressと脳虚血  [Not invited]

  第１９回日本脳循環代謝学会総会  2007
• もやもや病に対するSTA-MCA吻合術後・症候性過灌流とその関連因子についての検討  [Not invited]

  第１９回日本脳循環代謝学会総会  2007
• Efficacy of endoscopic third ventriculostomy using flexible neuroendoscopic system: outcome of 46 consecutive cases in Tohoku University  [Not invited]

  The 12th Asian-Australian Congress of Neurological Surgeons  2007
• 軟性鏡を用いた内視鏡的第三脳室開窓術の治療成績についての検討  [Not invited]

  第１４回日本神経内視鏡学会総会  2007
• 内視鏡的第三脳室開窓術の治療成績について  [Not invited]

  第４２回日本脳神経外科学会東北地方会  2007
• モヤモヤ病に対する直接血行再建術と治療成績；術後急性期脳血流評価の有用性  [Not invited]

  第３６回日本脳卒中の外科学会総会  2007
• 軟性鏡による内視鏡的第三脳室開窓術の治療成績  [Not invited]

  第１６回脳神経外科手術と機器学会  2007
• 病期進行と多彩な血管病変の合併を認めた成人発症もやもや病の１手術例  [Not invited]

  第２２回TKNJ Conference  2007
• もやもや病患者末梢血における制御型T細胞関連マーカー（CD4/25, Foxp3)の検討  [Not invited]

  第８回日本分子脳神経外科学会  2007
• Therapeutic value of STA-MCA anastomosis with postoperative CBF measurement during the acute stage in patients with moyamoya disease  [Not invited]

  Congress of Neurological Surgeons 2007 Annual Meeting  2007
• もやもや病に対するSTA-MCA吻合術後・症候性過灌流とその関連因子についての検討  [Not invited]

  第６６回日本脳神経外科学会総会  2007
• Oxidative stressと脳虚血  [Not invited]

  第１９回日本脳循環代謝学会総会  2007
• もやもや病に対するSTA-MCA吻合術後・症候性過灌流とその関連因子についての検討  [Not invited]

  第１９回日本脳循環代謝学会総会  2007
• Efficacy of endoscopic third ventriculostomy using flexible neuroendoscopic system: outcome of 46 consecutive cases in Tohoku University  [Not invited]

  The 12th Asian-Australian Congress of Neurological Surgeons  2007
• 軟性鏡を用いた内視鏡的第三脳室開窓術の治療成績についての検討  [Not invited]

  第１４回日本神経内視鏡学会総会  2007
• モヤモヤ病に対する血行再建術後急性期の脳灌流MRIを用いた脳循環動態の検討  [Not invited]

  第３５回日本脳卒中の外科学会総会  2006
• Symptomatic cerebral hyperperfusion following STA-MCA anastomosis in patients with adult-onset moyamoya disease: analysis by IMP-SPECT  [Not invited]

  The 8th Korea and Japanese Friendship Conference on Surgery for Cerebral Stroke  2006
• くも膜下出血急性期脳損傷におけるAkt/GSK3b生存シグナルの役割  [Not invited]

  第七回日本分子脳神経外科学会  2006
• Diagnostic value of perfusion weighted MRI for postoperative cerebral hyperperfusion in patients with moyamoya disease  [Not invited]

  Annual meeting of Congress of Neurological Surgeons  2006
• モヤモヤ病に対する血行債剣術前後の脳循環と臨床像：SPECT, PWIと術中赤外線画像装置による検討  [Not invited]

  第６５回日本脳神経外科学会総会  2006
• もやもや病に対する血行再建術前後の脳循環と臨床像脳灌流MRIと赤外線画像装置による検討  [Not invited]

  第１８回日本脳循環代謝学会総会  2006
• 脊髄空洞症を伴う水頭症に対し第三脳室開窓術が有効であった１手術例  [Not invited]

  第１３回日本神経内視鏡学会  2006
• Prediction of symptomatic cerebral hyperperfusion after STA-MCA anastomosis in patients with moyamoya disease by intraoperative infrared imaging system and postoperative CBF analysis  [Not invited]

  The 8th International Conference on Cerebrovascular Surgery  2006
• モヤモヤ病に対する血行再建術後急性期の脳灌流MRIを用いた脳循環動態の検討  [Not invited]

  第３５回日本脳卒中の外科学会総会  2006
• Symptomatic cerebral hyperperfusion following STA-MCA anastomosis in patients with adult-onset moyamoya disease: analysis by IMP-SPECT  [Not invited]

  The 8th Korea and Japanese Friendship Conference on Surgery for Cerebral Stroke  2006
• くも膜下出血急性期脳損傷におけるAkt/GSK3b生存シグナルの役割  [Not invited]

  第七回日本分子脳神経外科学会  2006
• Diagnostic value of perfusion weighted MRI for postoperative cerebral hyperperfusion in patients with moyamoya disease  [Not invited]

  Annual meeting of Congress of Neurological Surgeons  2006
• モヤモヤ病に対する血行債剣術前後の脳循環と臨床像：SPECT, PWIと術中赤外線画像装置による検討  [Not invited]

  第６５回日本脳神経外科学会総会  2006
• もやもや病に対する血行再建術前後の脳循環と臨床像脳灌流MRIと赤外線画像装置による検討  [Not invited]

  第１８回日本脳循環代謝学会総会  2006
• 脊髄空洞症を伴う水頭症に対し第三脳室開窓術が有効であった１手術例  [Not invited]

  第１３回日本神経内視鏡学会  2006
• Prediction of symptomatic cerebral hyperperfusion after STA-MCA anastomosis in patients with moyamoya disease by intraoperative infrared imaging system and postoperative CBF analysis  [Not invited]

  The 8th International Conference on Cerebrovascular Surgery  2006

Association Memberships

• 日本脳循環代謝学会   日本分子脳神経外科学会(2004/09- ジュニア世話人)   艮陵脳卒中研究会(2003/06- 世話人)   日本脳循環代謝学会(2006/01- 評議員)   日本脳循環代謝学会   日本分子脳神経外科学会(2004/09- ジュニア世話人)   艮陵脳卒中研究会(2003/06- 世話人)   日本脳循環代謝学会(2006/01- 評議員)   日本脳神経CI学会(2021/04-世話人)   

Research Projects

• Multiple advanced video analysis to elucidate the 'complexity' of microsurgery

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2021/04 -2026/03 

  Author : 杉山 拓, 杉森 博行, 松澤 等, 小笠原 克彦, 藤村 幹, 伊東 雅基

   

  本研究の目的は、外科手術の機能や安全性、術者スキルに関わる重要な要素を探索することであり、この先にアウトカム予測、有害イベント予測、術者スキル評価AIなどを目指すものである。 令和3年度は、頚動脈狭窄症に対する動脈内膜剥離術に焦点を当て、手術映像の解析に着手した。頚動脈を剥離する際の、頚動脈の動き（加速度）に着目し、これを手術映像から測定することで、“組織に対する愛護的な手術操作”の新たな指標と仮定した。１１７例の頚動脈内膜剥離術中映像の網羅的解析により、この新たな指標が、手術スキルおよび手術合併症に相関することが証明された。また、この指標を用いることにより、どの様な手術剥離法が客観的に有用であるか（組織に対して愛護的であるか）を示すことが可能になった。さらには、このような手術パフォーマンスの指標が、従来の研究で多く用いられてきた患者側の指標と同等以上に、治療成績にも相関することが多変量解析の結果からも証明し得た。本研究結果を、現在英語論文として投稿準備中である。 また、微小脳血管吻合のトレーニング映像を用いて、術具の先端を自動追跡する深層学習アルゴリズム、手術操作の対象となる微小血管をセグメンテーションするアルゴリズムの作成を開始し、おおむね精度の高いアルゴリズムが形成されてきている。これらを用いて、術具の軌道分析や、患者組織の変形分析などを行い、術者レベルや血管吻合成否に関与する因子の網羅的探索を継続している。
• Innovative Research of Neuroprotection for Delayed Cerebral Ischemia Associated with Cerebral Vasospasm after Subarachnoid Hemorrhage using Novel Hemoglobin-based Oxygen Carrier

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2022/04 -2025/03 

  Author : 月花 正幸, 伊東 雅基, 川堀 真人, 鐙谷 武雄, 小松 晃之, 藤村 幹
• 広範性脳損傷に対する間葉系幹細胞培養液由来エクソソームの経鼻的投与の検討

  日本学術振興会：科学研究費助成事業

  Date (from‐to) : 2022/04 -2025/03 

  Author : 穂刈 正昭, 藤村 幹, 川堀 真人
• 人工酸素運搬体を用いたmulti-targetの脳保護療法の開発

  日本学術振興会：科学研究費助成事業

  Date (from‐to) : 2022/04 -2025/03 

  Author : 鐙谷 武雄, 藤村 幹, 伊東 雅基, 小松 晃之, 川堀 真人
• Elucidation of moyamoya disease pathophysiology through an interaction of hemodynamics and endothelial cells

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2021/04 -2024/03 

  Author : 冨永 悌二, 藤村 幹, Rashad Sherif, 新妻 邦泰, 森戸 大介, 下田 由輝

   

  もやもや病は両側内頚動脈終末部が進行性に狭窄・閉塞し、付近に異常血管網の発達を認める原因不明の疾患であり、病態解明と新規治療開発が求められている。もやもや病の感受性遺伝子であるRNF213遺伝子が同定されたが、その変異単独でもやもや病は発症せず、それに加えて何らかの二次的因子が加わり発症するtwo hit theoryが提唱されている。 本研究の目的は、今までに明らかではなかった血流と血管内皮細胞の相互作用という切り口から、もやもや病の病因・病態を解明することである。 本年度は①～⑤の5つの要素に分けて研究を行った。 ①数値流体力学的解析（CFD解析）：もやもや病患者においてどのように血液が流れ、血管壁にはどのような力がかかるのかをCFDを用いて解析したが、もやもや病の血管形態には個人差も大きく、未だまとまった形の知見は得られていない。 ②流体培養を用いた解析：「流れ」の違いに応じて血管内皮細胞においてRNF213遺伝子発現が変化することが見いだされた。 ③免疫学的解析：RNF213遺伝子変異により抗原取り込みや処理が遅延することを明らかにした。 ④ 臨床応用につながるバイオマーカー探索：RNF213遺伝子変異マウスを用いて、バイオマーカー候補を探索中である。臨床例では、RNF213遺伝子変異がもやもや病患者において肺動脈狭窄を合併する危険因子である可能性が見いだされ、論文として報告した。 ⑤RNF213に関する解析：RNF213変異体の新たな遺伝子変異マウスが樹立されたため、それを用いた実験を行うための環境を構築した。 上記のようにそれぞれの要素につき研究の進捗を認めるが、最終目標であるもやもや病の病因解明には未だ至ってはいない。
• The efficacy of novel treatment method to block Feroptosis for ischemic stroke

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2021/04 -2024/03 

  Author : 栗栖 宏多, 鐙谷 武雄, 長内 俊也, 藤村 幹

   

  本年はラット脳虚血際還流障害モデルの作成を行ってきた。SDラットの右総頚動脈を露出し、スレッドを頚動脈に挿入し、1時間の一時閉塞を行い、その後、再還流を行うことによって、モデルを作成してきた。 しかしながら安定したモデル作成に苦慮しており、くも膜下出血を発症してしまう。スレッドのサイズを小さいものを選択することによって安定したモデルを作れるようになってきた。現在はコントロールのモデルを作成しながら、病理組織学的評価（HE, LFB）を行い、均一な大きさの虚血再還流モデルの作成を目指している。 作成したSDラットの正常脳組織を透過電子顕微鏡を用いて観察した。透過電子顕微鏡のため固定液の準備などを行なった。フェロプトーシスで縮小が見られるミトコンドリアの正常サイズのサンプルを収集した。 また、定期的な情報交換として、フェロプトーシス促進剤による癌への影響について研究している本学の研究グループと定期的にWEBカンファレンスを行なった。
• Comprehensive validation of circulating microRNA signatures for Moyamoya disease early detection as an epigenome blood biomarker

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2019/04 -2024/03 

  Author : 伊東 雅基, 内野 晴登, 杉山 拓, 藤村 幹, 佐藤 典宏, 矢部 一郎, 寳金 清博, 中山 若樹, 数又 研, 東海林 菊太郎, 浜内 祝嗣

   

  研究年度の3年目にあたる2021（R3）年度は、前年度末に完了した全対象者160名（もやもや病患者82名、健常比較対照者78名）の末梢血循環血漿から抽出精製した、血漿microRNAの発現量データの解析を行なった。すなわち、ハイスループットreal-time定量PCRアレイにより、関心microRNA17種類と内部および外部標準7種類（全24種）のmicroRNAのPCR測定値を、比較定量法により発現分析した。全160検体、24microRNAのうち、全被験者でCt値を検出可能であったのは、15microRNA（関心miRNA 8種類と内部および外部標準7種類）であったため、これら15microRNAの全発現量を用いてglobal normalizationによりdataの正規化をおこなった。続いて、15種の血漿microRNA発現profileを主成分分析により解析した結果、発現変動は第一主成分と第二主成分で二郡に分かれ、疾患群と比較対照群間で発現プロファイルに差があることが判明した。続いて、疾患群と対照群で関心microRNAの発現変動解析を実施した結果、3種類の関心microRNAで、二郡間での有意な発現変動を認めた。そのほかの関心microRNAについては、全体として発現量が極めて少ないためか、先行研究で認めた発現変動を確認できなかった。続いてmicroRNA発現量と、もやもや病の臨床的特徴との関連解析を開始した。その結果、microRNA発現量に関わらず、RNF213創始者変異（p.R4810K）を有する成人もやもや病患者では、直接・間接複合血行再建術後に、間接血行再建路が有意に発達することを見出した。間接血行再建路を介した血管新生反応には、microRNAによるエピゲノム制御ではなく、感受性遺伝子の遺伝的多型が関与していることが示唆された。
• シロスタゾールを用いたもやもや病における内因性幹細胞賦活と血管新生促進療法の開発

  日本学術振興会：科学研究費助成事業

  Date (from‐to) : 2020/04 -2023/03 

  Author : 藤村 幹, 冨永 悌二, 新妻 邦泰, 麦倉 俊司, 坂田 洋之

   

  もやもや病は異常血管網発達ならびに代償的な側副血行路を含めた血管新生能を有する原因不明の疾患である。小児や若年成人に好発し、浅側頭動脈・中大脳動脈吻合術（直接血行再建術）や側頭筋を用いた間接血行再建術を含めた外科治療の有効性が確立しているが、重症例に対する治療は未確立である。間接術は脳損傷を伴う重症例にも安全に行うことが可能であるが、間接術単独の場合は血管新生不良例が見られる点が問題である。血管新生能を高める試みがなされているがその効果は限定的であるのが現状である。今回、内因性多能性幹細胞とその活性化に期待が持てる薬剤に着目し、間接術からの血管新生の機序を解明し、その効果を促進する手法を開発することによりもやもや病の治療成績の向上が期待できると着想した。本研究の目的は、もやもや病患者クモ膜における内因性多能性幹細胞の発現と血行再建術後の血管新生の関連を明らかにし、「もやもや病に対するシロスタゾールを用いた内因性多能性幹細胞の賦活と血行再建術効果促進」の概念実証し、臨床レベルでもやもや病手術例に対するシロスタゾールを用いた内因性多能性幹細胞の賦活による血行再建術効果療法を確立することである。 ２年度目は、血行再建術を行ったもやもや病患者に由来する検体を用いて、患者クモ膜組織における内因性多能性幹細胞を免疫組織学的に検討した。18例の患者より得られたクモ膜について、多能性幹細胞の複数の指標について免疫組織染色を行ったところ多くの検体において多能性幹細胞マーカー陽性所見を認めた。また術後MRAを行い血管新生の程度と術前脳虚血、RNF213遺伝子異常との関連を検証し有意な結果を得た。もやもや病患者クモ膜において内因性多能性幹細胞が存在すること、RNF213遺伝子変異により血管新生が増幅されることが示唆された。
• Analysis of latent imaging findings in healthy subjects with moyamoya disease susceptibility gene RNF213 polymorphism using artificial intelligence

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2020/04 -2023/03 

  Author : 園部 真也, 冨永 悌二, 藤村 幹, 中川 敦寛, 新妻 邦泰, 麦倉 俊司

   

  ・研究の遂行について倫理委員会の承認を得た。 ・研究に使用するデータの利用許可を得た。また研究に使用するデータの大部分について利用準備を完了した。 ・研究の手法についてより詳細な吟味を行った。具体的には、研究の核を成す「血管の信号を解剖学的な理解に基づいて正確に抽出する」ことと「血管形状を数値に変換し各種のパラメーターを取り出す」ことについて手法を洗練した。それぞれについて分けて以下に記載する。 ・「血管の信号を解剖学的な理解に基づいて正確に抽出する」過程については、当初の研究計画では血管の信号を平面へ投射して計測する方法を予定していたが、平面へ投射せず立体的な位置関係を維持したまま信号を処理する方法が新たに考案された。後者の方がより正確に血管形状を数値化できることが判明したため、後者の手法を用いることとした。 ・「血管形状を数値に変換し各種のパラメーターを取り出す」過程について、試行錯誤を重ねた。様々な既存のモデルやアルゴリズムを試したが、それぞれ一長一短があり、血管形状の個人差に対応しきれないことによる不具合が存在することが判明した。特に、血管の走行に垂直な断面で血管を観察した際に正円でない場合（扁平な血管であるため断面が楕円の場合や狭窄を伴う血管であるため断面が不整形の場合）においてこれらの不具合が顕著であり、これを解決するような新しいモデルとアルゴリズムを有するプログラムの開発に着手した。同プログラムの開発について、およそ八割程度の達成が得られた。
• Intravoxel-incoherent-motion (IVIM) MRI as a noninvasive method for estimating cerebral blood volume in ischemic brain disease

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2015/04 -2018/03 

  Author : Tamura Hajime

   

  Intravoxel-incoherent-motion (IVIM) MRI is a noninvasive method for investigating vascular as well as extra-vascular component in living tissue by use of diffusion-weighted MRI. We investigated if this noninvasive method is useful for estimating cerebral blood volume in ischemic brain disease. We found that the vascular component was detectable, but observed signals were small in the study of normal volunteers. There were regions where reliable information was difficult to obtain such as parts of the frontal brain region.In clinical study, the vascular component was detectable for ischemic disease because of dilatation of blood vessels in those situations. We also found that blood oxygenation of the vascular components could be estimated.