Fujimura Miki

Faculty of Medicine Specialized Medicine Neurological DisorderProfessor
Hokkaido University HospitalProfessor
Institute for the Advancement of Higher EducationProfessor
Last Updated :2025/06/07

■Researcher basic information

Degree

  • Mar. 2000

Researchmap personal page

Research Keyword

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

Research Field

  • Life sciences, Neurosurgery

Educational Organization

■Career

Educational Background

  • Apr. 1996 - Mar. 2000, Tohoku University, Graduate School of Medicine, Department of Neurosurgery, Japan
  • 1994, Tohoku University, Japan

Committee Memberships

  • Apr. 2021 - Present
    日本脳神経CI学会, 世話人, Society
  • Apr. 2021 - Present
    日本術中画像情報学会, 理事, Society
  • Mar. 2021 - Present
    スパズム・シンポジウム, 世話人, Society
  • Mar. 2021 - Present
    日本脳卒中の外科学会, 理事, Society
  • Mar. 2021 - Present
    日本脳卒中学会, 理事, Society
  • 2021 - Present
    日本整容脳神経外科学会, 理事, Society
  • Nov. 2020 - Present
    日本神経内視鏡学会, 評議員, Society
  • Oct. 2018 - Present
    日本脳循環代謝学会, 幹事, Society
  • 2019 - 2023
    International Society of Cerebral Blood Flow and Metabolism, Director Board Member, Educational Committee Member, Society
  • May 2021
    日本脳神経外科コングレス, 運営委員、国際関係委員長, Society
  • The Mt. Fuji Workshop on CVD, 幹事(2020/2021年代表幹事), Society
  • 日本脳神経外科学会, 代議員、国際委員, Society

■Research activity information

Awards

  • Jan. 2015, 東北大学医学部奨学賞 金賞               
  • Jan. 2015, 宮城県医師会 医学奨励賞               
  • Mar. 2013, 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」               
    Japan

Papers

  • Systemic Immune-inflammation Index Is Associated with Symptomatic Cerebral Hyperperfusion after Revascularization Surgery in Moyamoya Disease.
    Taiji Yamamoto, Haruto Uchino, Masaki Ito, Taku Sugiyama, Miki Fujimura
    Neurologia medico-chirurgica, 24 Jan. 2025, [Domestic magazines]
    English, Scientific journal, Revascularization surgery for moyamoya disease poses risks of complications, requiring appropriate management. Although precise prediction is difficult, the systemic immune-inflammation index is a calculable marker that reflects systemic inflammatory conditions. We aimed to investigate the association between postoperative complications and the systemic immune-inflammation index. We included 91 hemispheres from 71 patients who underwent combined revascularization surgery for moyamoya disease. Symptomatic cerebral hyperperfusion, radiological ischemic and hemorrhagic complications, and temporal muscle swelling that caused brain shift were assessed. The systemic immune-inflammation index ratio was calculated from blood test results from the preoperative day and the day after surgery. The association between the systemic immune-inflammation index ratio and postoperative complications was assessed using univariate and multivariate analyses. A receiver operating characteristic analysis was performed to evaluate the diagnostic value of the systemic immune-inflammation index ratio for postoperative complications. The frequencies of postoperative symptomatic cerebral hyperperfusion, ischemic and hemorrhagic complications, and temporal muscle swelling were detected in 24 (26%), 15 (16%), 11 (12%), and 5 (5%) hemispheres, respectively. The systemic immune-inflammation index ratio was higher in the group with postoperative complications than in the group without (median 4.6 vs. 2.7). Multivariate analysis demonstrated the systemic immune-inflammation index ratio as an independent factor associated with symptomatic cerebral hyperperfusion (odds ratio 2.4, 95% confidence interval 1.5-4.0). The receiver operating characteristic analysis demonstrated that the optimal threshold of the systemic immune-inflammation index ratio was 4.3, with a specificity of 0.96 and sensitivity of 0.63. The systemic immune-inflammation index ratio is an indicator of postoperative complications, including symptomatic cerebral hyperperfusion in moyamoya disease, and can be used for effective postoperative management.
  • Validity of E-PASS Score for Evaluating Perioperative Minor Complications Associated with Carotid Endarterectomy.
    Yutaka Morishima, Masahito Kawabori, Yoichi M Ito, Masayuki Gekka, Koji Furukawa, Yoshimasa Niiya, Miki Fujimura
    Neurologia medico-chirurgica, 65, 1, 9, 14, 15 Jan. 2025, [Domestic magazines]
    English, Scientific journal, Carotid endarterectomy (CEA) is conducted to reduce the risk of cerebral infarction; therefore, a low complication rate is highly required. To predict long-term morbidity and mortality, various scoring systems have been considered; nonetheless, a model that can be utilized to estimate nonmajor temporary complications and minor complications is currently lacking. To evaluate the occurrence rate of perioperative complications in various surgical domains, the E-PASS (Estimation of Physiological Ability and Surgical Stress) score is employed. This study was carried out to investigate the utility of the E-PASS score as a predictive factor for the risk of minor complications in patients undergoing CEA. The retrospective analysis was performed for 104 consecutive series of CEA procedures carried out at Otaru Municipal Hospital. The correlation between E-PASS and the rate of minor complications was examined. Sensitivity and specificity were used to construct a receiver operating characteristic curve, and the area under the curve (AUC) was calculated for accuracy. Postoperative minor complications occurred in eight cases (7.7%), including six vagal nerve injuries and two pneumonia cases. Three categorical data-preoperative risk score, surgical stress scores, and comprehensive risk score (CRS) -showed a good relationship with the postoperative minor complication. Among them, CRS presented the highest sensitivity and specificity, as indicated by an AUC of 0.68. The CRS cutoff value was calculated as -0.068, with a 1.7% postoperative minor complication rate for those lower than -0.068 and 14.0% for those higher than -0.068. The E-PASS score was effective for evaluating and predicting postoperative minor complications in patients with CEA procedures.
  • 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, Japan Neurosurgical Society, 31 Dec. 2024
    Scientific journal
  • 破裂脳動脈瘤に対するコイル塞栓とクリッピング後の周術期管理の医療経済学的検討 新規脳血管攣縮予防薬導入による影響               
    栗栖 宏多, 長内 俊也, 大橋 和貴, 趙 捷宇, 小笠原 克彦, 杉山 拓, 藤村 幹
    日本脳神経血管内治療学会学術集会抄録集, 40回, 459, 459, (一社)日本脳神経血管内治療学会, Nov. 2024
    Japanese
  • もやもや病 もやもや病の頭蓋内血管negative remodelingと間接血行発達               
    内野 晴登, 伊東 雅基, 栗栖 宏多, 杉山 拓, 藤村 幹
    脳循環代謝, 36, 1, 67, 67, (一社)日本脳循環代謝学会, Nov. 2024
    Japanese
  • くも膜下出血後血管攣縮に対するクラゾセンタン-シロスタゾール併用療法 北大グループ前向き研究中間報告               
    杉山 拓, 穂刈 正昭, 新保 大輔, 下田 祐介, 月花 正幸, 岡本 迪成, 伊藤 康裕, 久保田 司, 藤原 雄介, 大木 聡悟, 山本 大慈, 齋藤 久泰, 内野 晴登, 栗栖 宏多, 藤村 幹
    脳循環代謝, 36, 1, 82, 82, (一社)日本脳循環代謝学会, Nov. 2024
    Japanese
  • Letter to the Editor Response.
    Kota Kurisu, Tomohiro Okuyama, Toshiya Osanai, Masaki Ito, Taku Sugiyama, Haruto Uchino, Miki Fujimura
    Journal of neurosurgery. Case lessons, 8, 18, 28 Oct. 2024, [International Magazine]
    English, Scientific journal
  • [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, Sep. 2024, [Domestic magazines]
    Japanese, Scientific journal, 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.
  • Artificial Intelligence for Patient Safety and Surgical Education in Neurosurgery
    Taku Sugiyama, Hiroyuki Sugimori, Mighui Tang, Miki Fujimura
    JMA Journal, Aug. 2024, [Peer-reviewed]
  • 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, 16 Jul. 2024, [International Magazine]
    English, Scientific journal, 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, 05 Jun. 2024, [Domestic magazines]
    English, Scientific journal, 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, 13 May 2024, [International Magazine]
    English, Scientific journal, 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, 09 May 2024, [International Magazine]
    English, Scientific journal, 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, 17 Apr. 2024, [International Magazine]
    English, Scientific journal, 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, Springer Science and Business Media LLC, 16 Apr. 2024
    Scientific journal
  • 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, 25 Mar. 2024, [International Magazine]
    English, Scientific journal, 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.), 18 Mar. 2024, [International Magazine]
    English, Scientific journal, 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, 04 Mar. 2024, [Domestic magazines]
    English, Scientific journal, 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, 18 Feb. 2024, [International Magazine]
    English, Scientific journal, 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, 01 Feb. 2024, [International Magazine]
    English, Scientific journal, 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.
  • Allogeneic Stem Cell Therapy for Acute Ischemic Stroke: The Phase 2/3 TREASURE Randomized Clinical Trial.
    Kiyohiro Houkin, Toshiya Osanai, Shinichiro Uchiyama, Kazuo Minematsu, Akihiko Taguchi, Katsuhiko Maruichi, Yoshimasa Niiya, Katsuyuki Asaoka, Yoshihiro Kuga, Katsumi Takizawa, Koichi Haraguchi, Shinichi Yoshimura, Kazumi Kimura, Koji Tokunaga, Atsuo Aoyama, Fusao Ikawa, Chikanori Inenaga, Tatsuya Abe, Atsushi Tominaga, Shinichi Takahashi, Kohsuke Kudo, Miki Fujimura, Taku Sugiyama, Masaki Ito, Masahito Kawabori, David C Hess, Sean I Savitz, Teruyuki Hirano
    JAMA neurology, 16 Jan. 2024, [International Magazine]
    English, Scientific journal, IMPORTANCE: Cell therapy is a promising treatment approach for stroke and other diseases. However, it is unknown whether MultiStem (HLCM051), a bone marrow-derived, allogeneic, multipotent adult progenitor cell product, has the potential to treat ischemic stroke. OBJECTIVE: To assess the efficacy and safety of MultiStem when administered within 18 to 36 hours of ischemic stroke onset. DESIGN, SETTING, AND PARTICIPANTS: The Treatment Evaluation of Acute Stroke Using Regenerative Cells (TREASURE) multicenter, double-blind, parallel-group, placebo-controlled phase 2/3 randomized clinical trial was conducted at 44 academic and clinical centers in Japan between November 15, 2017, and March 29, 2022. Inclusion criteria were age 20 years or older, presence of acute ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score of 8-20 at baseline), confirmed acute infarction involving the cerebral cortex and measuring more than 2 cm on the major axis (determined with diffusion-weighted magnetic resonance imaging), and a modified Rankin Scale (mRS) score of 0 or 1 before stroke onset. Data analysis was performed between May 9 and August 15, 2022. EXPOSURE: Patients were randomly assigned to either intravenous MultiStem in 1 single unit of 1.2 billion cells or intravenous placebo within 18 to 36 hours of ischemic stroke onset. MAIN OUTCOMES AND MEASURES: The primary end points were safety and excellent outcome at day 90, measured as a composite of a modified Rankin Scale (mRS) score of 1 or less, a NIHSS score of 1 or less, and a Barthel index score of 95 or greater. The secondary end points were excellent outcome at day 365, mRS score distribution at days 90 and 365, and mRS score of 0 to 1 and 0 to 2 at day 90. Statistical analysis of efficacy was performed using the Cochran-Mantel-Haenszel test. RESULTS: This study included 206 patients (104 received MultiStem and 102 received placebo). Their mean age was 76.5 (range, 35-95) years, and more than half of patients were men (112 [54.4%]). There were no between-group differences in primary and secondary end points. The proportion of excellent outcomes at day 90 did not differ significantly between the MultiStem and placebo groups (12 [11.5%] vs 10 [9.8%], P = .90; adjusted risk difference, 0.5% [95% CI, -7.3% to 8.3%]). The frequency of adverse events was similar between treatment groups. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, intravenous administration of allogeneic cell therapy within 18 to 36 hours of ischemic stroke onset was safe but did not improve short-term outcomes. Further research is needed to determine whether MultiStem therapy for ischemic stroke has a beneficial effect in patients who meet specific criteria, as indicated by the exploratory analyses in this study. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02961504.
  • 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, 02 Jan. 2024, [International Magazine]
    English, Scientific journal, 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, Japan Neurosurgical Society, 2024
    Scientific journal
  • 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, Japan Neurosurgical Society, 31 Dec. 2023
    Scientific journal
  • 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, 8, Suppl., S334, S334, (NPO)日本脳神経血管内治療学会, Nov. 2023
    Japanese
  • 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, 8, Suppl., S776, S776, (NPO)日本脳神経血管内治療学会, Nov. 2023
    Japanese
  • 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, 35, 1, 86, 86, (一社)日本脳循環代謝学会, Nov. 2023
    Japanese
  • 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, 35, 1, 102, 102, (一社)日本脳循環代謝学会, Nov. 2023
    Japanese
  • 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, 30 Aug. 2023, [Domestic magazines]
    English, Scientific journal, 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.), 04 Jul. 2023, [International Magazine]
    English, Scientific journal, 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, Jun. 2023, [International Magazine]
    English, Scientific journal, 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, 11 May 2023, [International Magazine]
    English, Scientific journal, 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, May 2023
    Scientific journal
  • 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, 20 Apr. 2023, [Domestic magazines]
    English, Scientific journal, 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, The Japanese Society for Neuroendovascular Therapy, 2023
    Scientific journal
  • 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, 23 Dec. 2022, [International Magazine]
    English, Scientific journal, 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, 7, Suppl., S162, S162, (NPO)日本脳神経血管内治療学会, Nov. 2022
    Japanese
  • 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, 34, 1, 124, 124, (一社)日本脳循環代謝学会, Oct. 2022
    Japanese
  • 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, 34, 1, 74, 74, (一社)日本脳循環代謝学会, Oct. 2022
    Japanese
  • 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, 34, 1, 122, 122, (一社)日本脳循環代謝学会, Oct. 2022
    Japanese
  • 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, 34, 1, 124, 124, (一社)日本脳循環代謝学会, Oct. 2022
    Japanese
  • 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, S. Karger AG, 05 Sep. 2022
    Scientific journal, 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, 31, 9, 579, 585, (一社)日本脳神経外科コングレス, Sep. 2022
    Japanese
  • 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, Hindawi Limited, 31 Jul. 2022
    Scientific journal, 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, Springer Science and Business Media LLC, 29 Jul. 2022
    Scientific journal
  • 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, 39, 159,169, 162,169, The Mt. Fuji Workshop on CVD事務局, Jul. 2022
    Japanese
  • 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, 21 Jun. 2022, [International Magazine]
    English, Scientific journal, 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, 16 Jun. 2022, [International Magazine]
    English, Scientific journal, 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, Jun. 2022, [International Magazine]
    English, 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, 22 Apr. 2022, [International Magazine]
    English, Scientific journal, 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, 15 Apr. 2022, [Domestic magazines]
    English, Scientific journal
  • 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, 50, 2, 130, 135, (一社)日本脳卒中の外科学会, Mar. 2022
    Japanese
  • 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, 50, 2, 130, 135, (一社)日本脳卒中の外科学会, Mar. 2022
    Japanese
  • 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, 22 Feb. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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, 18 Feb. 2022, [International Magazine]
    English, 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, 07 Feb. 2022, [International Magazine]
    English, Scientific journal, 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, 80, 増刊2 最新臨床脳卒中学(下), 109, 113, (株)日本臨床社, Feb. 2022
    Japanese
  • 【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, 31, 2, 81, 86, (一社)日本脳神経外科コングレス, Feb. 2022
    Japanese
  • 【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, 80, 増刊2 最新臨床脳卒中学(下), 109, 113, (株)日本臨床社, Feb. 2022
    Japanese
  • 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, [International Magazine]
    English, Scientific journal, 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, The Japanese Congress of Neurological Surgeons, 2022
    Scientific journal
  • 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, 45回, 228, 228, (一社)日本脳神経外傷学会, Jan. 2022
    Japanese
  • 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, [International Magazine]
    English, Scientific journal, 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, [International Magazine]
    English, Scientific journal, 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, [International Magazine]
    English, Scientific journal, 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, 6, Suppl., S133, S133, (NPO)日本脳神経血管内治療学会, Nov. 2021
    Japanese
  • 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, 33, 1, 73, 73, (一社)日本脳循環代謝学会, Nov. 2021
    Japanese
  • 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, 6, Suppl., S248, S248, (NPO)日本脳神経血管内治療学会, Nov. 2021
    Japanese
  • 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, 6, Suppl., S249, S249, (NPO)日本脳神経血管内治療学会, Nov. 2021
    Japanese
  • 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, 33, 1, 77, 77, (一社)日本脳循環代謝学会, Nov. 2021
    Japanese
  • 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, 33, 1, 70, 70, (一社)日本脳循環代謝学会, Nov. 2021
    Japanese
  • 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, 33, 1, 94, 94, (一社)日本脳循環代謝学会, Nov. 2021
    Japanese
  • 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, 6, Suppl., S248, S248, (NPO)日本脳神経血管内治療学会, Nov. 2021
    Japanese
  • 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, 6, Suppl., S249, S249, (NPO)日本脳神経血管内治療学会, Nov. 2021
    Japanese
  • 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, 33, 1, 73, 73, (一社)日本脳循環代謝学会, Nov. 2021
    Japanese
  • 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, 33, 1, 94, 94, (一社)日本脳循環代謝学会, Nov. 2021
    Japanese
  • 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, 09 Sep. 2021, [International Magazine]
    English, Scientific journal, 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, 15 Aug. 2021, [International Magazine]
    English, Scientific journal, 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, Aug. 2021, [International Magazine]
    English, Scientific journal, 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, 30 Jul. 2021, [International Magazine]
    English, Scientific journal, 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, Jul. 2021, [International Magazine]
    English, Scientific journal, 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, Jun. 2021, [International Magazine]
    English, Scientific journal, 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, 10 May 2021, [International Magazine]
    English, Scientific journal, 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, 13 Apr. 2021, [International Magazine]
    English, Scientific journal, 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, 48, 2, 163, 172, (公社)日本理学療法士協会, Apr. 2021
    Japanese
  • 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, 26 Mar. 2021, [International Magazine]
    English, Scientific journal, 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.
  • 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, Mar. 2021, [International Magazine]
    English, Scientific journal, 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, Mar. 2021, [Domestic magazines]
    Japanese, Scientific journal, 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, Feb. 2021, [International Magazine]
    English, Scientific journal, 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, 12 Jan. 2021, [International Magazine]
    English, Scientific journal, 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, [Domestic magazines]
    English, 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, [International Magazine]
    English, Scientific journal, 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, [International Magazine]
    English, Scientific journal, 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, [International Magazine]
    English, Scientific journal, 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, Dec. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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, 32, 1, 104, 104, (一社)日本脳循環代謝学会, Nov. 2020
    Japanese
  • 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, 32, 1, 106, 106, (一社)日本脳循環代謝学会, Nov. 2020
    Japanese
  • 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, 5, Suppl., 21, 21, (NPO)日本脳神経血管内治療学会, Nov. 2020
    Japanese
  • 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, 32, 1, 70, 70, (一社)日本脳循環代謝学会, Nov. 2020
    Japanese
  • 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, 32, 1, 112, 112, (一社)日本脳循環代謝学会, Nov. 2020
    Japanese
  • 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, 32, 1, 104, 104, (一社)日本脳循環代謝学会, Nov. 2020
    Japanese
  • 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, 32, 1, 106, 106, (一社)日本脳循環代謝学会, Nov. 2020
    Japanese
  • 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, 23 Oct. 2020, [International Magazine]
    English, Scientific journal, 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, 57, Suppl., S163, S163, (一社)日本核医学会, Oct. 2020
    Japanese
  • 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, Oct. 2020, [International Magazine]
    English, Scientific journal, 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, Oct. 2020, [International Magazine]
    English, Scientific journal
  • 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, Sep. 2020, [Domestic magazines]
    English, 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, Sep. 2020, [Peer-reviewed], [International Magazine]
    English, 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, Aug. 2020, [Peer-reviewed], [International Magazine]
    English, 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, 15 Jun. 2020, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, 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, May 2020, [Peer-reviewed], [International Magazine]
    English, 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, 07 Apr. 2020, [Peer-reviewed], [International Magazine]
    English, 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, Apr. 2020, [International Magazine]
    English, 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, Apr. 2020, [Domestic magazines]
    English, 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, Apr. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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, 13 Mar. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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, 28 Feb. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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, 21 Feb. 2020, [International Magazine]
    English, 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, 29, 2, 86, 93, 日本脳神経外科コングレス, Feb. 2020
    Japanese
  • 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, Feb. 2020, [Peer-reviewed], [International Magazine]
    English, 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, Japanese Congress of Neurological Surgeons, 2020
    Japanese, Scientific journal
  • 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, [International Magazine]
    English, Scientific journal, 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, [Peer-reviewed], [International Magazine]
    English, 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, 27 Dec. 2019, [International Magazine]
    English, Scientific journal, 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, Dec. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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, Nov. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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, 18 Oct. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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, Oct. 2019, [Peer-reviewed]
  • 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, Sep. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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, Sep. 2019, [Peer-reviewed]
  • 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, Jul. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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, Elsevier BV, Jul. 2019, [Peer-reviewed]
    Scientific journal
  • 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, 01 May 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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, May 2019, [Peer-reviewed]
  • 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, Apr. 2019, [Peer-reviewed]
  • 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, Springer-Verlag Wien, 13 Feb. 2019
    English, Scientific journal
  • 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, 08 Feb. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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, 01 Feb. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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, Japanese Congress of Neurological Surgeons, 2019
    Japanese, Scientific journal
  • 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, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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, 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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, 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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, 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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, Dec. 2018, [Peer-reviewed], [Domestic magazines]
    English, 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, Nov. 2018, [Peer-reviewed]
  • Hemorrhagic Moyamoya Disease : A Recent Update.
    Fujimura M, Tominaga T
    Journal of Korean Neurosurgical Society, Nov. 2018, [Peer-reviewed]
  • 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, Elsevier BV, Nov. 2018, [Peer-reviewed]
    Scientific journal
  • 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, Sep. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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, Sep. 2018, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, 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, Sep. 2018, [Peer-reviewed]
  • 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, 01 Aug. 2018, [Peer-reviewed]
    English, Scientific journal
  • 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, Aug. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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, Aug. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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, Jul. 2018, [Peer-reviewed]
  • 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, May 2018, [Peer-reviewed]
  • 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, Elsevier Inc., 01 May 2018, [Peer-reviewed]
    English, Scientific journal
  • 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, Mar. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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, American Association of Neurological Surgeons, 01 Mar. 2018, [Peer-reviewed]
    English, Scientific journal
  • 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, Springer Tokyo, 01 Feb. 2018, [Peer-reviewed]
    English, Scientific journal
  • 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, 15 Jan. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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, 46, 1, 1, 24, (一社)日本脳卒中の外科学会, Jan. 2018, [Peer-reviewed]
    Japanese
  • 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, Elsevier Inc., 01 Jan. 2018, [Peer-reviewed]
    English, Scientific journal
  • 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, Springer Verlag, 01 Jan. 2018, [Peer-reviewed]
    English, Scientific journal
  • 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, SAGE Publications Inc., 01 Dec. 2017, [Peer-reviewed]
    English, Scientific journal
  • 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, (一社)日本脳循環代謝学会, Nov. 2017
    English
  • 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, Springer Verlag, 01 Oct. 2017, [Peer-reviewed]
    English, Scientific journal
  • 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, W.B. Saunders, 01 Sep. 2017, [Peer-reviewed]
    English, Scientific journal
  • 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, W.B. Saunders, 01 Sep. 2017, [Peer-reviewed]
    English, Scientific journal
  • 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, Igaku-Shoin Ltd, 01 Sep. 2017, [Peer-reviewed]
    Japanese, Scientific journal
  • 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, Aug. 2017, [Peer-reviewed], [International Magazine]
    English, 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, Springer Verlag, 01 Jul. 2017, [Peer-reviewed]
    English, Scientific journal
  • 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, Springer Verlag, 01 Jul. 2017, [Peer-reviewed]
    English, Scientific journal
  • 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, Springer Verlag, 01 Jul. 2017, [Peer-reviewed]
    English, Scientific journal
  • 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, 06 Jun. 2017, [Peer-reviewed]
    English, Scientific journal
  • 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, American Association of Neurological Surgeons, 01 Apr. 2017, [Peer-reviewed]
    English, Scientific journal
  • 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, 26, 2, 112, 116, The Japanese Congress of Neurological Surgeons, Feb. 2017, [Peer-reviewed]
    Japanese, Scientific journal,

      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, 2017, [Peer-reviewed]
    English, Scientific journal
  • 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, W.B. Saunders, 01 Jan. 2017, [Peer-reviewed]
    English, Scientific journal
  • 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, W.B. Saunders, 01 Oct. 2016, [Peer-reviewed]
    English, Scientific journal
  • 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, Springer Verlag, 01 Oct. 2016, [Peer-reviewed]
    English, Scientific journal
  • リステリア髄膜炎後水頭症に対して内視鏡的第三脳室底開窓術が奏功した1例
    阿部 考貢, 川口 奉洋, 藤村 幹, 冨永 悌二
    Neurological Surgery, 44, 9, 761, 766, (株)医学書院, Sep. 2016
    Japanese
  • 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, Sep. 2016, [Peer-reviewed], [International Magazine]
    English, 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, Igaku-Shoin Ltd, 01 Sep. 2016, [Peer-reviewed]
    Japanese, Scientific journal
  • 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, American Society of Neuroradiology, 01 Jul. 2016, [Peer-reviewed]
    English, Scientific journal
  • 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, Elsevier B.V., 01 Jul. 2016, [Peer-reviewed]
    English, Scientific journal
  • 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, W.B. Saunders, 01 Jun. 2016, [Peer-reviewed]
    English, Scientific journal
  • 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, W.B. Saunders, 01 Jun. 2016, [Peer-reviewed]
    English, Scientific journal
  • 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, May 2016, [Peer-reviewed]
    English
  • 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, May 2016, [Peer-reviewed]
    English, Scientific journal
  • 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, Mar. 2016, [Peer-reviewed], [International Magazine]
    English, 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, S. Karger AG, 2016, [Peer-reviewed]
    English, Scientific journal
  • 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, 2016, [Peer-reviewed]
  • 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, Jan. 2016, [Peer-reviewed]
  • 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, Elsevier B.V., 2016, [Peer-reviewed]
    English, Scientific journal
  • 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, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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, Dec. 2015, [Peer-reviewed]
    English, Scientific journal
  • 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, Dec. 2015, [Peer-reviewed]
    Japanese, Scientific journal
  • 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, Dec. 2015, [Peer-reviewed]
    English, Scientific journal
  • 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, Oct. 2015, [Peer-reviewed]
    English, Scientific journal
  • 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, Oct. 2015, [Peer-reviewed]
    English, Scientific journal
  • 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, Lippincott Williams and Wilkins, 01 Sep. 2015, [Peer-reviewed]
    English, Scientific journal
  • 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, Sep. 2015, [Peer-reviewed]
    English
  • 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, Sep. 2015, [Peer-reviewed]
    English, Scientific journal
  • 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, Sep. 2015, [Peer-reviewed]
    English, Scientific journal
  • 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, Aug. 2015, [Peer-reviewed]
    English, Scientific journal
  • 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, Aug. 2015, [Peer-reviewed]
    English, Scientific journal
  • 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, Aug. 2015, [Peer-reviewed]
    English, Scientific journal
  • 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, Jul. 2015, [Peer-reviewed]
    English, Scientific journal
  • 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, Jul. 2015, [Peer-reviewed]
    English, Scientific journal
  • Required knowledge for stroke specialists (11) management of moyamoya disease
    Miki Fujimura, Teiji Tominaga
    Neurological Surgery, 43, 6, 557, 565, Igaku-Shoin Ltd, 01 Jun. 2015, [Peer-reviewed]
    Japanese, Scientific journal
  • [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, Apr. 2015, [Peer-reviewed], [Domestic magazines]
    Japanese, Scientific journal, 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, Igaku-Shoin Ltd, 01 Mar. 2015, [Peer-reviewed]
    Japanese, Scientific journal
  • Diagnosis of Moyamoya Disease: International Standard and Regional Differences
    Miki Fujimura, Teiji Tominaga
    NEUROLOGIA MEDICO-CHIRURGICA, 55, 3, 189, 193, Mar. 2015, [Peer-reviewed]
    English
  • 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, 43, 2, 136, 140, (一社)日本脳卒中の外科学会, Mar. 2015, [Peer-reviewed]
    Japanese, Scientific journal
  • 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, Feb. 2015, [Peer-reviewed]
    English, Scientific journal
  • 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, Japanese Congress of Neurological Surgeons, 2015, [Peer-reviewed]
    Japanese, Scientific journal
  • Cortical Microvascularization and Leptomeningeal Collaterals in Moyamoya Disease
    Shunji Mugikura, Miki Fujimura, Shoki Takahashi
    EUROPEAN NEUROLOGY, 73, 5-6, 351, 352, 2015, [Peer-reviewed]
    English
  • 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, Jan. 2015, [Peer-reviewed]
    English, Scientific journal
  • 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, Lippincott Williams and Wilkins, 17 Dec. 2014, [Peer-reviewed]
    English, Scientific journal
  • 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, 36回, 232, 248, サノフィ(株)仙台オフィス, Dec. 2014
    Japanese
  • 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, Nov. 2014, [Peer-reviewed]
  • 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, W.B. Saunders, 01 Sep. 2014, [Peer-reviewed]
    English, Scientific journal
  • 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, W.B. Saunders, 01 Sep. 2014, [Peer-reviewed]
    English, Scientific journal
  • 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, Aug. 2014, [Peer-reviewed]
  • 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, 13 Mar. 2014, [Peer-reviewed]
    English, Scientific journal
  • 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, Japanese Congress of Neurological Surgeons, 2014, [Peer-reviewed]
    English, Scientific journal
  • 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, Igaku-Shoin Ltd, 2014, [Peer-reviewed]
    Japanese, Scientific journal
  • 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, Jan. 2014, [Peer-reviewed], [International Magazine]
    English, 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, W.B. Saunders, 2014, [Peer-reviewed]
    English, Scientific journal
  • 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, Igaku-Shoin Ltd, 2014, [Peer-reviewed]
    Japanese, Scientific journal
  • 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, W.B. Saunders, 2014, [Peer-reviewed]
    English, Scientific journal
  • 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, Japan Neurosurgical Society, 2014, [Peer-reviewed]
    English, Scientific journal
  • 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, Jan. 2014, [Peer-reviewed]
    Japanese, Scientific journal
  • 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, 2014, [Peer-reviewed]
    English, Scientific journal
  • 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, American Association of Neurological Surgeons, 2014, [Peer-reviewed]
    English, Scientific journal
  • 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, Elsevier B.V., 2014, [Peer-reviewed]
    English, Scientific journal
  • 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, 35回, 46, 63, サノフィ(株)仙台オフィス, Dec. 2013
    Japanese
  • 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, Dec. 2013, [Peer-reviewed]
    English, Scientific journal
  • 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, Nov. 2013, [Peer-reviewed]
    English, Scientific journal
  • Issues in moyamoya disease: Consideration for its intrinsic physiologi-cal reorganization system
    Miki Fujimura, Teiji Tominaga
    Japanese Journal of Neurosurgery, 22, 9, 695, 698, Japanese Congress of Neurological Surgeons, 25 Sep. 2013, [Peer-reviewed]
    Japanese, Scientific journal
  • Moyamoya Disease in Pregnancy: A Single Institute Experience
    Miki Fujimura, Kozo Akagi, Hiroshi Uenohara, Teiji Tominaga
    NEUROLOGIA MEDICO-CHIRURGICA, 53, 8, 561, 564, Aug. 2013, [Peer-reviewed]
    English, Scientific journal
  • 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, Jun. 2013, [Peer-reviewed]
    English, Scientific journal
  • 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, Apr. 2013, [Peer-reviewed]
    English, Scientific journal
  • 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, Feb. 2013, [Peer-reviewed]
    English, Scientific journal
  • 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, Jan. 2013, [Peer-reviewed]
    English, Scientific journal
  • 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, Jan. 2013, [Peer-reviewed]
    English, Scientific journal
  • 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, Dec. 2012, [Peer-reviewed]
    Japanese, Scientific journal
  • 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, Nov. 2012, [Peer-reviewed]
    English, Scientific journal
  • 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, Sep. 2012, [Peer-reviewed]
    English, Scientific journal
  • 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, Jul. 2012, [Peer-reviewed]
    English, Scientific journal
  • 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, May 2012, [Peer-reviewed]
    English, Scientific journal
  • 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, Mar. 2012, [Peer-reviewed]
    English, Scientific journal
  • 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, Japan Neurosurgical Society, 2012, [Peer-reviewed]
    English, Scientific journal
  • 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, Japan Neurosurgical Society, 2012, [Peer-reviewed]
    English, Scientific journal
  • 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, Japan Neurosurgical Society, 2012, [Peer-reviewed]
    English, Scientific journal
  • 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, 2012, [Peer-reviewed]
    English, Scientific journal
  • 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, 25 Dec. 2011, [Peer-reviewed]
    English, Scientific journal
  • 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, 13 Dec. 2011
    English, International conference proceedings
  • 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, Nov. 2011, [Peer-reviewed]
    English, Scientific journal
  • 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, Oct. 2011, [Peer-reviewed]
    English, Scientific journal
  • 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, Oct. 2011, [Peer-reviewed]
    English, Scientific journal
  • 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, Sep. 2011, [Peer-reviewed]
    English, Scientific journal
  • 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, 10 Jul. 2011, [Peer-reviewed]
    Japanese, Scientific journal
  • 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, 10 Jul. 2011, [Peer-reviewed]
    Japanese, Scientific journal
  • 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, Apr. 2011, [Peer-reviewed]
    English, Scientific journal
  • 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, 2011, [Peer-reviewed]
    English, Scientific journal
  • 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, Jan. 2011, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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, Dec. 2010, [Peer-reviewed]
    English, Scientific journal
  • 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, Dec. 2010, [Peer-reviewed]
    Japanese, Research society
  • 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, Dec. 2010, [Peer-reviewed]
    Japanese, Scientific journal
  • 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, Nov. 2010, [Peer-reviewed]
    English, Scientific journal
  • 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, Jul. 2010, [Peer-reviewed]
    English, Scientific journal
  • 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, Jul. 2010, [Peer-reviewed]
    English, Scientific journal
  • 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, Jul. 2010, [Peer-reviewed]
    English, Scientific journal
  • 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, Jun. 2010, [Peer-reviewed]
    English, Scientific journal
  • 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, Apr. 2010, [Peer-reviewed]
    English, Scientific journal
  • 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, Apr. 2010, [Peer-reviewed]
    English, Scientific journal
  • 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, Apr. 2010, [Peer-reviewed]
    English, Scientific journal
  • 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, Apr. 2010, [Peer-reviewed]
    English, Scientific journal
  • 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, Apr. 2010, [Peer-reviewed]
    English, Scientific journal
  • Associated neurosurgical diseases
    Miki Fujimura, Teiji Tominaga
    Moyamoya Disease Update, 132, 138, Springer Japan, 2010, [Peer-reviewed]
    English, In book
  • Risk factors for complication
    Miki Fujimura, Teiji Tominaga
    Moyamoya Disease Update, 275, 280, Springer Japan, 2010, [Peer-reviewed]
    English, In book
  • Overview: Issues in young children and adults
    Teiji Tominaga, Miki Fujimura
    Moyamoya Disease Update, 287, 293, Springer Japan, 2010, [Peer-reviewed]
    English, In book
  • Headache in moyamoya disease
    Reizo Shirane, Miki Fujimura
    Moyamoya Disease Update, 110, 113, Springer Japan, 2010, [Peer-reviewed]
    English, In book
  • 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, [Peer-reviewed]
  • 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, Dec. 2009, [Peer-reviewed]
    English, Scientific journal
  • 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, Nov. 2009, [Peer-reviewed]
    English, Scientific journal
  • 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, Nov. 2009, [Peer-reviewed]
    English, Scientific journal
  • 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, Apr. 2009, [Peer-reviewed]
    English, Scientific journal
  • 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, Apr. 2009, [Peer-reviewed]
    English, Scientific journal
  • 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, Mar. 2009, [Peer-reviewed]
    English, Scientific journal
  • 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, Mar. 2009, [Peer-reviewed]
    Japanese, Scientific journal
  • 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, Feb. 2009, [Peer-reviewed]
    English, Scientific journal
  • 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, Feb. 2009, [Peer-reviewed]
    English, Scientific journal
  • 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, Nov. 2008, [Peer-reviewed]
    English, Scientific journal
  • Cerebral cavernous malformation - Its genetic and biological background
    Miki Fujimura, Teiji Tominaga
    Brain and Nerve, 60, 11, 1271, 1274, Nov. 2008, [Peer-reviewed]
    Japanese
  • 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, Oct. 2008, [Peer-reviewed]
    English, Scientific journal
  • 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, Jul. 2008, [Peer-reviewed]
    English, Scientific journal
  • 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, Apr. 2008, [Peer-reviewed]
    English, Scientific journal
  • 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, Apr. 2008, [Peer-reviewed]
  • 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, Apr. 2008, [Peer-reviewed]
    English, Scientific journal
  • 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, Mar. 2008, [Peer-reviewed]
    English, Scientific journal
  • Neuro-endoscopic management of mesencephalic intraparenchymal cyst: a case report.
    Endo H, Fujimura M, Watanabe M, Tominaga T
    Surg Neurol, 832, 19 Feb. 2008, [Peer-reviewed]
    English, Scientific journal
  • Neurenteric cyst of the craniocervical junction in an infant
    Hiroyuki Sakata, Miki Fujimura, Masaki Iwasaki, Teiji Tominaga
    NEUROLOGIA MEDICO-CHIRURGICA, 48, 2, 86, 89, Feb. 2008, [Peer-reviewed]
    English, Scientific journal
  • 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, 18 Jan. 2008, [Peer-reviewed]
    English, Scientific journal
  • 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, +, 2008, [Peer-reviewed]
    English, International conference proceedings
  • 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, Jan. 2008, [Peer-reviewed]
    English, Scientific journal
  • 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, +, 2008, [Peer-reviewed]
    English, International conference proceedings
  • 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, 13 Nov. 2007
    English, International conference proceedings
  • 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, 13 Nov. 2007
    English, International conference proceedings
  • 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, May 2007, [Peer-reviewed]
    Japanese, Scientific journal
  • [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, Nov. 2006, [Peer-reviewed]
  • [Cerebral cavernous malformation].
    Fujimura M, Tominaga T
    Nihon rinsho. Japanese journal of clinical medicine, 64 Suppl 8, 691, 694, Nov. 2006, [Peer-reviewed]
  • 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, Oct. 2006, [Peer-reviewed]
    Japanese, Scientific journal
  • 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, Aug. 2006, [Peer-reviewed]
    Japanese, Scientific journal
  • 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, Jun. 2006, [Peer-reviewed]
    Japanese, Scientific journal
  • 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, [Peer-reviewed]
    English, International conference proceedings
  • 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, May 2004, [Peer-reviewed]
    Japanese, Scientific journal
  • 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, May 2004, [Peer-reviewed]
    Japanese, Scientific journal
  • 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, Mar. 2004, [Peer-reviewed]
    Japanese, Scientific journal
  • 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, 2001, [Peer-reviewed]
    English, Scientific journal
  • 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, 23, 6, 455, 458, The Japanese Society on Surgery for Cerebral Stroke, 1995
    Japanese, 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.

Other Activities and Achievements

Books and other publications

  • 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

Lectures, oral presentations, etc.

  • 内視鏡的第三脳室開窓術の治療成績について               
    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               
    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               
    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               
    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               
    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               
    Congress of Neurological Surgeons 2007 Annual Meeting, 2007, Poster presentation
  • 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               
    第66回日本脳神経外科学会総会, 2007
  • Oxidative stressと脳虚血               
    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               
    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               
    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               
    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               
    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               
    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               
    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               
    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               
    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               
    Congress of Neurological Surgeons 2007 Annual Meeting, 2007, Poster presentation
  • 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               
    第66回日本脳神経外科学会総会, 2007
  • Oxidative stressと脳虚血               
    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               
    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               
    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               
    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               
    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               
    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               
    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               
    Annual meeting of Congress of Neurological Surgeons, 2006, Poster presentation
  • 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               
    第65回日本脳神経外科学会総会, 2006, Poster presentation
  • 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               
    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               
    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               
    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               
    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               
    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               
    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               
    Annual meeting of Congress of Neurological Surgeons, 2006, Poster presentation
  • 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               
    第65回日本脳神経外科学会総会, 2006, Poster presentation
  • 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               
    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               
    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               
    The 8th International Conference on Cerebrovascular Surgery, 2006

Affiliated academic society

  • 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 Themes

  • Multiple advanced video analysis to elucidate the 'complexity' of microsurgery
    Grants-in-Aid for Scientific Research
    01 Apr. 2021 - 31 Mar. 2026
    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。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 21K09091
  • Innovative Research of Neuroprotection for Delayed Cerebral Ischemia Associated with Cerebral Vasospasm after Subarachnoid Hemorrhage using Novel Hemoglobin-based Oxygen Carrier
    Grants-in-Aid for Scientific Research
    01 Apr. 2022 - 31 Mar. 2025
    月花 正幸, 伊東 雅基, 川堀 真人, 鐙谷 武雄, 小松 晃之, 藤村 幹
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 22K09275
  • 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
    科学研究費助成事業
    01 Apr. 2022 - 31 Mar. 2025
    穂刈 正昭, 藤村 幹, 川堀 真人
    日本学術振興会, 基盤研究(C), 北海道大学, 22K09274
  • 人工酸素運搬体を用いたmulti-targetの脳保護療法の開発
    科学研究費助成事業
    01 Apr. 2022 - 31 Mar. 2025
    鐙谷 武雄, 藤村 幹, 伊東 雅基, 小松 晃之, 川堀 真人
    日本学術振興会, 基盤研究(C), 北海道大学, 22K09224
  • Elucidation of moyamoya disease pathophysiology through an interaction of hemodynamics and endothelial cells
    Grants-in-Aid for Scientific Research
    05 Apr. 2021 - 31 Mar. 2024
    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。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Tohoku University, 21H04835
  • The efficacy of novel treatment method to block Feroptosis for ischemic stroke
    Grants-in-Aid for Scientific Research
    01 Apr. 2021 - 31 Mar. 2024
    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。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 21K09143
  • Comprehensive validation of circulating microRNA signatures for Moyamoya disease early detection as an epigenome blood biomarker
    Grants-in-Aid for Scientific Research
    01 Apr. 2019 - 31 Mar. 2024
    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。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 19H03765
  • 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
    科学研究費助成事業
    01 Apr. 2020 - 31 Mar. 2023
    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。
    日本学術振興会, 基盤研究(C), 20K09362
  • Analysis of latent imaging findings in healthy subjects with moyamoya disease susceptibility gene RNF213 polymorphism using artificial intelligence
    Grants-in-Aid for Scientific Research
    01 Apr. 2020 - 31 Mar. 2023
    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。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Tohoku University, 20K12057
  • Intravoxel-incoherent-motion (IVIM) MRI as a noninvasive method for estimating cerebral blood volume in ischemic brain disease
    Grants-in-Aid for Scientific Research
    01 Apr. 2015 - 31 Mar. 2018
    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.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Tohoku University, 15K09914