Faculty Profiles - SAITO Ryuta

Papers - SAITO Ryuta

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脳腫瘍研究のcutting edge-先端画像、実験/分子病理、デジタル病理- 限局型IDH wild-type diffuse astrocytomaの分子生物学的、臨床的特徴の検討について

本村和也, 木部祐士, 大岡史治, 青木恒介, 清水浩之, 山口純矢, 西川知秀, 齋藤竜太

Brain Tumor Pathology Vol. 39 ( Suppl. ) page： 073 - 073 2022.5

Angiographic characteristics of improper watershed shift after STA-MCA bypass in a patient with moyamoya disease: illustrative case. International journal Open Access

Fumiaki Kanamori, Yoshio Araki, Kinya Yokoyama, Kenji Uda, Takashi Mamiya, Shota Nohira, Kai Takayanagi, Kazuki Ishii, Masahiro Nishihori, Takashi Izumi, Ryuta Saito

Journal of neurosurgery. Case lessons Vol. 3 ( 16 ) 2022.4

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

BACKGROUND: In patients with moyamoya disease (MMD) who receive superficial temporal artery (STA) to middle cerebral artery (MCA) bypass, hypoperfusion remote from the anastomosis site rarely occurs. Watershed shift due to direct bypass has been proposed as the mechanism; however, no report has confirmed this phenomenon using angiography. OBSERVATIONS: A 48-year-old man presented with transient weakness in his left arm. Angiography revealed severe bilateral stenosis of the MCAs and moyamoya vessels. The right anterior cerebral artery (ACA) had short stenosis at A2 but ample blood supply to the cortical area of the right ACA and MCA regions. The patient was diagnosed with MMD and received a single STA-MCA bypass. The next day, he had difficulty communicating, and a cerebral infarction away from the anastomosis site was identified. Perfusion examination revealed hyperperfusion around the direct bypass and hypoperfusion away from the anastomosis site. Angiography revealed bypass patency; however, the original anterograde flow of the right ACA decreased significantly at the stenosed point, indicating an improper watershed shift. LESSONS: STA-MCA bypass for patients with MMD can cause an improper watershed shift decreasing cerebral flow. Donor flow should be prepared based on each angiographic characteristic, and the risk of the improper watershed shift should be considered.

DOI： 10.3171/CASE22104

Risk Factors for Cerebral Infarction Early After Revascularization in Children Younger than 5 Years with Moyamoya Disease. International journal

Yoshio Araki, Kenji Uda, Kinya Yokoyama, Fumiaki Kanamori, Michihiro Kurimoto, Yoshiki Shiba, Takashi Mamiya, Masahiro Nishihori, Kazuhito Takeuchi, Kuniaki Tanahashi, Yuichi Nagata, Yusuke Nishimura, Sho Okamoto, Masaki Sumitomo, Takashi Izumi, Ryuta Saito

World neurosurgery Vol. 160 page： E220 - E226 2022.4

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

OBJECTIVE: Cerebral revascularization is necessary for pediatric patients younger than 5 years with moyamoya disease (MMD). However, they have a high risk of developing cerebral infarction early after surgery. This study aimed to analyze the risk factors for developing cerebral infarction among these patients. METHODS: The charts of 21 consecutive patients with MMD (39 surgeries) younger than 5 years who had undergone revascularization at our hospital were retrospectively analyzed. Because cerebral infarction occurring within 1 month after surgery was the primary end point, other clinical information was evaluated, including each surgical procedure. Multivariate analysis of the risk factors for postoperative cerebral infarction was performed. RESULTS: Cerebral infarction occurred after 7 of 39 surgeries (17.9%). Of the 39 surgeries, 23 (59%) included direct and indirect combined revascularization. The incidence of cerebral infarction did not differ significantly between the combined (21.7%) and indirect (12.5%) groups (P = 0.46). Logistic regression showed no association between the revascularization procedure and the occurrence of cerebral infarction after surgery (P = 0.3). However, younger age at surgery was correlated with a higher risk of developing cerebral infarction in the early postoperative period (P = 0.05). CONCLUSIONS: No differences were found in the risk of developing cerebral infarction early after surgery as a result of surgical procedures. However, younger patients had higher postoperative risk. Further multicenter research should examine this issue for young pediatric patients with moyamoya at high risk of developing cerebral infarction.

DOI： 10.1016/j.wneu.2021.12.115

Modified Shoelace Dural Closure with Collagen Matrix in Extended Transsphenoidal Surgery. Open Access

Yuichi Nagata, Kazuhito Takeuchi, Hiroo Sasaki, Akihiro Mizuno, Hideyuki Harada, Kuniaki Tanahashi, Yoshio Araki, Ryuta Saito

Neurologia medico-chirurgica Vol. 62 ( 4 ) page： 203 - 208 2022.4

Language：English Publishing type：Research paper (scientific journal) Publisher：The Japan Neurosurgical Society

Extended endonasal transsphenoidal surgery (eTSS) offers a wide surgical field for various parasellar lesions; however, intraoperative high-flow cerebrospinal fluid (CSF) leakage is inevitable. Therefore, secure sellar reconstruction methods are essential to prevent postoperative CSF leakage. Although collagen matrix has been applied for dural reconstruction in neurosurgery, its suitability for application in extended eTSS remains unclear. Eighteen patients underwent modified shoelace dural closure using collagen matrix after lesionectomy via extended eTSS. In this technique, a collagen matrix, which was placed subdurally (inlay graft), was continuously sutured with both open dural edges like a shoelace. Then, another collagen matrix was placed epidurally (onlay graft), and rigid reconstruction was performed using the septal bone and a resorbable fixation mesh. Postoperative CSF leakage did not occur in 17 patients but did occur in 1 patient with tuberculum sellae meningioma. In this case, the CSF leakage point was detected just around the area between the coagulated dura and the adjacent collagen matrix. The collagen matrix harvested from this area was pathologically examined; neovascularization and fibroblastic infiltration into the collagen matrix were not detected. On the other hand, neovascularization and fibroblast infiltration into the collagen matrix were apparent on the surface of the collagen matrix harvested from the non-CSF leakage area. Our novel dural closure technique using collagen matrix could be an effective option for sellar reconstruction in extended eTSS; however, it should be applied in patients in whom normal dural edges are preserved.

DOI： 10.2176/jns-nmc.2021-0355

Challenging direct bypass surgery for very young children with moyamoya disease: technical notes. International journal

Neurosurgical review Vol. 45 ( 2 ) page： 1799 - 1807 2022.4

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

Cerebral revascularization for moyamoya disease (MMD) is an effective treatment for improving cerebral ischaemia and preventing rebleeding. Although direct bypass surgery is commonly performed on older children and adults, it is challenging in very young children due to the high difficulty level of the procedure. The subjects were MMD patients under 3 years of age on whom surgery was performed by a single surgeon (Y.A.). Preoperative clinical findings, information related to direct bypass surgery, bypass patency, and the incidence of postoperative stroke were investigated. Combined revascularization, including direct bypass surgery, was performed on 3 MMD patients (3 sides) under 3 years of age. The average diameter of the grafts used in direct bypass was 0.8 mm. The average recipient diameter was 0.8 ± 0.17 (range 0.6-1) mm. In all cases, the anastomotic procedure was completed using 11-0 monofilament nylon thread, and patency was confirmed. Direct bypass for MMD patients under 3 years old is technically challenging. However, despite the anatomical differences between very young children and elderly individuals, direct bypass surgery could certainly be completed. In addition, a rapid recovery from cerebral blood flow insufficiency could yield a promising neurological outcome.

DOI： 10.1007/s10143-021-01685-0

Advantages of petrosectomy for superficial temporal artery to superior cerebellar artery bypass based on three-dimensional distance measurements using cadaver heads. International journal Open Access

Kenji Uda, Kuniaki Tanahashi, Takashi Mamiya, Fumiaki Kanamori, Kinya Yokoyama, Masahiro Nishihori, Takashi Izumi, Yoshio Araki, Ryuta Saito

Neurosurgical review Vol. 45 ( 2 ) page： 1617 - 1624 2022.4

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

Superficial temporal artery (STA) to superior cerebellar artery (SCA) bypass is usually performed via the subtemporal approach (StA), anterior transpetrosal approach (ApA), or combined petrosal approach (CpA), but no study has yet reported a quantitative comparison of the operative field size provided by each approach, and the optimal approach is unclear. The objective of this study is to establish evidence for selecting the approach by using cadaver heads to measure the three-dimensional distances that represent the operative field size for STA-SCA bypass. Ten sides of 10 cadaver heads were used to perform the four approaches: StA, ApA with and without zygomatic arch osteotomy (ApA-ZO- and ApA-ZO+), and CpA. For each approach, the major-axis length and the minor-axis length at the anastomosis site (La-A and Li-A), the major-axis length and the minor-axis length at the brain surface (La-B and Li-B), the depth from the brain surface to the anastomosis site (Dp), and the operating angles of the major axis and the minor axis (OAa and OAi) were measured. Shallower Dp and wider operating angle were obtained in the order CpA, ApA-ZO+, ApA-ZO-, and StA. In all parameters, ApA-ZO- extended the operative field more than StA. ApA-ZO+ extended La-B and OAa more than ApA-ZO-, whereas it did not contribute to Dp and OAi. CpA significantly decreased Dp, and widened OAa and OAi more than ApA-ZO+. ApA and CpA greatly expanded the operative field compared with StA. These results provide criteria for selecting the optimal approach for STA-SCA bypass in light of an individual surgeon's anastomosis skill level.

DOI： 10.1007/s10143-021-01686-z

A novel endoscopic ventriculocisternostomy and stenting technique with a transparent acryl puncture needle for a trapped temporal horn: a technical report and literature review

Yamamoto Taiki, Takeuchi Kazuhito, Nagata Yuichi, Mizuno Akihiro, Harada Hideyuki, Saito Ryuta

NEUROSURGICAL REVIEW Vol. 45 ( 2 ) page： 1783 - 1789 2022.4

Language：Japanese Publisher：Neurosurgical Review

Trapped temporal horn is a rare type of noncommunicating focal hydrocephalus, and no standard treatment has been established yet for trapped temporal horn. Recent studies have shown the efficacy of endoscopic ventriculocisternostomy by opening the choroidal fissure; however, some surgical complications were reported during the procedure. Thus, we aimed to report a novel endoscopic ventriculocisternostomy and stenting technique for trapped temporal horn. In this technique, a 5.8-mm transparent acryl puncture needle with a 2.7-mm 0° rigid endoscope was used to open the choroidal fissure. It can fenestrate the choroidal fissure under real-time endoscopic observation of the critical neurovascular structures over the choroidal fissure. Moreover, the dull tip of the needle is less likely to injure the critical neurovascular structures, resulting in safer ventriculocisternostomy than the previously reported technique. Then, a stent is placed along the tract to prevent future obstruction of the stoma. Six trapped temporal horns in four patients were treated using the technique. All the patients showed improved symptoms with no surgical complications. None of the patients showed recurrence of trapped temporal horn during the mean follow-up period of 39.3 months. The combination of endoscopic ventriculocisternostomy and stenting with a transparent acryl puncture needle is a safe and effective treatment option for trapped temporal horn.

DOI： 10.1007/s10143-021-01634-x

Web of Science

Scopus

PubMed

3D培養法を用いた新規下垂体腺腫オルガノイドモデルの作成

佐々木博勇, 竹内和人, 棚橋邦明, 永田雄一, 水野晃宏, 原田英幸, 須賀英隆, 齋藤竜太

日本内分泌学会雑誌 Vol. 98 ( 1 ) page： 329 - 329 2022.4

小児頭蓋咽頭腫の長期成績からみた課題と展望小児頭蓋咽頭腫に対する神経内視鏡治療の実際と展望

竹内和人, 永田雄一, 加藤美穂子, 佐々木博勇, 齋藤竜太

小児の脳神経 Vol. 47 ( 2 ) page： 201 - 201 2022.4

機能性下垂体腺腫に対する外科治療術前評価から根治切除に向けて

永田雄一, 竹内和人, 棚橋邦明, 佐々木博勇, 水野晃宏, 原田英幸, 齋藤竜太

日本内分泌学会雑誌 Vol. 98 ( 1 ) page： 278 - 278 2022.4

頭蓋咽頭腫術後下垂体機能温存に上下垂体動脈血流が重要である

竹内和人, 永田雄一, 水野晃宏, 佐々木博勇, 原田英幸, 齋藤竜太

日本内分泌学会雑誌 Vol. 98 ( 1 ) page： 309 - 309 2022.4

特集脊椎脊髄疾患の再手術症例における手術のコツと留意点頸椎症における再手術

西村由介, 永島吉孝, 齋藤竜太

脊椎脊髄ジャーナル Vol. 34 ( 12 ) page： 896 - 901 2022.3

Increased Risk of Thyroid Dysfunction by PD-1 and CTLA-4 Blockade in Patients Without Thyroid Autoantibodies at Baseline. International journal Open Access

Shintaro Iwama, Tomoko Kobayashi, Yoshinori Yasuda, Takayuki Okuji, Masaaki Ito, Masahiko Ando, Xin Zhou, Ayana Yamagami, Takeshi Onoue, Yohei Kawaguchi, Takashi Miyata, Mariko Sugiyama, Hiroshi Takagi, Daisuke Hagiwara, Hidetaka Suga, Ryoichi Banno, Tetsunari Hase, Masahiro Morise, Keiko Wakahara, Kenji Yokota, Masashi Kato, Naoki Nishio, Chie Tanaka, Kazushi Miyata, Atsushi Ogura, Takanori Ito, Tsunaki Sawada, Tomoya Shimokata, Kaoru Niimi, Fumiharu Ohka, Masatoshi Ishigami, Momokazu Gotoh, Naozumi Hashimoto, Ryuta Saito, Hitoshi Kiyoi, Hiroaki Kajiyama, Yuichi Ando, Hideharu Hibi, Michihiko Sone, Masashi Akiyama, Yasuhiro Kodera, Hiroshi Arima

The Journal of clinical endocrinology and metabolism Vol. 107 ( 4 ) page： E1620 - E1630 2022.3

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

BACKGROUND: Previous studies showed that although the risk of thyroid dysfunction [thyroid immune-related adverse events (irAEs)] induced by anti-programmed cell death-1 antibodies (PD-1-Ab) was as low as 2% to 7% in patients negative for anti-thyroid antibodies (ATAs) at baseline, it was much higher (30%-50%) in patients positive for ATAs. However, whether a similar increase occurs with combination therapy using PD-1-Ab plus anti-cytotoxic T-lymphocyte antigen-4 antibody (CTLA-4-Ab) is unknown. METHODS: A total of 451 patients with malignancies treated with PD-1-Ab, CTLA-4-Ab, or a combination of PD-1-Ab and CTLA-4-Ab (PD-1/CTLA-4-Abs) were evaluated for ATAs at baseline and for thyroid function every 6 weeks for 24 weeks after treatment initiation and then observed until the last clinical visit. RESULTS: Of the 451 patients, 51 developed thyroid irAEs after immunotherapy [41 of 416 (9.9%) treated with PD-1-Ab, 0 of 8 (0%) treated with CTLA-4-Ab, and 10 of 27 (37.0%) treated with PD-1/CTLA-4-Abs]. The cumulative incidence of thyroid irAEs was significantly higher in patients who were positive vs negative for ATAs at baseline after both PD-1-Ab [28/87 (32.2%) vs 13/329 (4.0%), P < 0.001] and PD-1/CTLA-4-Abs [6/10 (60.0%) vs 4/17 (23.5%), P < 0.05] treatments. The risk of thyroid irAEs induced by PD-1/CTLA-4Abs, which was significantly higher than that induced by PD-1-Ab, in patients negative for ATAs at baseline was not statistically different from that induced by PD-1-Ab in patients positive for ATAs at baseline. CONCLUSIONS: This study showed that the incidence of thyroid irAEs was high and not negligible after PD-1/CTLA-4-Abs treatment even in patients negative for ATAs at baseline.

DOI： 10.1210/clinem/dgab829

Surgical management of brain metastasis as a part of systematic metastases from adenoid cystic carcinoma of the external auditory canal: illustrative case International journal Open Access

Shunichiro Kuramitsu, Kazuya Motomura, Yasuhiro Nakajima, Takashi Tsujiuchi, Ayako Motomura, Mamoru Matsuo, Nobuhisa Fukaya, Akinori Kageyama, Iori Kojima, Masasuke Ohno, Ryuta Saito

Journal of Neurosurgery: Case Lessons Vol. 3 ( 11 ) 2022.3

Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Neurosurgery Publishing Group (JNSPG)

BACKGROUND

Adenoid cystic carcinoma (ACC) of the external auditory canal (EAC) is a rare tumor that accounts for approximately 5% of all EAC tumors. ACC is generally known as a slow-growing tumor, but patients often experience recurrence or distant metastasis in the long clinical course. While the major pattern of recurrence is pulmonary metastasis, brain metastasis of ACC of the EAC is rare.

OBSERVATIONS

The authors describe the case of a 72-year-old male who was diagnosed with ACC of the EAC. Approximately 7 years later, brain magnetic resonance imaging revealed an intra-axial homogenously enhancing mass lesion that had no direct connection with the skull base in the left frontal lobe. The patient underwent tumor resection and histopathological examination revealed a mixture of cribriform and tubular patterns. The image and pathological characteristics of the tumor were similar to those of primary ACC or ACC from other sites of origin.

LESSONS

While patients with ACC of the EAC often experience recurrence or distant metastasis in the long clinical course, they survive for a relatively long period of time, even though an optimal treatment has not been established. The authors therefore recommend surgical resection for brain metastasis of ACC of the EAC to improve neurological symptoms.

DOI： 10.3171/CASE21673

Other Link： https://thejns.org/downloadpdf/journals/j-neurosurg-case-lessons/3/11/article-CASE21673.xml

Spatially separate cerebral infarction in the posterior cerebral artery territory after combined revascularization of the middle cerebral artery territory in an adult patient with moyamoya disease and fetal-type posterior communicating artery: illustrative case. International journal Open Access

Yoshio Araki, Kinya Yokoyama, Kenji Uda, Fumiaki Kanamori, Takashi Mamiya, Kai Takayanagi, Kazuki Ishii, Masahiro Nishihori, Kazuhito Takeuchi, Kuniaki Tanahashi, Yuichi Nagata, Takafumi Tanei, Yusuke Nishimura, Takashi Izumi, Ryuta Saito

Journal of neurosurgery. Case lessons Vol. 3 ( 12 ) 2022.3

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

BACKGROUND: Remote cerebral infarction after combined revascularization of the middle cerebral artery (MCA) territory is rare in patients with moyamoya disease (MMD) with a fetal-type posterior communicating artery (PCoA). OBSERVATIONS: A 57-year-old woman developed numbness in her right upper limb and transient motor weakness and was diagnosed with MMD. She also had a headache attack and a scintillating scotoma in the right visual field. Preoperative magnetic resonance angiography (MRA) showed stenosis of the left posterior cerebral artery (PCA). Combined revascularization was performed for the left MCA territory. No new neurological deficits were observed for 2 days after the operation, but right hemianopia, alexia, and agraphia appeared on postoperative day (POD) 4. Magnetic resonance imaging showed a new left occipitoparietal lobe infarction, and MRA showed occlusion of the distal left PCA. After that point, the alexia and agraphia gradually improved, but right hemianopia remained at the time of discharge on POD 18. LESSONS: Cerebral ischemia in the PCA territory may occur after combined revascularization of the MCA territory in patients with fetal-type PCoA. For these cases, a double-barrel bypass or indirect revascularization to induce a slow conversion could be considered on its own as a treatment option.

DOI： 10.3171/CASE21704

Magnetic resonance-guided focused ultrasound thalamotomy restored distinctive resting-state networks in patients with essential tremor. International journal

Sachiko Kato, Satoshi Maesawa, Epifanio Bagarinao, Daisuke Nakatsubo, Takahiko Tsugawa, Satomi Mizuno, Kazuya Kawabata, Takashi Tsuboi, Masashi Suzuki, Masashi Shibata, Sou Takai, Tomotaka Ishizaki, Jun Torii, Manabu Mutoh, Ryuta Saito, Toshihiko Wakabayashi, Masahisa Katsuno, Norio Ozaki, Hirohisa Watanabe, Gen Sobue

Journal of neurosurgery Vol. 138 ( 2 ) page： 306 - 317 2022.2

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

OBJECTIVE: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy ameliorates symptoms in patients with essential tremor (ET). How this treatment affects canonical brain networks has not been elucidated. The purpose of this study was to clarify changes of brain networks after MRgFUS thalamotomy in ET patients by analyzing resting-state networks (RSNs). METHODS: Fifteen patients with ET were included in this study. Left MRgFUS thalamotomy was performed in all cases, and MR images, including resting-state functional MRI (rsfMRI), were taken before and after surgery. MR images of 15 age- and sex-matched healthy controls (HCs) were also used for analysis. Using rsfMRI data, canonical RSNs were extracted by performing dual regression analysis, and the functional connectivity (FC) within respective networks was compared among pre-MRgFUS patients, post-MRgFUS patients, and HCs. The severity of tremor was evaluated using the Clinical Rating Scale for Tremor (CRST) score pre- and postoperatively, and its correlation with RSNs was examined. RESULTS: Preoperatively, ET patients showed a significant decrease in FC in the sensorimotor network (SMN), primary visual network (VN), and visuospatial network (VSN) compared with HCs. The decrease in FC in the SMN correlated with the severity of tremor. After MRgFUS thalamotomy, ET patients still exhibited a significant decrease in FC in a small area of the SMN, but they exhibited an increase in the cerebellar network (CN). In comparison between pre- and post-MRgFUS patients, the FC in the SMN and the VSN significantly increased after treatment. Quantitative evaluation of the FCs in these three groups showed that the SMN and VSN increased postoperatively and demonstrated a trend toward those of HCs. CONCLUSIONS: The SMN and CN, which are considered to be associated with the cerebello-thalamo-cortical loop, exhibited increased connectivity after MRgFUS thalamotomy. In addition, the FC of the visual network, which declined in ET patients compared with HCs, tended to normalize postoperatively. This could be related to the hypothesis that visual feedback is involved in tremor severity in ET patients. Overall, the analysis of the RSNs by rsfMRI reflected the pathophysiology with the intervention of MRgFUS thalamotomy in ET patients and demonstrated a possibility of a biomarker for successful treatment.

DOI： 10.3171/2022.5.JNS22411

Paradoxical symptomatic cerebral blood flow decreases after combined revascularization surgery for patients with pediatric moyamoya disease: illustrative case. International journal Open Access

Yoshio Araki, Kinya Yokoyama, Kenji Uda, Fumiaki Kanamori, Michihiro Kurimoto, Yoshiki Shiba, Takashi Mamiya, Kai Takayanagi, Kazuki Ishii, Masahiro Nishihori, Kazuhito Takeuchi, Kuniaki Tanahashi, Yuichi Nagata, Yusuke Nishimura, Sho Okamoto, Masaki Sumitomo, Takashi Izumi, Ryuta Saito

Journal of neurosurgery. Case lessons Vol. 3 ( 3 ) 2022.1

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

BACKGROUND: Transient neurological deficits (TNDs) develop after cerebral revascularization in patients with moyamoya disease (MMD). The authors report a rare pediatric MMD case with extensive decreased cerebral blood flow (CBF) and prolonged TNDs after combined revascularization. OBSERVATIONS: A 9-year-old boy presented with transient left upper limb weakness, and MMD was diagnosed. A right-sided combined surgery was performed. Two years after the surgery, frequent but transient facial (right-sided) and upper limb weakness appeared. The left internal carotid artery terminal stenosis had progressed. Therefore, a left combined revascularization was performed. The patient's motor aphasia and right upper limb weakness persisted for approximately 10 days after surgery. Magnetic resonance angiography showed that the direct bypass was patent, but extensive decreases in left CBF were observed using single photon emission tomography. With adequate fluid therapy and blood pressure control, the neurological symptoms eventually disappeared, and CBF improved. LESSONS: The environment of cerebral hemodynamics is heterogeneous after cerebral revascularization for MMD, and the exact mechanism of CBF decreases was not identified. TNDs are significantly associated with the onset of stroke during the early postoperative period. Therefore, appropriate treatment is desired after determining complex cerebral hemodynamics using CBF studies.

DOI： 10.3171/CASE21628

Reliability of IDH1-R132H and ATRX and/or p53 immunohistochemistry for molecular subclassification of Grade 2/3 gliomas.

Tomohide Nishikawa, Reiko Watanabe, Yotaro Kitano, Akane Yamamichi, Kazuya Motomura, Fumiharu Ohka, Kosuke Aoki, Masaki Hirano, Akira Kato, Junya Yamaguchi, Sachi Maeda, Yuji Kibe, Ryuta Saito, Toshihiko Wakabayashi, Yukinari Kato, Shuta Sato, Tomoyoshi Ogino, Atsushi Natsume, Ichiro Ito

Brain tumor pathology Vol. 39 ( 1 ) page： 14 - 24 2022.1

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

Since the World Health Organization 2016 classification (2016 WHO), genetic status has been incorporated into the diagnosis of Grade 2/3 gliomas (lower-grade gliomas). Therefore, immunohistochemistry (IHC) of IDH1-R132H, ATRX, and p53 have been used in place of genetic status. We report the associations between histological findings, IHC, and genetic status. We performed IHC of IDH1-R132H, ATRX, and p53 in 76 lower-grade gliomas and discussed its validity based on the 2016 WHO and the upcoming 2021 WHO classification. The sensitivity and specificity of anti-ATRX, p53, and IDH1-R132H IHC were 40.9%/98.1%, 78.6%/85.4%, and 90.5%/84.6%, respectively. Among 21 IDH1-mutant gliomas without 1p/19q codeletion, two gliomas (9.5%) mimicked the so-called classic for oligodendroglioma (CFO) in their morphology. Of the 42 gliomas with 1p/19q codeletion, four cases were difficult to diagnose as oligodendroglioma through morphological examination. Moreover, there were three confusing cases with ATRX mutations but with retained ATRX-IHC positivity. The lessons learned from this study are as follows: (1) ATRX-IHC and p53-IHC should be supplementary to morphological diagnosis, (2) rare IDH mutations other than IDH1 R132H should be considered, and (3) there is no complete alternative test to detect molecular features of glioblastoma under the 2021 WHO classification.

DOI： 10.1007/s10014-021-00418-x

Multitier Network Analysis Using Resting-state Functional MRI for Epilepsy Surgery. Open Access

Satoshi Maesawa, Epifanio Bagarinao, Daisuke Nakatsubo, Tomotaka Ishizaki, Sou Takai, Jun Torii, Sachiko Kato, Masashi Shibata, Toshihiko Wakabayashi, Ryuta Saito

Neurologia medico-chirurgica Vol. 62 ( 1 ) page： 45 - 55 2022.1

Language：English Publishing type：Research paper (scientific journal) Publisher：The Japan Neurosurgical Society

Resting-state functional MRI (rs-fMRI) has been utilized to visualize large-scale brain networks. We evaluated the usefulness of multitier network analysis using rs-fMRI in patients with focal epilepsy. Structural and rs-fMRI data were retrospectively evaluated in 20 cases with medically refractory focal epilepsy, who subsequently underwent surgery. First, structural changes were examined using voxel-based morphometry analysis. Second, alterations in large-scale networks were evaluated using dual-regression analysis. Third, changes in cortical hubs were analyzed and the relationship between aberrant hubs and the epileptogenic zone (EZ) was evaluated. Finally, the relationship between the hubs and the default mode network (DMN) was examined using spectral dynamic causal modeling (spDCM). Dual-regression analysis revealed significant decrease in functional connectivity in several networks including DMN in patients, although no structural difference was seen between groups. Aberrant cortical hubs were observed in and around the EZ (EZ hubs) in 85% of the patients, and a strong degree of EZ hubs correlated to good seizure outcomes postoperatively. In spDCM analysis, facilitation was often seen from the EZ hub to the contralateral side, while inhibition was seen from the EZ hub to nodes of the DMN. Some cognition-related networks were impaired in patients with focal epilepsy. The EZ hub appeared in the vicinity of EZ facilitating connections to distant regions in the early phase, which may eventually generate secondary focus, while inhibiting connections to the DMN, which may cause cognitive deterioration. Our results demonstrate pathological network alterations in epilepsy and suggest that earlier surgical intervention may be more effective.

DOI： 10.2176/nmc.oa.2021-0173

[Diffuse midline glioma].

Ryuta Saito

No shinkei geka. Neurological surgery Vol. 50 ( 1 ) page： 29 - 38 2022.1

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

Diffuse midline glioma(DMG), H3 K27M-mutant is an infiltrative midline high-grade glioma with predominantly astrocytic differentiation and a K27M mutation in either H3F3A or HIST1H3B/C. It is commonly located in the brain stem, thalamus, and spinal cord. DMG is predominant in children but can occur in adults. Brain stem disease, known as diffuse intrinsic pontine glioma(DIPG), is the representative: -80% harbor the H3 K27M mutation. Generally, the prognosis of DMG is poor: the 2-year survival rate is < 10%, despite intensive research and therapies. Consequently, radiation is the only treatment and there is no effective chemotherapeutic regimen. The recent findings concerning the genetic profiles of DMG shed light on precision medicine. Until today, approximately 250 clinical trials with molecular targeted therapy as a strategy have been conducted for different biological pathways in DMG. Unfortunately, none of them has shown significant efficacy for DMG. One of the problems in these clinical trials is insufficient knowledge of whether the used molecular targeted agents penetrate the blood-brain barrier. Continuous efforts to develop effective precision medicine against DMG should pave the way for overcoming DMG in the future.

DOI： 10.11477/mf.1436204529

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