研究者詳細

顔写真

シモダ　ヨシテル
下田　由輝
Yoshiteru Shimoda
所属
病院　脳・神経・精神科　脳神経外科
職名
助教
学位

  • 博士（医学）（東北大学）

研究キーワード 1

  • 脳腫瘍

研究分野 1

  • ライフサイエンス / 脳神経外科学 /

論文 57

  1. Perforating artery injury as a critical factor besides cortical dysfunction in motor deficit after peri-rolandic epilepsy surgery. 国際誌

    Atsuhiko Ninomiya, Shin-Ichiro Osawa, Kyoko Suzuki, Kazuo Kakinuma, Kazushi Ukishiro, Yoshiteru Shimoda, Kazutaka Jin, Mitsugu Uematsu, Shiho Sato, Shunji Mugikura, Hiroyoshi Suzuki, Hajime Miyata, Shingo Kayano, Nobukazu Nakasato, Hidenori Endo

    Journal of neurosurgery　1-13　2025年2月14日

    DOI： 10.3171/2024.10.JNS24878 　

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    OBJECTIVE: Surgery for peri-rolandic epilepsy requires appropriate consideration to balance the functional risk of postoperative motor deficit and seizure outcome. Based on voxel-based morphometric analysis, the authors hypothesized that cortical damage and ischemic subcortical damage related to surgery could affect postoperative motor deterioration. METHODS: Sixteen patients with peri-rolandic epilepsy who underwent resective surgery at a single institution were retrospectively investigated. Their imaging findings, postoperative seizure outcomes, and postoperative neurological deteriorations in motor function, as well as duration, were analyzed. Using the standardized MRI data of each case, the authors examined the surgically resected area on high-resolution 3D MR images and the high-intensity area on diffusion-weighted images, which were converted to voxel data. These voxel data were superimposed on a standard brain image for neuroimaging assessment. Postoperative motor deterioration of the orofacial region, upper limb, or lower limb was noted as no, transient, or permanent deterioration and analyzed in relation to the surgically resected area and subcortical damage. Univariate analysis of the clinical factors was conducted between cases with permanent upper- and/or lower-limb motor deterioration and those with no or transient deterioration. RESULTS: The mean follow-up period was 28 months. Ten patients (62.5%) achieved Engel class I. Fourteen patients (87.5%) experienced postoperative motor deteriorations in the following areas (no/transient/permanent): orofacial (11/5/0), upper limb (9/5/2), and lower limb (9/3/4). All cases with orofacial motor deterioration underwent cortical resection of the inferior third of the peri-rolandic cortex. Cortical resection of the precentral gyrus only, in contrast to both the precentral and postcentral gyri, was not associated with permanent upper- and/or lower-limb motor deterioration. Cortical resection involving the postcentral gyrus was significantly associated with permanent upper- and/or lower-limb motor deterioration in 4 cases (25.0%). Surgically related perforating artery injury caused ischemic subcortical damage, which was significantly associated with postoperative transient or permanent motor deterioration by extending to the corticospinal tract (CST). CONCLUSIONS: Postoperative motor deterioration for peri-rolandic epilepsy was related to both the resected cortex and ischemic subcortical damage. In peri-rolandic epilepsy, cortical resection of the precentral gyrus might not necessarily cause permanent upper- and/or lower-limb motor deterioration because of the functional reserve in other peri-rolandic areas outside the epileptic focus. On the other hand, cortical resection of the postcentral gyrus could cause permanent upper- and/or lower-limb motor deterioration because of injury to the vasculature, which is crucial for the descending motor pathway in the CST.

  2. Clinical effect of ventricular entry during resection of IDH-wildtype glioblastoma: A multi-institutional analysis. 国際誌

    Yoshiteru Shimoda, Ichiyo Shibahara, Masayuki Kanamori, Ken-Ichiro Matsuda, Ryuta Saito, Atsushi Hozawa, Toshihiro Kumabe, Hidenori Endo, Teiji Tominaga, Yukihiko Sonoda

    World neurosurgery　123643-123643　2025年1月8日

    DOI： 10.1016/j.wneu.2024.123643 　

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    PURPOSE: Glioblastomas contacting the subventricular zone (SVZ) are associated with poor prognosis and the impact of ventricular entry (VE) during resection remains controversial. Since glioblastomas with SVZ involvement often require VE, both SVZ involvement and VE are confounding factors. This study aimed to evaluate the effect of VE during glioblastoma resection by comparing patients with and without SVZ involvement. METHODS: This multi-institutional retrospective study reviewed newly diagnosed isocitrate dehydrogenase (IDH)-wildtype glioblastoma who underwent resection. The focus was on VE, complications, and recurrence patterns based on SVZ status. RESULTS: A total of 418 patients were included. with 278 (66.5%) undergoing VE and 140 (33.5 %) without. Patients with VE had significantly shorter overall survival (OS) than those without VE (18.6 vs. 25.6 months, p = 0.008). VE was more common in patients with SVZ tumors (94.2%) compared to non-SVZ tumors (26.3%, p < 0.0001). Notably, 44 patients with non-SVZ tumors experienced VE, whereas 15 patients with SVZ tumors did not. Regardless of SVZ status, VE did not affect the rates of complications, such as symptomatic subdural effusion, hydrocephalus, infection, or nonlocal recurrence. OS was similar with each group: for SVZ tumors, OS was 17.7 months with VE vs. 19.9 months without VE (p = 0.34), and for non-SVZ tumors, OS was 30.8 months with VE vs. 25.6 months without VE (p = 0.63). CONCLUSIONS: VE during glioblastoma resection does not impact complications or nonlocal recurrence. Surgeons may safely perform VE during resection of both SVZ and non-SVZ glioblastomas without adverse effects.

  3. 選択的麻酔薬動注と認知神経学的評価を組み合わせた精密な脳機能評価

    大沢 伸一郎, 鈴木 匡子, 柿沼 一雄, 勝頼 一登, 浮城 一司, 金森 政之, 下田 由輝, 新妻 邦泰, 松本 康史, 神 一敬, 中里 信和, 遠藤 英徳

    てんかん研究　42　(3)　664-665　2025年1月

    出版者・発行元： (一社)日本てんかん学会

    ISSN：0912-0890

    eISSN：1347-5509

  4. Efficacy and safety of carmustine wafers, followed by radiation, temozolomide, and bevacizumab therapy, for newly diagnosed glioblastoma with maximal resection.

    Masayuki Kanamori, Ichiyo Shibahara, Yoshiteru Shimoda, Yukinori Akiyama, Takaaki Beppu, Shigeo Ohba, Toshiyuki Enomoto, Takahiro Ono, Yuta Mitobe, Mitsuto Hanihara, Yohei Mineharu, Joji Ishida, Kenichiro Asano, Yasuyuki Yoshida, Manabu Natsumeda, Sadahiro Nomura, Tatsuya Abe, Hajime Yonezawa, Ryuichi Katakura, Soichiro Shibui, Toshihiko Kuroiwa, Hiroyoshi Suzuki, Hidehiro Takei, Haruo Matsushita, Ryuta Saito, Yoshiki Arakawa, Yukihiko Sonoda, Yuichi Hirose, Toshihiro Kumabe, Takuhiro Yamaguchi, Hidenori Endo, Teiji Tominaga

    International journal of clinical oncology　30　(1)　51-61　2025年1月

    DOI： 10.1007/s10147-024-02650-9 　

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    BACKGROUND: To improve the outcome in newly diagnosed glioblastoma patients with maximal resection, we aimed to evaluate the efficacy and safety of implantation of carmustine wafers (CWs), radiation concomitant with temozolomide and bevacizumab, and maintenance chemotherapy with six cycles of temozolomide and bevacizumab. METHOD: This prospective phase II study enrolled glioblastoma patients considered candidates for complete resection (> 90%) of a contrast-enhanced lesion. The CWs were intraoperatively implanted into the resection cavity after achieving maximal resection. Patients without a measurable contrast-enhanced lesion on magnetic resonance imaging within 48 h after resection received concomitant radiotherapy and chemotherapy with temozolomide and bevacizumab, followed by maintenance treatment with up to six cycles of temozolomide and bevacizumab. The primary endpoint was the 2-year overall survival rate in glioblastoma patients with protocol treatment. RESULTS: From October 2015 to April 2018, we obtained consent for the first registration from 70 patients across 17 institutions in Japan, and 49 patients were treated according to the protocol. We evaluated the safety in 49 patients who were part of the second registration and the efficacy in 45 glioblastoma patients treated according to the protocol. The profile of hematological and most of the non-hematological adverse effects was similar to that in previous studies, but stroke occurred in 12% of cases (6/49 patients). The estimated 2-year overall survival rate was 51.3%. CONCLUSION: Implantation of CWs, followed by concomitant radiation, temozolomide, and bevacizumab, and six cycles of temozolomide and bevacizumab may offer some benefit to survival in Japanese glioblastoma patients with maximal resection. TRIAL ID: jRCTs021180007.

  5. Residual Pattern of the Hyperintense Area on T2-Weighted Magnetic Resonance Imaging After Initial Treatment Predicts the Pattern and Location of Recurrence in Patients with Newly Diagnosed Glioblastoma. 国際誌

    Yoshiteru Shimoda, Masayuki Kanamori, Shota Yamashita, Ichiyo Shibahara, Rei Umezawa, Shunji Mugikura, Keiichi Jingu, Ryuta Saito, Yukihiko Sonoda, Toshihiro Kumabe, Hidenori Endo

    World neurosurgery　193　517-532　2024年11月12日

    DOI： 10.1016/j.wneu.2024.10.012 　

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    OBJECTIVE: This study examined the clinical significance of residual hyperintense area on T2-weighted magnetic resonance imaging (T2R) without gadolinium-enhanced lesions at the end of initial treatment (debulking surgery, concomitant radiotherapy, and temozolomide) in patients with glioblastoma. METHODS: Among 150 glioblastoma cases, 77 cases without enhanced lesions at the end of initial treatment and without factors modifying the distribution of residual hyperintense area or pattern of recurrence were included. We retrospectively reviewed the relationship of residual hyperintense area after initial treatment with progression-free survival (PFS), overall survival (OS), and pattern of recurrence. RESULTS: In these 77 cases, the median PFS and OS were 12.4 and 27.4 months, respectively. At the end of initial treatment, 55 (71.4%) cases had residual hyperintense area (T2 residual group, T2R), whereas 22 (28.6%) showed no hyperintense area (T2 disappeared group, disappeared hyperintense area on T2-weighted magnetic resonance imaging [T2D]). Based on univariate and multivariate analyses, the residual hyperintense area after initial treatment was not a prognostic factor for PFS or OS. Distant recurrences occurred more frequently in the T2D group than in the T2R group 50.0% versus 9.5%. In the T2R group, the recurrence site coincided with the residual hyperintense area in 36 (85.7%) of 42 recurrences. CONCLUSIONS: The T2R at the end of initial treatment can predict local recurrence. However, the distant recurrence occurred frequently in T2D group. Thus, attention should be paid to local recurrences in T2R group and distant recurrences in T2D group.

  6. 麻酔薬の頭蓋内選択的動注と認知神経学的評価を融合した任意脳領域の機能局在診断法

    大沢 伸一郎, 鈴木 匡子, 柿沼 一雄, 勝瀬 一登, 浮城 一司, 金森 政之, 下田 由輝, 新妻 邦泰, 松本 康史, 神 一敬, 中里 信和, 遠藤 英徳

    日本脳神経血管内治療学会学術集会抄録集　40回　330-330　2024年11月

    出版者・発行元： (一社)日本脳神経血管内治療学会

    eISSN：2759-6907

  7. Clinical significance of cerebral microbleeds in patients with germinoma who underwent long-term follow-up. 国際誌

    Masayuki Kanamori, Shunji Mugikura, Osamu Iizuka, Naoko Mori, Yoshiteru Shimoda, Ichiyo Shibahara, Rei Umezawa, Keiichi Jingu, Ryuta Saito, Yukihiko Sonoda, Toshihiro Kumabe, Kyoko Suzuki, Hidenori Endo

    Journal of neuro-oncology　170　(1)　173-184　2024年10月

    DOI： 10.1007/s11060-024-04753-9 　

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    PURPOSE: This study identified the factors affecting cerebral microbleed (CMBs) development. Moreover, their effects on intelligence and memory and association with stroke in patients with germinoma who had long-term follow-up were evaluated. METHODS: This study included 64 patients with germinoma who were histologically and clinically diagnosed with and treated for germinoma. These patients were evaluated cross-sectionally, with a focus on CMBs on susceptibility-weighted magnetic resonance imaging (SWI), brain atrophy assessed through volumetric analysis, and intelligence and memory. RESULTS: The follow-up period was from 32 to 412 (median: 175.5) months. In total, 43 (67%) patients had 509 CMBs and 21 did not have CMBs. Moderate correlations were observed between the number of CMBs and time from initial treatments and recurrence was found to be a risk factor for CMB development. Increased temporal CMBs had a marginal effect on the processing speed and visual memory, whereas brain atrophy had a statistically significant effect on verbal, visual, and general memory and a marginal effect on processing speed. Before SWI acquisition and during the follow-up periods, eight strokes occurred in four patients. All of these patients had ≥ 15 CMBs on SWI before stroke onset. Meanwhile, 33 patients with < 14 CMBs or 21 patients without CMBs did not experience stroke. CONCLUSION: Patients with a longer time from treatment initiation had a higher number of CMBs, and recurrence was a significant risk factor for CMB development. Furthermore, brain atrophy had a stronger effect on memory than CMBs. Increased CMBs predict the stroke onset.

  8. 後大脳動脈で灌流される海馬周囲構造への超選択的麻酔は記憶機能のモダリティ別評価を可能にする

    大沢 伸一郎, 鈴木 匡子, 柿沼 一雄, 勝瀬 一登, 菊地 花, 浮城 一司, 石田 誠, 下田 由輝, 新妻 邦泰, 神 一敬, 中里 信和, 遠藤 英徳

    てんかん研究　42　(2)　514-514　2024年9月

    出版者・発行元： (一社)日本てんかん学会

    ISSN：0912-0890

    eISSN：1347-5509

  9. Super-selective injection of propofol into the intracranial arteries enables Patient's self-evaluation of expected neurological deficit. 国際誌

    Shin-Ichiro Osawa, Kyoko Suzuki, Kazushi Ukishiro, Kazuo Kakinuma, Makoto Ishida, Kuniyasu Niizuma, Yoshiteru Shimoda, Hana Kikuchi, Ryuzaburo Kochi, Kazutaka Jin, Yasushi Matsumoto, Mitsugu Uematsu, Nobukazu Nakasato, Hidenori Endo, Teiji Tominaga

    Cortex; a journal devoted to the study of the nervous system and behavior　176　209-220　2024年5月19日

    DOI： 10.1016/j.cortex.2024.04.016 　

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    INTRODUCTION: It is hard to realize the extent of the expected postoperative neurological deficit for patients themselves. The provision of appropriate information can contribute not only to examining surgical indications but also to filling the gap between patient and expert expectations. We hypothesized that propofol infusion into the intracranial arteries (ssWada) could induce focal neurological symptoms with preserved wakefulness, enabling the patients to evaluate the postsurgical risk subjectively. METHODS: Presurgical evaluation using ssWada was performed in 28 patients with drug-resistant epilepsy. Based on anatomical knowledge, propofol was super-selectively infused into the intracranial arteries including the M1, M2, and M3 segments of the middle cerebral artery (MCA), A2 segment of the anterior cerebral artery, and P2 segment of the posterior cerebral artery to evaluate the neurological and cognitive symptoms. We retrospectively analyzed a total of 107 infusion trials, including their target vessels, and elicited symptoms of motor weakness, sensory disturbance, language, unilateral hemispatial neglect (UHN), and hemianopsia. We evaluated preserved wakefulness which enabled subjective evaluations of the symptoms and comparison of the subjective experience to the objective findings, besides adverse effects during the procedure. RESULTS: Preserved wakefulness was found in 97.2% of all trials. Changes in neurological symptoms were positively evaluated for motor weakness in 51.4%, sensory disturbance in 5.6%, language in 48.6%, UHN in 22.4%, and hemianopsia in 32.7%. Six trials elicited seizures. Multivariate analysis showed significant correlations between symptom and infusion site of language and left side, language and MCA branches, motor weakness and A2 or M2 superior division, and hemianopsia and P2. Transient adverse effect was observed in 8 cases with 12 infusion trials (11.2 %). CONCLUSION: The ssWada could elicit focal neurological symptoms with preserved wakefulness. The methodology enables specific evaluation of risk for cortical resection and subjective evaluation of the expected outcome by the patients.

  10. Distinguishing IDH mutation status in gliomas using FTIR-ATR spectra of peripheral blood plasma indicating clear traces of protein amyloid aggregation. 国際誌

    Saiko Kino, Masayuki Kanamori, Yoshiteru Shimoda, Kuniyasu Niizuma, Hidenori Endo, Yuji Matsuura

    BMC cancer　24　(1)　222-222　2024年2月16日

    DOI： 10.1186/s12885-024-11970-y 　

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    BACKGROUND: Glioma is a primary brain tumor and the assessment of its molecular profile in a minimally invasive manner is important in determining treatment strategies. Among the molecular abnormalities of gliomas, mutations in the isocitrate dehydrogenase (IDH) gene are strong predictors of treatment sensitivity and prognosis. In this study, we attempted to non-invasively diagnose glioma development and the presence of IDH mutations using multivariate analysis of the plasma mid-infrared absorption spectra for a comprehensive and sensitive view of changes in blood components associated with the disease and genetic mutations. These component changes are discussed in terms of absorption wavenumbers that contribute to differentiation. METHODS: Plasma samples were collected at our institutes from 84 patients with glioma (13 oligodendrogliomas, 17 IDH-mutant astrocytoma, 7 IDH wild-type diffuse glioma, and 47 glioblastomas) before treatment initiation and 72 healthy participants. FTIR-ATR spectra were obtained for each plasma sample, and PLS discriminant analysis was performed using the absorbance of each wavenumber in the fingerprint region of biomolecules as the explanatory variable. This data was used to distinguish patients with glioma from healthy participants and diagnose the presence of IDH mutations. RESULTS: The derived classification algorithm distinguished the patients with glioma from healthy participants with 83% accuracy (area under the curve (AUC) in receiver operating characteristic (ROC) = 0.908) and diagnosed the presence of IDH mutation with 75% accuracy (AUC = 0.752 in ROC) in cross-validation using 30% of the total test data. The characteristic changes in the absorption spectra suggest an increase in the ratio of β-sheet structures in the conformational composition of blood proteins of patients with glioma. Furthermore, these changes were more pronounced in patients with IDH-mutant gliomas. CONCLUSIONS: The plasma infrared absorption spectra could be used to diagnose gliomas and the presence of IDH mutations in gliomas with a high degree of accuracy. The spectral shape of the protein absorption band showed that the ratio of β-sheet structures in blood proteins was significantly higher in patients with glioma than in healthy participants, and protein aggregation was a distinct feature in patients with glioma with IDH mutations.

  11. Distant recurrence in the cerebellar dentate nucleus through the dentato-rubro-thalamo-cortical pathway in supratentorial glioma cases. 国際誌

    Masayuki Kanamori, Yohei Morishita, Yoshiteru Shimoda, Eiko Yamamori, Shiho Sato, Yoshinari Osada, Shin-Ichiro Osawa, Ichiyo Shibahara, Ryuta Saito, Yukihiko Sonoda, Toshihiro Kumabe, Hidenori Endo

    Acta neurochirurgica　166　(1)　83-83　2024年2月14日

    DOI： 10.1007/s00701-024-05981-8 　

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    BACKGROUND: Distant recurrence can occur by infiltration along white matter tracts or dissemination through the cerebrospinal fluid (CSF). This study aimed to clarify the clinical features and mechanisms of recurrence in the dentate nucleus (DN) in patients with supratentorial gliomas. Based on the review of our patients, we verified the hypothesis that distant DN recurrence from a supratentorial lesion occurs through the dentato-rubro-thalamo-cortical (DRTC) pathway. METHODS: A total of 380 patients with supratentorial astrocytoma, isocitrate dehydrogenase (IDH)-mutant (astrocytoma), oligodendroglioma, IDH mutant and 1p/19q-codeleted (oligodendroglioma), glioblastoma, IDH-wild type (GB), and thalamic diffuse midline glioma, H3 K27-altered (DMG), who underwent tumor resection at our department from 2009 to 2022 were included in this study. Recurrence patterns were reviewed. Additionally, clinical features and magnetic resonance imaging findings before treatment, at the appearance of an abnormal signal, and at further progression due to delayed diagnosis or after salvage treatment of cases with recurrence in the DN were reviewed. RESULTS: Of the 380 patients, 8 (2.1%) had first recurrence in the DN, 3 were asymptomatic when abnormal signals appeared, and 5 were diagnosed within one month after the onset of symptoms. Recurrence in the DN developed in 8 (7.4%) of 108 cases of astrocytoma, GB, or DMG at the frontal lobe or thalamus, whereas no other histological types or sites showed recurrence in the DN. At the time of the appearance of abnormal signals, a diffuse lesion developed at the hilus of the DN. The patterns of further progression showed that the lesions extended to the superior cerebellar peduncle, tectum, tegmentum, red nucleus, thalamus, and internal capsule along the DRTC pathway. CONCLUSION: Distant recurrence along the DRTC pathway is not rare in astrocytomas, GB, or DMG at the frontal lobe or thalamus. Recurrence in the DN developed as a result of the infiltration of tumor cells through the DRTC pathway, not dissemination through the CSF.

  12. Selenoprotein P expression in glioblastoma as a regulator of ferroptosis sensitivity: preservation of GPX4 via the cycling-selenium storage 国際誌

    Xi Zheng, Takashi Toyama, Stephanie Siu, Takayuki Kaneko, Hikari Sugiura, Shota Yamashita, Yoshiteru Shimoda, Masayuki Kanamori, Kotoko Arisawa, Hidenori Endo, Yoshiro Saito

    Scientific Reports　14　(1)　682-682　2024年1月5日

    出版者・発行元： Springer Science and Business Media LLC

    DOI： 10.1038/s41598-024-51259-5 　

    eISSN：2045-2322

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    Abstract Glioblastoma (GBM) is one of the most aggressive and deadly brain tumors; however, its current therapeutic strategies are limited. Selenoprotein P (SeP; SELENOP, encoded by the SELENOP gene) is a unique selenium-containing protein that exhibits high expression levels in astroglia. SeP is thought to be associated with ferroptosis sensitivity through the induction of glutathione peroxidase 4 (GPX4) via selenium supplementation. In this study, to elucidate the role of SeP in GBM, we analyzed its expression in GBM patients and found that SeP expression levels were significantly higher when compared to healthy subjects. Knock down of SeP in cultured GBM cells resulted in a decrease in GPX1 and GPX4 protein levels. Under the same conditions, cell death caused by RSL3, a ferroptosis inducer, was enhanced, however this enhancement was canceled by supplementation of selenite. These results indicate that SeP expression contributes to preserving GPX and selenium levels in an autocrine/paracrine manner, i.e., SeP regulates a dynamic cycling-selenium storage system in GBM. We also confirmed the role of SeP expression in ferroptosis sensitivity using patient-derived primary GBM cells. These findings indicate that expression of SeP in GBM can be a significant therapeutic target to overcome anticancer drug resistance.

  13. Ventriculoperitoneal Shunt Failure 3-year after Shunt Surgery Caused by Migration of Detached Ventricular Catheter into the Cranium: A Case Study of Idiopathic Normal-pressure Hydrocephalus

    Kazuo KAKINUMA, Keisuke MORIHARA, Yoshiteru SHIMODA, Nobuko KAWAKAMI, Shigenori KANNO, Mayuko OTOMO, Teiji TOMINAGA, Kyoko SUZUKI

    NMC Case Report Journal　10　9-14　2023年12月31日

    出版者・発行元： Japan Neurosurgical Society

    DOI： 10.2176/jns-nmc.2022-0162 　

    eISSN：2188-4226

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    Idiopathic normal-pressure hydrocephalus (iNPH) is a neurological disorder that typically presents with gait disturbance, cognitive impairment, and urinary incontinence. Although most patients respond to cerebrospinal-fluid shunting, some do not react well because of shunt failure. A 77-year-old female with iNPH underwent ventriculoperitoneal shunt implantation, and her gait impairment, cognitive dysfunction, and urge urinary incontinence improved. However, 3 years after shunting (at the age of 80), her symptoms gradually recurred for 3 months and she did not respond to shunt valve adjustment. Imaging studies revealed that the ventricular catheter detached from the shunt valve and migrated into the cranium. With immediate revision of the ventriculoperitoneal shunt, her gait disturbance, cognitive dysfunction, and urinary incontinence improved. When a patient whose symptoms have been relieved by cerebrospinal-fluid shunting experiences an exacerbation, it is important to suspect shunt failure, even if many years have passed since the surgery. Identifying the position of the catheter is crucial to determine the cause of shunt failure. Prompt shunt surgery for iNPH can be beneficial, even in elderly patients.

  14. 【臨床脳腫瘍学-最新の診断・治療と病態-】脳腫瘍の治療 脳腫瘍の放射線療法・他 腫瘍治療電場併用療法

    金森 政之, 下田 由輝, 遠藤 英徳

    日本臨床　81　(増刊9 臨床脳腫瘍学)　413-417　2023年12月

    出版者・発行元： (株)日本臨床社

    ISSN：0047-1852

  15. 【臨床脳腫瘍学-最新の診断・治療と病態-】脳腫瘍の治療 脳腫瘍関連合併症 脳腫瘍と静脈血栓塞栓症

    下田 由輝, 金森 政之, 遠藤 英徳

    日本臨床　81　(増刊9 臨床脳腫瘍学)　498-502　2023年12月

    出版者・発行元： (株)日本臨床社

    ISSN：0047-1852

  16. Extracellular glutamate and GABA transients at the transition from interictal spiking to seizures. 国際誌

    Yoshiteru Shimoda, Marco Leite, Robert T Graham, Jonathan S Marvin, Jeremy Hasseman, Ilya Kolb, Loren L Looger, Vincent Magloire, Dimitri M Kullmann

    Brain : a journal of neurology　2023年10月3日

    DOI： 10.1093/brain/awad336 　

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    Focal epilepsy is associated with intermittent brief population discharges (interictal spikes), which resemble sentinel spikes that often occur at the onset of seizures. Why interictal spikes self-terminate whilst seizures persist and propagate is incompletely understood. We used fluorescent glutamate and GABA sensors in an awake rodent model of neocortical seizures to resolve the spatiotemporal evolution of both neurotransmitters in the extracellular space. Interictal spikes were accompanied by brief glutamate transients which were maximal at the initiation site and rapidly propagated centrifugally. GABA transients lasted longer than glutamate transients and were maximal ∼1.5 mm from the focus where they propagated centripetally. Prior to seizure initiation GABA transients were attenuated, whilst glutamate transients increased, consistent with a progressive failure of local inhibitory restraint. As seizures increased in frequency, there was a gradual increase in the spatial extent of spike-associated glutamate transients associated with interictal spikes. Neurotransmitter imaging thus reveals a progressive collapse of an annulus of feed-forward GABA release, allowing seizures to escape from local inhibitory restraint.

  17. Simulation of the occipital transtentorial approach incorporating visualization of the cerebellar tentorium using three-dimensional computed tomography angiography and gadolinium-enhanced T1-weighted magnetic resonance imaging: technical note. 国際誌

    Yuto Shingai, Masayuki Kanamori, Yoshiteru Shimoda, Shingo Kayano, Hitoshi Nemoto, Shunji Mugikura, Ryuta Saito, Teiji Tominaga

    Neurosurgical review　46　(1)　259-259　2023年9月29日

    DOI： 10.1007/s10143-023-02170-6 　

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    The occipital transtentorial approach (OTA) is one of the useful approaches to the lesions of the pineal region, dorsal brainstem, and supracerebellar region. However, a wide operative field is sometimes difficult to obtain due to the tentorial sinus and bridging veins. This study evaluated the usefulness of preoperative simulation of OTA, specifically including the cerebellar tentorium in 9 patients. All patients underwent computed tomography angiography and venography and gadolinium-enhanced three-dimensional T1-weighted magnetic resonance images (Gd-3D-T1WI). The images were fused, and the cerebellar tentorium, vessels, and tumor were manually extracted from Gd-3D-T1WI to obtain the simulation images. Visualization of the cerebellar tentorium could discriminate between bridging veins from the occipital lobe and cerebellum, and recognize the site of bridging to the tentorial sinus and variants which may interfere with the tentorial incision. Simulation of the tentorial incision was also possible based on the relationships between the tumor, tentorial sinus, bridging vein, and cerebellar tentorium. The simulation suggested that safe tentorial incision was difficult in two sides because of the crossed tentorial sinus draining the left basal vein and draining veins from the glioblastoma. The OTA was performed in eight cases, and no difficulty was experienced in the tentorial incision in all cases. The simulation findings of the bridging vein and tentorial sinus were consistent with the intraoperative findings. Preoperative simulation including the cerebellar tentorium is useful for determining the optimum and safe side and required extent of the tentorial incision necessary for tumor resection with the OTA.

  18. Visualization of the lenticulostriate arteries, long insular arteries, and long medullary arteries on intra-arterial computed tomography angiography with ultrahigh resolution in patients with glioma. 国際誌

    Yoshinari Osada, Masayuki Kanamori, Shin-Ichiro Osawa, Shingo Kayano, Hiroki Uchida, Yoshiteru Shimoda, Shunji Mugikura, Teiji Tominaga, Hidenori Endo

    Acta neurochirurgica　165　(12)　4213-4219　2023年9月20日

    DOI： 10.1007/s00701-023-05794-1 　

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    PURPOSE: The anatomical association between the lesion and the perforating arteries supplying the pyramidal tract in insulo-opercular glioma resection should be evaluated. This study reported a novel method combining the intra-arterial administration of contrast medium and ultrahigh-resolution computed tomography angiography (UHR-IA-CTA) for visualizing the lenticulostriate arteries (LSAs), long insular arteries (LIAs), and long medullary arteries (LMAs) that supply the pyramidal tract in two patients with insulo-opercular glioma. METHODS: This method was performed by introducing a catheter to the cervical segment of the internal carotid artery. The infusion rate was set at 3 mL/s for 3 s, and the delay time from injection to scanning was determined based on the time-to-peak on angiography. On 2- and 20-mm-thick UHR-IA-CTA slab images and fusion with magnetic resonance images, the anatomical associations between the perforating arteries and the tumor and pyramidal tract were evaluated. RESULTS: This novel method clearly showed the relationship between the perforators that supply the pyramidal tract and tumor. It showed that LIAs and LMAs were far from the lesion but that the proximal LSAs were involved in both cases. Based on these results, subtotal resection was achieved without complications caused by injury of perforators. CONCLUSION: UHR-IA-CTA can be used to visualize the LSAs, LIAs, and LMAs clearly and provide useful preoperative information for insulo-opercular glioma resection.

  19. 膠芽腫に対する青色光単独治療への試み

    山下 将太, 下田 由輝, 金森 政之, 遠藤 英徳, 新妻 邦泰

    日本レーザー医学会誌　44　(3)　311-311　2023年9月

    出版者・発行元： (NPO)日本レーザー医学会

    ISSN：0288-6200

    eISSN：1881-1639

  20. Spontaneous Shrinkage of isocitrate dehydrogenase (IDH)-mutant astrocytoma caused by intra-tumoural cyst rupture: a case report. 国際誌

    Ryutaro Suzuki, Masayuki Kanamori, Ryuta Saito, Yoshiteru Shimoda, Mika Watanabe, Teiji Tominaga

    British journal of neurosurgery　1-5　2023年2月1日

    DOI： 10.1080/02688697.2023.2170328 　

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    BACKGROUND: T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign is a specific imaging finding of isocitrate dehydrogenase (IDH)-mutant astrocytomas. Histologically, a hypointense area on FLAIR images indicates the presence of microcysts. Here we report a case of IDH-mutant astrocytoma that shrunk spontaneously. CASE DESCRIPTION: A 26-year-old woman presented with a complaint of headache. Her magnetic resonance (MR) images revealed a lesion mass with a T2-FLAIR mismatch sign in the left frontal lobe. Subsequently, after 1 month, she was referred to our department, and we found that the lesion had unexpectedly shrunk; however, no further shrinkage was observed in the next 3 months. Furthermore, a biopsy was performed, and the results indicated a diagnosis of astrocytoma, IDH-mutant CNS WHO grade 3. Thus, she underwent subtotal resection. We found no neurological deficits in the patient, and she received 60 Gy of radiotherapy at the local site and chemotherapy with nimustine hydrochloride (ACNU), followed by the administration of ACNU every 8 weeks for 2 years. Overall, after 36 months of tumour resection, she was in good health and exhibited no recurrence. Notably, her histological and MR image findings suggested that the macroscopic cyst was formed by the fusion of microcysts, which is a characteristic feature of IDH-mutant astrocytoma with a T2-FLAIR mismatch sign, and that the tumour shrunk because of the rupture of the cyst in the Sylvian cistern. CONCLUSION: The present case report suggests that IDH-mutant astrocytoma cannot be ruled out even when the lesion shrinks spontaneously.

  21. A Case of Haemorrhagic-Onset Glioblastoma With Delayed Diagnosis. 国際誌

    Mayuko Otomo, Masayuki Kanamori, Shiho Sato, Yoshiteru Shimoda, Mika Watanabe, Tomohiro Kawaguchi, Ryuta Saito, Teiji Tominaga

    Cureus　15　(2)　e34672　2023年2月

    DOI： 10.7759/cureus.34672 　

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    Glioblastoma sometimes develops with acute onset due to intracerebral hemorrhage. Although it is sometimes difficult to diagnose patients with hemorrhagic-onset glioblastoma at the acute phase of intracerebral hemorrhage (ICH), the progressive enlargement of perifocal edema or the development of contrast-enhanced lesion triggers the diagnosis of glioblastoma within six months. Herein, we present a rare case of glioblastoma in which the diagnosis was delayed as long as 17 months after ICH. A 62-year-old man presented with a headache and aphasia. Computed tomography revealed ICH in the left temporal lobe. Magnetic resonance (MR) images revealed that the hematoma had a mix of isointense and surrounding hypointense lesions on T1-weighted MR images and gadolinium-enhanced lesions at the wall and the septum of the hematoma. An endoscopic evacuation of the hematoma was performed. No causative lesions were found during intraoperative and histological examinations. After seven months, abnormal signals were completely resolved on MR images, except for the small and stable enhanced lesion on three-dimensional gadolinium-enhanced T1-weighted MR imaging (3D Gd-T1WI) at the base of the hematoma, which did not change in size for seven months. However, a large gadolinium-enhanced lesion at the left temporal lobe developed 17 months after ICH. He underwent total resection of the lesion and was diagnosed with glioblastoma. He received radiation therapy and temozolomide but died of disseminated recurrence 31 months after ICH. In conclusion, this report presents a didactic case of glioblastoma in which the diagnosis of glioblastoma was delayed 17 months after ICH whereas hemorrhagic-onset glioblastoma was previously considered ruled out in cases in which six months or more have passed after ICH. In order not to overlook these cases, follow-up with 3D Gd-T1WI is essential in the case of suspected tumor-related ICH and close follow-up is recommended when the enhanced lesion does not resolve after a long period even if it does not grow.

  22. Salvage craniospinal irradiation for recurrent intracranial germinoma: a single institution analysis 国際誌

    Masayuki Kanamori, Yoshiteru Shimoda, Rei Umezawa, Osamu Iizuka, Shunji Mugikura, Kyoko Suzuki, Hisanori Ariga, Keiichi Jingu, Ryuta Saito, Yukihiko Sonoda, Toshihiro Kumabe, Teiji Tominaga

    Journal of Radiation Research　64　(2)　428-437　2023年1月5日

    出版者・発行元： Oxford University Press (OUP)

    DOI： 10.1093/jrr/rrac095 　

    ISSN：0449-3060

    eISSN：1349-9157

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    Abstract This study investigated the effectiveness and safety of low-dose salvage craniospinal irradiation (CSI) for recurrent germinoma. We retrospectively reviewed long-term tumor control and late adverse effects in 15 recurrent germinoma patients treated at our hospital between 1983 and 2019. Following the first recurrence of germinoma, seven were treated with 24–30 Gy of salvage CSI, three underwent non-CSI, and five were treated with only chemotherapy. CSI achieved a significantly better recurrence-free survival rate after the first recurrence compared to other strategies (100% vs 33%, p &amp;lt; 0.001: log-rank test). To evaluate the safety of salvage CSI, we assessed the outcomes at the final follow-up of seven patients who received salvage CSI at first recurrence and three patients who received salvage CSI at second recurrence. The median follow-up period was 220 months after initial treatment. Five patients who received 40–50 Gy of radiation therapy or underwent multiple radiation therapy before salvage CSI were classified into Group A, whereas five patients treated with platinum-based chemotherapy and 24–32 Gy of radiation therapy to the primary site, whole ventricle, or whole brain were classified into Group B. In Group A, one had endocrine dysfunction and the other had visual dysfunction. None were socially independent. Meanwhile, in Group B, no endocrine or visual dysfunction was found, and three patients were socially independent. Salvage CSI achieved excellent tumor control in recurrent germinoma and was safe in patients initially treated with low-dose radiation therapy and chemotherapy.

  23. Contemplation of the Effect of Nivolumab Plus Cabosantinib Therapy on Cerebral Hemorrhage in Patients with Brain Metastasis of Renal Cell Carcinoma: A Case Report. 国際誌

    Yasufumi Sato, Yoshihide Kawasaki, Yohei Satake, Yoshiteru Shimoda, Hiromichi Katayama, Takuma Sato, Shuichi Shimada, Naoki Kawamorita, Shinichi Yamashita, Masayuki Kanamori, Akihiro Ito

    Case reports in oncology　16　(1)　1573-1578　2023年

    DOI： 10.1159/000533785 　

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    Although the response to combination therapy has been reported in patients with brain metastases from advanced renal cancer, treatment-related cerebral hemorrhage has not been adequately studied. The CheckMate 9ER clinical trial of nivolumab and cabozantinib excluded patients with brain metastases. Therefore, the associated treatment outcomes in these patients with brain metastases are unclear. Herein, we report a case of bleeding from brain metastases in a patient with advanced renal cancer after gamma knife combination therapy with nivolumab and cabozantinib. Fortunately, the cerebral hemorrhage of the patient was alleviated by conservative treatment. Despite treatment interruption, the metastatic lesions reduced in size, and treatment was gradually resumed. In this case study, we report the risk of cerebral hemorrhage in combination therapy for brain metastasis cases, how to manage hemorrhage cases, and their prognosis.

  24. Investigation of cystine as differential diagnostic biomarker between astrocytomas and oligodendrogliomas based on global- and targeted analysis using liquid chromatography/tandem mass spectrometric analysis

    Masahiro Watanabe, Masamitsu Maekawa, Masayuki Kanamori, Minami Yamauchi, Ai Abe, Yoshiteru Shimoda, Ryuta Saito, Hidenori Endo, Nariyasu Mano

    Advances in Biomarker Sciences and Technology　5　76-85　2023年

    出版者・発行元： Elsevier BV

    DOI： 10.1016/j.abst.2023.09.001 　

    ISSN：2543-1064

  25. Delayed Recurrence of Choroid Plexus Carcinoma in the Sacral Spinal Cord 17 Years after Its Initial Presentation

    Arata NAGAI, Masayuki KANAMORI, Yoshiteru SHIMODA, Mika WATANABE, Ryuta SAITO, Toshihiro KUMABE, Toshimi AIZAWA, Teiji TOMINAGA

    NMC Case Report Journal　9　301-306　2022年12月31日

    出版者・発行元： Japan Neurosurgical Society

    DOI： 10.2176/jns-nmc.2022-0056 　

    eISSN：2188-4226

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    Choroid plexus carcinomas (CPCs) are rare malignant tumors of neuro-ectodermal origin, accounting for less than 1% of all intracranial tumors. The recurrence rates of CPCs are very high and typically occur in the short-term following surgery, even after gross total removal. Here we present a rare case of CPC with spinal metastasis, which occurred long after its initial presentation. A 25-year-old woman with a history of increased intracranial pressure underwent resection for a tumor of the fourth ventricle, with a histopathological diagnosis of CPC. After tumor resection, she received 30 Gy of radiation therapy to the craniospinal axis and 20 Gy to the primary site, followed by nimustine hydrochloride chemotherapy. The residual lesion completely responded to these treatments. She suffered sensory loss in the sacral region 13 years later, followed by refractory skin ulcer in the sacral region 17 years after the initial treatments. Magnetic resonance imaging at 17 years after the initial treatments showed tumor in the sacral region, which was enlarged upon follow-up after 18 months, causing incontinence and loss of urinary intention. She underwent tumor resection, with a histological diagnosis of recurrent CPC. She received salvage re-irradiation. This case shows that CPC can spread via the cerebrospinal fluid pathways and cause spinal metastasis, with relatively slow clinical course. The present case suggests that patients with CPCs may need long-term follow-up imaging of the total neural axis to identify late recurrence at both the primary site and spinal metastasis.

  26. 術後過灌流予測に向けた超音波血流計によるSTA-MCA bypassの血流波形計測

    古知 龍三郎, 遠藤 英徳, 鹿毛 敦史, 内田 浩喜, 下田 由輝, 冨永 悌二

    脳循環代謝　34　(1)　133-133　2022年10月

    出版者・発行元： (一社)日本脳循環代謝学会

    ISSN：0915-9401

    eISSN：2188-7519

  27. Successful recording of direct cortical motor-evoked potential from a pediatric patient under remimazolam anesthesia: a case report 国際誌

    Kotoe Kamata, Suguru Asagi, Yoshiteru Shimoda, Masayuki Kanamori, Nozomu Abe, Shigekazu Sugino, Teiji Tominaga, Masanori Yamauchi

    JA Clinical Reports　8　(1)　66-66　2022年8月22日

    出版者・発行元： Springer Science and Business Media LLC

    DOI： 10.1186/s40981-022-00555-y 　

    eISSN：2363-9024

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    Abstract Background Intraoperative motor-evoked potential (MEP) monitoring reduces postoperative motor deficits. Propofol-based total intravenous anesthesia is the gold standard for intraoperative myogenic MEPs. Although there is no contraindication to administering propofol in adults with peanut, soy, or egg allergies, its safety in children with these allergies remains unclear. Case presentation A 12-year-old girl required general anesthesia under intraoperative direct cortical MEP (dc-MEP) monitoring due to supratentorial glioma. Remimazolam-based anesthesia was selected, instead of propofol, due to the patient’s egg hypersensitivity. Stable myogenic MEPs were recorded throughout the surgery with remimazolam at 0.9 mg/kg/h and remifentanil at 0.35 μg/kg/min, following adjustments of stimulation intensity and titration of remimazolam infusion. Neither intraoperative memory nor motor deficits were present after surgery. Conclusions We present a pediatric case whose dc-MEP was recorded under remimazolam anesthesia. The cardiovascular stability and avoidance of propofol infusion syndrome with remimazolam were superior to propofol.

  28. Correction to: Methodological assessment of the reduction of dissemination risk and quantification of debris dispersion during dissection with a surgical aspirator. 国際誌

    Sosuke Kageyama, Atsuhiro Nakagawa, Tomohiro Kawaguchi, Kiyonobu Ohtani, Toshiki Endo, Manabu Kyan, Tetsuya Kusunoki, Yoshiteru Shimoda, Shin-Ichiro Osawa, Masayuki Kanamori, Kuniyasu Niizuma, Teiji Tominaga

    BMC research notes　15　(1)　279-279　2022年8月15日

    DOI： 10.1186/s13104-022-06167-0 　

  29. てんかん原性病変の切除範囲〜取り切ることの意義を考える〜 てんかん原性病変の切除範囲Focal cortical dysplasiaについて

    大沢 伸一郎, 浮城 一司, 下田 由輝, 鈴木 匡子, 神 一敬, 中里 信和, 冨永 悌二

    てんかん研究　40　(2)　273-274　2022年8月

    出版者・発行元： (一社)日本てんかん学会

    ISSN：0912-0890

    eISSN：1347-5509

  30. 混乱するlow-grade epilepsy-associated neuroepithelial tumors(LEAT)の概念 切除外科の視点からLEAT概念を考える

    大沢 伸一郎, 浮城 一司, 下田 由輝, 鈴木 匡子, 神 一敬, 中里 信和, 冨永 悌二

    てんかん研究　40　(2)　282-283　2022年8月

    出版者・発行元： (一社)日本てんかん学会

    ISSN：0912-0890

    eISSN：1347-5509

  31. てんかん診療の近未来〜デバイスと医薬品開発の最前線〜 ハイドロゲル-有機物を基材とする新規頭蓋内電極の開発

    大沢 伸一郎, 西澤 松彦, 中川 敦寛, 岩崎 真樹, 鈴木 泰汎, 下田 由輝, 中里 信和, 冨永 悌二

    てんかん研究　40　(2)　309-309　2022年8月

    出版者・発行元： (一社)日本てんかん学会

    ISSN：0912-0890

    eISSN：1347-5509

  32. Methodological assessment of the reduction of dissemination risk and quantification of debris dispersion during dissection with a surgical aspirator. 国際誌

    Sosuke Kageyama, Atsuhiro Nakagawa, Tomohiro Kawaguchi, Kiyonobu Ohtani, Toshiki Endo, Manabu Kyan, Tetsuya Kusunoki, Yoshiteru Shimoda, Shin-Ichiro Osawa, Masayuki Kanamori, Niizuma Kuniyasu, Teiji Tominaga

    BMC research notes　15　(1)　85-85　2022年3月2日

    DOI： 10.1186/s13104-022-05947-y 　

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    OBJECTIVE: We developed an actuator-driven pulsed water jet (ADPJ) device to achieve maximal lesion dissection with minimal risk of normal structural damage. Despite the unique dissection characteristics, there is a risk of dissemination of tissue dispersion; however, there is no established method to quantify the dispersion. Hence, this study aimed to assess the factors associated with dispersion and propose a simple experimental method using spectrophotometry to evaluate the degree of dispersion in a wet field. RESULTS: Methylene blue-stained brain phantom gelatin was immersed in a chamber with distilled water solution and dissected with an ADPJ. The dispersed gelatin solution was stirred and warmed to dissolve. The absorbance of the solution was measured spectrophotometrically. First, a reference standard curve was constructed to confirm the relationship between the absorbance and the amount of the dispersed gelatin. A clear proportional correlation was observed, which indicated that absorbance measurements can help evaluate the amount of dispersion. Using this method, we revealed that a high dissection force, insufficient suction, and inappropriate long distance between the nozzle tip and the target were associated with increased dispersion. This method might constitute a versatile and reliable approach to evaluate dispersion and aid in the development of surgical devices.

  33. Optogenetic stimulus-triggered acquisition of seizure resistance. 国際誌

    Yoshiteru Shimoda, Kaoru Beppu, Yoko Ikoma, Yosuke M Morizawa, Satoshi Zuguchi, Utaro Hino, Ryutaro Yano, Yuki Sugiura, Satoru Moritoh, Yugo Fukazawa, Makoto Suematsu, Hajime Mushiake, Nobukazu Nakasato, Masaki Iwasaki, Kenji F Tanaka, Teiji Tominaga, Ko Matsui

    Neurobiology of disease　163　105602-105602　2022年2月

    DOI： 10.1016/j.nbd.2021.105602 　

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    Unlike an electrical circuit, the hardware of the brain is susceptible to change. Repeated electrical brain stimulation mimics epileptogenesis. After such "kindling" process, a moderate stimulus would become sufficient in triggering a severe seizure. Here, we report that optogenetic neuronal stimulation can also convert the rat brain to a hyperexcitable state. However, continued stimulation once again converted the brain to a state that was strongly resistant to seizure induction. Histochemical examinations showed that moderate astrocyte activation was coincident with resilience acquisition. Administration of an adenosine A1 receptor antagonist instantly reverted the brain back to a hyperexcitable state, suggesting that hyperexcitability was suppressed by adenosine. Furthermore, an increase in basal adenosine was confirmed using in vivo microdialysis. Daily neuron-to-astrocyte signaling likely prompted a homeostatic increase in the endogenous actions of adenosine. Our data suggest that a certain stimulation paradigm could convert the brain circuit resilient to epilepsy without exogenous drug administration.

  34. 麻酔薬の超選択的頭蓋内動脈による神経症状誘発は脳実質切除後の機能転帰を予測する

    大沢 伸一郎, 鈴木 匡子, 浮城 一司, 柿沼 一雄, 新妻 邦泰, 下田 由輝, 神 一敬, 中里 信和, 冨永 悌二

    脳血管内治療　6　(Suppl.)　S337-S337　2021年11月

    出版者・発行元： (NPO)日本脳神経血管内治療学会

    ISSN：2423-9119

    eISSN：2424-1709

  35. 麻酔薬の超選択的頭蓋内動脈による神経症状誘発は脳実質切除後の機能転帰を予測する

    大沢 伸一郎, 鈴木 匡子, 浮城 一司, 柿沼 一雄, 新妻 邦泰, 下田 由輝, 神 一敬, 中里 信和, 冨永 悌二

    脳血管内治療　6　(Suppl.)　S337-S337　2021年11月

    出版者・発行元： (NPO)日本脳神経血管内治療学会

    ISSN：2423-9119

    eISSN：2424-1709

  36. Aphasic status epilepticus after glioma resection: two case reports. 国際誌

    Yoshiteru Shimoda, Masayuki Kanamori, Ryuta Saito, Shinichiro Osawa, Shunji Mugikura, Teiji Tominaga

    Acta neurochirurgica　163　(11)　3109-3113　2021年11月

    DOI： 10.1007/s00701-021-04984-z 　

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    Aphasic status epilepticus (ASE) is a subtype of focal nonconvulsive status epilepticus, in which language disturbance is the only objective clinical manifestation. We present two cases of patients who experienced delayed onset of temporal aphasia after the removal of glioma at the language-dominant hemisphere. In both cases, arterial spin labeling was useful for diagnosis and antiepileptic drug was effective. ASE should be considered a cause of persistent aphasia after glioma resection at or near the language area.

  37. 頭蓋内動脈への超選択的麻酔薬注入による詳細な神経症状評価と手術適応への寄与

    大沢 伸一郎, 鈴木 匡子, 浮城 一司, 柿沼 一雄, 新妻 邦泰, 下田 由輝, 神 一敬, 中里 信和, 冨永 悌二

    臨床神経生理学　49　(5)　449-449　2021年10月

    出版者・発行元： (一社)日本臨床神経生理学会

    ISSN：1345-7101

    eISSN：2188-031X

  38. 頭蓋内動脈への超選択的麻酔薬注入による詳細な神経症状評価と手術適応への寄与

    大沢 伸一郎, 鈴木 匡子, 浮城 一司, 柿沼 一雄, 新妻 邦泰, 下田 由輝, 神 一敬, 中里 信和, 冨永 悌二

    臨床神経生理学　49　(5)　449-449　2021年10月

    出版者・発行元： (一社)日本臨床神経生理学会

    ISSN：1345-7101

    eISSN：2188-031X

  39. Digital intravascular pressure wave recording during endovascular treatment reveals abnormal shunting flow in vertebral venous fistula of the vertebral artery: illustrative case. 国際誌

    Yoshiteru Shimoda, Shinya Sonobe, Kuniyasu Niizuma, Toshiki Endo, Hidenori Endo, Mayuko Otomo, Teiji Tominaga

    Journal of neurosurgery. Case lessons　2　(2)　CASE21172　2021年7月12日

    DOI： 10.3171/CASE21172 　

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    BACKGROUND: An arteriovenous fistula is an abnormal arteriovenous shunt between an artery and a vein, which often leads to venous congestion in the central nervous system. The blood flow near the fistula is different from normal artery flow. A novel method to detect the abnormal shunting flow or pressure near the fistula is needed. OBSERVATIONS: A 76-year-old woman presented to the authors' institute with progressive right upper limb weakness. Right vertebral angiography showed a fistula between the right extracranial vertebral artery (VA) and the right vertebral venous plexus at the C7 level. The patient underwent endovascular treatment for shunt flow reduction. Before the procedure, blood pressures were measured at the proximal VA, distal VA near the fistula, and just at the fistula and drainer using a microcatheter. The blood pressure waveforms were characteristically different in terms of resistance index, half-decay time, and appearance of dicrotic notch. The fistula was embolized with coils and N-butyl cyanoacrylate solution. LESSONS: During endovascular treatment, the authors were able to digitally record the vascular pressure waveform from the tip of the microcatheter and succeeded in calculating several parameters that characterize the shunting flow. Furthermore, these parameters could help recognize the abnormal blood flow, allowing a safer endovascular surgery.

  40. 頭蓋内胚腫治療後にてんかんを発症した症例群の検討

    下田 由輝, 金森 政之, 大沢 伸一郎, 齋藤 竜太, 園田 順彦, 隈部 俊宏, 中里 信和, 冨永 悌二

    てんかん研究　39　(2)　305-305　2021年7月

    出版者・発行元： (一社)日本てんかん学会

    ISSN：0912-0890

    eISSN：1347-5509

  41. Hepatitis B virus reactivation during temozolomide administration for malignant glioma.

    Takuhiro Shoji, Masayuki Kanamori, Jun Inoue, Ryuta Saito, Yoshinari Osada, Yoshiteru Shimoda, Masashi Chonan, Hiroshi Uenohara, Atsushi Masamune, Teiji Tominaga

    International journal of clinical oncology　26　(2)　305-315　2021年2月

    DOI： 10.1007/s10147-020-01814-7 　

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    INTRODUCTION: The purpose of this study is to clarify the clinical features of temozolomide (TMZ)-related hepatitis B virus (HBV) reactivation and to identify HBV reactivation predictive factors. METHOD: We retrospectively reviewed the clinical course of 145 patients newly diagnosed or with recurrent malignant glioma treated with TMZ. Before treatment, we screened patients for HB surface antigen (HBsAg) positivity (HBV carrier) and HBsAg negativity. Patients were also screened for antibody for HB core antigen (anti-HBc) positivity and/or for HB surface antigen positivity (resolved HBV infection). The patients were monitored by HBV DNA, alanine, and aspartate aminotransaminase during and after the completion of TMZ. HBV carriers and those with resolved HBV infections with HBV reactivation received preemptive entecavir treatment. In those with resolved HBV infections, we analyzed clinical characters for the predictive factors for HBV reactivation. RESULTS: In one of two HBV carriers, HBV DNA turned positive 8 months after the completion of TMZ and entecavir. In four (16.7%) of 24 resolved HBV infections, HBV DNA turned detectable at completion of concomitant radiation and TMZ or during monthly TMZ. HBV DNA turned negative with entecavir in all patients without liver dysfunction. In resolved HBV infections, those with a high anti-HBc titer had significantly higher incidence of HBV reactivation than those with low anti-HBc titers (60% vs. 5.3%: p = 0.018). CONCLUSION: Screenings, monitoring, and preemptive entecavir were important for preventing TMZ-related HBV reactivations. Anti-HBc titers could be the predictive markers for HBV reactivation in the those with resolved HBV infections.

  42. Hyperperfusion in the thalamus on arterial spin labelling indicates non-convulsive status epilepticus. 国際誌

    Satoru Ohtomo, Hiroshi Otsubo, Hiroaki Arai, Yoshiteru Shimoda, Yoichiro Homma, Teiji Tominaga

    Brain communications　3　(1)　fcaa223　2021年

    DOI： 10.1093/braincomms/fcaa223 　

    詳細を見る 詳細を閉じる

    Non-convulsive status epilepticus describes the syndrome of unexplained impaired consciousness in critically ill patients. Non-convulsive status epilepticus is very likely to lead to delayed diagnosis and poor outcomes because of the absence of convulsive symptoms. EEG is essential for the diagnosis of non-convulsive status epilepticus to establish the association between periodic discharges and rhythmic delta activity in addition to ictal epileptiform discharges according to the Salzburg criteria. Arterial spin labelling, a type of perfusion MRI, has been applied for rapid and non-invasive evaluation of the ictal state. Ictal cerebral cortical hyperperfusion is the most common finding to demonstrate focal onset seizures. Hyperperfusion of the thalamus on single photon emission computed tomography was found in patients with impaired awareness seizures. We hypothesized that thalamocortical hyperperfusion on arterial spin labelling identifies non-convulsive status epilepticus and such thalamic hyperperfusion specifically associates with periodic/rhythmic discharges producing impaired consciousness without convulsion. We identified 27 patients (17 females; age, 39-91 years) who underwent both arterial spin labelling and EEG within 24 h of suspected non-convulsive status epilepticus. We analysed 28 episodes of suspected non-convulsive status epilepticus and compared hyperperfusion on arterial spin labelling with periodic/rhythmic discharges. We evaluated 21 episodes as a positive diagnosis of non-convulsive status epilepticus according to the Salzburg criteria. We identified periodic discharges in 15 (12 lateralized and 3 bilateral independent) episodes and rhythmic delta activity in 13 (10 lateralized, 1 bilateral independent and 2 generalized) episodes. Arterial spin labelling showed thalamic hyperperfusion in 16 (11 unilateral and 5 bilateral) episodes and cerebral cortical hyperperfusion in 24 (20 unilateral and 4 bilateral) episodes. Thalamic hyperperfusion was significantly associated with non-convulsive status epilepticus (P = 0.0007; sensitivity, 76.2%; specificity, 100%), periodic discharges (P < 0.0001; 93.3%; 84.6%), and rhythmic delta activity (P = 0.0006; 92.3%; 73.3%). Cerebral cortical hyperperfusion was significantly associated with non-convulsive status epilepticus (P = 0.0017; 100%; 57.1%) and periodic discharges (P = 0.0349; 100%; 30.8%), but not with rhythmic delta activity. Thalamocortical hyperperfusion could be a new biomarker of non-convulsive status epilepticus according to the Salzburg criteria in critically ill patients. Specific thalamic hyperexcitability might modulate the periodic discharges and rhythmic delta activity associated with non-convulsive status epilepticus. Impaired consciousness without convulsions could be caused by predominant thalamic hyperperfusion together with cortical hyperperfusion but without ictal epileptiform discharges.

  43. A genetically encoded fluorescent sensor for in vivo imaging of GABA. 国際誌

    Jonathan S Marvin, Yoshiteru Shimoda, Vincent Magloire, Marco Leite, Takashi Kawashima, Thomas P Jensen, Ilya Kolb, Erika L Knott, Ondrej Novak, Kaspar Podgorski, Nancy J Leidenheimer, Dmitri A Rusakov, Misha B Ahrens, Dimitri M Kullmann, Loren L Looger

    Nature methods　16　(8)　763-770　2019年8月

    DOI： 10.1038/s41592-019-0471-2 　

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    Current techniques for monitoring GABA (γ-aminobutyric acid), the primary inhibitory neurotransmitter in vertebrates, cannot follow transients in intact neural circuits. To develop a GABA sensor, we applied the design principles used to create the fluorescent glutamate receptor iGluSnFR. We used a protein derived from a previously unsequenced Pseudomonas fluorescens strain and performed structure-guided mutagenesis and library screening to obtain intensity-based GABA sensing fluorescence reporter (iGABASnFR) variants. iGABASnFR is genetically encoded, detects GABA release evoked by electric stimulation of afferent fibers in acute brain slices and produces readily detectable fluorescence increases in vivo in mice and zebrafish. We applied iGABASnFR to track mitochondrial GABA content and its modulation by an anticonvulsant, swimming-evoked, GABA-mediated transmission in zebrafish cerebellum, GABA release events during interictal spikes and seizures in awake mice, and found that GABA-mediated tone decreases during isoflurane anesthesia.

  44. Subarachnoid small vein occlusion due to inflammatory fibrosis-a possible mechanism for cerebellar infarction in cryptococcal meningoencephalitis: a case report. 国際誌 査読有り

    Yoshiteru Shimoda, Satoru Ohtomo, Hiroaki Arai, Takashi Ohtoh, Teiji Tominaga

    BMC neurology　17　(1)　157-157　2017年8月9日

    DOI： 10.1186/s12883-017-0934-y 　

    ISSN：1471-2377

  45. Endoscopic third ventriculostomy for hydrocephalus in a patient with Klippel-Feil syndrome: a case report. 国際誌 査読有り

    Tomohisa Ishida, Takashi Inoue, Miki Fujimura, Yoshiteru Shimoda, Masayuki Ezura, Hiroshi Uenohara, Teiji Tominaga

    Clinical case reports　5　(8)　1344-1347　2017年8月

    DOI： 10.1002/ccr3.1063 　

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    A patient with Klippel-Feil syndrome presented with hydrocephalus secondary to intraventricular hemorrhage. Fusion of the cervical vertebrae may have impeded cerebrospinal fluid flow. Change in the properties of cerebrospinal fluid flow after hemorrhage may have induced noncommunicating hydrocephalus. Endoscopic third ventriculostomy was effective for the treatment of hydrocephalus associated with Klippel-Feil syndrome.

  46. Fourth Ventricle Outlet Obstruction with Expanding Space on the Surface of Cerebellum 国際誌 査読有り

    Yoshiteru Shimoda, Kensuke Murakami, Norio Narita, Teiji Tominaga

    WORLD NEUROSURGERY　100　711.e1-711.e5　2017年4月

    DOI： 10.1016/j.wneu.2017.01.088 　

    ISSN：1878-8750

    eISSN：1878-8769

  47. Satellite Sign: A Poor Outcome Predictor in Intracerebral Hemorrhage. 国際誌 査読有り

    Yoshiteru Shimoda, Satoru Ohtomo, Hiroaki Arai, Ken Okada, Teiji Tominaga

    Cerebrovascular diseases (Basel, Switzerland)　44　(3-4)　105-112　2017年

    DOI： 10.1159/000477179 　

    ISSN：1015-9770

    eISSN：1421-9786

  48. Subcortical band heterotopiaを伴う難治てんかんに対し脳梁離断術を行った3例

    大沢 伸一郎, 岩崎 真樹, 下田 由輝, 神 一敬, 柿坂 庸介, 植松 貢, 萩野谷 和裕, 中里 信和, 冨永 悌二

    てんかん研究　34　(2)　466-466　2016年9月

    出版者・発行元： (一社)日本てんかん学会

    ISSN：0912-0890

    eISSN：1347-5509

  49. Clinical profiles for seizure remission and developmental gains after total corpus callosotomy 国際誌 査読有り

    Masaki Iwasaki, Mitsugu Uematsu, Naomi Hino-Fukuyo, Shin-ichiro Osawa, Yoshiteru Shimoda, Kazutaka Jin, Nobukazu Nakasato, Teiji Tominaga

    BRAIN & DEVELOPMENT　38　(1)　47-53　2016年1月

    DOI： 10.1016/j.braindev.2015.04.010 　

    ISSN：0387-7604

    eISSN：1872-7131

  50. 定位放射線治療後の薬剤難治性てんかんに対する外科治療

    大沢 伸一郎, 岩崎 真樹, 下田 由輝, 神 一敬, 柿坂 庸介, 中里 信和, 川岸 潤, 城倉 英史, 冨永 悌二

    てんかん研究　33　(2)　494-494　2015年9月

    出版者・発行元： (一社)日本てんかん学会

    ISSN：0912-0890

    eISSN：1347-5509

  51. Interhemispheric Vertical Hemispherotomy: A Single Center Experience 国際誌 査読有り

    Masaki Iwasaki, Mitsugu Uematsu, Shin-ichiro Osawa, Yoshiteru Shimoda, Kazutaka Jin, Nobukazu Nakasato, Teiji Tominaga

    PEDIATRIC NEUROSURGERY　50　(5)　295-300　2015年

    DOI： 10.1159/000437145 　

    ISSN：1016-2291

    eISSN：1423-0305

  52. Recurrent Extracranial Internal Carotid Artery Vasospasm Diagnosed by Serial Magnetic Resonance Angiography and Superselective Transarterial Injection of a Calcium Channel Blocker 国際誌 査読有り

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

    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES　23　(5)　E383-E387　2014年5月

    DOI： 10.1016/j.jstrokecerebrovasdis.2013.12.050 　

    ISSN：1052-3057

    eISSN：1532-8511

  53. 頭蓋内電極による脳機能検査の新展開 高域ガンマ活動に着目した認知機能マッピング

    岩崎 真樹, 丹治 和世, 川口 典彦, 大沢 伸一郎, 西尾 慶之, 下田 由輝, 奥村 栄一, 鈴木 匡子, 神 一敬, 中里 信和, 冨永 悌二

    臨床神経生理学　41　(5)　324-324　2013年10月

    出版者・発行元： (一社)日本臨床神経生理学会

    ISSN：1345-7101

    eISSN：2188-031X

  54. 半球間裂アプローチによる大脳半球離断術

    岩崎 真樹, 大沢 伸一郎, 下田 由輝, 植松 貢, 神 一敬, 中里 信和, 冨永 悌二

    てんかん研究　31　(2)　372-372　2013年9月

    出版者・発行元： (一社)日本てんかん学会

    ISSN：0912-0890

    eISSN：1347-5509

  55. Clinicopathological Investigation of Vascular Endothelial Growth Factor and von Hippel-Lindau Gene-Related Protein Expression in Immunohistochemically Negative Pituitary Adenoma - Possible Involvement in Tumor Aggressiveness 国際誌 査読有り

    Yoshiteru Shimoda, Yoshikazu Ogawa, Mika Watanabe, Teiji Tominaga

    ENDOCRINE RESEARCH　38　(4)　242-250　2013年

    DOI： 10.3109/07435800.2013.774411 　

    ISSN：0743-5800

  56. Coexistence of Sporadic Cerebellar Hemangioblastoma and Pituitary Null Cell Adenoma: Simultaneous Expression of von Hippel-Lindau Gene Product -Case Report- 査読有り

    Yoshiteru Shimoda, Yoshikazu Ogawa, Hidenori Endo, Mika Watanabe, Teiji Tominaga

    NEUROLOGIA MEDICO-CHIRURGICA　52　(8)　591-594　2012年8月

    DOI： 10.2176/nmc.52.591 　

    ISSN：0470-8105

    eISSN：1349-8029

  57. Temporal Profile of De Novo Development of Moyamoya Vasculopathy in an Adult -Case Report 査読有り

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

    NEUROLOGIA MEDICO-CHIRURGICA　52　(5)　339-342　2012年5月

    DOI： 10.2176/nmc.52.339 　

    ISSN：0470-8105

    eISSN：1349-8029

︎全件表示 ︎最初の5件までを表示

MISC 21

  1. ハイドロゲル-有機物を基材とする新規頭蓋内電極の安全性と有効性-医師主導治験による検証-

    大沢伸一郎, 新妻邦泰, 中川敦寛, 新妻邦泰, 中川敦寛, 浮城一司, 下田由輝, 神一敬, 植松貢, 岩崎真樹, 西澤松彦, 中里信和, 冨永悌二, 遠藤英徳

    日本てんかん外科学会プログラム・抄録集　47th　2024年

  2. 中心溝周囲皮質のてんかん焦点切除症例における画像所見と運動機能低下の相関

    二宮敦彦, 大沢伸一郎, 鈴木匡子, 柿沼一雄, 浮城一司, 下田由輝, 鈴木博義, 宮田元, 神一敬, 植松貢, 中里信和, 遠藤英徳

    日本てんかん外科学会プログラム・抄録集　47th　2024年

  3. ハイドロゲル-有機物を基材とする生体親和性の高い新規電極の開発

    大沢伸一郎, 西澤松彦, 中川敦寛, 岩崎真樹, 鈴木泰汎, 下田由輝, 中里信和, 冨永悌二

    日本てんかん外科学会プログラム・抄録集　46th　2023年

  4. 術後過灌流予測に向けた超音波血流計によるSTA-MCA bypassの血流波形計測

    古知龍三郎, 遠藤英徳, 鹿毛敦史, 内田浩喜, 下田由輝, 冨永悌二

    脳循環代謝(Web)　34　(1)　2022年

    ISSN： 2188-7519

  5. 深部電極と硬膜下電極の併用留置による切除領域決定への寄与

    大沢伸一郎, 浮城一司, 鈴木匡子, 石田誠, 柿沼一雄, 植松貢, 下田由輝, 神一敬, 中里信和, 冨永悌二

    日本てんかん外科学会プログラム・抄録集　45th　2022年

  6. 切除外科の視点からLEAT概念を考える

    大沢伸一郎, 浮城一司, 下田由輝, 鈴木匡子, 神一敬, 中里信和, 冨永悌二

    てんかん研究　40　(2)　2022年

    ISSN： 0912-0890

  7. 頭蓋内動脈への超選択的麻酔薬注入による詳細な神経症状評価と手術適応への寄与

    大沢伸一郎, 鈴木匡子, 浮城一司, 柿沼一雄, 新妻邦泰, 新妻邦泰, 下田由輝, 神一敬, 中里信和, 冨永悌二

    臨床神経生理学(Web)　49　(5)　2021年

    ISSN： 2188-031X

  8. 麻酔薬の超選択的頭蓋内動脈による神経症状誘発は脳実質切除後の機能転帰を予測する

    大沢伸一郎, 鈴木匡子, 浮城一司, 柿沼一雄, 新妻邦泰, 新妻邦泰, 下田由輝, 神一敬, 中里信和, 冨永悌二

    脳血管内治療(Web)　6　(Supplement)　2021年

    ISSN： 2424-1709

  9. 急性硬膜外血腫の術後に,硬膜外での被膜形成を伴う血腫再貯留を来した1例

    三野正樹, 大沢伸一郎, 佐藤加奈子, ジャ ウェンティン, 下田由輝, 鹿毛淳史, 冨永悌二

    日本脳神経外傷学会プログラム・抄録集　44th　2021年

  10. 高齢者脳実質内腫瘍における非痙攣性てんかん重積

    金森政之, 大沢伸一郎, 下田由輝, 斎藤竜太, 冨永悌二

    日本老年脳神経外科学会プログラム・抄録集　34th (CD-ROM)　2021年

  11. 頭蓋内胚腫治療後にてんかんを発症した症例群の検討

    下田由輝, 金森政之, 大沢伸一郎, 齋藤竜太, 園田順彦, 隈部俊宏, 中里信和, 冨永悌二

    てんかん研究　39　(2)　2021年

    ISSN： 0912-0890

  12. 左頭頂葉切除後に非典型的言語野分布を呈した脳腫瘍例:超選択的Wada testによる検討

    柿沼一雄, 大沢伸一郎, 下田由輝, 金森政之, 浮城一司, 太田祥子, 親富祖まりえ, 川村藍, 冨永悌二, 中里信和, 鈴木匡子

    日本神経心理学会学術集会プログラム予稿集　45th　2021年

  13. 頭蓋内胚腫治療後にてんかんを発症した症例群の検討

    下田由輝, 金森政之, 大沢伸一郎, 大沢伸一郎, 齋藤竜太, 園田順彦, 隈部俊宏, 中里信和, 冨永悌二

    日本てんかん外科学会プログラム・抄録集　44th　2020年

  14. 頭葉眼窩皮質の海綿状血管腫による難治てんかんに外科治療を行った一例

    大沢伸一郎, 大沢伸一郎, 岩崎真樹, 下田由輝, 神一敬, 柿坂庸介, 岩城弘隆, 西尾慶之, 中里信和, 冨永悌二

    日本てんかん外科学会プログラム・抄録集　40th　2017年

  15. MRIで病巣を確認できない側頭葉てんかんの外科治療

    岩崎真樹, 岩崎真樹, 神一敬, 西尾慶之, 柿坂庸介, 大沢伸一郎, 下田由輝, 中里信和, 冨永悌二

    てんかん研究　34　(2)　2016年

    ISSN： 0912-0890

  16. T2 Relaxometryによる海馬てんかん原性の評価

    岩崎 真樹, 佐藤 志帆, 麦倉 俊司, 大沢 伸一郎, 下田 由輝, 神 一敬, 高橋 昭喜, 中里 信和, 冨永 悌二

    てんかん研究　33　(2)　468-468　2015年9月

    出版者・発行元： (一社)日本てんかん学会

    ISSN： 0912-0890

  17. 経シルビウス裂的な海馬到達法と海馬切除

    岩崎真樹, 大沢伸一郎, 下田由輝, 神一敬, 中里信和, 冨永悌二

    日本てんかん外科学会プログラム・抄録集　39th　2015年

  18. 小児難治てんかんに対する一期的全脳梁離断術の発作予後および発達予後

    岩崎真樹, 植松貢, 中山東城, 福與なおみ, 大沢伸一郎, 下田由輝, 神一敬, 萩野谷和裕, 中里信和, 冨永悌二

    てんかん研究　32　(2)　376　2014年9月10日

    ISSN： 0912-0890

  19. Indocyanine green videoangiographyにて減圧手技を評価したbow hunter症候群の1例

    小濱 みさき, 遠藤 俊毅, 下田 由輝, 冨永 悌二

    脊髄外科　28　(2)　159-164　2014年8月

    出版者・発行元： (一社)日本脊髄外科学会

    DOI： 10.2531/spinalsurg.28.159 　

    ISSN： 0914-6024

  20. 小児難治てんかんに対する全脳梁離断術の発作および発達予後

    岩崎真樹, 植松貢, 中山東城, 福與なおみ, 大沢伸一郎, 下田由輝, 神一敬, 萩野谷和裕, 中里信和, 冨永悌二

    日本てんかん外科学会プログラム・抄録集　37th　53　2014年1月

  21. 両側頭蓋内電極留置によって術前精査と逆側の発作起始を捉えた側頭葉てんかんの1手術例

    岩崎 真樹, 神 一敬, 加藤 量広, 大沢 伸一郎, 下田 由輝, 中里 信和, 冨永 悌二

    脳神経外科ジャーナル　23　(9)　744-749　2014年1月1日

    出版者・発行元： 日本脳神経外科コングレス

    DOI： 10.7887/jcns.23.744 　

    ISSN： 0917-950X

︎全件表示 ︎最初の5件までを表示

共同研究・競争的資金等の研究課題 5

  1. 腸内・腫瘍内細菌叢による膠芽腫治療の新機軸

    金森 政之, 山下 理宇, 齋藤 さかえ, 信國 宇洋, 下田 由輝

    2022年4月1日 ～ 2025年3月31日

  2. 慢性期脊髄損傷に対するMuse細胞を用いた新規治療法の開発

    遠藤 俊毅, 冨永 悌二, Rashad Sherif, 新妻 邦泰, 下田 由輝, 正本 和人, 伊藤 明

    2022年4月1日 ～ 2025年3月31日

  3. 血流と内皮細胞の相互作用から迫るもやもや病の発症機序解明

    冨永 悌二, 藤村 幹, Rashad Sherif, 新妻 邦泰, 森戸 大介, 下田 由輝

    提供機関：Japan Society for the Promotion of Science

    制度名：Grants-in-Aid for Scientific Research

    研究種目：Grant-in-Aid for Scientific Research (A)

    研究機関：Tohoku University

    2021年4月5日 ～ 2024年3月31日

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    もやもや病は両側内頚動脈終末部が進行性に狭窄・閉塞し、付近に異常血管網の発達を認める原因不明の疾患であり、病態解明と新規治療開発が求められている。もやもや病の感受性遺伝子であるRNF213遺伝子が同定されたが、その変異単独でもやもや病は発症せず、それに加えて何らかの二次的因子が加わり発症するtwo hit theoryが提唱されている。 本研究の目的は、今までに明らかではなかった血流と血管内皮細胞の相互作用という切り口から、もやもや病の病因・病態を解明することである。 本年度は①～⑤の5つの要素に分けて研究を行った。 ①数値流体力学的解析（CFD解析）：もやもや病患者においてどのように血液が流れ、血管壁にはどのような力がかかるのかをCFDを用いて解析したが、もやもや病の血管形態には個人差も大きく、未だまとまった形の知見は得られていない。 ②流体培養を用いた解析：「流れ」の違いに応じて血管内皮細胞においてRNF213遺伝子発現が変化することが見いだされた。 ③免疫学的解析：RNF213遺伝子変異により抗原取り込みや処理が遅延することを明らかにした。 ④ 臨床応用につながるバイオマーカー探索：RNF213遺伝子変異マウスを用いて、バイオマーカー候補を探索中である。臨床例では、RNF213遺伝子変異がもやもや病患者において肺動脈狭窄を合併する危険因子である可能性が見いだされ、論文として報告した。 ⑤RNF213に関する解析：RNF213変異体の新たな遺伝子変異マウスが樹立されたため、それを用いた実験を行うための環境を構築した。 上記のようにそれぞれの要素につき研究の進捗を認めるが、最終目標であるもやもや病の病因解明には未だ至ってはいない。

  4. 超音波併用脳内局所広範囲薬剤投与法を用いた画期的なアルツハイマー病新規治療法開発

    齋藤 竜太, 下田 由輝

    提供機関：Japan Society for the Promotion of Science

    制度名：Grants-in-Aid for Scientific Research

    研究種目：Grant-in-Aid for Challenging Research (Exploratory)

    研究機関：Nagoya University

    2020年7月30日 ～ 2023年3月31日

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    アルツハイマー病モデルマウス5xFADを用いて開発した超音波併用脳内局所広範囲薬剤投与法を用いた薬剤投与による新規治療開発を目指した。マウス脳内では、パラフィン切片を免疫抗体染色で染めることにより安定してアミロイド蓄積を評価する系を確立した。その上で、ネプリライシン、クルクミンは上記投薬で有効な薬剤分布が得られることを確認した。さらに、これらの薬剤を用いてアミロイド蓄積を解消することを試みた。結果としてネプリライシンが最も安定してアミロイド斑を低減させることを確認した。その上で、5xFADマウスを用いて、海馬への投薬技術を安定化させて、海馬へ投薬を実施した。

  5. 超音波波形解析による術中異常血管識別法の開発

    下田 由輝

    2019年4月1日 ～ 2023年3月31日

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    本研究の目的は、超小型超音波血流計を用いた術中に温存すべき血管の識別法の開発である。脳神経外科術中では血管が病変を灌流する異常血管であり、凝固切断が可能か、正常脳組織を灌流し、閉塞により後遺症を生ずるため温存すべきかの判断が、他の分野に比較して、特に重要である。その理由として、脳では機能が局在しており、他の場所による代償が効かないことが挙げられる。その識別方法として、R元年度には超小型超音波血流計で測定される波形を模擬モデル実験および理論解析を行い波形解析で特徴量となり得る要素を明らかにし、R2年度に血管吻合パターンの異なる動物実験異常血管網モデルを用いて検証した後、R3年度に臨床例で独立成分解析法を用いた波形解析を行うことにより dicrotic notchを含めた特徴量を抽出し、特異度の高い識別法を開発することを予定していた。本研究の開始当初は、術中に出現する血管にドップラー血流計を直接あて、ある一定時間その状態を保つことにより、血流速度を計測し、実際３症例で計測を行い、順調であった。しかし、症例数を重ねるにつれて、術前の病変部塞栓術の有無や、術者の腕によってデータの取得が不安定となることが明らかとなってきた。前回までに、血管内カテーテルを用いた圧波形データの測定から、シャント血流を予測する方針へと切り替えていた。しかし、ここでも問題が生じ、とくに細い血管では、細いカテーテルを圧派が伝わる際に、高周波数成分が減衰することが明らかとなり、ターゲットとしたいDicrotic notchが消退してしまうという問題に直面した。よって、現在は、太い血管をターゲットに、この技術を他の疾患（もやもや病、頸部内頚動脈狭窄症など、後述）に応用できる可能性を探っている。