Faculty Profiles - OOISHI Makoto

Papers - OOISHI Makoto

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Improved health-related quality of life after rehabilitation in patients with brain tumors is not affected by tumor type

Takahiro WATANABE, Shinichi NOTO, Manabu NATSUMEDA, Shinji KIMURA, Fumie IKARASHI, Satoshi TABATA, Mayuko TAKANO, Yoshihiro TSUKAMOTO, Makoto OISHI

European Journal of Physical and Rehabilitation Medicine 2025.2

Diagnosis of Leptomeningeal Disease in Diffuse Midline Gliomas by Detection of H3F3A K27M Mutation in Circulating Tumor DNA of Cerebrospinal Fluid. International journal

Satoshi Shibuma, Jotaro On, Manabu Natsumeda, Akihide Koyama, Haruhiko Takahashi, Jun Watanabe, Masaki Mitobe, Satoshi Nakata, Yuki Tanaka, Yoshihiro Tsukamoto, Masayasu Okada, Junichi Yoshimura, Mari Tada, Hiroshi Shimizu, Soichi Oya, Junko Murai, Kouichirou Okamoto, Hiroyuki Kawashima, Akiyoshi Kakita, Makoto Oishi

Pediatric blood & cancer e31535 2025.1

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: Leptomeningeal disease (LMD) in diffuse midline gliomas (DMGs) can lead to devastating symptoms such as severe pain, urinary incontinence, and tetraparesis, with limited treatment options. We determined whether detecting H3F3A K27M-mutant droplets in cerebrospinal fluid (CSF) circulating tumor deoxyribonucleic acid (ctDNA) could be a biomarker for detecting LMD in DMGs. METHODS: Twenty-five CSF samples were obtained from 22 DMG patients. Histological confirmation of H3F3A K27M mutation was obtained in 10 (45.5%) cases. ctDNA was extracted from CSF, and H3F3A K27M-mutant and wildtype droplets were detected using digital droplet polymerase chain reaction (ddPCR). LMD was diagnosed by CSF cytology and pre- and post-contrast head and spine magnetic resonance (MR) imaging. RESULTS: The number of H3F3A K27M-mutant droplets (median 27 [range: 1-379] vs. median 0 [range: 0-1]; p < 0.0001) and variant allele frequency (VAF) (median 48.9% [range: 7.5%-87.5%] vs. median 0.0% [range: 0.0%-50.0%]; p < 0.0001) were significantly higher in the LMD/early-LMD group compared to no-LMD group. In two cases (Cases 4 and 11) without clinical evidence of LMD, multiple H3F3A K27M-mutant droplets were detected in CSF ctDNA. In those cases, extensive spinal dissemination was detected 6 months after the initial liquid biopsy. One case (Case 15) with high Schlafen11 (SLFN11) expression responded well to treatment for LMD and survived for 532 days after the diagnosis of LMD. CONCLUSION: This study provides evidence that detecting H3F3A K27M-mutant droplets in CSF ctDNA is diagnostic for LMD and is more sensitive than traditional methods such as CSF cytology and MR imaging.

DOI： 10.1002/pbc.31535

Improvements in activities of daily living among patients with brain tumors are associated with age, baseline physical function, duration of rehabilitation, and tumor recurrence but not type. International journal

Takahiro Watanabe, Shinichi Noto, Manabu Natsumeda, Shinji Kimura, Fumie Ikarashi, Satoshi Tabata, Mayuko Takano, Yoshihiro Tsukamoto, Makoto Oishi

International journal of rehabilitation research. Internationale Zeitschrift fur Rehabilitationsforschung. Revue internationale de recherches de readaptation 2024.8

Language：English Publishing type：Research paper (scientific journal)

Genetic testing has improved the accuracy of diagnosis of brain tumors, and treatment is now tailored to the type of brain tumor. In contrast, the factors that influence the improvement in independence in activities of daily living (ADLs) following rehabilitation have not been clarified, particularly the role of tumor type. In this retrospective cohort study of 358 participants, we analyzed changes in the Functional Independence Measure (FIM) from pre-rehabilitation to post-rehabilitation provided in an acute care hospital. Multiple regression was used to determine whether FIM gain is associated with age, gender, preadmission Karnofsky Performance Status (KPS), number of rehabilitation days, average duration of daily therapy (min/day), and tumor recurrence and type (WHO grade 1, 2, 3, and 4 gliomas; primary central nervous system lymphomas; and metastatic brain tumors). The results showed that older age (β -0.183), tumor recurrence (β -0.137), preadmission KPS < 80 (β -0.180), and higher baseline total FIM score (β -0.470) were associated with lower FIM gain whereas the average duration of daily therapy (β 0.153) was associated with higher FIM gain. Brain tumor type was not associated with FIM gain. Improved independence in ADLs is more influenced by demographic, functional status, and treatment factors than differences in brain tumor type.

DOI： 10.1097/MRR.0000000000000641

難治性てんかんとしての海馬硬化症における神経成長関連タンパク質のリン酸化解析

岡田正康, 北浦弘樹, 柿田明美, 大石誠, 五十嵐道弘

JSBMS Letters 49 ( Suppl. ) 112 - 112 2024.8

Primary spinal cord gliomas: Pathologic features associated with prognosis. International journal

Yuki Tanaka, Manabu Natsumeda, Masayuki Ohashi, Rie Saito, Nayuta Higa, Toshiaki Akahane, Hideki Hashidate, Junko Ito, Satoshi Fujii, Atsushi Sasaki, Akihide Tanimoto, Ryosuke Hanaya, Kei Watanabe, Makoto Oishi, Hiroyuki Kawashima, Akiyoshi Kakita

Journal of neuropathology and experimental neurology 2024.7

Language：English Publishing type：Research paper (scientific journal)

Primary spinal cord gliomas are rare and are associated with high mortality. Unlike brain tumors, the clinicopathological features of spinal cord gliomas are not well defined. We analyzed clinical, histopathology, and immunohistochemical features and overall survival (OS) of 25 patients with primary spinal cord gliomas treated between 1994 and 2023 at 4 institutions. IDH1 R132H, H3K27M, and p53 were assessed by immunohistochemistry (IHC). Four (16%), 5 (20%), 2 (8%), and 13 (52%) patients were diagnosed as having grades 1, 2, 3, and 4 gliomas according to the World Health Organization (WHO) 2021 classification, respectively. One case (4%), with a circumscribed diffuse midline glioma, H3K27-altered, had a rare molecular profile and could not be graded. IHC demonstrated H3K27M positivity, indicative of H3F3A K27M or HIST1H3B K27M mutation, in 9 (36%) patients. H3K27me3-loss was evident in 13 (52%) patients. In one patient with a grade 1 tumor that showed negative staining for H3K27M and H3K27me3 loss, numbers of EZHIP-positive cells were increased, suggesting diffuse midline glioma, H3K27-altered (WHO grade 4). H3K27me3 loss, frequency of p53 positive cells (≥10%), MIB-1 index (≥10%), and high histopathological grades significantly correlated with poor OS. These results indicate the pathological and immunohistochemical characteristics of primary spinal cord gliomas that impact prognosis.

DOI： 10.1093/jnen/nlae084

A patient with neuronal intranuclear inclusion disease developed encephalitis‐like symptoms after cerebral angiography

Shin Koide, Shintaro Tsuboguchi, Shingo Koide, Itaru Ninomiya, Taiki Saito, Takanobu Ishiguro, Etsuji Saji, Yo Higuchi, Takeshi Ikeuchi, Makoto Oishi, Masato Kanazawa, Osamu Onodera

Neurology and Clinical Neuroscience 2024.6

Publishing type：Research paper (scientific journal) Publisher：Wiley

Abstract

Patients with neuronal intranuclear inclusion disease (NIID) can present with encephalitis‐like symptoms such as recurrent paroxysmal fever and unconsciousness. To date, no specific triggers for these symptoms have been reported. In our case, an 78‐year‐old woman became unconscious and developed fever after cerebral angiography. The patient had experienced four episodes of unconsciousness and fever in the past 7 years. Postangiography, she immediately became unconscious and developed fever. No vascular abnormalities were found and magnetic resonance imaging of the brain revealed expanding white matter lesions and hyperintense lesions along the corticomedullary junction. Genetic analysis revealed an abnormal GGC repeat expansion in NOTCH2NLC. Thus, we diagnosed the patient with NIID. We suggest that cerebral angiography is a possible trigger for encephalitis‐like symptoms in NIID.

DOI： 10.1111/ncn3.12839

Clinical and Hemodynamic Features of Aneurysm Rupture in Coil Embolization of Intracranial Aneurysms. International journal

Tomoaki Suzuki, Hitoshi Hasegawa, Kohei Shibuya, Hidemoto Fujiwara, Makoto Oishi

Diagnostics (Basel, Switzerland) 14 ( 11 ) 2024.6

Language：English Publishing type：Research paper (scientific journal)

Intraprocedural rupture (IPR) during coil embolization (CE) of an intracranial aneurysm is a significant clinical concern that necessitates a comprehensive understanding of its clinical and hemodynamic predictors. Between January 2012 and December 2023, 435 saccular cerebral aneurysms were treated with CE at our institution. The inclusion criterion was extravasation or coil protrusion during CE. Postoperative data were used to confirm rupture points, and computational fluid dynamics (CFD) analysis was performed to assess hemodynamic characteristics, focusing on maximum pressure (Pmax) and wall shear stress (WSS). IPR occurred in six aneurysms (1.3%; three ruptured and three unruptured), with a dome size of 4.7 ± 1.8 mm and a D/N ratio of 1.5 ± 0.5. There were four aneurysms in the internal carotid artery (ICA), one in the anterior cerebral artery, and one in the middle cerebral artery. ICA aneurysms were treated using adjunctive techniques (three balloon-assisted, one stent-assisted). Two aneurysms (M1M2 and A1) were treated simply, yet had relatively small and misaligned domes. CFD analysis identified the rupture point as a flow impingement zone with Pmax in five aneurysms (83.3%). Time-averaged WSS was locally reduced around this area (1.3 ± 0.7 [Pa]), significantly lower than the aneurysmal dome (p < 0.01). Hemodynamically unstable areas have fragile, thin walls with rupture risk. A microcatheter was inserted along the inflow zone, directed towards the caution area. These findings underscore the importance of identifying hemodynamically unstable areas during CE. Adjunctive techniques should be applied with caution, especially in small aneurysms with axial misalignment, to minimize the rupture risk.

DOI： 10.3390/diagnostics14111203

頭蓋骨転移した胸部SMARCA4欠損未分化腫瘍の1例

渋間啓, 西田京香, 小倉良介, 岡田正康, 棗田学, 加藤卓, 梅津哉, 大石誠, 柿田明美

Brain Tumor Pathology 41 ( Suppl. ) 159 - 159 2024.5

間脳下垂体腫瘍病理診断の現状と治療:PitNETを含め機能性PitNETの治療中に転移を来たし,下垂体転写因子の有無で鑑別した2症例の経験

岡田正康, 棗田学, 塚本佳広, 梅津哉, 柿田明美, 大石誠

Brain Tumor Pathology 41 ( Suppl. ) 079 - 079 2024.5

Recent advances in liquid biopsy of central nervous system lymphomas: case presentations and review of the literature

Manabu Natsumeda, Satoshi Shibuma, Haruhiko Takahashi, Jotaro On, Yoshihiro Mouri, Kaoru Tomikawa, Hidemoto Fujiwara, Jun Watanabe, Yoshihiro Tsukamoto, Masayasu Okada, Rui Takeda, Hiroshi Shimizu, Jun Takizawa, Akiyoshi Kakita, Makoto Oishi

Brain Tumor Pathology 41 ( 2 ) 85 - 91 2024.4

Preoperative interactive virtual simulation applying three-dimensional multifusion images using a haptic device for lumbosacral lipoma. International journal

Ryosuke Ogura, Hidemoto Fujiwara, Manabu Natsumeda, Tetsuya Hiraishi, Masakazu Sano, Makoto Oishi

Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery 40 ( 4 ) 1129 - 1136 2024.4

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Untethering surgery for lumbosacral lipoma is a preventive procedure, and avoidance of complications and good long-term outcomes are required. We introduced presurgical interactive virtual simulation (IVS) applying three-dimensional multifusion images using a haptic device aimed at improving operative outcomes. METHODS: Fourteen patients with newly diagnosed lumbosacral lipoma were recruited and underwent preoperative IVS. The median age at surgery was 8 months. A three-dimensional image analysis system was used to extract and fuse structures necessary for surgery, such as the lipoma, spinal cord and skin, from CT and MRI, and create three-dimensional multifusion images. The created images were individually converted to standard triangulated language format and loaded onto a workstation (Geomagic freeform™) that could be freely transformed, and the laminectomy range and lipoma extraction procedure were examined. Presurgical IVS was performed, and the actual surgery was performed. RESULTS: The disease types were dorsal, caudal, lipomyelomeningocele, transitional, and filum in 5, 5, 2, 1, and 1 patients, respectively. The surgical procedure and extent of the laminectomy were as planned for all patients. Resection of the lipomas tended to be less than expected preoperatively because of positive reactions on intraoperative monitoring. No postoperative complications were observed. The median postoperative follow-up period was 29 months, and there were no reoperations during the observation period. CONCLUSIONS: Although there are various types of lumbosacral lipoma, surgery can be safely performed by performing presurgical IVS. The short-term course is good; however, long-term follow-up is necessary for the appearance of neurological symptoms associated with growth and re-tethering.

DOI： 10.1007/s00381-023-06234-2

脳腫瘍1 Diffuse midline gliomaにおける髄液中H3K27M変異検出は髄膜播種を予測する

棗田学, 温城太郎, 渋間聡, 高橋陽彦, 渡邉潤, 塚本佳広, 小倉良介, 岡田正康, 大石誠

小児の脳神経 49 ( 2 ) 128 - 128 2024.4

画像診断小児神経外科手術における外視鏡と三次元融合画像の有用性

小倉良介, 吉田至誠, 藤原秀元, 棗田学, 平石哲也, 大石誠

小児の脳神経 49 ( 2 ) 167 - 167 2024.4

毛様細胞性星細胞腫(Non-NF1)の治療と現状

大石誠, 棗田学, 塚本佳広, 小倉良介, 三橋大樹, 平石哲也

小児の脳神経 49 ( 2 ) 207 - 207 2024.4

脳腫瘍1 Diffuse midline gliomaにおける髄液中H3K27M変異検出は髄膜播種を予測する

棗田学, 温城太郎, 渋間聡, 高橋陽彦, 渡邉潤, 塚本佳広, 小倉良介, 岡田正康, 大石誠

小児の脳神経 49 ( 2 ) 128 - 128 2024.4

神経皮膚黒色症剖検例における多領域ゲノム解析

高橋陽彦, 棗田学, 塚本佳広, 岡田正康, 原範和, 小山哲秀, 宮下哲典, 結城明彦, 清水宏, 柿田明美, 池内健, 大石誠

小児の脳神経 49 ( 2 ) 228 - 228 2024.4

[Interactive Virtual Simulation with Haptics for Neurosurgery].

Makoto Oishi, Ryosuke Ogura

No shinkei geka. Neurological surgery 52 ( 2 ) 279 - 288 2024.3

Language：Japanese Publishing type：Research paper (scientific journal)

We established a unique pre-surgical simulation method by applying interactive virtual simulation(IVS)using multi-fusion three-dimensional imaging data, presenting high-quality visualization of microsurgical anatomies. Our IVS provided a realistic environment for imitating surgical manipulations, such as dissecting bones, retracting brain tissues, and removing tumors, with tactile and kinesthetic sensations delivered through a specific haptic device. The great advantage of our IVS was in deciding the most appropriate craniotomy and bone resection to create the optimal surgical window and obtain the best working space with a thorough understanding of the lesion-bone relationship. Particularly for skull-base tumors, tailoring the procedures to individual patients for craniotomy and bone resection was sufficiently achieved using our IVS. In cases of large skull base meningiomas, our IVS was also helpful preoperatively regarding tumors, as several compartments were achievable in every potentially usable surgical direction. Additionally, the non-risky realistic microsurgical environments of the IVS provided improvement in the microsurgical senses and skills of young trainees through the repetition of surgical tasks. Finally, our presurgical IVS simulation method provided a realistic environment for practicing microsurgical procedures virtually and enabled us to ascertain the complex microsurgical anatomy, determine optimal surgical strategies, and efficiently educate neurosurgical trainees.

DOI： 10.11477/mf.1436204912

Reliable detection of genetic alterations in cyst fluid DNA for the diagnosis of brain tumors. International journal

Jotaro On, Manabu Natsumeda, Haruhiko Takahashi, Akihide Koyama, Satoshi Shibuma, Nao Shibata, Jun Watanabe, Shoji Saito, Yu Kanemaru, Yoshihiro Tsukamoto, Masayasu Okada, Ryosuke Ogura, Takeyoshi Eda, Mari Tada, Hiroshi Shimizu, Jun-Ichi Adachi, Kazuhiko Mishima, Ryo Nishikawa, Akiyoshi Kakita, Makoto Oishi

Journal of neuro-oncology 2024.1

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Liquid biopsy of cyst fluid in brain tumors has not been extensively studied to date. The present study was performed to see whether diagnostic genetic alterations found in brain tumor tissue DNA could also be detected in cell-free DNA (cfDNA) of cyst fluid in cystic brain tumors. METHODS: Cyst fluid was obtained from 22 patients undergoing surgery for a cystic brain tumor with confirmed genetic alterations in tumor DNA. Pathological diagnoses based on WHO 2021 classification and diagnostic alterations in the tumor DNA, such as IDH1 R132H and TERT promoter mutation for oligodendrogliomas, were detected by Sanger sequencing. The same alterations were analyzed by both droplet digital PCR (ddPCR) and Sanger sequencing in cyst fluid cfDNA. Additionally, multiplex ligation-dependent probe amplification (MLPA) assays were performed to assess 1p/19q status, presence of CDKN2A loss, PTEN loss and EGFR amplification, to assess whether differentiating between astrocytomas and oligodendrogliomas and grading is possible from cyst fluid cfDNA. RESULTS: Twenty-five genetic alterations were found in 22 tumor samples. All (100%) alterations were detected in cyst fluid cfDNA by ddPCR. Twenty of the 25 (80%) alterations were also detected by Sanger sequencing of cyst fluid cfDNA. Variant allele frequency (VAF) in cyst fluid cfDNA was comparable to that of tumor DNA (R = 0.62, Pearson's correlation). MLPA was feasible in 11 out of 17 (65%) diffuse gliomas, with close correlation of results between tumor DNA and cyst fluid cfDNA. CONCLUSION: Cell-free DNA obtained from cyst fluid in cystic brain tumors is a reliable alternative to tumor DNA when diagnosing brain tumors.

DOI： 10.1007/s11060-023-04555-5

Multi-omics analyses of choroid plexus carcinoma cell lines reveal potential targetable pathways and alterations. International journal

Dina Hesham, Jotaro On, Nouran Alshahaby, Nada Amer, Sameh Magdeldin, Masayasu Okada, Yoshihiro Tsukamoto, Tetsuya Hiraishi, Chihaya Imai, Shujiro Okuda, Toshifumi Wakai, Akiyoshi Kakita, Makoto Oishi, Shahenda El-Naggar, Manabu Natsumeda

Journal of neuro-oncology 166 ( 1 ) 27 - 38 2024.1

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Choroid plexus carcinomas (CPCs) are extremely rare brain tumors and carry a dismal prognosis. Treatment options are limited and there is an urgent need to develop models to further research. In the present study, we established two CPC cell lines and performed multi-omics analyses. These cell lines serve as valuable models to propose new treatments in these rare but deadly brain tumors. METHODS: Multi-omic profiling including, (i) methylation array (EPIC 850 K), (ii) whole genome sequencing (WGS), (iii) CANCERPLEX cancer genome panel testing, (iv) RNA sequencing (RNA-seq), and (v) proteomics analyses were performed in CCHE-45 and NGT131 cell lines. RESULTS: Both cell lines were classified as methylation class B. Both harbored pathogenic TP53 point mutations; CCHE-45 additionally displayed TP53 loss. Furthermore, alterations of the NOTCH and WNT pathways were also detected in both cell lines. Two protein-coding gene fusions, BZW2-URGCP, and CTTNBP2-ERBB4, mutations of two oncodrivers, GBP-4 and KRTAP-12-2, and several copy number alterations were observed in CCHE-45, but not NGT131. Transcriptome and proteome analysis identified shared and unique signatures, suggesting that variability in choroid plexus carcinoma tumors may exist. The discovered difference's importance and implications highlight the possible diversity of choroid plexus carcinoma and call for additional research to fully understand disease pathogenesis. CONCLUSION: Multi-omics analyses revealed that the two choroid plexus carcinoma cell lines shared TP53 mutations and other common pathway alterations and activation of NOTCH and WNT pathways. Noticeable differences were also observed. These cell lines can serve as valuable models to propose new treatments in these rare but deadly brain tumors.

DOI： 10.1007/s11060-023-04484-3

Case report: Progressive multifocal leukoencephalopathy co-occurring with neurosarcoidosis: early brain biopsy and appropriate therapy for PML resulted in a favorable prognosis. International journal

Qiannan Wang, Shintaro Tsuboguchi, Kouichirou Okamoto, Mari Tada, Akiyoshi Kakita, Kazuo Nakamichi, Makoto Oishi, Masato Kanazawa, Osamu Onodera

Frontiers in immunology 15 1447992 - 1447992 2024

Language：English Publishing type：Research paper (scientific journal)

Progressive multifocal leukoencephalopathy (PML) is a rare central nervous system disease caused by JC virus (JCV) infection. Human immunodeficiency virus (HIV) infection is the greatest risk factor for PML. Other immunological diseases, including systemic sarcoidosis, have also been reported as risk factors for PML. Herein, we report a case of PML co-occurring with neurosarcoidosis. Early diagnosis using brain biopsy and appropriate therapeutic interventions achieved favorable outcomes. PML in patients with active intracranial neurosarcoidosis is extremely rare. We believe that it is important to perform brain biopsy at an early stage to allow diagnosis, even for central nervous system involvement with a progressive parenchymal lesion in patients with sarcoidosis, if PML is possible.

DOI： 10.3389/fimmu.2024.1447992

Non-sinus type of transverse sinus dural arteriovenous fistulas on the arachnoid granulation of the dural sinus wall. International journal

Tomoaki Suzuki, Hitoshi Hasegawa, Kouichirou Okamoto, Kohei Shibuya, Hidemoto Fujiwara, Makoto Oishi

Surgical neurology international 15 43 - 43 2024

Language：English

BACKGROUND: The etiology of a non-sinus-type dural arteriovenous fistulas (DAVFs) with shunt points located on the sinus wall, previously described as on-the-wall-type DAVFs, is unknown. CASE DESCRIPTION: Two cases of non-sinus-type transverse sinus DAVF with a shunt point limited to the dural sinus wall, causing cortical venous reflux, were successfully treated with endovascular transarterial Onyx embolization. The Onyx cast showed multiple feeders from the occipital and middle meningeal arteries aggregated in the arachnoid granulation (AG), which dilated the draining vein. CONCLUSION: Non-sinus-type DAVFs with shunt points located on the AG may be one of the presentations of an on-the-wall-type DAVF.

DOI： 10.25259/SNI_930_2023

嚢胞形成PRL産生PitNETの治療成績

岡田正康, 小倉良介, 平石哲也, 米岡有一郎, 大石誠

新潟医学会雑誌 137 ( 12 ) 447 - 447 2023.12

未破裂内頸動脈後交通動脈分岐部瘤に対する血管内治療の現状と課題

藤原秀元, 長谷川仁, 鈴木倫明, 澁谷航平, 吉田至誠, 大石誠

脳血管内治療 8 ( Suppl. ) S440 - S440 2023.11

CFDによる破裂脳動脈瘤のブレブ血流解析破裂点となり得るブレブの血行力学的特徴

鈴木倫明, 長谷川仁, 吉田至誠, 渋谷航平, 藤原秀元, 大石誠

脳血管内治療 8 ( Suppl. ) S264 - S264 2023.11

破裂脳動脈瘤に対する当院における血管内治療の現状

鈴木倫明, 長谷川仁, 吉田至誠, 渋谷航平, 藤原秀元, 大石誠

脳血管内治療 8 ( Suppl. ) S310 - S310 2023.11

横-S状静脈洞部硬膜動静脈瘻難治例の特徴

吉田至誠, 渋谷航平, 藤原秀元, 鈴木倫明, 長谷川仁, 大石誠

脳血管内治療 8 ( Suppl. ) S199 - S199 2023.11

PICA and ASA involved typeの出血性解離性椎骨動脈瘤に対し,急性期にステント支援下コイル塞栓術を行い,慢性期にOA-PICA bypass併用コイル塞栓術を行った1例

鈴木倫明, 長谷川仁, 澁谷航平, 齋藤太希, 高橋陽彦, 大石誠, 藤井幸彦

脳卒中の外科 51 ( 6 ) 513 - 519 2023.11

Language：Japanese Publisher：(一社)日本脳卒中の外科学会

後下小脳動脈(posterior inferior cerebellar artery:PICA)と前脊髄動脈(anterior spinal artery:ASA)の双方を含むdominant sideの破裂解離性椎骨動脈瘤(ruptured vertebral artery dissecting aneurysm:rVADA)に対して,急性期にステント併用コイル塞栓術(stent-assisted coiling:SAC)を行い,再発を認めたため慢性期にOA-PICA bypass併用コイル塞栓術を行った症例を経験したので報告する.症例は50歳男性.突然の頭痛.全身痙攣にて発症.後頭蓋窩に厚いくも膜下出血を認め(Hunt and Kosnik grade III),dominant sideの左VAに破裂解離性椎骨動脈瘤を認めた.PICA and ASA involved typeのrVADAに対して,破裂急性期にSACにてPICAとASAの血流を温存して破裂部位を中心にコイル塞栓を行った.しかしながら,術後8日目にminor bleedingを認めたため,破裂部位の追加塞栓を行った.その後は自宅退院となり(mRS1),再出血を認めず経過していたが,術後2ヵ月目に偽腔の開大を認めたため,後頭動脈(occipital artery:OA)-PICA bypassを併用した解離部のコイル塞栓術を行い,最終的に根治することができた.Dominant side VAにおけるPICA and ASA involved type rVADAに対して破裂急性期のSACによるreconstructive treatmentと慢性期におけるOA-PICA bypass併用によるコイル塞栓術は有効な治療選択肢の1つとなり得る.(著者抄録)

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脳AVMに対する血管内治療の進歩と調和脳動静脈奇形に対する塞栓術の進歩と調和

長谷川仁, 鈴木倫明, 澁谷航平, 藤原秀元, 大石誠

脳血管内治療 8 ( Suppl. ) S73 - S73 2023.11

Clinical, imaging, and molecular features of radiation-induced glioblastomas developing more than 20 years after radiation therapy for intracranial germinomatous germ cell tumor: illustrative cases. International journal

Yoshihiro Tsukamoto, Manabu Natsumeda, Haruhiko Takahashi, Asuka Ueno, Kiichi Sakai, Kazuki Shida, Hiroki Seto, Taiki Saito, Satoshi Shibuma, Yoko Nakayama, Yuki Tanaka, Toshimichi Nakano, Atsushi Ohta, Katsuya Maruyama, Masayasu Okada, Takeyoshi Eda, Yasuhiro Seki, Yuichirou Yoneoka, Hiroshi Shimizu, Kouichirou Okamoto, Akiyoshi Kakita, Makoto Oishi

Journal of neurosurgery. Case lessons 6 ( 16 ) 2023.10

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Germinomatous germ cell tumor is highly sensitive to chemoradiotherapy; patients are expected to survive for decades. Many radiation-induced malignant gliomas (RIMGs) occur >10 years after radiotherapy. Standard therapy for RIMGs has not been established because of the lesion's rarity, the patient's shorter survival period, and the risk of radiation necrosis by repeat radiation. OBSERVATIONS: Two patients, a 32-year-old man and a 50-year-old man, developed glioblastomas more than 20 years after radiation monotherapy for germinoma with or without mature teratoma. The first patient showed a tumor in the left frontotemporal region with disseminated lesions and died 2 months after partial resection of the tumor without responding to the chemotherapy with temozolomide and bevacizumab. Methylation classifier analysis classified the pathology as closest to diffuse pediatric-type high-grade glioma, Rtk1 subtype. The second patient showed a tumor mass in the brainstem and left cerebellar peduncle, which worsened progressively during chemotherapy with temozolomide and bevacizumab. The tumor transiently responded to stereotactic radiotherapy with the CyberKnife. However, the patient died of RIMG recurrence-related aspiration pneumonia 11 months after the biopsy. Methylation classifier analysis classified the pathology as closest to infratentorial pilocytic astrocytoma. LESSONS: Chemoradiotherapy may improve the survival of patients with RIMGs. Furthermore, molecular features may influence the clinical, locoregional, and pathological features of RIMG.

DOI： 10.3171/CASE23361

Investigation of Mechanical Thrombectomy in Elderly Patients over 85 Years Old: A Multicenter Study.

Kohei Shibuya, Hitoshi Hasegawa, Tomoaki Suzuki, Haruhiko Takahashi, Kei Nishiyama, Makoto Oishi, Yukihiko Fujii

Neurologia medico-chirurgica 63 ( 9 ) 393 - 399 2023.9

Language：English Publishing type：Research paper (scientific journal)

In Japan, which has a super-aging society, there are increasing opportunities to perform mechanical thrombectomy for the elderly; however, there is no recorded evidence of thrombectomy for the elderly. This study examined the usefulness of thrombectomy in the elderly. We retrospectively analyzed patient data using a multicenter acute ischemic stroke registry (NGT-FAST). We examined outcomes in patients 75 years and older who underwent thrombectomies between January 1, 2021, and December 31, 2021. The patients were divided into two groups: the 75-84-year-old group and the 85+-year-old group. There was no difference in the pretreatment National Institutes of Health Stroke Scale score or Alberta Stroke Program Early Computed Tomography Score between the two groups, but the 85+-year-old group had a significantly lower rate of pre-stroke modified Rankin Scale (mRS) score of 0-2. There were no differences in time from onset to treatment or effective recanalization rate, but complications tended to be more common in the 85+-year-old group. The number of patients with a good outcome at discharge (an mRS score of 0-3) was significantly lower in the 85+-year-old group than in the 75-84-year-old group. In addition, 90.9% of patients in the 85+-year-old group with a pre-stroke mRS score of 3 deteriorated after treatment. The pre-stroke mRS score is very important in determining the indication for thrombectomy in the elderly because their preoperative condition is more likely to influence the outcome than that of younger patients.

DOI： 10.2176/jns-nmc.2023-0039

【「脳神経外科領域におけるPDTの現状と問題点」】当科における光線力学療法の経験および次世代への挑戦

棗田学, 温城太郎, 渡邉潤, 塚本佳広, 岡田正康, 小倉良介, 平石哲也, 大石誠, 藤井幸彦

日本レーザー医学会誌 44 ( 2 ) 95 - 101 2023.7

Language：Japanese Publisher：(NPO)日本レーザー医学会

2018年7月に当科に光線力学療法(photodynamic therapy:PDT)を導入してから2021年6月まで,当科でPDTを施行した悪性脳腫瘍症例の臨床的特徴および無増悪生存期間(progression free survival:PFS),全生存期間(overall survival:OS),主な合併症について検討した.初発膠芽腫9例におけるPFSの中央値は14ヵ月,OS中央値は未達であった.死亡例は早期に遠隔再発を来した1例のみであった.主な合併症は光過敏症が1例,脳表に可逆性のFLAIR高信号が3例,術後うつ状態が5例に認め,いずれも一過性であった.術後の長期間遮光管理が原因と思われるうつ症状には,早期遮光解除などの工夫が必要と思われた.実際の症例を提示し我々のPDT初期治療経験を紹介し,また,次世代治療と考える近赤外光線免疫療法(near-infrared photoimmunotherapy:NIR-PIT)の研究に関しても紹介する.NIR-PITは,癌細胞の表面抗原を標識とし,近赤外線照射により生じた熱エネルギーにより腫瘍細胞の細胞膜を破壊する画期的な治療法である.今回,我々は膠芽腫細胞株に特異的な表面抗原Xに対する抗体を用いたNIR-PITを行い,殺細胞効果を確認した.(著者抄録)

Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J01213&link_issn=&doc_id=20230803380003&doc_link_id=10.2530%2Fjslsm.jslsm-44_0024&url=https%3A%2F%2Fdoi.org%2F10.2530%2Fjslsm.jslsm-44_0024&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

【「脳神経外科領域におけるPDTの現状と問題点」】当科における光線力学療法の経験および次世代への挑戦

棗田学, 温城太郎, 渡邉潤, 塚本佳広, 岡田正康, 小倉良介, 平石哲也, 大石誠, 藤井幸彦

日本レーザー医学会誌 44 ( 2 ) 95 - 101 2023.7

Language：Japanese Publisher：(NPO)日本レーザー医学会

2018年7月に当科に光線力学療法(photodynamic therapy:PDT)を導入してから2021年6月まで,当科でPDTを施行した悪性脳腫瘍症例の臨床的特徴および無増悪生存期間(progression free survival:PFS),全生存期間(overall survival:OS),主な合併症について検討した.初発膠芽腫9例におけるPFSの中央値は14ヵ月,OS中央値は未達であった.死亡例は早期に遠隔再発を来した1例のみであった.主な合併症は光過敏症が1例,脳表に可逆性のFLAIR高信号が3例,術後うつ状態が5例に認め,いずれも一過性であった.術後の長期間遮光管理が原因と思われるうつ症状には,早期遮光解除などの工夫が必要と思われた.実際の症例を提示し我々のPDT初期治療経験を紹介し,また,次世代治療と考える近赤外光線免疫療法(near-infrared photoimmunotherapy:NIR-PIT)の研究に関しても紹介する.NIR-PITは,癌細胞の表面抗原を標識とし,近赤外線照射により生じた熱エネルギーにより腫瘍細胞の細胞膜を破壊する画期的な治療法である.今回,我々は膠芽腫細胞株に特異的な表面抗原Xに対する抗体を用いたNIR-PITを行い,殺細胞効果を確認した.(著者抄録)

Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J01213&link_issn=&doc_id=20230803380003&doc_link_id=10.2530%2Fjslsm.jslsm-44_0024&url=https%3A%2F%2Fdoi.org%2F10.2530%2Fjslsm.jslsm-44_0024&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Usefulness of silent magnetic resonance angiography for intracranial aneurysms treated with a flow re-direction endoluminal device. International journal

Tomoaki Suzuki, Hitoshi Hasegawa, Kouichirou Okamoto, Kazuhiro Ando, Kouhei Shibuya, Haruhiko Takahashi, Shoji Saito, Hidemoto Fujiwara, Makoto Oishi, Yukihiko Fujii

Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences 15910199231174546 - 15910199231174546 2023.5

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Flow re-direction endoluminal device (FRED) is a novel dual-layer flow-diverting stent to treat cerebral aneurysms with high obliteration rates, however, it induces inevitable metal-related artifacts. We compared silent magnetic resonance angiography (MRA), a new MRA method using ultra-short time of echo and arterial spin-labeling, with conventional time-of-flight (TOF)-MRA for imaging aneurysms treated using FRED. METHODS: Between May 2020 and September 2022, 16 patients with unruptured internal carotid aneurysms treated using FRED simultaneously underwent silent MRA and TOF-MRA after treatment, with 36 follow-up sessions in total. Two observers independently graded the quality of intra-aneurysmal flow and stented parent arteries under both types of MRA from 1 (not visible) to 4 (nearly equal to digital subtraction angiography [DSA]), with reference to DSA images as a standard criterion. RESULTS: The mean scores for intra-aneurysmal flow and stented parent arteries were significantly better for silent MRA (3.93 ± 0.21 and 3.82 ± 0.32, respectively) than for TOF-MRA (2.08 ± 0.99 and 1.92 ± 0.79, respectively) (P < 0.01). Intermodality agreements for intra-aneurysmal flow and stented parent arteries were 0.87 and 0.90, respectively. CONCLUSION: Silent MRA is superior to TOF-MRA for assessing patients treated with FRED, with potential as an alternative imaging modality to DSA.

DOI： 10.1177/15910199231174546

Superior Visualization of Neovascularization with Silent Magnetic Resonance Angiography Compared to Time-of-flight Magnetic Resonance Angiography after Bypass Surgery in Moyamoya Disease. International journal

Tomoaki Suzuki, Hitoshi Hasegawa, Kouichirou Okamoto, Kohei Shibuya, Haruhiko Takahashi, Hidemoto Fujiwara, Makoto Oishi, Yukihiko Fujii

World neurosurgery 2023.5

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: The evaluation of postsurgical neoangiogenesis in patients with moyamoya disease (MMD) is crucial for appropriate patient management. This study aimed to assess the visualization of neovascularization after bypass surgery using non-contrast-enhanced silent magnetic resonance angiography (MRA) with ultra-short echo time (UTE) and arterial spin labeling (ASL). METHODS: After bypass surgery, 13 patients with MMD were followed up for >6 months between September 2019 and November 2022. They underwent silent MRA in the same session as time-of-flight MRA (TOF-MRA) and digital subtraction angiography (DSA). Two observers independently rated the visualization of neovascularization in both types of MRA from 1 (not visible) to 4 (nearly equal to DSA), with reference to DSA images as the standard. RESULTS: The mean scores were significantly higher for silent MRA compared with TOF-MRA (3.81 ± 0.48 and 1.92 ± 0.70, respectively) (p <0.01). The inter-modality agreements were 0.83 and 0.71 for silent MRA and TOF-MRA, respectively. TOF-MRA depicted the donor artery and recipient cortical artery after direct bypass surgery, although fine neovascularization developed after indirect bypass surgery was poorly visualized. Silent MRA could reveal the developed bypass flow signal and perfused MCA territory, which was almost equal to the DSA images. CONCLUSIONS: Silent MRA achieves better visualization of postsurgical revascularization in patients with MMD than TOF-MRA. Moreover, it may have the potential to provide visualization of the developed bypass flow equivalent to DSA.

DOI： 10.1016/j.wneu.2023.04.119

胚種治療後20年以上経過後に発症した放射線誘発性膠芽腫の2症例の検討

塚本佳広, 高橋陽彦, 棗田学, 坂井貴一, 中山遥子, 田中裕貴, 岡本浩一郎, 大石誠, 柿田明美, 藤井幸彦

Brain Tumor Pathology 40 ( Suppl. ) 113 - 113 2023.5

FGFR3-TACC3 fusionを伴うIDH野生型神経膠腫はCTで石灰化を高率に有する

高橋陽彦, 棗田学, 塚本佳広, 清水宏, 岡本浩一郎, 峰晴陽平, 荒川芳輝, 大石誠, 柿田明美, 藤井幸彦

Brain Tumor Pathology 40 ( Suppl. ) 099 - 099 2023.5

プロラクチン産生下垂体腺腫が頸部に転移したPit-1陽性下垂体がんの一例

岡田正康, 植木雄志, 棗田学, 大石誠, 近藤修平, 梅津哉, 柿田明美, 藤井幸彦

Brain Tumor Pathology 40 ( Suppl. ) 144 - 144 2023.5

プロラクチン産生下垂体腺腫が頸部に転移したPit-1陽性下垂体がんの一例

岡田正康, 植木雄志, 棗田学, 大石誠, 近藤修平, 梅津哉, 柿田明美, 藤井幸彦

Brain Tumor Pathology 40 ( Suppl. ) 144 - 144 2023.5

TP53変異を有する脈絡叢癌培養細胞株の樹立およびマルチオミクス解析

棗田学, 温城太郎, 塚本佳広, 岡田正康, 大石誠, 久保暢大, 申将守, 今村勝, 今井千速, シャヘンダ・エル・ナガール, 藤井幸彦

新潟医学会雑誌 137 ( 5 ) 186 - 186 2023.5

Administration of glucocorticoids prior to liquid biopsy dramatically reduces the detection rate of <i>MYD88 L265P</i> mutation in cerebrospinal fluid of primary CNS lymphoma patients

Haruhiko Takahashi, Manabu Natsumeda, Jotaro On, Jun Watanabe, Mari Tada, Hiroshi Shimizu, Yoshihiro Tsukamoto, Masayasu Okada, Makoto Oishi, Jun Takizawa, Yasuhiko Hayashi, Yasufumi Masaki, Akiyoshi Kakita, Yukihiko Fujii

Leukemia & Lymphoma 64 ( 6 ) 1219 - 1222 2023.4

がんゲノム医療がもたらす小児脳腫瘍の展開 TP53変異を有する脈絡叢癌培養細胞株の樹立およびマルチオミクス解析

棗田学, 温城太郎, 塚本佳広, 岡田正康, 大石誠, 久保暢大, 申将守, 今村勝, 今井千速, エルナガール・シャヘンダ, 藤井幸彦

小児の脳神経 48 ( 2 ) 156 - 156 2023.4

がんゲノム医療がもたらす小児脳腫瘍の展開 TP53変異を有する脈絡叢癌培養細胞株の樹立およびマルチオミクス解析

棗田学, 温城太郎, 塚本佳広, 岡田正康, 大石誠, 久保暢大, 申将守, 今村勝, 今井千速, エルナガール・シャヘンダ, 藤井幸彦

小児の脳神経 48 ( 2 ) 156 - 156 2023.4

Preoperative three-dimensional multifusion imaging aiding successful microvascular decompression of a cerebellopontine angle lipoma: associated hemifacial spasm. Illustrative case. International journal

Hiroki Seto, Ryosuke Ogura, Tetsuya Hiraishi, Yoshihiro Tsukamoto, Taiki Saito, Satoshi Shibuma, Kohei Shibuya, Kouichirou Okamoto, Makoto Oishi, Yukihiko Fujii

Journal of neurosurgery. Case lessons 5 ( 12 ) 2023.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Cerebellopontine angle (CPA) lipoma-associated hemifacial spasm (HFS) is rare. As the removal of CPA lipomas has a high risk of worsening the neurological symptoms, surgical exploration is warranted only in selected patients. Preoperative identification of the lipoma affected site of the facial nerve, and offending artery are crucial for patient selection and successful microvascular decompression (MVD). OBSERVATIONS: Presurgical simulation using three-dimensional (3D) multifusion imaging showed a tiny CPA lipoma wedged between the facial and auditory nerves, as well as an affected facial nerve by the anterior inferior cerebellar artery (AICA) at the cisternal segment. Although a recurrent perforating artery from the AICA anchored the AICA to the lipoma, successful MVD was achieved without lipoma removal. LESSONS: The presurgical simulation using 3D multifusion imaging could identify the CPA lipoma, affected site of the facial nerve, and offending artery. It was helpful for patient selection and successful MVD.

DOI： 10.3171/CASE2318

Elevated ratio of C-type lectin-like receptor 2 level and platelet count (C2PAC) aids in the diagnosis of post-operative venous thromboembolism in IDH-wildtype gliomas. International journal

Kazuhiro Ando, Manabu Natsumeda, Masahide Kawamura, Kamon Shirakawa, Masayasu Okada, Yoshihiro Tsukamoto, Takeyoshi Eda, Jun Watanabe, Shoji Saito, Haruhiko Takahashi, Akiyoshi Kakita, Makoto Oishi, Yukihiko Fujii

Thrombosis research 223 36 - 43 2023.3

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: Podoplanin (PDPN) is known to induce platelet aggregation via interacting with the C-type lectin-like receptor-2 on platelets and is involved in postoperative venous thromboembolism (VTE) formation. In this study, we investigate the correlation between soluble C-type lectin-like receptor (sCLEC-2) levels and PDPN expression in patients with high grade gliomas and the relationship between sCLEC-2 levels and the occurrence of VTE. MATERIALS AND METHODS: Forty-four patients harboring high grade gliomas, treated surgically at the Department of Neurosurgery, Niigata University from April 2018 to August 2020, were included. Patients with high grade gliomas were divided into isocitrate dehydrogenase (IDH)- wildtype and mutant groups, and the presence or absence of VTE and the intensity of PDPN by immunohistochemistry were confirmed. Platelet counts, as well as plasma sCLEC-2 and PDPN were measured in these patients. Furthermore, the levels of sCLEC-2 concentration were divided by the platelet count (C2PAC index) for comparison. RESULTS: IDH-wildtype glioma patients highly expressed PDPN (P < 0.001) compared to IDH-mutant glioma patients. In total, 9 (20.5 %) patients were diagnosed with VTE during the follow-up period, of which 8 patients harbored IDH-wildtype gliomas, and one patient an IDH-mutant glioma. Mean sCLEC-2 levels and C2PAC index in patients with IDH-wildtype gliomas were significantly higher than that of low or no PDPN expression group, which included patients with IDH-mutant gliomas (P = 0.0004, P = 0.0002). In patients with IDH-wildtype gliomas, the C2PAC index in patients with VTE was significantly higher than in patients without VTE (P = 0.0492). The optimal cutoff point of C2PAC for predicting VTE in IDH-wildtype glioma patients was 3.7 with a sensitivity of 87.5 % and specificity of 51.9 %. CONCLUSION: Platelet activation is strongly involved in the development of VTE in patients with IDH-wildtype high grade gliomas, and C2PAC index is a potential marker to detect VTE formation after surgery.

DOI： 10.1016/j.thromres.2023.01.018

A Case of Paradoxical Cerebral Embolism Due to Pulmonary Arteriovenous Fistula Mimicking Vertebral Artery Dissection With Wallenberg Syndrome. International journal

Masaru Isogai, Tomoaki Suzuki, Shyunichi Kato, Yoshinori Taniguchi, Hitoshi Hasegawa, Makoto Oishi, Yukihiko Fujii

Cureus 15 ( 2 ) e34564 2023.2

Language：English

Pulmonary arteriovenous fistula (PAVF) leads to paradoxical cerebral embolism, which can be fatal if left untreated. We report a rare case of brainstem infarction with acute severe headache and Wallenberg syndrome caused by a PAVF mimicking vertebral artery (VA) dissection. A 40-year-old man presented with a sudden occipital headache accompanied by right hemisensory disturbance. Magnetic resonance imaging revealed left lateral medullary infarction and poor depiction of the left VA. However, it was clearly recanalized on day six, and there were no findings of VA dissection. Whole-body contrast-enhanced computed tomography (CT) revealed a PAVF in the right lung and a thrombus in the feeding artery. The patient was diagnosed with hereditary hemorrhagic telangiectasia due to recurrent epistaxis and peripheral vasodilation of the tongue. An anticoagulant was administered for preventing further ischemic stroke, and a follow-up CT confirmed the disappearance of the thrombus in three months. Thoracoscopic partial lung resection was performed five months after the onset, and no recurrence of ischemic stroke was observed.

DOI： 10.7759/cureus.34564

頸部リンパ節転移で"下垂体がん"の診断に至った症例

岡田正康, 棗田学, 大石誠, 米岡有一郎, 藤井幸彦

新潟医学会雑誌 137 ( 2 ) 71 - 71 2023.2

Usefulness of Y-shaped PulseRider-assisted coil embolization for basilar artery tip aneurysm with a misaligned axis: A case report. International journal

Kohei Shibuya, Hitoshi Hasegawa, Tomoaki Suzuki, Hidemoto Fujiwara, Satoshi Shibuma, Kazuki Shida, Makoto Oishi

Surgical neurology international 14 300 - 300 2023

Language：English

BACKGROUND: Endovascular treatment of wide-necked bifurcation aneurysms remains challenging. Although the advent of PulseRider and Web has expanded treatment options, aneurysms with a large deviation from the parent artery axis remains difficult to treat. We present the case of a wide-necked bifurcation aneurysm that was misaligned with the angle between the long axis of the parent artery and the aneurysm and was successfully treated with Y-shaped PulseRider-assisted coil embolization. CASE DESCRIPTION: A 64-year-old woman presented with an unruptured basilar tip aneurysm. Cerebral angiography showed a wide-necked aneurysm measuring 8.1 mm × 6.1 mm, neck 5.7 mm. The aneurysm was strongly tilted to the right and posterior relative to the basilar artery, and the bilateral posterior cerebral artery (PCA) and superior cerebellar artery (SCA) diverged from the aneurysm body. PulseRider-assisted coil embolization was performed. A Y-shaped PulseRider was selected to be placed in a hybrid fashion with the right arch in the aneurysm and the left arch in the branch. Adequate coil embolization with preservation of the bilateral PCA and SCA was possible, and cerebral angiography immediately after the treatment showed slight dome filling. Cerebral angiography 6 months after the procedure showed that the embolic status had improved to complete occlusion. CONCLUSION: For wide-neck bifurcation aneurysms with a misaligned axis, a Y-shaped PulseRider used in a hybrid fashion, in which the leaflet on the side with the tilted axis is placed in the aneurysm, allows the PulseRider to be deployed more closely to the aneurysm, thereby enabling good coil embolization.

DOI： 10.25259/SNI_449_2023

髄液よりH3K27M変異が検出可能なdiffuse midline gliomaの検討

棗田学, 温城太郎, 渡邉潤, 高橋陽彦, 塚本佳広, 岡田正康, 平石哲也, 吉村淳一, 大石誠, 藤井幸彦

小児の脳神経 47 ( 4 ) 358 - 364 2022.11

Language：Japanese Publisher：(一社)日本小児神経外科学会

Diffuse midline glioma(DMG)の80%以上がヒストンH3K27M変異を有する.橋に局在する病変は摘出術の適応はなく,針生検でも重篤な合併症が生じ得るためDMGに対してliquid biopsyの確立が切望される.我々は初発時に腰椎穿刺で採取した脳脊髄液よりH3K27Mを同定するのは困難と報告した.本稿では,多発病変および播種病変を有しliquid biopsyによりH3K27M変異と同定された2症例を紹介し,liquid biopsyの恩恵を受ける症例の特徴について迫る.(著者抄録)

Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J00650&link_issn=&doc_id=20230215270002&doc_link_id=10.34544%2Fjspn.47.4_358&url=https%3A%2F%2Fdoi.org%2F10.34544%2Fjspn.47.4_358&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

M2以遠の閉塞における機械的血栓回収療法は有効か?

渋谷航平, 長谷川仁, 鈴木倫明, 高橋陽彦, 渋間啓, 大石誠, 藤井幸彦

脳血管内治療 7 ( Suppl. ) S134 - S134 2022.11

Epigenetic upregulation of Schlafen11 renders WNT- and SHH- activated medulloblastomas sensitive to cisplatin. Reviewed International journal

Satoshi Nakata, Junko Murai, Masayasu Okada, Haruhiko Takahashi, Tyler H Findlay, Kristen Malebranche, Akhila Parthasarathy, Satoshi Miyashita, Ramil Gabdulkhaev, Ilan Benkimoun, Sabine Druillennec, Sara Chabi, Eleanor Hawkins, Hiroaki Miyahara, Kensuke Tateishi, Shinji Yamashita, Shiori Yamada, Taiki Saito, Jotaro On, Jun Watanabe, Yoshihiro Tsukamoto, Junichi Yoshimura, Makoto Oishi, Toshimichi Nakano, Masaru Imamura, Chihaya Imai, Tetsuya Yamamoto, Hideo Takeshima, Atsuo T Sasaki, Fausto J Rodriguez, Sumihito Nobusawa, Pascale Varlet, Celio Pouponnot, Satoru Osuka, Yves Pommier, Akiyoshi Kakita, Yukihiko Fujii, Eric H Raabe, Charles G Eberhart, Manabu Natsumeda

Neuro-oncology 25 ( 5 ) 899 - 912 2022.10

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Intensive chemotherapeutic regimens with craniospinal irradiation have greatly improved survival in medulloblastoma patients. However, survival markedly differs among molecular subgroups and their biomarkers are unknown. Through unbiased screening, we found Schlafen family member 11 (SLFN11), which is known to improve response to DNA damaging agents in various cancers, to be one of the top prognostic markers in medulloblastomas. Hence, we explored the expression and functions of SLFN11 in medulloblastoma. METHODS: SLFN11 expression for each subgroup was assessed by immunohistochemistry in 98 medulloblastoma patient samples and by analyzing transcriptomic databases. We genetically or epigenetically modulated SLFN11 expression in medulloblastoma cell lines and determined cytotoxic response to the DNA damaging agents cisplatin and topoisomerase I inhibitor SN-38 in vitro and in vivo. RESULTS: High SLFN11 expressing cases exhibited significantly longer survival than low expressing cases. SLFN11 was highly expressed in the WNT-activated subgroup and in a proportion of the SHH-activated subgroup. While WNT activation was not a direct cause of the high expression of SLFN11, a specific hypomethylation locus on the SLFN11 promoter was significantly correlated with high SLFN11 expression. Overexpression or deletion of SLFN11 made medulloblastoma cells sensitive and resistant to cisplatin and SN-38, respectively. Pharmacological upregulation of SLFN11 by the brain-penetrant histone deacetylase-inhibitor RG2833 markedly increased sensitivity to cisplatin and SN-38 in SLFN11-negative medulloblastoma cells. Intracranial xenograft studies also showed marked sensitivity to cisplatin by SLFN11-overexpression in medulloblastoma cells. CONCLUSIONS: High SLFN11 expression is one factor which renders favorable outcomes in WNT-activated and a subset of SHH-activated medulloblastoma possibly through enhancing response to cisplatin.

DOI： 10.1093/neuonc/noac243

Elucidating the multiple genetic alterations involved in the malignant transformation of a KRAS mutant neurenteric cyst. A case report. International journal

Shoji Saito, Manabu Natsumeda, Makoto Sainouchi, Toru Takino, Kohei Shibuya, Jotaro On, Yu Kanemaru, Ryosuke Ogura, Masayasu Okada, Makoto Oishi, Yoshifumi Shimada, Toshifumi Wakai, Shujiro Okuda, Yoichi Ajioka, Akiyoshi Kakita, Yukihiko Fujii

Neuropathology : official journal of the Japanese Society of Neuropathology 42 ( 6 ) 519 - 525 2022.9

Language：English

Neurenteric cyst (NC) shows benign histopathology and rarely demonstrate malignant transformation. We herein describe a case of NC that exhibited malignant transformation. A 65-year-old female presented with gait disturbance due to compression by a cystic mass on the dorsal surface of the medulla oblongata. Partial resection was performed twice, leading to improvement of her symptoms. Two years after the second surgery, gadolinium-perfused T1-weighted magnetic resonance imaging revealed an invasive lesion with contrast enhancement at the trigone of the left lateral ventricle for which partial resection followed by radiotherapy was performed. However, mass regrowth was observed, with the patient eventually succumbing to her disease 11 months after her third surgery. Histopathological analyses of the first and second surgical specimens identified pseudostratified cuboidal epithelial cells, with no nuclear or cellular atypia resembling gastrointestinal mucosa, lining the inner surface of the cystic wall. Based on these findings the lesion was diagnosed as NC. The third surgical specimen exhibited apparent malignant features of the epithelial cells with elongated and hyperchromatic nuclei, several mitotic figures, small necrotic foci, and a patternless or sheet-like arrangement. Based on these findings, the lesion was diagnosed as NC with malignant transformation. Next-generation sequencing revealed KRAS p.G12D mutation in all specimens. Additionally, the third surgical specimen harbored the following 12 de novo gene alterations: ARID1A loss, BAP1 p.F170L, CDKN1B loss, CDKN2A loss, CDKN2B loss, FLCN loss, PTCH1 loss, PTEN loss, PTPRD loss, SUFU loss, TP53 loss, and TSC1 loss. The aforementioned results suggest that KRAS mutation is associated with the development of the NC, and that the additional gene alterations contribute to malignant transformation of the NC.

DOI： 10.1111/neup.12822

Successful Treatment of Acute Uric Acid Nephropathy with Rasburicase in a Primary Central Nervous System Lymphoma Patient Showing a Dramatic Response to Methotrexate—Case Report

Yoshihiro Mouri, Manabu Natsumeda, Noritaka Okubo, Taro Sato, Taiki Saito, Kohei Shibuya, Shiori Yamada, Jotaro On, Yoshihiro Tsukamoto, Masayasu Okada, Makoto Oishi, Takeyoshi Eda, Junko Murai, Hiroshi Shimizu, Akiyoshi Kakita, Yukihiko Fujii

Journal of Clinical Medicine 11 ( 19 ) 5548 - 5548 2022.9

Publishing type：Research paper (scientific journal) Publisher：MDPI AG

Background: Primary central nervous system lymphomas (PCNSLs) are sensitive to chemotherapy. The standard treatment is high-dose methotrexate (MTX)-based chemotherapy. There are no reports of successful treatment of acute uric acid nephropathy with rasburicase after MTX administration in PCNSLs. Case presentation: A 54-year-old man with a history of gout presented with a change in character and cognitive dysfunction. MRI showed a large enhancing mass spanning the bilateral frontal lobes and the right temporal lobe. After endoscopic biopsy, an MTX, procarbazine, and vincristine (MPV) regimen was initiated for the treatment of the PCNSL. After the initiation of chemotherapy, the patient experienced a gout attack, and blood examination revealed acute renal failure (ARF) and hyperuricemia. The considered causes of ARF included MTX toxicity and acute uric acid nephropathy. As the dramatic effect of MTX was observed, treatment was continued despite ARF, most probably due to acute hyperuricemia due to tumor lysis, which was treated in parallel. After an improvement in renal function, MTX was resumed, and rasburicase was initiated to control hyperuricemia. A complete response was obtained after induction chemotherapy. Hyperuricemia was controlled with rasburicase, and renal function was preserved. Conclusions: Acute uric acid nephropathy should be considered when ARF occurs after the initiation of MTX in PCNSLs, especially in newly diagnosed PCNSL patients with large tumors or hyperuricemia.

DOI： 10.3390/jcm11195548

Characteristics of health-related quality of life and related factors in patients with brain tumors treated with rehabilitation therapy. International journal

Takahiro Watanabe, Shinichi Noto, Manabu Natsumeda, Shinji Kimura, Satoshi Tabata, Fumie Ikarashi, Mayuko Takano, Yoshihiro Tsukamoto, Makoto Oishi

Journal of patient-reported outcomes 6 ( 1 ) 94 - 94 2022.9

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Rehabilitation therapy during hospitalization is effective in improving activities of daily living (ADL) and physical function in patients with brain tumors. However, there are few studies on the effect of rehabilitation therapy on health-related quality of life (HRQOL) in patients with brain tumors. Additionally, the EuroQol-5Dimension-5Level (EQ-5D-5L) index score has not been reported as an outcome. This study aimed to investigate the HRQOL of patients with brain tumors who underwent rehabilitation therapy and investigated the factors affecting the EQ-5D-5L index score from various perspectives, including various brain tumor type and recurrence. In addition, we examined the relationship between the EQ-5D-5L index score, disease-specific HRQOL scale, and ADL. METHODS: Patients with brain tumors who underwent treatment and rehabilitation at Single tertiary care academic medical center were included in this cross-sectional study. We used the EQ-5D-5L, European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire core 30, and EORTC quality of life questionnaire brain cancer module to evaluate HRQOL. ADL were assessed using the functional independence measure (FIM). The relationship between each HRQOL assessment score and the FIM was analyzed, and the influence of related factors was assessed by multiple regression analysis. RESULTS: This study included 76 patients. The EQ-5D-5L index score was 0.689 for all patients with brain tumors and 0.574 for those with glioblastomas, which was the lowest value. There was a moderate correlation between the EQ-5D-5L index score and FIM (r = 0.627, p < 0.001). In addition, the EQ-5D-5L index score was significantly correlated with most of the items of the disease-specific HRQOL scale. Multiple regression analysis revealed that glioblastoma histology (coefficient: - 0.373, p = 0.005) and recurrence (coefficient: - 0.273, p = 0.020) were independent factors affecting the EQ-5D-5L index score. CONCLUSIONS: Patients with glioblastoma undergoing rehabilitation have reduced HRQOL, which was influenced by glioblastoma histology and recurrence.

DOI： 10.1186/s41687-022-00499-y

髄芽腫におけるSLFN11発現およびDNA障害型抗がん剤への感受性の検討

棗田学, 中田聡, 村井純子, 岡田正康, 塚本佳広, 大石誠, 藤井幸彦, Eberhart Charles G.

新潟医学会雑誌 136 ( 8 ) 273 - 274 2022.8

脳腫瘍研究のcutting edge-先端画像、実験/分子病理、デジタル病理- 髄芽腫におけるGLI3 single cell RNAシーケンス解析細胞レベルから見えて来たこと

棗田学, 宮下聡, 宮原弘明, 高橋晴彦, 塚本佳広, 大石誠, 吉村淳一, 柿田明美, 藤井幸彦

Brain Tumor Pathology 39 ( Suppl. ) 072 - 072 2022.5

小児・AYA世代のヒストン遺伝子変異びまん性神経膠腫症例の後方視的検討

塚本佳広, 高橋陽彦, 温城太郎, 小倉良介, 棗田学, 岡本浩一郎, 大石誠, 柿田明美, 藤井幸彦

Brain Tumor Pathology 39 ( Suppl. ) 100 - 100 2022.5

Long-Term Characteristics of De Novo Bleb Formation at the Aneurysm Neck After Coil Embolization in Unruptured Cerebral Aneurysms. International journal

Tomoaki Suzuki, Hitoshi Hasegawa, Kazuhiro Ando, Kohei Shibuya, Haruhiko Takahashi, Shoji Saito, Makoto Oishi, Yukihiko Fujii

World neurosurgery 161 e767-e775 2022.5

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: De novo bleb formation at the aneurysm neck after coil embolization of unruptured intracranial aneurysms is a rarely observed type of recurrence. The aim of this study was to elucidate the clinical characteristics of recurrent aneurysms in the long-term period. METHODS: Between January 2002 and December 2015, 290 unruptured intracranial aneurysms were treated with coil embolization at our institution. Patients who underwent retreatment due to aneurysm recurrence were divided into 2 patterns of recanalization: de novo bleb formation at the neck of a coiled sac (type DNV) and an enlarged residual cavity without de novo bleb formation (type non-DNV). RESULTS: Twenty-seven patients with aneurysms (9.3%) underwent retreatment (type DNV, 7; type non-DNV, 20). The initial aneurysm size of type DNV aneurysms was significantly smaller than that of type non-DNV (6.1 ± 2.2 mm vs. 10.1 ± 3.6 mm; P < 0.01), and time to retreatment in type DNV was significantly longer than that in type non-DNV (9.4 ± 5.3 years vs. 2.0 ± 2.0 years; P < 0.01). Two type DNV basilar artery (BA) aneurysms ruptured after a few years; however, the other type DNV aneurysms, including 4 anterior circulation aneurysms (including the internal carotid artery), were observed to grow gradually without rupture for >10 years until retreatment. CONCLUSIONS: De novo bleb formation at the neck of a coiled sac emerges with insidious growth during long-term follow-up. Constant caution should be exercised, even in cases of small- and medium-sized anterior circulation aneurysms. A risk of rupture risk may be anticipated, especially in BA lesions.

DOI： 10.1016/j.wneu.2022.02.092

Non-contrast-enhanced silent magnetic resonance angiography for assessing cerebral aneurysms after PulseRider treatment.

Tomoaki Suzuki, Hitoshi Hasegawa, Kazuhiro Ando, Kohei Shibuya, Haruhiko Takahashi, Shoji Saito, Makoto Oishi, Yukihiko Fujii

Japanese journal of radiology 40 ( 9 ) 979 - 985 2022.4

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Conventional time-of-flight (TOF) magnetic resonance angiography (MRA) failed to depict clear visualization of coiled cerebral aneurysms with PulseRider due to metal-induced susceptibility artifacts. Our aim was to overcome the metal artifact using a novel imaging technique of non-contrast-enhanced ultrashort echo-time magnetic resonance angiography (UTE-MRA). MATERIALS AND METHODS: Five unruptured intracranial aneurysms were treated using PulseRider and the patients underwent silent MRA (UTE-MRA). The images were compared with TOF-MRA and digital subtraction angiography (DSA). RESULTS: Silent MRA can visualize the residual cavity of the coiled aneurysms, which was not well visualized and rather defective when using TOF-MRA. While a segment of the proximal marker composed of stainless steel was poorly visualized, the other parts of the parent artery and the arteries of bifurcation, including the aneurysmal neck, were clearly visualized, equivalent to that of DSA. CONCLUSIONS: UTE-MRA achieves better visualization of cerebral aneurysms after PulseRider treatment than TOF-MRA.

DOI： 10.1007/s11604-022-01276-z

髄芽腫におけるSLFN11発現およびDNA障害型抗がん剤への感受性および予後の検討

棗田学, 中田聡, 村井純子, 岡田正康, 塚本佳広, 大石誠, 吉村淳一, 藤井幸彦, チャールズ・エバーハート

小児の脳神経 47 ( 2 ) 175 - 175 2022.4

Visualization of cortical activation in human brain by flavoprotein fluorescence imaging. International journal

Daiju Mitsuhashi, Ryuichi Hishida, Makoto Oishi, Tetsuya Hiraishi, Manabu Natsumeda, Katsuei Shibuki, Yukihiko Fujii

Journal of neurosurgery 1 - 9 2022.2

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: To develop an innovative brain mapping and neuromonitoring method during neurosurgery, the authors set out to establish intraoperative flavoprotein fluorescence imaging (iFFI) to directly visualize cortical activations in human brain. The significance of iFFI was analyzed by comparison with intraoperative perfusion-dependent imaging (iPDI), which is considered the conventional optical imaging, and by performing animal experiments. METHODS: Seven patients with intracerebral tumors were examined by iFFI and iPDI following craniotomy, using a single operative microscope equipped with a laser light source for iFFI and xenon lamp for iPDI. Images were captured by the same charge-coupled device camera. Responses to bipolar stimulation at selected points on the cortical surface were analyzed off-line, and relative signal changes were visualized by overlaying pseudocolor intensity maps onto cortical photographs. Signal changes exceeding 3 SDs from baseline were defined as significant. The authors also performed FFI and PDI on 10 mice using similar settings, and then compared signal patterns to intraoperative studies. RESULTS: Signals acquired by iFFI exhibited biphasic spatiotemporal changes consisting of an early positive signal peak (F1) and a delayed negative signal peak (F2). In contrast, iPDI signals exhibited only 1 negative peak (P1) that was significantly delayed compared to F1 (p < 0.02) and roughly in phase with F2. Compared to F2 and P1, F1 was of significantly lower amplitude (p < 0.02) and located closer to the bipolar stimulus center (p < 0.03), whereas F2 and P1 were more widespread, irregular, and partially overlapping. In mice, the spatiotemporal characteristics of FFI and PDI resembled those of iFFI and iPDI, but the early positive signal was more robust than F1. CONCLUSIONS: This is the first report in humans of successful intraoperative visualization of cortical activations by using iFFI, which showed rapid evoked cortical activity prior to perfusion-dependent signal changes. Further technical improvements can lead to establishment of iFFI as a real-time intraoperative tool.

DOI： 10.3171/2022.1.JNS212542

Novel Repositioning Therapy for Drug-Resistant Glioblastoma: In Vivo Validation Study of Clindamycin Treatment Targeting the mTOR Pathway and Combination Therapy with Temozolomide. International journal

Takeyoshi Eda, Masayasu Okada, Ryosuke Ogura, Yoshihiro Tsukamoto, Yu Kanemaru, Jun Watanabe, Jotaro On, Hiroshi Aoki, Makoto Oishi, Nobuyuki Takei, Yukihiko Fujii, Manabu Natsumeda

Cancers 14 ( 3 ) 2022.2

Language：English Publishing type：Research paper (scientific journal)

Multimodal therapy including surgery, radiation treatment, and temozolomide (TMZ) is performed on glioblastoma (GBM). However, the prognosis is still poor and there is an urgent need to develop effective treatments to improve survival. Molecular biological analysis was conducted to examine the signal activation patterns in GBM specimens and remains an open problem. Advanced macrolides, such as azithromycin, reduce the phosphorylation of p70 ribosomal protein S6 kinase (p70S6K), a downstream mammalian target of rapamycin (mTOR) effector, and suppress the proliferation of T-cells. We focused on its unique profile and screened for the antitumor activity of approved macrolide antibiotics. Clindamycin (CLD) reduced the viability of GBM cells in vitro. We assessed the effects of the candidate macrolide on the mTOR pathway through Western blotting. CLD attenuated p70S6K phosphorylation in a dose-dependent manner. These effects on GBM cells were enhanced by co-treatment with TMZ. Furthermore, CLD inhibited the expression of the O6-methylguanine-DNA methyltransferase (MGMT) protein in cultured cells. In the mouse xenograft model, CLD and TMZ co-administration significantly suppressed the tumor growth and markedly decreased the number of Ki-67 (clone MIB-1)-positive cells within the tumor. These results suggest that CLD suppressed GBM cell growth by inhibiting mTOR signaling. Moreover, CLD and TMZ showed promising synergistic antitumor activity.

DOI： 10.3390/cancers14030770

Meningoencephalocele in the Lateral Sphenoid Sinus Showing Malformation of Cortical Development: A Case Report.

Taro Sato, Tetsuya Hiraishi, Mari Tada, Manabu Natsumeda, Jotaro On, Haruhiko Takahashi, Taiki Saito, Noritaka Okubo, Makoto Oishi, Akiyoshi Kakita, Yukihiko Fujii

NMC case report journal 9 281 - 287 2022

Language：English

Meningoencephalocele in the lateral sphenoid sinus (SS) has been determined to be a rare entity often detected by cerebrospinal fluid (CSF) rhinorrhea. To date, the pathology of meningoencephalocele in the lateral SS has remained to be unclear in many cases. In this study, we report on a case of a 72-year-old woman with an arteriovenous malformation who presented with CSF rhinorrhea. Radiologic investigations revealed a left temporal meningoencephalocele in the lateral SS. We removed the meningoencephalocele and performed skull base repair, after which the CSF rhinorrhea resolved. Pathological examination showed congenital cortical abnormalities with dysmorphic neurons in various shapes and acquired chronic tissue alterations including fibrillary gliosis and scattered Rosenthal fibers. These findings may further aid in understanding the etiopathogenesis of meningoencephalocele in the lateral SS.

DOI： 10.2176/jns-nmc.2022-0152

Endovascular treatment of an infectious aneurysm using the selective provocative test and transcranial motor evoked potential monitoring under general anesthesia: a case report. International journal

Kazuhiro Ando, Tetsuya Hiraishi, Makoto Oishi, Hitoshi Hasegawa, Bumpei Kikuchi, Manabu Natsumeda, Tomoaki Suzuki, Shoji Saito, Tomoyoshi Ota, Yuichi Yoshida, Yukihiko Fujii

Acta neurochirurgica 164 ( 5 ) 1265 - 1269 2021.9

Language：English Publishing type：Research paper (scientific journal)

The selective provocative test (SPT) under local anesthesia aids in protecting against ischemic complications during endovascular treatment. However, the use of this test under general anesthesia is not well described. Herein, we present a case of a 51-year-old man with a ruptured fusiform aneurysm in the middle cerebral artery M4 segment, which was thought to possibly supply the motor cortex. Internal trapping of the affected vessel and aneurysm by endovascular intervention was successfully performed after SPT using transcranial motor evoked potential (MEP) monitoring under general anesthesia. Transcranial MEP is suitable for neurological assessment during SPT under general anesthesia.

DOI： 10.1007/s00701-021-05001-z

脳神経外科領域におけるPDTの現状と問題点当科における光線力学療法の経験および次世代への挑戦

棗田学, 塚本佳広, 温城太郎, 渡邉潤, 江田岳誉, 平石哲也, 佐野正和, 大石誠, 藤井幸彦

日本レーザー医学会誌 42 ( 3 ) 161 - 161 2021.9

Reactive astrocytes contribute to epileptogenesis in patients with cavernous angioma. International journal

Hiroki Kitaura, Tetsuya Hiraishi, Yosuke Itoh, Makoto Oishi, Yukihiko Fujii, Masafumi Fukuda, Akiyoshi Kakita

Epilepsy research 176 106732 - 106732 2021.7

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Patients with cavernous angioma (CA) often suffer from severe epilepsy, and surgical resection is often performed to attenuate these epileptic seizures. Several studies have suggested that surgical removal of the surrounding hemosiderin-pigmented tissues adjacent to CA achieves better seizure control than restricted lesionectomy. Pathological examination of the resected foci reveals not only hemosiderin pigmentation but also various degrees of inflammatory change, such as hemosiderin-laden macrophages, gliosis and fibrosis. However, there is some controversy regarding the epileptogenic potential of these regions due to the uncertain nature of the mechanisms contributing to these histopathological changes. METHODS: To investigate the correlations between neuron hyperexcitability and evident pathological changes, we performed ex vivo flavoprotein fluorescence imaging using surgically resected epileptogenic foci surrounding CA. The mirror surfaces of the tissues used for the physiological experiment were also subjected to morphological examination. RESULTS: Hemosiderin-laden macrophages and many gemistocytic astrocytes were observed in the area adjacent to CA, where horizontal spreading excitations were detected significantly more frequently. Outside these areas, we found fine granular iron deposits and only a few fibrillary astrocytes, and weakly propagating excitations were detected. Furthermore, areas of enhanced activation were more clearly correlated with the glial proliferation index than with iron deposition. CONCLUSION: These results suggest that the epileptogenesis in patients with CA may be based on a biological process, such as alteration of glial function, rather than direct chemical reactions involving iron deposition.

DOI： 10.1016/j.eplepsyres.2021.106732

Predicting BRAF V600E mutation in glioblastoma: utility of radiographic features.

Manabu Natsumeda, Michael Chang, Ramil Gabdulkhaev, Haruhiko Takahashi, Yoshihiro Tsukamoto, Yu Kanemaru, Masayasu Okada, Makoto Oishi, Kouichirou Okamoto, Fausto J Rodriguez, Akiyoshi Kakita, Yukihiko Fujii, Karisa C Schreck

Brain tumor pathology 38 ( 3 ) 228 - 233 2021.7

Language：English Publishing type：Research paper (scientific journal)

Detection of BRAF V600E mutation in glioblastomas (GBMs) is important because of potential therapeutic implications. Still, the relative paucity of these mutations makes molecular detection in all GBMs controversial. In the present study, we analyzed clinical, radiographic and pathologic features of 12 BRAF V600E-mutant GBMs and 12 matched controls from 2 institutions. We found that a majority of BRAF V600E-mutant GBMs displayed a combination of well-circumscribed lesions, large cystic components with thin walls and solid cortical component on MRI, but with some overlap with matched BRAF wildtype controls (p = 0.069). BRAF V600E-mutant GBMs were also apt to gross total resection (83% vs 17%, p = 0.016) and morphologically displayed epithelioid features (83% vs 0%, p < 0.0001). Identification of these clinical, radiographic, and pathologic characteristics should prompt testing for BRAF V600E in IDH-wildtype GBM.

DOI： 10.1007/s10014-021-00407-0

Four-dimensional multifusion imaging for assessment of meningioma hemodynamics

Ryosuke Ogura, Makoto Oishi, Tetsuya Hiraishi, Haruhiko Takahashi, Kohei Shibuya, Tomoaki Suzuki, Manabu Natsumeda, Kouichirou Okamoto, Yukihiko Fujii

Interdisciplinary Neurosurgery 24 101118 - 101118 2021.6

Delayed Bleeding of Unruptured Intracranial Aneurysms After Coil Embolization: A Retrospective Case Series. International journal

Kazuhiro Ando, Hitoshi Hasegawa, Tomoaki Suzuki, Shoji Saito, Kohei Shibuya, Haruhiko Takahashi, Makoto Oishi, Yukihiko Fujii

World neurosurgery 149 e135-e145 2021.5

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Delayed bleeding of unruptured intracranial aneurysms (UIAs) after coil embolization is rare; this study aimed to analyze the occurrence of delayed bleeding of UIAs after coil embolization. METHODS: We retrospectively analyzed patients with UIAs after coil embolization between January 2002 and December 2018 and assessed the features of UIAs with delayed bleeding after coil embolization. RESULTS: Analysis included 307 patients with 335 UIAs. Mean follow-up was 7.1 ± 4.9 years, and total follow-up was 2365 aneurysm-years. There were 271 (80.9%) aneurysms located in the anterior circulation and 64 (19.1%) aneurysms located in the posterior circulation. Significant differences were observed between the 2 groups in terms of maximum size of the aneurysm (P < 0.01), width of the aneurysm neck (P < 0.01), and number of retreatment cases (P < 0.01). During the follow-up period, delayed bleeding occurred in 4 aneurysms (annual bleeding rate of 0.17%); all were located in the posterior circulation. The original size was not relatively large (mean 8.6 ± 2.4 mm). All aneurysms bled within 5 years (mean 35 ± 9.6 months) after the initial treatment. Two were de novo aneurysms that developed adjacent to the coiled aneurysms and were not detected on follow-up magnetic resonance angiography. CONCLUSIONS: Cautious follow-up of UIAs with digital subtraction angiography is important, articularly within the first 5 years after the procedure. If there are changes in the anatomic outcomes, short-term reassessment or additional treatment should be actively considered, particularly for aneurysms in the posterior circulation.

DOI： 10.1016/j.wneu.2021.02.061

脳腫瘍遺伝子異常の画像診断 IDH変異型神経膠腫における3T-MRSを用いた2HGの検出

棗田学, 五十嵐博中, 本橋邦夫, 塚本佳広, 小倉良介, 岡本浩一郎, 大石誠, 柿田明美, 藤井幸彦

Brain Tumor Pathology 38 ( Suppl. ) 059 - 059 2021.5

小児脳腫瘍の新展開髄芽腫におけるGLI3発現および役割の解明完結編

棗田学, 宮原弘明, 吉村淳一, 塚本佳広, 大石誠, エバーハート・チャールズ, 柿田明美, 藤井幸彦

Brain Tumor Pathology 38 ( Suppl. ) 058 - 058 2021.5

High grade astrocytomaに準じて治療したprimary anaplastic pleomorphic xanthoastrocytomaの4症例の検討

塚本佳広, 棗田学, 温城太郎, 小倉良介, 清水宏, 岡本浩一郎, 大石誠, 藤井幸彦, 柿田明美

Brain Tumor Pathology 38 ( Suppl. ) 078 - 078 2021.5

悪性神経膠腫におけるテモゾロミド療法前後のミスマッチ修復蛋白発現の検討

山田史織, 棗田学, 高橋陽彦, 安藤和弘, 温城太郎, 塚本佳広, 岡田正康, 大石誠, 柿田明美, 藤井幸彦

Brain Tumor Pathology 38 ( Suppl. ) 076 - 076 2021.5

Development and natural course of lateral posterior choroidal artery aneurysms arising from fragile choroidal collaterals in moyamoya disease: illustrative cases. International journal

Tomoaki Suzuki, Hitoshi Hasegawa, Kouichirou Okamoto, Kazuhiro Ando, Kohei Shibuya, Haruhiko Takahashi, Shoji Saito, Makoto Oishi, Yukihiko Fujii

Journal of neurosurgery. Case lessons 1 ( 15 ) CASE2110 2021.4

Language：English

BACKGROUND: Choroidal collaterals are a risk factor for hemorrhagic stroke, even in the nonhemorrhagic hemisphere, among patients with moyamoya disease (MMD). Peripheral choroidal aneurysms rupture in fragile collaterals; however, the development and natural course of these aneurysms remain elusive. OBSERVATIONS: A 51-year-old woman, who had experienced a right cerebral hemorrhage 3 years earlier, presented with asymptomatic minor bleeding from a left lateral choroidal artery aneurysm in a predeveloped choroidal anastomosis. Although the aneurysm spontaneously thrombosed within 2 months, the choroidal collaterals persisted. After bypass surgery, the choroidal anastomosis regressed, and neither a de novo aneurysm nor a hemorrhagic stroke occurred. A 75-year-old woman with MMD, who had experienced a left frontal infarction 6 years earlier, experienced recurrent right intraventricular hemorrhage from a ruptured lateral choroidal artery aneurysm that developed in the choroidal anastomosis. The aneurysm spontaneously regressed 3 days after the rebleeding with no recurrence over the following 7 years. LESSONS: Choroidal artery aneurysms may develop in the choroidal anastomosis and rupture in the nonsurgical or contralateral hemispheres. Patients with MMD who have a history of hemorrhagic or ischemic stroke and impaired cerebral blood flow require careful observation. Although aneurysms may rapidly regress spontaneously, bypass surgery can stabilize hemodynamic stress and prevent further hemorrhage.

DOI： 10.3171/CASE2110

Low Detection Rate of H3K27M Mutations in Cerebrospinal Fluid Obtained from Lumbar Puncture in Newly Diagnosed Diffuse Midline Gliomas. International journal

Jotaro On, Manabu Natsumeda, Jun Watanabe, Shoji Saito, Yu Kanemaru, Hideaki Abe, Yoshihiro Tsukamoto, Masayasu Okada, Makoto Oishi, Junichi Yoshimura, Akiyoshi Kakita, Yukihiko Fujii

Diagnostics (Basel, Switzerland) 11 ( 4 ) 2021.4

Language：English Publishing type：Research paper (scientific journal)

Recent studies have suggested the feasibility of detecting H3K27M mutations in the cerebrospinal fluid of diffuse midline glioma (DMG) patients. However, cerebrospinal fluid from patients in these studies were collected mainly during biopsy, ventriculo-peritoneal shunt procedures or postmortem. We assessed circulating tumor DNA (ctDNA) extracted from cerebrospinal fluid (CSF) and plasma in a series of 12 radiographically suspected and/or pathologically confirmed diffuse midline glioma patients and assessed for H3F3A K27M mutation using digital droplet PCR. In 10 patients, CSF was obtained by lumbar puncture at presentation. A definitive detection of H3F3A K27M mutation was achieved in only one case (10%); H3F3A K27M mutation was suspected in three other cases (30%). H3F3A K27M mutation was detected in two patients in CSF obtained by ventricular tap during a ventriculo-peritoneal shunt for obstructive hydrocephalus. Cases in which a definitive assessment was possible (definite H3F3A K27M or definite H3F3A wildtype) tended to be younger (median 7.5 years vs. 40.5 years; p = 0.07) and have a higher concentration of CSF protein (median 123 mg/dL vs. 27.5 mg/dL; p = 0.21) compared to nondefinite cases. Low proliferation and apoptotic rates seemed to be characteristics of DMG unfavorable for liquid biopsy. More advanced lesions with necrosis and evidence of dissemination were unlikely to be candidates for lumbar puncture due to the fear of exacerbating obstructive hydrocephalus. Methods to safely sample CSF and a more sensitive detection of ctDNA are necessary for reliable liquid biopsy of DMG at presentation.

DOI： 10.3390/diagnostics11040681

Diffuse midline gliomaにおけるliquid biopsyの現状及び課題

棗田学, 温城太郎, 渡邉潤, 塚本佳広, 岡田正康, 大石誠, 藤井幸彦

小児の脳神経 46 ( 2 ) 183 - 183 2021.4

Unilateral oculomotor nerve palsy caused by arterial compression accompanying subarachnoid hemorrhage: a case report. International journal

Shoji Saito, Hitoshi Hasegawa, Toru Takino, Kazuhiro Ando, Kohei Shibuya, Haruhiko Takahashi, Jotaro On, Tomoaki Suzuki, Makoto Oishi, Yukihiko Fujii

Acta neurochirurgica 163 ( 3 ) 813 - 816 2021.3

Language：English Publishing type：Research paper (scientific journal)

Unilateral oculomotor nerve palsy, often caused by aneurysmal compression, is one of the decisive findings for confirming the site of a ruptured aneurysm. However, arterial compression can also cause unilateral oculomotor nerve palsy. Here, we present the case of a 59-year-old woman with a ruptured right internal carotid-posterior communicating artery aneurysm accompanied by contralateral oculomotor nerve palsy. The nerve was found to be compressed by the posterior cerebral artery and was isolated from the ruptured aneurysm. When confirming a ruptured aneurysm based on the evidence of unilateral oculomotor palsy, the arteries surrounding the nerve must be thoroughly assessed.

DOI： 10.1007/s00701-020-04633-x

[Melanocytic Tumors].

Kouichirou Okamoto, Manabu Natsumeda, Makoto Oishi, Yukihiko Fujii

No shinkei geka. Neurological surgery 49 ( 2 ) 389 - 394 2021.3

Language：Japanese Publishing type：Research paper (scientific journal)

Primary melanocytic neoplasms of the central nervous system(CNS)presumably arise from leptomeningeal melanocytes that are derived from the neural crest. Melanocytic neoplasms associated with neurocutaneous melanosis likely derive from melanocyte precursor cells that reach the CNS after somatic mutations, mostly, of the NRAS. They should be distinguished from other melanotic tumors involving the CNS, including metastatic melanoma and other primary tumors that undergo melanization, such as melanocytic schwannomas, medulloblastomas, paragangliomas, and various gliomas, because these lesions require different patient workups and therapy. Primary melanocytic neoplasms of the CNS that are diffuse and do not form macroscopic masses are called melanocytoses, whereas malignant diffuse or multifocal lesions are collectively called melanomatoses. Benign and intermediate-grade tumoral lesions are called melanocytomas. Discrete malignant tumors are called melanomas. CT and MRI of melanocytosis and melanomatosis show diffuse thickening and enhancement of the leptomeninges, often with focal or multifocal nodularity. Depending on the melanin content, diffuse and circumscribed melanocytic tumors of the CNS may show some characteristics on CT and MRI: iso- to hyperattenuation on CT and paramagnetic properties of melanin on MRI resulting in an isointense signal on T1WIs and iso- to hypointensity on T2WIs.

DOI： 10.11477/mf.1436204403

[Multinodular and Vacuolating Neuronal Tumor of the Cerebrum(MVNT)].

Kouichirou Okamoto, Manabu Natsumeda, Makoto Oishi, Yukihiko Fujii

No shinkei geka. Neurological surgery 49 ( 2 ) 383 - 387 2021.3

Language：Japanese Publishing type：Research paper (scientific journal)

Multinodular and vacuolating neuronal tumors of the cerebrum(MVNTs)are rare brain tumors that were described first in 2013. MVNTs have been added to the World Health Organization Classification of Tumors of the Central Nervous System in 2016(2016WHO), although an MVNT is a clinical-pathological lesion with uncertain class assignment. It remains unclear whether MVNTs should be considered a true neoplasm or malformative lesion. Their prevalence and pathophysiology are unknown. MVNTs typically occur in adults, predominantly in the cerebral subcortical region, and are most frequently associated with seizures or seizure equivalents. MVMTs can also present incidentally without seizures. MVNTs have been reported to show highly suggestive imaging features, especially on MRI scans. MVNTs consist of small T2 and T2-FLAIR hyperintense nodules in subcortical and juxtacortical areas with rare or no post-contrast enhancement. Most MVNTs reported in the literature involve the supratentorial part of the brain. Recently, lesions exhibiting a remarkably similar pattern of imaging findings were described in the posterior fossa, which are referred to as multinodular and vacuolating posterior fossa of unknown significance(MV-PLUS). Both MVNT and MV-PLUS are considered "leave-me-alone" lesions because of the absence of malignancy criteria and the lack of evolutivity on follow-up MRI scans.

DOI： 10.11477/mf.1436204402

[Dysplastic Cerebellar Gangliocytoma(Lhermitte-Duclos Disease)].

Kouichirou Okamoto, Manabu Natsumeda, Makoto Oishi, Yukihiko Fujii

No shinkei geka. Neurological surgery 49 ( 2 ) 395 - 399 2021.3

Language：Japanese Publishing type：Research paper (scientific journal)

Dysplastic cerebellar gangliocytoma or Lhermitte-Duclos disease(LDD)is a rare benign cerebellar lesion composed of dysplastic ganglion cells that conform to the existing cortical architecture. In this disease, the enlarged ganglion cells are predominantly located within the internal granular layer, and they thicken the cerebellar folia. The architecture of the affected cerebellar hemisphere with the enlarged cerebellar folia and the cystic changes, in some cases, present as "tiger-striped striations," a characteristic imaging finding that is not specific to LDD. This imaging feature may be observed in medulloblastoma and isolated cerebellar Rosai-Dorfman disease. This cerebellar lesion is a major central nervous system manifestation of Cowden syndrome, an autosomal dominant condition that causes various hamartomas and neoplasms. A molecular-based study estimated the prevalence of Cowden syndrome to be 1 case per 200,000. In a study involving 211 patients with Cowden syndrome, 32% developed LDD. LDD can be diagnosed in young children and older adults within the eighth decades of life. PTEN mutations have been identified in virtually all adult-onset LDDs, but not in childhood-onset cases.

DOI： 10.11477/mf.1436204404

【脳神経画像Critical Findings-おさえておきたい症状とCT/MRI画像所見】特徴的な画像所見を示す新しい概念の脳腫瘍大脳多結節空胞状神経細胞腫瘍(MVNT)

岡本浩一郎, 棗田学, 大石誠, 藤井幸彦

Neurological Surgery 49 ( 2 ) 383 - 387 2021.3

Language：Japanese Publisher：(株)医学書院

＜文献概要＞Point ・大脳多結節空胞状神経細胞腫瘍(MVNT)は,痙攣,頭痛あるいは偶然発見される大脳半球の脳回に沿う皮質深部〜皮質下神経系腫瘍性病変(WHO 2016 gradeI相当)である.・MRIで1〜5mmの結節が3〜10個以上集合する7〜57mmの大きさで,mass effectは乏しくGd増強効果を示さない.・増大せず,痙攣を来す一部の例を除き生検や病変摘出などの外科的処置を必要としない"leave-me-alone" lesionと考えらえる.

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01228&link_issn=&doc_id=20210406190024&doc_link_id=10.11477%2Fmf.1436204402&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1436204402&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

【脳神経画像Critical Findings-おさえておきたい症状とCT/MRI画像所見】特徴的な画像所見を示す新しい概念の脳腫瘍異形成性小脳神経節細胞腫(レルミット・ダクロス病)

岡本浩一郎, 棗田学, 大石誠, 藤井幸彦

Neurological Surgery 49 ( 2 ) 395 - 399 2021.3

Language：Japanese Publisher：(株)医学書院

＜文献概要＞Point ・レルミット・ダクロス病は,小脳回が腫大し変形する比較的境界明瞭な小脳半球の稀な良性腫瘍,あるいは過誤腫性病変である.・虎縞様層構造(tiger-striped striation)が特徴的MRI所見で,拡散制限はない.・カウデン症候群の主要な中枢神経系の病変で,小児〜高齢者の広い年齢層で認められる.・カウデン症候群の診断がついていない場合,カウデン症候群に伴う全身の過誤腫性・腫瘍性病変の検索を行う.

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01228&link_issn=&doc_id=20210406190026&doc_link_id=10.11477%2Fmf.1436204404&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1436204404&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

【脳神経画像Critical Findings-おさえておきたい症状とCT/MRI画像所見】特徴的な画像所見を示す新しい概念の脳腫瘍黒色腫(メラニン細胞)系腫瘍

岡本浩一郎, 棗田学, 大石誠, 藤井幸彦

Neurological Surgery 49 ( 2 ) 389 - 394 2021.3

Language：Japanese Publisher：(株)医学書院

＜文献概要＞Point ・単純CTで高吸収,T1WIで高信号を認める場合,出血・石灰化に加えメラニン含有性病変を考える.・頭蓋内にメラニン含有性病変を認めた場合,皮膚病変(母斑)の有無を確認する.・無症状でも大きな,あるいは多発する先天性母斑を認める場合,神経皮膚黒色症を疑う.・神経皮膚黒色症の40〜60%に悪性黒色腫が発生し,予後不良である.

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01228&link_issn=&doc_id=20210406190025&doc_link_id=10.11477%2Fmf.1436204403&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1436204403&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

GLI3 Is Associated With Neuronal Differentiation in SHH-Activated and WNT-Activated Medulloblastoma. International journal

Manabu Natsumeda, Hiroaki Miyahara, Junichi Yoshimura, Satoshi Nakata, Takanori Nozawa, Junko Ito, Yu Kanemaru, Jun Watanabe, Yoshihiro Tsukamoto, Masayasu Okada, Makoto Oishi, Junko Hirato, Takafumi Wataya, Sama Ahsan, Kensuke Tateishi, Tetsuya Yamamoto, Fausto J Rodriguez, Hitoshi Takahashi, Volker Hovestadt, Mario L Suva, Michael D Taylor, Charles G Eberhart, Yukihiko Fujii, Akiyoshi Kakita

Journal of neuropathology and experimental neurology 80 ( 2 ) 129 - 136 2021.1

Language：English Publishing type：Research paper (scientific journal)

Glioma-associated oncogene homolog 3 (GLI3), whose main function is to inhibit GLI1, has been associated with neuronal differentiation in medulloblastoma. However, it is not clear what molecular subtype(s) show increased GLI3 expression. GLI3 levels were assessed by immunohistochemistry in 2 independent cohorts, including a total of 88 cases, and found to be high in both WNT- and SHH-activated medulloblastoma. Analysis of bulk mRNA expression data and single cell RNA sequencing studies confirmed that GLI1 and GLI3 are highly expressed in SHH-activated medulloblastoma, whereas GLI3 but not GLI1 is highly expressed in WNT-activated medulloblastoma. Immunohistochemical analysis has shown that GLI3 is expressed inside the neuronal differentiated nodules of SHH-activated medulloblastoma, whereas GLI1/2 are expressed in desmoplastic areas. In contrast, GLI3 is diffusely expressed in WNT-activated medulloblastoma, whereas GLI1 is suppressed. Our data suggest that GLI3 may be a master regulator of neuronal differentiation and morphology in these subgroups.

DOI： 10.1093/jnen/nlaa141

Hemodynamic features of an intracranial aneurysm rupture predicted by perianeurysmal edema: A case report. International journal

Tomoaki Suzuki, Hitoshi Hasegawa, Kazuhiro Ando, Kohei Shibuya, Haruhiko Takahashi, Shoji Saito, Jotaro On, Makoto Oishi, Yukihiko Fujii

Surgical neurology international 12 49 - 49 2021

Language：English

Background: Perianeurysmal edema (PAE) has been suggested as an indicator of potential aneurysm rupture; however, the hemodynamic features of these aneurysms are still unknown. A computational fluid dynamic (CFD) analysis was performed to evaluate the hemodynamic features of a very rare case of a ruptured middle cerebral artery (MCA) aneurysm with PAE. Case Description: A 65-year-old woman presented with disturbed consciousness. A subarachnoid hemorrhage due to an azygos anterior cerebral artery (ACA) aneurysm rupture was suspected. An unruptured MCA aneurysm with PAE was identified in the left temporal lobe. Although the ACA aneurysm was clipped to prevent re-bleeding, the MCA aneurysm subsequently ruptured 6 days later. Clipping of the MCA aneurysm was performed, and hemosiderin deposits suggestive of sentinel bleeding were found on the surface of the aneurysm dome. CFD analysis revealed unstable hemodynamic stress at the expanded bleb area after rupture, localized to the rupture site. Moreover, this analysis revealed flow impingement with pressure elevation and low wall shear stress, which indicated increased inflammation and aneurysm wall thinning that likely led to rupture. Conclusion: Hemosiderin deposits at the aneurysm wall and PAE indicates leakage from a cerebral aneurysm. Hemodynamic stress at the aneurysm may promote an inflammatory response and lead to wall weakening accompanied by PAE. Based on our findings, we recommend that surgical intervention should be considered as the first line of treatment for such aneurysms to prevent rupture.

DOI： 10.25259/SNI_780_2020

Phosphorylated T172 in GAP-43: A novel molecular marker of axonal growth and regeneration in primate neurons identifi ed by phosphoproteomics

Okada Masayasu, Kawasaki Asami, Kaneko Naoko, Natsumeda Manabu, Oishi Makoto, Fujii Yukihiko, Igarashi Michihiro

Cytometry Research 31 ( 1 ) 7 - 13 2021

Language：Japanese Publisher：Japan Cytometry Society

<p>For post-translational protein modifications such as phosphorylation, the involved residues have been recently identified by mass spectrometers. However, it is not easy to efficiently detect the therapeutic target from the vast amount of proteomic data. Neuronal growth cones are specialized, highly motile structures formed at the tip of axons, that are indispensable for synaptogenesis in the developing brain and for neuronal plasticity in the adult brain. However, there is lack of information on the molecular basis of growth cones in the mammalian brain. We performed a phosphoproteomic analysis of growth cone membrane fractions (2 mg) isolated from the rat forebrain on postnatal day 1. We chose the more abundant peptides as research-targets, based on the hypothesis that abundant phosphorylated sites are involved in important biological functions. The phosphopeptides detected with high frequency at the 1st (Serine [S] 96) and 9th (Threonine [T] 172) positions were the phosphorylation sites of neuronal growth-associated protein - 43 kDa (GAP 43). C-jun N-terminal kinase (JNK) was responsible for phosphorylation at these sites, which increased during neuronal development and axonal regeneration. T172 phosphorylation was also confi rmed in rodents and primates. This review introduces our methodology for fi nding novel phospho-proteins as therapeutic molecular targets for specifi c diseases, along with their regulatory kinases. We believe that our serial approach, as illustrated here, can be applied to various research fi elds. In future research, we propose to demonstrate that pT172 antibody can be utilized as an axonal growth and regeneration marker in humans.</p>

DOI： 10.18947/cytometryresearch.31.1_7

Pott's puffy tumour: a rare and life-threatening disease. International journal

Nahoko Ikoma, Yuta Aizawa, Takanobu Sasaki, Makoto Oishi, Naka Saito, Hiroshi Yoshida, Akihiko Saitoh

The Lancet. Infectious diseases 20 ( 12 ) 1482 - 1482 2020.12

Safety and feasibility of the distal transradial approach: A novel technique for diagnostic cerebral angiography. International journal

Shoji Saito, Hitoshi Hasegawa, Tomoyoshi Ota, Toru Takino, Yuichi Yoshida, Kazuhiro Ando, Kohei Shibuya, Haruhiko Takahashi, Tomoaki Suzuki, Makoto Oishi, Yukihiko Fujii

Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences 26 ( 6 ) 713 - 718 2020.12

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: We aimed to evaluate the safety and feasibility of the distal transradial approach (DTRA) as a novel technique for cerebral angiography based on our institutional initial experience. METHODS: We retrospectively analyzed our institutional database of consecutive diagnostic cerebral angiographies performed with DTRA from December 2018 to August 2019. Patient demographics and clinical and procedural data were recorded. RESULTS: In total, 51 diagnostic cerebral angiographies in 51 patients (age, 15-83 years; mean age, 59.4 years, SD 13.5; 35 (69%) females) were performed or attempted with DTRA. Ultrasound evaluation showed that the mean inner distal radial artery diameter was significantly smaller than the mean inner forearm radial artery diameter (2.19 mm vs. 2.56 mm, P < 0.001). Cannulation via the distal radial artery was successful in 47 (92%) procedures. In the four procedures that failed, operators converted to the ipsilateral transradial approach without repositioning or redraping. Selective catheterization of the intended vessel was achieved in 64 (91%) of 70 vessels. In the remaining six, operators achieved the objective of the examination with angiography injecting from proximal and conversion to another approach was not required. One patient experienced temporary numbness around the puncture site after the procedure. No radial artery occlusion was identified in the patients who underwent ultrasound evaluation. CONCLUSION: Our results demonstrate that DTRA could become a standard approach for diagnostic cerebral angiography owing to the low complication rate and the high cannulation success rate.

DOI： 10.1177/1591019920925709

栄養動脈塞栓術を行い摘出したhypervascular cerebellopontine angle pilocytic astrocytomaの一例

吉村淳一, 棗田学, 長谷川仁, 大石誠, 藤井幸彦

小児の脳神経 45 ( 3 ) 256 - 256 2020.10

脳腫瘍の遺伝子診断とゲノム医療2 ゲノム医療を想定したBRAF V600E変異を有する脳腫瘍の臨床病理像

棗田学, 金丸優, 齋藤祥二, 塚本佳広, 岡田正康, 大石誠, 柿田明美, 藤井幸彦

Brain Tumor Pathology 37 ( Suppl. ) 076 - 076 2020.8

[Endovascular Revascularization for Acute Ischemic Stroke Related to Blunt Carotid Injury:A Case Report].

Shoji Saito, Hitoshi Hasegawa, Daisuke Sato, Kazuhiro Ando, Kunio Motohashi, Manabu Natsumeda, Bumpei Kikuchi, Makoto Oishi, Yukihiko Fujii

No shinkei geka. Neurological surgery 48 ( 6 ) 527 - 532 2020.6

Language：Japanese Publishing type：Research paper (scientific journal)

Although blunt carotid artery injury is known as an important cause of ischemic stroke, the role of the endovascular treatment for acute ischemic stroke related to blunt carotid injuries remains unclear. We report the case of a patient with acute ischemic stroke secondary to blunt carotid artery injury who was treated with endovascular revascularization. A 46-year-old man suffered from sudden left-sided hemiparesis a day after a strike from a Japanese fencing staff on his right neck. 3D-CT angiography revealed tandem internal carotid artery occlusions of the cervical and C1 portions. We performed endovascular revascularization with carotid artery stenting and direct aspiration of the thrombus and achieved complete recanalization. The patient recovered almost completely. We conclude that endovascular revascularization should not be withheld from patients with acute ischemic stroke related to blunt carotid injury.

DOI： 10.11477/mf.1436204223

Vascular Hyperintensity on Fluid-Attenuated Inversion Recovery Indicates the Severity of Hypoperfusion in Acute Stroke. International journal

Toshiharu Nomura, Kouichirou Okamoto, Hironaka Igarashi, Masato Watanabe, Hitoshi Hasegawa, Makoto Oishi, Yukihiko Fujii

Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 29 ( 2 ) 104467 - 104467 2020.2

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND AND AIM: Although fluid-attenuated inversion recovery vascular hyperintensities may be frequently seen in acute large-artery ischemic stroke, reports on their prognostic utility had been conflicting due to lack of quantitative evaluation of the perfusion status based on the signal intensity. We hypothesized that greater hyperintensity represents more severe hypoperfusion. METHODS: Overall, 27 patients with acute occlusion of the proximal middle cerebral artery were divided into 2 groups, based on their signal intensity in the insular segment of middle cerebral artery on the affected side, relative to that of the insular cortex: the low signal intensity group (hypo- or isointense signals, n = 12) and the high signal intensity group (hyperintense signals, n = 15). Using dynamic susceptibility contrast magnetic resonance imaging, we assessed the time of the maximum value of the residue function and mean transit time, in the entire middle cerebral artery cortical area and diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score regions, including the corona radiata. RESULTS: The high signal intensity group had significantly longer time of the maximum value of the residue function in all the diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score regions, except the M3 and M6 regions, and significantly longer mean transit time in the M1 and M4 regions. CONCLUSIONS: Quantitative analysis of the perfusion parameters revealed more severely compromised and widely disturbed perfusion status in the high signal intensity group than in the low signal intensity group.

DOI： 10.1016/j.jstrokecerebrovasdis.2019.104467

Possibility of Worsening Flow Diversion Effect Due to Morphological Changes of a Stented Artery With Multiple Overlapping Stents for Partially Thrombosed Vertebral Artery Aneurysms. International journal

Tomoaki Suzuki, Hitoshi Hasegawa, Kazuhiro Ando, Kouhei Shibuya, Haruhiko Takahashi, Shoji Saito, Makoto Oishi, Yukihiko Fujii

Frontiers in neurology 11 611124 - 611124 2020

Language：English Publishing type：Research paper (scientific journal)

Background: Morphological changes of a stented artery can cause a flow diversion effect to reduce intra-aneurysmal flow; however, there is a potential for the negative effect of increased intra-aneurysmal flow. We present cases with multiple overlapping stents for a partially thrombosed vertebral artery aneurysm and characterize the hemodynamic properties of a recurrent case by focusing on the morphological changes of the stented artery. Methods: Between October 2017 and April 2019, four consecutive cases of symptomatic unruptured large and giant partially thrombosed vertebral artery aneurysms were treated with multiple overlapping low-profile visualized intraluminal support stents and no coils. Both angiographic and clinical outcomes were assessed. Computational fluid dynamics analysis was performed to clarify hemodynamic features. The degree of pressure elevation was calculated as the pressure difference (Pd). Wall shear stress (WSS) was also calculated. Results: In three of the four cases, successful flow reduction was achieved with no morphological change of the stented arteries. The patients' symptoms were gradually improved. The remaining case required additional stents after the initial treatment. In the recurrent case, Pd was noticeably elevated at the aneurysm neck after treatment, and WSS was generally increased in the area due to altered blood flow into the aneurysm dome caused by morphological changes of the stented artery. Conclusion: Overlapping stents can be used for the treatment of large and giant thrombosed vertebral artery aneurysms with flow diversion effect; however, morphological changes of the stented artery requires careful attention as it may lead to an increase in the intra-aneurysmal flow, causing negative outcomes.

DOI： 10.3389/fneur.2020.611124

Comparison of circulating tumor DNA between body fluids in patients with primary central nervous system lymphoma. International journal

Jun Watanabe, Manabu Natsumeda, Yu Kanemaru, Masayasu Okada, Makoto Oishi, Akiyoshi Kakita, Yukihiko Fujii

Leukemia & lymphoma 60 ( 14 ) 3587 - 3589 2019.12

High Detection Rate of MYD88 Mutations in Cerebrospinal Fluid From Patients With CNS Lymphomas. International journal

Jun Watanabe, Manabu Natsumeda, Masayasu Okada, Daiki Kobayashi, Yu Kanemaru, Yoshihiro Tsukamoto, Makoto Oishi, Akiyoshi Kakita, Yukihiko Fujii

JCO precision oncology 3 1 - 13 2019.12

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Biopsy is the gold standard for the diagnosis of primary CNS lymphoma (PCNSL). However, surgical biopsy has problems of morbidity related to hemorrhagic complications and false-negative findings, so safer and more reliable diagnostic methods are required. The aim of this study is to detect the MYD88 mutation, an important driver mutation, in the cerebrospinal fluid (CSF) of patients with CNS lymphoma. PATIENTS AND METHODS: Twenty-six patients with CNS lymphoma (20 primary CNS lymphoma and six CNS relapse from systemic lymphoma) were studied. We extracted cell-free DNA (cfDNA) from CSF by lumbar puncture. cfDNA was extracted from 1 mL of CSF, and Sanger sequencing and droplet digital polymerase chain reaction (ddPCR) were performed. Furthermore, we performed DNA sequencing of MYD88 in 21 cases with available surgically obtained formalin-fixed paraffin-embedded (FFPE) tissue and compared the results. RESULTS: The median cfDNA amount extracted from 1 mL CSF was 219 ng/mL (25th to 75th percentile, 129 to 333 ng/mL). MYD88 mutations were detected from CSF in 76.9% (20 of 26 cases), and L265P in exon 5 was the most frequent mutation in 19 out of 20 (95.0%) cases. S219C in exon 3 was detected in one case. In four patients, MYD88 mutation was confirmed by ddPCR but not by Sanger sequencing. In all 21 cases with sufficient FFPE tissue for DNA analysis, the detection of MYD88 mutation from cfDNA was consistent with those of tumor-derived DNA from FFPE tissue. CONCLUSION: This pilot study provided evidence that the somatic driver mutation MYD88 can be reliably detected by combination of Sanger sequencing and ddPCR in the cfDNA taken from 1 mL of CSF in patients with CNS lymphomas.

DOI： 10.1200/PO.18.00308

Podoplanin Expression and IDH-Wildtype Status Predict Venous Thromboembolism in Patients with High-Grade Gliomas in the Early Postoperative Period. International journal

Jun Watanabe, Manabu Natsumeda, Masayasu Okada, Yu Kanemaru, Yoshihiro Tsukamoto, Makoto Oishi, Akiyoshi Kakita, Yukihiko Fujii

World neurosurgery 128 e982-e988 2019.8

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Venous thromboembolism (VTE) often is encountered in patients with high-grade gliomas. The underlying mechanisms are unclear, as is the optimal prophylactic protocol. The purpose of the present study was to identify risk factors of VTE and examine the validity of early VTE detection in high-grade gliomas. METHODS: We reviewed the medical records of 165 patients with newly diagnosed high-grade glioma treated at Niigata University Hospital during the years 2009 to 2016. If the serum D-dimer levels increased to 5.0 μg/mL or more, computed tomography was performed to detect VTE. Furthermore, immunohistochemistry with antibodies against podoplanin was performed on available 101 tumor tissues. RESULTS: Of the 165 patients, 44 (26.7%) developed VTE. Of the 44 patients, 34 (79.5%) developed VTE within 7 days after surgery. No fatal VTE occurred and major complications secondary to anticoagulation occurred in only 2 (1.2%) patients. On multivariate analysis, lower Karnofsky Performance Scale status, podoplanin expression, and isocitrate dehydrogenase-wildtype status were independently associated with the risk of VTE (P < 0.05). CONCLUSIONS: We found that most VTEs occurred early in the postoperative period and commonly in patients with lower Karnofsky Performance Scale status and isocitrate dehydrogenase-wildtype gliomas, which expressed podoplanin.

DOI： 10.1016/j.wneu.2019.05.049

Dramatic response of BRAF V600E-mutant epithelioid glioblastoma to combination therapy with BRAF and MEK inhibitor: establishment and xenograft of a cell line to predict clinical efficacy. International journal

Yu Kanemaru, Manabu Natsumeda, Masayasu Okada, Rie Saito, Daiki Kobayashi, Takeyoshi Eda, Jun Watanabe, Shoji Saito, Yoshihiro Tsukamoto, Makoto Oishi, Hirotake Saito, Masayuki Nagahashi, Takahiro Sasaki, Rintaro Hashizume, Hidefumi Aoyama, Toshifumi Wakai, Akiyoshi Kakita, Yukihiko Fujii

Acta neuropathologica communications 7 ( 1 ) 119 - 119 2019.7

Language：English Publishing type：Research paper (scientific journal)

Epithelioid glioblastoma is a rare aggressive variant of glioblastoma (GBM) characterized by a dismal prognosis of about 6 months and frequent leptomeningeal dissemination. A recent study has revealed that 50% of epithelioid GBMs harbor three genetic alterations - BRAF V600E mutation, TERT promoter mutations, and homozygous deletions of CDKN2A/2B. Emerging evidence support the effectiveness of targeted therapies for brain tumors with BRAF V600E mutation. Here we describe a dramatic radiographical response to combined therapy with BRAF and MEK inhibitors in a patient with epithelioid GBM harboring BRAF V600E mutation, characterized by thick spinal dissemination. From relapsed tumor procured at autopsy, we established a cell line retaining the BRAF V600E mutation, TERT promoter mutation and CDKN2A/2B loss. Intracranial implantation of these cells into mice resulted in tumors closely resembling the original, characterized by epithelioid tumor cells and dissemination, and invasion into the perivascular spaces. We then confirmed the efficacy of treatment with BRAF and MEK inhibitor both in vitro and in vivo. Epithelioid GBM with BRAF V600E mutation can be considered a good treatment indication for precision medicine, and this patient-derived cell line should be useful for prediction of the tumor response and clarification of its biological characteristics.

DOI： 10.1186/s40478-019-0774-7

Malignant Hyperthermia and Cerebral Venous Sinus Thrombosis After Ventriculoperitoneal Shunt in Infant with Schizencephaly and COL4A1 Mutation. International journal

Jun Watanabe, Kouichirou Okamoto, Tsukasa Ohashi, Manabu Natsumeda, Hitoshi Hasegawa, Makoto Oishi, Satoko Miyatake, Naomichi Matsumoto, Yukihiko Fujii

World neurosurgery 127 446 - 450 2019.7

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Schizencephaly is a rare congenital central nervous system malformation characterized by linear, thickened clefts of the cerebral mantle. Recently, germline mutations in collagen type IV alpha 1 (COL4A1) have been reported to be a genetic cause of schizencephaly as a result of prenatal stroke. Patients with COL4A1 mutation demonstrate a variety of disease phenotypes. However, little is known about the potential complications of patients with COL4A1 mutations before and after neurologic surgery. CASE DESCRIPTION: A 9-month-old boy with schizencephaly and a congenital cataract underwent a ventriculoperitoneal shunt for progressive hydrocephalus. Postoperatively, he developed malignant hyperthermia and cerebral venous thrombosis. Early treatment with dantrolene sodium and hydration was effective. Genetic testing revealed a germline COL4A1 mutation. CONCLUSIONS: To our knowledge, malignant hyperthermia and cerebral venous thrombosis have not been reported in the literature in patients with COL4A1 mutations after surgery. Schizencephaly arising from COL4A1 mutations might be a disease prone to these adverse effects because this mutation is known to be associated with venous tortuosity, venous vulnerability, and muscle spasms due to basement membrane protein abnormalities. We need to better understand the wide spectrum of clinical phenotypes of COL4A1 mutations and potential complications in order to better manage surgery of patients with schizencephaly.

DOI： 10.1016/j.wneu.2019.04.156

小児症例における内視鏡下経鼻経蝶形骨洞手術の解剖学的制限と安全性の検討

温城太郎, 岡田正康, 中村公彦, 米岡有一郎, 大石誠, 藤井幸彦

小児の脳神経 44 ( 2 ) 166 - 166 2019.4

EGFRvIII Is Expressed in Cellular Areas of Tumor in a Subset of Glioblastoma.

Takanori Nozawa, Masayasu Okada, Manabu Natsumeda, Takeyoshi Eda, Hideaki Abe, Yoshihiro Tsukamoto, Kouichirou Okamoto, Makoto Oishi, Hitoshi Takahashi, Yukihiko Fujii, Akiyoshi Kakita

Neurologia medico-chirurgica 59 ( 3 ) 89 - 97 2019.3

Language：English Publishing type：Research paper (scientific journal)

Epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific cell surface antigen often expressed in glioblastoma and has drawn much attention as a possible therapeutic target. We performed immunohistochemistry on histology sections of surgical specimens taken from 67 cases with glioblastoma, isocitrate dehydrogenase-wild type, and evaluated the morphological characteristics and distribution of the EGFRvIII-positive tumor cells. We then evaluated the localization of EGFRvIII-expression within the tumor and peritumoral areas. EGFRvIII immunopositivity was detected in 15 specimens taken from 13 patients, including two recurrent specimens taken from the same patient at relapse. Immunofluorescence staining demonstrated that EGFRvIII-positive cells were present in cells positive for glial fibrillary acidic protein (GFAP), and some showed astrocytic differentiation with multiple fine processes and others did not shown. The EGFRvIII-positive cells were located in cellular areas of the tumor, but not in the invading zone. In the two recurrent cases, EGFRvIII-positive cells were markedly decreased in one case and retained in the other. With regard to overall survival, univariate analysis indicated that EGFRvIII-expression in patients with glioblastoma was not significantly associated with a favorable outcome. Double-labeling immunofluorescence staining of EGFRvIII and GFAP showed that processes of large, well differentiated, GFAP-positive glia extend to and surround less differentiated, EGFRvIII-positive glial cells in cellular areas of tumor. However, in the tumor periphery, EGFRvIII-positive tumor cells were not observed. This finding suggests that EGFRvIII is involved in tumor proliferation, but that invading glioma cells lose their EGFRvIII expression.

DOI： 10.2176/nmc.oa.2018-0078

[Posterior Quadrantectomy for Infant with Refractory Epilepsy:A Case Report].

Taiki Saito, Makoto Oishi, Masafumi Fukuda, Yoshihiro Tsukamoto, Tsukasa Ohashi, Jun Watanabe, Takuma Nemoto, Tadashi Kawaguchi, Yukihiko Fujii

No shinkei geka. Neurological surgery 47 ( 3 ) 349 - 356 2019.3

Language：Japanese Publishing type：Research paper (scientific journal)

We present the case of an 11-month-old girl with linear nevus sebaceous syndrome who underwent posterior quadrantectomy(PQ)for intractable epilepsy due to cortical dysplasia extending from the temporal, parietal, and occipital lobes in the right hemisphere. Epileptic spasms started at 4 months after birth, and the frequency of her seizures gradually increased to 10 episodes per day. Electroencephalograms in the interictal periods showed hypsarrhythmia. Magnetic resonance imaging(MRI)suggested cortical dysplasia in the right temporal, parietal, and occipital lobes. Ictal single-photon emission computed tomography revealed increased cerebral blood flow in similar areas as the cortical dysplasia suggested on MRI. Several antiepileptic drugs were administered to control the epileptic spasms, without success. In addition, her developmental delay gradually became evident. Because the epileptic foci extended into the posterior region of the right hemisphere, we did not execute a focused resection, but performed a PQ. The epileptic spasms completely disappeared after surgery and her developmental delay gradually improved. Early surgical intervention via PQ is useful in patients with drug-resistant epilepsy in whom the epileptic foci have extended into the temporal, parietal, and occipital lobes. This intervention not only controls intractable seizures but also helps to facilitate normal development.

DOI： 10.11477/mf.1436203943

MGMT Expression Contributes to Temozolomide Resistance in H3K27M-Mutant Diffuse Midline Gliomas. International journal

Hideaki Abe, Manabu Natsumeda, Masayasu Okada, Jun Watanabe, Yoshihiro Tsukamoto, Yu Kanemaru, Junichi Yoshimura, Makoto Oishi, Rintaro Hashizume, Akiyoshi Kakita, Yukihiko Fujii

Frontiers in oncology 9 1568 - 1568 2019

Language：English Publishing type：Research paper (scientific journal)

Diffuse midline gliomas (DMGs) show resistance to many chemotherapeutic agents including temozolomide (TMZ). Histone gene mutations in DMGs trigger epigenetic changes including DNA hypomethylation, one of which is a frequent lack of O6-methyl-guanine-DNA methyltransferase (MGMT) promoter methylation, resulting in increased MGMT expression. We established the NGT16 cell line with HIST1H3B K27M and ACVR1 G328E gene mutations from a DMG patient and used this cell line and other DMG cell lines with H3F3A gene mutation (SF7761, SF8628, JHH-DIPG1) to analyze MGMT promoter methylation, MGMT protein expression, and response to TMZ. Three out of 4 DMG cell lines (NGT16, SF8628, and JHH-DIPG1) had unmethylated MGMT promoter, increased MGMT expression, and showed resistance to TMZ treatment. SF7761 cells with H3F3A gene mutation showed MGMT promoter methylation, lacked MGMT expression, and sensitivity to TMZ treatment. NGT16 line showed response to ALK2 inhibitor K02288 treatment in vitro. We confirmed in vitro that MGMT expression contributes to TMZ resistance in DMG cell lines. There is an urgent need to develop new strategies to treat TMZ-resistant DMGs.

DOI： 10.3389/fonc.2019.01568

治療に難渋しているACTH産生下垂体腺腫の1例

岡田正康, 米岡有一郎, 温城太郎, 本橋邦夫, 菊池文平, 長谷川仁, 大石誠, 藤井幸彦

新潟医学会雑誌 132 ( 11-12 ) 399 - 400 2018.12

Polysomnography as an indicator for cervicomedullary decompression to treat foramen magnum stenosis in achondroplasia. International journal

Masakazu Sano, Nao Takahashi, Keisuke Nagasaki, Makoto Oishi, Junichi Yoshimura, Yukihiko Fujii

Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery 34 ( 11 ) 2275 - 2281 2018.11

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Management of cervicomedullary compression due to foramen magnum stenosis in achondroplasia remains controversial, especially for patients with no symptoms or mild symptoms. We examined the effectiveness of polysomnography (PSG) as an indicator for cervicomedullary decompression treatment. METHODS: We retrospectively reviewed nine achondroplasia cases (mean age 1 year and 9 months) treated from 2008 to 2015. All patients were examined by PSG, magnetic resonance imaging (MRI), and otolaryngeal fibroscopy. We analyzed demographic data, clinical presentation, degree and type of respiratory impairment, severity of foramen magnum stenosis and concomitant cervicomedullary compression, treatment (conservative or surgical), and clinical outcome. RESULTS: Eight of nine patients presented with no severe symptoms in the daytime. However, MRI revealed four severe, four moderate, and one mild case of cervicomedullary compression, and PSG demonstrated severe sleep apnea in four cases and moderate sleep apnea in five cases. All sleep apnea cases were obstructive or obstructive-dominant. Fibroscopy revealed no upper airway stenosis in six cases and mild stenosis in three cases. Four patients who had severe sleep-related respiratory disturbance on PSG and severe or moderate cervicomedullary compression were treated by cervicomedullary decompression. Three of these patients demonstrated improved sleep respiration soon after surgery, while one required temporary tracheostomy due to bilateral vocal cord paralysis caused by compression during intratracheal intubation. CONCLUSION: Polysomnography can be a useful indicator for cervicomedullary decompression surgery, especially in cases of seemingly asymptomatic achondroplasia with severe foramen magnum stenosis.

DOI： 10.1007/s00381-018-3880-0

Absolute risk and predictors of the growth of acute spontaneous intracerebral haemorrhage: a systematic review and meta-analysis of individual patient data. International journal

Rustam Al-Shahi Salman, Joseph Frantzias, Robert J Lee, Patrick D Lyden, Thomas W K Battey, Alison M Ayres, Joshua N Goldstein, Stephan A Mayer, Thorsten Steiner, Xia Wang, Hisatomi Arima, Hitoshi Hasegawa, Makoto Oishi, Daniel A Godoy, Luca Masotti, Dar Dowlatshahi, David Rodriguez-Luna, Carlos A Molina, Dong-Kyu Jang, Antonio Davalos, José Castillo, Xiaoying Yao, Jan Claassen, Bastian Volbers, Seiji Kazui, Yasushi Okada, Shigeru Fujimoto, Kazunori Toyoda, Qi Li, Jane Khoury, Pilar Delgado, José Álvarez Sabín, Mar Hernández-Guillamon, Luis Prats-Sánchez, Chunyan Cai, Mahesh P Kate, Rebecca McCourt, Chitra Venkatasubramanian, Michael N Diringer, Yukio Ikeda, Hans Worthmann, Wendy C Ziai, Christopher D d'Esterre, Richard I Aviv, Peter Raab, Yasuo Murai, Allyson R Zazulia, Kenneth S Butcher, Seyed Mohammad Seyedsaadat, James C Grotta, Joan Martí-Fàbregas, Joan Montaner, Joseph Broderick, Haruko Yamamoto, Dimitre Staykov, E Sander Connolly, Magdy Selim, Rogelio Leira, Byung Hoo Moon, Andrew M Demchuk, Mario Di Napoli, Yukihiko Fujii, Craig S Anderson, Jonathan Rosand

The Lancet. Neurology 17 ( 10 ) 885 - 894 2018.10

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Intracerebral haemorrhage growth is associated with poor clinical outcome and is a therapeutic target for improving outcome. We aimed to determine the absolute risk and predictors of intracerebral haemorrhage growth, develop and validate prediction models, and evaluate the added value of CT angiography. METHODS: In a systematic review of OVID MEDLINE-with additional hand-searching of relevant studies' bibliographies- from Jan 1, 1970, to Dec 31, 2015, we identified observational cohorts and randomised trials with repeat scanning protocols that included at least ten patients with acute intracerebral haemorrhage. We sought individual patient-level data from corresponding authors for patients aged 18 years or older with data available from brain imaging initially done 0·5-24 h and repeated fewer than 6 days after symptom onset, who had baseline intracerebral haemorrhage volume of less than 150 mL, and did not undergo acute treatment that might reduce intracerebral haemorrhage volume. We estimated the absolute risk and predictors of the primary outcome of intracerebral haemorrhage growth (defined as >6 mL increase in intracerebral haemorrhage volume on repeat imaging) using multivariable logistic regression models in development and validation cohorts in four subgroups of patients, using a hierarchical approach: patients not taking anticoagulant therapy at intracerebral haemorrhage onset (who constituted the largest subgroup), patients taking anticoagulant therapy at intracerebral haemorrhage onset, patients from cohorts that included at least some patients taking anticoagulant therapy at intracerebral haemorrhage onset, and patients for whom both information about anticoagulant therapy at intracerebral haemorrhage onset and spot sign on acute CT angiography were known. FINDINGS: Of 4191 studies identified, 77 were eligible for inclusion. Overall, 36 (47%) cohorts provided data on 5435 eligible patients. 5076 of these patients were not taking anticoagulant therapy at symptom onset (median age 67 years, IQR 56-76), of whom 1009 (20%) had intracerebral haemorrhage growth. Multivariable models of patients with data on antiplatelet therapy use, data on anticoagulant therapy use, and assessment of CT angiography spot sign at symptom onset showed that time from symptom onset to baseline imaging (odds ratio 0·50, 95% CI 0·36-0·70; p<0·0001), intracerebral haemorrhage volume on baseline imaging (7·18, 4·46-11·60; p<0·0001), antiplatelet use (1·68, 1·06-2·66; p=0·026), and anticoagulant use (3·48, 1·96-6·16; p<0·0001) were independent predictors of intracerebral haemorrhage growth (C-index 0·78, 95% CI 0·75-0·82). Addition of CT angiography spot sign (odds ratio 4·46, 95% CI 2·95-6·75; p<0·0001) to the model increased the C-index by 0·05 (95% CI 0·03-0·07). INTERPRETATION: In this large patient-level meta-analysis, models using four or five predictors had acceptable to good discrimination. These models could inform the location and frequency of observations on patients in clinical practice, explain treatment effects in prior randomised trials, and guide the design of future trials. FUNDING: UK Medical Research Council and British Heart Foundation.

DOI： 10.1016/S1474-4422(18)30253-9

MGMT Expression Contributes to Temozolomide Resistance in H3K27M-Mutant Diffuse Midline Gliomas and MGMT Silencing to Temozolomide Sensitivity in IDH-Mutant Gliomas.

Hideaki Abe, Manabu Natsumeda, Yu Kanemaru, Jun Watanabe, Yoshihiro Tsukamoto, Masayasu Okada, Junichi Yoshimura, Makoto Oishi, Yukihiko Fujii

Neurologia medico-chirurgica 58 ( 7 ) 290 - 295 2018.7

Language：English Publishing type：Research paper (scientific journal)

Histone H3 mutations are frequently found in diffuse midline gliomas (DMGs), which include diffuse intrinsic pontine gliomas and thalamic gliomas. These tumors have dismal prognoses. Recent evidence suggests that one reason for the poor prognoses is that O6-methylguanine-DNA methyltransferase (MGMT) promoter frequently lacks methylation in DMGs. This review compares the epigenetic changes brought about by histone mutations to those by isocitrate dehydrogenase-mutant gliomas, which frequently have methylated MGMT promoters and are known to be sensitive to temozolomide.

DOI： 10.2176/nmc.ra.2018-0044

High Incidence of Deep Vein Thrombosis in the Perioperative Period of Neurosurgical Patients. International journal

Manabu Natsumeda, Takeo Uzuka, Jun Watanabe, Masafumi Fukuda, Yasuhisa Akaiwa, Kazuhiko Hanzawa, Masahiko Okada, Makoto Oishi, Yukihiko Fujii

World neurosurgery 112 e103-e112 2018.4

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: A prospective study was designed to elucidate incidence and predictors of deep venous thrombosis (DVT) in patients undergoing craniotomies. MATERIALS AND METHODS: Ninety-two patients who underwent craniotomies received pre- and postoperative venous ultrasonography and/or contrast-enhanced spiral computed tomography for diagnosis of DVT. The primary endpoint was DVT occurrence. Serial levels of serum D-dimer, soluble fibrin, and thrombin-antithrombin complex (TAT) were analyzed. RESULTS: Twenty-four of 92 patients (26.1%) had DVT, of whom 10 (41.7%) were diagnosed preoperatively. In patients with preoperative DVT, age, incidence of decreased performance status and leg paresis, levels of D-dimer, soluble fibrin, and TAT were significantly greater. In patients with postoperative DVT, length of surgery, incidence of decreased postoperative performance status, levels of D-dimer on postoperative days (POD) 3, 7, and 14, and TAT on POD7 were significantly greater. Patients with postoperative DVT had elevated D-dimer levels on POD 7 compared with POD 3. The D-dimer cutoff of 2.65 μg/mL at POD 7 could be used to identify DVT with 85.7% sensitivity and 72.3% specificity. A cutoff of 5.25 μg/mL at POD 7 yielded a specificity of 96.9%. Decreased performance status and elevated D-dimer were independent predictors for preoperative DVT, prolonged operation time, and elevated D-dimer on POD 7 for postoperative DVT. CONCLUSIONS: DVT frequently was observed in patients before and after undergoing craniotomies. Patients with decreased performance status should be preoperatively screened for DVT by checking D-dimer levels. Elevated D-dimer levels on POD 7 compared with POD 3 and D-dimer levels greater than 2.65 μg/mL at POD7 suggest the presence of DVT.

DOI： 10.1016/j.wneu.2017.12.139

Application of brain diffusion-weighted imaging performed using readout segmentation of long variable Echo Trains Reviewed

Go Ishida, Makoto Oishi, Ken Morii, Kenji Hasegawa, Akihiko Saito, Mitsuya Sato, Osamu Takizawa, Katsutoshi Murata, Da Porter, Hitoshi Matsuzawa, Yukihiko Fujii

Neurological Surgery 43 ( 1 ) 31 - 40 2015.1

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Igaku-Shoin Ltd

We report the preliminary use of the readout segmentation of long variable echo trains (RESOLVE) sequence, a novel magnetic resonance (MR) scanning technique based on a readout segmented echo planar imaging (EPI) strategy. RESOLVE enables high-resolution diffusion-weighted imaging (DWI) by minimizing susceptibility distortions and T2′ blurring. The software for this sequence was provided by Siemens AG, Germany. Previously, we determined appropriate sequence parameters to obtain sufficiently high-resolution images through phantom studies. Then, we applied the sequence to some clinical cases with neurological disorders and analyzed the RESOLVE-DWI data with diffusion tensor imaging (DTI) techniques. In this article, we report clinical application of the RESOLVE sequence in two cases, one with cerebellar infarction and one with an intracranial epidermoid cyst. In both cases, RESOLVE-DWI clearly exposed structures that were obscured or severely distorted by artifacts on usual single-shot EPI-DWI. DTI analyses for RESOLVE-DWI data provided detailed information about fiber tracts and cranial nerves.

DOI： 10.11477/mf.1436202942

3D Computer graphics simulation to obtain optimal surgical exposure during microvascular decompression of the glossopharyngeal nerve. International journal

Tetsuya Hiraishi, Toshio Matsushima, Masatou Kawashima, Yukiko Nakahara, Yuichi Takahashi, Hiroshi Ito, Makoto Oishi, Yukihiko Fujii

Neurosurgical review 36 ( 4 ) 629 - 35 2013.10

Language：English Publishing type：Research paper (scientific journal)

The affected artery in glossopharyngeal neuralgia (GPN) is most often the posterior inferior cerebellar artery (PICA) from the caudal side or the anterior inferior cerebellar artery (AICA) from the rostral side. This technical report describes two representative cases of GPN, one with PICA as the affected artery and the other with AICA, and demonstrates the optimal approach for each affected artery. We used 3D computer graphics (3D CG) simulation to consider the ideal transposition of the affected artery in any position and approach. Subsequently, we performed microvascular decompression (MVD) surgery based on this simulation. For PICA, we used the transcondylar fossa approach in the lateral recumbent position, very close to the prone position, with the patient's head tilted anteriorly for caudal transposition of PICA. In contrast, for AICA, we adopted a lateral suboccipital approach with opening of the lateral cerebellomedullary fissure, to visualize better the root entry zone of the glossopharyngeal nerve and to obtain a wide working space in the cerebellomedullary cistern, for rostral transposition of AICA. Both procedures were performed successfully. The best surgical approach for MVD in patients with GPN is contingent on the affected artery--PICA or AICA. 3D CG simulation provides tailored approach for MVD of the glossopharyngeal nerve, thereby ensuring optimal surgical exposure.

DOI： 10.1007/s10143-013-0479-5

Glioneuonal tumorの周囲脳組織のイメージング解析と病理組織学的所見の検討

福多真史, 北浦弘樹, 大石誠, 高尾哲郎, 平石哲也, 澁木克栄, 柿田明美, 藤井幸彦

てんかん研究 31 ( 2 ) 405 - 405 2013.9

Interactive presurgical simulation applying advanced 3D imaging and modeling techniques for skull base and deep tumors. International journal

Makoto Oishi, Masafumi Fukuda, Naoki Yajima, Kenzo Yoshida, Machiko Takahashi, Tetsuya Hiraishi, Tetsuro Takao, Akihiko Saito, Yukihiko Fujii

Journal of neurosurgery 119 ( 1 ) 94 - 105 2013.7

Language：English Publishing type：Research paper (scientific journal)

OBJECT: In this paper, the authors' goal was to report their novel presurgical simulation method applying interactive virtual simulation (IVS) using 3D computer graphics (CG) data and microscopic observation of color-printed plaster models based on these CG data in surgery for skull base and deep tumors. METHODS: For 25 operations in 23 patients with skull base or deep intracranial tumors (meningiomas, schwannomas, epidermoid tumors, chordomas, and others), the authors carried out presurgical simulation based on 3D CG data created by image analysis for radiological data. Interactive virtual simulation was performed by modifying the 3D CG data to imitate various surgical procedures, such as bone drilling, brain retraction, and tumor removal, with manipulation of a haptic device. The authors also produced color-printed plaster models of modified 3D CG data by a selective laser sintering method and observed them under the operative microscope. RESULTS: In all patients, IVS provided detailed and realistic surgical perspectives of sufficient quality, thereby allowing surgeons to determine an appropriate and feasible surgical approach. Surgeons agreed that in 44% of the 25 operations IVS showed high utility (as indicated by a rating of "prominent") in comprehending 3D microsurgical anatomies for which reconstruction using only 2D images was complicated. Microscopic observation of color-printed plaster models in 12 patients provided further utility in confirming realistic surgical anatomies. CONCLUSIONS: The authors' presurgical simulation method applying advanced 3D imaging and modeling techniques provided a realistic environment for practicing microsurgical procedures virtually and enabled the authors to ascertain complex microsurgical anatomy, to determine the optimal surgical strategies, and also to efficiently educate neurosurgical trainees, especially during surgery for skull base and deep tumors.

DOI： 10.3171/2013.3.JNS121109

Ictal near-infrared spectroscopy and electrocorticography study of supplementary motor area seizures. International journal

Yosuke Sato, Masafumi Fukuda, Makoto Oishi, Atsushi Shirasawa, Yukihiko Fujii

Journal of biomedical optics 18 ( 7 ) 76022 - 76022 2013.7

Language：English Publishing type：Research paper (scientific journal)

The seizure onset zone (SOZ) and propagation pathways in supplementary motor area (SMA) seizures are difficult to identify because of the short duration and swift propagations of this seizure type. Herein, we studied ictal cerebral blood flow changes, seizure electrical activities, and clinical signs employing simultaneous near-infrared spectroscopy (NIRS) and electrocorticography (ECoG) recordings in a brain tumor patient with SMA seizures. Increased cerebral blood flow was observed from the SOZ in the ipsilateral SMA and spread to the ipsilateral premotor cortex, ipsilateral sensorimotor cortex, and also the contralateral hemisphere. These propagation patterns were concordant with ictal ECoG seizure activities and clinical signs. Removal of the SOZ and surrounding areas, where the higher blood flow and higher frequency oscillations had been identified, achieved a good outcome for this patient. Our ictal NIRS-ECoG technique is robust and useful for detecting the SOZ and seizure propagations.

DOI： 10.1117/1.JBO.18.7.076022

Significance of horizontal propagation of synchronized activities in human epileptic neocortex investigated by optical imaging and immunohistological study. International journal

Tetsuya Hiraishi, Hiroki Kitaura, Makoto Oishi, Masafumi Fukuda, Shigeki Kameyama, Hitoshi Takahashi, Akiyoshi Kakita, Yukihiko Fujii

Epilepsy research 104 ( 1-2 ) 59 - 67 2013.3

Language：English Publishing type：Research paper (scientific journal)

To characterize the physiological condition of human epileptic neocortex, we employed flavoprotein fluorescence imaging (FFI), an optical imaging method which detects intrinsic signals accompanying neural activation, and immunohistologically studied human cortical specimens. The experimented materials were cortical tissues surrounding various intracerebral lesions obtained from 5 patients with epilepsy (epileptic patients: EPs) and 5 without epilepsy (non-epileptic patients: NEPs). These tissues were immersed in oxygenated artificial cerebrospinal fluid immediately after removal in the operating room. Signal changes of FFI in the cortical layers subjected to electrical stimulation were observed under bicuculline methiodide perfusion. Immunohistological staining for parvalbumin (PV), calbindin, and calretinin were performed on the same specimens to evaluate expressions of calcium-binding protein positive cells. The FFI study showed the characteristic cortical propagation pattern of elicited activities horizontally along the cortical layers in EPs but not in NEPs. The propagated area with more than 0.5% signal changes was significantly larger in EPs than in NEPs (p=0.008). Only the expression of PV positive neurons was significantly lower in EPs than in NEPs (p=0.006). The propagated area on FFI and the decrease in PV positive neurons correlated significantly (R=-0.78, p=0.04). The present study visualized the unique horizontal propagation of signal changes on FFI and demonstrated a correlation of this propagation with immunohistological decreases in PV positive neurons in human epileptic cortex. Further investigations may elucidate the mechanism of hyper-excitability and hyper-synchronization in epileptic cortical tissue itself.

DOI： 10.1016/j.eplepsyres.2012.09.014

[Intraoperative monitoring of motor evoked potentials during glioma removal].

Masafumi Fukuda, Makoto Oishi, Tetsuro Takao, Tetsuya Hiraishi, Tsutomu Kobayashi, Hiroshi Aoki, Ryosuke Ogura, Akihiko Saito, Yukihiko Fujii

No shinkei geka. Neurological surgery 41 ( 3 ) 219 - 27 2013.3

Language：Japanese Publishing type：Research paper (scientific journal)

OBJECTIVE: To determine whether motor evoked potentials(MEPs)provide reliable monitoring of the motor system during resection of gliomas in or adjacent to the motor cortex or pyramidal tract. MATERIALS AND METHODS: MEP recording was performed during 64 operations in 55 patients harboring gliomas. Intraoperative MEP findings were classified into 3 groups:Group A was defined as having no significant MEP changes, Group B as having reversible MEP changes(?50% amplitude decrease or loss), and Group C as having irreversible changes. Postoperative motor function was evaluated according to the presence/absence of deterioration immediately after surgery and 1 month later, as compared to preoperative motor status RESULTS: Immediately after surgery, 13 of 39(33%)patients in Group A, 6 of 17(35%)in Group B, and 7 of 8(88%)in Group C experienced deterioration of motor function. One month after surgery, 4 of 39(10%)patients in Group A, 3 of 17(18%)in Group B, and 4 of 8(50%)showed deterioration of motor function. Both immediately(χ2=8.3, p<0.05)and 1 month(χ2=6.9, p<0.05)after surgery, MEP alterations correlated significantly with postoperative deterioration of motor function. Despite MEPs being stable throughout surgery(Group A), there were some patients with deterioration of motor function initially appearing to represent false negative monitoring. However, these deteriorations were confirmed to have been caused by secondary hemorrhage, venous return dysfunction, postoperative convulsion, or resection of the supplementary motor area. CONCLUSIONS: MEP monitoring provides reliable information on the motor system during glioma surgery. Although false negative MEP results may exist in some patients, most data were not influenced by intraoperative manipulation but rather were attributable to secondary postoperative events.

グリオーマ摘出術中の運動誘発電位モニタリングの有用性と限界

福多真史, 大石誠, 高尾哲郎, 平石哲也, 小林勉, 青木洋, 小倉良介, 斉藤明彦, 藤井幸彦

Neurological Surgery 41 ( 3 ) 219 - 227 2013.3

Language：Japanese Publisher：(株)医学書院

運動野および錐体路近傍のグリオーマ摘出術55例64回(男34例、女21例、平均43.5歳)を対象に、術中皮質刺激による運動誘発電位(MEP)モニタリングの有用性について検討した。術中MEPの振幅低下を認めなかったのは39例(A群)、一時的に振幅低下や反応消失を認め、最終的に回復したのは17例(B群)、回復なしが8例(C群)であった。術翌日に上肢の運動機能が術前に比較して悪化していたのはA群13例(33%)、B群6例(35%)、C群7例(88%)で、3群間に有意差が認められた。A群悪化例のうち、補足運動野症候群を呈したのが6例、術直後のけいれん発作、静脈灌流障害、術直後の出血による悪化が各1例であった。C群で悪化を認めなかった1例は、MEPが最終的に50%以下となった症例であった。術後1ヵ月目の悪化はA群4例、B群3例、C群4例と減少し、A群の内訳は補足運動野症候群の回復過程、術後の頻回なけいれん発作、腫瘍の再増大、照射中の浮腫増強であった。

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2013&ichushi_jid=J01228&link_issn=&doc_id=20130311040004&doc_link_id=10.11477%2Fmf.1436101949&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1436101949&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Facial nerve dysfunction after drainage of cerebrospinal fluid during vestibular schwannoma surgery. International journal

Tetsuya Hiraishi, Masafumi Fukuda, Makoto Oishi, Yukihiko Fujii

Clinical neurology and neurosurgery 115 ( 1 ) 102 - 5 2013.1

Hemodynamic and electrophysiological connectivity in the language system: simultaneous near-infrared spectroscopy and electrocorticography recordings during cortical stimulation. International journal

Yosuke Sato, Makoto Oishi, Masafumi Fukuda, Yukihiko Fujii

Brain and language 123 ( 1 ) 64 - 7 2012.10

Language：English Publishing type：Research paper (scientific journal)

We applied near-infrared spectroscopy (NIRS) and electrocorticography (ECoG) recordings during cortical stimulation to a temporal lobe epilepsy patient who underwent subdural electrode implantation. Using NIRS, changes in blood concentrations of oxyhemoglobin (HbO(2)) and deoxyhemoglobin (HbR) during cortical stimulation of the left language areas were measured in each hemisphere. NIRS revealed that 2 Hz stimulation with 5 mA produced no significant hemodynamic changes in either hemisphere. By contrast, 50 Hz stimulation elicited significant increases in both HbO(2) and HbR at the stimulation site. Furthermore, with 50 Hz stimulation of the left superior temporal gyrus, the increases in HbO(2) and HbR were observed not only at the stimulation site but also concurrently at the left inferior frontal gyrus. This suggests the existence of functional connectivity in the language system. The present study demonstrates that simultaneous NIRS and ECoG studies during cortical stimulation allow a novel analysis of cerebral connectivity.

DOI： 10.1016/j.bandl.2012.07.006

Interactive virtual simulation using a 3D computer graphics model for microvascular decompression surgery. International journal

Makoto Oishi, Masafumi Fukuda, Tetsuya Hiraishi, Naoki Yajima, Yosuke Sato, Yukihiko Fujii

Journal of neurosurgery 117 ( 3 ) 555 - 65 2012.9

Language：English Publishing type：Research paper (scientific journal)

OBJECT: The purpose of this paper is to report on the authors' advanced presurgical interactive virtual simulation technique using a 3D computer graphics model for microvascular decompression (MVD) surgery. METHODS: The authors performed interactive virtual simulation prior to surgery in 26 patients with trigeminal neuralgia or hemifacial spasm. The 3D computer graphics models for interactive virtual simulation were composed of the brainstem, cerebellum, cranial nerves, vessels, and skull individually created by the image analysis, including segmentation, surface rendering, and data fusion for data collected by 3-T MRI and 64-row multidetector CT systems. Interactive virtual simulation was performed by employing novel computer-aided design software with manipulation of a haptic device to imitate the surgical procedures of bone drilling and retraction of the cerebellum. The findings were compared with intraoperative findings. RESULTS: In all patients, interactive virtual simulation provided detailed and realistic surgical perspectives, of sufficient quality, representing the lateral suboccipital route. The causes of trigeminal neuralgia or hemifacial spasm determined by observing 3D computer graphics models were concordant with those identified intraoperatively in 25 (96%) of 26 patients, which was a significantly higher rate than the 73% concordance rate (concordance in 19 of 26 patients) obtained by review of 2D images only (p < 0.05). Surgeons evaluated interactive virtual simulation as having "prominent" utility for carrying out the entire surgical procedure in 50% of cases. It was evaluated as moderately useful or "supportive" in the other 50% of cases. There were no cases in which it was evaluated as having no utility. The utilities of interactive virtual simulation were associated with atypical or complex forms of neurovascular compression and structural restrictions in the surgical window. Finally, MVD procedures were performed as simulated in 23 (88%) of the 26 patients . CONCLUSIONS: Our interactive virtual simulation using a 3D computer graphics model provided a realistic environment for performing virtual simulations prior to MVD surgery and enabled us to ascertain complex microsurgical anatomy.

DOI： 10.3171/2012.5.JNS112334

Movement-related cortical activation with voluntary pinch task: simultaneous monitoring of near-infrared spectroscopy signals and movement-related cortical potentials. International journal

Yosuke Sato, Masafumi Fukuda, Makoto Oishi, Yukihiko Fujii

Journal of biomedical optics 17 ( 7 ) 076011 - 076011 2012.7

Language：English Publishing type：Research paper (scientific journal)

This study was designed to evaluate hemodynamic and electrophysiological motor cortex responses to voluntary finger pinching in humans, with simultaneous recording of near-infrared spectroscopy (NIRS) signals and movement-related cortical potentials (MRCP). Six healthy, right-handed subjects performed 100 trials of voluntary right-thumb index-finger pinching with about a 10-second interval at their own pace. Throughout the session, 48 regions over the bilateral motor cortex were assessed by NIRS, while MRCP and electromyogram (EMG) were simultaneously monitored. MRCP started 1536 ± 58 ms before EMG onset and peaked 127 ± 24 ms after EMG onset. NIRS data showed bilateral prefrontal cortex at 0.5 ± 0.1 s before EMG onset and bilateral dorsal premotor cortex activations at 0.6 ± 0.1 s before EMG onset. The hand area of the sensorimotor cortex was activated left-dominantly, seen obviously peaked at 3.7 ± 0.2 s after EMG onset. The comparison between MRCP and NIRS results raised the possibility that the vascular response to neural activity occurs within 4 s with a voluntary pinch task. These results indicate that our technique allows detailed study of the motor control. Our method is a promising strategy for event-related motor control and neurovascular coupling studies.

DOI： 10.1117/1.JBO.17.7.076011

Periventricular nodular heterotopia functionally couples with the overlying hippocampus Reviewed

Hiroki Kitaura, Makoto Oishi, Nobuyuki Takei, Yong-Juan Fu, Tetsuya Hiraishi, Masafumi Fukuda, Hitoshi Takahashi, Katsuei Shibuki, Yukihiko Fujii, Akiyoshi Kakita

EPILEPSIA 53 ( 7 ) e127 - e131 2012.7

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

Patients with periventricular nodular heterotopia (PVNH) often have severe epilepsy. However, it is unclear how the heterotopia contributes to epileptogenesis. Recently, electrophysiologic studies using intraoperative depth electrodes have indicated that interaction between the heterotopia and overlying cortex is crucial for seizure onset. We performed an in vitro physiologic study using slices of resected brain from a 22-year-old man with PVNH, who manifested medically refractory mesial temporal lobe epilepsy. Preoperative evaluation indicated that the right mesial temporal structure and PVNH were the epileptogenic focus. The resected tissue was immediately immersed in cold artificial cerebrospinal fluid, and then slices of the brain tissue including the heterotopic nodules and overlying hippocampus were prepared. We electrically stimulated the incubated slices, and the elicited neural activities were analyzed as changes in the flavoprotein fluorescence signals. When we stimulated either the heterotopic nodule or the overlying hippocampus, clear functional coupling of neural activities between these structures was observed. The coupling response evoked by stimulation of the subiculum and developing within the heterotopic nodule was enhanced by application of bicuculline. Therefore, activities of the hippocampus and the nodule are closely correlated.

DOI： 10.1111/j.1528-1167.2012.03509.x

Epidermoid cyst involving the medial temporal lobe: surgical pathologic features of the epileptogenic lesion. International journal

Tetsuya Hiraishi, Makoto Oishi, Hiroki Kitaura, Masae Ryufuku, Yong-Juan Fu, Masafumi Fukuda, Hitoshi Takahashi, Yukihiko Fujii, Akiyoshi Kakita

Neuropathology : official journal of the Japanese Society of Neuropathology 32 ( 2 ) 196 - 201 2012.4

Language：English Publishing type：Research paper (scientific journal)

Epidermoid cysts in the middle fossa are rare and may involve the temporal lobe and lateral ventricle. Affected patients often suffer from seizures, but the pathomechanisms underlying the epileptogenic lesions have remained unclear. Here we report the surgical pathological features of the hippocampus in a 31-year-old woman with mesial temporal lobe epilepsy (mTLE), in whom an epidermoid cyst involving the right basal cistern and inferior horn of the lateral ventricle was evident. The ictal electrocorticogram indicated seizure onset at the parahippocampal gyrus. An anterior temporal lobectomy and amygdalohippocampectomy were performed. Histologically, the hippocampus showed marked atrophy with severe loss of pyramidal neurons in the cornu Ammonis subfields and granule cell loss in the dentate gyrus. At the ventricular surface of the hippocampus, there were small granulomatous lesions with spicularly anchored keratin substance. These features indicated multiple and chronic stab wounds by the cyst contents and consequent local inflammatory responses within the parenchyma. The predisposition to adhesion between the tumor and hippocampus may have caused neurons to develop abnormal irritability to certain chemical mediators present in the cyst. Epileptogenicity involving the atrophic hippocampus and medial temporal lobes nearby may have developed in association with these processes. This case appears to provide information that is useful for surgical planning in patients with mTLE and epidermoid cysts involving the medial temporal lobe.

DOI： 10.1111/j.1440-1789.2011.01243.x

Pharyngeal motor evoked potentials elicited by transcranial electrical stimulation for intraoperative monitoring during skull base surgery. International journal

Masafumi Fukuda, Makoto Oishi, Tetsuya Hiraishi, Akihiko Saito, Yukihiko Fujii

Journal of neurosurgery 116 ( 3 ) 605 - 10 2012.3

Language：English Publishing type：Research paper (scientific journal)

OBJECT: The purpose of this study was to determine whether monitoring of pharyngeal motor evoked potentials (PhMEPs) elicited by transcranial electrical stimulation during skull base tumor surgery might be useful for predicting postoperative swallowing deterioration. METHODS: The authors analyzed PhMEPs in 21 patients during 22 surgical procedures for the treatment of skull base tumors. Corkscrew electrodes positioned at C3 or C4 and Cz were used to deliver supramaximal stimuli (220-550 V). Pharyngeal MEPs were recorded from the posterior wall of the pharynx through a modified endotracheal tube. The correlation between the final/baseline PhMEP ratio and postoperative swallowing function was examined. RESULTS: Postoperative swallowing function was significantly (p < 0.05), although not strongly (r = -0.47), correlated with the final/baseline PhMEP ratio. A PhMEP ratio < 50% was recorded during 4 of 22 procedures; in all 4 of these cases, the patients experienced postoperative deterioration of swallowing function. After 18 procedures, the PhMEP ratios remained > 50%; nevertheless, after 4 (22.2%) of these 18 procedures, patients showed deterioration of swallowing function. CONCLUSIONS: Intraoperative PhMEP monitoring can be useful for predicting swallowing deterioration following skull base surgery, especially in patients with swallowing disturbances that are mainly due to reduction in the motor functions of the pharyngeal muscles.

DOI： 10.3171/2011.10.JNS111343

Near-infrared spectroscopic study and the Wada test for presurgical evaluation of expressive and receptive language functions in glioma patients: with a case report of dissociated language functions. International journal

Yosuke Sato, Takeo Uzuka, Hiroshi Aoki, Manabu Natsumeda, Makoto Oishi, Masafumi Fukuda, Yukihiko Fujii

Neuroscience letters 510 ( 2 ) 104 - 9 2012.2

Language：English Publishing type：Research paper (scientific journal)

Near-infrared spectroscopy (NIRS) has proven to be useful for the evaluation of language lateralization in healthy subjects, infants, and epileptic patients. This study for the first time investigated the expressive and receptive language functions separately, using NIRS in presurgical glioma patients. We also describe a special case with dissociated pattern of language functions. Ten glioma patients were examined. Using NIRS, the hemodynamic changes during a verb generation task or story listening task were measured in the cerebral hemisphere on either side covering the language areas. Following the NIRS study, the Wada test was performed in all the patients. The NIRS study revealed increases of oxyhemoglobin and decreases of deoxyhemoglobin in the language areas elicited by both tasks. In 9 patients, who were all right-handed, the expressive and receptive language functions were lateralized to the left hemisphere. The results of the NIRS study were completely consistent with those of the Wada test. In the remaining 1 patient with a right sided insular glioma, who was right-handed, the NIRS study revealed stronger activation of the right inferior frontal region during the verb generation task, and stronger activation of the left superior temporal region during the story listening task. This dissociated language function was validated by the Wada test and the postoperative neurological course. These results demonstrate that a NIRS study using our technique is extremely valuable for preoperative assessment of the language functions and exemplifies how a preoperative NIRS study can allow detection of unforeseen language lateralization.

DOI： 10.1016/j.neulet.2012.01.011

Monitoring of abnormal muscle response and facial motor evoked potential during microvascular decompression for hemifacial spasm. International journal

Masafumi Fukuda, Makoto Oishi, Tetsuro Takao, Tetsuya Hiraishi, Yosuke Sato, Yukihiko Fujii

Surgical neurology international 3 118 - 118 2012

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: To determine whether the monitoring of abnormal muscle response (AMR) and facial motor evoked potential (FMEP) during microvascular decompression (MVD) for hemifacial spasm (HFS) might be useful for predicting the postoperative clinical course and final outcomes. METHODS: We analyzed 45 HFS patients who underwent both AMR and FMEP monitoring during MVD. Patients were divided into two groups on the basis of post-MVD disappearance (group AMR-A) or persistence (group AMR-B) of AMR. With regard to FMEPs, patients were classified into one of the two groups according to the ratio of the final to baseline FMEP amplitudes recorded for the orbicularis oculi muscle: one group with a ratio of <50% (group FMEP-A), and the other with a ratio of ≥50% (group FMEP-B). RESULTS: Twenty-one of the 26 (81%) patients in group AMR-A were assigned to group FMEP-A, whereas 9 of the 17 (53%) patients in group AMR-B were assigned to FMEP-B (P < 0.05). In 38 of the 40 (95%) patients in whom the AMRs disappeared or persisted at amplitudes <50% that at the baseline, HFS had subsided at the final follow-up. Forty of the 42 (95%) patients whose FMEP amplitude ratios indicated reduction in the amplitudes from the baseline, had complete relief of the symptoms. Nineteen of the 20 (95%) patients whose AMRs disappeared after MVD experienced immediate relief of their symptoms after the operation. With regard to 14 of the 20 (70%) patients whose AMRs persisted at the final recordings, the symptoms of HFS improved over time and eventually subsided (P < 0.001). CONCLUSIONS: Intraoperative monitoring of both AMR and FMEP during MVD may be useful in predicting the postoperative outcomes in HFS patients. The AMR-related findings may help to predict whether HFS disappears immediately after surgery or some time later.

DOI： 10.4103/2152-7806.102328

[Depiction of the cranial nerves around the cavernous sinus by 3D reversed FISP with diffusion weighted imaging (3D PSIF-DWI)].

Go Ishida, Makoto Oishi, Shinya Jinguji, Yuichiro Yoneoka, Mitsuya Sato, Yukihiko Fujii

No shinkei geka. Neurological surgery 39 ( 10 ) 953 - 61 2011.10

Language：Japanese Publishing type：Research paper (scientific journal)

To evaluate the anatomy of cranial nerves running in and around the cavernous sinus, we employed three-dimensional reversed fast imaging with steady-state precession (FISP) with diffusion weighted imaging (3D PSIF-DWI) on 3-T magnetic resonance (MR) system. After determining the proper parameters to obtain sufficient resolution of 3D PSIF-DWI, we collected imaging data of 20-side cavernous regions in 10 normal subjects. 3D PSIF-DWI provided high contrast between the cranial nerves and other soft tissues, fluid, and blood in all subjects. We also created volume-rendered images of 3D PSIF-DWI and anatomically evaluated the reliability of visualizing optic, oculomotor, trochlear, trigeminal, and abducens nerves on 3D PSIF-DWI. All 20 sets of cranial nerves were visualized and 12 trochlear nerves and 6 abducens nerves were partially identified. We also presented preliminary clinical experiences in two cases with pituitary adenomas. The anatomical relationship between the tumor and cranial nerves running in and around the cavernous sinus could be three-dimensionally comprehended by 3D PSIF-DWI and the volume-rendered images. In conclusion, 3D PSIF-DWI has great potential to provide high resolution "cranial nerve imaging", which visualizes the whole length of the cranial nerves including the parts in the blood flow as in the cavernous sinus region.

Spatiotemporal dynamics of epileptiform propagations: Imaging of human brain slices Reviewed

Hiroki Kitaura, Tetsuya Hiraishi, Hiroatsu Murakami, Hiroshi Masuda, Masafumi Fukuda, Makoto Oishi, Masae Ryufuku, Yong-Juan Fu, Hitoshi Takahashi, Shigeki Kameyama, Yukihiko Fujii, Katsuei Shibuki, Akiyoshi Kakita

NEUROIMAGE 58 ( 1 ) 50 - 59 2011.9

Language：English Publishing type：Research paper (scientific journal) Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE

Seizure activities often originate from a localized region of the cerebral cortex and spread across large areas of the brain. The properties of these spreading abnormal discharges may account for clinical phenotypes in epilepsy patients, although the manner of their propagation and the underlying mechanisms are not well understood. In the present study we performed flavoprotein fluorescence imaging of cortical brain slices surgically resected from patients with partial epilepsy caused by various symptomatic lesions. Elicited neural activities in the epileptogenic tissue spread horizontally over the cortex momentarily, but those in control tissue taken from patients with brain tumors who had no history of epilepsy demonstrated only localized responses. Characteristically, the epileptiform propagation comprised early and late phases. When the stimulus intensity was changed gradually, the early phase showed an all-or-none behavior, whereas the late phase showed a gradual increase in the response. Moreover, the two phases were propagated through different cortical layers, suggesting that they are derived from distinct neural circuits. Morphological investigation revealed the presence of hypertrophic neurons and loss of dendritic spines, which might participate in the aberrant activities observed by flavoprotein fluorescence imaging. These findings indicate that synchronized activities of the early phase may play a key role in spreading abnormal discharges in human cortical epilepsies. (C) 2011 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.neuroimage.2011.05.046

Intraoperative facial nerve motor evoked potential monitoring during skull base surgery predicts long-term facial nerve function outcomes. International journal

Masafumi Fukuda, Makoto Oishi, Tetsuya Hiraishi, Akihiko Saito, Yukihiko Fujii

Neurological research 33 ( 6 ) 578 - 82 2011.7

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: This study was designed to clarify whether facial nerve motor evoked potentials (FNMEPs) elicited by transcranial electrical stimulation during skull base surgery are useful for predicting long-term facial nerve function. METHODS: We analyzed FNMEP findings in 35 patients with skull base tumors. Mean follow-up was 24.4 months. Corkscrew electrodes positioned at C3 or C4 and Cz were used to deliver supramaximal stimuli. FNMEPs were recorded from the orbicularis oculi and oris muscles. RESULTS: The correlation between the final-to-baseline FNMEP ratio and initial or long-term facial nerve function was examined. Initial post-operative facial nerve function correlated significantly with the FNMEP ratios in the orbicularis oculi (r = -0.53, P < 0.005) and orbicularis oris (r = -0.80, P < 0.001) muscles. The correlations between FNMEP ratios and facial nerve function remained significant during long-term follow-up (orbicularis oculi muscle: r = -0.43, P < 0.05; orbicularis oris muscle: r = -0.71, P < 0.001). All patients in whom the FNMEP ratio in the orbicularis oculi muscles remained above 50% were assigned to the satisfactory facial nerve function (House-Brackmann Grades i and ii) group at the final examination. DISCUSSION: FNMEP monitoring can predict facial nerve function not only immediately after surgery but also long-term.

DOI： 10.1179/016164110X12700393823697

Usefulness of motor-evoked potential monitoring during coil embolization of anterior choroidal artery aneurysms: technical reports. International journal

Tetsuya Hiraishi, Masafumi Fukuda, Makoto Oishi, Kazuhiko Nishino, Junsuke Shinbo, Takatoshi Sorimachi, Yasushi Ito, Yukihiko Fujii

Neurological research 33 ( 4 ) 360 - 2 2011.5

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: To determine whether transcranial motor-evoked potential (TCMEP) monitoring is useful for detecting blood flow insufficiency in the anterior choroidal artery (AChA) and reflects motor function during coil embolization of AChA aneurysms. METHODS: We analysed MEP findings in seven patients who underwent coil embolization for AChA aneurysms. Corkscrew electrodes positioned at C3 and C4 were used to deliver supra-maximal stimuli (230-550 V). TCMEPs were recorded from the brachioradialis, abductor pollicis brevis, anterior tibialis, and abductor hallucis muscles during all endovascular surgery procedures. RESULTS: Three of seven patients showed transient decreases in TCMEP amplitudes obtained from the lower extremities after coil insertion into the aneurysms, although digital subtraction angiography (DSA) showed no blood flow insufficiency in the AChAs. In two of these three patients, extraction of the coils resulted in recovery of TCMEP amplitudes. In the other patient, the amplitude recovered gradually during repeated TCMEP recordings. One of the three patients experienced transient hemiparesis and aphasia 3 hours after treatment. No patients experienced permanent morbidity post-operatively. DISCUSSION: Decreases in TCMEP amplitude during endovascular treatment for AChA aneurysms are likely to reflect motor dysfunction due to a subtle blood flow insufficiency in the AChA, not detectable by DSA. TCMEP monitoring is a simple and safe monitoring method during coil embolization of AChA aneurysms.

DOI： 10.1179/016164110X12807570

Clinicopathological factors related to regrowth of vestibular schwannoma after incomplete resection. International journal

Masafumi Fukuda, Makoto Oishi, Tetsuya Hiraishi, Manabu Natsumeda, Yukihiko Fujii

Journal of neurosurgery 114 ( 5 ) 1224 - 31 2011.5

Language：English Publishing type：Research paper (scientific journal)

OBJECT: The authors retrospectively analyzed various clinicopathological factors to determine which are related to regrowth during a long-term follow-up period in patients who underwent incomplete vestibular schwannoma (VS) resection. METHODS: This study involved 74 patients (25 men and 49 women) in whom a VS was treated surgically via the lateral suboccipital approach, and who had postoperative follow-up periods exceeding 5 years. The mean follow-up was 104.1 months (range 60-241 months), and the mean patient age at surgery was 48.1 years (range 19-75 years). The tumors ranged in size from 0 mm (localized within the internal auditory canal) to 56 mm (28.3 ± 12.2 mm [mean ± SD]). RESULTS: Gross-total resection (GTR) was performed in 41 (55%) of the 74 patients; subtotal resection ([STR]; 90-99%) in 25 (34%); and partial resection ([PR]; < 90%) in 8 (11%). Regrowth rates in the GTR, STR, and PR groups were 2.4% (1 of 41 cases), 52% (13 of 25), and 62.5% (5 of 8), respectively, and the times to regrowth ranged from 6 to 76 months (median 31.9 months). The regrowth-free survival curves differed significantly between the complete (GTR) and incomplete (STR and PR) resection groups. Eighteen (54.5%) of the 33 patients who underwent incomplete resection showed evidence of regrowth during follow-up. Univariate and multivariate analyses of various factors revealed that both the thickness of the residual tumor, based on MR imaging after surgery, and the MIB-1 index were positively related to residual tumor regrowth. The receiver operating characteristic curves, plotted for both the thickness of the residual tumor and the MIB-1 index, identified the optimal cutoff points for these values as 7.4 mm (sensitivity 83.3%, specificity 86.7%) and 1.6 (sensitivity 83.3%, specificity 66.7%), respectively. CONCLUSIONS: Greater residual tumor thickness, based on MR imaging after the initial surgery, and a higher MIB-1 index are both important factors related to postoperative tumor regrowth in patients who have undergone incomplete VS resection. These patients require frequent neuroimaging investigation during follow-up to assure early detection of tumor regrowth.

DOI： 10.3171/2010.11.JNS101041

Transarterial embolisation for refractory bilateral chronic subdural hematomas in a case with dentatorubral-pallidoluysian atrophy Reviewed

Yoshihiro Tsukamoto, Makoto Oishi, Junnsuke Shinbo, Yukihiko Fujii

ACTA NEUROCHIRURGICA 153 ( 5 ) 1145 - 1147 2011.5

Presurgical simulation with advanced 3-dimensional multifusion volumetric imaging in patients with skull base tumors. International journal

Makoto Oishi, Masafumi Fukuda, Go Ishida, Akihiko Saito, Tetsuya Hiraishi, Yukihiko Fujii

Neurosurgery 68 ( 1 Suppl Operative ) 188 - 99 2011.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Despite recent diagnostic and technical advancements in the field of neurosurgery, surgical treatment for tumors in the skull base region, ie, skull base tumors (SBTs), remains a challenge. OBJECTIVE: To validate the utility of presurgical simulation for the treatment of SBTs by 3-dimensional multifusion volumetric imaging (3D MFVI), including volume rendering and image fusion, to combine data from various imaging modalities. METHODS: We performed presurgical simulation using 3D MFVI for 21 SBTs (acoustic neurinomas, jugular neurinomas, meningiomas, chordomas, and others) in 20 patients. We collected targeted data from computed tomography, magnetic resonance imaging, computed tomography or magnetic resonance angiography, and digital subtraction angiography and combined these data using image-analyzing software. The simulations were used to assess the 3D relationships among the microsurgical anatomical components, the appropriate surgical approach, and the resectable parts of the tumor. Finally, we compared the results of the simulation with the operative results. RESULTS: In all patients, the 3D MFVI techniques enabled adequate visualization of the microsurgical anatomy and facilitated presurgical simulation, thereby allowing the surgeons to determine an appropriate and feasible surgical approach. All procedures to open the bone window were performed in accordance with the simulations, except for the surgical exposure of the acoustic canal for 2 acoustic neurinomas. In 3 of the 21 cases, tumor removal could not be performed according to the simulations because of unexpected bleeding or other restrictions. CONCLUSION: The 3D MFVI technique was of a sufficiently high quality to enable visualization of the 3D microsurgical anatomy. This promising method can facilitate determination of the most appropriate approach and safe and precise surgical procedures for SBTs.

DOI： 10.1227/NEU.0b013e318207b3ad

[Depiction of the trigeminal nerve deviated by a tumor lesion, using probabilistic diffusion tensor tractography].

Go Ishida, Makoto Oishi, Masafumi Fukuda, Mitsuya Sato, Yukihiko Fujii

No shinkei geka. Neurological surgery 39 ( 3 ) 255 - 62 2011.3

Language：Japanese Publishing type：Research paper (scientific journal)

We attempted presurgical visualization of the trigeminal nerve deviated by tumor compression using the probabilistic diffusion tractography (PDT) technique, which is used to analyze diffusion tensor imaging (DTI) data. We acquired DTI data of 3 patients with a tumor lesion around the trigeminal nerve (2 patients with trigeminal neurinomas and 1 with epidermoid) using the 3T magnetic resonance imaging system. The DTI data was analyzed by PDT using the Diffusion Toolbox, and the software of FMRIB (FDT; www.fmrib.ox.ac.uk/fsl). In all 3 patients, PDT allowed successful visualization of the trigeminal nerve which is further distal to the trigeminal ganglion, even when heavy T2-weighted imaging and conventional fiber-tracking analysis of the DTI data revealed only the cisternal segment of the nerves. Especially in 2 cases with the tumor mainly located in the Meckel's cave, the location of the nerve was determined only by PDT. All these findings obtained by PDT were concordant with the intraoperative observation of the actual nerves. In conclusion, PDT is a useful technique for visualization of the trigeminal nerve even when it is severely deviated by tumor compression, and this technique could have potential for evaluating other cranial nerves in surgical cases with a tumor in the skull base.

Trigeminal neuralgia associated with the specific bridging pattern of transverse pontine vein: diagnostic value of three-dimensional multifusion volumetric imaging. International journal

Makoto Oishi, Masafumi Fukuda, Yoshiyuki Noto, Tadashi Kawaguchi, Tetsuya Hiraishi, Yukihiko Fujii

Stereotactic and functional neurosurgery 89 ( 4 ) 226 - 33 2011

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: We report the specific bridging pattern of a transverse pontine vein (TPV) associated with trigeminal neuralgia (TN), which was evaluated by 3-dimensional (3D) multifusion volumetric imaging (MFVI). METHODS: In 3 cases with TN (V1 or V1-2 territory), constructive interference in steady state (CISS) imaging confirmed no arterial compression but indicated a vein draining into Meckel's cave. Virtual endoscopic (VE) analysis for CISS images and 3D MFVI (in 2 cases) including venous information was obtained by a multidetector row computed tomography (MDCT) system. Additionally, we investigated the bridging pattern of veins around Meckel's cave on 3D MFVI of 50 cerebellopontine angle (CPA) regions without any lesions. RESULTS: In all 3 patients, VE of CISS or 3D MFVI identified a bridging vein from the TPV causing the focal deformity of the trigeminal nerve near Meckel's cave. All those patients achieved a pain-free state after surgically coagulating and cutting the vein. In investigating 3D MFVI of 50 CPA regions, this type of the bridging vein was found in 4 (8%) including the presented 2 cases. CONCLUSIONS: The specific bridging pattern of the TPV draining into Meckel's cave can be associated with TN. The 3D MFVI analysis using venous information obtained by MDCT was useful to evaluate surgical anatomy including the offending vein which can be missed.

DOI： 10.1159/000326778

Prediction of the microsurgical window for skull-base tumors by advanced three-dimensional multi-fusion volumetric imaging.

Makoto Oishi, Masafumi Fukuda, Go Ishida, Akihiko Saito, Tetsuya Hiraishi, Yukihiko Fujii

Neurologia medico-chirurgica 51 ( 3 ) 201 - 7 2011

Language：English Publishing type：Research paper (scientific journal)

The surgery of skull base tumors (SBTs) is difficult due to the complex and narrow surgical window that is restricted by the cranium and important structures. The utility of three-dimensional multi-fusion volumetric imaging (3-D MFVI) for visualizing the predicted window for SBTs was evaluated. Presurgical simulation using 3-D MFVI was performed in 32 patients with SBTs. Imaging data were collected from computed tomography, magnetic resonance imaging, and digital subtraction angiography. Skull data was processed to imitate actual bone resection and integrated with various structures extracted from appropriate imaging modalities by image-analyzing software. The simulated views were compared with the views obtained during surgery. All craniotomies and bone resections except opening of the acoustic canal in 2 patients were performed as simulated. The simulated window allowed observation of the expected microsurgical anatomies including tumors, vasculatures, and cranial nerves, through the predicted operative window. We could not achieve the planned tumor removal in only 3 patients. 3-D MFVI afforded high quality images of the relevant microsurgical anatomies during the surgery of SBTs. The intraoperative déjà-vu effect of the simulation increased the confidence of the surgeon in the planned surgical procedures.

Fiber tract visualization and intraoperative functional neuronavigation Reviewed

Yukihiko Fujii, Hitoshi Matsuzawa, Makoto Oishi, Takeo Uzuka, Tsutomu Nakada

Japanese Journal of Neurosurgery 20 ( 4 ) 247 - 253 2011

Language：English Publishing type：Research paper (scientific journal) Publisher：Japanese Congress of Neurological Surgeons

Visualization of neural fibers using diffusion tensor imaging (DTI) is becoming an indispensable tool in neurosurgery. Currently, two techniques, three-dimensional anisotropy contrast (3DAC) imaging and tractography, are frequently utilized. 3DAC images provide three-dimensional fiber-directional information in true color contrast and exquisitely high anatomical resolution sensitive to physiological anisotropism. Images are obtained by performing processes in image form (pictorial mathematics) without the necessity of eigenvalue estimation. Hence, image quality is identical to conventional magnetic resonance images such as T1 weighted and T2 weighted images. 3DAC has been shown to provide images with extraordinary contrast to detect not only major neural tracts but also fine neural fibers and nuclei, including in the brainstem and spinal cord. Tractography is widely used in neurosurgical settings, especially for presurgical planning to identify neural tracts. The direction of the largest diffusion determined by DTI parallels the dominant fiber orientation in each voxel, representing the mean longitudinal direction of neural fibers, which can be utilized for fiber tract tracing, i. e., tractography. Tractography is generally performed in two different ways, i. e., by deterministic or probabilistic methods. Advantages of the latter method over the former include the ability to clearly represent uncertainty and to reconstruct crossing fibers in the data, though the former is computationally intensive because of its requirement of thousands of iterations. There is widespread misunderstanding that tractography images actually represent real tracts and their pathology. In order to avoid such a potentially serious mistake, clinicians should clearly understand that, unlike 3DAC, tractography is in fact an artificial image. Recently, functional neuronavigation, i. e., intraoperative navigation integrated with preoperative functional images, was introduced into neurosurgical practice. Functional neuronavigation combined with visualization of thefiber tract is also expected to significantly reduce postoperative neurological deficits. In this venue, accuracy ofthe navigation is critical. It is, therefore, imperative that neurosurgeons understand the pros and cons of each of the techniques to be incorporated. The most reliable scenario will be the combination of intraoperative images, such as computed tomographic images and magnetic resonance images, appropriately integrated with functional data obtained preoperatively.

DOI： 10.7887/jcns.20.247

[Effects of abnormal muscle response monitoring on manipulation of microvascular decompression].

Masafumi Fukuda, Makoto Oishi, Tetsuya Hiraishi, Yukihiko Fujii

No shinkei geka. Neurological surgery 38 ( 6 ) 531 - 8 2010.6

Language：Japanese Publishing type：Research paper (scientific journal)

OBJECTIVE: Intraoperative abnormal muscle response (AMR) monitoring is used as an indicator of postoperative outcome in patients with hemifacial spasm (HFS). We investigated whether AMR findings influence manipulation of microvascular decompression and improve the postoperative results. MATERIALS AND METHODS: Subjects were 102 HFS patients who underwent AMR monitoring during surgery. The value of AMR monitoring was classified into four categories: a guiding, a confirming, an indirect confirming, or an inconclusive role. The relationship between AMR monitoring results and surgical outcome was analyzed. RESULTS: The overall cure rate was 92.2%. A guiding role of AMR monitoring was apparent in 13.7% of patients, and a confirming role was demonstrated in 53.9% of patients. The cure rate was 92.9% in patients defined as guiding, and 96.4% in patients defined as confirming cases. When the AMR remained disappearance until completion of decompression in patients assigned in indirect confirming, 13 of 15 patients (86.7%) experienced resolution postoperatively. In patients defined as inconclusive cases, 14 of 16 patients (87.5%) in whom AMR still presented but its amplitude decreased at the end of surgery experienced complete resolution. CONCLUSIONS: This study demonstrates that meticulous evaluation of AMR findings intraoperatively can help to improve the results of surgery. We believe that intraoperative AMR monitoring is useful in microvascular decompression for HFS.

Facial nerve motor-evoked potential monitoring during microvascular decompression for hemifacial spasm. International journal

Masafumi Fukuda, Makoto Oishi, Tetsuya Hiraishi, Yukihiko Fujii

Journal of neurology, neurosurgery, and psychiatry 81 ( 5 ) 519 - 23 2010.5

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: To determine whether monitoring facial nerve motor-evoked potentials (FNMEPs) elicited by transcranial electrical stimulation during microvascular decompression (MVD) for hemifacial spasm (HFS) is useful for predicting postoperative outcome. METHODS: The authors analysed FNMEP findings in 25 patients with HFS. Corkscrew electrodes positioned at C3 or C4 and Cz were used to deliver supramaximal stimuli (152-450 V). FNMEPs were recorded from the orbicularis oculi, mentalis and oris muscles. Differences in amplitude or response duration between the final (at dural closure) and baseline FNMEP were evaluated. Final-to-baseline FNMEPs ratios (shown as percentages) obtained from the three muscles were examined. RESULTS: In the orbicularis oculi muscles, both duration and amplitude in the final FNMEP were significantly reduced compared with the baseline FNMEP (p<0.001 and p<0.0005, respectively). The FNMEP ratio obtained from the orbicularis oculi muscle (44.8+/-25.4%) was significantly lower than the other two muscles (95.8+/-51.2% for the mentalis muscle and 84.5+/-34.6% for the orbicularis oris muscle; p<0.0001). In one patient who showed the same degree of symptoms immediately after surgery as in the preoperative state, neither LSRs nor FNMEP from the orbicularis oculi muscle changed. CONCLUSIONS: The FNMEP amplitude from the orbicularis oculi muscle decreased after MVD in HFS patients whose symptoms were resolved postoperatively, thus suggesting normalisation of facial nerve excitability. FNMEP monitoring during MVD surgery as well as LSR monitoring could predict postoperative outcome in HFS patients.

DOI： 10.1136/jnnp.2009.181495

Long-term outcomes after surgical treatment of jugular foramen schwannoma. International journal

Masafumi Fukuda, Makoto Oishi, Akihiko Saito, Yukihiko Fujii

Skull base : official journal of North American Skull Base Society ... [et al.] 19 ( 6 ) 401 - 8 2009.11

Language：English Publishing type：Research paper (scientific journal)

The purpose of this article is to clarify long-term outcomes following surgery for jugular foramen schwannomas. Fifteen adult patients underwent surgery, predominantly via the lateral suboccipital approach, for jugular foramen schwannomas between December 1987 and May 2007. All information was collected retrospectively from patient medical records at a university hospital. The main outcome measures were tumor regrowth and IX-X nerve function at median 84.3 months (range, 12 to 166 months) following surgery. Near total removal was achieved in 10 patients, and the remaining 5 patients had subtotal removal. Tumor regrowth was observed in 9 of 15 patients at 6 to 89 months (mean, 31.2 months) after surgery. The actual tumor control rate was 70.0 +/- 12.8% at 5 years. Fourteen of 15 patients exhibited IX-X nerve dysfunction immediately after surgery, but 8 of these 14 patients experienced amelioration of the symptoms at the final follow-up period. No patients required additional treatment. We found in our study that for jugular foramen schwannoma, tumor volume should be reduced as much as possible to avoid severe IX-X nerve damages postoperatively. If a small amount of tumor remains, long-term follow-up is necessary.

DOI： 10.1055/s-0029-1220197

[Presurgical evaluaton for lateral suboccipital craniotomy using contrast-enhanced CT volumetric imaging].

Makoto Oishi, Masafumi Fukuda, Akihiko Saito, Tetsuya Hiraishi, Yukihiko Fuji

No shinkei geka. Neurological surgery 37 ( 5 ) 459 - 65 2009.5

Language：Japanese Publishing type：Research paper (scientific journal)

To safely and precisely accomplish lateral suboccipital craniotomy (LSOC), we have presurgically evaluated the three-dimensional (3-D) relationships of various vascular structures and cranial landmarks in the occipito-cervical region by volumetric imaging of 3-D contrast enhanced computed tomography (CECT). The 3-D anatomies visualized by adjusting the window width, window level, and opacity level of the specific CT value for each structure were an occpital artery (OA), mastoid and posterior condylar emissary veins (MEV and PCEV), which were useful in dissecting muscles and exposing the cranial surface, and the relationship of the transverse-sigmoid sinus CTSS) and the asterion, which was necessary and decisive for making a key burr hole to perform craniotomy. The morphologic analysis for our 48 cases with cerebello-pontine angle tumor or neurovascular compression syndrome showed running patterns of OA, varieties of MEV and PCEV in their sizes and connections, right dominance of TSS, and the various relationship between the TSS and the asterion. Especially, the exact location of the TSS compared to the astenon was found to be inferior in 56%, right below in 38%, and superior in 6%. In conclusion, presurgical evaluation using volumetric imaging of 3-D CECT is a convenient and valuable method for obtaining the anatomic information required for performing LSOC safely and precisely in individual patients.

Three-dimensional visualization of neurovascular compression: presurgical use of virtual endoscopy created from magnetic resonance imaging. International journal

Tetsuro Takao, Makoto Oishi, Masafumi Fukuda, Go Ishida, Mitsuya Sato, Yukihiko Fujii

Neurosurgery 63 ( 1 Suppl 1 ) ONS139-45; discussion ONS145-6 2008.7

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: To assess the usefulness of presurgical simulation of microvascular decompression (MVD) by virtual endoscopy (VE), a new tool to analyze three-dimensionally reconstructed magnetic resonance data sets in patients with trigeminal neuralgia or hemifacial spasm (HFS). METHODS: In 17 patients (10 with trigeminal neuralgia and seven with HFS) determined to be candidates for MVD, we performed presurgical simulation of MVD using VE. We used constructive interference in steady-state imaging and magnetic resonance angiography to obtain the original images. VE findings were compared with surgical findings. RESULTS: The three-dimensional relations between visible structures seen on VE were consistent with intraoperative findings in all patients. In total, 20 (91%) of 22 neurovascular compression sites in all 17 patients were correctly delineated on VE, with the exception of two small branches identified as offending vessel in two patients with HFS. Perforators that were not apparent on VE limited our ability to accomplish transpositioning of the offending vessels as simulated. The positions of structures that can affect individual surgical approaches, such as the petrosal vein, cerebellar flocculus, and vertebral artery, were also adequately predicted on VE. All patients had excellent surgical outcomes. CONCLUSION: Presurgical VE in patients with trigeminal neuralgia or HFS is a novel technique that provides excellent visualization of the three-dimensional relations between neurovascular structures and allows simulation of MVD.

DOI： 10.1227/01.neu.0000335028.77779.7c

[Facial nerve motor evoked potentials elicited by transcranial electrical stimulation for intraoperative monitoring].

Masafumi Fukuda, Makoto Oishi, Akihiko Saito, Tetsuro Takao, Yukihiko Fujii

No shinkei geka. Neurological surgery 36 ( 4 ) 315 - 21 2008.4

Language：Japanese Publishing type：Research paper (scientific journal)

OBJECTIVE: To determine whether monitoring facial nerve motor evoked potentials (FNMEPs) elicited by transcranial electrical stimulation during skull base tumor surgery is useful for predicting facial nerve outcome. METHODS: We analyzed FNMEP findings in 31 patients with skull base tumor. Surgery was performed twice in 2 of the 31 patients because of tumor regrowth. FNMEP monitoring was conducted 33 times in the present study. Corkscrew electrodes positioned at C3 or C4 and Cz were used to deliver supramaximal stimuli (140-550V). FNMEPs were recorded from the orbicularis oculi and oris muscles. Correlation between the final-to-baseline FNMEP ratio and postoperative facial nerve function (House & Brackmann grade) was examined. RESULTS: Valid FNMEPs were obtained in 26 of the 33 (78.8%) recordings from the orbicularis oculi muscle and in 31 of the 33 (93.9%) recordings from the orbicularis oris muscle. Facial nerve function correlated significantly with the FNMEP ratios in the orbicularis oculi (r = -0.52 N=26, p < 0.01) and orbicularis oris (r = -0.60, N=31, p < 0.001) muscles. An FNMEP ratio of -50% consistently predicted immediate postoperative facial palsy, although the degree of palsy differed among the patients. CONCLUSIONS: Intraoperative FNMEP monitoring is useful for predicting facial nerve function after skull base surgery.

Etiopathological factors related to hydrocephalus associated with vestibular schwannoma. International journal

Masafumi Fukuda, Makoto Oishi, Tadashi Kawaguchi, Masatoshi Watanabe, Tetsuro Takao, Ryuichi Tanaka, Yukihiko Fujii

Neurosurgery 61 ( 6 ) 1186 - 92 2007.12

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: We retrospectively analyzed various clinical factors to determine whether or not these factors are etiopathologically related to the development of hydrocephalus in patients with vestibular schwannomas. METHODS: There were 68 patients (29 men, 39 women) in this study who underwent resection of a vestibular schwannoma. The age at the time of surgery ranged from 19 to 76 years (mean age, 51.4 yr). The maximum diameter of the tumor in the cerebellopontine cistern ranged from 0 (localized within the internal auditory canal) to 56 mm (mean, 32.0 +/- 12.9 mm). Cerebrospinal fluid (CSF) protein concentration in the cerebellomedullary cistern was measured intraoperatively in all patients. RESULTS: Sixteen (23.5%) of the 68 patients exhibited radiographic evidence of hydrocephalus. Univariate analysis of various factors revealed that both tumor size and CSF protein concentration were positively related to development of hydrocephalus (P < 0.05 and P < 0.01, respectively). However, in multiple logistic regression analysis, only the CSF protein concentration was predictive for development of hydrocephalus (P = 0.022). There was a trend toward increased CSF protein concentration in patients with a large tumor (> or = 40 mm) compared with those with a small tumor (< 40 mm) (P = 0.06). CONCLUSION: A high CSF protein concentration in fluid from the cerebellomedullary cistern is one of the most important factors contributing to hydrocephalus associated with vestibular schwannoma. It is important to judge whether or not any further treatment is required for hydrocephalus, in addition to tumor resection, especially in patients with communicating hydrocephalus.

[The utility of presurgical simulation of microvascular decompression by MR virtual endoscopy].

Makoto Oishi, Masafumi Fukuda, Tetsuro Takao, Go Ishida, Mitsuya Sato, Yukihiko Fujii

No shinkei geka. Neurological surgery 35 ( 11 ) 1087 - 95 2007.11

Language：Japanese Publishing type：Research paper (scientific journal)

OBJECTIVE: We conducted the present study to assess the utility of virtual endoscopy (VE) created by volume rendering of MR images in presurgical simulation for trigeminal neuralgia (TN) and hemifacial spasm (HFS). METHODS: In 12 patients (six with TN and six with HFS), we presurgically evaluated the anatomy of the cerebellopontine angle (CPA) region and simulated an appropriate surgical approach by VE of heavy T2-weighted imaging and MR angiography. RESULTS: The three-dimensional (3-D) relations of neurovascular structures in the CPA region were compatible between on-VE and on-the-intraoperative view in all patients. The compression sites and the major offending vessels were correctly depicted, except for two small branches as the offending vessel. The other important structures affecting the surgical procedure were identified as major petrosal veins in all patients with TN, a vertebral artery in three with HFS, and a large cerebellar flocculus in three with HFS. Transposition of the offending vessels was performed as simulated in all patients with TN and in three patients with HFS. All patients had an excellent surgical outcome. CONCLUSIONS: Presurgical simulation by VE in patients with TN and HFS is a novel method that provides excellent visualization of the 3-D relations of neurovascular structures in the CPA region and allows us to accomplish successful and safe surgery.

Stereotactic radiofrequency thermocoagulation for hypothalamic hamartoma with intractable gelastic seizures. International journal

Junpei Homma, Shigeki Kameyama, Hiroshi Masuda, Takehiko Ueno, Ayataka Fujimoto, Makoto Oishi, Masafumi Fukuda

Epilepsy research 76 ( 1 ) 15 - 21 2007.8

Language：English Publishing type：Research paper (scientific journal)

Management of hypothalamic hamartoma with intractable gelastic epilepsy remains controversial. We have used stereotactic thermocoagulation for treatment of hypothalamic hamartoma with intractable gelastic epilepsy since 1997. Herein, we review our experience in five cases to clarify the usefulness of this treatment. A total of five patients with hypothalamic hamartoma were treated by stereotactic thermocoagulation at our hospital during the period October 1997 through February 2004. In all patients, the hamartoma was less than 10mm in diameter and was located on the floor of the third ventricle with sessile attachment to the wall. To identify ictal onset, chronic intracranial electroencephalography was performed in three patients with the use of a depth electrode implanted in the hamartoma. Attempts were made to induce gelastic seizure by electrical stimulation of the hamartoma in three patients. After magnetic resonance imaging-guided targeting, radiofrequency thermocoagulation of the boundary between the hamartoma and normal hypothalamus was performed to achieve disconnection effects. Marked reductions in seizure frequency were obtained in all cases, with three patients becoming seizure-free after the procedure. No intraoperative complications occurred except in one patient who experienced acute and transient panidrosis with hot flushes during coagulation. Our results suggest that stereotactic thermocoagulation of hypothalamic hamartoma is an acceptable treatment option for patients with intractable gelastic seizures.

[A case of solitary fibrous tumor in the cerebral convexity indicating its non-dural origin].

Masakazu Sano, Akihiko Saito, Yasushi Nishihira, Makoto Oishi, Akiyoshi Kakita, Hitoshi Takahashi, Yukihiko Fujii

No shinkei geka. Neurological surgery 35 ( 7 ) 697 - 702 2007.7

Language：Japanese Publishing type：Research paper (scientific journal)

We report a case of solitary fibrous tumor (SFT) in the cerebral convexity, and present characteristic radiological and surgical findings to determine its origin. The patient was a 59-year-old man with mental dullness and mild gait disturbance. CT scan and MR images showed a highly enhanced large mass lesion mimicking a meningioma in the left parietal convexity. However, neither dural enhancement nor tail sign indicative of meningioma was observed. Angiography showed prominent feedings from branches of the internal carotid and basilar arteries rather than the external carotid artery. For this reason, presurgically, we suggested hemangiopericytoma or other specific meningiomas as a differential diagnoses. Surgery confirmed that the tumor had no attachment to the dura mater and was covered by the arachnoid membrane. The bottom of the tumor adhered tightly to brain tissue. The origin was considered to be the brain surface, pia mater or a part of the arachnoid membrane. Histopathologically, the tumor was diagnosed as a SFT with findings of "attemless pattern" and diffuse CD34 staining. The radiological and surgical findings of the present case indicated in the cerebral convexity as a unique site of origin of SFT.

[New diagnostic imaging methods in neurosurgery: advent of anatomical and functional neuroimaging].

Makoto Oishi, Takeo Uzuka, Yuichiro Yoneoka, Yukihiko Fujii, Hironaka Igarashi

No shinkei geka. Neurological surgery 35 ( 3 ) 291 - 300 2007.3

Language：Japanese Publishing type：Research paper (scientific journal)

Progress in imaging techniques has contributed to improvements in reliable diagnosis and surgical decision making in neurosurgery. From the viewpoint of neurosurgeons, there are two major needs in the development of imaging techniques. One is greater accuracy in demonstrating the anatomy of the brain at microscopic resolutions and the other is visualization of function or metabolism that is invisible on surgical views. Use of 3.0 T magnetic resonance imaging (MRI) in clinical patients has revealed anatomy appropriate for microsurgery at high resolution, and three-dimensional reconstruction of MRI on high-specification computers helps neurosurgeons to understand the anatomy of the brain in individual patients. Functional imaging methods such as functional MRI, positron emission tomography, and magnetoencephalography have provided new insights in brain surgery, visualizing various cerebral functions on anatomic images. Recently, diffusion tensor imaging is used to visualize neural tracts passing through subcortical white matter and MR spectroscopy is used to show the metabolic status of lesions. These tools are also forms of functional imaging. New noninvasive imaging techniques are still being developed to visualize function more easily. Here, we summarize the roles of recent imaging techniques in our previous studies and discuss the future of imaging in neurosurgery.

Unusual giant cerebral venous varix associated with brain abscess: variant of hereditary hemorrhagic telangiectasia--case report.

Makoto Oishi, Osamu Sasaki, Shinji Nakazato, Kenji Suzuki, Keiko Kitazawa, Tetsuro Takao, Tetsuo Koike

Neurologia medico-chirurgica 47 ( 2 ) 74 - 8 2007.2

Language：English Publishing type：Research paper (scientific journal)

A 35-year-old man suffered secondary generalized tonic-clonic convulsions due to a large brain abscess. Neuroimaging incidentally revealed another tumor-like lesion. Cerebral angiography confirmed that the lesion was an unusual giant venous varix associated with a high-flow pial arteriovenous fistula (AVF) and showed one more small arteriovenous malformation (AVM). Pulmonary AVF, which can cause brain abscess, was also detected. Surgical ligation of the AVF and removal of the small AVM via individual craniotomies resulted in successful extirpation of the cerebrovascular malformations. Although the typical mucocutaneous symptoms were absent in this patient, the combination of arteriovenous anomalies was highly suggestive of hereditary hemorrhagic telangiectasia.

Magnetoencephalography in patients with tuberous sclerosis and localization-related epilepsy. International journal

Takanori Kamimura, Jun Tohyama, Makoto Oishi, Noriyuki Akasaka, Osamu Kanazawa, Mutsuo Sasagawa, Mitsuhiro Kato, Kousaku Ohno, Hiroshi Masuda, Shigeki Kameyama, Makoto Uchiyama

Epilepsia 47 ( 6 ) 991 - 7 2006.6

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: To clarify the usefulness of magnetoencephalography (MEG) for diagnosis of the spatial relations between spike foci and suspicious epileptogenic tubers on MRI in patients with tuberous sclerosis (TS) and to compare MEG spike foci with single-photon emission computed tomography (SPECT) findings. METHODS: We analyzed magnetic fields of epileptic spike discharges in 15 patients with TS and localization-related epilepsy (LRE) by using MEG (a whole-head 204-channel magnetometer system). We investigated the spatial relation between the equivalent current dipoles (ECDs) of interictal spike discharges and visible cortical tubers on MRI. We also compared results of MEG and MRI with SPECT findings. RESULTS: MEG detected a cluster of ECDs around one cortical tuber in six of 15 patients and clusters of ECDs around two cortical tubers in five patients. Interictal SPECT was disappointing in detection of epileptic foci in TS. However, MEG spike foci showed spatial consistency with ictal hyperperfusion areas in two patients. Three patients with single ECD clusters underwent surgical treatment: two have been seizure free, and one has obtained seizure reduction of >90%. CONCLUSIONS: ECDs were located around visible tuber nodules. MEG enabled precise localization of the epileptic foci and provided crucial information for surgical treatment in patients with TS and partial epilepsy. TS patients showing a single ECD cluster on MEG may be appropriate candidates for surgical treatment.

Single and multiple clusters of magnetoencephalographic dipoles in neocortical epilepsy: significance in characterizing the epileptogenic zone. International journal

Makoto Oishi, Shigeki Kameyama, Hiroshi Masuda, Jun Tohyama, Osamu Kanazawa, Mutsuo Sasagawa, Hiroshi Otsubo

Epilepsia 47 ( 2 ) 355 - 64 2006.2

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: To characterize the epileptogenic zone in neocortical epilepsy (NE) by using magnetoencephalography (MEG). METHODS: We defined and compared locations of single and multiple clusters of equivalent current dipoles (ECDs) for interictal spikes with MRI findings, ictal-onset zones (IOZs) from subdural electroencephalography (SDEEG), resected areas, and postsurgical outcomes of 20 patients who underwent cortical resection for medically intractable NE. RESULTS: Fourteen patients had single clusters; six had multiple clusters. Overlap of clusters and IOZs defined group A (nine patients), in which a single cluster coincided with the IOZ; group B1 (four patients), in which a single cluster was within or partially overlapped the IOZ; group B2 (five patients), in which multiple-cluster sections overlapped IOZs; group C (two patients; one single; one multiple), in which no overlap was seen. More single clusters (nine of 14) than multiple clusters (none of six) coincided with the IOZ (p = 0.014). More patients with single clusters (10 of 14) than patients with multiple clusters (one of six) had seizure-free outcomes (p = 0.049). Eight of nine patients in group A, versus three of 11 in groups B1, B2, and C, achieved seizure-free outcomes (p = 0.0098). Correlations between MRI findings and postsurgical outcomes were not statistically significant; eight of 13 patients with single lesions, one of four with no lesions, and two of three with multifocal lesions had seizure-free outcomes. CONCLUSIONS: In neocortical epilepsy, MEG ECD clusters correlated with SDEEG IOZs. Single clusters indicated discrete epileptogenic zones that required complete resection for seizure-free outcome. Multiple clusters necessitated that the multiple or extensive epileptogenic zones be completely identified and delineated by SDEEG.

Characterizing magnetic spike sources by using magnetoencephalography-guided neuronavigation in epilepsy surgery in pediatric patients. International journal

Koji Iida, Hiroshi Otsubo, Yuuri Matsumoto, Ayako Ochi, Makoto Oishi, Stephanie Holowka, Elizabeth Pang, Irene Elliott, Shelly K Weiss, Sylvester H Chuang, O Carter Snead 3rd, James T Rutka

Journal of neurosurgery 102 ( 2 Suppl ) 187 - 96 2005.3

Language：English Publishing type：Research paper (scientific journal)

OBJECT: The authors sought to validate magnetoencephalography spike sources (MEGSSs) in neuronavigation during epilepsy surgery in pediatric patients. METHODS: The distributions of MEGSSs in 16 children were defined and classified as clusters (Class I), greater than or equal to 20 MEGSSs with 1 cm or less between MEGSSs; small clusters (Class II), 6 to 19 with 1 cm or less between; and scatters (Class III), less than 6 or greater than 1 cm between spike sources. Using neuronavigation, the MEGSSs were correlated to epileptic zones from intra- and extraoperative electrocorticography (ECoG), surgical procedures, disease entities, and seizure outcomes. Thirteen patients underwent MEGSSs: nine had clusters; two had small clusters, one with and one without clusters; and three had scatters alone. All 13 had scatters. Clusters localized within and extended from areas of cortical dysplasia and at margins of tumors or cystic lesions. All clusters were colocalized to ECoG-defined epileptic zones. Four of 10 patients with clusters and/or small clusters underwent complete excisions, and six underwent partial excision with or without multiple subpial transections. In the three patients with scatters alone, ECoG revealed epileptic zones buried within MEGSS areas; these regions of scatters were completely excised and treated with multiple subpial transections. Coexisting scatters were left untreated in nine of 10 patients. Postoperatively, nine of 13 patients were seizure free; the four patients with residual seizures had clusters in unresected eloquent cortex. Three patients in whom no MEGSSs were demonstrated underwent lesionectomies and were seizure free. CONCLUSIONS: Magnetoencephalography spike source clusters indicate an epileptic zone requiring complete excision. Coexisting scatters remote from clusters are nonepileptogenic and do not require excision. Scatters alone, however, should be examined by ECoG; an epileptic zone may exist within these distributions.

Cortical activation in area 3b related to finger movement: an MEG study. International journal

Makoto Oishi, Shigeki Kameyama, Masafumi Fukuda, Kuniko Tsuchiya, Toru Kondo

Neuroreport 15 ( 1 ) 57 - 62 2004.1

Language：English Publishing type：Research paper (scientific journal)

To evaluate cortical activation reflecting sensory feedback after finger movement, we recorded movement-related cerebral fields (MRCFs) following voluntary finger movement and somatosensory evoked fields for mixed (median) and pure cutaneous (radial) nerve stimulations (mSEFs and rSEFs) in six normal subjects. Equivalent current dipoles for movement-evoked field 1 (MEF1) in MRCFs and the component (70m) obtained in mSEFs, not clearly in rSEFs, were similarly distributed in each subject. They were located in area 3b, but both mean locations were significantly (p < 0.01) medial to N20m in mSEFs. MEF1 and 70m reflect similar cortical activities related to finger movement and have the same neuronal generator in area 3b, which is different from that of N20m.

Epileptic spikes: magnetoencephalography versus simultaneous electrocorticography. International journal

Makoto Oishi, Hiroshi Otsubo, Shigeki Kameyama, Nobuhito Morota, Hiroshi Masuda, Masaomi Kitayama, Ryuichi Tanaka

Epilepsia 43 ( 11 ) 1390 - 5 2002.11

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: To test the sensitivity of extracranial magnetoencephalography (MEG) for epileptic spikes in different cerebral sites. METHODS: We simultaneously recorded MEG and electrocorticography (ECoG) by using subdural electrodes with 1-cm interelectrode distances for one patient with lateral frontal epilepsy and one patient with basal temporal epilepsy. We analyzed MEG spikes associated with ECoG spikes and compared the maximal amplitude and number of electrodes involved. We estimated and evaluated the locations and moments of the equivalent current dipoles (ECDs) of MEG spikes. RESULTS: In patient 1, MEG detected 100 (53%) of 188 ECoG lateral frontal spikes, including 31 (46%) of 67 spikes that activated three subdural electrodes. MEG spike amplitudes correlated with ECoG spike amplitudes and the number of electrodes activated (p < 0.01). ECDs were perpendicular to the superior frontal sulcus. In patient 2, MEG detected 31 (26%) of 121 ECoG basal temporal spikes, but none that activated only three subdural electrodes. ECDs were localized in the entorhinal and parahippocampal gyri, oriented perpendicular to those basal temporal cortical surfaces. The ECD strength was 136.6 +/- 71.5 nAm in the frontal region, but 274.5 +/- 150.6 nAm in the temporal region (p < 0.01). CONCLUSIONS: When lateral frontal ECoG spikes extend >3 cm2 across the fissure, MEG can detect >50%, correlating with spatial activation and voltage. In the basal temporal region, MEG requires higher-amplitude discharges over a more extensive area. MEG shows a significantly higher sensitivity to lateral convexity epileptic discharges than to discharges in isolated deep basal temporal regions.

Fusiform gyrus epilepsy: the use of ictal magnetoencephalography. Case report. International journal

Makoto Oishi, Shigeki Kameyama, Nobuhito Morota, Masaru Tomikawa, Manabu Wachi, Akiyoshi Kakita, Hitoshi Takahashi, Ryuichi Tanaka

Journal of neurosurgery 97 ( 1 ) 200 - 4 2002.7

Language：English Publishing type：Research paper (scientific journal)

The authors report successful presurgical identification of an epileptic focus in the fusiform gyrus by using ictal magnetoencephalography (MEG), which was performed with the aid of an advanced whole-brain neuromagnetometer. A 22-year-old man had suffered from medically refractory complex partial seizures since he was 10 years of age. Seizure symptoms, magnetic resonance imaging, and ictal single-photon emission computerized tomography examinations indicated right temporal lobe epilepsy; however, ictal electroencephalography, including sphenoidal recordings, failed even to lateralize the seizure focus. The MEG studies revealed that equivalent current dipoles of interictal activities were scattered bilaterally around the medial temporal structures, but those of ictal onset and postictal activities formed a cluster in the left fusiform gyrus. After confirmation of each ictal and interictal MEG finding by using long-term electrocorticography recordings, focal cortical resection of the left inferior temporal and fusiform gyri was performed. The histopathological diagnosis was cortical dysplasia, and the patient has achieved a good seizure outcome, now 15 months after the operation. Ictal and also postictal MEG may be more specific than interictal MEG for identifying the ictal onset zone.

[Presurgical functional mapping of the sensorimotor area using evoked magnetic fields].

Makoto Oishi, Shigeki Kameyama, Masatoshi Watanabe, Tadashi Kawaguchi, Nobuhito Morota, Masaru Tomikawa, Hiroshi Masuda, Hideaki Takahashi, Ryuichi Tanaka

No shinkei geka. Neurological surgery 30 ( 4 ) 391 - 7 2002.4

Language：Japanese Publishing type：Research paper (scientific journal)

In the present study, we evaluated the usefulness of magnetoencephalography (MEG) for presurgical identification of not only the central sulcus by somatosensory evoked magnetic fields (SEFs), which is a well-known, reliable technique, but also the primary hand motor area by movement-related cerebral magnetic fields (MRCFs). Subjects were 10 patients with brain tumor (6 glial tumors, 3 cavernous angiomas, and 1 metastatic tumor) around the sensorimotor area. Identification of the central sulcus by SEF responses to multiple sites of stimulation (median nerve, tibial nerve, thumb, and lower lip) was performed in all patients, and identification of the hand motor area by MRCF responses to the index finger extension task was made in 9. All MEG data were superimposed on sectional or three-dimensional magnetic resonance (MR) images. The central sulcus was clerAly identified by SEFs in all patients, even in 5 whose MR images showed severe distortion, and the primary hand motor area was identified by MRCFs in 6 of 9 patients. The central sulcus and primary motor area identified by MEG were confirmed by cortical recording of somatosensory evoked potentials in response to median nerve stimulation in 7 patients and motor evoked potentials in response to direct cortical stimulation in 5. All patients underwent tumor removal guided by functional mapping by MEG and experienced no surgical complications. In conclusion, MEG is a useful tool in presurgical functional mapping of the sensorimotor area. This is the first report of a case in which identification of the hand motor area by MRCFs was used in a clinical setting.

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