記述言語：英語   掲載種別：研究論文（学術雑誌）  

Thalamic electrical stimulation offers a therapeutic approach for refractory epilepsy patients ineligibles for resective surgery. Yet, there is currently no consensus on the optimal stimulation site. We hypothesized that targeting thalamic nuclei with precise anatomical and functional connections (hodological matching) to cortical seizure onset zones (SOZs) could enhance neuromodulatory effects. Thus, we examined three subnuclei (pulvinar, anterior, and ventral intermediate/oral posterior, VIM/VOP) in 41 focal epilepsy patients. Combining neuroimaging and electrophysiology, we identified hodologically-matched targets: pulvinar for posterior-quadrant and temporal SOZs, anterior for frontotemporal, and VIM/VOP for rolandic. Analysis of 274 seizures revealed the critical role of matched nuclei in seizure termination. Stimulation of hodologically-matched (but not unmatched) nuclei immediately suppressed interictal epileptiform discharges. Finally, in 10 chronically implanted patients, matched stimulation substantially reduced seizure frequency (87.5%), compared to unmatched targets (8.3%) over time. Our results underscore the potential of hodological thalamic targeting to modulate epileptiform activity in focal epilepsy.

DOI： 10.1038/s41467-025-64922-w

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND PURPOSE: The relationship between digital 18F-fluorodeoxyglucose positron emission tomography (dFDG-PET) findings and glucose metabolism-related genetic alterations remains unclear in primary central nervous system lymphoma (PCNSL). This study aimed to evaluate whether dFDG-PET can serve as a noninvasive tool to detect MYD88 mutation-driven glycolytic activity in PCNSL. MATERIALS AND METHODS: We retrospectively analyzed the imaging and molecular data of 54 patients with PCNSL (55 lesions). MRI and FDG-PET parameters, including the maximum standardized uptake value (SUVmax) and tumor-to-background ratio (TBR), were assessed. Tumor specimens were subjected to histopathological and genomic evaluations, including the MYD88 mutation status. RESULTS: Among 55 tumors, 34 (61.8%) were examined with dFDG-PET and 21 (38.2%) with analog 18F-FDG-PET (aFDG-PET). In the dFDG-PET group, MYD88-mutant tumors showed significantly higher SUVmax (30.2 ± 9.9) and TBR (6.1 ± 1.5) compared to wild-type tumors (SUVmax: 19.3 ± 7.2, P = 0.006; TBR: 3.5 ± 1.3, P < 0.001). In the aFDG-PET group, the SUVmax was significantly higher in MYD88-mutant tumors (P = 0.01), whereas the TBR differences were not statistically significant (P = 0.38). Receiver operating characteristic analysis of TBR in dFDG-PET yielded an area under the curve of 0.913 (95% CI: 0.954-1.000) with a cutoff value of 4.49, achieving 88% sensitivity and 88% specificity for MYD88 mutation detection. Multivariate logistic regression identified SUVmax and TBR from dFDG-PET as independent predictors of MYD88 mutation status. The transcriptomic analysis confirmed the significant upregulation of glycolysis-related genes, including hexokinase 2, in MYD88-mutant tumors, supporting increased glycolytic activity. CONCLUSIONS: dFDG-PET may serve as a valuable noninvasive imaging modality to detect MYD88 mutation-driven enhanced glycolysis in patients with PCNSL. ABBREVIATIONS: dPET＝ Digital positron emission tomography; PCNSL＝ Primary central nervous system lymphoma; SUVmax＝maximum standardized uptake value; TBR＝ tumor-to background ratio.

DOI： 10.3174/ajnr.A8935

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/epi.18317

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Precise anatomical implantation of a microelectrode array is fundamental for successful brain-computer interface (BCI) surgery, ensuring high-quality, robust signal communication between the brain and the computer interface. Robotic neurosurgery can contribute to this goal, but its application in BCI surgery has been underexplored. Here, the authors present a novel robot-assisted surgical technique to implant rigid intracortical microelectrode arrays for the BCI. Using this technique, the authors performed surgery in a 31-year-old male with tetraplegia due to a traumatic C4 spinal cord injury that occurred a decade earlier. Each of the arrays was embedded into the parenchyma with a single insertion without complication. Postoperative imaging verified that the devices were placed as intended. With the motor cortex arrays, the participant successfully accomplished 2D control of a virtual arm and hand, with a success rate of 20 of 20 attempts, and recording quality was maintained at 100 and 200 days postimplantation. Intracortical microstimulation of the somatosensory cortex arrays elicited sensations in the fingers and palm. A robotic neurosurgery technique was successfully translated into BCI device implantation as part of an early feasibility trial with the long-term goal of restoring upper-limb function. The technique was demonstrated to be accurate and subsequently contributed to high-quality signal communication.

DOI： 10.3171/2024.7.JNS241296

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Targeted electrical stimulation to specific thalamic regions offers a therapeutic approach for patients with refractory focal and generalized epilepsy who are not candidates for resective surgery. However, clinical outcome varies significantly, in particular for focal epilepsy, influenced by several factors, notably the precise anatomical and functional alignment between cortical regions generating epileptic discharges and the targeted thalamic stimulation sites. Here we hypothesized that targeting thalamic nuclei with precise anatomical and functional connections to epileptic cortical areas (an approach that we refer to as hodological matching) could enhance neuromodulatory effects on focal epileptic discharges. To investigate this, we examined three thalamic subnuclei (pulvinar nucleus, anterior nucleus, and ventral intermediate nucleus/ventral oral posterior nuclei) in a retrospective study involving 32 focal epilepsy patients. Specifically, we first identified hodologically organized thalamocortical fibers connecting these nuclei to individual seizure onset zones (SOZs), combining neuroimaging and electrophysiological techniques. Further, analysis of 216 spontaneous seizures revealed the critical role of matched thalamic nuclei in seizure development and termination. Importantly, electrical stimulation of hodologically-matched thalamic nuclei immediately suppressed intracortical interictal epileptiform discharges, contrasting with ineffective outcomes from stimulation of unmatched targets. Finally, we retrospectively evaluated 7 patients with a chronic hodologically-matched neurostimulation system, which led to a clinically relevant reduction in seizure frequency (median reduction 86.5%), that outstands the current clinical practice of unmatched targets (39%). Our results underscore the potential of hodological thalamic targeting to modulate epileptiform activity in specific cortical regions, highlighting the promise of precision medicine in thalamic neuromodulation for focal refractory epilepsy.

DOI： 10.21203/rs.3.rs-5507011/v1

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記述言語：日本語   出版者・発行元：(一社)日本臨床神経生理学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND OBJECTIVES: Intracranial electrophysiology of thalamic nuclei has demonstrated involvement of thalamic areas in the propagation of seizures in focal drug-resistant epilepsy. Recent studies have argued that thalamus stereoencephalography (sEEG) may aid in understanding the epileptogenic zone and treatment options. However, the study of thalamic sEEG-associated hemorrhage incidence has not been investigated in a cohort study design. In this article, we present the largest retrospective cohort study of sEEG patients and compare hemorrhage rates between those with and without thalamic sEEG monitoring. METHODS: Retrospective chart review of clinical and epilepsy history, electrode implantation, rationale, and outcomes was performed for 76 patients (age 20-69 years) with drug-resistant epilepsy who underwent sEEG monitoring at our institution (2019-2022). A subset of 38% of patients (n = 30) underwent thalamic monitoring of the anterior thalamic nucleus (n = 14), pulvinar nucleus (n = 25), or both (n = 10). Planned perisylvian orthogonal sEEG trajectories were extended to 2- to 3-cm intraparenchymally access thalamic area(s).The decision to incorporate thalamic monitoring was made by the multidisciplinary epilepsy team. Statistical comparison of hemorrhage rate, type, and severity between patients with and without thalamic sEEG monitoring was made. RESULTS: Our approach for thalamic monitoring was not associated with local intraparenchymal hemorrhage of thalamic areas or found along extended cortical trajectories, and symptomatic hemorrhage rates were greater for patients with thalamic coverage (10% vs 0%, P = .056), although this was not found to be significant. Importantly, patients with perisylvian electrode trajectories, with or without thalamic coverage, did not experience a higher incidence of hemorrhage ( P = .34). CONCLUSION: sEEG of the thalamus is a safe and valuable tool that can be used to interrogate the efficacy of thalamic neuromodulation for drug-resistant epilepsy. While patients with thalamic sEEG did have higher incidence of hemorrhage at any monitoring site, this finding was apparently not related to the method of perisylvian implantation and did not involve any trajectories targeting the thalamus.

DOI： 10.1227/neu.0000000000002919

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/epi.17986

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Isolated abducens nerve palsy (IANP), caused by secondary communicating hydrocephalus, has been rarely documented; in addition, its mechanism and appropriate treatment are not understood well. This study presents a case of bilateral IANP with hydrocephalus in a 62-year-old man who was successfully treated with cerebrospinal fluid (CSF) diversion to correct an enlarged retroclival space during the follow-up of recurrent brain tumor in the right parieto-occipital lobe. The patient was treated with three resections, temozolomide, and irradiation before developing IANP. Magnetic resonance imaging (MRI) revealed a recurrent tumor and ventriculomegaly with an expanded retroclival cisternal space. The patient underwent subtotal tumor resection and external ventricular drain placement in the anterior horn of the lateral ventricle. His bilateral IANP persisted for 4 days after surgery but gradually improved and disappeared by Day 7. Four weeks later, the patient underwent ventriculoperitoneal (VP) shunt surgery to establish a permanent CSF diversion that continued to control the symptoms. Retrospective MRI review revealed the distance between the clivus and pontomedullary junction on the sagittal section (retroclival-pontomedullary distance; RPD) of 9.0, 12.8, 10.7, and 10.6 mm before IANP, on IANP onset, on postoperative Day 4, and post VP shunt surgery, respectively. In conclusion, VP shunt surgery was an appropriate approach for IANP with communicating hydrocephalus to correct the enlarged retroclival cisternal space. RPD thus may be used as one of possible evaluation methods for IANP with hydrocephalus, which can be caused by various factors.

DOI： 10.2176/jns-nmc.2024-0092

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: The use of anti-epileptic drugs (AEDs) in degenerative dementia (DD) remains uncertain. We aimed to evaluate the association of early AED administration with subsequent DD occurrence. METHODS: Using a large nationwide database, we enrolled patients newly diagnosed with epilepsy from 2014 to 2019 (n = 104,225), and using propensity score matching, we divided them into treatment (those prescribed AEDs in 2014) and control groups. The primary outcome was subsequent DD occurrence in 2019. RESULTS: Overall, 4489 pairs of patients (2156 women) were matched. The odds ratio (treatment/control) for DD occurrence was 0.533 (95% confidence interval: 0.459-0.617). The DD proportions significantly differed between the treatment (340/4489 = 0.076) and control (577/4489 = 0.129) groups. DISCUSSION: Among patients newly diagnosed with epilepsy, compared to non-use, early AED use was associated with a lower occurrence of subsequent DD. Further investigations into and optimization of early intervention for epilepsy in DD are warranted. HIGHLIGHTS: Anti-epileptic drug (AED) use before epilepsy diagnosis was linked with a lower subsequent degenerative dementia (DD) occurrence.Identifying the epileptic phenotype was crucial for justifying early AED use in DD.AED use with an epilepsy diagnosis did not pose an additional risk of DD.The potential contribution of combination drug therapy to the strategy was noted.

DOI： 10.1002/trc2.70001

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND OBJECTIVES: Insulo-opercular surgery can cause ischemic motor complications. A source of this is the arteries around the superior limiting sulcus (SLS), which reach the corona radiata, but the detailed anatomy remains unclear. To characterize arteries around the SLS including the long insular arteries (LIAs) and long medullary arteries, we classified them and examined their distribution in relation to the SLS, which helps reduce the risk of ischemia. METHODS: Twenty adult cadaveric hemispheres were studied. Coronal brain slices were created perpendicular to the SLS representing insular gyri (anterior short, middle short, posterior short, anterior long, and posterior long). The arteries within 10-mm proximity of the SLS that reached the corona radiata were excavated and classified by the entry point. RESULTS: A total of 122 arteries were identified. Sixty-three (52%), 20 (16%), and 39 (32%) arteries penetrated the insula (LIAs), peak of the SLS, and operculum (long medullary arteries), respectively. 100 and six (87%) arteries penetrated within 5 mm of the peak of the SLS. The arteries were distributed in the anterior short gyrus (19%), middle short gyrus (17%), posterior short gyrus (20%), anterior long gyrus (19%), and posterior long gyrus (25%). Seven arteries (5.7%) had anastomoses after they penetrated the parenchyma. CONCLUSION: Approximately 90% of the arteries that entered the parenchyma and reached the corona radiata were within a 5-mm radius of the SLS in both the insula and operculum side. This suggests that using the SLS as a landmark during insulo-opercular surgery can decrease the chance of ischemia.

DOI： 10.1227/ons.0000000000000879

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: The 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors uses an integrated approach involving histopathology and molecular profiling. Since majority of adult malignant brain tumors are gliomas and primary central nervous system lymphomas (PCNSL), rapid differentiation of these diseases is required for therapeutic decisions. Additionally, diffuse gliomas require molecular information on single nucleotide variants (SNV), such as IDH1/2. Here, we report an intraoperative integrated diagnostic (i-ID) system to classify CNS malignant tumors, which updates legacy frozen section (FS) diagnosis through incorporation of a quantitative polymerase chain reaction (qPCR)-based genotyping assay. EXPERIMENTAL DESIGN: FS evaluation, including GFAP and CD20 rapid immunohistochemistry, was performed on adult malignant CNS tumors. PCNSL was diagnosed through positive CD20 and negative GFAP immunostaining. For suspected glioma, genotyping for IDH1/2, TERT SNV, and CDKN2A copy number alteration was routinely performed, whereas H3F3A and BRAF SNV were assessed for selected cases. i-ID was determined based on the 2021 WHO classification and compared with the permanent integrated diagnosis (p-ID) to assess its reliability. RESULTS: After retrospectively analyzing 153 cases, 101 cases were prospectively examined using the i-ID system. Assessment of IDH1/2, TERT, H3F3AK27M, BRAFV600E, and CDKN2A alterations with i-ID and permanent genomic analysis was concordant in 100%, 100%, 100%, 100%, and 96.4%, respectively. Combination with FS and intraoperative genotyping assay improved diagnostic accuracy in gliomas. Overall, i-ID matched with p-ID in 80/82 (97.6%) patientswith glioma and 18/19 (94.7%) with PCNSL. CONCLUSIONS: The i-ID system provides reliable integrated diagnosis of adult malignant CNS tumors.

DOI： 10.1158/1078-0432.CCR-23-1660

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記述言語：英語  

DOI： 10.1016/j.clinph.2023.08.014

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：(株)メディカ出版  

症例は58歳女性で、15年前に左顔面がしびれる感覚発作を経験し、10年前から同様の発作が定期的に出現するようになった。近医の画像診断で海綿状血管奇形(CM)を指摘されて、抗てんかん薬による治療が開始され感覚発作は消失した。しかし、7年前から頸部の間代発作を呈するようになり、薬剤抵抗性に発作が持続したため7ヵ月前に当科紹介となり、包括的てんかん精査を経て手術のため入院した。てんかん原性領域はCMの内側で、機能的には発作症候の始まりである頸部の支配領域に位置すると推定してCMおよびその内側の皮質の切除を計画した。電極留置12日後に焦点切除術を施行し、切除外側はヘモジデリン沈着部を残したCMの核出にとどめ、内側ではCM周辺のヘモジデリンの沈着した皮質に切除を加えた。術前に3剤内服していた抗てんかん薬は漸減し、ラモトリギン単剤で術後2年以上発作は抑制されている。

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The excitatory glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) contribute to epileptogenesis. Thirty patients with epilepsy and 31 healthy controls are scanned using positron emission tomography with our recently developed radiotracer for AMPARs, [11C]K-2, which measures the density of cell-surface AMPARs. In patients with focal-onset seizures, an increase in AMPAR trafficking augments the amplitude of abnormal gamma activity detected by electroencephalography. In contrast, patients with generalized-onset seizures exhibit a decrease in AMPARs coupled with increased amplitude of abnormal gamma activity. Patients with epilepsy had reduced AMPAR levels compared with healthy controls, and AMPARs are reduced in larger areas of the cortex in patients with generalized-onset seizures compared with those with focal-onset seizures. Thus, epileptic brain function can be regulated by the enhanced trafficking of AMPAR due to Hebbian plasticity with increased simultaneous neuronal firing and compensational downregulation of cell-surface AMPARs by the synaptic scaling.

DOI： 10.1016/j.xcrm.2023.101020

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Insular epilepsy (IE) is an increasingly recognized cause of drug-resistant epilepsy amenable to surgery. However, concerns of suboptimal seizure control and permanent neurological morbidity hamper widespread adoption of surgery for IE. We performed a systematic review and individual participant data meta-analysis to determine the efficacy and safety profile of surgery for IE and identify predictors of outcomes. Of 2483 unique citations, 24 retrospective studies reporting on 312 participants were eligible for inclusion. The median follow-up duration was 2.58 years (range, 0-17 years), and 206 (66.7%) patients were seizure-free at last follow-up. Younger age at surgery (≤18 years; HR = 1.70, 95% CI = 1.09-2.66, P = .022) and invasive EEG monitoring (HR = 1.97, 95% CI = 1.04-3.74, P = .039) were significantly associated with shorter time to seizure recurrence. Performing MR-guided laser ablation or radiofrequency ablation instead of open resection (OR = 2.05, 95% CI = 1.08-3.89, P = .028) was independently associated with suboptimal or poor seizure outcome (Engel II-IV) at last follow-up. Postoperative neurological complications occurred in 42.5% of patients, most commonly motor deficits (29.9%). Permanent neurological complications occurred in 7.8% of surgeries, including 5% and 1.4% rate of permanent motor deficits and dysphasia, respectively. Resection of the frontal operculum was independently associated with greater odds of motor deficits (OR = 2.75, 95% CI = 1.46-5.15, P = .002). Dominant-hemisphere resections were independently associated with dysphasia (OR = 13.09, 95% CI = 2.22-77.14, P = .005) albeit none of the observed language deficits were permanent. Surgery for IE is associated with a good efficacy/safety profile. Most patients experience seizure freedom, and neurological deficits are predominantly transient. Pediatric patients and those requiring invasive monitoring or undergoing stereotactic ablation procedures experience lower rates of seizure freedom. Transgression of the frontal operculum should be avoided if it is not deemed part of the epileptogenic zone. Well-selected candidates undergoing dominant-hemisphere resection are more likely to exhibit transient language deficits; however, the risk of permanent deficit is very low.

DOI： 10.1002/epi4.12663

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Low-grade epilepsy-associated tumors (LEATs) are common in the temporal lobe and can cause drug-resistant epilepsy. Complete resection of LEATs is sufficient for seizure relief. However, hippocampal resection might result in postoperative cognitive impairment. This study aimed to clarify the necessity of hippocampal resection for seizure and cognitive outcomes in patients with temporal lobe LEATs and a normal hippocampus. The study included 32 patients with temporal lobe LEATs and without hippocampal abnormalities. All patients underwent gross total resection as treatment for drug-resistant epilepsy at our tertiary epilepsy center from 2005 to 2020, followed by at least a 12-month follow-up period. Seizure and cognitive outcomes were compared between patients who underwent additional hippocampal resection (Resected group) and those who did not (Preserved group). Among the participants, 14 underwent additional hippocampal resection and 28 (87.5%) achieved seizure freedom irrespective of hippocampal resection. The seizure-free periods were not different between the two groups. Additional hippocampal resection resulted in a significantly negative impact on the postoperative verbal index. In conclusion, additional hippocampal resection in patients with temporal lobe LEATs without hippocampal abnormalities is unnecessary because lesionectomy alone results in good seizure control. Additional hippocampal resection may instead adversely affect the postoperative language function.

DOI： 10.3390/brainsci12101381

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: The impact of the coronavirus disease 2019 (COVID-19) pandemic on epilepsy care across Japan was investigated by conducting a multicenter retrospective cohort study. METHODS: This study included monthly data on the frequency of (1) visits by outpatients with epilepsy, (2) outpatient electroencephalography (EEG) studies, (3) telemedicine for epilepsy, (4) admissions for epilepsy, (5) EEG monitoring, and (6) epilepsy surgery in epilepsy centers and clinics across Japan between January 2019 and December 2020. We defined the primary outcome as epilepsy-center-specific monthly data divided by the 12-month average in 2019 for each facility. We determined whether the COVID-19 pandemic-related factors (such as year [2019 or 2020], COVID-19 cases in each prefecture in the previous month, and the state of emergency) were independently associated with these outcomes. RESULTS: In 2020, the frequency of outpatient EEG studies (-10.7%, p<0.001) and cases with telemedicine (+2,608%, p=0.031) were affected. The number of COVID-19 cases was an independent associated factor for epilepsy admission (-3.75*10-3 % per case, p<0.001) and EEG monitoring (-3.81*10-3 % per case, p = 0.004). Further, the state of emergency was an independent factor associated with outpatient with epilepsy (-11.9%, p<0.001), outpatient EEG (-32.3%, p<0.001), telemedicine for epilepsy (+12,915%, p<0.001), epilepsy admissions (-35.3%; p<0.001), EEG monitoring (-24.7%: p<0.001), and epilepsy surgery (-50.3%, p<0.001). SIGNIFICANCE: We demonstrated the significant impact that the COVID-19 pandemic had on epilepsy care. These results support those of previous studies and clarify the effect size of each pandemic-related factor on epilepsy care.

DOI： 10.1002/epi4.12616

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The use of mechanical thrombectomy (MT) for treatment of acute large vessel occlusion has recently increased. Prompt and timely guiding catheter (GC) induction is necessary to improve prognosis of MT and reduce the time for recanalization. However, difficulties in GC induction are encountered in some patients. This GC induction depends mainly on the aortic arch structure. Therefore, this study focused on assessing presence of tracheal shift on chest X-ray images as pre-treatment evaluation method for GC induction due to its wide availability as an indicator for status of the mediastinum. METHODS: We retrospectively examined 33 patients who underwent MT at our facilities between April 2017 and March 2021. The patients were divided into two groups according to presence or absence of tracheal shift on chest X-ray images. Background characteristics and treatment courses in these two groups were compared. RESULTS: Among 33 patients, tracheal shift was observed on the chest X-ray images of 14 patients. Furthermore, tracheal shift was positively correlated with the time of GC induction (32.9 min vs. 11.6 min, [p < 0.05]) and the female sex (p = 0.03). Additionally, tracheal shift exhibited correlations with multiple risk factors of atherosclerosis (p = 0.04). CONCLUSIONS: In patients with tracheal shift, GC induction could be expectedly difficult. Therefore, advanced disinfection of the right upper arm and affected side of the neck during MT in preparation for changing an approach route is required.

DOI： 10.1177/19714009221084237

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Molecular targeted therapy using BRAF and/or MEK inhibitors has been applied to BRAFV600E mutant high-grade gliomas (HGGs); however, the therapeutic effect is limited by the emergence of drug resistance. EXPERIMENTAL DESIGN: We established multiple paired BRAFV600E mutant HGG patient-derived xenograft (PDX) models based on tissues collected prior to and at relapse after molecular targeted therapy. Using these models, we dissected treatment resistant mechanisms for molecular targeted therapy and explored therapeutic targets to overcome resistance in BRAFV600E HGG models in vitro and in vivo. RESULTS: We found that, despite causing no major genetic and epigenetic changes, BRAF and/or MEK inhibitor treatment deregulated multiple negative feedback mechanisms, which led to the re-activation of the MAPK pathway through c-Raf and AKT signaling. This altered oncogenic signaling primarily mediated resistance to molecular targeted therapy in BRAFV600E mutant HGG. To overcome this resistance mechanism, we performed a high-throughput drug screening to identify therapeutic agents that potently induce additive cytotoxicity with BRAF and MEK inhibitors. We discovered that HSP90 inhibition combined with BRAF/MEK inhibition coordinately deactivated the MAPK and AKT/mTOR pathways, and subsequently induced apoptosis via dephosphorylation of GSK3β (Ser9) and inhibition of Bcl-2 family proteins. This mediated potent cytotoxicity in vitro and in vivo in refractory models with acquired resistance to molecular-targeted therapy. CONCLUSIONS: The combination of an HSP90 inhibitor with BRAF or MEK inhibitors can overcome the limitations of the current therapeutic strategies for BRAFV600E mutant HGG.

DOI： 10.1158/1078-0432.CCR-21-3622

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記述言語：英語  

DOI： 10.1016/j.yebeh.2021.108481

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: This study aimed to investigate the factors affecting the unwillingness of physicians involved in epilepsy care to continue telemedicine during the coronavirus disease 2019 (COVID-19) pandemic in Japan. METHOD: This was a national-level cross-sectional survey initiated by Japan Young Epilepsy Section (YES-Japan) which is a national chapter of The Young Epilepsy Section of the International League Against Epilepsy (ILAE-YES). We asked physicians who conducted telemedicine in patients with epilepsy (PWE) during the COVID-19 pandemic at four clinics and 21 hospitals specializing in epilepsy care in Japan from March 1 to April 30, 2021. The following data were collected: (1) participant profile, (2) characteristics of PWE treated by telemedicine, and (3) contents and environmental factors of telemedicine. Statistically significant variables (p < 0.05) in the univariate analysis were analyzed in a multivariate binary logistic regression model to detect the independently associated factors with the unwillingness to continue telemedicine. RESULT: Among the 115 respondents (response rate: 64%), 89 were included in the final analysis. Of them, 60 (67.4%) were willing to continue telemedicine, and 29 (32.6%) were unwilling. In the univariate binary logistic regression analysis, age (Odds ratio [OR] = 1.84, 95% confidence interval [CI] 1.10-3.09, p = 0.02), psychiatrist (OR = 5.88, 95% CI 2.15-16.08, p = 0.001), hospital (OR = 0.10, 95% CI 0.01-0.94, p = 0.04), the number of COVID-19 risk factors in the participant (OR = 2.88, 95% CI 1.46-5.69, p = 0.002), the number of COVID-19 risk factors in the cohabitants (OR = 2.52, 95% CI 1.05-6.01, p = 0.04), COVID-19 epidemic area (OR = 4.37, 95% CI 1.18-16.20, p = 0.03), consultation time during telemedicine (OR = 2.51, 95% CI 1.32-4.76, p = 0.005), workload due to telemedicine (OR = 4.17, 95% CI 2.11-8.24, p < 0.001) were statistically significant. In the multivariate binary logistic regression analysis, workload due to telemedicine (OR = 4.93, 95% CI 1.96-12.35) was independently associated with the unwillingness to continue telemedicine. CONCLUSION: This national-level cross-sectional survey found that workload due to telemedicine among physicians involved in epilepsy care was independently associated with the unwillingness to continue telemedicine.

DOI： 10.1016/j.yebeh.2021.108487

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掲載種別：研究論文（学術雑誌）   出版者・発行元：The Japan Epilepsy Society  

DOI： 10.3805/eands.14.1

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掲載種別：研究論文（学術雑誌）   出版者・発行元：The Japan Epilepsy Society  

DOI： 10.3805/eands.14.58

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Presurgical identification of the epileptogenic zone is a critical determinant of seizure control following surgical resection in epilepsy. Excitatory glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor is a major component of neurotransmission. Although elevated α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor levels are observed in surgically resected brain areas of patients with epilepsy, it remains unclear whether increased α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor-mediated currents initiate epileptic discharges. We have recently developed the first PET tracer for α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor, [11C]K-2, to visualize and quantify the density of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors in living human brains. Here, we detected elevated [11C]K-2 uptake in the epileptogenic temporal lobe of patients with mesial temporal lobe epilepsy. Brain areas with high [11C]K-2 uptake are closely colocalized with the location of equivalent current dipoles estimated by magnetoencephalography or with seizure onset zones detected by intracranial electroencephalogram. These results suggest that epileptic discharges initiate from brain areas with increased α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors, providing a biological basis for epileptic discharges and an additional non-invasive option to identify the epileptogenic zone in patients with mesial temporal lobe epilepsy.

DOI： 10.1093/braincomms/fcac023

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Scientific Scholar  

<sec id="st1">
<title>Background: </title>
Nonconvulsive status epilepticus (NCSE) is induced by common neurosurgical conditions, for example, trauma, stroke, tumors, and surgical interventions in the brain. The aggressiveness of the treatment for NCSE depends on its neurological prognosis. Aphasic status epilepticus (ASE) is a subtype of focal NCSE without consciousness impairment. The impact of ASE on neurological prognosis is poorly documented. We describe a case of postoperative ASE resulting in verbal and memory deficits.


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<title>Case Description: </title>
A 54-year-old, right-handed man with focal impaired awareness seizures underwent partial resection for a left temporal lobe tumor. No neurological deficits were observed immediately after surgery. Three days later, however, a focal to bilateral tonic-clonic seizure (FBTCS) occurred, followed by aphasia. Electroencephalography revealed 1.5 Hz left-sided periodic discharges. He was diagnosed with ASE. Multiple anti-seizure drugs were ineffective for the resolution of the patient’s verbal disturbance. Nine days after the FBTCS, deep sedation with intravenous anesthetics was performed and the ASE stopped. Thereafter, his symptoms gradually improved. However, the prolonged ASE resulted in verbal and memory deficits. Automated hippocampal volumetry revealed an approximate decrease of 20% on the diseased side on magnetic resonance imaging 3 months after surgery.


</sec>
<sec id="st3">
<title>Conclusion: </title>
Prolonged ASE can induce verbal and memory deficits. Early intervention with intravenous anesthetics is required to obtain a favorable neurological prognosis.


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DOI： 10.25259/sni_1120_2021

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その他リンク： http://surgicalneurologyint.com/surgicalint-articles/verbal-and-memory-deficits-caused-by-aphasic-status-epilepticus-after-resection-of-a-left-temporal-lobe-glioma/

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.yebeh.2021.108361

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掲載種別：研究論文（学術雑誌）  

Objective: To identify the risk factors for psychological distress in electroencephalography (EEG) technicians during the coronavirus disease 2019 (COVID-19) pandemic. Method: In this national-level cross-sectional survey initiated by Japan Young Epilepsy Section (YES-Japan), a questionnaire was administered to 173 technicians engaged in EEG at four clinics specializing in epilepsy care and 20 hospitals accredited as (quasi-) epilepsy centers or epilepsy training facilities in Japan from March 1 to April 30, 2021. We collected data on participants’ profiles, information about work, and psychological distress outcome measurements, such as the K-6 and Tokyo Metropolitan Distress Scale for Pandemic (TMDP). Linear regression analysis was used to identify the risk factors for psychological distress. Factors that were significantly associated with psychological distress in the univariate analysis were subjected to multivariate analysis. Results: Among the 142 respondents (response rate: 82%), 128 were included in the final analysis. As many as 35.2% of EEG technicians have been under psychological distress. In multivariate linear regression analysis for K-6, female sex, examination for patients (suspected) with COVID-19, and change in salary or bonus were independent associated factors for psychological distress. Contrastingly, in multivariate linear regression analysis for TMDP, female sex, presence of cohabitants who had to be separated from the respondent due to this pandemic, and change in salary or bonus were independent associated factors for psychological distress. Conclusion: We successfully identified the risk factors associated with psychological distress in EEG technicians during the COVID-19 pandemic. Our results may help in understanding the psychological stress in EEG technicians during the COVID-19 pandemic and improving the work environment, which is necessary to maintain the mental health of EEG technicians.

DOI： 10.1016/j.yebeh.2021.108361

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Pediatric epilepsy surgery is known to be effective, but early surgery in infancy is not well characterized. Extensive cortical dysplasia, such as hemimegalencephaly, can cause refractory epilepsy shortly after birth, and early surgical intervention is indicated. However, the complication rate of early pediatric surgery is significant. In this study, the authors assessed the risk-benefit balance of early pediatric epilepsy surgery as relates to developmental outcomes. METHODS: This is a retrospective descriptive study of 75 patients who underwent their first curative epilepsy surgery at an age under 3 years at the authors' institution between 2006 and 2019 and had a minimum 1-year follow-up of seizure and developmental outcomes. Clinical information including surgical complications, seizure outcomes, and developmental quotient (DQ) was collected from medical records. The effects of clinical factors on DQ at 1 year after surgery were evaluated. RESULTS: The median age at surgery was 6 months, peaking at between 3 and 4 months. Operative procedures included 27 cases of hemispherotomy, 19 cases of multilobar surgery, and 29 cases of unilobar surgery. Seizure freedom was achieved in 82.7% of patients at 1 year and in 71.0% of patients at a mean follow-up of 62.8 months. The number of antiseizure medications (ASMs) decreased significantly after surgery, and 19 patients (30.6%) had discontinued their ASMs by the last follow-up. Postoperative complications requiring cerebrospinal fluid (CSF) diversion surgery, such as hydrocephalus and cyst formation, were observed in 13 patients (17.3%). The mean DQ values were 74.2 ± 34.3 preoperatively, 60.3 ± 23.3 at 1 year after surgery, and 53.4 ± 25.1 at the last follow-up. Multiple regression analysis revealed that the 1-year postoperative DQ was significantly influenced by preoperative DQ and postoperative seizure freedom but not by the occurrence of any surgical complication requiring CSF diversion surgery. CONCLUSIONS: Early pediatric epilepsy surgery has an acceptable risk-benefit balance. Seizure control after surgery is important for postoperative development.

DOI： 10.3171/2021.4.PEDS21123

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Implantation of subdural electrodes on the brain surface is still widely performed as one of the "gold standard methods" for the presurgical evaluation of epilepsy. Stereotactic insertion of depth electrodes to the brain can be added to detect brain activities in deep-seated lesions to which surface electrodes are insensitive. This study tried to clarify the efficacy and limitations of combined implantation of subdural and depth electrodes in intractable epilepsy patients. Fifty-three patients with drug-resistant epilepsy underwent combined implantation of subdural and depth electrodes for long-term intracranial electroencephalography (iEEG) before epilepsy surgery. The detectability of early ictal iEEG change (EIIC) were compared between the subdural and depth electrodes. We also examined clinical factors including resection of MRI lesion and EIIC with seizure freedom. Detectability of EIIC showed no significant difference between subdural and depth electrodes. However, the additional depth electrode was useful for detecting EIIC from apparently deep locations, such as the insula and mesial temporal structures, but not in detecting EIIC in patients with ulegyria (glial scar). Total removal of MRI lesion was associated with seizure freedom. Depth electrodes should be carefully used after consideration of the suspected etiology to avoid injudicious usage.

DOI： 10.3390/brainsci11030307

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Partial deletions in chromosomes 1p and 19q are found in a subset of astrocytic tumors; however, it remains unclear how these alterations affect their histological features and prognosis. Herein, we present 3 cases of isocitrate dehydrogenase (IDH)-mutant astrocytoma with chromosome 19q13 deletion. In the first case, the primary tumor harbored an IDH1 mutation with chromosome 1p/19q partial deletions, which covered 19q13 and exhibited a durable initial response to radiotherapy and temozolomide (TMZ) treatment. However, the tumor lost the chromosome 1p/19q partial deletions at recurrence and became resistant to TMZ. Histologically, an oligodendroglioma-like feature was found in the primary tumor but not in the recurrent tumor. Capicua transcriptional repressor (CIC), located on 19q13, was less expressed in the primary tumor but was highly expressed in the recurrent tumor. Similar histological findings were observed in 2 other astrocytic tumors with IDH1 or IDH2 mutations. These tumors also had chromosome 19q13 deletion, including the CIC gene, weakly expressed CIC, and oligodendroglioma-like morphology. These tumors recurred at 6 and 32 months, respectively. These findings suggest that IDH-mutant astrocytoma with chromosome 19q13 partial deletion, including the CIC gene, may induce an oligodendroglioma-like phenotype, but the clinical prognosis may not be similar to that of genetically defined oligodendroglioma.

DOI： 10.1093/jnen/nlaa161

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記述言語：英語  

Background: Intraventricular tumors can generally result in obstructive hydrocephalus as they grow. Rarely, however, some intraventricular tumors develop superficial siderosis (SS) and trigger hydrocephalus, even though the tumor has hardly grown. Here, we present an illustrative case of SS and nonocclusive hydrocephalus caused by subependymoma of the lateral ventricles. Case Description: A 78-year-old man with an intraventricular tumor diagnosed 7 years ago had been suffering from gait disturbance for 2 years. He also developed cognitive impairment. Intraventricular tumors showed little growth on annual magnetic resonance imaging (MRI). MRI T2-star weighted images (T2*WI) captured small intratumoral hemorrhages from the beginning of the follow-up. Three years before, at the same time as the onset of ventricular enlargement, T2*WI revealed low intensity in the whole tumor and cerebral surface. Subsequent follow-up revealed that this hemosiderin deposition had spread to the brain stem and cerebellar surface, and the ventricles had expanded further. Cerebrospinal fluid (CSF) examination revealed xanthochromia. The tumor was completely removed en bloc. Histopathological findings were consistent with those of subependymoma. Although CSF findings improved, SS and hydrocephalus did not improve. Therefore, the patient underwent a lumboperitoneal shunt for CSF diversion after tumor resection. Conclusion: Some intraventricular tumors cause SS and nonobstructive hydrocephalus due to microbleeding, even in the absence of tumor growth. T2*WI and, if necessary, timely CSF examination can allow identification of presymptomatic SS. This follow-up strategy may provide a favorable course by facilitating early intervention in patients with intraventricular lesions, not just subependymomas.

DOI： 10.25259/SNI_868_2021

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Primary central nervous system lymphoma (PCNSL) is an isolated type of lymphoma of the central nervous system and has a dismal prognosis despite intensive chemotherapy. Recent genomic analyses have identified highly recurrent mutations of MYD88 and CD79B in immunocompetent PCNSL, whereas LMP1 activation is commonly observed in Epstein-Barr virus (EBV)-positive PCNSL. However, a lack of clinically representative preclinical models has hampered our understanding of the pathogenic mechanisms by which genetic aberrations drive PCNSL disease phenotypes. Here, we establish a panel of 12 orthotopic, patient-derived xenograft (PDX) models from both immunocompetent and EBV-positive PCNSL and secondary CNSL biopsy specimens. PDXs faithfully retained their phenotypic, metabolic, and genetic features, with 100% concordance of MYD88 and CD79B mutations present in PCNSL in immunocompetent patients. These models revealed a convergent functional dependency upon a deregulated RelA/p65-hexokinase 2 signaling axis, codriven by either mutated MYD88/CD79B or LMP1 with Pin1 overactivation in immunocompetent PCNSL and EBV-positive PCNSL, respectively. Notably, distinct molecular alterations used by immunocompetent and EBV-positive PCNSL converged to deregulate RelA/p65 expression and to drive glycolysis, which is critical for intracerebral tumor progression and FDG-PET imaging characteristics. Genetic and pharmacologic inhibition of this key signaling axis potently suppressed PCNSL growth in vitro and in vivo. These patient-derived models offer a platform for predicting clinical chemotherapeutics efficacy and provide critical insights into PCNSL pathogenic mechanisms, accelerating therapeutic discovery for this aggressive disease. SIGNIFICANCE: A set of clinically relevant CNSL xenografts identifies a hyperactive RelA/p65-hexokinase 2 signaling axis as a driver of progression and potential therapeutic target for treatment and provides a foundational preclinical platform. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/23/5330/F1.large.jpg.

DOI： 10.1158/0008-5472.CAN-20-2425

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We present a case of a 14-year old boy with tumor-associated refractory epilepsy. Positron emission tomography imaging demonstrated a region with heterogeneous high 11C-methionine uptake and a region with homogenous low 18F-fluorodeoxyglucose uptake within the tumor. Histopathological and genomic analyses confirmed the tumor as BRAF V600E-mutated polymorphous low-grade neuroepithelial tumor of the young (PLNTY). Within the high-methionine-uptake region, we observed increased protein levels of L-type amino acid transporter 1 (LAT1), a major transporter of methionine; c-Myc; and constituents of the mitogen-activated protein kinase (MAPK) pathway. We also found that LAT1 expression was linked to the BRAF V600E mutation and subsequent activation of MAPK signaling and c-Myc. Pharmacological and genetic inhibition of the MAPK pathway suppressed c-Myc and LAT1 expression in BRAF V600E-mutated PLNTY and glioblastoma cells. The BRAF inhibitor dabrafenib moderately suppressed cell viability in PLNTY. Collectively, our results indicate that BRAF V600E mutation-activated MAPK signaling and downstream c-Myc induces specific metabolic alterations in PLNTY, and may represent an attractive target in the treatment of the disease.

DOI： 10.1186/s40478-020-01023-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Cognitive risk associated with insular cortex resection is not well understood. The authors reviewed cognitive and developmental outcomes in pediatric patients who underwent resection of the epileptogenic zone involving the insula. METHODS: A review was conducted of 15 patients who underwent resective epilepsy surgery involving the insular cortex for focal cortical dysplasia, with a minimum follow-up of 12 months. The median age at surgery was 5.6 years (range 0.3-13.6 years). Developmental/intelligence quotient (DQ/IQ) scores were evaluated before surgery, within 4 months after surgery, and at 12 months or more after surgery. Repeated measures multivariate ANOVA was used to evaluate the effects on outcomes of the within-subject factor (time) and between-subject factors (resection side, anterior insular resection, seizure control, and antiepileptic drug [AED] reduction). RESULTS: The mean preoperative DQ/IQ score was 60.7 ± 22.8. Left-side resection and anterior insular resection were performed in 9 patients each. Favorable seizure control (International League Against Epilepsy class 1-3) was achieved in 8 patients. Postoperative motor deficits were observed in 9 patients (permanent in 6, transient in 3). Within-subject changes in DQ/IQ were not significantly affected by insular resection (p = 0.13). Postoperative changes in DQ/IQ were not significantly affected by surgical side, anterior insular resection, AED reduction, or seizure outcome. Only verbal function showed no significant changes before and after surgery and no significant effects of within-subject factors. CONCLUSIONS: Resection involving the insula in children with impaired development or intelligence can be performed without significant reduction in DQ/IQ, but carries the risk of postoperative motor deficits.

DOI： 10.3171/2020.5.PEDS2058

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Cerebral bypass surgery, such as the STA-MCA bypass, is one of the essential procedures for cerebral revascularization. However, very narrow or thin blood vessels increase the risk of anastomotic problems, as seen in Moyamoya disease. For such vessels, we have devised the "lifting method" in the recipient arteriotomy. Here, we introduce this novel optional technique and evaluate its effects. METHODS: The "lifting method" is a procedure of lifting the incision edge in a linear incision on the recipient vessel to widen the ostium. We attempted the "lifting method" in 23 consecutive cases (41 arteries) and, as a historical control, compared it with the conventional method of 25 consecutive cases (37 arteries) for the previous 3 years. We compared patient age, years of surgical experience, recipient vessel diameter, anastomotic events and final patency. As a sub-analysis, the same evaluations were done for Moyamoya disease cases. Furthermore, the time required for the lifting procedure was measured retrospectively. RESULTS: The incidence of anastomotic events in the conventional method was 13.5% overall and 19% in Moyamoya disease. No events occurred with the "lifting method" (P <0.05). There was no significant difference in other factors including final patency between the two groups. The time required for lifting procedure averaged at 1 minute 15 seconds. CONCLUSIONS: The "lifting method" widens and secures the ostium in a recipient vessel and greatly facilitates operability. This is a foolproof method enabling safe and reliable anastomosis even in conditions of narrow or thin vessels.

DOI： 10.1016/j.wneu.2020.06.077

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: This study aimed to elucidate the clinical features of water-electrolyte disturbance (WED) as a sequela of hemispherotomy. METHODS: We performed a retrospective chart review to identify the clinical features of diabetes insipidus (DI) as a complication in < 12-month-old patients who underwent hemispherectomy or hemispherotomy for severe epilepsy between 2007 and 2018. Central DI was diagnosed if a patient developed polyuria (urine output > 5 mL/kg/h), abnormally high serum osmolality (> 300 mOsm/kg), high serum sodium level (> 150 mEq/L), either abnormally low urine specific gravity (< 1.005) or low urine osmolality (< 300 mOsm/kg) or both, and effective control of polyuria with arginine vasopressin (AVP). The clinical course of post-hemispherotomy WED, complications other than WED, and seizure outcomes were analyzed. RESULTS: The review identified that 3 of 23 infants developed WED. All patients developed polyuria within 2 days after surgery, with high serum osmolality and hypotonic urine; AVP was effective in treating these symptoms. The clinical course was compatible with central DI. Two patients subsequently developed hyponatremia in a biphasic or triphasic manner. All patients had multiple seizures that were probably related to WED. Two patients developed asymptomatic cerebral sinovenous thrombosis, possibly because of the surgical procedure and dehydration; anticoagulant treatment was provided. All patients were treated for WED for up to 2 months and had no residual pituitary dysfunction. CONCLUSION: Systemic complications other than intracranial ones can occur in patients who have undergone hemispherotomy. Perioperative systemic management of young infants undergoing this procedure should include careful water and electrolyte balance monitoring.

DOI： 10.1007/s00381-019-04452-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although aberrations in the number and function of glutamate AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors are thought to underlie neuropsychiatric disorders, no methods are currently available for visualizing AMPA receptors in the living human brain. Here we developed a positron emission tomography (PET) tracer for AMPA receptors. A derivative of 4-[2-(phenylsulfonylamino)ethylthio]-2,6-difluoro-phenoxyacetamide radiolabeled with 11C ([11C]K-2) showed specific binding to AMPA receptors. Our clinical trial with healthy human participants confirmed reversible binding of [11C]K-2 in the brain according to Logan graphical analysis (UMIN000020975; study design: non-randomized, single arm; primary outcome: dynamics and distribution volumes of [11C]K-2 in the brain; secondary outcome: adverse events of [11C]K-2 during the 4-10 d following dosing; this trial met prespecified endpoints). In an exploratory clinical study including patients with epilepsy, we detected increased [11C]K-2 uptake in the epileptogenic focus of patients with mesial temporal lobe epilepsy, which was closely correlated with the local AMPA receptor protein distribution in surgical specimens from the same individuals (UMIN000025090; study design: non-randomized, single arm; primary outcome: correlation between [11C]K-2 uptake measured with PET before surgery and AMPA receptor protein density examined by biochemical study after surgery; secondary outcome: adverse events during the 7 d following PET scan; this trial met prespecified endpoints). Thus, [11C]K-2 is a potent PET tracer for AMPA receptors, potentially providing a tool to examine the involvement of AMPA receptors in neuropsychiatric disorders.

DOI： 10.1038/s41591-019-0723-9

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記述言語：英語  

DOI： 10.1002/mds.27909

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記述言語：日本語   出版者・発行元：(一社)日本脳神経血管内治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Intractable epilepsy patients with ulegyria could be candidates for resective surgery. Complete resection of ulegyria in the epileptogenic hemisphere is associated with favorable seizure outcome, although the risk of postoperative functional deficits is higher. The authors evaluated the extent of resection and postsurgical outcomes in epilepsy patients with ulegyria who underwent intracranial electroencephalography (iEEG) monitoring prior to resection to clarify the efficacy of iEEG-guided partial resection of ulegyria. METHODS: Ten consecutive epilepsy patients with ulegyria (7 males and 3 females, age range at surgery 7-34 years) underwent iEEG prior to resective surgery between 2011 and 2017 with a minimum follow-up of 12 months (range 12-72 months). The diagnosis of ulegyria was based on the typical pattern of cortical atrophy especially at the bottom of the sulcus on MRI. An iEEG study was indicated after comprehensive preoperative evaluations, including high-field MRI, long-term video-EEG, magnetoencephalography, and FDG-PET. The resection planning was based on iEEG analysis. Total lesionectomy was not always performed, as preservation of cortical function was prioritized. RESULTS: Ulegyria was seen in the occipital and/or parietal lobe in 9 patients and bilaterally in 5 patients. Ictal EEG onset involved the temporal neocortex in 6 patients. Intracranial electrodes were implanted unilaterally in all except 1 patient with bilateral lesions. The extent of MRI lesion was covered by the electrodes. Seizure onset zones (SOZs) and irritative zones (IZs) were identified in all patients. SOZs and IZs were completely resected in 8 patients but were only partially removed in the remaining 2 patients because the eloquent cortices and the epileptogenic zones overlapped. Ulegyria of the epileptogenic side was totally resected in 1 patient. Seizure freedom was achieved in 4 patients, including 3 after partial lesionectomy. Extended resection of the temporal neocortex was performed in 4 patients, although postoperative seizure freedom was achieved only in 1 of these patients. Visual field deficit was seen in 4 patients. Three of 5 patients with bilateral lesions achieved seizure freedom after unilateral resective surgery. CONCLUSIONS: Intracranial EEG-guided partial lesionectomy provides a reasonable chance of postoperative seizure freedom with a lower risk of functional deficits. Patients with bilateral ulegyria should not be excluded from consideration as surgical candidates.

DOI： 10.3171/2019.8.JNS191642

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.eplepsyres.2019.05.012

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To characterize the spatiotemporal dynamics of auditory and picture naming-related cortical activation in Japanese-speaking patients. METHODS: Ten patients were assigned auditory naming and picture naming tasks during extraoperative intracranial EEG recording in a tertiary epilepsy center. Time-frequency analysis determined at what electrode sites and at what time windows during each task the amplitude of high-gamma activity (65-95 Hz) was modulated. RESULTS: The superior-temporal gyrus on each hemisphere showed high-gamma augmentation during sentence listening, whereas the left middle-temporal and inferior-frontal gyri showed high-gamma augmentation peaking around stimulus offset. Auditory naming-specific high-gamma augmentation was noted in the bilateral superior-temporal gyri as well as left frontal-parietal-temporal perisylvian network regions, whereas picture naming-specific augmentation was noted in the occipital-fusiform regions, bilaterally. The inferior pre- and postcentral gyri on each hemisphere showed modality-common high-gamma augmentation time-locked to overt responses. CONCLUSIONS: The spatiotemporal dynamics of auditory and picture naming-related high-gamma augmentation in Japanese-speaking patients were qualitatively similar to those previously reported in studies of English-speaking patients. SIGNIFICANCE: The cortical dynamics for auditory sentence recognition are at least partly shared by cohorts speaking two distinct languages. Multicenter studies regarding the clinical utility of high-gamma language mapping across Eastern and Western hemispheres may be feasible.

DOI： 10.1016/j.clinph.2019.04.008

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掲載種別：研究論文（学術雑誌）   出版者・発行元：American Society of Neuroradiology (ASNR)  

DOI： 10.3174/ajnr.a6067

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1177/1093526619855488

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Cerebellar dysmaturation and injury is associated with a wide range of neuromotor, neurocognitive and behavioral disorders as well as with preterm birth. We used diffusion tensor MR imaging to investigate a disruption in structural cortico-ponto-cerebellar (CPC) connectivity in children with infantile-onset severe epilepsy. METHODS: We performed CPC tract reconstructions in 24 hemimegalencephaly (HME) patients, 28 West syndrome (WS) of unknown etiology patients, and 25 pediatric disease control subjects without a history of epilepsy nor brain abnormality on MRI. To identify the CPC tract, we placed a seeding ROI separately in each right and left cerebral peduncle. We evaluated the distribution patterns of the CPC tracts to the cerebellum and their correlation with clinical findings. RESULTS: In control and WS of unknown etiology groups, both sides' CPC tracts descended to bilateral hemispheres in 20 (80.0%) and 21 (75.0%); mixed (bilateral on one side and unilateral on the other side) in five (20.0%) and five (17.9%); and unilateral in zero (0.0%) and two (7.1%), respectively. However, in the HME, both sides' CPC tracts descended to bilateral hemispheres in four (16.7%); mixed in 13 (54.1%); and unilateral in seven (29.2%). These CPC patterns differed significantly between the HME and other groups (p < 0.001). Among HME patients, those with a unilateral cerebellar distribution on both sides had significantly earlier seizure onset (p = 0.049) and more frequent seizures (p = 0.052) at a trend level compared to those with bilateral and mixed distributions. CONCLUSION: Disrupted CPC tracts were observed more frequently in HME patients than in WS of unknown etiology patients and controls, and they may be correlated with earlier seizure onset and more frequent seizures in HME patients. DTI is a useful and non-invasive method for speculating the pathology in the developing brain.

DOI： 10.1016/j.braindev.2019.01.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Ictal clinical semiology indicates where the patient's seizure arises from and how it progresses. A patient's description of a focal sensory seizure may support a surgical decision even when MRI and PET abnormalities are absent. Ictal deafness is a focal auditory seizure characterized by suppression of hearing, presumably originating from the auditory cortex in the temporal lobe. However, the precise localization has not been confirmed with surgical cases. We present a case in which the region from where ictal deafness arose was confirmed by intracranial electroencephalography, with successful epilepsy surgery and review other published cases.

DOI： 10.1684/epd.2019.1042

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.11477/mf.1436203790

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記述言語：日本語   出版者・発行元：(株)医学書院  

2015年に国際抗てんかん連盟は、てんかん重積の新たな定義を発表し、てんかん重積はてんかん発作が異常に遷延し、脳に長期的な影響を残すリスクを生じる状態とした。てんかん重積はけいれん症状の有無によりけいれん性と非けいれん性てんかん重積(NCSE)に分けられる、NCSEの診断には脳波モニタリングが重要である。治療に対する反応性により、早期、確定、難治、超難治てんかん重積に分けられる。成人における抗てんかん薬の投与量を示した。

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Surgical treatment of the insula is notorious for its high probability of motor complications, particularly when resecting the superoposterior part. Ischemic damage to the pyramidal tract in the corona radiata has been regarded as the cause of these complications, resulting from occlusion of the perforating arteries to the pyramidal tract through the insular cortex. The authors describe a strategy in which a small piece of gray matter is spared at the bottom of the periinsular sulcus, where the perforating arteries pass en route to the pyramidal tract, in order to avoid these complications. This method was successfully applied in 3 patients harboring focal cortical dysplasia in the posterior insula and frontoparietal operculum surrounding the periinsular sulcus. None of the patients developed permanent postoperative motor deficits, and seizure control was achieved in all 3 cases. The method described in this paper can be adopted for functional preservation of the pyramidal tract in the corona radiata when resecting epileptogenic pathologies involving insular and opercular regions.

DOI： 10.3171/2017.1.JNS161278

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.eplepsyres.2017.10.003

Web of Science

PubMed

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記述言語：英語  

DOI： 10.1016/j.wneu.2017.07.016

Web of Science

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.ajpath.2017.01.015

Web of Science

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本臨床神経生理学会  

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記述言語：日本語   出版者・発行元：(一社)日本定位・機能神経外科学会  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J02885&link_issn=&doc_id=20160120490007&doc_link_id=%2Fff8kinou%2F2015%2F005400%2F007%2F0033-0038%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fff8kinou%2F2015%2F005400%2F007%2F0033-0038%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語  

A 66-year-old woman who was previously diagnosed with idiopathic thrombocytopenic purpura (ITP) presented with mild right-sided hemiparesis and drowsiness. Head computed tomography (CT) imaging demonstrated a massive left chronic subdural hematoma (CSDH) with a midline shift. Because initial laboratory data showed a significantly decreased blood platelet count (0.3 × 104/mm3), medical treatments such as platelet transfusion, intravenous immunoglobulin (IVIG), and high-dose corticosteroid therapy, were initiated. She clinically and radiologically responded well to these treatments without any surgical intervention. In addition to presenting our case, we searched the PubMed and Ichushi Web databases to comprehensively illustrate clinical characteristics and treatment outcomes of similar cases. Including the present case, we found 19 reports and 23 cases of CSDH associated with ITP in the literature, and assessed 17 reports and 21 cases that were written in English and Japanese. None or mild neurological symptom were seen in 13 cases, and severe, such as coma and hemiparesis, were described in the younger 8 cases with significant difference. All except one were first treated with medical therapies. Most cases of the former group responded well to conservative therapy. On the other hand, most in the latter eventually needed surgical treatment in addition except recent two cases including the present case. CSDH associated with ITP is rarely described, and its management remains controversial. However, this report highlights multiple continuous medical treatments under strict observation and general care might be a useful alternative to avoid surgery in cases presenting with severe neurological deficits and extremely low platelet counts.

DOI： 10.2176/nmccrj.2014-0209

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Medknow Publications  

DOI： 10.4103/2152-7806.132583

Scopus

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総ページ数：xii, 150p   記述言語：日本語  

CiNii Books

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総ページ数：287p   記述言語：日本語  

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記述言語：日本語   出版者・発行元：(一社)日本臨床神経生理学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：東京 : メディカルレビュー社  

CiNii Books

CiNii Research

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その他リンク： https://ndlsearch.ndl.go.jp/books/R000000004-I032602169

記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：(一社)日本病理学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）  

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記述言語：日本語   出版者・発行元：大阪 : てんかん治療研究振興財団  

CiNii Books

CiNii Research

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その他リンク： https://ndlsearch.ndl.go.jp/books/R000000004-I032540222

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本臨床神経生理学会  

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記述言語：日本語   出版者・発行元：(一社)日本小児神経外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床神経生理学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床神経生理学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床神経生理学会  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：日本脳腫瘍病理学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床神経生理学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床神経生理学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床神経生理学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：日本脳神経CI学会  

海馬硬化症のMRIでは海馬の萎縮とT2高信号が多くの症例で認められるが、5〜10%の症例では明らかな萎縮は伴わないと報告されている。一方、萎縮が明らかでない海馬硬化症の検出にT2 relaxometry(T2R)が有用との報告もある。今回、T2Rが海馬のてんかん原性評価に有用であるか検討した。対象は、2012〜2015年に難治てんかんの改善目的に海馬切除を含む外科治療を行った30例および健常対照群30例とした。検討の結果、萎縮を伴わない海馬のT2R異常は、頭蓋内脳波における側頭葉内側のてんかん発作起始と有意に関連していることが明らかになった。

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：東京 : 日本臨床社  

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その他リンク： https://ndlsearch.ndl.go.jp/books/R000000004-I029081994

記述言語：日本語   出版者・発行元：(一社)日本小児神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本小児神経外科学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本臨床神経生理学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：(一社)日本小児神経学会  

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記述言語：英語   出版者・発行元：(一社)日本小児神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本小児神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本小児神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：(一社)日本小児神経学会  

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記述言語：日本語   出版者・発行元：日本定位・機能神経外科学会事務局  

CiNii Books

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その他リンク： http://search.jamas.or.jp/link/ui/2016123794

記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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記述言語：日本語   出版者・発行元：日本脳腫瘍病理学会  

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J-GLOBAL

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

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J-GLOBAL

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記述言語：日本語  

J-GLOBAL

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種別：学会・研究会等 

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