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」　　　　　　　　　　　　　　　

Oct. 2011, The 5th Japanese-Korean Joint Stroke Conference, Best Poster Presentation Award　　　　　　　　　　　　　　　

2007, 第２８回東北脳血管障害研究会奨励賞「中村隆賞」　　　　　　　　　　　　　　　
Japan

A simulation study of the cost of cerebral vasospasm treatments with clazosentan: A mathematical model using time-driven activity-based costing.
Jieyu Zhao, Kota Kurisu, Kazuki Ohashi, Toshiya Osanai, Katsuhiko Ogasawara, Miki Fujimura
PloS one, 21, 1, e0340076, 2026, [International Magazine]
English, Scientific journal, In this work, we aimed to assess the impact of clazosentan on clinical labour time costs within Japan's value-based healthcare system using time-driven activity-based costing. Time-driven activity-based costing was employed to analyse the labour time costs associated with preventing cerebral vasospasm following aneurysmal subarachnoid haemorrhage. Time-driven activity-based costing simplifies cost analysis by utilising time as the primary cost driver. We compared two treatment approaches: conventional therapy with fasudil hydrochloride and postoperative therapy with clazosentan. Scenario and sensitivity analyses were performed to assess the impact of physicians' costs on the results. The use of clazosentan for the prevention of cerebral vasospasm significantly reduced human resource costs, particularly in cases where symptomatic vasospasm did not occur, yielding savings of approximately 51,343 yen. The greatest cost reductions were observed among nursing staff, with a 30% decrease in the absence of symptomatic vasospasm and a 15% reduction when symptomatic vasospasm was present. The cost reductions for physicians were comparatively smaller, particularly in cases where symptomatic vasospasm occurred. Sensitivity analyses indicated that clazosentan reduced overall costs by approximately 35,000-50,000 yen; however, costs increased in the presence of symptomatic vasospasm. Clazosentan for subarachnoid haemorrhage treatment significantly reduces human resource costs, especially in nursing staff. These findings support the potential of clazosentan for broader clinical use, given its cost-savings and clinical benefits in reducing cerebral vasospasm following aneurysmal subarachnoid haemorrhage.

Clazosentan Affects Temporal Profile of Endothelin-A Expression in Macro- and Microcirculation after Subarachnoid Hemorrhage.
Yuyuan Zheng, Masahito Kawabori, Yoichiro Fujioka, Shuho Gotoh, Ryota Tatezawa, Takuma Ikeda, Taishi Honda, Yo Nakahara, Erika Yoshie, Zheng Li, Yusuke Ohba, Miki Fujimura
Neurologia medico-chirurgica, 20 Dec. 2025, [Domestic magazines]
English, Scientific journal, Subarachnoid hemorrhage is a life-threatening cerebrovascular event, and cerebral vasospasm remains a major cause of poor neurological outcomes. Clazosentan, an endothelin-A receptor antagonist, has been recently approved in Japan to reduce post-subarachnoid hemorrhage vasospasm; however, recurrent vasospasm after cessation of therapy has occasionally been reported, which underlying mechanisms remain unclear. Moreover, endothelin-A receptor is also expressed on pericytes; however, the effects of clazosentan on microvascular endothelin-A receptor remain unexplored. In this study, we employed a rat subarachnoid hemorrhage model to investigate the temporal dynamics of vasospasm and endothelin-A receptor expression in both large arteries and microvessels, and to evaluate the effects of clazosentan administration. Sprague-Dawley rats were assigned to naïve controls, subarachnoid hemorrhage with saline, or subarachnoid hemorrhage with continuous clazosentan administration for 7 days via osmotic pumps. Vasospasm was assessed by arterial wall thickness, and endothelin-A receptor expression was quantified using immunohistochemistry and immunofluorescence, including staining with α-SMA, CD31, and PDGF-β. Clazosentan significantly attenuated vasospasm in the middle and anterior cerebral arteries, and recurrent vasospasm was observed 3 days after cessation of clazosentan, coinciding with sustained upregulation of endothelin-A receptor in these vessels. In microvessels, pericyte density transiently decreased, peaking at a nadir on day 3 post-subarachnoid hemorrhage, while endothelin-A receptor expression on pericytes was highest at the same time point, and further elevated by clazosentan treatment. These findings indicate that clazosentan induces endothelin-A receptor upregulation in both macro- and microcirculation, potentially contributing to recurrent vasospasm after treatment, and highlight the critical role of pericytes in post-subarachnoid hemorrhage vascular regulation.

Distinct impact of RNF213 p.R4810K genotype on transdural collateral formation across Japanese Asian and Polish Caucasian Moyamoya patients.
Dariusz Szarek, Masaki Ito, Haruto Uchino, Katarzyna Lubkowska, Kikutaro Tokairin, Miki Fujimura
Neurosurgical review, 49, 1, 81, 81, 18 Dec. 2025, [International Magazine]
English, Scientific journal, Interethnic differences in natural transdural collaterals-an angiographical hallmark of Moyamoya disease (MMD)-may reflect the genetic and pathophysiological mechanisms underlying ethnic disparities. However, international comparative studies incorporating both angiographic and genetic data are limited. This study investigated differences in cerebral angioarchitecture and clinical presentation between Japanese Asian and Polish Caucasian patients with MMD, with a focus on the RNF213 p.R4810K variant, a known East Asian founder mutation. We retrospectively analyzed consecutive 94 Japanese and 33 Polish patients who underwent diagnostic cerebral angiography and RNF213 p.R4810K genotyping between 2015 and 2025. Suzuki's angiographical stages and the presence of natural-transdural, periventricular, and leptomeningeal collaterals, mainly via posterior cerebral artery (PCA), were evaluated. Interethnic comparisons progressed from full cohort comparisons to genotype-based subgroup analyses with adjustments for angiographical stage and RNF213 p.R4810K genotype. The RNF213 p.R4810K wild-type was present in 31% of Japanese and 100% of Polish patients. A trend toward more hemorrhagic presentation in Japanese was noted (17% vs. 12%, P = 0.10). Polish patients were significantly younger at diagnosis (P = 0.0014). Among 230 un-operated hemispheres, angiographic stages did not significantly differ (P = 0.23). After adjustment, overall prevalence of natural transdural collaterals was similar (41% in entire Japanese and 60% in Polish cohort, P = 0.20), but significantly higher in Polish than in Japanese patients with the wild-type genotype (60% vs 34%, P = 0.0098). Periventricular collaterals were significantly more common in Japanese, independent of genotype (P < 0.0001). No interethnic difference was observed in leptomeningeal collaterals. In conclusion, Polish MMD patients exhibit more natural transdural and fewer periventricular collaterals than Japanese with the wild-type genotype. These genetic and ethnic differences suggest distinct mechanisms of collateral formation across ethnic groups, with implications for genotype-driven pathophysiology and clinical presentation in MMD.

Reverse translational research of transient magnetic resonance imaging hyperintensity following intracranial stem cell therapy.
Yi Qi, Masahito Kawabori, Yo Nakahara, Khin Khin Tha, Sumio Ohtsuki, Miki Fujimura
Stem cell research & therapy, 16, 1, 646, 646, 18 Nov. 2025, [International Magazine]
English, Scientific journal, BACKGROUND: Neurological disorders, such as stroke and traumatic brain injury are the most significant global health challenges, leading to long-term physical and cognitive impairments. Cell transplantation therapy holds substantial promise for facilitating recovery, with numerous clinical trials currently underway. Intracerebral stem cell infusion offers the advantage of directly delivering a sufficient number of stem cells to the targeted area. Both our team and other researchers have observed a notable phenomenon following intracerebral stem cell therapy in clinical trials, wherein transient edema, as detected by Fluid Attenuated Inversion Recovery (FLAIR) magnetic resonance (MR) imaging, can be monitored between one and two weeks post-transplantation, with a subsequent resolution occurring approximately one month later. Notably, patient recovery appears to accelerate during the period of elevated FLAIR signals. However, the precise mechanisms underlying this distinctive phenomenon remain poorly understood. Therefore, this reverse translational research employs proteomics and histological analysis to investigate the mechanisms driving this phenomenon, thereby enhancing our understanding of stem cell therapy. METHODS: Bone marrow-derived mesenchymal stem cells (BMSCs) were isolated from Sprague-Dawley (SD) rats, with passage 3 cells utilized for subsequent experiments. A total of one million cells, suspended in 10 µL of phosphate-buffered saline, were intracerebrally transplanted into the striatum of SD rats. Serial magnetic resonance imaging (FLAIR) scans were performed up to three weeks post-transplantation. Brain tissues were collected from the pre-signal (1 week post-transplantation), signal (2 weeks post-transplantation), and post-signal (3 weeks post-transplantation) groups for proteomic analysis, network analysis, and immunofluorescence imaging. RESULTS: Consistent with clinical trials, transient FLAIR hyperintense signals were not detected until approximately two weeks post-intracranial stem cell therapy. These signals emerged around week two and diminished by week three. Proteomic analysis of brain specimens from the pre-signal and signal groups identified 231 differentially expressed proteins, which were primarily involved in vesicle-mediated transport, synaptic remodeling, and cellular communication. Glial fibrillary acidic protein (GFAP), Aquaporin-4 (AQP4), and Apolipoprotein E (APOE) were identified as key hub proteins. Immunofluorescence studies further confirmed that expression levels of GFAP, AQP4, and APOE increased around two weeks post-transplantation and significantly decreased by week three, coinciding with the resolution of the FLAIR signal. CONCLUSIONS: Our findings suggest that the transient FLAIR hyperintensity observed following intracerebral stem cell therapy is primarily attributed to transient glial cell activation, resulting in increased AQP4 expression and transient brain water influx. Additional mechanisms, including vesicle-mediated transport, secretion, synaptic activity, and lipid signaling, also contribute to the transient FLAIR hyperintensity signals and may play a role in the manifestation of clinical symptoms.

Primary spinal cord malignant B-cell lymphoma successfully treated with tirabrutinib at relapse: a case report.
Yukitomo Ishi, Hiroaki Motegi, Soichiro Takamiya, Ai Shimizu, Takashi Mori, Sogo Oki, Motoyuki Iwasaki, Shigeru Yamaguchi, Miki Fujimura
European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society, 17 Nov. 2025, [International Magazine]
English, Scientific journal

Experimental Development and Internal Validation of a Clinical Prediction Model for the Occurrence of Idiopathic C5 Palsy after Laminoplasty.
Ikuma Echizenya, Motoyuki Iwasaki, Yasukazu Hijikata, Kazuyoshi Yamazaki, Toru Sasamori, Shunsuke Yano, Kazutoshi Hida, Miki Fujimura
Neurologia medico-chirurgica, 14 Nov. 2025, [Domestic magazines]
English, Scientific journal, C5 palsy is a significant yet poorly understood complication following cervical posterior surgery. Currently, few predictive models exist for estimating the preoperative risk of C5 palsy. This study aimed to develop and internally validate such a predictive model. We included patients aged 18 years or older who underwent cervical laminoplasty for cervical spondylosis or ossification of the posterior longitudinal ligament at a single institution. Demographic and radiographic data were collected. Key radiographic parameters included the C2-7 Cobb angle, C7 slope, presence of ossification of the posterior longitudinal ligament, anterior projection of the superior articular process of C5, and the width of the intervertebral foramen at C4/5, measured on computed tomography. Logistic regression with optimism adjustment was used to develop the model. A total of 180 patients were analyzed, with 18 cases (10.0%) of C5 palsy. Logistic regression identified width of the intervertebral foramen, C7 slope, age, and sex as significant predictors. The model demonstrated an area under the curve of 0.797 (95% confidence interval: 0.695-0.900) and a Brier score of 11.7%. After internal validation using bootstrapping, the optimism-adjusted area under the receiver operating characteristic curve was 0.736 (95% confidence interval 0.629-0.830). Final regression coefficients were 0.054 for C7 slope, -0.039 for age, -1.161 for female sex, and -0.721 for width of the intervertebral foramen. In conclusion, we developed and internally validated a preoperative prediction model for C5 palsy following double-door laminoplasty. Predictors such as width of the intervertebral foramen, C7 slope, age, and sex may aid in risk assessment and surgical planning.

Coil embolization via donor superficial temporal artery for de novo aneurysm associated with revascularization surgery in a patient with moyamoya disease: illustrative case.
Toma Shirai, Kota Kurisu, Masaki Ito, Toshiya Osanai, Haruto Uchino, Miki Fujimura
Journal of neurosurgery. Case lessons, 10, 18, 03 Nov. 2025, [International Magazine]
English, Scientific journal, BACKGROUND: De novo aneurysm formation at the anastomotic site of superficial temporal artery (STA)-middle cerebral artery (MCA) bypass surgery for moyamoya disease (MMD) is an exceptionally rare but clinically significant complication. Previously reported cases were treated with direct microsurgery, where preservation of established pial synangiosis was a major concern. The authors herein report the first case successfully treated with endovascular coil embolization, achieving complete preservation of pial synangiosis and a favorable clinical outcome. OBSERVATIONS: A 53-year-old man had undergone combined revascularization surgery for MMD 14 years earlier. Although the patient remained asymptomatic, follow-up MR angiography revealed a gradually enlarging de novo aneurysm with daughter sac formation at the anastomotic site. Cerebral angiography demonstrated a narrow-neck saccular aneurysm and a well-developed donor STA, allowing access for endovascular treatment. A microcatheter was advanced into the aneurysm via a distal access catheter placed in the STA, and coil embolization with five coils achieved complete obliteration. The patient recovered uneventfully, and follow-up imaging confirmed the durable occlusion. LESSONS: Endovascular therapy represents a valuable treatment option for de novo aneurysm after STA-MCA anastomosis in MMD, as it completely preserves established collaterals. Careful patient selection and meticulous procedural planning are essential to ensure safety and efficacy. https://thejns.org/doi/10.3171/CASE25666.

Feasibility and Reliability of a Novel Tele-stroke Care Unit System in a Japanese Hospital.
Haruto Uchino, Toshiya Osanai, Yusuke Shimoda, Hisayasu Saito, Miki Fujimura
Neurologia medico-chirurgica, 18 Sep. 2025, [Domestic magazines]
English, Scientific journal, Stroke care units, which provide intensive management for acute stroke, are widely used in Japan. However, recent legal restrictions on physicians' overtime may challenge continuous specialist coverage, particularly in resource-limited settings. To address this issue, we developed a tele-stroke care units system that provides remote support from stroke specialists. We aimed to evaluate the feasibility and reliability of this system for remote neurological assessment. The system integrates live-streaming and medical image viewing between a local stroke care unit and a remote university hospital through the International Organization for Standardization 27001-compliant Join LiveView application (Allm, Inc., Japan). Remote physicians accessed real-time videos through ceiling-mounted pan-tilt-zoom cameras and communicated bidirectionally using a wireless speaker. We assessed the audiovisual quality, conducted remote National Institutes of Health Stroke Scale examinations in 20 patients with stroke, and compared the results with those of bedside assessments. Remote physicians successfully evaluated all National Institutes of Health Stroke Scale categories using camera-zoom functions, with or without local staff assistance. Video and audio quality were sufficient for clinical assessment and communication. Median total National Institutes of Health Stroke Scale scores were 7.5 (bedside) and 6.5 (remote). Excellent or perfect inter-rater reliability was observed in all 13 categories, with a total score correlation coefficient of 0.998 (p < 0.0001). The tele-stroke care unit system showed sufficient audiovisual quality for effective remote neurological assessment and may serve as a practical solution for acute stroke management in facilities facing workforce shortages, thereby contributing to sustainable stroke care.

Symptomatic cerebral hyperperfusion after occipital artery-posterior cerebral artery bypass in a patient with moyamoya disease: illustrative case.
Jin Kimata, Kikutaro Tokairin, Haruto Uchino, Masaki Ito, Miki Fujimura
Journal of neurosurgery. Case lessons, 10, 9, 01 Sep. 2025, [International Magazine]
English, Scientific journal, BACKGROUND: Moyamoya disease (MMD) is a progressive, steno-occlusive cerebrovascular disorder. Posterior cerebral artery (PCA) stenosis can develop after successful anterior circulation revascularization. Although symptomatic cerebral hyperperfusion (CHP) is a recognized complication of anterior revascularization, it is rarely reported following occipital artery (OA)-PCA bypass. OBSERVATIONS: The authors report the case of a 50-year-old woman with MMD who developed symptomatic hemodynamic compromise due to progressive right PCA stenosis 10 years after bilateral superficial temporal artery-middle cerebral artery bypass and indirect revascularization. She underwent OA-PCA bypass with encephalo-myo-synangiosis. On postoperative day 1, single-photon emission CT revealed focal CHP in the right parietal lobe, with cerebral blood flow (CBF) increasing to 160% of preoperative levels. The patient developed a pulsatile headache and left-sided tongue numbness. By postoperative day 7, CBF had decreased to 110%, and perfusion had improved throughout the right parietal-occipital region. With strict blood pressure control and minocycline administration, both symptoms and CHP resolved. At the 1-year follow-up, the patient remained symptom free without stroke recurrence. LESSONS: Symptomatic CHP can occur after OA-PCA bypass in MMD. Perioperative CHP management, including blood pressure control and anti-inflammatory therapy, is essential for optimal outcomes of posterior circulation bypass. https://thejns.org/doi/10.3171/CASE25486.

Repeated recurrence after endovascular treatment for cerebral aneurysms: predictive clinical factors and optimal therapeutic management.
Kota Kurisu, Hiroyuki Sakata, Yasushi Matsumoto, Atsushi Kanoke, Shunsuke Omodaka, Miki Fujimura, Hidenori Endo
Neurosurgical review, 48, 1, 603, 603, 16 Aug. 2025, [International Magazine]
English, Scientific journal, Despite significant advances in endovascular treatment (EVT) of cerebral aneurysms, post-treatment recurrence necessitating multiple retreatments remains a severe concern. Herein, we investigated the clinical characteristics of aneurysms necessitating multiple retreatments after EVT (refractory aneurysms: R-ANs) and explored appropriate management strategies. This retrospective cohort study enrolled 1,045 aneurysms initially treated with EVT between 2016 and 2022. R-ANs were defined as cases requiring two or more retreatment sessions due to repeated recurrence or regrowth. Clinical data were retrospectively reviewed, and predictive factors were identified. Furthermore, the treatments performed and clinical outcomes were investigated. Of 1,045 aneurysms, 101 (9.7%) exhibited recurrence or regrowth requiring retreatment. Among these, 23 aneurysms (2.2%) requiring two or more retreatment sessions, which were classified as R-ANs. As for the predictive factors of R-AN development, large size (> 10 mm), and circumferential aneurysmal wall enhancement on vessel wall imaging (VWI) were identified as relevant and independent predictive factors, with odds ratios of 3.92 (95% CI, 1.36- 11.62), 8.02 (95% CI, 2.02- 53.6), respectively. In terms of therapeutic outcomes, repeat EVT sessions provided favorable long-term clinical outcomes (aneurysm stabilization, 85.0%; favorable occlusion, 65.0%) and low periprocedural complication rates (2.6%). This study identified the relevant predictive factors for R-AN development, suggesting that careful follow-up is essential in patients with these factors. Furthermore, repeated EVT sessions appears to be a safe and efficient treatment strategy for such challenging cases.

Recurrence patterns and clinical outcomes in adult cerebellar glioblastoma.
Sogo Oki, Shigeru Yamaguchi, Yukitomo Ishi, Hiroaki Motegi, Masayuki Gekka, Zen-Ichi Tanei, Hiromi Kanno-Okada, Emi Takakuwa, Satoshi Tanaka, Takashi Mori, Kentaro Nishioka, Hidefumi Aoyama, Shinya Tanaka, Miki Fujimura
Acta neurochirurgica, 167, 1, 217, 217, 08 Aug. 2025, [International Magazine]
English, Scientific journal, BACKGROUND: Cerebellar glioblastoma in adults is a rare brain tumor with poor outcomes. This study aimed to assess the clinical characteristics, genetic features, and prognosis of a series of cerebellar glioblastomas, with special attention to their recurrence patterns. METHODS: We retrospectively analyzed patients who underwent treatment between 2008 and 2023. The patient characteristics, treatment methods, genetic features, and prognoses were assessed. RESULTS: Among 274 cases of histological glioblastomas, eleven patients with cerebellar glioblastomas were identified. Pathological results revealed microvascular proliferation and/or necrosis in all cases. All patients underwent surgery and local radiotherapy combined with temozolomide chemotherapy. The median progression-free survival and overall survival were 15.3 months and 22.8 months, respectively. Subventricular zone involvement was recognized in ten patients. Of the eight patients who experienced recurrence, seven had distant or disseminated recurrence, and only one experienced local recurrence. None of the tumors harbored mutations in the IDH1/2, H3F3A, or TERT promoters. Three patients showed negative expression of O6-methylguanine DNA methyltransferase (MGMT), and four patients showed positive expression. CONCLUSIONS: In our cohort, cerebellar glioblastomas showed clinical characteristics such as recurrence patterns and genetic features such as IDH, H3F3A, and TERT promoter regions that differed from those of typical supratentorial gliomas. Further studies are necessary to fully elucidate the clinical characteristics.

Incidence and Clinical Characteristics of Moyamoya Disease in Advanced Suzuki Disease Stages.
Haruto Uchino, Masaki Ito, Miki Fujimura
Neurologia medico-chirurgica, 31 Jul. 2025, [Domestic magazines]
English, Scientific journal, Moyamoya disease is a progressive steno-occlusive cerebrovascular disease. Intrinsically, its shifts the brain's vascular supply from the internal carotid to the external carotid system, known as internal-to-external carotid conversion, which is categorized by Suzuki's angiographic staging system. Although Suzuki's staging system remains the global standard for assessing longitudinal angiographic progression, the clinical characteristics of patients in the advanced stages, particularly in stage 6, are not well understood. Therefore, in this study, we investigated the incidence and clinical features in patients with moyamoya disease in advanced Suzuki stages. We retrospectively analyzed 280 hemispheres from 156 patients diagnosed with moyamoya disease through cerebral angiography between 1980 and 2023 at our institution. Angiographic features, including Suzuki disease stage and collateral pathways, were evaluated. Clinical outcomes, surgical indications, and postoperative courses were also assessed. Seventeen hemispheres (6.1%) were classified as Suzuki stage 5, and 6 hemispheres (2.1%) as stage 6, all in adult patients. Transdural collaterals, including ethmoidal and vault moyamoya vessels, were found in more than 80% of these advanced cases. Leptomeningeal collaterals from the posterior cerebral artery were frequently observed, whereas posterior cerebral artery stenosis was rare. Approximately half of the patients underwent revascularization surgery. No postoperative stroke recurrence was observed during the follow-up period of median 84 months. Suzuki stages 5 and 6 of moyamoya disease are rare; cases with stage 6 are particularly uncommon but show distinct angiographic features marked by internal-to-external carotid conversion and increased reliance on posterior circulation. Surgical revascularization is feasible and may be performed safely without stroke recurrence, even in patients with advanced disease stages.

Artificial intelligence-integrated video analysis of vessel area changes and instrument motion for microsurgical skill assessment.
Taku Sugiyama, Minghui Tang, Hiroyuki Sugimori, Marin Sakamoto, Miki Fujimura
Scientific reports, 15, 1, 27898, 27898, 31 Jul. 2025, [International Magazine]
English, Scientific journal, Mastering microsurgical skills is essential for neurosurgical trainees. Video-based analysis of target tissue changes and surgical instrument motion provides an objective, quantitative method for assessing microsurgical proficiency, potentially enhancing training and patient safety. This study evaluates the effectiveness of an artificial intelligence (AI)-based video analysis model in assessing microsurgical performance and examines the correlation between AI-derived parameters and specific surgical skill components. A dual AI framework was developed, integrating a semantic segmentation model for artificial blood vessel analysis with an instrument tip-tracking algorithm. These models quantified dynamic vessel area fluctuation, tissue deformation error count, instrument path distance, and normalized jerk index during a single-stitch end-to-side anastomosis task performed by 14 surgeons with varying experience levels. The AI-derived parameters were validated against traditional criteria-based rating scales assessing instrument handling, tissue respect, efficiency, suture handling, suturing technique, operation flow, and overall performance. Rating scale scores correlated with microsurgical experience, exhibiting a bimodal distribution that classified performance into good and poor groups. Video-based parameters showed strong correlations with various skill categories. Receiver operating characteristic analysis demonstrated that combining these parameters improved the discrimination of microsurgical performance. The proposed method effectively captures technical microsurgical skills and can assess performance.

Intra-Arterial Administration of Stem Cells and Exosomes for Central Nervous System Disease.
Taishi Honda, Masahito Kawabori, Miki Fujimura
International journal of molecular sciences, 26, 15, 31 Jul. 2025, [International Magazine]
English, Scientific journal, Central nervous system (CNS) disorders present significant therapeutic challenges due to the limited regenerative capacity of neural tissues, resulting in long-term disability for many patients. Consequently, the development of novel therapeutic strategies is urgently warranted. Stem cell therapies show considerable potential for mitigating brain damage and restoring neural connectivity, owing to their multifaceted properties, including anti-apoptotic, anti-inflammatory, neurogenic, and vasculogenic effects. Recent research has also identified exosomes-small vesicles enclosed by a lipid bilayer, secreted by stem cells-as a key mechanism underlying the therapeutic effects of stem cell therapies, and given their enhanced stability and superior blood-brain barrier permeability compared to the stem cells themselves, exosomes have emerged as a promising alternative treatment for CNS disorders. A key challenge in the application of both stem cell and exosome-based therapies for CNS diseases is the method of delivery. Currently, several routes are being investigated, including intracerebral, intrathecal, intravenous, intranasal, and intra-arterial administration. Intracerebral injection can deliver a substantial quantity of stem cells directly to the brain, but it carries the potential risk of inducing additional brain injury. Conversely, intravenous transplantation is minimally invasive but results in limited delivery of cells and exosomes to the brain, which may compromise the therapeutic efficacy. With advancements in catheter technology, intra-arterial administration of stem cells and exosomes has garnered increasing attention as a promising delivery strategy. This approach offers the advantage of delivering a significant number of stem cells and exosomes to the brain while minimizing the risk of additional brain damage. However, the investigation into the therapeutic potential of intra-arterial transplantation for CNS injury is still in its early stages. In this comprehensive review, we aim to summarize both basic and clinical research exploring the intra-arterial administration of stem cells and exosomes for the treatment of CNS diseases. Additionally, we will elucidate the underlying therapeutic mechanisms and provide insights into the future potential of this approach.

Feasibility and non-inferiority of mobile telementoring for digital subtraction angiography: a single-center observational study.
Toshiya Osanai, Haruto Uchino, Kikutaro Tokairin, Kota Kurisu, Miki Fujimura
Journal of neurointerventional surgery, 10 Jul. 2025, [International Magazine]
English, Scientific journal, BACKGROUND: Telementoring is an emerging approach in surgical education that offers remote supervision and guidance through digital platforms. This study aimed to evaluate the feasibility and non-inferiority of a mobile-based telementoring system for digital subtraction angiography (DSA) and compare it with traditional face-to-face mentoring. METHODS: This prospective, single-center observational study included 71 patients who underwent DSA between April 2021 and May 2024. Patients were categorized into control (n=48, face-to-face mentoring) and telementoring (n=23) groups. A mobile telementoring system (JOIN, Allm Inc., Tokyo, Japan), which enabled real-time image sharing and voice communication between the examiner and the remote supervisor, was employed. The primary endpoints were contrast volume, procedural time, and radiation dose, with a non-inferiority margin of 20% applied. RESULTS: No significant differences were observed between the two groups in contrast volume (88.3±39.6 mL vs 97.1±36.4 mL, p=0.499), procedural time (44.1±17.7 min vs 50.7±19.0 min, p=0.308), or radiation dose (427.9±262.2 mGy vs 506.6±307.1 mGy, p=0.346). Non-inferiority was confirmed across all primary endpoints. No procedural complications occurred. Qualitative feedback indicated high user satisfaction, with the system facilitating effective remote supervision and decision-making. CONCLUSIONS: This study demonstrates the feasibility and non-inferiority of a mobile telementoring system for DSA, effectively supporting real-time remote guidance and reducing the need for on-site supervision. Its implementation may enhance access to expert mentoring, particularly in regions with limited specialist availability, contributing to equitable and efficient cerebrovascular care.

Efficacy and safety of stem cell therapy for acute and subacute ischemic stroke: a systematic review and meta-analysis.
Toshiya Osanai, Soichiro Takamiya, Yasuhiro Morii, Katsuhiko Ogasawara, Kiyohiro Houkin, Miki Fujimura
Scientific reports, 15, 1, 21214, 21214, 01 Jul. 2025, [International Magazine]
English, Scientific journal, The efficacy of stem cell therapy for ischemic stroke in terms of functional outcomes remains unclear. We conducted a systematic review and meta-analysis of randomized controlled trials (PROSPERO: CRD42024503763) to assess the efficacy and safety of stem cell therapy for acute/subacute ischemic stroke, focusing on long-term outcomes. Studies of patients undergoing stem cell transplantation within 1 month of stroke onset were included. We searched five databases for publications up to January 17, 2024. Summary data were extracted from published reports. The primary outcome was the modified Rankin Scale (mRS) score. Measures of effect were risk ratios (RRs) with 95% confidence intervals (CIs). A random-effects model was used when I2 was > 25%; otherwise, a fixed-effects model was used. Common serious adverse events were epilepsy, gastrointestinal disorders, and cardiac disorders. The risk of bias was assessed using the Cochrane Risk of Bias tool version 2. In total, 13 trials involving 872 (519 men) patients were included. The 1-year incidence of mRS scores 0-1 was higher in the cell-therapy group (45/195) than that in the control group (23/179; RR = 1.74 [95% CI = 1.09-2.77]; p = 0.020; I2 = 0%). The 90-day incidence of mRS scores 0-2 was also higher (RR = 1.31 [95% CI = 1.01-1.70]; p = 0.044; I2 = 0%). No significant differences were observed in serious adverse events or mortality. Stem cell therapy for acute/subacute ischemic stroke within 1 month of onset is safe and significantly improves long-term functional outcomes, although the mechanisms of action need to be elucidated and treatment protocols standardized to establish stem cell therapy as a standard care option for ischemic stroke.

Clinical features, radiological findings, and outcome in patients with symptomatic mild carotid stenosis: a MUSIC study.
Daina Kashiwazaki, Kohei Chida, Kazumichi Yoshida, Kiyofumi Yamada, Motohiro Morioka, Katsuhiko Maruichi, Emiko Hori, Naoki Akioka, Yasushi Takagi, Junta Moroi, Susumu Miyamoto, Toru Iwama, Masaki Chin, Kenji Kamiyama, Kojiro Wada, Nobuyuki Sakai, Tsuyoshi Izumo, Yusuke Nishikawa, Mitsuhito Mase, Kohkichi Hosoda, Katsumi Takizawa, Eiichi Kobayashi, Michiya Kubo, Atsushi Fujita, Taku Sugiyama, Miki Fujimura, Hideyuki Yoshioka, Hiroyuki Kinouchi, Takeharu Kunieda, Ataru Nishimura, Shinichi Yoshimura, Yoshiaki Shiokawa, Hiroshi Abe, Hiroharu Kataoka, Kuniaki Ogasawara, Masaaki Uno, Makoto Sasaki, Satoshi Kuroda
Journal of neurosurgery, 143, 1, 285, 295, 01 Jul. 2025, [International Magazine]
English, Scientific journal, OBJECTIVE: Plaque composition, but not degree of stenosis, may play a key role in the development of recurrent ischemic events in patients with symptomatic mild (< 50%) carotid artery stenosis. This multicenter prospective cohort study was aimed to determine their clinical and radiological features and to evaluate the benefits of carotid endarterectomy (CEA) for them. METHODS: This study included 124 patients with cerebrovascular or retinal ischemic events ipsilateral to mild carotid stenosis. Best medical therapy (BMT) was administered to all participants. CEA or carotid artery stenting was implemented at each institution's discretion. Baseline and 6-, 12-, and 24-month follow-up data were collected. The primary endpoint was ipsilateral ischemic stroke. Secondary endpoints included any stroke, ipsilateral transient ischemic attack, ipsilateral ocular symptoms, any death, and plaque progression requiring CEA/carotid artery stenting. The multivariate Cox proportional hazards model was used to evaluate the predictors for each endpoint. RESULTS: Of 124 patients, 70 (56.5%) had a history of ipsilateral ischemic stroke and 51 (43.5%) had been treated with antiplatelet agents. The mean (± SD) degree of stenosis was 22.4% ± 13.7%. Plaque composition was categorized as fibrous plaque in 22 patients, lipid-rich or necrotic core in 25, and intraplaque hemorrhage (IPH) in 69. BMT was indicated for 59 patients, and CEA was performed in 63. The incidence of primary endpoint was significantly higher in the BMT group than in the CEA group (15.1% vs 1.7%; HR 0.18; 95% CI 0.05-0.84; p = 0.03). The predictors for primary endpoint were CEA (HR 0.18; 95% CI 0.05-0.84; p = 0.03) and IPH (HR 1.92; 95% CI 1.26-4.28; p = 0.04). The incidence of secondary endpoint was significantly higher in the BMT group than in the CEA group (31.4% vs 7.3%; HR 0.32; 95% CI 0.13-0.79; p = 0.01). The predictors for secondary endpoints were also CEA (HR 0.32; 95% CI 0.13-0.79; p = 0.01) and IPH (HR 1.52; 95% CI 1.06-4.39; p = 0.03). CONCLUSIONS: IPH may highly predict subsequent cerebrovascular events, whereas CEA may reduce these risks during a 2-year follow-up in patients with symptomatic mild carotid stenosis.

Association between RNF213 p.R4810K and Progression of Cerebral Artery Negative Remodeling in Moyamoya Disease.
Haruto Uchino, Masaki Ito, Taku Sugiyama, Kota Kurisu, Noriyuki Fujima, Miki Fujimura
Neurologia medico-chirurgica, 65, 6, 290, 295, 15 Jun. 2025, [Domestic magazines]
English, Scientific journal, Negative remodeling, characterized by a decrease in the outer diameter of the terminal (C1) segment of the internal carotid artery and the proximal (M1) segment of the middle cerebral artery, is a hallmark of moyamoya disease. However, the role of the disease-susceptibility gene RNF213 in negative remodeling in moyamoya disease remains unclear. This study investigated the effect of RNF213 p.R4810K polymorphism on the degree of negative remodeling in moyamoya disease. We analyzed 70 hemispheres of 38 adult patients with moyamoya disease who underwent RNF213 p.R4810K gene analysis. Vascular outer diameters of the distal C1 and proximal M1 segments were measured using constructive interference in steady-state images obtained from 3-tesla magnetic resonance imaging. Suzuki stages were determined via cerebral angiography, and comparisons were made between RNF213-mutant and wild-type hemispheres. Among the analyzed hemispheres, 39 (56%) were RNF213-mutant, and 31 were wild-type. Suzuki stages were distributed as follows: 0 in 8 hemispheres, 1-2 in 15, 3-4 in 40, and 5-6 in 7. At stage 3-4, the C1 outer diameter was significantly smaller in RNF213-mutant hemispheres compared to wild-type (median 2.1 vs 2.6 mm, p < 0.05). A significant reduction in vascular outer diameters in the advanced disease stage was observed only in the mutant group between stages 0 and 3-4 (C1: median 3.0 vs 2.1 mm, p < 0.05; M1: median 2.2 vs 1.5 mm, p < 0.001). These findings suggest the association between RNF213 p.R4810K polymorphism and the progression of negative remodeling at the carotid fork in advanced disease stages of moyamoya disease.

Diagnostic Values of the "To and Fro" Conflict Sign on Intraoperative Indocyanine Green Video Angiography as a Warning Sign of the Focal Cerebral Hyperperfusion and Watershed Shift Phenomenon after Superficial Temporal Artery-Middle Cerebral Artery Bypass for Adult Patients with Moyamoya Disease.
Ryosuke Tashiro, Miki Fujimura, Taketo Nishizawa, Keita Tominaga, Atushi Kanoke, Hidenori Endo
Cerebrovascular diseases (Basel, Switzerland), 1, 8, 12 Jun. 2025, [International Magazine]
English, Scientific journal, INTRODUCTION: The focal cerebral hyperperfusion (CHP) is a potential complication after superficial temporal artery-middle cerebral artery (STA-MCA) bypass for moyamoya disease (MMD) that can result in delayed intracerebral hemorrhage and/or neurological deterioration. The focal CHP could accompany hemodynamic ischemia due to the "watershed shift (WS) phenomenon." Preoperative prediction of the focal CHP and WS phenomenon remains challenging. Here, we aimed to assess the diagnostic value of the "to and fro" conflict sign, conflicting blood flow around the vascular territory of the recipient arteries on an indocyanine green video angiography (ICG-VA) for predicting the focal CHP and WS phenomenon. METHODS: Ninety-seven consecutive adult patients with MMD, undergoing 106 surgeries, were enrolled. Serial quantitative analysis of cerebral blood flow was routinely conducted using n-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography preoperatively and postoperative day 1 and 7 after STA-MCA bypass. The association between the "to and fro" conflict sign on ICG-VA and the focal CHP/WS phenomenon incidence was then analyzed. RESULTS: The incidence of the focal CHP and WS phenomenon was 29.2% (31/106) and 10.4% (11/106), respectively. The "to and fro" conflict sign was evident in 35.5% (11/31) and 54.5% (6/11) of MMD patients with the focal CHP and WS phenomenon, respectively. The "to and fro" conflict sign was significantly associated with both the focal CHP and WS phenomena. CONCLUSION: The "to and fro" conflict sign on ICG-VA may serve as an intraoperative warning sign of the focal CHP and WS phenomenon after STA-MCA bypass in adult patients with MMD, providing neurosurgeons with a valuable tool for early detection.

Clinical factors associated with delayed ischemic and non-ischemic adverse events in clazosentan therapy after aneurysmal subarachnoid hemorrhage: early insights from a multicenter prospective registry.
Taku Sugiyama, Masaaki Hokari, Daisuke Shimbo, Haruto Uchino, Yusuke Shimoda, Michinari Okamoto, Yasuhiro Ito, Masayuki Gekka, Hisayasu Saito, Taiji Yamamoto, Yusuke Fujiwara, Miki Fujimura
Neurosurgical review, 48, 1, 482, 482, 05 Jun. 2025, [International Magazine]
English, Scientific journal, Clazosentan (CLZ) therapy prevents delayed ischemia following aneurysmal subarachnoid hemorrhage (aSAH), but non-ischemic adverse events necessitate optimized protocols. This study presents outcomes of contemporary CLZ therapy under a unified protocol and identifies factors influencing delayed ischemic and non-ischemic adverse events following aSAH. This multicenter prospective registry analyzed data from 80 aSAH patients receiving CLZ therapy (April 2023 - October 2024). Primary endpoints were delayed ischemic events and non-ischemic adverse events; secondary endpoint was favorable outcome (modified Rankin Scale 0-2) at discharge or six weeks post-onset. Delayed ischemic events occurred in 19 patients (23.8%), including delayed ischemic neurological deterioration (8.8%), moderate-to-severe cerebral vasospasm (20.0%), and symptomatic delayed cerebral infarction (7.5%). Non-ischemic adverse events were observed in 22 patients (27.5%). Favorable outcomes were achieved in 52 patients (65.0%). Delayed ischemic events were associated with female sex, poor severity grades, higher Fischer scale scores, and elevated neutrophil-to-lymphocyte ratios. Non-ischemic adverse events were associated with older age, anemia, hypoproteinemia, and elevated cardiothoracic ratios. Multivariate analysis identified non-ischemic adverse events as significant for unfavorable outcomes (FDR p <.001), whereas delayed ischemic events were not (FDR p =.705). Among non-ischemic adverse events, pulmonary edema was the strongest factor associated with unfavorable outcomes. In conclusion, CLZ therapy with appropriate candidate selection and management protocol appears promising as a treatment option to prevent delayed ischemia after aSAH, though potential confounders warrant careful consideration. Addressing clinical risk factors for non-ischemic adverse events may further enhance treatment outcomes. Clinical trial number Not applicable.

[Diagnosis and Management Guidelines for Moyamoya Disease].
Miki Fujimura
No shinkei geka. Neurological surgery, 53, 3, 457, 462, May 2025, [Domestic magazines]
Japanese, Scientific journal, Moyamoya disease(MMD) is a rare cerebrovascular disease characterized by progressive stenosis of the internal carotid artery terminus and an abnormal formation of a vascular network at the base of the brain. Superficial temporal artery-middle cerebral artery(STA-MCA) bypass, either as a direct or combined revascularization procedure, is a reasonable management choice for patients with symptomatic MMD. STA-MCA bypass prevents cerebral ischemic attacks by improving cerebral blood flow. Recent evidence further suggests that direct revascularization reduces the potential risk of rebleeding in patients with MMD with posterior hemorrhage who have an extremely high annual rebleeding rate. Despite the favorable long-term outcomes of STA-MCA bypass, cerebral hyperperfusion syndrome is a potential complication of this procedure that can result in focal neurologic deficits and/or delayed intracerebral hemorrhage. Therefore, recent guideline recommendations indicate that STA-MCA bypass is a reasonable choice for symptomatic patients with MMD, together with intensive perioperative care for blood pressure control.

Association between intracranial vascular vulnerability and indirect revascularization development in moyamoya disease.
Haruto Uchino, Masaki Ito, Kota Kurisu, Taku Sugiyama, Miki Fujimura
Neurosurgical review, 48, 1, 387, 387, 25 Apr. 2025, [International Magazine]
English, Scientific journal, Negative remodeling, characterized by a decrease in the outer diameter of cerebral arteries, is a hallmark of moyamoya disease (MMD). Postoperative fluid-attenuated inversion recovery (FLAIR) cortical hyperintensity (FCH), indicative of leptomeningeal vasogenic edema, and indirect bypass development are also distinctive features. We investigated the relationships between negative remodeling and these postoperative phenomena. We analyzed 42 hemispheres from 37 adult patients with MMD who underwent combined direct and indirect revascularization. Negative remodeling was assessed by measuring the terminal portion (C1) vessel diameter of the internal carotid artery on preoperative heavy T2-weighted images. FCH was scored from 0 to 6 based on its extent on FLAIR images obtained 2 days postoperatively; indirect bypass development was evaluated qualitatively using magnetic resonance angiography 6 months post-surgery. The participants' median age was 45 years; 76% were female and 90% presented with ischemic onset. The median C1 diameter was 2.39 mm, median FCH score was 2.5, and favorable indirect bypass development was observed in 64% of cases. Smaller preoperative C1 diameters (2.27 mm vs. 3.02 mm, p < 0.0001) and higher FCH scores (median 3 vs. 2, p < 0.05) correlated with favorable indirect bypass development. Smaller C1 diameters also aligned with extensive FCH (2.94 mm vs. 2.20 mm, p < 0.001). Multivariate analysis revealed a significant association between reduced preoperative C1 diameter and favorable indirect bypass development (odds ratio 0.019, 95% confidence interval 0.010-0.17, p < 0.01). These findings suggest that advanced intracranial vascular remodeling in MMD correlates with vascular vulnerability and favorable indirect bypass development.

Human platelet lysate produced from leukoreduction filter contents enables sufficient MSC growth.
Shinobu Wakamoto, Tomoko Furukawa, Masahito Kawabori, Mitsuaki Akino, Shiho Kato, Hisae Fuse, Sumio Ohtsuki, Yoshihiro Torimoto, Miki Fujimura, Shuichi Kino
Stem cell research & therapy, 16, 1, 205, 205, 23 Apr. 2025, [International Magazine]
English, Scientific journal, BACKGROUND: Stem cell therapy holds significant potential for promoting recovery, with numerous products currently under development. Blood-derived supplements are often essential for successful stem cell expansion, with fetal bovine serum (FBS) being the most commonly used supplement. However, FBS has drawbacks, including the risk of immune responses, ethical concerns about animal welfare, and potential zoonotic infections. Human platelet lysate (hPL), derived from lysed platelets, contains various growth factors and has been proposed as an alternative to FBS. However, obtaining sufficient human platelets for clinical use remains challenging. Leukoreduction filters, used during blood transfusion manufacturing to remove leukocytes, also retain significant amounts of platelets and plasma. This study investigates the feasibility and efficacy of filter-derived hPL (f-hPL) for mesenchymal stem cell (MSC) expansion. METHODS: Leukoreduction filters were collected after their use in the manufacturing of whole blood transfusion products. Each filter was reverse-perfused with saline to extract residual blood contents. Platelets (f-platelet) and supernatant were separated by multiple centrifugation steps. f-Platelet were lysed with varying concentrations of fresh frozen plasma (FFP) to determine the optimal protein concentration for the lysate solution. Then, plasma left in the leukoreduction filters were used to generate lysate solution (f-plasma) at optimal protein concentration. f-Platelet (1.1 × 109/mL) and f-plasma (27 mg/mL protein) were combined in a freezing bag and subjected to three freeze-thaw cycles to produce f-hPL. Both small- and large-scale f-hPL were manufactured, and MSCs expansion and quality assessments were perfomed to evaluate the efficacy of f-hPL. RESULTS: A total of 3.5 ± 0.6 × 1010 f-platelets were obtained from a single leukoreduction filter, yielding a collection efficiency of 37.1 ± 5.3%. The optimal protein concentration of lysate solution for cell expansion was > 27 mg/mL. Subsequently, six leukoreduction filters used to produce enough f-platelet and p-plasma for 100 mL of f-hPL. MSCs cultured in medium supplemented with 10% f-hPL demonstrated superior expansion, with cell proliferation rates 20% higher than those observed with commercial hPL and 300% higher than those cultured with FBS. The expanded MSCs met the International Society for Cell & Gene Therapy criteria for cell surface markers and differentiation potential. MSCs expanded with f-hPL expressed similar to or higher amounts of hepatocyte growth factor compared with those cultured with FBS and human AB serum. Furthermore, f-hPL significantly enhanced cell proliferation up to P12 and effectively prevented cell senescence. CONCLUSION: f-hPL derived from leukoreduction filters demonstrated strong capacity for MSCs expansion. The use of discarded blood materials for regenerative medicine represents a sustainable and efficient approach, with significant therapeutic potential.

Intranasal administration of stem cell-derived exosome alleviates cognitive impairment against subarachnoid hemorrhage.
Shuho Gotoh, Masahito Kawabori, Sho Yamaguchi, Yo Nakahara, Erika Yoshie, Kohtarou Konno, Yuki Mizuno, Yoichiro Fujioka, Yusuke Ohba, Yuji Kuge, Masahiko Watanabe, Miki Fujimura
Experimental neurology, 386, 115143, 115143, Apr. 2025, [International Magazine]
English, Scientific journal, INTRODUCTION: Brain damage caused by subarachnoid hemorrhage (SAH) currently lacks effective treatment, leading to stagnation in the improvement of functional outcomes for decades. Recent studies have demonstrated the therapeutic potential of exosomes released from mesenchymal stem cells (MSC), which effectively attenuate neuronal apoptosis and inflammation in neurological diseases. Due to the challenge of systemic dilution associated with intravenous administration, intranasal delivery has emerged as a novel approach for targeting the brain. In this study, we investigate the effects of intranasally administered MSC-derived exosomes in a SAH animal model and elucidate their mode of action. METHODS: Exosomes were isolated from the cell supernatants of amnion-derived MSC. SAH was induced in 8-week-old Sprague-Dawley rats using an autologous blood prechiasmatic cistern injection model. A total of 1.2 × 1010 particles of exosomes in 200 μL of PBS or PBS alone were intranasally administered immediately and 24 h post-injury. Neurological function was assessed up to 7 days after injury, and histological analysis was performed to evaluate their anti-apoptotic and anti-inflammatory effects. The biodistribution of exosomes was assessed using PET/CT imaging of 64Cu labeled exosome. In vitro analyses were performed using primary glial cells and cell lines to evaluate the anti-inflammatory effects of the exosomes. RESULTS: Animals treated with exosomes exhibited significant improvement in cognitive function compared with PBS treated animal. Apoptotic cells and inflammation were reduced for the exosome group in the hippocampal CA1 area and in cortex, resulting in better neuronal cell survival. Blood brain barrier permeability was also preserved in the exosome group. Nuclear imaging revealed that exosomes were primarily transferred to the olfactory nerve and cerebrum; furthermore, exosomes were also observed in the trigeminal nerve and brainstem, where exosomes were co-localized with microglia and with endothelial cells. In vitro assessment showed that exosome administration ameliorated inflammation and prevented the death of glial cells. CONCLUSIONS: MSC-derived exosomes were successfully transferred into the brain through intranasal administration and alleviated brain damage following SAH.

Intraoperative Cortical Indocyanine Green Extravasation as a Predictor of Cerebral Hyperperfusion following Direct Revascularization for Moyamoya Disease: Impact of Prolonged Observations of Indocyanine Green Videoangiography.
Masaki Ito, Haruto Uchino, Miki Fujimura
Cerebrovascular diseases (Basel, Switzerland), 1, 8, 20 Mar. 2025, [International Magazine]
English, Scientific journal, INTRODUCTION: Local vasogenic edema following direct revascularization for moyamoya disease (MMD) is considered to result from an intrinsic vulnerability of blood-brain barrier (BBB) and is consequently associated with transient focal cerebral hyperperfusion (CHP). However, intraoperative identification of the local vasogenic edema remains challenging. To address this, we implemented a prolonged observation of indocyanine green videoangiography (ICG-VAG) as an extension of routine clinical practice. This approach aimed to investigate intraoperative cortical ICG extravasation following direct revascularization, as an indicator of BBB dysfunction in patients with MMD, providing real-time intraoperative evidence of compromised vascular integrity. METHODS: This prospective observational study included 50 consecutive combined direct/indirect revascularization surgeries performed for MMD at our institution between December 2022 and February 2025. After confirming the patency of the direct anastomosis using ICG-VAG in the early phase, we conducted an additional observation of ICG-VAG in the late phase, approximately 5 min after the initial assessment, to evaluate cortical changes around the anastomotic site. We analyzed the correlation between intraoperative cortical ICG extravasation observed in the late phase of ICG-VAG and postoperative complications, including CHP. RESULTS: ICG-VAG confirmed patent direct anastomoses in all 50 revascularizations, and postoperative CHP occurred in 16 surgeries (32%) between postoperative days 1 and 7. Among these cases, intraoperative cortical ICG extravasation was detected in the late phase of ICG-VAG in nine of 50 surgeries (18%). This extravasation presented as focal or patchy leakage of ICG dye near the anastomotic site and/or flow-augmented cortical areas without evident cortical contusion or subarachnoid hemorrhage under the light-field surgical microscope. There were no significant differences in preoperative baseline clinical characteristics between patients with and without cortical ICG extravasation. However, intraoperative cortical ICG extravasation was significantly correlated with postoperative CHP (odds ratio: 12; 95% confidence interval: 2.5-94; p = 0.0044) and local vasogenic edema on magnetic resonance imaging (odds ratio: 20; 95% confidence interval: 2.2-444; p = 0.015). CONCLUSION: Intraoperative cortical ICG extravasation, observed in the late phase of ICG-VAG, may serve as a direct indicator of the intrinsic vulnerability of BBB in patients with MMD. Prolonged ICG-VAG observation could be a simple and effective intraoperative tool to predict postoperative CHP and local vasogenic edema in patients undergoing direct revascularization for MMD, thereby enabling intensive postoperative monitoring for high-risk cases.

Treatment of Unruptured Large and Giant Paraclinoid Aneurysms in Japan at the Time of Flow Diverter Introduction: A Nationwide, Multicenter Survey by the Japanese Society on Surgery for Cerebral Stroke.
Kazuya Kanemaru, Hideyuki Yoshioka, Koji Hashimoto, Nobuo Senbokuya, Hajime Arai, Miki Fujimura, Kensuke Suzuki, Ko Matsuda, Nobuyuki Sakai, Ryo Nishikawa, Yuichi Murayama, Jun C Takahashi, Tooru Inoue, Shinichi Yoshimura, Teiji Tominaga, Hiroyuki Kinouchi
World neurosurgery, 195, 123571, 123571, Mar. 2025, [International Magazine]
English, Scientific journal, OBJECTIVE: Large or giant paraclinoid aneurysms have been treated with various strategies, including clipping, coiling, and parent artery occlusion (PAO). In addition, flow diverters (FDs) have been introduced for the management of these aneurysms. The aim of this study was to examine the management of unruptured large/giant paraclinoid aneurysms in Japan when FDs were being introduced by a nationwide survey. METHODS: A total of 576 unruptured large/giant paraclinoid aneurysms treated in Japan between January 2012 and December 2016 were retrospectively studied. RESULTS: Half of the large paraclinoid aneurysms were treated by coiling (50.3%), whereas giant aneurysms were occluded mainly by PAO (51.4%). A high nearly complete occlusion rate was achieved with clipping (94.1%), coiling (85.9%), PAO (82.4%), and FDs (77.6%). Coiling had higher risks of recurrence (28.3%) and retreatment (20.3%). Major procedure-related complications were observed in 9.7%. Ischemic complications were common in PAO (9.5%), with cranial nerve symptoms common in clipping (10.9%). All treatment modalities achieved good clinical outcomes (93.5%-96.6%). Although not significant, pre-existing visual disturbance improved most frequently by clipping (53.7%), but also worsened most frequently by clipping (24.4%). Consequently, FD achieved a high occlusion rate with minimal complication and retreatment rates. CONCLUSIONS: All treatment modalities offer high rates of complete occlusion and good clinical outcomes. Coiling has the disadvantage of high rates of recurrence and retreatment. Clipping and PAO have the disadvantage of a high rate of major procedure-related complications; however, PAO can provide comparable treatment outcomes even in cases with refractory giant aneurysms. FDs are the optimal choice for the management for large/giant paraclinoid aneurysms due to its safety and efficacy.

Treatment of Unruptured Large and Giant Carotid Cavernous Aneurysms in Japan at the Time of Flow Diverter Introduction: A Nationwide, Multicenter Survey by the Japanese Society on Surgery for Cerebral Stroke.
Hideyuki Yoshioka, Kazuya Kanemaru, Koji Hashimoto, Nobuo Senbokuya, Hajime Arai, Nobuyuki Sakai, Toshihiko Wakabayashi, Miki Fujimura, Susumu Miyamoto, Isao Date, Kensuke Suzuki, Tooru Inoue, Toshihiko Kuroiwa, Satoshi Kuroda, Teiji Tominaga, Hiroyuki Kinouchi
World neurosurgery, 195, 123629, 123629, Mar. 2025, [International Magazine]
English, Scientific journal, BACKGROUND: Flow diverters (FDs) were introduced for management of large or giant cavernous carotid aneurysms (CCAs) in addition to conventional modalities, dramatically changing treatment strategies. This study examined the management of unruptured large/giant CCAs in Japan when FDs were being introduced using a nationwide survey. METHODS: A total of 540 unruptured large/giant CCAs treated at neurosurgical teaching departments in Japan between 2012 and 2016 were retrospectively studied. RESULTS: Large CCAs were treated equally by parent artery occlusion (PAO), FD, and coiling, but giant aneurysms were occluded mainly by PAO. PAO was combined with revascularization in most cases. The nearly complete obliteration rate at final follow-up was higher after PAO (92.4%) than after FD (60.1%) and coiling (70.3%), and PAO was the most effective for ophthalmoparesis. Coiling had higher risks of recurrence and retreatment. Procedure-related major complications were observed in 9.6%. Cranial nerve symptoms were the most common complications, with coiling having significantly higher risks. All treatment modalities achieved good clinical outcomes (92.1%-96.1%); however, 5 delayed rupture cases were observed (1 PAO, 4 FD), resulting in 5 deaths (1 PAO, 1 FD). CONCLUSIONS: The nationwide survey reported here determined the status of treatment for unruptured large/giant CCAs in Japan when FDs were being introduced. Because PAO has disadvantages including the long-term hemodynamic effects of ICA occlusion, reconstructive treatment using FDs is optimal for this type of aneurysm; however, PAO can be an option in selected cases given the higher rates of complete occlusion and symptom improvement.

Disease progression, transient ischemic attack, and de novo parenchymal lesions in asymptomatic moyamoya disease: results of a 5-year interim analysis of the AMORE study.
Satoshi Kuroda, Shusuke Yamamoto, Takeshi Funaki, Miki Fujimura, Hiroharu Kataoka, Tomohito Hishikawa, Jun C Takahashi, Hidenori Endo, Tadashi Nariai, Toshiaki Osato, Nobuhito Saito, Norihiro Sato, Emiko Hori, Daina Kashiwazaki, Yoichi M Ito, Susumu Miyamoto
Journal of neurosurgery, 142, 3, 658, 666, 01 Mar. 2025, [International Magazine]
English, Scientific journal, OBJECTIVE: Recently, the authors have reported the 5-year risk of stroke in patients with asymptomatic moyamoya disease (MMD). In this report, the aim was to clarify patients' 5-year risk of disease progression, transient ischemic attack (TIA), and de novo parenchymal lesions and to identify their predictors. METHODS: This multicenter, prospective cohort study (Asymptomatic Moyamoya Registry [AMORE]) in Japan is still ongoing. Participants were enrolled if they were 20-70 years of age, had bilateral or unilateral MMD, experienced no episodes suggestive of TIA and stroke, were functionally independent (modified Rankin Scale score of 0 or 1), and had been followed up for 10 years. Clinical and radiological data were obtained at enrollment and annually thereafter for 5 years. In this 5-year interim analysis, the authors defined disease progression, TIA, and de novo parenchymal lesions as the secondary endpoints. The predictors for these events were identified, using a stratification analysis method. RESULTS: A total of 103 patients were enrolled and prospectively followed up for 5 years. On annual MRA examinations, disease progression occurred in 39 hemispheres in 26 patients. The incidence of disease progression was 5.9% per patient-year, and the predictors included younger age (OR 5.72, 95% CI 1.28-25.56; p = 0.0223) and hypercholesterolemia (OR 5.41, 95% CI 1.37-21.28; p = 0.0158). TIA occurred in 12 hemispheres in 10 patients, for an incidence of 2.3% per patient-year. The disease progression prior to TIA was a significant predictor for TIA (OR 5.00, 95% CI 1.31-19.0; p = 0.0184). De novo microbleeds were found in 11 hemispheres in 10 patients (2.3% per patient-year). The presence of microbleeds at enrollment was a significant predictor for de novo microbleeds (OR 5.53, 95% CI 1.17-26.13; p = 0.0309). CONCLUSIONS: Patients with asymptomatic MMD may carry a significant risk of disease progression, TIA, and de novo microbleeds during the first 5 years after initial diagnosis. Practitioners should very carefully follow up with them to improve their outcome, using MRI and MRA at regular intervals. Clinical trial registration no.: UMIN000006640 (https://www.umin.ac.jp).

Mature teratoma with a germinoma component presenting with undetectable placental alkaline phosphatase in cerebrospinal fluid: illustrative case.
Sogo Oki, Shigeru Yamaguchi, Michinari Okamoto, Yukitomo Ishi, Hiromi Kanno-Okada, Emi Takakuwa, Yukayo Terashita, Shinsuke Hirabayashi, Kentaro Nishioka, Takayuki Hashimoto, Atsushi Manabe, Miki Fujimura
Journal of neurosurgery. Case lessons, 9, 8, 24 Feb. 2025, [International Magazine]
English, Scientific journal, BACKGROUND: Diagnosing intracranial mixed germ cell tumors (GCTs) can be challenging due to intratumoral heterogeneity. Placental alkaline phosphatase (PLAP) in the cerebrospinal fluid (CSF) is a highly sensitive and specific marker for identifying pure germinomas and germinoma components within mixed GCTs. OBSERVATIONS: The authors present the case of a 6-year-old boy presenting with a 5-day history of vomiting and headache. Magnetic resonance imaging revealed a heterogeneously enhanced mass with cystic areas in the pineal region. Preoperative serum levels of alpha-fetoprotein and human chorionic gonadotropin, as well as CSF PLAP levels, were not elevated, leading to a preliminary diagnosis of mature teratoma. The tumor was completely resected, and pathological examination of the resected tissue confirmed a mature teratoma with germinoma components. Given the diagnosis of mixed GCT with a germinoma component, the patient underwent postoperative radiation chemotherapy. There has been no recurrence after 8 years of follow-up. LESSONS: In this case, the preoperative CSF PLAP level failed to predict the presence of a germinoma component. This report highlights a potential limitation of CSF PLAP as a diagnostic marker, noting that CSF PLAP may be undetectable if the germinoma is confined to a localized area. https://thejns.org/doi/10.3171/CASE24588.

Post-operative vestibular function outcomes evaluated by video Head Impulse Test in patients with non-vestibular schwannoma cerebellopontine angle tumors.
Keishi Fujiwara, Shinya Morita, Hiroaki Motegi, Shigeru Yamaguchi, Yukitomo Ishi, Kimiko Hoshino, Atsushi Fukuda, Hideaki Takeda, Yuji Nakamaru, Miki Fujimura, Akihiro Homma
Auris, nasus, larynx, 52, 1, 50, 58, Feb. 2025, [International Magazine]
English, Scientific journal, OBJECTIVES: To evaluate post-operative semicircular canal function in patients with non-vestibular schwannoma (VS) cerebellopontine angle (CPA) tumors by video Head Impulse Test (vHIT). METHODS: Fourteen patients with non-VS CPA tumors who underwent surgery. The gain in vestibulo-ocular reflex (VOR) was examined pre- and post-operatively for the semicircular canals in patients with non-VS CPA tumors. RESULTS: Ten of 14 patients showed semicircular canal dysfunction in one or more of the semicircular canals pre-operatively and VOR gain was significantly correlated with hearing function. Two patients showed improvement in one or more semicircular canals at 1 month after surgery compared to the pre-operative results. Significant improvements in VOR gain were observed when comparing VOR gain at 1 month and 6 months after surgery. CONCLUSIONS: Detailed evaluation of semicircular canal function was achieved by using vHIT in patients with non-VS CPA tumors. The good prognosis for vestibular function as evaluated by vHIT post-operatively was confirmed in patients with non-VS CPA tumors when compared to those in patients with VS. As improvement may occur post-operatively, surgical approaches that preserve the vestibular nerves and semicircular canals should be chosen for patients with non-VS CPA tumors, regardless of preoperative vestibular function. Even if vestibular function deteriorates immediately after surgery, it may improve over time if the nerve is preserved.

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, 65, 3, 120, 125, 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.

Spontaneous Superior Ophthalmic Vein Thrombosis Resulted in Posterior Fossa Venous Congestion in a Case of Cavernous Sinus Dural Arteriovenous Fistula: Successful Treatment with Direct Interruption Surgery.
Yoshiro Yamada, Kota Kurisu, Masaki Ito, Toshiya Osanai, Taku Sugiyama, Miki Fujimura
NMC case report journal, 12, 565, 570, 2025, [Domestic magazines]
English, Scientific journal, Cavernous sinus dural arteriovenous fistulas are generally considered to have a benign clinical course, as spontaneous thrombosis of the fistula or draining veins can result in regression of the lesion. However, we encountered a rare case in which this hemodynamic change led to rapid neurological deterioration, necessitating microsurgical intervention. A 72-year-old woman presenting with chemosis and exophthalmos was diagnosed with a cavernous sinus dural arteriovenous fistula. Cerebral angiography revealed 2 venous drainage routes: the superior ophthalmic vein anteriorly and the superior petrosal sinus towards the petrosal vein posteriorly. Approximately 2 weeks after diagnosis, while awaiting elective endovascular treatment, the patient developed spontaneous thrombosis of the superior ophthalmic vein. This redirected shunt flow exclusively into the petrosal vein, leading to venous congestion in the posterior fossa. Consequently, the patient experienced rapid neurological deterioration accompanied by brain edema in the cerebellum and brainstem. Furthermore, the loss of transvenous access rendered curative endovascular treatment unfeasible. The patient was therefore treated with urgent microsurgical interruption of the petrosal vein via a retrosigmoid approach. This resulted in complete neurological recovery and angiographic obliteration of the cavernous sinus dural arteriovenous fistulas. This case highlights the importance of close observation while waiting for the intervention for cavernous sinus dural arteriovenous fistulas with cortical venous reflux, given the risk of spontaneous hemodynamic change. It also underscores the role of microsurgical intervention as a salvage option when endovascular treatment becomes unfeasible.

Successful Clazosentan Therapy for Subarachnoid Hemorrhage after Coil Embolization of Ruptured Posterior Cerebral Artery Aneurysm in a Patient with Moyamoya Disease: A Case Report.
Haruto Uchino, Taku Sugiyama, Masaaki Hokari, Yoshitaka Yamaguchi, Toshiya Osanai, Miki Fujimura
NMC case report journal, 12, 505, 509, 2025, [Domestic magazines]
English, Scientific journal, Moyamoya disease is a progressive steno-occlusive cerebrovascular disorder that may be complicated by intracranial aneurysms, particularly, in the posterior circulation, which are at higher risk of rupture than those in the general population. Clazosentan, a selective endothelin A receptor antagonist, has been approved in Japan for the prevention of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. However, cerebral hemodynamics after subarachnoid hemorrhage and safety of clazosentan in patients with moyamoya disease remain unknown. We report the case of a 46-year-old man with bilateral moyamoya disease who presented with severe subarachnoid hemorrhage caused by a ruptured saccular aneurysm in the right P2 segment of the posterior cerebral artery. Coil embolization was successfully performed, and clazosentan (10 mg/hr), along with cilostazol, was administered to prevent vasospasm. Fluid balance was carefully managed, and no clazosentan-related adverse events were observed. Follow-up radiological examinations showed no evidence of cerebral vasospasm or ischemic lesions. The patient made a favorable recovery and was discharged with a modified Rankin scale score of 1. Four months later, revascularization surgery was performed to reduce hemodynamic stress and the risk of hemorrhage from choroidal collaterals. The aneurysm remained occluded, the choroidal channels regressed, and no recurrent strokes occurred during 1 year of follow-up. To the best of our knowledge, this is the first report of successful clazosentan therapy for aneurysmal subarachnoid hemorrhage in a patient with moyamoya disease. Careful perioperative management allowed the safe use of clazosentan without complications. Further studies are needed to evaluate its broader safety and efficacy in this population.

Medical Management of Adult Moyamoya Disease: A Review and Relevant Cases With Ischemic Events.
Oh Young Bang, Miki Fujimura
Journal of stroke, 27, 1, 1, 18, Jan. 2025, [International Magazine]
English, Scientific journal, Moyamoya disease (MMD) is a rare and progressive cerebrovascular disorder characterized by stenosis or occlusion of the internal carotid arteries resulting in the development of fragile collateral vessels at the base of the brain. Surgical revascularization is the primary treatment option for preventing ischemic and hemorrhagic events; however, the role of medical management has become increasingly recognized, particularly in cases involving asymptomatic patients or those at a high risk for surgical complications. In this review, we aimed to investigate the current guidelines and evidence supporting various medical management strategies for MMD, including the importance of controlling risk factors and judicious use of antithrombotic therapy. Given the considerable variability in patient presentation, such as age of onset, symptomatology, and comorbid conditions, it is crucial to adopt tailored therapeutic approaches that address each patient's unique characteristics. The existing literature on medical management is limited. However, individualized strategies may effectively mitigate the risk of ischemic events and improve the overall patient outcomes. Further research is essential to develop comprehensive and standardized treatment protocols for medical management of adult patients with MMD. In addition, ongoing trials and efforts to develop disease-modifying agents are discussed.

A Case of Surgically Treated Adult Split Cord Malformation Type 2 with Tethered Cord Syndrome.
Keisuke Ohmae, Motoyuki Iwasaki, Izumi Koyanagi, Miki Fujimura
NMC case report journal, 12, 1, 5, 2025, [Domestic magazines]
English, Scientific journal, Split cord malformation (SCM) is a rare congenital anomaly characterised by the division of the spinal cord into 2 distinct hemicords, often accompanied by bony or cartilaginous septum. We experienced a surgical case diagnosed as SCM with tethered cord syndrome (TCS) due to spinal lipoma. A 54-year-old female presented with a history of gradually progressive paraparesis and bladder dysfunction for a few months. Her magnetic resonance imaging revealed low-positioned conus medullaris below the level of S3 due to spinal lipoma and accompanied by other small multiple lipomas and a split cord below the level of L4/L5 without bony separation. The final diagnosis was SCM type II with TCS. Under careful intraoperative inspection, fibrous connecting strings were arising from the dorsal interface of the split cord to the dorsal arachnoid membrane as one of the responsible tethering structures. Circumferential meticulous dissection was performed around the split cord, followed by standard dissection of tethered conus owing to lipoma at the caudal end. Her symptoms were alleviated immediately after surgery. Although the surgical procedure has not been established because of its rarity, dissection around the split cord should precede the usual untethering of the caudal spinal cord.

Relationship Between Location of Cell Transplantation and Recovery for Intracerebral Stem Cell Transplantation for Chronic Traumatic Brain Injury: Post-hoc Analysis of STEMTRA Trial.
Masahito Kawabori, Yasuaki Karasawa, Jun Suenaga, Hajime Nakamura, Hideaki Imai, Takao Yasuhara, Naoki Tani, Tatsuya Sasaki, Takashi Kawasaki, Kenta Totsuka, Dai Chida, Yoichi M Ito, Tetsuya Yamamoto, Isao Date, Shota Tanaka, Haruhiko Kishima, Miki Fujimura
Neurotrauma reports, 6, 1, 106, 114, 2025, [International Magazine]
English, Scientific journal, Traumatic brain injury is a world-leading cause of disability. Current treatments are not sufficient to promote neurological recovery. Intracerebral transplantation of allogeneic mesenchymal stem cells, specifically SB623, has shown promise in achieving better neurological recovery compared with a sham surgery group in the STEMTRA trial. However, the optimal location for cell transplantation remains unclear, as transplanted lesions vary between patients. This study aimed to explore the relationship between functional recovery and the location of transplanted lesions. This study included all Japanese subjects from the STEMTRA trial who were assigned to the cell transplantation group. Functional recovery was assessed by the difference in Fugl-Meyer Motor Scale (FMMS) scores between the screening period and 24 or 48 weeks post-transplantation. An FMMS score improvement of >8 was defined as an improved group. Lesions responsible for motor deficits were categorized into three groups: motor cortex (Cortex), deep white matter (DWM), or both (Cortex and DWM). Data on the 15 transplanted sites per patient were obtained from surgical navigation software, and the distance from the damaged area to the transplanted sites was calculated. Twelve patients were included in this post-hoc analysis. No patients in the 2.5 × 106 cells group showed improvement and were therefore excluded from further analysis. Five patients were categorized into the Cortex group and four into the DWM group. The distance between the transplanted site and the injury point ranged from 0 to 39 mm. A moderate to strong trend of correlations was observed, suggesting that a shorter distance is preferable for the motor cortex group, while a greater distance is preferable for the DWM group. The optimal site for stem cell transplantation may be different from the damaged site of the patient; however, a further large number cohort is necessary to elucidate this hypothesis.

Role and Efficacy of Direct Surgery in the Management of Intracranial Dural Arteriovenous Fistulas.
Taku Sugiyama, Toshiya Osanai, Masaki Ito, Haruto Uchino, Miki Fujimura
Acta neurochirurgica. Supplement, 136, 61, 67, 2025, [International Magazine]
English, Scientific journal, PURPOSE: Although endovascular treatment (EVT) is often the treatment of choice for intracranial dural arteriovenous fistula (dAVF), direct surgery is an efficient option for many types of dAVFs. Herein, we present a relatively large case series of direct surgical patients to discuss the role and efficacy of direct surgery in managing intracranial dAVFs. METHODS: 43 consecutive patients with dAVFs (ethmoid, n = 11; middle fossa, n = 1; convexity, n = 2; tentorium, n = 11; superior sagittal sinus, n = 2; transverse-sigmoid sinus, n = 11; and cranio-vertebral junction [CVJ], n = 5) treated with direct surgery were retrospectively assessed. Here, 21 (48.8%) and six (14.0%) patients presented with intracranial hemorrhage (ICH) and nonhemorrhagic neurological deficits, respectively. Factors for the selection of direct surgery, prior EVT, surgical procedure, and surgical outcomes were investigated. RESULTS: The ethmoidal location and massive ICH presentation were associated with the predominant selection of direct surgery. Incomplete obliteration via prior EVT was frequently observed in CVJ dAVF, as well as in tentorial dAVFs with pial arterial supply. Permanent surgery-related complications and incomplete obliteration were observed in 7.0% and 2.4% of the patients, respectively. Regarding long-term outcomes, recurrence was not observed postoperatively during the 1336 patient-month follow-up period, and favorable outcomes (modified Rankin scale of 0-2) at the last evaluation were achieved in 82.5% of patients. CONCLUSION: Direct surgery is an effective therapeutic option for dAVFs located in the ethmoid, CVJ, or tentorium; those presenting with massive ICH; and those with pial arterial supply.

Efficacy and Safety of Combined Revascularization Surgery for Moyamoya Disease: Standard Procedure and Perioperative Management.
Miki Fujimura, Masaki Ito, Haruto Uchino, Masahito Kawabori, Taku Sugiyama
Acta neurochirurgica. Supplement, 136, 99, 104, 2025, [International Magazine]
English, Scientific journal, OBJECTIVE: Revascularization surgery such as superficial temporal artery-middle cerebral artery (STA-MCA) bypass is a standard management choice for symptomatic moyamoya disease (MMD) patients, with either ischemic or hemorrhagic presentation. We sought to clarify the efficacy and safety of institutional standardized revascularization procedures for MMD. MATERIALS AND METHODS: The present study includes 37 consecutive patients with MMD (2-60 years old, 42.0 on average) undergoing revascularization surgery on 42 affected hemispheres. Direct-indirect combined revascularization surgery was performed on most hemispheres (41/42, 97.6%), including STA-MCA bypass (39 hemispheres) and occipital artery-posterior cerebral artery bypass (2 hemispheres). All patients underwent standardized perioperative management with strict blood pressure control (110-130 mmHg) based on routine single-photon emission computed tomography (SPECT) 1 and 7 days after surgery. Then we investigated the outcome of surgeries, focusing mainly on that of combined revascularization procedures. RESULTS: The outcome of 42 surgeries was favorable in all cases, except for one adult (2.3%) manifesting with cerebral hyperperfusion syndrome leading to neurological worsening. None of the patients developed perioperative cerebral infarction (0/42; 0%), and the patency of the direct bypass was confirmed via MRA in all patients undergoing combined procedure (41/41, 100%). Two patients suffered wound-healing delay, one of which required resuture. CONCLUSION: The combined revascularization surgery is a safe and effective treatment for MMD, while local cerebral hyperperfusion is a potential complication that should be avoided through intensive perioperative care.

Intraventricular continuous BDNF administration ameliorates neuroinflammation and enhances neurogenesis against rodent intracerebral hemorrhage model.
Ting-Chun Lin, Masahito Kawabori, Erika Yoshie, Yo Nakahara, Li-Kai Tsai, Miki Fujimura
Frontiers in neurology, 16, 1606606, 1606606, 2025, [International Magazine]
English, Scientific journal, OBJECTIVE: Brain-derived neurotrophic factor (BDNF) is a pivotal growth factor for neuronal survival; however, its precise role following intracerebral hemorrhage (ICH) remains poorly understood. This study sought to investigate whether intraventricular administration of BDNF could enhance neurogenesis and ameliorate neuroinflammation, resulting in improvement of neurological outcomes in a rat ICH model. METHODS: Male Sprague-Dawley rats were utilized to create an acute ICH model by collagenase infusion into the internal capsule. An intraventricular minipump was subcutaneously implanted, with the catheter tip inserted into the contralateral ventricle to deliver BDNF for 7 consecutive days. The rats were assigned to one of three experimental groups; the BDNF group, the anti-BDNF antibody group, and the sham group. Functional assessment was conducted up to 14 days post-ICH, and immunohistochemical analysis was performed to evaluate neurogenesis, apoptosis, and neuroinflammation in the perihematomal area and the subventricular zone (SVZ). RESULTS: Brain-derived neurotrophic factor treatment significantly increased the proliferation of neural stem cells in the perihematomal region. It also reduced the neuroinflammation 14 days post-ICH. Additionally, BDNF treatment demonstrated a favorable neurological function at 14 days post-ICH. CONCLUSION: Intraventricular administration of BDNF demonstrated favorable recovery after ICH by reducing inflammation and enhancing neurogenesis.

Long-term outcome and social-intellectual ability of patients with basal ganglia germinoma
Michinari Okamoto, Shigeru Yamaguchi, Ryosuke Sawaya, Yukitomo Ishi, Hiroaki Motegi, Yukayo Terashita, Minako Sugiyama, Yuko Cho, Kentaro Nishioka, Takashi Mori, Takayuki Hashimoto, Hidefumi Aoyama, Atsushi Manabe, Miki Fujimura
Pediatric Neurology, 165, 16, 21, Elsevier BV, Jan. 2025, [International Magazine]
English, Scientific journal, BACKGROUND: In this study, we aimed at delineating the still ambiguous clinical characteristics and long-term outcomes of basal ganglia (BG) germinoma from the aspect of recurrence-free survival as well as social and intellectual activity. METHODS: We retrospectively reviewed medical records and imaging data for 12 patients with BG germinoma diagnosed and treated between 1996 and 2020, collecting the most recent status via medical records or telephone from the patients. RESULTS: The tumors involved the right and left sides and bilateral locations in three, seven, and two cases, respectively. The median follow-up period was 179 months. Six patients exhibited onset neuropsychologic symptoms, for example, cognitive decline or behavior disorder. We evaluated the intelligence quotient (IQ) in 10 patients and observed significantly lower IQ scores in six patients with neuropsychologic symptoms. Patients with right-sided lesions displayed average IQ levels (median 106), whereas those with left-sided or bilateral lesions had reduced IQ (median 67). A complete response was achieved by primary chemoradiotherapy in all patients. Three patients who underwent focal or whole-ventricle irradiation experienced recurrence, whereas no recurrence was observed in patients who received whole-brain irradiation (WBI). Concerning the neurocognitive outcomes, three and six patients with unilateral right and left lesions were living self-independently (Karnofsky Performance Status [KPS] ≧ 70), whereas the three remaining patients (one with left and two with bilateral lesions) had a dependent status (KPS <70). CONCLUSIONS: WBI is crucial for disease control in BG germinoma. Furthermore, lesion laterality might affect neuropsychologic symptoms including IQ at diagnosis and neurocognitive outcomes in BG germinoma.

Impact of RNF213 p.R4810K variant on postoperative temporal muscle swelling used in encephalo-myo-synangiosis after combined revascularization for Moyamoya disease.
Makoto Mizushima, Masaki Ito, Haruto Uchino, Taku Sugiyama, Miki Fujimura
Neurosurgical review, 48, 1, 15, 15, 31 Dec. 2024, [International Magazine]
English, Scientific journal, Postoperative neurological deterioration due to brain compression by the swollen temporal muscle pedicle used in encephalo-myo-synangiosis (EMS) is a potential complication of combined revascularization for Moyamoya disease (MMD). However, the factors contributing to this phenomenon remain poorly understood. This study aimed to identify factors associated with postoperative temporal muscle swelling following combined revascularization. A total of 37 consecutive combined revascularization using temporal muscle pedicle performed between 2021 and 2023 were analyzed. Postoperative temporal muscle volume was measured through serial CT scans on postoperative days (POD) 0, 1, 7, 14, and 30. Multiple regression analysis was performed to assess factors contributing to swelling, including RNF213 p.R4810K variant, a known genetic risk for Asian MMD. Surgical outcomes and collateral vessel development were also examined. Results showed a significant increase in muscle pedicle volume on POD 1 and 7 across all 37 hemispheres, followed by a marked decrease by POD 30, compared to POD 0. These chronological volume changes were significant in adults (n = 31) but not in pediatric patients (n = 6). Multiple regression analysis identified the RNF213 p.R4810K as sole significant factor positively associated with maximal muscle volume (regression coefficient 0.485, P = 0.0078). Favorable surgical outcomes were achieved in 36 of 37 cases (97.3%) over a mean follow-up of 2.2 years, with indirect collateral development confirmed in 27 adult (87%) and 6 pediatric (100%) hemispheres. Results suggest the RNF213 p.R4810K variant is associated with increased postoperative temporal muscle swelling after combined revascularization, especially in adult MMD patients, indicating a potential genetic influence on this complication.

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, [Domestic magazines]
English, Scientific journal, Moyamoya disease (MMD) is a rare idiopathic cerebrovascular disorder that causes transient ischemic attack (TIA) and ischemic stroke in the pediatric population. Herein, we report an extremely rare case of Moyamoya syndrome (MMS) and late-onset idiopathic aqueduct stenosis, a unique form of non-communicating hydrocephalus. A 17-year-old female presented with an intractable headache and occasional faintness. Pertinent medical history included a fourth ventricle epidermoid cyst without any evidence of aqueduct stenosis, which was surgically removed when she was two years of age. The patient subsequently experienced a TIA and was diagnosed with MMD at 14 years of age. Under the definitive diagnosis of MMS associated with a brain tumor, the patient underwent surgical revascularization of the symptomatic right hemisphere without complications. Although the ischemic symptoms resolved postoperatively, a medically intractable headache with occasional faintness persisted. Serial magnetic resonance imaging ultimately revealed newly developed non-communicating hydrocephalus due to acquired aqueduct stenosis at the age of 17. After careful exclusion of the development of either or both a periventricular anastomosis and vault moyamoya vessels along the surgical route using cerebral angiography, we performed an endoscopic third ventriculostomy (ETV) via the right anterior horn without complications. A complete resolution of her chronic headache with the shrinkage of the third ventriculomegaly was observed postoperatively. In cases of MMS associated with symptomatic aqueduct stenosis, transdural collaterals on the cranial vault and periventricular collaterals should be meticulously evaluated preoperatively using cerebral angiography to safely perform an ETV.

Phase I/II trial of intracerebral transplantation of autologous bone marrow stem cells combined with recombinant peptide scaffold for patients with chronic intracerebral haemorrhage: a study protocol.
Masahito Kawabori, Hideo Shichinohe, Kaoru Kahata, Arisa Miura, Kenichiro Maeda, Yoichi M Ito, Masahiko Mukaino, Ryo Kogawa, Kentaro Nakamura, Shuho Gotoh, Kota Kurisu, Miki Fujimura
BMJ open, 14, 12, e083959, 02 Dec. 2024, [International Magazine]
English, Scientific journal, INTRODUCTION: Intracerebral haemorrhage (ICH) stands as a leading global cause of death and disability, posing a significant challenge with limited treatment options, especially for chronic patients. Recent advances in stem cell therapies have opened new avenues for therapeutic potential. Our previous preclinical research has demonstrated that intracerebral transplantation of bone marrow stromal cells (BMSCs) combined with a recombinant human collagen type I scaffold enables higher cell survival and engraftment and holds promising potential. In this article, we present the protocol for a novel clinical trial, named 'Research on Advanced Intervention using Novel Bone MarrOW stem cells for chronic intracerebral haemorrhage' (RAINBOW-Hx). METHODS AND ANALYSIS: RAINBOW-Hx is a phase I/II, open-label, uncontrolled study with the primary objective of assessing the safety and efficacy of intracerebral transplantation of autologous BMSCs combined with the scaffold (HUFF-01) in patients with chronic ICH. Eight patients, experiencing moderate to severe neurological deficits for 12 months or longer, will be enrolled. The haemorrhage location will be limited to the basal ganglia and thalamus. Approximately 50 mL of bone marrow will be extracted from the iliac bone of each patient, and BMSCs will be cultured using autologous platelet lysate. 3 days before transplantation, BMSCs will be combined with the scaffold to generate HUFF-01. Each patient will receive a 50 000 HUFF-01 dose, containing approximately 50 million BMSCs, through stereotactic transplantation into the haemorrhagic cavity. Neurological assessments, MRI, 18F-fluorodeoxyglucose positron emission tomography and 123I-Iomazenil single-photon emission CT will be performed for 1 year after administration. ETHICS AND DISSEMINATION: The trial protocols were reviewed and approved by the Institutional Review Board of the Hokkaido University Hospital (R5-11), and this study is conducted according to Good Clinical Practice guidelines and the principles of the Declaration of Helsinki. The results of this trial will be submitted for publication in a peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: jRCT2013230053, Japan Registry of Clinical Trials.

The time threshold to reperfusion for DWI reversal in acute ischemic stroke depends on pre-interventional ADC value
Soichiro Takamiya, Daisuke Oura, Riku Ihara, Yoshimasa Niiya, Koji Furukawa, Masayuki Gekka, Asuka Nakazaki, Miki Fujimura
Neuroradiology, 66, 12, 2205, 2213, Dec. 2024
Scientific journal

The time threshold to reperfusion for DWI reversal in acute ischemic stroke depends on pre-interventional ADC value.
Soichiro Takamiya, Daisuke Oura, Riku Ihara, Yoshimasa Niiya, Koji Furukawa, Masayuki Gekka, Asuka Nakazaki, Miki Fujimura
Neuroradiology, 66, 12, 2205, 2213, Dec. 2024, [International Magazine]
English, Scientific journal, PURPOSE: The aims of this study are to explore the apparent diffusion coefficient (ADC)-dependent thresholds for time to reperfusion in reversible lesions following mechanical thrombectomy for acute ischemic stroke, and to investigate the associated risks of hemorrhagic transformation. METHODS: We conducted a retrospective case-control study, enrolling patients with large-vessel occlusion who underwent mechanical thrombectomy in Otaru General Hospital from 2016 to 2021. Reversible lesions were identified using volumetric ADC data, and the mean time from image to reperfusion (TIR) in each ADC range was compared between groups with and without reversible lesions, as well as those with and without parenchymal hematoma. The Wilcoxon rank sum test and chi-square test were used for comparison between two groups, and receiver operating characteristic curves were created to determine optimal thresholds. RESULTS: Seventy-five patients were included and 581 volumetric data were obtained. The mean TIR in the group with reversible lesions was shorter than in that without, and time thresholds were 131, 123 and 112 min for ADC values > 540 × 10-6, 500-540 × 10-6 and 440-500 × 10-6 mm2/s, respectively. Furthermore, in patients with parenchymal hematoma, the mean TIR was significantly longer, and the average ADC value was significantly lower than those without hematoma. CONCLUSION: The time thresholds for the irreversible ischemic core may vary depending on the ADC value, and they may be shorter when the ADC value is lower. Moreover, both the low ADC value and the late reperfusion might be associated with an increased risk of parenchymal hematoma.

Preoperative Predictors of Foramen Magnum Decompression with Dural Splitting for Amelioration of Syringomyelia Associated with Chiari Type 1 Malformation.
Soichiro Takamiya, Ikuma Echizenya, Kazuyoshi Yamazaki, Motoyuki Iwasaki, Syunsuke Yano, Toshitaka Seki, Kazutoshi Hida, Miki Fujimura
World neurosurgery, 191, e567-e574, Nov. 2024, [International Magazine]
English, Scientific journal, OBJECTIVE: Among several procedures for syringomyelia associated with Chiari type 1 malformation (CM-1), foramen magnum decompression (FMD) with dural splitting is one of the treatment choices with low complication rates. However, some meta-analyses have suggested that FMD with dural splitting may be inferior to FMD with duraplasty based on clinical outcomes; therefore, a predictor of a good surgical outcome with dural splitting is essential. This study aimed to clarify the preoperative parameters for good outcomes in patients with FMD with dural splitting, including the volumetric perspective. METHODS: We reviewed the cases of patients diagnosed with CM-1 and syringomyelia who underwent FMD with dural splitting at our institution. We included patients who underwent magnetic resonance imaging from 6 months to 1 year after surgery and measured radiological parameters using preoperative computed tomography and preoperative/follow-up magnetic resonance imaging. RESULTS: Thirty-one patients were enrolled. Among all radiological parameters, the volume of the herniated tonsils (Vtonsil) in improved group was significantly smaller, and the difference between the expected volume increment and Vtonsil (Vincr-Vtonsil) in improved group was significantly larger than those in non-improved group. To predict the improvement of the syrinx, Vincr-Vtonsil of 0.77 mL was the optimal cutoff value and yielded 100% sensitivity and 48.0% specificity. CONCLUSIONS: Vtonsil and Vincr-Vtonsil, which are novel predictors based on the volumetric perspective, might be the optimal predictors for improvement of the syrinx associated with CM-1 by 1 year after surgery.

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

[Endovascular Treatment of Delayed Cerebral Vasospasms].
Kota Kurisu, Yusuke Shimoda, Toshiya Osanai, Miki Fujimura
No shinkei geka. Neurological surgery, 52, 5, 1023, 1030, Sep. 2024, [Domestic magazines]
Japanese, Scientific journal, Delayed cerebral vasospasm is a major complication following subarachnoid hemorrhage and a primary cause of delayed cerebral ischemia. While various preventive treatments exist, some patients still develop severe vasospasm, highlighting the need for better rescue therapies. This article explores endovascular treatment as a rescue option for vasospasm, focusing on the clinical characteristics and roles of intra-arterial vasodilator injection therapy and percutaneous transluminal angioplasty(PTA). Despite a lack of strong evidence from large clinical trials, advancements in endovascular technology have positioned both intra-arterial vasodilator injection therapy and PTA as promising and safe rescue options for severe vasospasm. Careful selection of the appropriate approach is crucial for achieving optimal clinical outcomes, considering the unique characteristics, advantages, and limitations of each method. Further clinical trials are necessary to definitively confirm this hypothesis.

[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.

Moyamoya syndrome after proton beam therapy in a pediatric patient with a pineal germ cell tumor and a germline polymorphism in RNF213.
Ting-Chun Lin, Haruto Uchino, Masaki Ito, Shigeru Yamaguchi, Yukitomo Ishi, Miki Fujimura
Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery, 40, 11, 3873, 3878, 21 Aug. 2024, [International Magazine]
English, Scientific journal, The effects of RNF213, which leads to moyamoya disease susceptibility, on radiation-induced moyamoya syndrome (MMS) remain unknown. We report a case of MMS after proton beam therapy (PBT) was deployed to treat a brain tumor in a patient with an RNF213 polymorphism. An 8-year-old boy underwent whole ventricular and local PBT for a pineal germ cell tumor and was diagnosed with radiation-induced MMS 9 months later. He underwent right and left revascularization surgeries for cerebral hemodynamic compromise at 17- and 18-years of age, respectively. Genetic analysis revealed a heterozygous germline polymorphism RNF213 p.R4810K. This is the first report to suggest an association between RNF213 polymorphism and radiation-induced MMS.

Artificial Intelligence for Patient Safety and Surgical Education in Neurosurgery
Taku Sugiyama, Hiroyuki Sugimori, Mighui Tang, Miki Fujimura
JMA Journal, 8, 1, 76, 85, Aug. 2024, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, Neurosurgery has evolved alongside technological innovations; however, these advances have also introduced greater complexity into clinical practice. Neurosurgery remains a demanding and high-risk field that requires a broad range of skills. Artificial intelligence (AI) has immense potential in neurosurgery given its ability to rapidly analyze large volumes of clinical data generated in modern clinical environments. An expanding body of literature has demonstrated that AI enhances various aspects of neurosurgery, including diagnostics, prognostication, decision-making, data management, education, and clinical studies. AI applications are expected to reduce medical errors and costs, broaden healthcare accessibility, and ultimately boost patient safety and surgical education. Nevertheless, AI application in neurosurgery remains practically limited because of several challenges, such as the diversity and volume of clinical training data collection, concerns regarding data quality, algorithmic bias, transparency (explainability and interpretability), ethical issues, and regulatory implications. To comprehensively discuss the potential benefits, future directions, and limitations of AI in neurosurgery, this review examined recent studies on AI technology and its applications in this field, focusing on intraoperative decision support and surgical education.

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, 190, e153-e157, 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.

血行再建に残された課題 CEAにおける患者安全と外科教育のための手術映像分析研究 頸動脈剥離における組織加速度評価　　　　　　　　　　　　　　　
杉山 拓, 伊東 雅基, 杉森 博行, 唐 明輝, 中村 俊孝, 小笠原 克彦, 藤村 幹
The Mt. Fuji Workshop on CVD, 41, 76,82, 83, The Mt. Fuji Workshop on CVD事務局, Jul. 2024
Japanese

Clinical outcome, radiological findings, and genetic features of IDH-mutant brainstem glioma in adults
Sogo Oki, Yukitomo Ishi, Ryosuke Sawaya, Michinari Okamoto, Hiroaki Motegi, Zen-ichi Tanei, Masumi Tsuda, Takashi Mori, Kentaro Nishioka, Hiromi Kanno-Okada, Hidefumi Aoyama, Shinya Tanaka, Shigeru Yamaguchi, Miki Fujimura
ACTA NEUROCHIRURGICA, 166, 1, 263, 263, 12 Jun. 2024, [International Magazine]
English, Scientific journal

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, 64, 7, 272, 277, 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.

Intranasal administration of stem cell-derived exosomes for central nervous system diseases.
Shuho Gotoh, Masahito Kawabori, Miki Fujimura
Neural regeneration research, 19, 6, 1249, 1255, 01 Jun. 2024, [International Magazine]
English, Scientific journal, Exosomes, lipid bilayer-enclosed small cellular vesicles, are actively secreted by various cells and play crucial roles in intercellular communication. These nanosized vesicles transport internalized proteins, mRNA, miRNA, and other bioactive molecules. Recent findings have provided compelling evidence that exosomes derived from stem cells hold great promise as a therapeutic modality for central nervous system disorders. These exosomes exhibit multifaceted properties including anti-apoptotic, anti-inflammatory, neurogenic, and vasculogenic effects. Furthermore, exosomes offer several advantages over stem cell therapy, such as high preservation capacity, low immunogenicity, the ability to traverse the blood-brain barrier, and the potential for drug encapsulation. Consequently, researchers have turned their attention to exosomes as a novel therapeutic avenue. Nonetheless, akin to the limitations of stem cell treatment, the limited accumulation of exosomes in the injured brain poses a challenge to their clinical application. To overcome this hurdle, intranasal administration has emerged as a non-invasive and efficacious route for delivering drugs to the central nervous system. By exploiting the olfactory and trigeminal nerve axons, this approach enables the direct transport of therapeutics to the brain while bypassing the blood-brain barrier. Notably, exosomes, owing to their small size, can readily access the nerve pathways using this method. As a result, intranasal administration has gained increasing recognition as an optimal therapeutic strategy for exosome-based treatments. In this comprehensive review, we aim to provide an overview of both basic and clinical research studies investigating the intranasal administration of exosomes for the treatment of central nervous system diseases. Furthermore, we elucidate the underlying therapeutic mechanisms and offer insights into the prospect of this approach.

Pre- and post-operative semicircular canal function evaluated by video head impulse test in patients with vestibular schwannoma.
Keishi Fujiwara, Shinya Morita, Hiroaki Motegi, Shigeru Yamaguchi, Yukitomo Ishi, Kimiko Hoshino, Atsushi Fukuda, Makoto Kobayashi, Yuji Nakamaru, Miki Fujimura, Akihiro Homma
Auris, nasus, larynx, 51, 3, 542, 547, Jun. 2024, [International Magazine]
English, Scientific journal, OBJECTIVES: To evaluate pre- and post-operative semicircular canal function in patients with vestibular schwannoma (VS) by the video Head Impulse Test (vHIT). METHODS: Nineteen patients with VS who underwent surgery were enrolled in this study. The gain in vestibulo-ocular reflex (VOR) and the degree of scatter in catch-up saccades were examined pre- and post-operatively for the semicircular canals in VS patients. RESULTS: Ten of 19 cases (52.6 %) with VS were defined as demonstrating both superior vestibular nerve (SVN) and inferior vestibular nerve (IVN) impairment from the results of pre-operative vHIT. Hearing level and subjective vestibular symptoms showed significant correlations with pre-operative semicircular canal function. Compared to pre-operative vHIT results, VOR gains within 1 month after surgery were significantly reduced in all three canals; however, significant differences had disappeared in the anterior and posterior semicircular canals at 6 months after surgery. Cases of unknown origin had a significantly greater reduction in posterior semicircular canal function after surgery compared with those with disease of IVN origin. CONCLUSIONS: As vHIT could evaluate pre-operative vestibular nerve impairment, post-operative VOR gain reduction and the degree of vestibular compensation, semicircular canal function evaluated by vHIT provides a good deal of useful information regarding VS patients undergoing surgery compared to caloric testing, and vHIT should be performed pre- and post-operatively for patients with VS.

Moyamoya Vasculopathy and Moyamoya-Related Systemic Vasculopathy: A Review With Histopathological and Genetic Viewpoints.
Takeo Abumiya, Miki Fujimura
Stroke, 55, 6, 1699, 1706, Jun. 2024, [International Magazine]
English, Scientific journal, Systemic vasculopathy has occasionally been reported in cases of moyamoya disease (MMD). Since the pathological relationship between moyamoya vasculopathy (MMV) and moyamoya-related systemic vasculopathy (MMRSV) remains unclear, it was examined herein by a review of histopathologic studies in consideration of clinicopathological and genetic viewpoints. Although luminal stenosis was a common finding in MMV and MMRSV, histopathologic findings of vascular remodeling markedly differed. MMV showed intimal hyperplasia, marked medial atrophy, and redundant tortuosity of the internal elastic lamina, with outer diameter narrowing called negative remodeling. MMRSV showed hyperplasia, mainly in the intima and sometimes in the media, with disrupted stratification of the internal elastic lamina. Systemic vasculopathy has also been observed in patients with non-MMD carrying the RNF213 (ring finger protein 213) mutation, leading to the concept of RNF213 vasculopathy. RNF213 vasculopathy in patients with non-MMD was histopathologically similar to MMRSV. Cases of MMRSV have sometimes been diagnosed with fibromuscular dysplasia. Fibromuscular dysplasia is similar to MMD not only in the histopathologic findings of MMRSV but also from clinicopathological and genetic viewpoints. The significant histopathologic difference between MMV and MMRSV may be attributed to a difference in the original vascular wall structure and its resistance to pathological stress between the intracranial and systemic arteries. To understand the pathogeneses of MMD and MMRSV, a broader perspective that includes RNF213 vasculopathy and fibromuscular dysplasia as well as an examination of the 2- or multiple-hit theory consisting of genetic factors, vascular structural conditions, and vascular environmental factors, such as blood immune cells and hemodynamics, are needed.

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, 180, 180, Springer Science and Business Media LLC, 16 Apr. 2024, [International Magazine]
English, Scientific journal, PURPOSE: The systemic immune-inflammation index (SII), a marker of systemic inflammation, can be calculated using peripheral blood tests. Although the SII has been reported as a feasible biomarker in various cerebrovascular diseases, no studies have explored in dural arteriovenous fistula (DAVF). A retrospective cohort study was performed to test whether the SII reflects the clinical characteristics of DAVF and whether this index could serve as a feasible biomarker. METHODS: This study included 28 patients who underwent endovascular treatment (39 sessions) for DAVF between 2014 and 2023. The SII was calculated using the following formula: platelet count multiplied by neutrophil count divided by lymphocyte count. We investigated the correlation between the SII and various clinical characteristics of DAVF, including symptom manifestation, and digital subtraction angiography findings. Additionally, we compared pre- and post-endovascular treatment changes in the SII. RESULTS: A significantly higher SII was observed in patients with multiple lesions, clinical symptoms (particularly aggressive symptoms), pseudophelebitic pattern (PPP), and sinus occlusion. Multivariate regression analysis revealed that the presence of symptoms (coefficient 270.9, P = 0.021) and PPP (coefficient 272.4, P = 0.017) were independent factors contributing to SII elevation. Notably, following endovascular treatment, there was a significant decrease in the elevated SII in patients whose symptoms resolved (P = 0.039) and where the DAVF was angiographically cured (P = 0.012). CONCLUSION: Elevation of the SII in patients with advanced DAVF and its decrease following endovascular treatment suggests that the SII reflects the disease condition and indicates its potential as a promising biomarker.

Efficacy of Mobile Telemedicine System for Digital Subtraction Angiography of Moyamoya Disease Compared with Picture Archiving and Communication System.
Toshiya Osanai, Haruto Uchino, Masaki Ito, Miki Fujimura
JMA journal, 7, 2, 282, 285, 15 Apr. 2024, [Domestic magazines]
English, 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.

Intranasal Administration of Mesenchymal Stem Cell-Derived Exosome Alleviates Hypoxic-Ischemic Brain Injury.
Takuma Ikeda, Masahito Kawabori, Yuyuan Zheng, Sho Yamaguchi, Shuho Gotoh, Yo Nakahara, Erika Yoshie, Miki Fujimura
Pharmaceutics, 16, 4, 23 Mar. 2024, [International Magazine]
English, Scientific journal, Hypoxic-ischemic brain injury arises from inadequate oxygen delivery to the brain, commonly occurring following cardiac arrest, which lacks effective treatments. Recent studies have demonstrated the therapeutic potential of exosomes released from mesenchymal stem cells. Given the challenge of systemic dilution associated with intravenous administration, intranasal delivery has emerged as a promising approach. In this study, we investigate the effects of intranasally administered exosomes in an animal model. Exosomes were isolated from the cell supernatants using the ultracentrifugation method. Brain injury was induced in Sprague-Dawley rats through a transient four-vessel occlusion model. Intranasal administration was conducted with 3 × 108 exosome particles in 20 µL of PBS or PBS alone, administered daily for 7 days post-injury. Long-term cognitive behavioral assessments, biodistribution of exosomes, and histological evaluations of apoptosis and neuroinflammation were conducted. Exosomes were primarily detected in the olfactory bulb one hour after intranasal administration, subsequently distributing to the striatum and midbrain. Rats treated with exosomes exhibited substantial improvement in cognitive function up to 28 days after the insult, and demonstrated significantly fewer apoptotic cells along with higher neuronal cell survival in the hippocampus. Exosomes were found to be taken up by microglia, leading to a decrease in the expression of cytotoxic inflammatory markers.

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.), 5, 5, 432, 444, 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, 64, 5, 197, 204, 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.

Increased CD44 expression in primary meningioma: its clinical significance and association with peritumoral brain edema.
Ryosuke Sawaya, Shigeru Yamaguchi, Yukitomo Ishi, Michinari Okamoto, Sumire Echizenya, Hiroaki Motegi, Noriyuki Fujima, Miki Fujimura
Journal of neurosurgery, 141, 1, 1, 8, 09 Feb. 2024, [International Magazine]
English, Scientific journal, OBJECTIVE: CD44 is a major cell surface receptor involved in cell adhesion and migration. The overexpression of CD44 is a poor prognostic factor in many neoplasms, including meningiomas. The aim of this study was to investigate the association between CD44 gene expression and clinical signatures of primary meningiomas. METHODS: CD44 gene expression was quantitatively evaluated by snap freezing tumor tissues obtained from 106 patients with primary meningioma. The relationships between CD44 expression and clinical signatures of meningiomas, including histological malignancy, tumor volume, and peritumoral brain edema (PTBE), were analyzed. PTBE was assessed using the Steinhoff classification (SC) system (from SC 0 to SC III). RESULTS: CD44 gene expression in WHO grade 2 and 3 meningiomas was significantly higher than that in grade 1 meningiomas. In addition, CD44 expression increased with the severity of PTBE. Particularly, among the grade 1 meningiomas or small-sized tumors (maximum tumor diameter < 43 mm), CD44 expression in tumors with severe PTBE (SC II or III) was significantly higher than that in tumors without or with mild PTBE (SC 0 or I). Multivariate logistic regression analysis also revealed that overexpression of CD44 was an independent significant factor of severe PTBE development in primary meningiomas. CONCLUSIONS: In addition to tumor cell aggressiveness, CD44 expression promotes the development of PTBE in meningioma. Since PTBE is a strong factor of tumor-related epilepsy or cognitive dysfunction in patients with meningioma, CD44 is thus a potential therapeutic target in meningioma with PTBE.

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, 81, 2, 154, 162, 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.

Deep learning-based video-analysis of instrument motion in microvascular anastomosis training.
Taku Sugiyama, Hiroyuki Sugimori, Minghui Tang, Yasuhiro Ito, Masayuki Gekka, Haruto Uchino, Masaki Ito, Katsuhiko Ogasawara, Miki Fujimura
Acta neurochirurgica, 166, 1, 6, 6, 12 Jan. 2024, [International Magazine]
English, Scientific journal, PURPOSE: Attaining sufficient microsurgical skills is paramount for neurosurgical trainees. Kinematic analysis of surgical instruments using video offers the potential for an objective assessment of microsurgical proficiency, thereby enhancing surgical training and patient safety. The purposes of this study were to develop a deep-learning-based automated instrument tip-detection algorithm, and to validate its performance in microvascular anastomosis training. METHODS: An automated instrument tip-tracking algorithm was developed and trained using YOLOv2, based on clinical microsurgical videos and microvascular anastomosis practice videos. With this model, we measured motion economy (procedural time and path distance) and motion smoothness (normalized jerk index) during the task of suturing artificial blood vessels for end-to-side anastomosis. These parameters were validated using traditional criteria-based rating scales and were compared across surgeons with varying microsurgical experience (novice, intermediate, and expert). The suturing task was deconstructed into four distinct phases, and parameters within each phase were compared between novice and expert surgeons. RESULTS: The high accuracy of the developed model was indicated by a mean Dice similarity coefficient of 0.87. Deep learning-based parameters (procedural time, path distance, and normalized jerk index) exhibited correlations with traditional criteria-based rating scales and surgeons' years of experience. Experts completed the suturing task faster than novices. The total path distance for the right (dominant) side instrument movement was shorter for experts compared to novices. However, for the left (non-dominant) side, differences between the two groups were observed only in specific phases. The normalized jerk index for both the right and left sides was significantly lower in the expert than in the novice groups, and receiver operating characteristic analysis showed strong discriminative ability. CONCLUSION: The deep learning-based kinematic analytic approach for surgical instruments proves beneficial in assessing performance in microvascular anastomosis. Moreover, this methodology can be adapted for use in clinical settings.

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, 40, 5, 1603, 1607, 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.

Adult Moyamoya Disease and Moyamoya Syndrome: What Is New?
Shinichiro Uchiyama, Miki Fujimura
Cerebrovascular diseases extra, 14, 1, 86, 94, 2024, [International Magazine]
English, Scientific journal, BACKGROUND: Recent advances are in the genetics, diagnosis, pathophysiology, and management of moyamoya disease (MMD), and moyamoya syndrome (MMS), a term used to describe moyamoya-like vasculopathy associated with various systemic diseases or conditions. SUMMARY: Ring finger protein (RNF213) has been reported to be a susceptibility gene not only for MMD but also for atherosclerotic intracranial arterial stenosis and ischemic stroke attributable to large artery atherosclerosis. The latest guidelines by the Research Committee on MMD of the Japanese Ministry of Health, Labor, and Welfare, removed limitations of the previous definition that required bilateral involvement of the intracranial carotid artery to make the diagnosis, given the increasing evidence of progression to bilateral involvement in unilateral MMD. 3-dimensional constructive interference in steady-state MRI is useful for the differential diagnosis of MMD from atherosclerosis. Recent advances in the pathophysiology of MMD suggest that genetic and environmental factors play important roles in vascular angiogenesis and remodeling via complex mechanisms. The latest Japanese Guidelines and American Scientific Statement described that antiplatelet therapy can be considered reasonable. Endovascular interventional stent placement fails to prevent ischemic events and does not halt MMD progression. In the Japan Adult Moyamoya trial, a randomized controlled trial for bilateral extracranial-intracranial direct bypass versus conservative therapy in patients with MMD, who had intracranial hemorrhage, recurrent bleeding, completed stroke, or crescendo transient ischemic attack was significantly fewer with direct bypass than with conservative care. KEY MESSAGES: This review presents updated information on genetics, diagnosis, pathophysiology, and treatment of adult MMD and MMS. Despite recent advances, many mysteries still exist in the etiologies of moyamoya vasculopathy. The diagnostic criteria and treatment guidelines have been updated but not yet been globally established. Ongoing and future studies investigating underlying pathophysiological mechanisms of MMD and MMS may clarify potentially effective medical, surgical, or endovascular treatments.

A Case of Rivaroxaban-induced Hematomyelia of Thoracic Spinal Cord in Patient with Acute Renal Failure.
Motoyuki Iwasaki, Ikuma Echizenya, Miki Fujimura
NMC case report journal, 11, 207, 211, 2024, [Domestic magazines]
English, Scientific journal, Hematomyelia associated with direct oral anticoagulants (DOACs) is rare. In this report, a case of a 78-year-old male with paraplegia due to hematomyelia after medication of rivaroxaban, which is the first case in which acute renal failure is closely associated with the onset and underwent surgical evacuation is presented. The patient was initially misdiagnosed as a spinal cord infarction, and appropriate therapeutic intervention was not provided. One year later, the patient's symptoms did not improve, he is dependent on a wheelchair for daily activities, and cystostomy was performed. During administration of DOACs, hemorrhagic lesion should be strongly suspected in a patient with acute renal failure.

Identifying G6PC3 as a Potential Key Molecule in Hypoxic Glucose Metabolism of Glioblastoma Derived from the Depiction of 18F-Fluoromisonidazole and 18F-Fluorodeoxyglucose Positron Emission Tomography.
Michinari Okamoto, Shigeru Yamaguchi, Ryosuke Sawaya, Sumire Echizenya, Yukitomo Ishi, Sadahiro Kaneko, Hiroaki Motegi, Takuya Toyonaga, Kenji Hirata, Miki Fujimura
BioMed research international, 2024, 2973407, 2973407, 2024, [Peer-reviewed], [International Magazine]
English, Scientific journal, PURPOSE: Glioblastoma is the most aggressive primary brain tumor, characterized by its distinctive intratumoral hypoxia. Sequential preoperative examinations using fluorine-18-fluoromisonidazole (18F-FMISO) and fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) could depict the degree of glucose metabolism with hypoxic condition. However, molecular mechanism of glucose metabolism under hypoxia in glioblastoma has been unclear. The aim of this study was to identify the key molecules of hypoxic glucose metabolism. METHODS: Using surgically obtained specimens, gene expressions associated with glucose metabolism were analyzed in patients with glioblastoma (n = 33) who underwent preoperative 18F-FMISO and 18F-FDG PET to identify affected molecules according to hypoxic condition. Tumor in vivo metabolic activities were semiquantitatively evaluated by lesion-normal tissue ratio (LNR). Protein expression was confirmed by immunofluorescence staining. To evaluate prognostic value, relationship between gene expression and overall survival was explored in another independent nonoverlapping clinical cohort (n = 17) and validated by The Cancer Genome Atlas (TCGA) database (n = 167). RESULTS: Among the genes involving glucose metabolic pathway, mRNA expression of glucose-6-phosphatase 3 (G6PC3) correlated with 18F-FDG LNR (P = 0.03). In addition, G6PC3 mRNA expression in 18F-FMISO high-accumulated glioblastomas was significantly higher than that in 18F-FMISO low-accumulated glioblastomas (P < 0.01). Protein expression of G6PC3 was consistent with mRNA expression, which was confirmed by immunofluorescence analysis. These findings indicated that the G6PC3 expression might be facilitated by hypoxic condition in glioblastomas. Next, we investigated the clinical relevance of G6PC3 in terms of prognosis. Among the glioblastoma patients who received gross total resection, mRNA expressions of G6PC3 in the patients with poor prognosis (less than 1-year survival) were significantly higher than that in the patients who survive more than 3 years. Moreover, high mRNA expression of G6PC3 was associated with poor overall survival in glioblastoma, as validated by TCGA database. CONCLUSION: G6PC3 was affluently expressed in glioblastoma tissues with coincidentally high 18F-FDG and 18F-FMISO accumulation. Further, it might work as a prognostic biomarker of glioblastoma. Therefore, G6PC3 is a potential key molecule of glucose metabolism under hypoxia in glioblastoma.

Clinical outcomes for olfactory neuroblastoma.
Akira Nakazono, Hiroaki Motegi, Masanobu Suzuki, Yuji Nakamaru, Shigeru Yamaguchi, Yukitomo Ishi, Satoshi Kano, Nayuta Tsushima, Aya Honma, Takayoshi Suzuki, Shogo Kimura, Seijiro Hamada, Jun Taguchi, Yasushi Shimizu, Takashi Mori, Koichi Yasuda, Hidefumi Aoyama, Ichiro Kinoshita, Miki Fujimura, Akihiro Homma
Frontiers in oncology, 14, 1329572, 1329572, 2024, [International Magazine]
English, Scientific journal, BACKGROUND: Olfactory neuroblastoma (ONB) is a rare malignant tumor arising from the olfactory neuroepithelium. The standard of care for ONB is surgical resection; however, detailed treatment protocols vary by institution. Our treatment protocol consists of endoscopic skull base surgery (ESBS) for endoscopically resectable cases and induction chemotherapy followed by craniotomy combined with ESBS for locally advanced cases, with postoperative radiotherapy performed for all cases. Chemoradiotherapy (CRT) is performed in unresectable cases. In this study, we evaluate our treatment protocol and outcomes for ONB. METHODS: A retrospective review of patients with ONB was conducted. Outcomes included survival outcomes and perioperative data. RESULTS: Fifteen patients (53.6%) underwent ESBS, 12 (42.9%) underwent craniotomy combined with ESBS, and 1 (3.6%) received CRT. The 5- and 10-year overall survival rates for all patients were 92.9% and 82.5%, respectively, with a median follow-up period of 81 months. The 5- and 10-year disease-free survival rates were 77.3% and 70.3%, respectively, and the 5- and 10-year local control rates were 88.2% and 80.2%, respectively. Patients undergoing ESBS demonstrated a significantly shorter operating time, period from operation to ambulation, hospitalization period, and less blood loss than those undergoing craniotomy combined with ESBS. CONCLUSION: Our treatment protocol was found to afford favorable outcomes. Patients who underwent endoscopic resection showed lower complication rates and better perioperative data than those who underwent craniotomy combined with ESBS. With appropriate case selection, ESBS is considered a useful approach for ONB.

The Capacitated Maximal Covering Location Problem Improves Access to Stroke Treatment: A Cross-Sectional Simulation Study.
Kyohei Bando, Kazuki Ohashi, Kensuke Fujiwara, Toshiya Osanai, Yasuhiro Morii, Takumi Tanikawa, Miki Fujimura, Katsuhiko Ogasawara
Health services insights, 17, 11786329241263699, 11786329241263699, 2024, [International Magazine]
English, Scientific journal, Disparities in accessing advanced stroke treatment have been recognized as a policy challenge in multiple countries, including Japan, necessitating priority solutions. Nevertheless, more practical healthcare policies must be implemented due to the limited availability of healthcare staff and financial resources in most nations. This study aimed to evaluate the supply and demand balance of mechanical thrombectomy (MT) and identify areas with high priority for enhancing stroke centers. The target area of this study was Hokkaido, Japan. We adopted the capacitated maximal covering location problem (CMCLP) to propose an optimal allocation without increasing the number of medical facilities. Four realistic scenarios with varying levels of total MT supply capacity for Primary stroke centers and assuming a range of 90 minutes by car from the center were created and simulated. From scenarios 1 to 4, the coverage increased by approximately 53% to 85%, scenarios 2 and 3 had 5% oversupply, and scenario 4 had an oversupply of approximately 20%. When the supply capacity cap was eliminated and 8 PSCs received 31 or more patients, they became priority enhancement targets. The CMCLP estimates demand coverage considering the supply and demand balance and indicates areas and facilities where MT supply capacity enhancement is a priority.

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, 64, 3, 108, 115, Japan Neurosurgical Society, 2024, [Domestic magazines]
English, Scientific journal, The opportunity to treat older patients with Moyamoya disease (MMD) is increasing. However, the surgical outcomes after combined direct and indirect revascularization for elderly patients with MMD are not fully understood, especially for those ≥60 years old. This retrospective study examined 232 consecutive hemispheres of 165 adults with MMD who underwent combined revascularization. Clinical features and surgical outcomes were compared between the elderly (≥60 years) and nonelderly group (<60 years). Thirteen (5.6%, 64.4 ± 4.0 years old) and 219 hemispheres (94.4%, 40.2 ± 10.8 years old) were included in the elderly and nonelderly group, respectively. The proportion of clinical presentations before surgery did not differ. However, the prevalence of hypertension and hyperlipidemia was significantly higher in the elderly group than in the nonelderly group. Meanwhile, hyperthyroidism was observed only in the nonelderly group. No significant intergroup differences were observed in the incidence of perioperative complications occurring within four weeks postsurgery. Notably, the elderly group was more prone to develop perioperative intracerebral hemorrhage (odds ratio (OR) 3.14, 95% confidence interval (CI) 0.45-13.5) than the nonelderly group. During a median follow-up period of 7.8 years, the incidence of stroke recurrence occurring later than four weeks postsurgery was not significantly different between the groups (hazard ratio, 1.19; 95% CI 0.133-10.6). The prevalence of independent outcomes (76.9% vs. 90.4%, P = 0.14) and mortality (7.7% vs. 1.4%, P = 0.21) did not differ significantly between the elderly and nonelderly groups, respectively. Perioperative intracerebral hemorrhage may be common in the elderly and should be considered to achieve a favorable surgical outcome.

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, [Domestic magazines]
English, Scientific journal, During microvascular decompression (MVD) for trigeminal neuralgia (TGN), the mastoid emissary veins (MEV) are routinely sacrificed using the suboccipital retrosigmoid approach. The technical nuances when the MEV is an important collateral venous pathway for the obstructive internal jugular vein (IJV) have not been described thus far. Herein, we demonstrate for the first time a modified surgical technique for MVD to preserve the MEV. A 62-year-old man with a 10-year history of TGN refractory to carbamazepine was referred to our hospital for MVD. Preoperative imaging revealed that the superior cerebellar artery was the offending vessel. Computed tomography angiography also revealed that his contralateral IJV pathway was hypoplastic, and the ipsilateral pathway was severely stenosed by the external compression of the elongated styloid process and the transverse process of the first cervical vertebra. The ipsilateral MEV and the connecting occipital veins were enlarged as the sole collateral pathways of intracranial venous drainage. A modified MVD technique, including an upside-down L-shaped skin incision, layer-by-layer dissection of the occipital muscles, and denuding of the intraosseous part of the MEV, was used to cure the TGN with the preservation of the venous pathway. After surgery, the pain completely diminished without any complications. In conclusion, such technical modifications would be applicable in cases where the MEV needs to be preserved during posterior fossa surgery. Preoperative screening of the venous system is also recommended.

Neuroprotective effects of a hemoglobin-based oxygen carrier (stroma-free hemoglobin nanoparticle) on ischemia reperfusion injury
Ryota Tatezawa, Takeo Abumiya, Yasuhiro Ito, Masayuki Gekka, Wataru Okamoto, Kohta Ishii, Natsumi Kohyama, Teruyuki Komatsu, Miki Fujimura
Brain Research, 1821, 148592, 148592, 15 Dec. 2023, [International Magazine]
English, Scientific journal

Neuroprotective effects of a hemoglobin-based oxygen carrier (stroma-free hemoglobin nanoparticle) on ischemia reperfusion injury.
Ryota Tatezawa, Takeo Abumiya, Yasuhiro Ito, Masayuki Gekka, Wataru Okamoto, Kohta Ishii, Natsumi Kohyama, Teruyuki Komatsu, Miki Fujimura
Brain research, 1821, 148592, 148592, 15 Dec. 2023, [International Magazine]
English, Scientific journal, The application of hemoglobin (Hb)-based oxygen carriers (HBOCs) to the treatment of cerebral ischemia has been investigated. A cluster of 1 Hb and 3 human serum albumins (Hb-HSA3) was found to exert neuroprotective effects on ischemia/reperfusion injury. Stroma-free hemoglobin nanoparticles (SFHbNP), a subsequently developed HBOC consisting of a spherical polymerized stroma-free Hb core with a HSA shell, contains the natural antioxidant enzyme catalase and, thus, is expected to exert additive effects. We herein investigated whether SFHbNP exerted enhanced neuroprotective effects in a rat transient middle cerebral artery occlusion (tMCAO) model. Rats were subjected to 2-hour tMCAO and divided into the following 3 groups with the intravenous administration of the respective reagents: (1) phosphate-buffered saline (PBS), as a vehicle (2) Hb-HSA3, and (3) SFHbNP. After 24-hour reperfusion, infarct and edema volumes decreased in the order of the PBS, Hb-HSA3, and SFHbNP groups, with a significant difference (p < 0.05) between the PBS and SFHbNP groups. Similar reductions were observed in oxidative stress, leukocyte recruitment, and blood-brain barrier disruption in the order of the PBS, Hb-HSA3, and SFHbNP groups. In the early phase of reperfusion within 6 h, microvascular HBOC perfusion and cerebral blood flow were maintained at high levels during the reperfusion period in the Hb-HSA3 and SFHbNP groups. However, a difference was observed in tissue oxygen partial pressure levels, which significantly decreased after 6-hour reperfusion in the Hb-HSA3 group, but remained high in the SFHbNP group. A superior oxygen transport ability appears to be related to the enhanced neuroprotective effects of SFHbNP.

Predictors indicating the continuous need for a knee-ankle-foot orthosis in stroke patients at 1 month after onset.
Naohide Tsujimoto, Hiroaki Abe, Toru Okanuka, Takashi Seki, Miki Fujimura
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association, 32, 12, 107425, 107425, Dec. 2023, [International Magazine]
English, Scientific journal, OBJECTIVES: To investigate predictors indicating the continuous need for a knee-ankle-foot orthosis (KAFO) at 1 month after stroke onset in patients who cannot walk without a KAFO in the acute period. MATERIALS AND METHODS: We enrolled patients with severe hemiplegia (n = 139) who were unable to walk without a KAFO on day 10 from stroke onset. The patients were divided into two groups depending on the need for a KAFO at 1 month after the onset: the KAFO group and non-KAFO group. Logistic regression analysis was used to identify predictors of the continuous need for a KAFO at 1 month after stroke onset. In addition, significant predictors were analyzed using receiver operating characteristic curves. RESULTS: The number of patients in the KAFO group and non-KAFO group was 72 (51.8 %) and 67 (48.2 %), respectively. Motor deficit, sensation disorder, severity of pusher syndrome, and body mass index were identified as predictors of the continuous need for a KAFO. Moreover, active range of motion of knee extension on the affected side was found to have the highest predictive ability, with an area under the receiver operating characteristic curve of 0.89 (95 % confidence interval, 0.83-0.94). CONCLUSIONS: In this study, multiple factors were associated with the continuous need for a KAFO at 1 month after stroke onset. In particular, active range of motion of knee extension on the affected side is suggested to be a highly accurate predictor for the need for a KAFO in the subacute phase.

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

Recent Management Option for Hemorrhagic Stroke during Direct Oral Anticoagulant Therapy.
Miki Fujimura
JMA journal, 6, 4, 565, 566, 16 Oct. 2023, [Domestic magazines]
English

Carotid Endarterectomy for a Case with an Extremely Twisted Internal Carotid Artery.
Sogo Oki, Masaki Ito, Masayuki Gekka, Tomohiro Yamauchi, Miki Fujimura
JMA journal, 6, 4, 548, 551, 16 Oct. 2023, [Domestic magazines]
English, Scientific journal, The internal carotid artery (ICA) typically runs posterolaterally to the external carotid artery (ECA) at the level of the common carotid artery (CCA) bifurcation in the neck. The "twisted ICA" is an anatomical variation, wherein the ICA is medial to the ECA. Several studies on the twisted ICA have discussed its anatomical definition, incidence, clinical features, and surgical results in patients with luminal stenosis. Computed tomography angiography (CTA)-based analyses of surgically treated cohorts documented a twist angle, reaching up to 95°. Carotid endarterectomy (CEA) was successfully performed for these patients. This study reports a case of a significantly twisted ICA with severe luminal stenosis that was successfully treated with CEA. An 81-year-old male was incidentally diagnosed with asymptomatic right ICA stenosis based on magnetic resonance (MR) angiography. Three-dimensional (3D)-CTA showed that the ICA revealed 74% stenosis of the ICA, based on the North American Symptomatic Carotid Endarterectomy Trial criteria. The 3D-CTA showed the ICA medial to the ipsilateral ECA at the level of the CCA bifurcation in the neck. It extended proximally to the pharynx, and the twist angle was 102°. Black-blood MR of the carotid plaque exhibited a high intensity on T1-weighted imaging, indicating vulnerability. Intraoperatively, the position of the ICA was corrected using multiple hooks instead of a surgical retractor. He showed no permanent deficits, such as an ipsilateral cerebral infarction, although transient postoperative hoarseness was observed. This case report documented a significantly twisted ICA with luminal stenosis, successfully treated via CEA, by correcting the carotid position using multiple hooks with gentle manipulation.

[Medulloblastoma].
Shigeru Yamaguchi, Miki Fujimura
No shinkei geka. Neurological surgery, 51, 5, 858, 866, Sep. 2023, [Domestic magazines]
Japanese, Scientific journal, In the 5th edition of the WHO classification, medulloblastomas, which are representative pediatric brain tumors, are categorized into four groups: WNT, SHH-TP53 wild, SHH-TP53 mutant, and non-WNT/non-SHH, based on their molecular background. While the histopathological findings still hold importance in predicting prognosis, the histopathological classification is no longer utilized in this edition. SHH medulloblastomas are further subdivided into two groups based on the presence or absence of TP53 mutation, as their clinical characteristics and prognosis differ. Group 3 and Group 4 medulloblastomas, recognized as distinct molecular groups in clinical practice, are combined into a single group called "non-WNT/non-SHH", because they lack specific molecular pathway activation. Furthermore, based on methylation profiling, dividing SHH medulloblastoma into four subgroups and non-WNT/non-SHH medulloblastoma into eight subgroups was proposed. Understanding the unique clinical characteristics and prognosis associated with each group is crucial. However, it is important to acknowledge that our current understanding of prognosis is based on treatment approaches guided by clinical risk factors such as postoperative residual tumor volume and the presence of metastatic disease. This molecular-based classification holds promise in guiding the development of optimal treatment strategies for patients with medulloblastoma.

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, 63, 10, 482, 489, 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.

Slow-growing WNT medulloblastoma with atypical magnetic resonance imaging findings: illustrative case.
Makoto Mizushima, Michinari Okamoto, Shigeru Yamaguchi, Sogo Oki, Hiroaki Motegi, Minako Sugiyama, Atsushi Manabe, Ai Shimizu, Kentaro Nishioka, Takayuki Hashimoto, Junko Hirato, Yonehiro Kanemura, Miki Fujimura
Journal of neurosurgery. Case lessons, 6, 7, 14 Aug. 2023, [International Magazine]
English, Scientific journal, BACKGROUND: Medulloblastomas, with four molecular subgroups, are generally rapid-growing tumors with significant contrast enhancement and well-defined margins. However, each subgroup's clinical features, including disease time course and imaging characteristics, are not well defined. OBSERVATIONS: The authors describe the case of a 15-year-old female who presented with a 7-month history of impaired left-hand movement and was found to have a lesion on the dorsal side of the fourth ventricle. T2-weighted magnetic resonance imaging (MRI) at the patient's first presentation showed diffuse hyperintense signal without apparent mass, and gadolinium-enhanced T1-weighted imaging showed very slight contrast enhancement. In 1 month, her symptoms progressed, and follow-up MRI revealed an increase in the size of the lesion, showing greater diffusion restriction and contrast enhancement. She underwent gross-total resection, and pathology was consistent with classic medulloblastoma. Genetic analysis of the tumor confirmed the wingless (WNT) molecular subgroup. Adjuvant chemotherapy and proton beam therapy were performed. At the 18-month follow-up, MRI showed no recurrence of disease. LESSONS: Slow-growing medulloblastoma is very rare and not known to be associated with a specific molecular subgroup. Here, the authors report a case of slow-growing WNT medulloblastoma, indicating that slow growth may be a feature of this subgroup.

A Noonan-like pediatric patient with a de novo CBL pathogenic variant and an RNF213 polymorphism p.R4810K presenting with cardiopulmonary arrest due to left main coronary artery ostial atresia.
Ayako Chida-Nagai, Hidefumi Tonoki, Naomasa Makita, Hiroyuki Ishiyama, Masafumi Ihara, Yuji Maruo, Takao Tsujioka, Daisuke Sasaki, Gaku Izumi, Hirokuni Yamazawa, Nobuyasu Kato, Masaki Ito, Miki Fujimura, Osamu Sasaki, Atsuhito Takeda
American journal of medical genetics. Part A, 191, 12, 2837, 2842, 09 Aug. 2023, [International Magazine]
English, Scientific journal, Left main coronary artery ostial atresia (LMCAOA) is an extremely rare condition. Here, we report the case of a 14-year-old boy with Noonan syndrome-like disorder in whom LMCAOA was detected following cardiopulmonary arrest. The patient had been diagnosed with Noonan syndrome-like disorder with a pathogenic splice site variant of CBL c.1228-2 A > G. He suddenly collapsed when he was running. After administering two electric shocks using an automated external defibrillator, the patient's heartbeat resumed. Cardiac catheterization confirmed the diagnosis of LMCAOA. Left main coronary artery angioplasty was performed. The patient was discharged without neurological sequelae. Brain magnetic resonance imaging revealed asymptomatic Moyamoya disease. In addition, RNF213 c.14429 G > A p.R4810K was identified. There are no reports on congenital coronary malformations of compound variations of RNF213 and CBL. In contrast, the RNF213 p.R4810K polymorphism has been established as a risk factor for angina pectoris and myocardial infarction in adults, and several congenital coronary malformations due to genetic abnormalities within the RAS/MAPK signaling pathway have been reported. This report aims to highlight the risk of sudden death in patients with RASopathy and RNF213 p.R4810K polymorphism and emphasize the significance of actively searching for coronary artery morphological abnormalities in these patients.

Formation of internal carotid artery aneurysms following gamma knife radiosurgery for pituitary adenomas: a case series and literature review.
Shota Yamashita, Atsushi Saito, Hidefumi Jokura, Tomohiro Kawaguchi, Miki Fujimura, Yoshikazu Ogawa, Teiji Tominaga
Acta neurochirurgica, 165, 8, 2257, 2265, Aug. 2023, [International Magazine]
English, Scientific journal, Only two aneurysm formations in the internal carotid artery after gamma knife radiosurgery (GKRS) for pituitary adenomas are reported so far. Here, out of the 482 patients who underwent GKRS for pituitary adenomas at our institute, at least five developed aneurysms within the area of high single-dose irradiation. Three patients presented with epistaxis due to aneurysmal rupture and one presented with abducens paralysis due to nerve compression, while one was asymptomatic. The interval between irradiation and aneurysmal detection ranged from 14 to 21 years. Aneurysm formation in those conditions may be higher than previously thought.

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.), 25, 4, 343, 352, 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.

Treatment of aneurysmal subarachnoid hemorrhage in subacute phase; retrospective comparison of treatment in sub- and hyper-acute phases.
Kota Kurisu, Masaaki Hokari, Kazuki Uchida, Katsuyuki Asaoka, Minoru Ajiki, Tatsuro Takada, Koji Itamoto, Miki Fujimura
Clinical neurology and neurosurgery, 230, 107781, 107781, Jul. 2023, [International Magazine]
English, Scientific journal, OBJECTIVE: As soon as possible treatment initiation for aneurysmal subarachnoid hemorrhage (aSAH) is recommended. However, some patients require treatment in "subacute" phase of aSAH, defined in this study as "more than one day after the onset". To establish an optimal treatment strategy for these patients, we retrospectively analyzed the clinical experience of treating ruptured aneurysm with either clipping or coiling in subacute phase. METHODS: Patients treated for aSAH between 2015 and 2021were analyzed. Patients were divided into the hyperacute phase (within 24 h) and subacute phase (later than 24 h) groups. The subacute group was analyzed to determine whether the selected procedure and its timing affected postoperative course and clinical outcomes. In addition, we conducted a multivariate logistic regression analysis to determine the independent factors that affect clinical outcomes. RESULTS: Of 215 patients, 31 were treated in the subacute phase. While cerebral vasospasm at initial imaging was more frequently observed in subacute group, there was no difference in incidence of postoperative vasospasms. Patients in subacute group seemed to have better clinical outcomes due to the milder severity at the time of treatment initiation. Risk of angiographic vasospasm seemed to be higher in patients treated with clipping than coiling, while no difference was seen in clinical outcomes. Multivariate logistic regression analysis showed that the timing and selected treatment did not significantly affect the clinical outcome or the occurrence of delayed vasospasm. CONCLUSIONS: Treatment of aSAH in the subacute phase may also result in favorable clinical outcomes, similar to patients treated in the hyperacute phase with mild presentation. However, further investigations are required to establish the optimal treatment strategies for such patients.

パーキンソン病脳深部刺激療法術後5年目における治療有効性の評価　　　　　　　　　　　　　　　
白井 慎一, 江口 克紀, 山崎 和義, 松島 理明, 川堀 真人, 平田 健司, 藤村 幹, 矢部 一郎
パーキンソン病・運動障害疾患コングレスプログラム・抄録集, 17回, 86, 86, Movement Disorder Society of Japan (MDSJ), Jul. 2023
Japanese

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.

Successful treatment with urgent revascularization and parent artery occlusion for a ruptured intratumoral aneurysm following prior meningioma surgery: illustrative case.
Tomohiro Okuyama, Kota Kurisu, Masaaki Hokari, Kei Miyata, Kazuki Uchida, Katsuyuki Asaoka, Koji Itamoto, Miki Fujimura
Journal of neurosurgery. Case lessons, 5, 21, 22 May 2023, [International Magazine]
English, Scientific journal, BACKGROUND: An intratumoral aneurysm encased within the associated intracranial tumor is rare, and hemorrhage caused by its rupture is even more rare. While urgent and adequate surgical treatment is important, the treatment can be difficult given the limited understanding of this rare condition. OBSERVATIONS: A 69-year-old man who had undergone meningioma surgery 30 years prior presented with a disturbance in consciousness. Magnetic resonance imaging revealed massive intracerebral and subarachnoid hemorrhage. A round, partially calcified mass, which was diagnosed as recurrent meningioma, was also observed. Subsequent cerebral angiography revealed that the source of the hemorrhage was an intratumoral aneurysm in the dorsal internal carotid artery (ICA) encased within the recurrent meningioma. Urgent surgical ICA trapping and high-flow graft bypass were conducted. The postoperative course was uneventful, and he was referred to another hospital for rehabilitation. LESSONS: This is the first case report of a ruptured intratumoral aneurysm being treated with urgent combined revascularization and parent artery trapping surgery. This surgical approach may be a feasible treatment option for such a challenging condition. Additionally, this case highlights the importance of diligent long-term follow-up after skull-base surgery, as minor intraoperative vascular wall injury may trigger the development and rupture of an intracerebral aneurysm.

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.

A flow self-regulating superficial temporal artery-middle cerebral artery bypass based on side-to-side anastomosis for adult patients with moyamoya disease.
Jianjian Zhang, Jin Yu, Can Xin, Miki Fujimura, Tsz Yeung Lau, Miao Hu, Xiao Tian, Mingrui Luo, Tianshu Tao, Ling Li, Changyin Wang, Wei Wei, Xiang Li, Jincao Chen
Journal of neurosurgery, 138, 5, 1347, 1356, 01 May 2023, [International Magazine]
English, Scientific journal, OBJECTIVE: Side-to-side (S-S) superficial temporal artery-middle cerebral artery (STA-MCA) bypass was reportedly used to treat a special moyamoya disease (MMD) patient with collaterals arising from the donor STA. However, the S-S technique is not routinely performed to date, and its benefits are still unknown for adult MMD. The purpose of this study was to investigate the possibility of routine use of the S-S technique for adult MMD. METHODS: The authors retrospectively analyzed the clinical data of 50 adult patients (65 hemispheres, including 30 in the end-to-side [E-S] group and 35 in the S-S group) with MMD who underwent STA-MCA bypass. The patient demographic characteristics, clinical courses, technical details, intraoperative blood flow data, postoperative and preoperative relative cerebral blood flow (rCBF) values, modified Rankin Scale (mRS) scores, and short-term revascularization results were compared between the 2 groups. RESULTS: There were no significant differences observed in terms of the baseline characteristics, bypass patency rates, postoperative/preoperative rCBF values, incidence of cerebral hyperperfusion syndrome (CHS), mRS scores, and short-term revascularization results between the 2 groups (all p > 0.05). Intraoperative blood flow analysis showed that the increase of STA flow in the E-S group was significantly higher than that of proximal STA flow in the S-S group (p = 0.008). Although the increases of proximal and distal recipient flow in the E-S group seemed greater than those in the S-S group, the results were not statistically significant (p = 0.086 for proximal flow and p = 0.076 for distal flow). CHS symptoms in the S-S group were milder and with much shorter duration. The follow-up angiographic data of the representative case demonstrated that both frontal and parietal STA branches and the occipital artery participated in postoperative collateralization. CONCLUSIONS: S-S anastomosis can achieve comparable clinical effects to standard E-S construction. S-S anastomosis used in adult MMD demonstrated mild CHS symptoms with short duration and had the potential to arouse all scalp arteries as donor sources for revascularization through the intact distal STA branch via flow self-regulation.

Clinical characteristics of endovascular treatment for acute ischemic stroke with atherosclerotic etiology: Factors associating its clinical outcome.
Kota Kurisu, Kazuki Uchida, Tomohiro Okuyama, Kei Miyata, Yoshitaka Yamaguchi, Minoru Ajiki, Tatsuro Takada, Masaaki Hokari, Katsuyuki Asaoka, Koji Itamoto, Miki Fujimura
Clinical neurology and neurosurgery, 228, 107680, 107680, May 2023, [International Magazine]
English, Scientific journal, OBJECTIVE: Clinical characteristics of endovascular treatment (EVT) for acute ischemic stroke (AIS) secondary to atherosclerosis are not fully delineated. An optimal treatment strategy with considerations of stroke etiology has not yet been established. Here-in, we performed retrospective analysis of EVT for atherosclerotic AIS. METHODS: Data from patients with AIS who underwent EVT between 2017 and 2022 were analyzed. Clinical characteristics, procedural data, and outcomes were assessed. Further analysis was conducted to elucidate the factors associated with clinical outcomes. And data of patients with poor clinical outcomes (mRS, 5 or 6) were evaluated further to determine the primary cause. RESULTS: Among 194 patients who received EVT, 40 (20.6%) were diagnosed with AIS with an atherosclerotic etiology. The rates of successful reperfusion (TICI 2b or 3) and good clinical outcomes (mRS, 0-2) were 95.0% and 45.0%, respectively. No procedure-related complications were noted. Older age (p = 0.007), more severe baseline NIHSS score (p = 0.004), lesion in the posterior circulation (p = 0.025), and recanalization failure (p = 0.027) were more frequently observed in patients with poor clinical outcomes. Brainstem infarction and postprocedural intracerebral hemorrhage were the main reasons for poor clinical outcomes. CONCLUSION: The EVT for atherosclerotic AIS were effective and safe. Older age, more severe NIHSS score, lesions in the posterior circulation, and recanalization failure were the factors associated with poor clinical outcomes. It is important to recognize that these factors may aggravate the clinical response to this promising therapy, even in patient successful recanalization was attained.

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, [International Magazine]
English, 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.

Supratentorial multifocal gliomas associated with Ollier disease harboring IDH1 R132H mutation: A case report.
Hiroshi Ikeda, Shigeru Yamaguchi, Yukitomo Ishi, Kento Wakabayashi, Ai Shimizu, Hiromi Kanno-Okada, Takeshi Endo, Mitsutoshi Ota, Michinari Okamoto, Hiroaki Motegi, Norimasa Iwasaki, Miki Fujimura
Neuropathology : official journal of the Japanese Society of Neuropathology, 43, 5, 413, 420, 20 Mar. 2023, [International Magazine]
English, Scientific journal, Somatic mosaicism of isocitrate dehydrogenase 1/2 (IDH1/2) mutation is a cause of Ollier disease (OD), characterized by multiple enchondromatosis. A 35-year-old woman who was diagnosed with OD at age 24 underwent resection surgery for multifocal tumors located at the right and left frontal lobes that were discovered incidentally. No apparent spatial connection was observed on preoperative magnetic resonance imaging. Pathological examinations revealed tumor cells with a perinuclear halo in the left frontal lobe tumor, whereas astrocytic tumor cells were observed in the right frontal lobe tumor. Based on positive IDH1 R132H immunostaining and the result of 1p/19q fluorescent in situ hybridization, pathological diagnoses were IDH mutant and 1p/19q-codeleted oligodendroglioma in the right frontal lobe tumor and IDH mutant astrocytoma in the left frontal lobe tumor, respectively. The DNA sequencing revealed IDH1 R132H mutation in the peripheral blood sample and frontal lobe tumors. This case suggested that in patients with OD, astrocytoma and oligodendroglioma can co-occur within the same individual simultaneously, and IDH1 R132H mutation was associated with supratentorial development of gliomas.

The Prediction of Neurological Prognosis for Cervical Spondylotic Myelopathy Using Diffusion Tensor Imaging.
Soichiro Takamiya, Motoyuki Iwasaki, Takumi Yokohama, Daisuke Oura, Yoshimasa Niiya, Miki Fujimura
Neurospine, 20, 1, 248, 254, Mar. 2023, [International Magazine]
English, Scientific journal, OBJECTIVE: Although cervical spondylotic myelopathy (CSM) can be easily diagnosed using magnetic resonance imaging (MRI), prediction of surgical effect using preoperative radiological examinations remains difficult. In previous studies, it was reported that diffusion tensor imaging (DTI) may be used for the prediction of surgical effect; however, these studies did not consider the influences of spinal cord compression even though the values of DTI indexes can be distorted by compressive lesions in patients with CSM. Therefore, it is uncertain whether preoperative DTI indexes can actually predict the surgical effect. The aim of this study was to investigate DTI metrics that are hardly affected by spinal cord compression and can accurately predict neurological status after decompressive surgery. METHODS: Twenty-one patients with CSM who underwent surgery and 10 healthy volunteers were enrolled in this study. The subjects underwent cervical MRI, and values of DTI indexes including axial diffusivity (AD), radial diffusivity (RD), apparent diffusion coefficient (ADC), and fractional anisotropy (FA) were recorded at each intervertebral level. Further, the Japanese Orthopaedic Association (JOA) score of each patient with CSM was recorded before and after surgery for neurological status evaluation. Preoperative and postoperative values of DTI indexes were compared, and correlations between preoperative DTI parameters and postoperative neurological recovery were assessed. RESULTS: After surgery, the lesion-adjacent (LA) ratios of RD and ADC increased (p = 0.04 and p = 0.062, respectively), while the LA ratio of FA decreased (p = 0.075). In contrast, the LA ratio of AD hardly changed. A negative correlation was observed between preoperative LA ratio of AD and JOA recovery rate 6 months after surgery (r = -0.379, p = 0.091). Based on preoperative LA ratio of AD, the patients were divided into a low AD group and a high AD group, and JOA recovery rate 6 months after surgery was found to be higher in the low AD group than in the high AD group (p = 0.024). CONCLUSION: In patients with CSM, preoperative LA ratio of AD is seldom affected by spinal cord compression, and it negatively correlates with JOA recovery rate 6 months after surgery.

The Pathogenetic Mechanism for Moyamoya Vasculopathy Including a Possible Trigger Effect of Increased Flow Velocity.
Takeo Abumiya, Miki Fujimura
JMA journal, 6, 1, 16, 24, 16 Jan. 2023, [Domestic magazines]
English, Scientific journal, Moyamoya disease (MMD), which commonly exhibits moyamoya vasculopathy characterized by chronic progressive steno-occlusive lesions in the circle of Willis with "moyamoya" collateral vessels, has been well known for its unique demographic and clinical features. Although the discovery of the susceptibility gene RNF213 for MMD revealed the factor for its predominance in East Asians, the mechanisms underlying other predominant conditions (females, children, young to middle-aged adults, and anterior circulation) and lesion formation are yet to be determined. As MMD and moyamoya syndrome (MMS), which secondarily produces moyamoya vasculopathy due to pre-existing diseases, have the same vascular lesions despite differences in their original pathogenesis, they may share a common trigger for the development of vascular lesions. Thus, we herein consider a common trigger from a novel perspective on blood flow dynamics. Increased flow velocity in the middle cerebral arteries is an established predictor of stroke in sickle cell disease, which is often complicated by MMS. Flow velocity is also increased in other diseases complicated by MMS (Down syndrome, Graves' disease, irradiation, and meningitis). In addition, increased flow velocity occurs under the predominant conditions of MMD (females, children, young to middle-aged adults, and anterior circulation), suggesting a relationship between flow velocity and susceptibility to moyamoya vasculopathy. Increased flow velocity has also been detected in the non-stenotic intracranial arteries of MMD patients. In a pathogenetic overview of chronic progressive steno-occlusive lesions, a novel perspective including the trigger effect of increased flow velocity may provide insights into the mechanisms underlying their predominant conditions and lesion formation.

Stem Cell Therapies for Intracerebral Hemorrhage: Review of Preclinical and Clinical Studies.
Soichiro Takamiya, Masahito Kawabori, Miki Fujimura
Cell transplantation, 32, 9636897231158153, 9636897231158153, 2023, [International Magazine]
English, Scientific journal, Despite recent developments in the treatments for ischemic stroke, such as tissue plasminogen activator (t-PA) and thrombectomy, effective therapies for intracerebral hemorrhage (ICH) remain scarce. Stem cell therapies have attracted considerable attention owing to their potential neuro-regenerative ability; preclinical and clinical studies have been conducted to explore strategies for achieving functional recovery following ICH. In this review, we summarize the findings of preclinical studies on stem cell therapies of ICH, with a focus on different animal models, stem cell sources, transplantation methods, and their potential mechanisms of action. We also provide an overview of data from clinical trials to discuss the current status and future perspectives. Understanding the effectiveness and limitations of stem cell therapy and the future prospects could expand the applications of this novel therapeutic approach for ICH.

Fatal case of subdural empyema caused by Campylobacter rectus and Slackia exigua.
Yuki Munekata, Saki Yamamoto, Shun Kato, Yutaro Kitagawa, Ken Enda, Nanase Okazaki, Satoshi Tanikawa, Zen-Ichi Tanei, Yohei Ikebe, Takahiro Osawa, Soichiro Takamiya, Hideki Ujiie, Masahiro Onozawa, Satoshi Hirano, Miki Fujimura, Shinya Tanaka
Autopsy & case reports, 13, e2023433, 2023, [International Magazine]
English, Scientific journal, We report a fatal subdural empyema caused by Campylobacter rectus in a 66-year-old female who developed acute onset of confusion, dysarthria, and paresis in her left extremities. A CT scan showed hypodensity in a crescentic formation with a mild mid-line shift. She had a bruise on her forehead caused by a fall several days before admission, which initially raised subdural hematoma (SDH) diagnosis, and a burr hole procedure was planned. However, her condition deteriorated on the admission night, and she died before dawn. An autopsy revealed that she had subdural empyema (SDE) caused by Campylobacter rectus and Slackia exigua. Both microorganisms are oral microorganisms that rarely cause extra-oral infection. In our case, head trauma caused a skull bone fracture, and sinus infection might have expanded to the subdural space causing SDE. CT/MRI findings were not typical for either SDH or SDE. Early recognition of subdural empyema and prompt initiation of treatment with antibiotics and surgical drainage is essential for cases of SDE. We present our case and a review of four reported cases.

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, 17, 6, 120, 124, The Japanese Society for Neuroendovascular Therapy, 2023, [Domestic magazines]
English, Scientific journal, OBJECTIVE: In endovascular treatment, it is important to evaluate the access route for placing a catheter into the common carotid artery (CCA) promptly and safely prior to the procedure. We examined whether non-contrast MRA using time-spatial labeling inversion pulse (Time-SLIP) can be used in patients prior to endovascular thrombectomy for acute ischemic stroke. We compared Time-SLIP MRA to contrast-enhanced (CE) MRA and evaluated the efficacy in the evaluation of access routes. METHODS: We retrospectively reviewed 31 patients admitted between October 2018 and December 2018 for cerebral infarction at our hospital. Blood vessels were imaged from the aortic arch to the CCA. A radiologist blindly evaluated quality score, stenosis, shape of the aorta, and degree of tortuosity. RESULTS: There were no "non-diagnostic" images. The sensitivity, specificity, positive predictive value, and negative predictive value for stenosis were 83%, 96%, 83%, and 96%, respectively. The sensitivity for the aorta type classification was 100%. The sensitivity for mild tortuosity was 93%, for moderate was 100%, and for severe was 100%. CONCLUSION: Time-SLIP MRA can be an alternative to CE MRA in access route assessment for patients with cerebral infarction who are not eligible for acute thrombectomy therapy.

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

血栓回収療法の適応拡大にともなう医師負担を考慮した、血管内治療提供体制の構築　　　　　　　　　　　　　　　
長内 俊也, 大橋 和貴, 坂東 恭平, 森井 康博, 藤原 健祐, 谷川 琢海, 小笠原 克彦, 藤村 幹
脳血管内治療, 7, Suppl., S52, S52, (NPO)日本脳神経血管内治療学会, Nov. 2022
Japanese

Gluing blood into gel by electrostatic interaction using a water-soluble polymer as an embolic agent.
Zhiping Jin, Hailong Fan, Toshiya Osanai, Takayuki Nonoyama, Takayuki Kurokawa, Hideki Hyodoh, Kotaro Matoba, Akiko Takeuchi, Jian Ping Gong, Miki Fujimura
Proceedings of the National Academy of Sciences of the United States of America, 119, 42, e2206685119, 18 Oct. 2022, [International Magazine]
English, Scientific journal, Liquid embolic agents are widely used for the endovascular embolization of vascular conditions. However, embolization based on phase transition is limited by the adhesion of the microcatheter to the embolic agent, use of an organic solvent, unintentional catheter retention, and other complications. By mimicking thrombus formation, a water-soluble polymer that rapidly glues blood into a gel without triggering coagulation was developed. The polymer, which consists of cationic and aromatic residues with adjacent sequences, shows electrostatic adhesion with negatively charged blood substances in a physiological environment, while common polycations cannot. Aqueous polymer solutions are injectable through clinical microcatheters and needles. The formed blood gel neither adhered to the catheter nor blocked the port. Postoperative computed tomography imaging showed that the polymer can block the rat femoral artery in vivo and remain at the injection site without nontarget embolization. This study provides an alternative for the development of waterborne embolic agents.

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

Long-term consequences of residual lesions after chemoradiotherapy in patients with germinoma at onset.
Shigeru Yamaguchi, Michinari Okamoto, Yukitomo Ishi, Ryosuke Sawaya, Hiroaki Motegi, Minako Sugiyama, Taisuke Harada, Noriyuki Fujima, Takashi Mori, Takayuki Hashimoto, Emi Takakuwa, Atsushi Manabe, Kohsuke Kudo, Hidefumi Aoyama, Miki Fujimura
Journal of neurosurgery. Pediatrics, 30, 5, 1, 8, 09 Sep. 2022, [International Magazine]
English, Scientific journal, OBJECTIVE: In patients with intracranial germ cell tumors, residual lesions are sometimes observed after completion of primary chemoradiotherapy. Although salvage resection of these end-of-treatment residual lesions is recommended for patients with nongerminomatous germ cell tumors, the necessity of early salvage resection for those with germinoma is not clear. The aim of this study was to investigate the frequency of residual germinoma lesions after primary chemoradiotherapy, as well as their management, long-term consequences, and prognosis. METHODS: The authors retrospectively reviewed patients who were primarily treated for germinoma between 2002 and 2021. Residual lesions were evaluated with MRI with and without contrast enhancement within 2 weeks after chemoradiotherapy. The decision to perform salvage resection of residual lesions was at the discretion of the treating physicians. The change in appearance of residual lesions was assessed with serial MRI. Overall survival (OS), progression-free survival (PFS), and recurrence pattern were also investigated. RESULTS: Sixty-nine patients were treated with chemoradiotherapy for germinoma, with a mean follow-up period of 108 months. Residual lesions were radiologically observed in 30 patients (43.5%). Among these, 5 patients (3 with pineal lesions and 2 with basal ganglia lesions) underwent salvage resection. Pathological examination revealed teratomatous components in 3 patients, whereas no tumoral components were identified in 2 patients. One patient with a basal ganglia lesion showed worsening of hemiparesis postoperatively. The remaining 25 patients received watchful observation without surgical intervention. Chronological periodic radiological change in residual lesions was evaluated in 21 patients. One year after primary treatment, the size of the residual lesions was stable and had decreased in 10 and 11 patients, respectively. None of the lesions increased in size. The 10-year PFS and OS rates were 96.7% and 97.3% in patients without residual lesions (n = 39), and 87.1% and 100% in patients with residual lesions (n = 30), respectively. Presence of residual lesions had no significant effect on PFS or OS. All recurrences occurred at distant sites or via dissemination without progression of the primary tumor site, regardless of the presence of residual lesion. CONCLUSIONS: End-of-treatment residual lesions are not rare in patients with germinoma, and these residual lesions seldom show progression. Because of the potential risk of surgical complications, the indication for early salvage surgery for residual lesions should be carefully determined. Watchful observation is recommended for the majority of these cases.

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, [International Magazine]
English, 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, [International Magazine]
English, 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, 39, 1, 307, 310, Springer Science and Business Media LLC, 29 Jul. 2022, [International Magazine]
English, Scientific journal, BACKGROUND: Hydrocephalus is one of the most common presentations of occipital encephaloceles and usually develops within the first year of life. This case report presents a rare case of late-onset obstructive hydrocephalus associated with occipital encephalocele with an extraordinarily large occipital skull defect. CASE REPORT: At birth, a newborn girl presented with an absence of a vast amount of occipital cranium and skin and was diagnosed with occipital hydroencephalomeningocele. Under meticulous sterile management, the affected area was successfully epithelialized, and the patient was discharged without infectious complication. Despite an obstructed cerebral aqueduct, she grew without any signs of hydrocephalus until the age of 7 years. Her gait gradually worsened, and imaging tests at the age of 8 years revealed markedly enlarged lateral and third ventricles but not the fourth ventricle. Endoscopic third ventriculostomy successfully relieved her symptoms with improvement of hydrocephalus. CONCLUSION: This is the first case of late-onset obstructive hydrocephalus associated with an occipital encephalocele characterized by large-scale cranial bony defects. Although further investigation is required to elucidate the mechanism of hydrocephalus, this rare phenomenon should be noted during neurological and radiological follow-up.

Diagnostic Criteria for Moyamoya Disease - 2021 Revised Version.
Satoshi Kuroda, Miki Fujimura, Jun Takahashi, Hiroharu Kataoka, Kuniaki Ogasawara, Toru Iwama, Teiji Tominaga, Susumu Miyamoto
Neurologia medico-chirurgica, 62, 7, 307, 312, 15 Jul. 2022, [Domestic magazines]
English, Scientific journal, In this report, we, the Research Committee on Moyamoya Disease (Spontaneous Occlusion of the circle of Willis), describe in detail the changes in the new "Diagnostic Criteria 2021" for moyamoya disease and its scientific basis to make it widely known to the world. The revised criteria cover all aspects of the disease, including a definition of the disease concept, diagnostic imaging, and the concept of quasi-moyamoya disease (moyamoya syndrome).

[Surgical Approaches to Pediatric Moyamoya Disease]
Miki Fujimura, Masaki Ito
No Shinkei Geka., 50, 4, 819, 825, Jul. 2022, [Peer-reviewed], [Domestic magazines]
Japanese, Scientific journal, Moyamoya disease(MMD)is a chronic, occlusive cerebrovascular disease with unknown etiology, characterized by progressive stenosis of the internal carotid artery terminus and abnormal vascular network formation at the base of the brain. MMD has bimodal age distribution, with peaks in children and young adults, and surgical revascularization is a reasonable management choice for pediatric and adult patients with ischemic MMD. The superficial temporal artery-middle cerebral artery anastomosis with indirect pial synangiosis(combined revascularization)is a preferred surgical procedure for adult and pediatric MMD patients, providing early cerebral hemodynamic improvement and long-term favorable outcomes. Pediatric patients with MMD can present intrinsic postoperative hemodynamic complications, such as watershed shift ischemia and transient global hypoperfusion, even after successful revascularization. Therefore, perioperative management based on the early hemodynamic study is critical to avoid surgical complications, including perioperative cerebral infarction.

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

脳深部刺激療法術後4年の経過に関する12例の検討　　　　　　　　　　　　　　　
白井 慎一, 江口 克紀, 山崎 和義, 松島 理明, 加納 崇裕, 笹森 徹, 平田 健司, 大槻 美佳, 北川 まゆみ, 寳金 清博, 佐々木 秀直, 藤村 幹, 矢部 一郎
パーキンソン病・運動障害疾患コングレスプログラム・抄録集, 16回, 80, 80, Movement Disorder Society of Japan (MDSJ), 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, 165, e446-e451, 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, Scientific journal, 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, 85, 2, 227, 232, 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

Clinical and radiological findings of glioblastomas harboring a BRAF V600E mutation.
Yukitomo Ishi, Shigeru Yamaguchi, Michinari Okamoto, Ryosuke Sawaya, Shogo Endo, Hiroaki Motegi, Shunsuke Terasaka, Zen-Ichi Tanei, Kanako C Hatanaka, Shinya Tanaka, Miki Fujimura
Brain tumor pathology, 39, 3, 162, 170, 01 Apr. 2022, [Domestic magazines]
English, Scientific journal, The aim of this study was to analyze the clinical and radiological characteristics of glioblastomas (GBMs) harboring a BRAF mutation. Sequencing analysis of BRAF, IDH1/2, and TERT promoters was performed on GBM samples of patients older than 15 years. The clinical, pathological, and radiological data of patients were retrospectively reviewed. Patients were classified into three groups according to their BRAF and IDH1/2 status: BRAF group, IDH group, and BRAF/IDH-wild-type (WT) group. Among 179 GBM cases, we identified nine cases with a BRAF mutation and nine with IDH mutation. The WT group had 161 cases. Age at onset in the BRAF group was significantly lower compared to the WT group and was similar to the IDH group. In cases with negative IDH1-R132H staining and age < 55 years, 15.2% were BRAF-mutant cases. Similar to the IDH group, overall survival of the BRAF group was significantly longer compared with the WT group. Among nine cases in the BRAF group, three cases had hemorrhagic onset and prior lesions were observed in two cases. In conclusion, age < 55 years, being IDH1-R132H negative, with hemorrhagic onset or the presence of prior lesions are factors that signal recommendation of BRAF analysis for adult GBM patients.

Moyamoya Vasculopathy: Cause, Clinical Manifestations, Neuroradiologic Features, and Surgical Management.
Mariano Velo, Giovanni Grasso, Miki Fujimura, Fabio Torregrossa, Marcello Longo, Francesca Granata, Antonio Pitrone, Sergio Lucio Vinci, Ludovica Ferraù, Paolino La Spina
World neurosurgery, 159, 409, 425, Mar. 2022, [International Magazine]
English, Scientific journal, In moyamoya disease, the progressive occlusion of the distal portion of the internal carotid artery and its major branches is typically responsible for the formation of an extensive network of collateral vessels at the base of the brain. When moyamoya collateral network develops in association with various systemic or acquired diseases, the term moyamoya syndrome is used to denote this phenomenon. Sudden changes in the supraclinoid internal carotid artery and middle cerebral artery can be recognized with noninvasive neurovascular imaging techniques, which also allow a differential diagnosis with similar diseases such as degenerative steno-occlusive disease, cerebral vasculitis, and twig-like middle cerebral artery. Once the diagnosis is established, the definitive treatment for moyamoya disease is surgical revascularization, with the goal of increasing cerebral blood flow and preventing recurrent stroke. We provide a comprehensive review of the clinical and radiologic features in moyamoya vasculopathy along with its surgical management.

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

内頸動脈瘤術後に急激な意識障害をきたした神経線維腫症1型の一剖検例　　　　　　　　　　　　　　　
京野 里虹, 種井 善一, 岡崎 ななせ, 長内 俊也, 小田 義崇, 谷川 聖, 杉野 弘和, 津田 真寿美, 藤村 幹, 田中 伸哉
日本病理学会会誌, 111, 1, 356, 356, (一社)日本病理学会, 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, 85, 1, 88, 93, 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, 188, 6, 1863, 1867, 18 Feb. 2022, [International Magazine]
English, Scientific journal, 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.

Variations and natural history of primary intraparenchymal lesions associated with neurofibromatosis type 2.
Yukitomo Ishi, Taisuke Harada, Hiroyuki Kameda, Hiromi Okada, Isao Yokota, Michinari Okamoto, Ryosuke Sawaya, Hiroaki Motegi, Shigeru Yamaguchi, Shunsuke Terasaka, Kohsuke Kudo, Miki Fujimura
Neuroradiology, 64, 2, 393, 396, Feb. 2022, [International Magazine]
English, Scientific journal, The study aimed to investigate the clinical implications and natural history of primary intraparenchymal lesions in patients with neurofibromatosis type 2. Radiological findings of 15 neurofibromatosis type 2 cases were retrospectively collected. Twenty-seven primary intraparenchymal lesions were observed in 7 out of 15 patients (47%). Cortical/subcortical T2 hyperintense lesions and enlarged Virchow-Robin spaces were the most common findings in five and four patients, respectively. During the follow-up period (median 84 months), one new primary intraparenchymal lesion was identified and increased lesions were observed in two cases on contrast-enhanced MRI. Surgical resection was performed in one case pathologically diagnosed with atypical meningioma. Twenty-five other lesions without contrast enhancement presented no apparent growth during follow-up. Although most primary intraparenchymal lesions are benign, a subset of cases would present newly developed or increased lesions on contrast-enhanced MRI. Careful monitoring is necessary for such cases, and pathological confirmation should be considered.

【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

Cystic Intracranial Recurrence of Olfactory Neuroblastoma without Accumulation on Fluorine-18-fluorodeoxyglucose Positron Emission Tomography.
Yukitomo Ishi, Shigeru Yamaguchi, Kanako C Hatanaka, Emi Takakuwa, Hiroaki Motegi, Taishi Honda, Hiroyuki Kobayashi, Shunsuke Terasaka, Akihiro Homma, Miki Fujimura, Kiyohiro Houkin
Acta medica Okayama, 76, 1, 93, 98, Feb. 2022, [Domestic magazines]
English, Scientific journal, A 66-year-old man underwent multimodal treatment for olfactory neuroblastoma (ONB). When he was 72 years old, a cystic intracranial lesion without accumulation on fluorine-18-fluorodeoxyglucose positron emission tomography was detected. Surgical resection was performed when the patient was 73 years old. The pathological examination revealed recurrence of ONB, and the patient underwent focal irradiation. At age 81, he presented with a second recurrence in the right occipital lobe with radiological and pathological findings similar to the prior recurrence. This case suggests that pathological confirmation should be considered in cases with atypical radiological findings following the treatment of ONB.

Moyamoya Disease-Standards and Advances in Revascularization Procedure and Peri-operative Management.
Miki Fujimura
Advances and technical standards in neurosurgery, 44, 175, 186, 2022, [International Magazine]
English, Scientific journal, Moyamoya disease (MMD) is a chronic, occlusive cerebrovascular disease with unknown etiology characterized by progressive stenosis at the terminal portion of the internal carotid artery and the abnormal vascular network formation at the base of the brain. Superficial temporal artery-middle cerebral artery (STA-MCA) bypass is a preferred surgical procedure for ischemic-onset MMD patients by improving cerebral blood flow. Recent evidence further indicates that flow-augmentation bypass has a potential role for preventing re-bleeding in hemorrhagic-onset MMD patients. Based on such cumulative evidence, there is a worldwide increase in the number of MMD patients undergoing bypass surgery, thus thorough understanding of the basic pathology of MMD including peri-operative hemodynamics is critical for avoiding surgical complications. The author sought to demonstrate the standard surgical procedure of STA-MCA bypass with indirect pial synangiosis for adult MMD patients and its pitfall in the early postoperative period, introducing the characteristic peri-operative hemodynamic condition of adult MMD after surgery, such as local cerebral hyperperfusion and intrinsic hemodynamic ischemia caused by watershed shift phenomenon.

[The Potential of Personalized/Precision Medicine for Meningiomas].
Shigeru Yamaguchi, Miki Fujimura
No shinkei geka. Neurological surgery, 50, 1, 132, 140, Jan. 2022, [Domestic magazines]
Japanese, Scientific journal, Meningiomas are one of the most common primary brain tumors. The majority of patients with meningiomas can undergo curative resection or remain asymptomatic for a lifetime, but a minority of them have tumors with cumbersome clinicopathological features causing life-threatening disease. Although several cytotoxic agents and hormonal therapies have been tried for refractory and unresectable meningiomas, there are no effective drugs available for meningiomas so far. In the last decade, due to the rapid progress in comprehensive genomic research for individual tumors, novel somatic and recurrent mutations were discovered in meningiomas. The discovered somatic mutations were mostly mutually exclusive with NF2 gene alterations, and importantly, several of these mutations, such as AKT1 and SMO, are potentially actionable mutations for precision/personalized medicine. In addition, immunotherapy is another attractive treatment option for refractory meningiomas due to the development of immune checkpoint inhibitors. Herein, we describe the possibility of precision medicine for meningiomas according to each molecular aberrancy and present the currently ongoing clinical trials including hormonal therapy, targeted kinase inhibitors, and immunotherapy.

[Precision Medicine for Moyamoya Disease].
Miki Fujimura
No shinkei geka. Neurological surgery, 50, 1, 216, 221, Jan. 2022, [Domestic magazines]
Japanese, Scientific journal, Moyamoya disease(MMD)is a chronic, occlusive cerebrovascular disease characterized by progressive stenosis at the internal carotid artery terminus and abnormal vascular network formation at the base of the brain. Although its etiology is still unknown, recent genetic analysis identified RNF213 as an important susceptibility gene for MMD. A single nucleotide polymorphism in c.14576G>A(p.R4810K)in RNF213 was identified in 80% of patients with MMD in Japan, and RNF213 mutation was found to be significantly associated with earlier disease onset and more severe disease. More recent studies identified a significant correlation between RNF213 mutation and the intrinsic cerebral hemodynamics, such as local cerebral hyperperfusion after direct revascularization surgery for patients with MMD. These results indicate that RNF213 could be a useful biomarker for the prediction of the clinical course of MMD and/or the outcomes of revascularization surgery. Further investigation is warranted to clarify the exact mechanism by which RNF213 mutation leads to the steno-occlusive changes at the internal carotid artery terminus, development of abnormal vascular networks at the base of the brain, and ultimate cerebrovascular events in patients with MMD. This information could also be helpful in the implementation of precision medicine by providing critical information regarding the molecular target candidates in the management of MMD.

Successful Treatment of Intracranial Methotrexate-associated Lymphoproliferative Disorder without Epstein-Barr Virus Infection Using Rituximab, Methotrexate, Procarbazine, and Vincristine: A Case Report.
Makoto Mizushima, Yukitomo Ishi, Hiroshi Ikeda, Ikuma Echizenya, Takuya Otsuka, Tomoko Mitsuhashi, Shigeru Yamaguchi, Miki Fujimura
NMC case report journal, 9, 237, 242, 2022, [Domestic magazines]
English, Scientific journal, Methotrexate-associated lymphoproliferative disorder (MTX-LPD) occurs in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX). MTX-LPD is typically associated with Epstein-Barr virus (EBV) infection and regresses with MTX discontinuation. On the other hand, EBV-negative MTX-LPDs are less common and are more likely to show partial or no regression after MTX discontinuation. There were no standard chemotherapeutic options for refractory MTX-LPD. We present a case of EBV-negative MTX-LPD in the central nervous system (CNS) that was successfully treated with rituximab, methotrexate, procarbazine, and vincristine (R-MPV), followed by reduced-dose whole-brain radiotherapy (rdWBRT), following the same treatment protocol as primary CNS lymphoma. A 59-year-old woman with RA treated with MTX presented with gradually developing staggered gait, memory deficit, and disorientation. Multiple lesions with heterogeneous contrast enhancement were discovered using brain magnetic resonance imaging. The patient was suspected of having MTX-LPD, but discontinuing MTX did not result in regression of the brain lesions. She underwent a biopsy from the left parietal lesion. The tissue was pathologically diagnosed as diffuse large B-cell lymphoma. Furthermore, pathological examination through EBV-encoded ribonucleic acid in situ hybridization demonstrated a lack of EBV infection. She was ultimately diagnosed with EBV-negative CNS MTX-LPD. We applied chemotherapy with R-MPV and rdWBRT. The patient achieved a complete response. In the case of CNS MTX-LPD without EBV infection, chemotherapy with R-MPV followed by rdWBRT may be considered.

Detection of the Moment of Nerve Decompression Using Continuous Monitoring of Evoked Facial Nerve Electromyograms in a Patient with Facial Nerve Schwannoma: Case Report.
Asuka Nakazaki, Shigeru Yamaguchi, Hiroaki Motegi, Yukitomo Ishi, Michinari Okamoto, Miki Fujimura
NMC case report journal, 9, 213, 216, 2022, [Domestic magazines]
English, Scientific journal, Facial nerve function improvement is a challenging goal in facial nerve schwannoma (FNS) surgery. Intraoperative continuous monitoring of evoked facial nerve electromyograms (CFN-EMGs) is performed in acoustic neuroma surgery to preserve facial nerve function. CFN-EMGs were applied in decompression surgery for FNS with severe facial paresis. A 39-year-old woman presented with a sudden onset of vertigo, left hearing disturbance, and severe left facial palsy with House-Brackmann (HB) grade 5. FNS was strongly suspected based on the patient's clinical course and magnetic resonance imaging findings, and the patient underwent surgical decompression of the internal auditory canal (IAC) to improve facial nerve function 9 weeks after onset. CFN-EMG responses suddenly improved after removing the posterior wall of the IAC and incising its dura matter. Since the patient's facial nerve paresis improved to HB grade 2 after surgery, CFN-EMGs could detect the moment of facial nerve decompression. This would be the first report to show that CFN-EMGs applied in decompression surgery for FNS could detect the effects of decompression during surgery in real-time. Thus, CFN-EMGs may be an effective monitoring method in decompression surgery for FNS.

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, 159, 314, 326, 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.

Ollier病に合併した多発神経膠腫の一例　　　　　　　　　　　　　　　
池田 寛, 山口 秀, 伊師 雪友, 若林 健人, 清水 亜衣, 岡本 迪成, 茂木 洋晃, 藤村 幹
Brain Tumor Pathology, 38, Suppl., 079, 079, 日本脳腫瘍病理学会, May 2021
Japanese

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, 6, 4, 542, 552, 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.

【脳神経画像Critical Findings-おさえておきたい症状とCT/MRI画像所見】CT/MRIで見落とし・誤認してはいけない疾患 CT isoattenuated/MRI isointense lesions くも膜下出血
遠藤 英徳, 藤村 幹, 冨永 悌二
Neurological Surgery, 49, 2, 220, 228, (株)医学書院, Mar. 2021
Japanese

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.

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
57, 61, Springer, 2021
English, 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.

Cerebral Hyperperfusion and Concomitant Reversible Lesion at the Splenium after Direct Revascularization Surgery for Adult Moyamoya Disease: Possible Involvement of MERS and Watershed Shift Phenomenon.
Ryosuke Tashiro, Miki Fujimura, Taketo Nishizawa, Atsushi Saito, Teiji Tominaga
NMC case report journal, 8, 1, 451, 456, 2021, [Domestic magazines]
English, Scientific journal, Superficial temporal artery (STA)-middle cerebral artery (MCA) bypass is the standard surgical treatment for moyamoya disease (MMD). Local cerebral hyperperfusion (CHP) is one of the potential complications, which could enhance intrinsic inflammation and oxidative stress in MMD patients and accompany concomitant watershed shift (WS) phenomenon, defined as the paradoxical decrease in the cerebral blood flow (CBF) near the site of CHP. However, CHP and simultaneous remote reversible lesion at the splenium have never been reported. A 22-year-old man with ischemic-onset MMD underwent left STA-MCA bypass. Although asymptomatic, local CHP and a paradoxical CBF decrease at the splenium were evident on N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography 1 day after surgery. The patient was maintained under strict blood pressure control, but he subsequently developed transient delirium 4 days after surgery. MRI revealed a high-signal-intensity lesion with a low apparent diffusion coefficient at the splenium. After continued intensive management, the splenial lesion disappeared 14 days after surgery. The patient was discharged without neurological deficits. Catheter angiography 2 months later confirmed marked regression of posterior-to-anterior collaterals via the posterior pericallosal artery, suggesting dynamic watershed shift between blood flow supplies from the posterior and anterior circulation. Mild encephalitis/encephalopathy with a reversible splenial lesion could explain the pathophysiology of the postoperative splenial lesion in this case, which is associated with generation of oxidative stress, enhanced inflammation, and metabolic abnormalities. Rapid postoperative hemodynamic changes, including local CHP and concomitant WS phenomenon, might participate in the formation of the splenial lesion.

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, Scientific journal, 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.

単球のシングルセルRNAシークエンス分析から明らかになった脳卒中に及ぼす糖尿病の影響の機序(Single-cell RNA-sequencing analysis of monocytes reveals mechanism of diabetic effect on stroke)　　　　　　　　　　　　　　　
面高 俊介, 藤村 幹, Liu Jialing, 冨永 悌二
脳循環代謝, 32, 1, 80, 80, (一社)日本脳循環代謝学会, Nov. 2020
English

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, 135, 2, 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, Scientific journal, 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, Scientific journal, 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, Scientific journal, 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, Scientific journal, 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, Scientific journal, 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, Scientific journal, 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, 33, 1, 1, 4, 21 Feb. 2020, [International Magazine]
English, Scientific journal, 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, Scientific journal, 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, Scientific journal, 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, 134, 1, 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

Revascularization of the anterior cerebral artery by Y-shaped superficial temporal artery interposition graft for the treatment of a de novo aneurysm arising at the site of A₃-A₃ bypass: technical case report.
Endo H, Sugiyama SI, Endo T, Fujimura M, Shimizu H, Tominaga T
Journal of neurosurgery, 1, 5, Dec. 2017, [Peer-reviewed]

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

再生医療の基礎と臨床UP to DATE Muse細胞による脳梗塞治療　　　　　　　　　　　　　　　
新妻 邦泰, 坂田 洋之, 内田 浩喜, 森田 隆弘, 阿部 考貢, 藤村 幹, 出澤 真理, 冨永 悌二
脳循環代謝, 28, 1, 127, 127, (一社)日本脳循環代謝学会, Nov. 2016
Japanese

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, 69歳女性。発熱を主訴に近医を受診、髄膜炎を疑われ紹介入院となった。頭部CTでは明らかな異常所見はみられなかったが、第3病日目に項部硬直を認め、髄液検査では細菌性髄膜炎と矛盾しない所見であった。だが、起因菌は同定されなかった。その後も解熱せず、第9病日目にはJCS:100に悪化、頭部CTでは顕著な脳室拡大を認め、再度の髄液検査でListeria monocytogensのRNAが検出された。抗菌薬を変更し、腰椎ドレナージを開始するも脳室拡大が改善せず、第11病日目には脳室ドレナージを施行、意識状態の改善が得られた。以後、第28病日目の髄液培養検査でListeria monocytogensが陰性となり、抗菌薬を中止したが、頭部MRIでは側脳室と第三脳室の拡大と中脳水道狭窄が認められた。そこで治療に際しては、脳室ドレナージの排液量に依存して意識状態が変動するため水頭症治療が必要と考えたが、MRIでは第三脳室と側脳室の拡大は認めるが第四脳室の拡大は伴わず、中脳水道狭窄が疑われた。第三脳室の平坦化と終板の前方偏位が認められ、内視鏡的第三脳室底開窓術の適応と判断した。その結果、術後、ドレーンからの排出を止めても神経症状の悪化は認めず、術後7日目にドレーン抜去、感染徴候や水頭症の進行なく経過して術後1ヵ月後にリハビリテーション目的で転院となった。

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

Current Status of Revascularization Surgery for Moyamoya Disease: Special Consideration for Its 'Internal Carotid-External Carotid (IC-EC) Conversion' as the Physiological Reorganization System
Miki Fujimura, Teiji Tominaga
TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE, 236, 1, 45, 53, May 2015, [Peer-reviewed]
English

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

Quantitative analysis of early postoperative cerebral blood flow contributes to the prediction and diagnosis of cerebral hyperperfusion syndrome after revascularization surgery for moyamoya disease
Miki Fujimura, Kuniyasu Niizuma, Hidenori Endo, Kenichi Sato, Takashi Inoue, Hiroaki Shimizu, Teiji Tominaga
NEUROLOGICAL RESEARCH, 37, 2, 131, 138, 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

Double catheterとEnterprise VRDを用いて治療した右眼動脈部動脈瘤の1例
千葉 哲矢, 木村 尚人, 下田 由輝, 藤村 幹, 江面 正幸, 上野原 広司
JNET: Journal of Neuroendovascular Therapy, 6, 5, 306, 306, (NPO)日本脳神経血管内治療学会, Nov. 2012
Japanese

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

Significance of focal cerebral hyperperfusion as a cause of transient neurologic deterioration after extracranial-intracranial bypass for moyamoya disease: Comparative study with non-moyamoya patients using n-isopropyl-p-[ 123I]iodoamphetamine single-photon emission computed tomography
Miki Fujimura, Hiroaki Shimizu, Takashi Inoue, Shunji Mugikura, Atsushi Saito, Teiji Tominaga
Neurosurgery, 68, 4, 957, 965, Apr. 2011, [Peer-reviewed]
English, 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, 71, 979, 348, 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.

もやもや病のエピゲノム病態修飾因子-血漿microRNA-探索
伊東雅基, 内野晴登, 東海林菊太郎, 杉山拓, 川堀真人, 岩田育子, 矢部一郎, 寳金清博, 藤村幹, 日本分子脳神経外科学会プログラム・抄録集, 24th, 2024

大学病院における多診療科連携型軽度認知障害センターの構築
岩田育子, 松島理明, 宇土仁木, 池辺洋平, 平田健司, 杉山拓, 森田真也, 渡邊裕, 向野雅彦, 中村昭伸, 佐久嶋研, 熊谷聡美, 藤村幹, 工藤與亮, 矢部一郎, Dementia Japan, 38, 4, 2024

高齢もやもや病患者に対する血行再建術:長期治療成績の検討
藤村幹, 栗栖宏多, 伊東雅基, 内野晴登, 杉山拓, 日本老年脳神経外科学会プログラム・抄録集, 37th, 2024

Preservation of collateral venous pathway during microvascular decompression for trigeminal neuralgia associated with ipsilateral internal jugular vein occlusion
杉山拓, 藤村幹, 日本脳神経減圧術学会プログラム・抄録集, 26th, 2024

もやもや病におけるRNF213変異の血管negative remodeling促進効果
内野晴登, 伊東雅基, 杉山拓, 栗栖宏多, 藤村幹, 日本脳神経CI学会総会プログラム・抄録集, 47th, 2024

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

Comprehensive validation of circulating microRNA signatures for Moyamoya disease
伊東雅基, 内野晴登, 東海林菊太郎, 杉山拓, 川堀真人, 岩田育子, 矢部一郎, 寶金清博, 藤村幹, 月刊メディカル・サイエンス・ダイジェスト, 50, 6, 2024

パーキンソン病脳深部刺激療法術後5年目における治療有効性の評価　　　　　　　　　　　　　　　
白井 慎一, 江口 克紀, 山崎 和義, 松島 理明, 川堀 真人, 平田 健司, 藤村 幹, 矢部 一郎, パーキンソン病・運動障害疾患コングレスプログラム・抄録集, 17回, 86, 86, Jul. 2023
Movement Disorder Society of Japan (MDSJ), 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, 大前敬介, 伊東雅基, 杉山拓, 石井伸明, 藤村幹, 脳血管内治療(Web), 8, Supplement, 2023

特殊な血管性病変とその治療 解離性脳動脈瘤
杉山拓, 藤村幹, Clinical Neuroscience, 41, 10, 2023

高齢者における頚動脈内膜剥離術の臨床的特徴および治療成績の検討
池田寛, 杉山拓, 伊東雅基, 内野晴登, 長内俊也, 藤村幹, 日本老年脳神経外科学会プログラム・抄録集, 36th, 2023

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

成人もやもや病のMRA末梢動脈信号強度と間接血行発達度の関連
内野晴登, 伊東雅基, 杉山拓, 川堀真人, 長内俊也, 藤村幹, 日本脳神経CI学会総会プログラム・抄録集, 46th, 2023

脳深部刺激療法術後4年の経過に関する12例の検討　　　　　　　　　　　　　　　
白井 慎一, 江口 克紀, 山崎 和義, 松島 理明, 加納 崇裕, 笹森 徹, 平田 健司, 大槻 美佳, 北川 まゆみ, 寳金 清博, 佐々木 秀直, 藤村 幹, 矢部 一郎, パーキンソン病・運動障害疾患コングレスプログラム・抄録集, 16回, 80, 80, Jul. 2022
Movement Disorder Society of Japan (MDSJ), Japanese

成人もやもや病複合血行再建術後バイパス路発達におけるRNF213創始者変異の意義
伊東雅基, 川堀真人, 杉山拓, 東海林菊太郎, 舘澤諒大, 内野晴登, 数又研, 寳金清博, 藤村幹, Mt. Fuji Workshop on CVD, 39th, 2022

A Pilot study of the Usefulness of Telementoring in Teaching Endovascular Therapy
長内俊也, 大川原舞, 前田拓真, 山口裕之, 藤村幹, 脳血管内治療(Web), 7, Supplement, 2022

三次元融合画像による術前シミュレーションが有効であった脳幹部海綿状血管腫の一例
大木聡悟, 茂木洋晃, 澤谷亮佑, 岡本迪成, 越前谷すみれ, 杉山拓, 山口秀, 藤村幹, 日本脳腫瘍の外科学会プログラム・抄録集, 27th, 2022

成人もやもや病に対する直接・間接複合血行再建術後のバイパス路発達の術前要因
伊東雅基, 内野晴登, 川堀真人, 杉山拓, 数又研, 宝金清博, 藤村幹, 日本分子脳神経外科学会プログラム・抄録集, 22nd, 2022

高齢者虚血型もやもや病の疫学と治療
藤村幹, 伊東雅基, 杉山拓, 遠藤英徳, 冨永悌二, 日本老年脳神経外科学会プログラム・抄録集, 35th (CD-ROM), 2022

Brainstem/spinal cord gliomas with IDH mutation: report of four cases
澤谷亮佑, 伊師雪友, 山口秀, 岡本迪成, 茂木洋晃, 高宮宗一朗, 関俊隆, 大塚拓也, 若林健人, 松野吉宏, 種井善一, 田中伸哉, 藤村幹, 日本脳腫瘍学会学術集会プログラム・抄録集, 39th, 2021

もやもや病に対するバイパス術と実臨床における疾患感受性遺伝子RNF213の意義
藤村幹, 伊東雅基, 杉山拓, 内野晴登, 東海林菊太郎, 日本分子脳神経外科学会プログラム・抄録集, 21st, 2021

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(Web), 33, 1, 2021

基本をマスター 脳神経外科手術のスタンダード 内頸動脈瘤に対するhigh flow bypass
遠藤 英徳, 藤村 幹, 冨永 悌二, 脳神経外科速報, 30, 3, 258, 265, Mar. 2020
(株)メディカ出版, Japanese

成人もやもや病に対するバイパス術後の遅発性過灌流とRNF213遺伝子c.14576G>A多型の関連についての検討
藤村幹, 田代亮介, 勝木将人, 西澤威人, 遠又靖丈, 新妻邦泰, 冨永悌二, 脳循環代謝(Web), 32, 1, 2020

三叉神経根近傍の脳幹脳動静脈奇形に対する塞栓術の治療成績　　　　　　　　　　　　　　　
遠藤 英徳, 松本 康史, 佐藤 健一, 大沢 伸一郎, 藤村 幹, 新妻 邦泰, 冨永 悌二, 脳血管内治療, 4, Suppl., S199, S199, Nov. 2019
(NPO)日本脳神経血管内治療学会, Japanese

外科的血行再建と脳循環 成人もやもや病に対するSTA-MCAバイパス術後急性期の脳循環動態と臨床像についての検討　　　　　　　　　　　　　　　
藤村 幹, 田代 亮介, 亀山 昌幸, 佐藤 健一, 遠藤 英徳, 新妻 邦泰, 冨永 悌二, 脳循環代謝, 31, 1, 87, 87, Nov. 2019
(一社)日本脳循環代謝学会, Japanese

外科的血行再建と脳循環 術中ICGによるCEA術後過灌流予測　　　　　　　　　　　　　　　
井上 敬, 坂田 洋之, 井上 智夫, 江面 正幸, 上之原 広司, 斉藤 敦志, 藤村 幹, 遠藤 英徳, 新妻 邦泰, 冨永 悌二, 脳循環代謝, 31, 1, 88, 88, Nov. 2019
(一社)日本脳循環代謝学会, Japanese

成人もやもや病に対するSTA-MCAバイパス術後の特異な脳循環動態 watershed shift現象の臨床像に関する検討　　　　　　　　　　　　　　　
田代 亮介, 藤村 幹, 亀山 昌幸, 麦倉 俊司, 遠藤 英徳, 新妻 邦泰, 冨永 悌二, 脳循環代謝, 31, 1, 112, 112, Nov. 2019
(一社)日本脳循環代謝学会, Japanese

側副血行発達の異なる系統マウスにおける微小循環の検討　　　　　　　　　　　　　　　
鹿毛 淳史, 西嶌 泰生, 藤村 幹, 新妻 邦泰, 遠藤 英徳, Liu Jialing, 冨永 悌二, 脳循環代謝, 31, 1, 120, 120, Nov. 2019
(一社)日本脳循環代謝学会, Japanese

専門医に求められる最新の知識 脳血管障害 脳底動脈瘤に対するバイパスと血管内治療を併用したハイブリッド治療戦略
遠藤 英徳, 佐藤 健一, 藤村 幹, 杉山 慎一郎, 千葉 朋浩, 冨永 悌二, 脳神経外科速報, 29, 9, 960, 966, Sep. 2019
(株)メディカ出版, Japanese

脳動脈瘤の出血源診断における造影MRIの有用性　　　　　　　　　　　　　　　
面高 俊介, 遠藤 英徳, 新妻 邦泰, 遠藤 俊毅, 佐藤 健一, 藤村 幹, 松本 康史, 井上 敬, 冨永 悌二, 東北脳血管障害研究会学術集会記録集, 40回, 0076, 0091, Dec. 2018
サノフィ(株)仙台オフィス, Japanese

バイオマーカーによる脳卒中診断　　　　　　　　　　　　　　　
井上 敬, 石田 邦久, 新妻 邦泰, 井上 智夫, 齋藤 敦志, 江面 正幸, 遠藤 英徳, 藤村 幹, 冨永 悌二, 脳循環代謝, 30, 1, 119, 119, Oct. 2018
日本脳循環代謝学会, Japanese

小児もやもや病に対する直接間接複合バイパス術―長期治療成績と課題―
藤村幹, 遠藤英徳, 新妻邦泰, 冨永悌二, Mt. Fuji Workshop on CVD, 36, 1, 4, Jul. 2018
(株)にゅーろん社, Japanese

脳血管障害の基礎知識 脳卒中専門医に知っておいてほしいキーワード外科系(第13回) 頭蓋内内頸動脈系の動脈解離
遠藤 英徳, 冨永 悌二, 藤村 幹, 松本 康史, 分子脳血管病, 17, 1, 62, 65, Jan. 2018
(株)先端医学社, Japanese

Current Indications and Problems of CEA and CAS
遠藤英徳, 藤村幹, 松本康史, 遠藤俊毅, 佐藤健一, 新妻邦泰, 井上敬, 冨永悌二, 脳神経外科ジャーナル, 27, 7, 514‐521(J‐STAGE), 521, 2018
(一社)日本脳神経外科コングレス, Japanese

治療困難な脳動脈瘤に対するバイパス術併用血管内治療　　　　　　　　　　　　　　　
佐藤 健一, 藤村 幹, 遠藤 英徳, 松本 康史, 冨永 悌二, 脳血管内治療, 2, Suppl., S121, S121, Nov. 2017
(NPO)日本脳神経血管内治療学会, Japanese

もやもや病を究める もやもや病の脳循環研究 SPECTを用いた術後急性期病態の解明　　　　　　　　　　　　　　　
藤村 幹, 麦倉 俊司, 遠藤 英徳, 新妻 邦泰, 藤原 悟, 冨永 悌二, 脳循環代謝, 29, 1, 144, 144, Nov. 2017
日本脳循環代謝学会, Japanese

頭蓋外内バイパス術後急性期に低灌流にもかかわらず症候性血管原性浮腫を生じた成人もやもや病の1例　　　　　　　　　　　　　　　
田代 亮介, 藤村 幹, 麦倉 俊司, 新妻 邦泰, 遠藤 英徳, 冨永 悌二, 脳循環代謝, 29, 1, 193, 193, Nov. 2017
日本脳循環代謝学会, Japanese

Multi-delay ASLによるCEA周術期脳循環動態評価　　　　　　　　　　　　　　　
遠藤 英徳, 藤村 幹, 遠藤 俊毅, 面高 俊介, 大友 一匡, 新妻 邦泰, 冨永 悌二, 脳循環代謝, 29, 1, 180, 180, Nov. 2017
日本脳循環代謝学会, Japanese

Choroidal arteryを標的としたAVM塞栓術の治療成績　　　　　　　　　　　　　　　
遠藤 英徳, 松本 康史, 佐藤 健一, 新妻 邦泰, 遠藤 俊毅, 藤村 幹, 冨永 悌二, 脳血管内治療, 2, Suppl., S32, S32, Nov. 2017
(NPO)日本脳神経血管内治療学会, Japanese

仙骨部脊髄動静脈シャント疾患に対する外科治療　　　　　　　　　　　　　　　
遠藤 俊毅, 佐藤 健一, 藤村 幹, 面高 俊介, 遠藤 英徳, 松本 康史, 冨永 悌二, 脳血管内治療, 2, Suppl., S110, S110, Nov. 2017
(NPO)日本脳神経血管内治療学会, Japanese

造影MRIを用いた多発脳動脈瘤の出血源診断　　　　　　　　　　　　　　　
面高 俊介, 遠藤 英徳, 新妻 邦泰, 遠藤 俊毅, 藤村 幹, 佐藤 健一, 松本 康史, 冨永 悌二, 脳血管内治療, 2, Suppl., S269, S269, Nov. 2017
(NPO)日本脳神経血管内治療学会, Japanese

Further Implications of Off-Label Use of Acetazolamide in the Management of Moyamoya Disease in Japan
Shunji Mugikura, Miki Fujimura, Shoki Takahashi, Kei Takase, RADIOLOGY, 284, 1, 301, 302, Jul. 2017
English, Report scientific journal

脳動脈瘤治療の標準化と最適化 脳動脈瘤塞栓術の標準化と最適化　　　　　　　　　　　　　　　
松本 康史, 佐藤 健一, 遠藤 俊毅, 遠藤 英徳, 藤村 幹, 冨永 悌二, The Mt. Fuji Workshop on CVD, 35, 72, 77, Jul. 2017
(株)にゅーろん社, Japanese

Can Combined Bypass Surgery at Middle Cerebral Artery Territory Save Anterior Cerebral Artery Territory in Adult Moyamoya Disease? COMMENT
Miki Fujimura, Teiji Tominaga, NEUROSURGERY, 80, 3, 438, 438, Mar. 2017
English, Others

10分で速習! スライドでわかる脳神経外科手術のポイント VA-PICA ANに対する手術のコツとピットフォール
遠藤 英徳, 藤村 幹, 遠藤 俊毅, 冨永 悌二, 脳神経外科速報, 27, 3, 265, 272, Mar. 2017
(株)メディカ出版, Japanese

新規脳梗塞治療薬SMTP-7の開発
新妻邦泰, 藤村幹, 清水宏明, 冨永悌二, 脳循環代謝(Web), 29, 1, 2017

内頚動脈前壁チマメ状動脈瘤の病態と治療戦略
遠藤英徳, 藤村幹, 清水宏明, 遠藤俊毅, 藤原悟, 冨永悌二, 日本臨床脳神経外科学会プログラム・抄録集, 20th, 2017

マウス一過性中大脳動脈閉塞モデルにおけるimaging mass spectrometryによるメタボローム解析
阿部考貢, 新妻邦泰, 鹿毛淳史, 藤村幹, 三枝大輔, 宇留野晃, 山本雅之, 冨永悌二, 日本分子脳神経外科学会プログラム・抄録集, 18th, 2017

下垂体腺腫治療後の内頸動脈瘤形成 その成因と治療　　　　　　　　　　　　　　　
坂田 洋之, 遠藤 英徳, 藤村 幹, 小川 欣一, 城倉 英史, 川岸 潤, 佐藤 健一, 松本 康史, 遠藤 俊毅, 冨永 悌二, 東北脳血管障害研究会学術集会記録集, 38回, 0271, 0283, Dec. 2016
サノフィ(株)仙台オフィス, Japanese

成人もやもや病に対する直接間接複合バイパス術 脳循環画像に基づいた周術期管理の効果とpitfall　　　　　　　　　　　　　　　
藤村 幹, 坂田 洋之, 新妻 邦泰, 遠藤 英徳, 井上 敬, 冨永 悌二, 脳循環代謝, 28, 1, 182, 182, Nov. 2016
日本脳循環代謝学会, Japanese

CEA術前脳循環予備能測定は必要か?　　　　　　　　　　　　　　　
井上 敬, 江面 正幸, 上之原 広司, 遠藤 英徳, 藤村 幹, 冨永 悌二, 脳循環代謝, 28, 1, 218, 218, Nov. 2016
日本脳循環代謝学会, Japanese

Arterial Spin Labelingを使用したCEA周術期脳循環動態評価　　　　　　　　　　　　　　　
遠藤 英徳, 藤村 幹, 遠藤 俊毅, 井上 敬, 清水 宏明, 冨永 悌二, 脳循環代謝, 28, 1, 208, 208, Nov. 2016
日本脳循環代謝学会, Japanese

後方循環血行力学的脳虚血に対して血行再建を行った2例　　　　　　　　　　　　　　　
長田 佳整, 遠藤 英徳, 遠藤 俊毅, 佐藤 健一, 松本 康史, 藤村 幹, 冨永 悌二, 脳循環代謝, 28, 1, 216, 216, Nov. 2016
日本脳循環代謝学会, Japanese

Choroidal arteryを標的としたAVM塞栓術の治療成績　　　　　　　　　　　　　　　
遠藤 英徳, 松本 康史, 佐藤 健一, 近藤 竜史, 新妻 邦泰, 遠藤 俊毅, 藤村 幹, 冨永 悌二, 脳血管内治療, 1, Suppl., S98, S98, Nov. 2016
(NPO)日本脳神経血管内治療学会, Japanese

待機手術を施行した脊髄軟膜動静脈瘻の1治療例　　　　　　　　　　　　　　　
新妻 邦泰, 佐藤 健一, 遠藤 俊毅, 眞野 唯, 赤松 洋祐, 藤村 幹, 冨永 悌二, 脳血管内治療, 1, Suppl., S130, S130, Nov. 2016
(NPO)日本脳神経血管内治療学会, Japanese

食道癌・咽頭癌に関連する感染性仮性総頸動脈破裂の一治療例　　　　　　　　　　　　　　　
新妻 邦泰, 川口 奉洋, 佐々木 貴史, 藤村 幹, 小川 武則, 香取 幸夫, 松本 康史, 冨永 悌二, 脳血管内治療, 1, Suppl., S208, S208, Nov. 2016
(NPO)日本脳神経血管内治療学会, Japanese

OUTCOME AND RISK FACTORS FOR MENINGITIS AFTER CRANIOTOMY IN PATIENTS WITH SUBARACHNOID HEMORRHAGE
T. Inoue, M. Fujimura, H. Endo, T. Tominaga, INTERNATIONAL JOURNAL OF STROKE, 11, SUPP 3, 66, 66, Oct. 2016
English, Summary international conference

脳主幹動脈閉塞に対する緊急EC-IC bypassの治療成績
遠藤 英徳, 藤村 幹, 清水 宏明, 井上 敬, 藤原 悟, 冨永 悌二, The Mt. Fuji Workshop on CVD, 34, 196, 200, Aug. 2016
脳主幹動脈閉塞に対する緊急extracranial-intracranial(EC-IC) bypassの治療成績について検討した。前方循環の脳主幹動脈閉塞に対して緊急EC-IC bypass術を施行した11例を対象とした。閉塞部位は内頸動脈が7例、中大脳動脈(M1)が4例で、閉塞機転の原因は、動脈硬化7例、動脈解離3例、放射線治療後1例であった。症状出現から手術開始までの時間は6.5〜96時間であった。Single bypassを9例、double bypassを2例に行い、M4の遮断時間は18〜54分であった。Modified NIHSSは9例で術後改善し、中央値の推移は術直前6、術翌日5、術後7日目3であった。術後7日目のmodified NIHSSは術直前と比較して有意に改善した。腎不全に起因する全身状態悪化をきたした1例で梗塞増大による症状悪化を認めた。6ヵ月後に画像追跡を行った9例全例でbypassの開存を確認した。6ヵ月後の転帰は、良好(mRS 0-2)が8例(73%)であった。, (株)にゅーろん社, Japanese

EDARAVONE (MCI-186) ALLEVIATES ACUTE BRAIN INJURY AFTER SUBARACHNOID HEMORRHAGE IN RATS
K. Niizuma, A. Ito, T. Sasaki, M. Fujimura, P. H. Chan, T. Tominaga, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 36, 359, 360, Jun. 2016
English, Summary international conference

MOUSE MODEL OF LACUNAR INFARCTS WITH LONG-LASTING FUNCTIONAL DISABILITIES
H. Uchida, K. Niizuma, H. Sakata, M. Fujimura, M. Dezawa, T. Tominaga, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 36, 215, 215, Jun. 2016
English, Summary international conference

QUANTITATIVE MEASUREMENT OF CEREBRAL BLOOD FLOW USING SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY WITH VENOUS BLOOD SAMPLING
T. Inoue, H. Shimizu, M. Fujimura, K. Sato, H. Endo, K. Niizuma, H. Sakata, T. Tominaga, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 36, 402, 402, Jun. 2016
English, Summary international conference

Arterial Spin Labelingを使用したCEA周術期脳循環動態評価
遠藤英徳, 藤村幹, 遠藤俊毅, 井上敬, 清水宏明, 冨永悌二, 脳循環代謝(Web), 28, 1, 2016

Current status of the revascularization surgery for moyamoya disease
Miki Fujimura, Teiji Tominaga, Japanese Journal of Neurosurgery, 25, 10, 844, 850, 2016
Japanese Congress of Neurological Surgeons, Japanese, Book review

The pathophysiology of moyamoya disease: An update
Oh Young Bang, Miki Fujimura, Seung-Ki Kim, Journal of Stroke, 18, 1, 12, 20, 2016
Korean Stroke Society, English, Book review

A case of ruptured infectious anterior cerebral artery aneurysm treated by interposition graft bypass using the superficial temporal artery
Takatsugu Abe, Hidenori Endo, Hiroaki Shimizu, Miki Fujimura, Toshiki Endo, Hiroyuki Sakata, Mika Watanabe, Teiji Tominaga, Surgical Neurology International, 7, 1, 01 Jan. 2016
Medknow Publications, English, Book review

三叉神経根近傍の脳幹脳動静脈奇形 臨床的特徴と治療成績　　　　　　　　　　　　　　　
遠藤 英徳, 佐藤 健一, 大沢 伸一郎, 松本 康史, 藤村 幹, 藤原 悟, 冨永 悌二, 東北脳血管障害研究会学術集会記録集, 37回, 248, 266, Dec. 2015
サノフィ(株)仙台オフィス, Japanese

ONYXはAVMの治療成績を向上させたか? 脳動静脈奇形に対する集学的治療における血管内治療
新妻 邦泰, 佐藤 健一, 松本 康史, 遠藤 英徳, 藤村 幹, 近藤 竜史, 川岸 潤, 冨永 悌二, JNET: Journal of Neuroendovascular Therapy, 9, 6, S191, S191, Nov. 2015
(NPO)日本脳神経血管内治療学会, Japanese

脳動静脈奇形に対する集学的治療における血管内治療　　　　　　　　　　　　　　　
佐藤 健一, 松本 康史, 遠藤 英徳, 藤村 幹, 近藤 竜史, 川岸 潤, 冨永 悌二, JNET: Journal of Neuroendovascular Therapy, 9, 6, 228, 228, Nov. 2015
(NPO)日本脳神経血管内治療学会, Japanese

小児もやもや病に対する直接間接複合バイパス術 長期治療成績の検討　　　　　　　　　　　　　　　
藤村 幹, ラシャド・シェリフ, 遠藤 英徳, 新妻 邦泰, 坂田 洋之, 佐藤 健一, 冨永 悌二, 脳循環代謝, 27, 1, 139, 139, Oct. 2015
日本脳循環代謝学会, Japanese

破裂内頸動脈瘤に対するEC-IC bypassの治療成績　　　　　　　　　　　　　　　
遠藤 英徳, 藤村 幹, 清水 宏明, 井上 敬, 佐藤 健一, 藤原 悟, 冨永 悌二, 脳循環代謝, 27, 1, 142, 142, Oct. 2015
日本脳循環代謝学会, Japanese

CEA術後過灌流予測における脳循環予備能測定の意義　　　　　　　　　　　　　　　
井上 敬, 江面 正幸, 上之原 広司, 遠藤 英徳, 藤村 幹, 藤原 悟, 富永 悌二, 脳循環代謝, 27, 1, 152, 152, Oct. 2015
日本脳循環代謝学会, Japanese

深部脳動静脈奇形周囲にcerebral proliferative angiopathyの2次的形成を認めた小児例　　　　　　　　　　　　　　　
坂田 洋之, 藤村 幹, 佐藤 健一, 新妻 邦泰, 遠藤 英徳, 冨永 悌二, 脳循環代謝, 27, 1, 190, 190, Oct. 2015
日本脳循環代謝学会, Japanese

クモ膜下出血後急性期脳血流の時間的・空間的変化と臨床転帰との相関についての検討
佐藤 健一, 遠藤 英徳, 藤村 幹, 井上 敬, 清水 宏明, 冨永 悌二, 脳循環代謝, 27, 1, 190, 190, Oct. 2015
日本脳循環代謝学会, Japanese

【脳卒中における脳循環代謝画像のすべて-初心者からエキスパートまで-】脳卒中の各病態における脳循環代謝画像の意義 くも膜下出血後脳血流の時間的・空間的変化 3-D SRT softwareを用いたSPECT解析　　　　　　　　　　　　　　　
佐藤 健一, 清水 宏明, 井上 敬, 藤村 幹, 遠藤 英徳, 冨永 悌二, The Mt. Fuji Workshop on CVD, 33, 98,108, 102,108, Jul. 2015
脳動脈瘤破裂によるくも膜下出血(SAH)後、遅発性脳虚血(DCI)予防治療中の88例(男27例、女61例、平均年齢61.2歳)を対象に、SPECT検査を急性期に2回施行し3次元SRTソフトウェアを用いて脳血流量を評価し、局所脳血流量の変化と対応領域の脳梗塞出現の有無および臨床転帰について後方視的に検討した。88症例の脳全体1936領域中40領域でDCIによる脳梗塞巣を認めた。各領域のradio-signal countを両側小脳半球のradio-signal countの平均で除したrCBF比が、正常ボランティア10例の平均と比較して1回目も2回目もhypoperfusion(90%未満)であった領域の13.0%、1回目がnormoperfusion(90%〜110%未満)で2回目がhypoperfusionであった領域の19.1%に脳梗塞巣を認めた。またSAH急性期治療中にrCBFが増加する領域と減少する領域が混在する42例ではそれ以外の群と比較して3ヵ月後の臨床転帰が有意に不良で、転帰不良の原因の50%はDCIによるものであった。, (株)にゅーろん社, Japanese

開頭術または血管内塞栓術後の残存・再発脳動脈瘤に対する開頭術
清水 宏明, 柳澤 俊晴, 遠藤 英徳, 井上 敬, 藤村 幹, 松本 康史, 冨永 悌二, 脳卒中の外科, 43, 3, 212, 217, May 2015
2001年以降に開頭術またはコイル塞栓術を施行し、術後に動脈瘤の残存、再発または破裂を呈して開頭術を施行した14名(男3、女11、平均年齢58歳)を対象に、臨床症状や再手術の成績について再調査した。初回発症形式は、くも膜下出血8名、未破裂動脈瘤6名で、開頭術を8名(クリッピング術7、ラッピング術1)、コイル塞栓術を6名に施行した。再手術前の症状は、破裂1名、動脈瘤頸部残存2名、動脈瘤の増大11名であった。どちらの術式でも、初回手術で不完全閉塞の場合に再発リスクが上昇し、コイル塞栓術の場合は10mm以上の大きさも再発リスクになることが示された。, (一社)日本脳卒中の外科学会, Japanese

1型糖尿病に合併した成人・類もやもや病の1手術例
赤松 洋祐, 藤村 幹, 坂田 洋之, 遠藤 英徳, 板橋 亮, 冨永 悌二, Neurological Surgery, 43, 3, 227, 233, Mar. 2015
32歳女。6歳時に1型糖尿病を発症しインスリン自己注射を行っていた。右眼前暗黒感で受診し、MRIで頭蓋内虚血性病変を指摘された。123I-IMP SPECTでは、左前頭葉・頭頂葉において左前頭葉の梗塞巣周囲に広がる安静時血流低下を認めた。左大脳半球に直接・間接血行再建術を施行した。周術期の血糖コントロールは持続皮下インスリン注入療法にボーラスインスリン療法を併用した。過灌流症候群の予防を目的として、術直後より予防的降圧とミノサイクリン塩酸塩投与を開始した。術翌日、7日目のSPECT上も明らかな過灌流はみられなかった。術後MRAでは良好なSTAの開通性を確認し、拡散強調像でも新たな虚血性病変はなく、術後2週間で神経学的欠損症状もなく自宅退院した。術後3ヵ月間、脳血管イベントはなく経過している。, (株)医学書院, Japanese

【脳動脈瘤と脳動静脈奇形の最新治療】開頭・血管内手術を利用した複合脳動脈瘤手術
清水 宏明, 松本 康史, 遠藤 英徳, 井上 敬, 藤村 幹, 冨永 悌二, 脳神経外科ジャーナル, 24, 3, 165, 172, Mar. 2015
日本脳神経外科コングレス, Japanese

クモ膜下出血後脳血流の時間的・空間的変化 3DSRT softwareを用いたSPECT解析
佐藤 健一, 清水 宏明, 井上 敬, 藤村 幹, 遠藤 英徳, 冨永 悌二, 脳血管攣縮, 30, 56, 56, Mar. 2015
スパズム・シンポジウム事務局, Japanese

Cerebral blood flow measurement using single photon emission computed tomography with venous blood sampling
T. Inoue, S. Fujiwara, M. Ezura, H. Uenohara, M. Fujimura, T. Tominaga, CEREBROVASCULAR DISEASES, 39, 18, 18, 2015
English, Summary international conference

出血発症した三叉神経根近傍の脳幹部動静脈奇形4例の治療経験
大沢 伸一郎, 遠藤 英徳, 佐藤 健一, 松本 康史, 藤村 幹, 藤原 悟, 冨永 悌二, JNET: Journal of Neuroendovascular Therapy, 8, 6, 368, 368, Dec. 2014
(NPO)日本脳神経血管内治療学会, Japanese

Laser speckle flowgraphyを用いてバイパス術前後の眼循環評価を行った内頸動脈閉塞症の一例　　　　　　　　　　　　　　　
面高 俊介, 遠藤 英徳, 藤村 幹, 清水 宏明, 藤原 悟, 冨永 悌二, 東北脳血管障害研究会学術集会記録集, 36回, 138, 150, Dec. 2014
サノフィ(株)仙台オフィス, Japanese

非出血性脳動脈解離の外科治療　　　　　　　　　　　　　　　
遠藤 英徳, 清水 宏明, 鈴木 一郎, 近藤 竜史, 松本 康史, 藤村 幹, 井上 敬, 佐藤 健一, 藤原 悟, 冨永 悌二, 東北脳血管障害研究会学術集会記録集, 36回, 290, 314, Dec. 2014
サノフィ(株)仙台オフィス, Japanese

頸椎脱臼骨折整復術前の予防的椎骨動脈塞栓術の二例　　　　　　　　　　　　　　　
新妻 邦泰, 川口 奉洋, 佐藤 健一, 藤村 幹, 遠藤 俊毅, 笹治 達郎, 松本 康史, 冨永 悌二, JNET: Journal of Neuroendovascular Therapy, 8, 6, 382, 382, Dec. 2014
(NPO)日本脳神経血管内治療学会, Japanese

[Usefulness of pulsed water jet in dissecting sphenoid ridge meningioma while preserving arteries].
Toshiki Endo, Atsuhiro Nakagawa, Miki Fujimura, Yukihiko Sonoda, Hiroaki Shimizu, Teiji Tominaga, No shinkei geka. Neurological surgery, 42, 11, 1019, 25, Nov. 2014, [Domestic magazines]
We report the utility of a pulsed water jet device in meningioma surgery. The presented case is that of a 61-year-old woman with left visual disturbance. MRI demonstrated heterogeneously enhanced mass with intratumoral hemorrhage, indicating sphenoid ridge meningioma on her left side. The tumor invaded the cavernous sinus and left optic canal, engulfing the internal carotid artery in the carotid cistern and encased middle cerebral arteries. During the operation, the pulsed water jet device was useful for dissecting the tumor away from the arteries since it was safe in light of preserving parent arteries. The jet did not cause any vascular injury and did not induce vasospasm as shown by postoperative symptomatology and MRIs. With the aid of pulsed water jet, we could achieve total resection of the tumor except for the piece within the cavernous sinus. The patient had no new neurological deficits after the operation. We consider the pulsed water jet as a useful device, especially when the need to dissect meningioma from parent arteries exists. The jet can help neurosurgeons simultaneously achieve tumor resection and preservation of blood vessels., Japanese

破裂瘤の治療後早期に破裂した前交通動脈瘤の一例 血行力学的変化の検討　　　　　　　　　　　　　　　
新妻 邦泰, 杉山 慎一郎, 遠藤 英徳, 佐藤 健一, 松本 康史, 藤村 幹, 冨永 悌二, 脳循環代謝, 26, 1, 166, 166, Nov. 2014
日本脳循環代謝学会, Japanese

破裂内頸動脈瘤に対するEC-IC bypass術後急性期の脳循環動態
遠藤 英徳, 藤村 幹, 佐藤 健一, 清水 宏明, 藤原 悟, 冨永 悌二, 脳循環代謝, 26, 1, 176, 176, Nov. 2014
日本脳循環代謝学会, Japanese

CEA術前後にSPECTは必須か?　　　　　　　　　　　　　　　
井上 敬, 藤村 幹, 佐藤 健一, 遠藤 英徳, 新妻 邦泰, 坂田 洋之, 江面 正幸, 上之原 広司, 藤原 悟, 冨永 悌二, 脳循環代謝, 26, 1, 200, 200, Nov. 2014
日本脳循環代謝学会, Japanese

もやもや病疾患感受性遺伝子RNF213 R4859K変異マウスにおける経時的頭部MRA所見に関する検討　　　　　　　　　　　　　　　
鹿毛 淳史, 藤村 幹, 新妻 邦泰, 坂田 洋之, 伊藤 明, 前田 美香, 呉 繁夫, 冨永 悌二, 脳循環代謝, 26, 1, 180, 180, Nov. 2014
日本脳循環代謝学会, Japanese

もやもや病疾患感受性遺伝子RNF213ノックアウトマウスの一過性局所脳虚血への反応性の検討　　　　　　　　　　　　　　　
伊藤 明, 藤村 幹, 新妻 邦泰, 坂田 洋之, 鹿毛 淳史, 呉 繁夫, 冨永 悌二, 脳循環代謝, 26, 1, 208, 208, Nov. 2014
日本脳循環代謝学会, Japanese

Experimental Model of Lacunar Infarcts in Mice with Long-Lasting Functional Disabilities
Hiroki Uchida, Hiroyuki Sakata, Miki Fujimura, Kuniyasu Niizuma, Mari Dezawa, Teiji Tominaga, CEREBROVASCULAR DISEASES, 38, 9, 9, Sep. 2014
English, Summary international conference

A Case of Anterior Communicating Artery Aneurysm Ruptured after the Treatment of Another Ruptured Aneurysm
Kuniyasu Niizuma, Shin-ichiro Sugiyama, Hidenori Endo, Kenichi Sato, Yasushi Matsumoto, Miki Fujimura, Teiji Tominaga, CEREBROVASCULAR DISEASES, 38, 46, 47, Sep. 2014
English, Summary international conference

【脳動脈瘤の最新知識-成因・病態から最先端治療まで-】Clippingとparent artery occlusion/flow alterationの使い分けを要する内頸動脈瘤の治療
清水 宏明, 遠藤 英徳, 井上 敬, 藤村 幹, 松本 康史, 冨永 悌二, 脳神経外科ジャーナル, 23, 9, 721, 728, Sep. 2014
日本脳神経外科コングレス, Japanese

Actuator-driven pulsed water jet surgery system: Initial clinical experience
Atsuhiro Nakagawa, Toshiki Endo, Yukihiko Sonoda, Ryuta Saito, Masaki Iwasaki, Miki Fujimura, Tomohiro Kawaguchi, Hidenori Endo, Yoshikazu Ogawa, Teiji Tominaga, Transactions of Japanese Society for Medical and Biological Engineering, 52, 0, 63, O-64, 17 Aug. 2014
Japan Soc. of Med. Electronics and Biol. Engineering, Japanese, Report scientific journal

脳血管内治療における数値流体力学 CFD(Computational Fluid Dynamics)の最前線 初心者のための脳動脈瘤CFD解析のパラダイムシフト　　　　　　　　　　　　　　　
木村 尚人, 高尾 洋之, 中山 敏男, 面高 俊介, 杉山 伸一郎, 新妻 邦泰, 藤村 幹, 井上 敬, 江面 正幸, 山本 誠, 村山 雄一, 冨永 悌二, 脳神経外科速報, 24, 7, 758, 762, Jul. 2014
Japanese, Introduction scientific journal

Genetics and Biomarkers of Moyamoya Disease: Significance of RNF213 as a Susceptibility Gene
Miki Fujimura, Shinya Sonobe, Yasuo Nishijima, Kuniyasu Niizuma, Hiroyuki Sakata, Shigeo Kure, Teiji Tominaga, J Stroke, 16, 2, 65, 72, May 2014
Published online: May 30, 2014, English, Introduction scientific journal

もやもや病合併妊娠:移行期医療の現状と問題点
藤村幹, 林俊哲, 白根礼造, 上之原広司, 冨永悌二, 小児の脳神経, 39, 1, 112, 112, 30 Apr. 2014
(一社)日本小児神経外科学会, Japanese

第三脳室開窓術後にSIADHによる低ナトリウム血症を呈した1例　　　　　　　　　　　　　　　
重枝 諒太, 遠藤 英徳, 藤村 幹, 小川 欣一, 清水 宏明, 冨永 悌二, Neurological Surgery, 42, 4, 335, 339, Apr. 2014
症例は25歳男性で、意識障害、歩行障害を主訴に当院入院となった。入院時、臨床経過および頭部MRI所見より、Shunt不全による水頭症再発と診断し、内視鏡的第三脳室開窓術を施行した。術後、意識レベルは改善し、独歩可能となったが、術後6日目より再び意識レベルの悪化、独歩不可能となり、血液検査所見、体重の推移から、SIADHによる低ナトリウム血症と診断した。水制限を開始したところ、意識レベルは改善し、独歩可能な状態となった。水制限は3日間で終了したが、術後10日目に血清Naは改善し、術後24日目に自宅退院となった。, (株)医学書院, Japanese

当施設における症候性脳血管攣縮 当院でのくも膜下出血治療方針の転換および開頭術転帰不良因子の検討
井上 敬, 清水 宏明, 藤村 幹, 遠藤 英徳, 冨永 悌二, 脳血管攣縮, 29, 1, 3, Feb. 2014
2003年〜2012年に破裂動脈瘤によるクモ膜下出血に対し、発症72時間以内に開頭クリッピング術またはコイル塞栓術を施行した1066例の成績を報告した。内訳はクリッピング術575例、塞栓術491例で、2007年以降はコイル塞栓術を第一選択とする方針に変更しており、クリッピング術の占める割合は変更前67%、変更後44%であった。転帰良好例(mRS 0〜2)が占める割合は2007年以前71%、以降76%であった。2007年以降の開頭クリッピング術において、転帰良好例は87%であった。症候性脳血管攣縮を来たした症例は22.3%で、永続的神経脱落症状は8.1%に認めた。髄膜炎は9.5%に発症した。入院時WFNS重症例および髄膜炎の発症が転帰不良と関係しており、脳血管攣縮の発症そのものは関連がなかった。, スパズム・シンポジウム事務局, Japanese

モヤモヤ病におけるMRAによる前方・後方循環病期分類　　　　　　　　　　　　　　　
麦倉 俊司, 村田 隆紀, 高橋 昭喜, 藤村 幹, Japanese Journal of Radiology, 32, Suppl., 8, 8, Feb. 2014
(公社)日本医学放射線学会, Japanese

クモ膜下出血後脳血流の時間的・空間的変化-3DSRT softwareを用いたSPECT解析
佐藤健一, 清水宏明, 井上敬, 藤村幹, 冨永悌二, 日本脳循環代謝学会総会プログラム・抄録号, 26th, 2014

外科治療と循環代謝 もやもや病に対する頭蓋外内血行再建術前後の吻合部局所CBF変化と過灌流症候群の関連についての検討　　　　　　　　　　　　　　　
藤村 幹, 新妻 邦泰, 遠藤 英徳, 井上 敬, 清水 宏明, 冨永 悌二, 脳循環代謝, 25, 1, 114, 114, Nov. 2013
日本脳循環代謝学会, Japanese

内頸動脈遮断時の脳血液循環時間と脳血流量の関係について　　　　　　　　　　　　　　　
佐藤 健一, 清水 宏明, 井上 敬, 藤村 幹, 遠藤 英徳, 冨永 悌二, 脳循環代謝, 25, 1, 128, 128, Nov. 2013
日本脳循環代謝学会, Japanese

各種バイパス術における術後急性期の脳循環 手術侵襲による影響との鑑別を含めて
清水 宏明, 遠藤 英徳, 藤村 幹, 井上 敬, 佐藤 健一, 冨永 悌二, 脳循環代謝, 25, 1, 156, 156, Nov. 2013
日本脳循環代謝学会, Japanese

内頸動脈遮断時の脳血液循環時間と脳血流量の関係　　　　　　　　　　　　　　　
佐藤 健一, 清水 宏明, 藤村 幹, 井上 敬, 松本 康史, 遠藤 英徳, 冨永 悌二, JNET: Journal of Neuroendovascular Therapy, 7, 6, 178, 178, Nov. 2013
(NPO)日本脳神経血管内治療学会, Japanese

Cerebral Hyperperfusion Syndrome After Superficial Temporal Artery- middle Cerebral Artery Bypass for Severe Intracranial Steno-occlusive Disease: A Case Control Study COMMENT
Miki Fujimura, NEUROSURGERY, 72, 6, 942, 943, Jun. 2013
English, Others

High Flow EC-IC Bypass and Aneurysmal Trapping for Ruptured IC Anterior Wall Aneurysm: Postoperative Evaluation of SPECT and MRI/MRA Findings in the Acute Stage
藤村幹, 藤村幹, 清水宏明, 井上敬, 木村尚人, 江面正幸, 上之原広司, 冨永悌二, 脳卒中の外科, 41, 3, 2013

増大した未破裂脳動脈瘤破裂率の検討
井上敬, 清水宏明, 藤原悟, 上之原広司, 藤村幹, 冨永悌二, 日本脳ドック学会総会プログラム・抄録集, 22nd, 2013

動脈血放射性カウント推定法:定量SPECTへの応用
井上敬, 藤村幹, 清水宏明, 江面正幸, 上之原広司, 藤原悟, 冨永悌二, 脳循環代謝, 25, 1, 2013

ワルファリン内服下マウス中大脳動脈閉塞モデルにおける,新規血栓溶解薬SMTP-7の治療効果
伊藤明, 新妻邦泰, 清水宏明, 藤村幹, 冨永悌二, 脳循環代謝, 25, 1, 2013

出血性椎骨動脈解離に対するinternal coil trappingにおける術後延髄梗塞の転帰への影響
遠藤 英徳, 松本 康史, 近藤 竜史, 佐藤 健一, 藤村 幹, 井上 敬, 清水 宏明, 藤原 悟, 高橋 明, 冨永 悌二, JNET: Journal of Neuroendovascular Therapy, 6, 5, 207, 207, Nov. 2012
(NPO)日本脳神経血管内治療学会, Japanese

けいれん発作後経時的イオマゼニール結合能評価
井上 敬, 清水 宏明, 藤村 幹, 遠藤 英徳, 荻田 庄吾, 藤原 悟, 冨永 悌二, 脳循環代謝, 24, 1, 170, 170, Nov. 2012
日本脳循環代謝学会, Japanese

CFD解析による脳動脈瘤壁硬化病変予測の可能性
新妻 邦泰, 杉山 慎一郎, 井上 敬, 遠藤 英徳, 藤村 幹, 佐藤 健一, 清水 宏明, 高橋 明, 冨永 悌二, 脳循環代謝, 24, 1, 195, 195, Nov. 2012
日本脳循環代謝学会, Japanese

5. もやもや病の研究課題 : 生理的代償機構とその破綻の解明(PS3-2 虚血性疾患の課題と展望,プレナリーセッション,脳神経外科学の課題,第32回日本脳神経外科コングレス総会)
藤村 幹, 冨永 悌二, 脳神経外科ジャーナル, 21, 87, 87, 20 Apr. 2012
日本脳神経外科コングレス, Japanese

Efficacy and Limitation of Prophylactic Blood Pressure Lowering to Avoid Hyperperfusion Syndrome after Revascularization Surgery for Moyamoya Disease
藤村幹, 清水宏明, 井上敬, 斉藤敦志, 冨永悌二, 脳卒中の外科, 40, 2, 2012

マウス中大脳動脈閉塞モデルにおける梗塞領域再現性向上の工夫と2次元的脳血流リアルタイムモニタリング
赤松洋祐, 清水宏明, 斉藤敦志, 藤村幹, 冨永悌二, 脳循環代謝, 24, 1, 2012

60歳以上の高齢発症もやもや病に対する頭蓋外内バイパス術の治療成績
藤村幹, 清水宏明, 井上敬, 木村尚人, 江面正幸, 上之原広司, 冨永悌二, 脳循環代謝, 24, 1, 2012

Usefulness of Rapid Saturation of Cropidogrel to Non-Cardiogenic Cerebral Infarction - Pilot Study
Naoto Kimura, Masayuki Ezura, Miki Fujimura, Akira Ito, Misaki Aizawa, Kenichi Tsukita, Koichi Narikawa, Yasushi Suzuki, Hiroshi Uenohara, CEREBROVASCULAR DISEASES, 34, 75, 76, 2012
English, Summary international conference

脳外科術中高感度赤外モニタリングシステム　　　　　　　　　　　　　　　
荒船龍彦, 鷲尾利克, 鎮西清行, 佐久間一郎, 中川敦寛, 藤村幹, 冨永悌二, 第51回日本生体医工学会大会 プログラム・抄録集, 177, 178, 2012

Revascularization Surgery for Pediatric Moyamoya Disease : Significance of Peri-operative Management to avoid Surgical Complication
FUJIMURA Miki, TOMINAGA Teiji, No Shinkei Geka Journal, 20, 11, 802, 808, 20 Nov. 2011
Background: Moyamoya disease is a chronic occlusive cerebrovascular disease with unknown etiology, which is one of the most common causes of child-onset stroke in Japan. Surgical revascularizations, both direct and indirect procedures, prevent cerebral ischemic attack by improving cerebral blood flow, while neurological deterioration during the acute stage after revascularization is not rare. The objective of this study was to clarify the concept of revascularization surgery for pediatric moyamoya disease while considering the risk of surgical complications in the acute stage. Patients and methods: The present study includes 19 consecutive patients with moyamoya disease aged from 2 to 14 years old (mean 8.5), who underwent superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis with indirect pial synangiosis for 32 affected hemispheres. Single-photon emission computed tomography (SPECT) was performed 1 and 7 days after surgery in all cases to evaluate hemodynamic alteration after surgery. Long-term outcome was evaluated by the neurological status 3 months after surgery, and the underlying pathology of surgical complications in the acute stage was diagnosed based on SPECT and magnetic resonance findings. Results: In 28 of 32 hemispheres (87.5%), patients showed a complete disappearance of ischemic attack, 4 of 32 hemispheres (12.5%) showed a reduction of ischemic attack, while none showed deterioration of their symptoms (0%). Transient focal neurologic deterioration due to cerebral hyperperfusion was evident in 2 patients (6.3%), and was resolved by blood pressure lowering. One patient developed pseudo-laminar necrosis probably due to a thrombosis one week after surgery (3.1%), which did not affect his long-term outcome. Conclusion: STA-MCA anastomosis with pial synangiosis is a safe and effective treatment for pediatric moyamoya disease. Routine cerebral blood flow measurement in the acute stage is essential to avoid surgical complications including both cerebral ischemia and hyperperfusion., The Japanese Congress of Neurological Surgeons, Japanese

亜急性期のPTAが奏功した内頸動脈閉塞症の2例
高木 英誠, 江面 正幸, 木村 尚人, 藤村 幹, 上之原 広司, JNET: Journal of Neuroendovascular Therapy, 5, 4, 234, 234, Nov. 2011
(NPO)日本脳神経血管内治療学会, Japanese

ラットくも膜下出血後のacute brain injuryに対するedaravoneの治療効果
新妻 邦泰, 藤村 幹, 遠藤 英徳, 清水 宏明, Chan Pak H, 冨永 悌二, 脳循環代謝, 23, 1, 167, 167, Nov. 2011
日本脳循環代謝学会, Japanese

全ゲノム関連解析による最初のもやもや病遺伝子 RNF213の同定
鎌田 文顕, 青木 洋子, 成澤 あゆみ, 阿部 裕, 小松崎 匠子, 菅野 潤子, 新堀 哲也, 松原 洋一, 呉 繁夫, 菊池 敦生, 土屋 滋, 藤村 幹, 冨永 悌二, 小野 栄夫, 石井 直人, 大和田 祐二, 真下 陽一, 鈴木 洋一, 羽田 明, 日本小児科学会雑誌, 115, 9, 1478, 1478, Sep. 2011
(公社)日本小児科学会, Japanese

【脳血管バイパス術】内頸動脈系閉塞性脳血管病変に対するSTA-MCA bypass術後の急性期画像評価
遠藤 英徳, 藤村 幹, 井上 敬, 清水 宏明, 冨永 悌二, 脳卒中の外科, 39, 3, 163, 168, May 2011
2008年4月〜2009年12月に浅側頭動脈・中大脳動脈(STA-MCA)吻合術を施行した閉塞性脳血管病変8例(男性7例、女性1例、平均62.3歳)を対象に、内頸動脈系閉塞性脳血管病変に対する術後急性期画像評価の有用性を検討した。全例で術前にXe-SPECTを撮影し、発症急性期に血行再建術を行った1例を除く7例で術前にDiamox負荷Xe-SPECTを施行した。安静時脳血流は8例中6例で低下し、脳循環予備能は7例全例で低下していた。内頸動脈系閉塞性脳血管病変に対するSTA-MCA吻合術は安全かつ有効な治療と考えられた。術後急性期の画像評価により、過灌流の有無、バイパス開存性、虚血性・出血性合併症の有無が早期から把握され、病態把握に基づいた安全な周術期管理が可能になると思われた。, (一社)日本脳卒中の外科学会, Japanese

3. Revascularization Surgery for Child-onset Moyamoya Disease : Significance of Perioperative Management to Avoid Surgical Complication in the Acute Stage(PS2-3 Problems in Pediatric Neurosurgery,Plenary Session,Professional Spirit and Research Mind of Neurosurgeons,The 31st Annual Meeting of The Japanese Congress of Neurological Surgeons)
Fujimura Miki, Japanese journal of neurosurgery, 20, 76, 76, 10 Apr. 2011
The Japanese Congress of Neurological Surgeons, Japanese

術後過還流により無症候性脳出血を呈した梗塞・出血混合発症型もやもや病の1例
伊藤明, 藤村幹, 井上敬, 清水宏明, 冨永悌二, 東北脳血管障害研究会学術集会記録集, 33rd, 2011

マウス中大脳動脈閉塞モデルにおける梗塞領域再現性向上の工夫と脳血流リアルタイムモニタリング
赤松洋祐, 清水宏明, 斉藤敦志, 藤村幹, 冨永悌二, 脳循環代謝, 23, 1, 2011

くも膜下出血発症15日以降の症候性脳血管攣縮16例の検討
斉藤敦志, 井上敬, 清水宏明, 藤村幹, 冨永悌二, 脳循環代謝, 23, 1, 2011

脳動脈瘤破裂点の流体力学的特徴:コンピュータ流体解析による検討
面高俊介, 井上敬, 船本健一, 杉山慎一郎, 藤村幹, 清水宏明, 早瀬敏幸, 高橋明, 冨永悌二, 脳循環代謝, 23, 1, 2011

Posterior Circulation and High Prevalence of Ischemic Stroke among Young Pediatric Patients with Moyamoya Disease: Evidence of Angiography-Based Differences by Age at Diagnosis
S. Mugikura, S. Higano, R. Shirane, M. Fujimura, Y. Shimanuki, S. Takahashi, AMERICAN JOURNAL OF NEURORADIOLOGY, 32, 1, 192, 198, Jan. 2011
English

類もやもや病に合併した大型中大脳動脈瘤の一手術例
遠藤 英徳, 藤村 幹, 井上 敬, 藤原 悟, 清水 宏明, 冨永 悌二, 東北脳血管障害研究会学術集会記録集, 32回, 51, 54, Dec. 2010
症例は69歳女性で、一過性構音障害で近医にてMRI上異常所見を指摘され当院に入院した。FLAIR及びT2WIで基底槽と左シルビウス裂に沿ったクモ膜下出血と左大脳半球に陳旧性脳梗塞、脳血管撮影では両側内頸動脈終末部近傍に閉塞・狭窄性変化と周囲にもやもや血管の増生、左中大脳動脈分岐部にblebを伴う径14mmの大型嚢状動脈瘤とその近位のM1に高度狭窄、SPECTで左大脳半球の著明な循環予備能低下を認めた。類もやもや病と診断し開頭手術を行った。左前頭側頭開頭で脳表のクモ膜下出血を除去し、シルビウス裂を剥離してM1を遠位に辿り、動脈瘤をclippingした。脳虚血防止にsuperficial temporal artery-middle cerebral artery bypassを行って終了した。術翌日のMRI・MRAで出血性・虚血性合併症は認めず、IMP-SPECTで脳血流量の著明な増加を認め、過灌流予防に厳重な血圧管理を行った。術後3週間で神経脱落症状なく自宅退院した。, サノフィ(株)仙台オフィス, Japanese

もやもや病における脳血流量の検討
酒見 紀久子, 小田桐 逸人, 佐藤 多智雄, 児玉 裕康, 南部 武幸, 藤村 幹, 富永 悌二, 梁川 功, 岡田 賢, 福田 寛, 核医学技術, 30, 2, 145, 148, Apr. 2010, [Peer-reviewed]
もやもや病疾患の初回安静時Diamox負荷時の123I-IMP脳血流SPECT画像を解析ソフトiSSP/SEEを用いて比較検討した。もやもや病と診断した12例を対象とした。初回安静時検査からDiamox負荷検査時までの検査間隔は2〜4日以内で、血行再建術後の1日および7日目にも123I-IMP SPECT撮像を行った。脳血流量値は初回安静時とDiamox負荷時とも対照側に比べて病巣側が有意に低値を示した。Diamox負荷による脳血流量上昇は、病巣側と対照側の脳血流量に差があり、病巣側において上昇が少なかった。再建術後1日目の脳血流量は初回安静時より高値を示したが、7日目では病巣側と対照側の脳血流量は差が認められず、正常状態に戻った。, (NPO)日本核医学技術学会, Japanese

小児もやもや病の治療戦略 小児もやもや病に対するSTA-MCA吻合術の治療成績について 術後急性期脳血流評価による周術期合併症の回避
藤村 幹, 井上 敬, 遠藤 英徳, 斎藤 敦志, 清水 宏明, 冨永 悌二, 小児の脳神経, 35, 2, 181, 181, Apr. 2010
(一社)日本小児神経外科学会, Japanese

Untitled Commentary
Miki Fujimura, Teiji Tominaga, WORLD NEUROSURGERY, 73, 2, Feb. 2010
English, Others

静脈血採血による定量スペクト
井上敬, 藤村幹, 清水宏明, 藤原悟, 冨永悌二, 脳循環代謝, 22, 1, 2010

皮質静脈逆流を伴う硬膜動静脈瘻における脳実質侵襲の評価:拡散強調画像による検討
佐藤健一, 清水宏明, 藤村幹, 井上敬, 松本康史, 冨永悌二, 脳循環代謝, 22, 1, 2010

高磁場MRIにより血管形態の変化を詳細に観察し得た前大脳動脈解離による脳梗塞の1例
佐藤祥一郎, 板橋亮, 矢澤由加子, 古井英介, 藤村幹, 井上敬, 藤原悟, 東北脳血管障害研究会学術集会記録集, 31st, 63, 66, 05 Dec. 2009
Japanese

ラット全脳虚血後の遅発性海馬CA1神経細胞死におけるPUMAの役割について
新妻 邦泰, 藤村 幹, 遠藤 英徳, 斉藤 敦志, 清水 宏明, チャン・パク・フー, 冨永 悌二, 脳循環代謝, 21, 1, 115, 115, Nov. 2009
日本脳循環代謝学会, Japanese

もやもや病に対するEC-IC bypass術後急性期3D-TOF MRAを用いた症候性過灌流の診断と予測についての検討
藤村 幹, 麦倉 俊司, 新妻 邦泰, 清水 宏明, 冨永 悌二, 脳循環代謝, 21, 1, 138, 138, Nov. 2009
日本脳循環代謝学会, Japanese

Comparison between lectin-like oxidized low density lipoprotein receptor 1 expression and preoperative echogenic findings of vulnerable carotid plaque
A. Saito, M. Fujimura, T. Inoue, H. Shimizu, T. Tominaga, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 29, S502, S503, Oct. 2009
English, Summary international conference

Mechanism of Primary Blast Injury: Insight from Microexplosive Generated Shock Wave-Induced Brain Injury Animal Model and Engineering Experiments
Atsuhiro Nakagawa, Miki Fujimura, Hironobu Okuyama, Tokitada Hashimoto, Kaoruko Kato, Mika Watanabe, Kazuyoshi Takayama, Teiji Tominaga, NEUROSURGERY, 65, 2, 413, 414, Aug. 2009
English, Summary international conference

The Leptomeningeal "Ivy Sign" on Fluid-Attenuated Inversion Recovery MR Imaging in Moyamoya Disease: A Sign of Decreased Cerebral Vascular Reserve?
N. Mori, S. Mugikura, S. Higano, T. Kaneta, M. Fujimura, A. Umetsu, T. Murata, S. Takahashi, AMERICAN JOURNAL OF NEURORADIOLOGY, 30, 5, 930, 935, May 2009
English

colloid cystの2例　　　　　　　　　　　　　　　
李 麗, 麦倉 俊司, 日向野 修一, 梅津 篤司, 村田 隆紀, 高橋 昭喜, 藤村 幹, 冨永 悌二, Japanese Journal of Radiology, 27, Suppl., 15, 15, Apr. 2009
(公社)日本医学放射線学会, Japanese

硬膜動静脈奇形の病態と治療成績:multimodality treatmentにおける外科的治療の役割
清水宏明, 佐藤健一, 松本康史, 近藤竜史, 井上敬, 藤村幹, 冨永悌二, Journal of Neuroendovascular Therapy, 3, 4, 2009

重症くも膜下出血の予後予測における急性期拡散強調画像の有用性
佐藤健一, 清水宏明, 藤村幹, 井上敬, 松本康史, 冨永悌二, 脳循環代謝, 21, 1, 2009

重症くも膜下出血の予後予測における急性期拡散強調画像の有用性
佐藤健一, 清水宏明, 井上敬, 藤村幹, 松本康史, 冨永悌二, 日本脳神経外科学会総会抄録集(CD-ROM), 68th, 2009

虚血発症頭蓋内内頚動脈解離の診断と治療
清水宏明, 松本康史, 近藤竜史, 井上敬, 藤村幹, 斉藤敦志, 高橋明, 冨永悌二, 日本脳神経外科学会総会抄録集(CD-ROM), 68th, 2009

頚動脈プラークに対する新たなdrug delivery systemの試み
斉藤敦志, 石井竜弘, 清水宏明, 藤村幹, 冨永悌二, 日本脳神経外科学会総会抄録集(CD-ROM), 68th, 2009

ラット全脳虚血後の遅発性海馬CA1神経細胞死におけるPIDDosomeの役割について
新妻邦泰, 藤村幹, 遠藤英徳, 斉藤敦志, 清水宏明, CHAN PH, 冨永悌二, 日本脳神経外科学会総会抄録集(CD-ROM), 68th, 2009

もやもや病ならびに他の閉塞性脳血管障害に対するEC-IC bypass術後の過灌流と予後についての比較検討
藤村幹, 清水宏明, 井上敬, 斎藤敦志, 藤原悟, 冨永悌二, 日本脳神経外科学会総会抄録集(CD-ROM), 68th, 2009

Immunoliposomeを用いた頚動脈プラークに対するdrug delivery system
斉藤敦志, 藤村幹, 清水宏明, 冨永悌二, 脳循環代謝, 21, 1, 2009

脊髄損傷後の脳機能局在変化とNogo受容体 機能MRIによる検討
遠藤 俊毅, 藤村 幹, Olson Lars, 冨永 悌二, 脊髄外科, 22, 2, 122, 125, Dec. 2008
(一社)日本脊髄外科学会, Japanese

もやもや病術後過灌流評価における3D‐SSPの有用性について
金田朋洋, 高浪健太郎, 吉田さやか, 阿部恵子, 高橋昭喜, 藤村幹, 三田村篤, 細貝良行, 丸岡伸, 福田寛, 核医学, 45, 4, 377, 377, Nov. 2008
(一社)日本核医学会, Japanese

チマメないし解離性破裂内頸動脈瘤の治療戦略　　　　　　　　　　　　　　　
遠藤 英徳, 清水 宏明, 藤村 幹, 井上 敬, 冨永 悌二, 日本脳神経外科学会総会CD-ROM抄録集, 67回, 2H, O33, Oct. 2008
(一社)日本脳神経外科学会, Japanese

脳脊髄機能MRIをもちいた脊髄損傷後の脳脊髄可塑性の描出とその意義　　　　　　　　　　　　　　　
遠藤 俊毅, 藤村 幹, Olson Lars, 冨永 悌二, 日本脳神経外科学会総会CD-ROM抄録集, 67回, 3J, 10, Oct. 2008
(一社)日本脳神経外科学会, Japanese

colloid cystの二例　　　　　　　　　　　　　　　
李 麗, 麦倉 俊司, 日向野 修一, 梅津 篤司, 村田 隆紀, 高橋 昭喜, 藤村 幹, 冨永 悌二, 核医学, 45, 2, 143, 143, May 2008
(一社)日本核医学会, Japanese

モヤモヤ病におけるleptomeningeal ivy signの臨床的意義　　　　　　　　　　　　　　　
森 菜緒子, 麦倉 俊司, 日向野 修一, 梅津 篤司, 高橋 昭喜, 藤村 幹, Radiation Medicine, 26, Suppl.I, 9, 9, Apr. 2008
(公社)日本医学放射線学会, Japanese

脳動脈瘤治療の施設内paradigm shift:短期結果と今後の展望
清水宏明, 藤村幹, 井上敬, 松本康史, 近藤竜史, 高橋明, 冨永悌二, 日本脳神経外科学会総会抄録集(CD-ROM), 67th, 2008

もやもや病に対するSTA-MCA吻合術の治療成績:急性期合併症と長期成績について
藤村幹, 清水宏明, 冨永悌二, 日本脳神経外科学会総会抄録集(CD-ROM), 67th, 2008

Medullary streaksを観察し得た急性期脳梗塞の一例　　　　　　　　　　　　　　　
中川敦寛, 藤村幹, 冨永悌二, 麦倉俊司, 黒田宙, 野村亮介, 篠澤洋太郎, 第30回東北脳血管障害研究会学術集会記録集, 57, 60, 2008

Commentary
Teiji Tominaga, Miki Fujimura, Surgical Neurology, 68, 6, 682, Dec. 2007
English, Report scientific journal

Reduction in oxidative stress by SOD1 overexpression attenuates acute brain injury after subarachnoid hemorrhage via activation of Akt/GSK3β survival signaling
ENDO HIDENORI, FUJIMURA MIKI, CHAN PAK H, TOMINAGA TEIJI, 神経外傷, 30, 2, 102, 108, Dec. 2007
くも膜下出血(SAH)後の急性期脳損傷と酸化ストレスとの関係を解明するため、copper/zinc-superoxide dismutase(SOD1)過剰発現ラットを用いAkt/GSK3β生存シグナル経路に着目して研究を行った。その結果、SOD1過剰発現によってSAH後のスーパーオキシド増加に伴う酸化型ハイドロエチジンの増加と大脳皮質でのアポトーシスが抑制され、SAH 24時間後の死亡率は有意に減少した。また、SAH後の大脳皮質の神経細胞においてAktとGSK3βのリン酸化が促進し、これらはSOD1過剰発現下で持続的に増加した。SOD1の過剰発現は酸化ストレスを軽減し、Akt/GSK3β生存シグナル経路の活性化を介して神経保護作用を発揮することが示された。, (一社)日本脳神経外傷学会, Japanese

Association of cavernous malformation within vestibular schwannoma: Immunohistochemical analysis of matrix metalloproteinase-2 and-9 - Case report
Hiroyuki Sakata, Miki Fujimura, Mika Watanabe, Teiji Tominaga, NEUROLOGIA MEDICO-CHIRURGICA, 47, 11, 509, 512, Nov. 2007
English

甲状腺機能亢進症を合併した(類)もやもや病手術例の検討 周術期管理と術後急性期脳循環動態について　　　　　　　　　　　　　　　
遠藤 英徳, 藤村 幹, 冨永 悌二, 日本脳神経外科学会総会CD-ROM抄録集, 66回, 3K, P55, Oct. 2007
(一社)日本脳神経外科学会, Japanese

もやもや病に対する直接血行再建術後急性期の病態について 3-Tesla MRIを用いた検討　　　　　　　　　　　　　　　
小濱 みさき, 藤村 幹, 麦倉 俊司, 冨永 悌二, 日本脳神経外科学会総会CD-ROM抄録集, 66回, 3K, P55, Oct. 2007
(一社)日本脳神経外科学会, Japanese

Symptomatic hyperperfusion after superficial temporal artery-middle cerebral artery anastomosis in a child with moyamoya disease
Miki Fujimura, Tomohiro Kaneta, Hiroaki Shimizu, Teiji Tominaga, CHILDS NERVOUS SYSTEM, 23, 10, 1195, 1198, Oct. 2007
English

36 幼児期に発症した頭蓋頚椎移行部のNeuroenteric cystの1手術例(北日本脳神経外科連合会第30回学術集会)
坂田 洋之, 藤村 幹, 岩崎 真樹, 冨永 悌二, 新潟医学会雑誌, 121, 4, 224, 225, Apr. 2007
新潟大学, Japanese

Pressure-dependent effect of shock waves on rat brain: induction of neuronal apoptosis mediated by a caspase-dependent pathway
Kaoruko Kato, Miki Fujimura, Atsuhiro Nakagawa, Atsushi Saito, Tomohiro Ohki, Kazuyoshi Takayama, Teiji Tominaga, JOURNAL OF NEUROSURGERY, 106, 4, 667, 676, Apr. 2007
English

くも膜下出血急性期脳損傷 SOD1過剰発現による酸化ストレス減少とAkt/GSK3β生存シグナル活性化の影響　　　　　　　　　　　　　　　
遠藤 英徳, 藤村 幹, チャン・パク, 冨永 悌二, 日本神経外傷学会プログラム・抄録集, 30回, 67, 67, Mar. 2007
(一社)日本脳神経外傷学会, Japanese

Temporary neurologic deterioration due to cerebral hyperperfusion after superficial temporal artery-middle cerebral artery anastomosis in patients with adult-onset moyamoya disease
Miki Fujimura, Tomohiro Kaneta, Shunji Mugikura, Hiroaki Shimizu, Teiji Tominaga, SURGICAL NEUROLOGY, 67, 3, 273, 282, Mar. 2007
English

Expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) in cerebral cavernous malformations: immunohistochemical analysis of MMP-2,-9 and TIMP-2
M. Fujimura, M. Watanabe, H. Shimizu, T. Tominaga, ACTA NEUROCHIRURGICA, 149, 2, 179, 183, Feb. 2007
English

感度波長域7-14μmの赤外線画像開頭術中モニタリング:適応と術中~術後急性期管理における臨床的意義
中川敦寛, 藤村幹, 荒船龍彦, 山口喬弘, 清水宏明, 佐久間一郎, 冨永悌二, 日本脳神経外科学会総会抄録集(CD-ROM), 66th, 2007

もやもや病に対するSTA-MCA吻合術後・症候性過灌流とその関連因子についての検討
藤村幹, 清水宏明, 冨永悌二, 脳循環代謝, 19, 2, 2007

もやもや病に対するSTA-MCA吻合術後・症候性過灌流とその関連因子についての検討
藤村幹, 清水宏明, 冨永悌二, 日本脳神経外科学会総会抄録集(CD-ROM), 66th, 2007

赤外線画像システムIRIS Vを用いたもやもや病血行再建術中脳表モニタリング:術後経過との相関に関する検討
中川敦寛, 藤村幹, 清水宏明, 高山和喜, 冨永悌二, 新潟医学会雑誌, 121, 4, 2007

Prediction of Postoperative Cerebral Hyperperfusion in Patients with Moyamoya Disease by Intraoperative Monitoring of Cerebral Hemodynamics Using IRIS-V Infrared Imaging System: Two Case Report
NAKAGAWA Atsuhiro, FUJIMURA Miki, SUZUKI Hideaki, OHKI Tomohiro, TAKAYAMA Kazuyoshi, TOMINAGA Teiji, Nosotchu no Geka Kenkyukai koenshu, 35, 2, 136, 141, 2007
Surgical revascularization for moyamoya disease prevents cerebral ischemic attacks by improving cerebral blood flow (CBF). But little is known about the change in intraoperative cerebral hemodynamics and its effect on postoperative neurological status, including symptomatic cerebral hyperperfusion. To address this issue, we applied a novel infrared imaging system (IRIS-V infrared imaging system) for intraoperative monitoring of surface hemodynamics in 2 patients with moyamoya disease. We investigated the correlation between clinical, radiological findings, and changes of the gradation value in infrared imaging using imaging software. The camera showed apparent revascularization during surgery in both cases. In case 1, a 36-year-old male who presented with transient ischemic attack (TIA) underwent superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis with pial synangiosis. His cerebrovascular reactivity was significantly compromised as shown by preoperative IMP-SPECT. Intraoperative infrared imaging disclosed an increase in brain surface temperature due to increase in blood flow around the anastomosis. The gradation value gradually increased after recanalization of bypass during several minutes. Postoperative IMP-SPECT showed a focal increase in CBF around the site of anastomosis 1 day after surgery. Beginning on the next day, he suffered fluctuated aphasia, numbness and fine movement disturbance on his right hand for 7 days. Intensive blood pressure control relieved his symptoms, and he was discharged without neurological deficit. The anatomical location and the temporal profile of hyperperfusion accorded with the neurological deficits.
In case 2, a 29-year-old female who presented with TIA had already undergone surgical revascularization on the symptomatic right side. Then she underwent left STA-MCA anastomosis on the asymptomatic side with decreased cerebrovascular reserve capacity. Intraoperative infrared imaging disclosed no significant increase in brain surface color around the site of anastomosis except for the apparent revascularization through STA-MCA bypass. The gradation value did change significantly before or after recanalization of bypass. Postoperative IMP-SPECT showed a mild increase in CBF on the entire MCA territory without focal intense accumulation. Her postoperative course was uneventful, and she was discharged without neurological deterioration.
Characteristic patterns of the intraoperative cerebral hemodynamics as delineated by IRIS-V may be the optimal predictor for postoperative transient symptomatic hyperperfusion after direct bypass in patients with moyamoya disease.
, The Japanese Society on Surgery for Cerebral Stroke, Japanese

脳虚血後の遅発性海馬CA1神経細胞死におけるp53の役割について　　　　　　　　　　　　　　　
遠藤英徳, 藤村幹, チャンパク, 冨永悌二, 脳卒中, 29, 2, 385, 385, 2007

もやもや病周術期における痙攣と血行再建術後急性期の脳循環動態との関連について　　　　　　　　　　　　　　　
成澤あゆみ, 藤村幹, 清水宏明, 冨永悌二, Neurological Surgery, 35, 5, 467, 474, 2007

Malignant transformation of high-grade astrocytoma associated with neurocysticercosis in a patient with Turcot syndrome
Kuniyasu Niizuma, Miki Fujimura, Toshihiro Kumabe, Tominaga Tominaga, JOURNAL OF CLINICAL NEUROSCIENCE, 14, 1, 53, 55, Jan. 2007
English

高感度赤外線画像システムIRIS-Vを用いたもやもや病術中血行動態モニタリングによる術後過灌流の予測 2症例の検討
中川敦寛, 藤村幹, 鈴木秀明, 大木友博, 高山和喜, 冨永悌二, 脳卒中の外科, 35, 2, 136, 141, 2007
Surgical revascularization for moyamoya disease prevents cerebral ischemic attacks by improving cerebral blood flow (CBF). But little is known about the change in intraoperative cerebral hemodynamics and its effect on postoperative neurological status, including symptomatic cerebral hyperperfusion. To address this issue, we applied a novel infrared imaging system (IRIS-V infrared imaging system) for intraoperative monitoring of surface hemodynamics in 2 patients with moyamoya disease. We investigated the correlation between clinical, radiological findings, and changes of the gradation value in infrared imaging using imaging software. The camera showed apparent revascularization during surgery in both cases. In case 1, a 36-year-old male who presented with transient ischemic attack (TIA) underwent superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis with pial synangiosis. His cerebrovascular reactivity was significantly compromised as shown by preoperative IMP-SPECT. Intraoperative infrared imaging disclosed an increase in brain surface temperature due to increase in blood flow around the anastomosis. The gradation value gradually increased after recanalization of bypass during several minutes. Postoperative IMP-SPECT showed a focal increase in CBF around the site of anastomosis 1 day after surgery. Beginning on the next day, he suffered fluctuated aphasia, numbness and fine movement disturbance on his right hand for 7 days. Intensive blood pressure control relieved his symptoms, and he was discharged without neurological deficit. The anatomical location and the temporal profile of hyperperfusion accorded with the neurological deficits.
In case 2, a 29-year-old female who presented with TIA had already undergone surgical revascularization on the symptomatic right side. Then she underwent left STA-MCA anastomosis on the asymptomatic side with decreased cerebrovascular reserve capacity. Intraoperative infrared imaging disclosed no significant increase in brain surface color around the site of anastomosis except for the apparent revascularization through STA-MCA bypass. The gradation value did change significantly before or after recanalization of bypass. Postoperative IMP-SPECT showed a mild increase in CBF on the entire MCA territory without focal intense accumulation. Her postoperative course was uneventful, and she was discharged without neurological deterioration.
Characteristic patterns of the intraoperative cerebral hemodynamics as delineated by IRIS-V may be the optimal predictor for postoperative transient symptomatic hyperperfusion after direct bypass in patients with moyamoya disease.
, The Japanese Society on Surgery for Cerebral Stroke, Japanese

脳虚血後の遅発性海馬CA1神経細胞死におけるp53の役割について　　　　　　　　　　　　　　　
遠藤英徳, 藤村幹, チャンパク, 冨永悌二, 脳卒中, 29, 2, 385, 385, 2007

もやもや病周術期における痙攣と血行再建術後急性期の脳循環動態との関連について　　　　　　　　　　　　　　　
成澤あゆみ, 藤村幹, 清水宏明, 冨永悌二, Neurological Surgery, 35, 5, 467, 474, 2007

Association of cavernous malformation within vestibular schwannoma: immunohistochemical analysis of matrix metalloproteinase-2 and -9.
Sakata Hiroyuki, Fujimura Miki, Watanabe Mika, Tominaga Teiji, Neurol Med Chir (Tokyo), 47, 11, 509, 512, 2007

Surgical treatment of paraventricular cavernous angioma: Fibre tracking for visualizing the corticospinal tract and determining surgical approach
Kuniyasu Niizuma, Miki Fujimura, Toshihiro Kumabe, Shuichi Higano, Teiji Tominaga, JOURNAL OF CLINICAL NEUROSCIENCE, 13, 10, 1028, 1032, Dec. 2006
English

くも膜下出血急性期脳損傷 SOD1過剰発現による酸化ストレス減少とAkt/GSK3β生存シグナル活性化の影響　　　　　　　　　　　　　　　
遠藤 英徳, 藤村 幹, チャン・パク, 冨永 悌二, 脳循環代謝, 18, 3, 110, 110, Nov. 2006
日本脳循環代謝学会, Japanese

もやもや病に対する血行再建術前後の脳循環と臨床像:SPECT・脳灌流MRIと術中赤外線画像装置による検討
藤村幹, 成澤あゆみ, 中川敦寛, 清水宏明, 冨永悌二, 脳循環代謝, 18, 3, 2006

モヤモヤ病血行再建術後の痙攣:術後局所過灌流との関連について
成澤あゆみ, 藤村幹, 清水宏明, 冨永悌二, 日本脳神経外科学会総会抄録集(CD-ROM), 65th, 2006

モヤモヤ病に対する血行再建術前後の脳循環と臨床像:SPECT・PWIと術中赤外線画像装置による検討
藤村幹, 麦倉俊司, 金田朋洋, 中川敦寛, 清水宏明, 冨永悌二, 日本脳神経外科学会総会抄録集(CD-ROM), 65th, 2006

Transient Focal Neurological Deficit Due to Hyperperfusion after Superficial Temporal Artery-Middle Cerebral Artery Anastomosis in Patients with Moyamoya Disease
藤村幹, 清水宏明, 冨永悌二, 脳卒中の外科, 34, 1, 37, 41, 2006

脳虚血後の細胞死調節因子IAP family proteinの反応経路について　　　　　　　　　　　　　　　
斉藤敦志, 藤村幹, 冨永悌二, 脳循環代謝, 18, 1, 26, 26, 2006

定型的画像所見を呈さなかった両側基底核部および大脳半球白質に浸潤する中枢神経系hCG産生胚腫による思春期早発症の1例　　　　　　　　　　　　　　　
杉山慎一郎, 隈部俊宏, 三野正樹, 藤村幹, 藤原幾磨, 冨永悌二, Neurological Surgery, 34, 6, 619, 624, 2006

もやもや病に対する血行再建術後急性期の臨床像と脳循環動態 脳灌流MRIを用いた検討　　　　　　　　　　　　　　　
藤村幹, 麦倉俊司, 清水宏明, 冨永悌二, Neurological Surgery, 34, 8, 801, 809, 2006

高感度赤外線画像システムIRIS Vを用いたもやもや病術中血行動態モニタリング　　　　　　　　　　　　　　　
中川敦寛, 藤村幹, 大木友博, 鈴木秀明, 高山和喜, 冨永悌二, Neurological Surgery, 34, 10, 1017, 1025, 2006

【インターベンション時代の脳卒中学(改訂第2版) 超急性期から再発予防まで】 脳血管障害各論 脳血管奇形 海綿状血管腫 (日本臨床)　　　　　　　　　　　　　　　
藤村幹, 冨永悌二, 日本臨床, 64, 増刊8 インターベンション時代の脳卒中学(下), 691, 694, 2006

【インターベンション時代の脳卒中学(改訂第2版) 超急性期から再発予防まで】 脳血管障害各論 くも膜下出血と脳動脈瘤 脳血管攣縮 DINDの発生機序と予防および治療 (日本臨床)　　　　　　　　　　　　　　　
冨永悌二, 藤村幹, 日本臨床, 64, 増刊8 インターベンション時代の脳卒中学(下), 650, 653, 2006

Transient focal neurological deficit due to hyperperfusion after superficial temporal middle cerebral artery anastomosis in patients with moyamoya disease
Miki Fujimura, Hiroaki Shimizu, Teiji, Tominaga, Surgery for Cerebral Stroke, 34, 1, 37, 41, 2006

脳虚血後の細胞死調節因子IAP family proteinの反応経路について　　　　　　　　　　　　　　　
斉藤敦志, 藤村幹, 冨永悌二, 脳循環代謝, 18, 1, 26, 26, 2006

定型的画像所見を呈さなかった両側基底核部および大脳半球白質に浸潤する中枢神経系hCG産生胚腫による思春期早発症の1例　　　　　　　　　　　　　　　
杉山慎一郎, 隈部俊宏, 三野正樹, 藤村幹, 藤原幾磨, 冨永悌二, Neurological Surgery, 34, 6, 619, 624, 2006

もやもや病に対する血行再建術後急性期の臨床像と脳循環動態 脳灌流MRIを用いた検討　　　　　　　　　　　　　　　
藤村幹, 麦倉俊司, 清水宏明, 冨永悌二, Neurological Surgery, 34, 8, 801, 809, 2006

高感度赤外線画像システムIRIS Vを用いたもやもや病術中血行動態モニタリング　　　　　　　　　　　　　　　
中川敦寛, 藤村幹, 大木友博, 鈴木秀明, 高山和喜, 冨永悌二, Neurological Surgery, 34, 10, 1017, 1025, 2006

【インターベンション時代の脳卒中学(改訂第2版) 超急性期から再発予防まで】 脳血管障害各論 脳血管奇形 海綿状血管腫 (日本臨床)　　　　　　　　　　　　　　　
藤村幹, 冨永悌二, 日本臨床, 64, 増刊8 インターベンション時代の脳卒中学(下), 691, 694, 2006

【インターベンション時代の脳卒中学(改訂第2版) 超急性期から再発予防まで】 脳血管障害各論 くも膜下出血と脳動脈瘤 脳血管攣縮 DINDの発生機序と予防および治療 (日本臨床)　　　　　　　　　　　　　　　
冨永悌二, 藤村幹, 日本臨床, 64, 増刊8 インターベンション時代の脳卒中学(下), 650, 653, 2006

Surgical treatment of paraventricular cavernous angioma: fibre tracking for visualizing the corticospinal tract and determining surgical approach.
Niizuma Kuniyasu, Fujimura Miki, Kumabe Toshihiro, Higano Shuichi, Tominaga Teiji, J Clin Neurosci, 13, 10, 1028, 1032, 2006

Delayed lymphocytic infundibuloneurohypo-physitis following successful transsphenoidal treatment of Cushing's disease
T Kawaguchi, H Ikeda, M Fujimura, T Yoshimoto, T Tominaga, JOURNAL OF CLINICAL NEUROSCIENCE, 12, 3, 320, 323, Apr. 2005
English

Ectopic recurrence of craniopharyngioma
T Kawaguchi, M Fujimura, R Shirane, T Shoji, M Watanabe, T Tominaga, JOURNAL OF CLINICAL NEUROSCIENCE, 12, 3, 307, 309, Apr. 2005
English

A case of cellular blue naevus with intracranial invasion and malignant transformation
N Noshita, M Fujimura, T Kumabe, R Shirane, M Watanabe, T Tominaga, ACTA NEUROCHIRURGICA, 147, 2, 211, 213, Feb. 2005
English, Others

Thrombosed vertebral artery aneurysm presenting with hemorrhage and bulbar compression: report of two cases
S Shiraishi, M Fujimura, H Kon, O Motohashi, M Kameyama, K Ishii, T Onuma, CLINICAL NEUROLOGY AND NEUROSURGERY, 107, 2, 123, 127, Feb. 2005
English

もやもや病に対する血行再建術後急性期の臨床像と脳循環動態・放射線学的変化の検討:術後過潅流について
藤村幹, 清水宏明, 冨永悌二, 日本脳神経外科学会総会抄録集(CD-ROM), 64th, 2005

ラット大脳への衝撃波照射による神経細胞死の検討　　　　　　　　　　　　　　　
加藤薫子, 中川敦寛, 藤村幹, 斉藤敦志, 大木友博, 平野孝幸, 高山和喜, 冨永悌二, 平成17年度 衝撃波シンポジウム講演論文集, 337, 339, 2005

STA-MCA吻合術後にfocal hyperperfusionを呈したもやもや病の２症例　　　　　　　　　　　　　　　
藤村幹, 清水宏明, 金田朋洋, 冨永悌二, 東北脳SPECT研究会講演集, 14, 1, 20, 25, 2005

Congestive myelopathyを呈した肋間動静脈シャントの一治験例　　　　　　　　　　　　　　　
斉藤敦志, 高橋敏行, 江面正幸, 藤村幹, 隈部俊宏, 冨永悌二, 東北脳血管障害研究会27回学術集会記録集, 81, 85, 2005

Diagnostic value of super-selective bilateral cavernous sinus sampling with hypothalamic stimulating hormone loading in patients with ACTH-producing pituitary adenoma
M Fujimura, H Ikeda, A Takahashi, M Ezura, T Yoshimoto, T Tominaga, NEUROLOGICAL RESEARCH, 27, 1, 11, 15, Jan. 2005
English

Neuroprotective effect of an antioxidant in ischemic brain injury - Involvement of neuronal apoptosis
M Fujimura, T Tominaga, PH Chan, NEUROCRITICAL CARE, 2, 1, 59, 66, 2005
English

STA-MCA吻合術後にfocal hyperperfusionを呈したもやもや病の２症例　　　　　　　　　　　　　　　
藤村幹, 清水宏明, 金田朋洋, 冨永悌二, 東北脳SPECT研究会講演集, 14, 1, 20, 25, 2005

Congestive myelopathyを呈した肋間動静脈シャントの一治験例　　　　　　　　　　　　　　　
斉藤敦志, 高橋敏行, 江面正幸, 藤村幹, 隈部俊宏, 冨永悌二, 東北脳血管障害研究会27回学術集会記録集, 81, 85, 2005

Combined three-dimensional anisotropy contrast imaging and magnetoencephalography guidance to preserve visual function in a patient with an occipital lobe tumor
T Inoue, M Fujimura, T Kumabe, N Nakasato, S Higano, T Tominaga, MINIMALLY INVASIVE NEUROSURGERY, 47, 4, 249, 252, Aug. 2004
English

Hydrocephalus due to cerebrospinal fluid overproduction by bilateral choroid plexus papillomas
M Fujimura, T Onuma, M Kameyama, O Motohashi, H Kon, K Yamamoto, K Ishii, T Tominaga, CHILDS NERVOUS SYSTEM, 20, 7, 485, 488, Jul. 2004
English

Cerebral infarction in the caudate nucleus associated with acute epidural hematoma and diffuse brain injury in a child after severe head injury
M Fujimura, M Kameyama, O Motohashi, H Kon, K Ishii, T Onuma, CHILDS NERVOUS SYSTEM, 20, 6, 430, 433, Jun. 2004
English

Exclusively extradural arteriovenous malformation with neurogenic claudication - Case illustration
K Niizuma, M Fujimura, T Takahashi, A Takahashi, M Watanabe, T Tominaga, JOURNAL OF NEUROSURGERY, 100, 4, 397, 397, Apr. 2004
English, Others

Routine clinical adoption of magnetic resonance imaging was associated with better outcome after surgery in elderly patients with a malignant astrocytic tumour: a retrospective review
M Fujimura, T Kumabe, T Tominaga, H Jokura, R Shirane, T Yoshimoto, ACTA NEUROCHIRURGICA, 146, 3, 251, 255, Mar. 2004
English, Book review

マウスクモ膜下出血後のneurogenesisとapoptosis　　　　　　　　　　　　　　　
三野正樹, 上井英之, 近藤健男, 藤村幹, 冨永悌二, 脳循環代謝, 16, 1, 49, 50, 2004

Neuronal death/survival signaling pathways in cerebral ischemia. (NeuroRx)
Sugawara Taku, Fujimura Miki, Noshita Nobuo, Kim Gyung Whan, Saito Atsushi, Hayashi Takeshi, Narasimhan Purnima, Maier Carolina M, Chan Pak H, NeuroRx, 1, 1, 17, 25, 2004

The 7th Japanese and Korean Friendship Conference on Suegrery for Cerebral Stroke　　　　　　　　　　　　　　　
藤村幹, 脳神経外科, 32, 7, 760, 761, 2004

Neuronal death/survival signaling pathways in cerebral ischemia. (NeuroRx)
Sugawara Taku, Fujimura Miki, Noshita Nobuo, Kim Gyung Whan, Saito Atsushi, Hayashi Takeshi, Narasimhan Purnima, Maier Carolina M, Chan Pak H, NeuroRx, 1, 1, 17, 25, 2004

Intractable vomiting as an early clinical symptom of cerebrospinal fluid seeding to the fourth ventricle in patients with high-grade astrocytoma
M Fujimura, T Kumabe, H Jokura, R Shirane, T Yoshimoto, T Tominaga, JOURNAL OF NEURO-ONCOLOGY, 66, 1-2, 209, 216, Jan. 2004
English

PTEN gene mutation and high MIB-4 labeling index may contribute to dissemination in patients with glioblastoma
H Kato, M Fujimura, T Kumabe, C Ishioka, R Kanamaru, T Yoshimoto, JOURNAL OF CLINICAL NEUROSCIENCE, 11, 1, 37, 41, Jan. 2004
English

The 7th Japanese and Korean Friendship Conference on Suegrery for Cerebral Stroke　　　　　　　　　　　　　　　
藤村幹, 脳神経外科, 32, 7, 760, 761, 2004

Temporal changes of neurogenesis in the mouse hippocampus after experimental subarachnoid hemorrhage
M Mino, H Kamii, M Fujimura, T Kondo, S Takasawa, H Okamoto, T Yoshimoto, NEUROLOGICAL RESEARCH, 25, 8, 839, 845, Dec. 2003
English

A case of germinoma in the septum pellucidum manifesting as amnesia and hemiparesis
K Sato, T Nagayama, M Fujimura, K Okamoto, M Kamiya, Y Nakazato, ACTA NEUROCHIRURGICA, 145, 10, 923, 926, Oct. 2003
English

Two cases of impending herniation due to multiple traumatic acute subdural hematomas: Combination of burr hole evacuation and craniotomy
O Motohashi, M Kameyama, H Kon, M Fujimura, T Onuma, NEUROLOGICAL SURGERY, 31, 5, 529, 535, May 2003
Japanese

Role of superoxide in poly(ADP-ribose) polymerase upregulation after transient cerebral ischemia
P Narasimhan, M Fujimura, N Noshita, PH Chan, MOLECULAR BRAIN RESEARCH, 113, 1-2, 28, 36, May 2003
English

Fatal rupture following intra-aneurysmal embolization for the distal posterior inferior cerebellar artery aneurysm with parent artery preservation
M Fujimura, M Nishijima, H Midorikawa, K Umezawa, T Hayashi, M Kaimori, CLINICAL NEUROLOGY AND NEUROSURGERY, 105, 2, 117, 120, Apr. 2003
English

A case of vertebral artery occlusion following heading play in soccer
O Motohashi, M Kameyama, H Kon, M Fujimura, T Onuma, NEUROLOGICAL SURGERY, 31, 4, 431, 434, Apr. 2003
Japanese

Spinal lipoma associated with terminal syringohydromyelia and a spinal arachnoid cyst in a patient with cloacal exstrophy
M Fujimura, Y Kusaka, R Shirane, CHILDS NERVOUS SYSTEM, 19, 4, 254, 257, Apr. 2003
English

Optochiasmal arachnoiditis following cotton wrapping of anterior communicating artery aneurysm treated by surgical removal of granuloma
M Fujimura, M Nishijima, K Umezawa, T Hayashi, Y Mino, T Sakuraba, H Midorikawa, JOURNAL OF CLINICAL NEUROSCIENCE, 10, 2, 254, 257, Mar. 2003
English

脳室内における衝撃波医療応用に向けた基礎実験　　　　　　　　　　　　　　　
中川敦寛, 斎藤務, 日下康子, 大木友博, 神部真理子, 藤村幹, 平野孝幸, 上之原広司, 佐藤泰彦, 白根礼造, 高山和喜, 冨永悌二, 平成15年度 衝撃波シンポジウム講演論文集, 363, 364, 2003

Mild hypothermia attenuates cytochrome C release but does not alter Bcl-2 expression or caspase activation after experimental stroke
MA Yenari, S Iwayama, DY Cheng, GH Sun, M Fujimura, Y Morita-Fujimura, PH Chan, GK Steinberg, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 22, 1, 29, 38, Jan. 2002
English

A case of calvarial eosinophilic granuloma with rapid expansion and wide skull invasion: immunohistochemical analysis of Ki-67
M Fujimura, M Nishijima, K Umezawa, T Hayashi, M Kaimori, JOURNAL OF CLINICAL NEUROSCIENCE, 9, 1, 72, 76, Jan. 2002
English

Overexpression of copper/zinc superoxide dismutase in transgenic rats protects vulnerable neurons against ischemic damage by blocking the mitochondrial pathway of caspase activation
T Sugawara, N Noshita, A Lewen, Y Gasche, M Ferrand-Duke, M Fujimura, Y Morita-Fujimura, PH Chan, JOURNAL OF NEUROSCIENCE, 22, 1, 209, 217, Jan. 2002
English

Matrix metalloproteinase inhibition prevents oxidative stress-associated blood-brain barrier disruption after transient focal cerebral ischemia
Y Gasche, JC Copin, T Sugawara, M Fujimura, PH Chan, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 21, 12, 1393, 1400, Dec. 2001
English

Superoxide during reperfusion contributes to caspase-8 expression and apoptosis after transient focal stroke
Y Morita-Fujimura, M Fujimura, T Yoshimoto, PH Chan, STROKE, 32, 10, 2356, 2361, Oct. 2001
English

術後患者管理の変遷によるクモ膜下出血症例の治療成績,及び,脳血管れん縮発生頻度の推移
梅沢邦彦, 藤村幹, 林俊哲, 西島美知春, 青森県立中央病院医誌, 46, 3, 174, 176, 20 Sep. 2001
青森県立中央病院, Japanese

Interhemispheric cyst causing leg monoparesis in the elderly - Case report
T Hayashi, M Nishijima, K Umezawa, M Fujimura, M Kaimori, NEUROLOGIA MEDICO-CHIRURGICA, 41, 9, 463, 465, Sep. 2001
English

Oxidative stress-dependent release of mitochondrial cytochrome c after traumatic brain injury
A Lewen, M Fujimura, T Sugawara, P Matz, JC Copin, PH Chan, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 21, 8, 914, 920, Aug. 2001
English

Oxidative cellular damage and the reduction of APE/Ref-1 expression after experimental traumatic brain injury
A Lewen, T Sugawara, Y Gasche, M Fujimura, PH Chan, NEUROBIOLOGY OF DISEASE, 8, 3, 380, 390, Jun. 2001
English

Manganese superoxide dismutase affects cytochrome c release and caspase-9 activation after transient focal cerebral ischemia in mice
N Noshita, T Sugawara, M Fujimura, Y Morita-Fujimura, PH Chan, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 21, 5, 557, 567, May 2001
English

術後患者管理の変遷によるくも膜下出血症例の治療成績および脳血管れん縮発生頻度の推移
梅沢邦彦, 西島美知春, 藤村幹, 林俊哲, 脳血管れん縮, 16, 358, 361, 20 Mar. 2001
術後管理の変遷によるくも膜下出血症例の治療成績と脳血管攣縮発生頻度の推移を検討した.対象は,発症72時間以内に直達手術を行ったくも膜下出血症例165例で,前期(urokinase髄注期)66例,中期(塩酸papaverine動注期)72例,後期(塩酸papaverine髄注期)27例に分け成績を比較した.2ヵ月後の転帰(GOS)は,前期がG:61.7%,MD:23.7%,SD:7.6%,V:0%,D:7.6%で,中期がG:64%,MD:17%,SD:14%,V:2.8%,D:4.2%,後期がG:85.3%,MD:11.1%,SD:3.7%,V:0%,D:0%であった.CT上LDAが認められて判定した脳血管攣縮発生率は前期が28.8%,中期が27.8%,そして後期が7.4%であった.塩酸papaverine髄注による副作用は,ほぼ全例に一過性の頭痛が生じたが,永続する障害を残したものはなかった.以上のことからも,症候性脳血管攣縮出現後の塩酸papaverine動注では脳梗塞の発生率は抑えきれず,術後よりの低濃度の塩酸papaverine連日髄注で脳梗塞発生を大きく軽減し,治療成績を向上させることができると考えられた, スパズム・シンポジウム事務局, Japanese

Overexpression of copper-zinc superoxide dismutase attenuates acute activation of activator protein-1 after transient focal cerebral ischemia in mice
CY Huang, M Fujimura, YY Chang, PH Chan, STROKE, 32, 3, 741, 747, Mar. 2001
English

Severe subarachnoid hemorrhage with pulmonary edema successfully treated by intra-aneurysmal embolization using guglielmi detachable coils - Two case reports
M Fujimura, M Nishijima, K Umezawa, H Kon, T Tanaka, H Midorikawa, NEUROLOGIA MEDICO-CHIRURGICA, 41, 3, 135, 139, Mar. 2001
English

SOD1 down-regulates NF-kappa B and c-mye expression in mice after transient focal cerebral ischemia
CY Huang, M Fujimura, N Noshita, YY Chang, PH Chan, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 21, 2, 163, 173, Feb. 2001
English

Increased cytochrome c-mediated DNA fragmentation and cell death in manganese-superoxide dismutas-deficient mice after exposure to subarachnoid hemolysate
PG Matz, M Fujimura, A Lewen, Y Morita-Fujimura, PH Chan, STROKE, 32, 2, 506, 515, Feb. 2001
English

Severe subarachnoid hemorrhage with pulmonary edema successfully treated by intra-aneurysmal embolization using Guglielmi detachable coils
Miki Fujimura, Michiharu Nishijima, Kunihiko Umezawa, Hiroyuki Kon, Teruhiko Tanaka, Hiroshi Midorikawa, Neurologia Medico-Chirurgica, 41, 3, 135, 139, 2001
English, Book review

マウス局所脳虚血後のAP endonucleaseの発現動態とDNA障害に関する基礎的検討 Superoxideの役割について　　　　　　　　　　　　　　　
藤村幹, 吉本高志, 近藤健男, 森田維子, 藤村, ChanPak.H, 脳循環代謝, 13, 1, 38, 39, 2001

Reduction of copper,zinc-superoxide dismutase in knockout mice does not affect edema or infarction volumes and the early release of mitochondrial cytochrome c after permanent focal cerebral ischemia
M Fujimura, Y Morita-Fujimura, JC Copin, T Yoshimoto, PH Chan, BRAIN RESEARCH, 889, 1-2, 208, 213, Jan. 2001
English

急性くも膜下出血症例における血管内手術の有用性
林俊哲, 西島美知春, 梅沢邦彦, 藤村幹, 緑川宏, 松尾国弘, 日本脳神経外科学会総会抄録集, 59th, Abstract, 327, 327, 24 Oct. 2000
(一社)日本脳神経外科学会, Japanese

術後治療の変遷によるクモ膜下出血症例の治療成績,及び脳血管れん縮発生頻度の推移
梅沢邦彦, 藤村幹, 林俊哲, 西島美知春, 日本脳神経外科学会総会抄録集, 59th, Abstract, 122, 122, 24 Oct. 2000
(一社)日本脳神経外科学会, Japanese

Effect of hypotension severity on hippocampal CA1 neurons in a rat global ischemia model
T Sugawara, M Kawase, A Lewen, N Noshita, Y Gasche, M Fujimura, PH Chan, BRAIN RESEARCH, 877, 2, 281, 287, Sep. 2000
English

Reduction of the DNA base excision repair protein, XRCC1, may contribute to DNA fragmentation after cold injury-induced brain trauma in mice
M Fujimura, Y Morita-Fujimura, N Noshita, T Yoshimoto, PH Chan, BRAIN RESEARCH, 869, 1-2, 105, 111, Jun. 2000
English

The cytosolic antioxidant copper/zinc-superoxide dismutase prevents the early release of mitochondrial cytochrome c in ischemic brain after transient focal cerebral ischemia in mice
M Fujimura, Y Morita-Fujimura, N Noshita, T Sugawara, M Kawase, PH Chan, JOURNAL OF NEUROSCIENCE, 20, 8, 2817, 2824, Apr. 2000
English

Subarachnoid hemolysate produces DNA fragmentation in a pattern similar to apoptosis in mouse brain
PG Matz, M Fujimura, PH Chan, BRAIN RESEARCH, 858, 2, 312, 319, Mar. 2000
English

Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke
GT Manley, M Fujimura, TH Ma, N Noshita, F Filiz, AW Bollen, P Chan, AS Verkman, NATURE MEDICINE, 6, 2, 159, 163, Feb. 2000
English

マウス局所脳虚血後のミトコンドリアからのcytochrome cの漏出とapoptosis;SOD-2の役割について　　　　　　　　　　　　　　　
藤村幹, 川瀬誠, 森田維子, 藤村, 近藤健男, ChanPak H, 吉本高志, 脳卒中, 22, 1, 184, 184, 2000

マウス局所脳虚血再灌流後のmatrix metalloproteinase-9の誘導と活性化 血液脳関門の破綻との関連について　　　　　　　　　　　　　　　
藤村幹, YvanKasche, 森田維子, 藤村, 近藤健男, ChanPak H, 吉本高志, 日本脳神経外科学会59回総会抄録集, 79, 79, 2000

マウス局所脳虚血後のミトコンドリアからの cytochrome c 漏出とアポトーシス.　　　　　　　　　　　　　　　
藤村幹, 森田-藤村維子, 川瀬誠, 近藤健男, 吉本高志, PH Chan, 脳卒中, 22, 3, 472, 476, 2000
Japanese

一過性全脳虚血後のApurinic/Apyrimidinic Endonuclease発現動態 ApoptosisにおけるDNA修復機能　　　　　　　　　　　　　　　
川瀬誠, 藤村幹, 藤村維子, 近藤健男, ChanPak H, 吉本高志, 脳循環代謝, 11, 4, 388, 389, 2000

局所脳虚血および凍結脳外傷後のmitochondriaからのcytochrome c漏出とapoptosis superoxide dismutasesの役割について　　　　　　　　　　　　　　　
藤村幹, 森田維子, 藤村, 近藤健男, ChanPak H, 吉本高志, 神経免疫研究, 13, 79, 84, 2000

Overexpression of copper and zinc superoxide dismutase in transgenic mice prevents the induction and activation of matrix metalloproteinases after cold injury-induced brain trauma
Y Morita-Fujimura, M Fujimura, Y Gasche, JC Copin, PH Chan, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 20, 1, 130, 138, Jan. 2000
English

Neuroprotective effects of an antioxidant in cortical cerebral ischemia: prevention of early reduction of the apurinic/apyrimidinic endonuclease DNA repair enzyme
YY Chang, M Fujimura, Y Morita-Fujimura, GW Kim, CY Huang, HS Wu, M Kawase, JC Copin, PH Chan, NEUROSCIENCE LETTERS, 277, 1, 61, 64, Dec. 1999
English

Early decrease of XRCC1, a DNA base excision repair protein, may contribute to DNA fragmentation after transient focal cerebral ischemia in mice
M Fujimura, Y Morita-Fujimura, T Sugawara, PH Chan, STROKE, 30, 11, 2456, 2462, Nov. 1999
English

Copper-zinc superoxide dismutase prevents the early decrease of apurinic/apyrimidinic endonuclease and subsequent DNA fragmentation after transient focal cerebral ischemia in mice
M Fujimura, Y Morita-Fujimura, P Narasimhan, JC Copin, M Kawase, PH Chan, STROKE, 30, 11, 2408, 2415, Nov. 1999
English

Mitochondrial release of cytochrome c corresponds to the selective vulnerability of hippocampal CA1 neurons in rats after transient global cerebral ischemia
T Sugawara, M Fujimura, Y Morita-Fujimura, M Kawase, PH Chan, JOURNAL OF NEUROSCIENCE, 19, 22, art. no., RC39, Nov. 1999
English

Early appearance of activated matrix metalloproteinase-9 after focal cerebral ischemia in mice: A possible role in blood-brain barrier dysfunction
Y Gasche, M Fujimura, Y Morita-Fujimura, JC Copin, M Kawase, J Massengale, PH Chan, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 19, 9, 1020, 1028, Sep. 1999
English

Exacerbation of delayed cell injury after transient global ischemia in mutant mice with CuZn superoxide dismutase deficiency
M Kawase, K Murakami, M Fujimura, Y Morita-Fujimura, Y Gasche, T Kondo, RW Scott, PH Chan, STROKE, 30, 9, 1962, 1968, Sep. 1999
English

Early appearance of activated matrix metalloproteinase-9 and blood-brain barrier disruption in mice after focal cerebral ischemia and reperfusion
M Fujimura, Y Gasche, Y Morita-Fujimura, J Massengale, M Kawase, PH Chan, BRAIN RESEARCH, 842, 1, 92, 100, Sep. 1999
English

Inhibition of interleukin-1 beta converting enzyme family proteases (caspases) reduces cold injury-induced brain trauma and DNA fragmentation in mice
Y Morita-Fujimura, M Fujimura, M Kawase, K Murakami, GW Kim, PH Chan, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 19, 6, 634, 642, Jun. 1999
English

Release of mitochondrial cytochrome c and DNA fragmentation after cold injury-induced brain trauma in mice: possible role in neuronal apoptosis
Y Morita-Fujimura, M Fujimura, M Kawase, SF Chen, PH Chan, NEUROSCIENCE LETTERS, 267, 3, 201, 205, Jun. 1999
English

Early decrease of apurinic/apyrimidinic endonuclease expression after transient focal cerebral ischemia in mice
M Fujimura, Y Morita-Fujimura, M Kawase, PH Chan, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 19, 5, 495, 501, May 1999
English

Manganese superoxide dismutase mediates the early release of mitochondrial cytochrome C and subsequent DNA fragmentation after permanent focal cerebral ischemia in mice
M Fujimura, Y Morita-Fujimura, M Kawase, JC Copin, B Calagui, CJ Epstein, PH Chan, JOURNAL OF NEUROSCIENCE, 19, 9, 3414, 3422, May 1999
English

Reduction of apurinic/apyrimnidinic endonuclease expression after transient global cerebral ischemia in rats - Implication of the failure of DNA repair in neuronal apoptosis
M Kawase, M Fujimura, Y Morita-Fujimura, PH Chan, STROKE, 30, 2, 441, 448, Feb. 1999
English

CD38 disruption impairs glucose-induced increases in cyclic ADP-ribose, [Ca2+](i), and insulin secretion
Ichiro Kato, Yasuhiko Yamamoto, Miki Fujimura, Naoya Noguchi, Shin Takasawa, Hiroshi Okamoto, Journal of Biological Chemistry, 274, 4, 1869, 1872, 22 Jan. 1999
English

一過性全脳虚血後のApurinic/Apyrimidinic Endonuclease発現低下 ApoptosisにおけるDNA修復機能　　　　　　　　　　　　　　　
川瀬誠, 近藤健男, 藤村幹, 藤村維子, ChanPak H, 吉本高志, 日本脳神経外科学会58回総会抄録集, 248, 248, 1999

CD38 disruption impairs glucose-induced increases in cyclic ADP-ribose, [Ca2+](i), and insulin secretion
Kato, I, Y Yamamoto, M Fujimura, N Noguchi, S Takasawa, H Okamoto, JOURNAL OF BIOLOGICAL CHEMISTRY, 274, 4, 1869, 1872, Jan. 1999
English

Copper-zinc superoxide dismutase prevents the early decrease of apurinic/apyrimidinic endonuclease and subsequent DNA fragmentation after transient focal cerebral ischemia in mice
FUJIMURA M, Stroke, 30, 11, 2408, 2415, 1999

Early decrease in apurinic/apyrimidinic endonuclease is followed by DNA fragmentation after cold injury-induced brain trauma in mice
Y Morita-Fujimura, M Fujimura, M Kawase, PH Chan, NEUROSCIENCE, 93, 4, 1465, 1473, 1999
English

Early decrease of apurinic/apyrimidinic endonuclease expression after transient focal cerebral ischemia in mice.　　　　　　　　　　　　　　　
Fujimura M, Morita-Fujimura Y, Kawase M, Chan P H, J Cereb Blood Flow Metab, 19, 5, 495, 501, 1999

Cytosolic redistribution of cytochrome c after transient focal cerebral ischemia in rats
M Fujimura, Y Morita-Fujimura, K Murakami, M Kawase, PH Chan, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 18, 11, 1239, 1247, Nov. 1998
English

An autopsy case of a ruptured cerebral aneurysm treated with interlocking detachable coils
Y Otawara, T Sugawara, H Seki, M Fujimura, N Tomichi, NEUROLOGICAL SURGERY, 25, 9, 829, 833, Sep. 1997
Japanese

An autopsy case of a ruptured cerebral aneurysm treated with interlocking detachable coils
Yasunari Otawara, Takayuki Sugawara, Hirobumi Seki, Miki Fujimura, Nobukazu Tomichi, Neurological Surgery, 25, 9, 829, 833, Sep. 1997
Japanese

Carcinomatous change in the cranial metastasis from a metastasizing mixed tumor of the salivary gland -Case report-
Miki Fujimura, Takayuki Sugawara, Hirobumi Seki, Yasunari Otawara, Tsutomu Sakuma, Yoshishige Nakano, Takashi Yoshimoto, Neurologia Medico-Chirurgica, 37, 7, 546, 550, Jul. 1997
English

Nicotinamide inhibits inducible nitric oxide synthase mRNA in primary rat glial cells
M Fujimura, T Tominaga, T Yoshimoto, NEUROSCIENCE LETTERS, 228, 2, 107, 110, Jun. 1997
English

Attenuation of nitric oxide synthase induction in IRF-1-deficient glial cells
M Fujimura, T Tominaga, Kato, I, S Takasawa, M Kawase, T Taniguchi, H Okamoto, T Yoshimoto, BRAIN RESEARCH, 759, 2, 247, 250, Jun. 1997
English

A ruptured aneurysm at the distal end of the basilar artery fenestration associated with multiple fenestrations of the vertebrobasilar system: Case report
M Fujimura, T Sugawara, H Higuchi, T Oku, H Seki, SURGICAL NEUROLOGY, 47, 5, 469, 472, May 1997
English

Giant thrombosed fusiform aneurysm at the branch of the middle cerebral artery presenting with intramural hemorrhage: A case report
Miki Fujimura, Hirobumi Seki, Takayuki Sugawara, Tsutomu Sakuma, Yasunari Ohtawara, Norio Harata, Neurological Surgery, 25, 2, 151, 155, Feb. 1997
Japanese

Giant thrombosed fusiform aneurysm at the branch of the middle cerebral artery presenting with intramural hemorrhage: A case report
M Fujimura, H Seki, T Sugawara, T Sakuma, Y Ohtawara, N Harata, NEUROLOGICAL SURGERY, 25, 2, 151, 155, Feb. 1997
Japanese

Inducible nitric oxide synthase following hypoxia in rat cultured glial cells
M Kawase, H Kinouchi, Kato, I, A Akabane, T Kondo, S Arai, M Fujimura, H Okamoto, T Yoshimoto, BRAIN RESEARCH, 738, 2, 319, 322, Nov. 1996
English

Perivascular coating with fibrin glue of cerebral arteries in patients with aneurysmal subarachnoid hemorrhage; Incidence of chronic hydrocephalus
M Fujimura, T Sugawara, H Seki, T Oku, K Niimura, Y Otawara, H Higuchi, TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE, 179, 4, 267, 272, Aug. 1996
English

Cine-mode magnetic resonance imaging of a thoracic intradural arachnoid cyst: Case report
M Fujimura, T Tominaga, K Koshu, H Shimizu, T Yoshimoto, SURGICAL NEUROLOGY, 45, 6, 533, 536, Jun. 1996
English

Cine-mode magnetic resonance imaging of a thoracic intradural arachnoid cyst: Case report
Miki Fujimura, Teiji Tominaga, Keiji Koshu, Hiroaki Shimizu, Takashi Yoshimoto, Surgical Neurology, 45, 6, 533, 536, 1996
Elsevier Inc., English

Anomalous Internal Carotid Artery-Anterior Cerebral Artery Anastomosis Associated with Fenestration and Cerebral Aneurysm: —Case Report—
Miki Fujimura, Hirobumi Seki, Takayuki Sugawara, Tatsuya Oku, Hiroshi Higuchi, Nobukazu Tomichi, Neurologia medico-chirurgica, 36, 4, 229, 233, 1996
English

GANGLIOGLIOMA IN THE BASAL GANGLIA TOTALLY RESECTED BY A TRANS-DISTAL SYLVIAN APPROACH
M FUJIMURA, T KAYAMA, T KUMABE, T YOSHIMOTO, TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE, 175, 3, 211, 218, Mar. 1995
English, Introduction scientific journal

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

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

間葉系幹細胞シートを用いたもやもや病の間接血行再建術における包括的研究
科学研究費助成事業
01 Apr. 2023 - 31 Mar. 2027
藤村 幹, 伊東 雅基, 川堀 真人, 久下 裕司
ラット慢性脳虚血モデル（4 vessel occlusion model、両側椎骨動脈遮断の翌日に両側の内頚動脈遮断を追加する）の習得を行い、低い死亡率（約10%)にて全脳虚血が誘発される状態を作成する事が可能となった。全脳虚血の確認には心臓から墨汁液を灌流する事で全身の血管に墨汁が充填されるが、脳に関しては細い側副血行を介する事から墨汁が入っていかない事によって確認した。このモデルに対して、ヒト羊膜由来間葉系幹細胞（Amnion derived mesenchymal stem cell)からなる幹細胞シートをCellSaic社のアップセルを使用して作成し、脳表に貼り付けることによる血流回復の検討を行った。貼り付けは当初硬膜越しに行っていたが、通常のモヤモヤ病患者の手術に類似する形態を目指して、より血管を呼び込む効果が高いと考えられる硬膜下に貼り付ける方法に変更した。これらのシートを貼り付けた後に、骨を戻さず側頭筋を脳表に貼り付け、モヤモヤ病患者と同じように血管新生を誘発できるかについて検討する事にした。
しかし予想に反し、ヒト幹細胞シートを貼り付けた群においては、脳表の神経細胞の脱落が顕著に認められており、運動機能的にも回復は認められなかった。これはヒト由来のシート張付けによって強力な炎症反応とそれに引き続く形での脳の損傷が生じている事が原因と考えられた。これまでの我々の報告とも違った結果となり、異種に対する免疫反応が生じている事が原因と考えられた。これに対してラット由来の卵膜シートを検討する事としてその製造方法の改良に着手し、製法が確立された
日本学術振興会, 基盤研究(B), 北海道大学, 23K27706

Epigenetic regulation analysis in angiogenesis/pial synangiosis on the meninges in Moyamoya disease
Grants-in-Aid for Scientific Research
Apr. 2024 - Mar. 2027
伊東 雅基, 藤村 幹, 内野 晴登, 東海林 菊太郎
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 24K12213

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
本研究では、動物モデルで鼻内に投与されたエクソソームの効果を検討した。エクソソームは、超遠心法（10万G）を用いて羊膜由来間葉系幹細胞上清から分離した。得られたエクソソームはExosparklerを用いて蛍光Labelingを行った。スプレーグ・ドーリー・ラットに一過性の四血管閉塞モデル（両側椎骨動脈遮断翌日に20分間の両側内頚動脈遮断を行う）を用いて脳損傷を誘発し、エクソソーム鼻内投与は、1日あたり20μLのPBS中に3×10^8個のエクソソーム粒子または単独のPBSを経鼻的に投与して、損傷後7日間毎日投与を行った。長期の認知行動評価（8方向アーム試験）、エクソソームの生体分布（免疫学的染色）、およびアポトーシス（Apoptag染色）と神経炎症（CD68・Iba1）の組織学的評価を行った。エクソソームは、鼻内投与後1時間で主に嗅球に検出され、その後、24時間で中脳まで分布していた。エクソソームを投与されたラットは、刺激後28日後の認知機能の有意な改善を示した。エクソソーム投与によって海馬におけるアポトーシスの細胞が有意に減少し、同部位における神経細胞の死亡率も低下していた。エクソソームは主にミクログリアに取り込まれており、細胞毒性の炎症マーカーの発現が減少し、これが作用機序であると推測される結果が得られた。エクソソームの内容物に対する検討についてはmicroarrayによってmir125a-3pが候補である事が分かり、これのmimicとinhibitorを用いたin-vitro検証を行ったところ、効果が確認された
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
当該研究では抗酸化作用を付与したヘモグロビン人工酸素運搬体（HBOC）に一酸化炭素（CO）を結合しmulti-targetの脳保護効果を検討することを目的としている。前年度の報告書にある通り、当初の申請書には記載のないヘモグロビンナノ粒子（HbNP）が新たに開発され、使用薬剤の候補となった。HbNPはカタラーゼを内在して抗酸化作用を有するが、このHbNPを他の抗酸化能付与後のHBOCと比較した予備実験の結果、HbNPが最も脳保護効果を持っていたため、その後の研究ではHbNPに絞って実験を進める方針とした。HbNPが新規開発された製剤であることより、まずCO結合前のHbNP自体の脳保護効果を検討した。ラット脳虚血再灌流モデルを使用し、2時間虚血後の再灌流開始時に治療薬として、HbNPと比較対象としてHb-HSA3（以前より我々の研究室において用いていたHb-Albuminクラスター型のHBOCの一種）を静脈内に投与し、24時間後での梗塞体積、等を評価した。その結果、HbNPはHb-HSA3と比較して梗塞体積をより縮小させていた。次いで、脳組織内での炎症反応（ミエロペルオキシダーゼ）、酸化ストレス（４HNP）、微小血管障害（IgG血管外漏出）の状態を免疫染色、Western blottingにより検討した。いずれの検討項目においても、HbNPがより抑制する傾向を認めた。さらに、再灌流6時間以内の脳血流(CBF）、組織酸素分圧（PtO2）の評価を行った。その結果、CBFはHbNPとHb-HSA3で差を認めなかったが、PtO2はHbNPで数値が高く維持されていた。これらの実験結果からHbNPは再灌流早期に酸素運搬能を高く保つことで神経保護効果を示すものと考えられた。これらの結果を国内、国際学会で発表し、さらに英文雑誌Brain Researchにおいて掲載発表した。
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
Tominaga Teiji
Moyamoya disease, discovered in Japan, is an idiopathic condition characterized by progressive stenosis and occlusion of the bilateral internal carotid arteries, along with the development of abnormal vascular networks. The aim of this study is to elucidate the mechanisms of onset and progression of moyamoya disease, which remain unknown, from the perspective of interactions between blood flow and vascular endothelium. We conducted elemental studies including computational fluid dynamics analysis, fluid culture analysis, immunological analysis, biomarker exploration, and analysis of RNF213 function. As a result, it was shown that the RNF213 gene changes in a shear stress-dependent manner due to blood flow, implicating it in inflammation through leukocyte adhesion and migration, suggesting that interactions between blood flow and vascular endothelium contribute to the pathology.
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
Kota Kurisu
The relationship between ferotosis inhibition and intracellular iron accumulation with deferoxamine (DFO) in a model of rat cerebral ischaemia and re-reflux injury models. The rat ischaemia-reflux model caused more ferroptosis and more iron in cells. DFO stopped iron from building up in cells, but didn't stop the cell death that causes ferroptosis. DFO did not help with neurological symptoms. These results show that the mechanisms for reducing intracellular iron and inhibiting ferroptosis in cerebral ischaemia-reflux injury are different. The dose of DFO used in this study may only affect iron metabolism.
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
Ito Masaki
We hypothesized that circulating microRNAs might play a role in epigenetic regulation in the pathogenesis of Moyamoya disease (MMD), given that RNF213 gene fails to account for its full spectrum of clinical presentations. In this study, we quantified plasma microRNA expression using quantitative PCR panels and compared it between two groups: MMD (n=82) and age/sex-matched healthy controls (n=78). Principal component analysis revealed distinct differences in the plasma microRNA expression profiles between the two groups. Differential expression analysis identified significant changes in three microRNA entities, including hsa-miR-328-3p. The plasma expression level of miR-328-3p was significantly associated with clinical features, including onset age, sex, angiographical disease stage, PCA involvement, and RNF213 p.R4810K. Moreover, significant expression of miR-328-3p was confirmed in the arachnoid membrane in MMD. Therefore, plasma microRNAs may serve as epigenetic regulators in MMD.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 19H03765

Cilostazol may enhance the endogenous stem cell activity and thereby increase pial synangiosis after revascularization surgery for Moyamoya disease
Grants-in-Aid for Scientific Research
01 Apr. 2020 - 31 Mar. 2023
Miki Fujimura
Moyamoya disease (MMD) is a chronic occlusive cerebrovascular disease with unknown etiology. Surgical revascularization is the standard management option for symptomatic MMD, but optimum treatment for the patients with poor clinical condition, especially those of small children, is not established. We investigated the expression of endogenous pluripotent stem cells in the arachnoid membrane of the surgical specimen from MMD patients (n=40), and we found the predominant expression of endogenous pluripotent stem cells in MMD patients. Furthermore, we found that patients with the genetic variant of RNF213, a susceptibility gene for MMD, represented enhanced pial synangiosis after revascularization surgery for MMD. These results suggest the pharmacological enhancement of endogenous stem cells could be the possible management strategy for MMD patients with poor clinical condition.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (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
Sonobe Shinya
Moyamoya disease is a cerebrovascular disease. It is characterized by the small diameter of the terminal part of the internal carotid artery. Patients with moyamoya disease often have the p.R4810K polymorphism in the RNF213 gene (RNF213 mutation). However, it was not known how the RNF213 mutation affects the development of moyamoya disease. In this study, we showed that those with the RNF213 mutation had a smaller diameter of the terminal part of the internal carotid artery, even without moyamoya disease. This result indicates that the RNF213 mutation affects cerebral blood vessels, and that the cumulative effect causes moyamoya disease.
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