川合 謙介 (カワイ ケンスケ)

  • 脳神経外科学講座 教授
メールアドレス: kenkawai-tkyjichi.ac.jp
Last Updated :2021/11/23



  • 医学博士(東京大学)


J-Global ID


  • 砂ネズミ   側頭葉てんかん   ラット   軟膜下皮質多切術   難治性てんかん   大脳皮質   スフィンゴシン1リン酸   GABA   AMPA型受容体   Seizure   glutamic acid decarboxylase   機能脳神経外科学   皮質脳波   術中皮質脳波   聴原性痙攣   機能温存的治療   グルタミン酸受容体   易痙攣性   迷走神経刺激療法   immunocy tochemistry   inferior colliculus   cerebral ischemia   一過性全脳虚血   心肺蘇生   局所脳虚血   アポトーシス   視床   遅発性神経細胞死   脳虚血   記憶   海馬   てんかん   


  • ライフサイエンス / 脳神経外科学
  • ライフサイエンス / 生体材料学
  • ライフサイエンス / 生体医工学
  • ライフサイエンス / 耳鼻咽喉科学
  • ライフサイエンス / 脳神経外科学
  • ライフサイエンス / 医療薬学
  • ライフサイエンス / 生理学
  • ライフサイエンス / 神経科学一般
  • ライフサイエンス / 神経科学一般
  • ライフサイエンス / 神経科学一般
  • ライフサイエンス / 神経科学一般


  • 2016年01月 - 現在  自治医科大学脳神経外科教授
  • 2013年09月 - 2015年12月  NTT東日本関東病院脳神経外科部長
  • 2013年09月 - 2015年12月  東京医療保健大学教授
  • 2008年06月 - 2013年08月  東京大学大学院脳神経外科准教授
  • 2003年06月 - 2008年05月  東京大学医学部脳神経外科講師
  • 2000年04月 - 2003年05月  東京都立神経病院脳神経外科
  • 1996年06月 - 2000年03月  東京大学脳神経外科助手
  • 1993年04月 - 1996年03月  帝京大学脳神経外科助手
  • 1990年01月 - 1992年08月  米国国立衛生研究所NINDS, Stroke BranchVisiting fellow


  •         - 1987年   東京大学   医学部   医学科


  • 日本神経科学会   日本神経学会   日本てんかん外科学会   日本てんかん学会   日本脳神経外科学会   



  • Nobuhiro Mikuni, Naotaka Usui, Hiroshi Otsubo, Kensuke Kawai, Haruhiko Kishima, Taketoshi Maehara, Seiichiro Mine, Takamichi Yamamoto
    Neurologia medico-chirurgica 2021年10月 
    This study investigated the number of epilepsy surgeries performed over time in Japan, and conducted a questionnaire survey of the Japan Neurosurgical Society (JNS) training program core hospitals to determine the current status and future objectives of surgical therapies and epilepsy training programs for physicians in Japan. This article presents part of a presentation delivered as a presidential address at the 44th Annual Meeting of the Epilepsy Surgery Society of Japan held in January 2021. The number of epilepsy surgeries performed per year has increased in Japan since 2011 to around 1,200 annually between 2015 and 2018. The questionnaire survey showed that 50% of the responding hospitals performed epilepsy surgery and 29% had an epilepsy center, and that these hospitals provided senior residents with education regarding epilepsy surgery. The presence of an epilepsy center in a hospital was positively correlated with the availability of long-term video electroencephalography monitoring beds as well as the number of epilepsy surgeries performed at the hospital. In regions with no medical facilities offering specialized surgical therapies for epilepsy, the JNS training program core hospitals may help improve epilepsy diagnosis and treatment. They may also increase the number of safe and effective surgeries by establishing epilepsy centers that can perform long-term video electroencephalography monitoring, providing junior neurosurgeons with training regarding epilepsy, and playing a core role in surgical therapies for epilepsy in tertiary medical areas in close cooperation with neighboring medical facilities.
  • Ayumi Matsumoto, Karin Kojima, Fuyuki Miya, Akihiko Miyauchi, Kazuhisa Watanabe, Sadahiko Iwamoto, Kensuke Kawai, Mitsuhiro Kato, Yukitoshi Takahashi, Takanori Yamagata
    Brain & development 43 8 857 - 862 2021年09月 
    BACKGROUND: The DYNC1H1 gene encodes the heavy chain of cytoplasmic dynein 1, a core structure of the cytoplasmic dynein complex. Dominant DYNC1H1 mutations are implicated in Charcot-Marie-Tooth disease, axonal, type 20, spinal muscular atrophy, lower extremity-predominant 1, and autosomal dominant mental retardation 13 with neuronal migration defects. We report two patients with DYNC1H1 mutations who had intractable epilepsy and intellectual disability (ID), one with and one without pachygyria. CASE REPORTS: Patient 1 had severe ID. At the age of 2 months, she presented myoclonic seizures and tonic seizures, and later experienced atonic seizures and focal impaired-awareness seizures (FIAS). EEG showed slow waves in right central areas during myoclonic seizures. Brain MRI revealed pachygyria, predominantly in the occipital lobe. After callosal transection her atonic seizures disappeared, but FIAS remained. Patient 2 was diagnosed with autism spectrum disorder (ASD) and severe ID. At the age of 7 years, he presented generalized tonic-clonic seizures, myoclonic seizures, and FIAS. Interictal EEG showed generalized spike-and-wave complexes, predominantly in the left frontal area. Brain MRI was unremarkable. Exome sequencing revealed novel de novo mutations in DYNC1H1: c.4691A > T, p.(Glu1564Val) in Patient 1 and c.12536 T > C, p.(Leu4179Ser) in Patient 2. CONCLUSIONS: DYNC1H1 comprises a stem, stalk, and six AAA domains. Patient 2 is the second report of an AAA6 domain mutation without malformations of cortical development. The p.(Gly4072Ser) mutation in the AAA6 domain was also reported in a patient with ASD. It may be that the AAA6 domain has little effect on neuronal movement of DYNC1H1 along microtubules.
  • Yoshihide Sehara, Yuka Hayashi, Kenji Ohba, Ryosuke Uchibori, Masashi Urabe, Ayumu Inutsuka, Kuniko Shimazaki, Kensuke Kawai, Hiroaki Mizukami
    Human gene therapy 2021年08月 
    The safety and high efficiency of adeno-associated virus (AAV) vectors has facilitated their wide scale use to deliver therapeutic genes for experimental and clinical purposes in diseases affecting the central nervous system (CNS). AAV1, 2, 5, 8, 9, and rh10 are the most commonly used serotypes for CNS applications. Most AAVs are known to transduce genes predominantly into neurons. However, the precise tropism of AAVs in the dentate gyrus (DG), the region where persistent neurogenesis occurs in the adult brain, is not fully understood. We stereotaxically injected 1.5 × 1010 viral genomes of AAV2, 5, or rh10 carrying green fluorescent protein (GFP) into the right side of gerbil hippocampus, and performed immunofluorescent analysis using differentiation stage-specific markers one week after injection. We found that AAV5 showed a significantly larger number of double positive cells for GFP and Sox2 in the DG, compared to the AAV2 and rh10 groups. On the other hand, AAVrh10 presented a substantially larger number of double positive cells for GFP and NeuN in the DG, compared to AAV2 and AAV5. Our findings indicated that AAV5 showed high transduction efficiency to neural stem cells and precursor cells, while AAVrh10 showed much higher efficiency to mature neurons in the DG.
  • Shinsaku Yoshitomi, Shin-Ichiro Hamano, Masaharu Hayashi, Hiroshi Sakuma, Shinichi Hirose, Atsushi Ishii, Ryoko Honda, Akio Ikeda, Katsumi Imai, Kazutaka Jin, Akiko Kada, Akiyoshi Kakita, Mitsuhiro Kato, Kensuke Kawai, Tamihiro Kawakami, Katsuhiro Kobayashi, Toyojiro Matsuishi, Takeshi Matsuo, Shin Nabatame, Nobuhiko Okamoto, Susumu Ito, Akihisa Okumura, Akiko Saito, Hideaki Shiraishi, Hiroshi Shirozu, Takashi Saito, Hidenori Sugano, Yukitoshi Takahashi, Hitoshi Yamamoto, Tetsuhiro Fukuyama, Ichiro Kuki, Yushi Inoue
    Epileptic disorders : international epilepsy journal with videotape 23 4 579 - 589 2021年08月 
    OBJECTIVE: To unveil current medical and psychosocial conditions of patients with West syndrome in Japan. METHODS: A cross-sectional analysis was performed in patients with West syndrome registered in the Rare Epilepsy Syndrome Registry (RES-R) of Japan. Furthermore, new-onset patients registered in the RES-R were observed prospectively and their outcomes after one and two years of follow-up were compared with data at onset. RESULTS: For the cross-sectional study, 303 patients with West syndrome were included. Seizures (such as spasms, tonic seizures and focal seizures) occurred daily in 69.3% of the patients at registration. Seizure frequency of less than one per year was observed in cases of unknown etiology (22.6%), genetic etiology (23.8%) and malformation of cortical development (MCD; 19.1%). Neurological findings were absent in 37.0%, but a high rate of abnormality was seen in patients with Aicardi syndrome, hypoxic-ischemic encephalopathy (HIE), genetic etiology and MCD other than focal cortical dysplasia, accompanied by a >50% rate of bedridden patients. Abnormal EEG was found in 96.7%, and CT/MRI was abnormal in 62.7%. Treatments included antiepileptic drug therapy (94.3%), hormonal therapy (72.6%), diet therapy (8.3%) and surgery (15.8%). Intellectual/developmental delay was present in 88.4%, and was more severe in patients with Aicardi syndrome, genetic etiology and HIE. Autism spectrum disorder was found in 13.5%. For the longitudinal study, 27 new-onset West syndrome patients were included. The follow-up study revealed improved seizure status after two years in 66.7%, but worsened developmental status in 55.6%, with overall improvement in 51.9%. SIGNIFICANCE: The study reveals the challenging neurological, physical and developmental aspects, as well as intractable seizures, in patients with West syndrome. More than a half of the children showed developmental delay after onset, even though seizures were reduced during the course of the disease.
  • Kosuke Matsuzono, Tomoya Yagisawa, Keisuke Ohtani, Yohei Ishishita, Takashi Yamaguchi, Takafumi Mashiko, Tadashi Ozawa, Reiji Koide, Ryota Tanaka, Kensuke Kawai, Shigeru Fujimoto
    The Journal of international medical research 49 8 3000605211035197 - 3000605211035197 2021年08月 
    Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma, but its diagnosis is challenging in some cases. A brain biopsy is the gold standard for diagnosing PCNSL, but its invasiveness can be problematic. Thus, noninvasive imaging examinations have been developed for the pre-surgical diagnosis of PCNSL, including gadolinium-enhanced magnetic resonance imaging (MRI), 123I-N-isopropyl-p-iodoamphetamine single-photon emission computed tomography (123I-IMP SPECT), and positron emission tomography with 18F-fluorodeoxyglucose (18F-FDG PET). Here, we report the case of a 71-year-old woman with negative imaging findings for PCNSL, but who was diagnosed with PCNSL by a brain biopsy and histological analysis. Her imaging results were negative for gadolinium-enhanced cranial MRI, with low uptake in 123I-IMP SPECT and hypometabolism in 18F-FDG PET. However, a stereotactic brain biopsy from an abnormal lesion revealed that many round cells had infiltrated into the brain. Moreover, many infiltrating cells were positive for cluster of differentiation (CD)20 and CD79a, and proliferation marker protein Ki-67-positive cells accounted for nearly 80% of all cells. Based on these results, our final pathological diagnosis was PCNSL. The present case highlights the possibility of a PCNSL diagnosis even when all imaging-related examinations display negative results.
  • Taku Uchiyama, Akira Gomi, Sumihito Nobusawa, Noriyoshi Fukushima, Daisuke Matsubara, Kensuke Kawai
    Brain tumor pathology 38 3 250 - 256 2021年07月 
    Rosette-forming glioneuronal tumors (RGNTs) are benign WHO grade 1 tumors that occur in the ventricular system, particularly the fourth ventricle. RGNTs and dysembryoplastic neuroepithelial tumors (DNTs) are both categorized as neuronal and mixed neuronal-glial tumors and may be difficult to distinguish. Coexistence of the two tumor types has been reported. Here, we report a pediatric case of RGNT with DNT-like features showing intraventricular dissemination. The tumor occurred in the medial temporal lobe and presented with specific pathological glioneuronal elements including floating neurons, which are typical in DNTs, but was diagnosed as RGNT because of the presence of neurocytic rosettes. Genetic analysis detected fibroblast growth factor receptor 1 internal tandem duplication (FGFR1-ITD) of the tyrosine kinase domain, which was previously reported to be specific for DNT. RGNTs with FGFR1-ITD may show atypical clinical presentation and pathological features.
  • Mariko Tada, Kenji Kirihara, Yohei Ishishita, Megumi Takasago, Naoto Kunii, Takanori Uka, Seijiro Shimada, Kenji Ibayashi, Kensuke Kawai, Nobuhito Saito, Daisuke Koshiyama, Mao Fujioka, Tsuyoshi Araki, Kiyoto Kasai
    Cerebral cortex (New York, N.Y. : 1991) 31 10 4518 - 4532 2021年04月 
    Gamma oscillations are physiological phenomena that reflect perception and cognition, and involve parvalbumin-positive γ-aminobutyric acid-ergic interneuron function. The auditory steady-state response (ASSR) is the most robust index for gamma oscillations, and it is impaired in patients with neuropsychiatric disorders such as schizophrenia and autism. Although ASSR reduction is known to vary in terms of frequency and time, the neural mechanisms are poorly understood. We obtained high-density electrocorticography recordings from a wide area of the cortex in 8 patients with refractory epilepsy. In an ASSR paradigm, click sounds were presented at frequencies of 20, 30, 40, 60, 80, 120, and 160 Hz. We performed time-frequency analyses and analyzed intertrial coherence, event-related spectral perturbation, and high-gamma oscillations. We demonstrate that the ASSR is globally distributed among the temporal, parietal, and frontal cortices. The ASSR was composed of time-dependent neural subcircuits differing in frequency tuning. Importantly, the frequency tuning characteristics of the late-latency ASSR varied between the temporal/frontal and parietal cortex, suggestive of differentiation along parallel auditory pathways. This large-scale survey of the cortical ASSR could serve as a foundation for future studies of the ASSR in patients with neuropsychiatric disorders.
  • Yoshihide Sehara, Yoshihito Ando, Takumi Minezumi, Nozomi Funayama, Kensuke Kawai, Mikio Sawada
    Cognitive and behavioral neurology : official journal of the Society for Behavioral and Cognitive Neurology 34 1 70 - 75 2021年03月 
    Global autobiographical amnesia is a rare disorder that is characterized by a sudden loss of autobiographical memories covering many years of an individual's life. Generally, routine neuroimaging studies such as CT and MRI yield negative findings in individuals with global autobiographical amnesia. However, in recent case reports, functional analyses such as SPECT and fMRI have revealed changes in activity in various areas of the brain when compared with controls. Studies using iomazenil (IMZ) SPECT with individuals with global autobiographical amnesia have not been reported. We report the case of a 62-year-old Japanese woman with global autobiographical amnesia who had disappeared for ∼4 weeks. [123I]-IMZ SPECT showed reduced IMZ uptake in her left medial temporal lobe and no significant reduction on N-isopropyl-[123I] p-iodoamphetamine (IMP) SPECT in the identical region. Because IMZ binds to the central benzodiazepine receptor, this dissociation between IMZ and IMP SPECT was thought to reflect the breakdown of inhibitory neurotransmission in the left medial temporal lobe. Moreover, when the woman recovered most of her memory 32 months after fugue onset, the IMZ SPECT-positive lesion had decreased in size. Because the woman had long suffered verbal abuse from her former husband's sister and brother, which can also cause global autobiographical amnesia, it is difficult to conclude whether the IMZ SPECT-positive lesion in the left medial temporal lobe was the cause or the result of her global autobiographical amnesia. Although only one case, these observations suggest that IMZ SPECT may be useful in uncovering the mechanisms underlying global autobiographical amnesia.
  • Motoki Inaji, Takamichi Yamamoto, Kensuke Kawai, Taketoshi Maehara, Werner K Doyle
    Neurologia medico-chirurgica 61 1 1 - 11 2021年01月 
    Patients with drug-resistant focal onset epilepsy are not always suitable candidates for resective surgery, a definitive intervention to control their seizures. The alternative surgical treatment for these patients in Japan has been vagus nerve stimulation (VNS). Besides VNS, epileptologists in the United States can choose a novel palliative option called responsive neurostimulation (RNS), a closed-loop neuromodulation system approved by the US Food and Drug Administration in 2013. The RNS System continuously monitors neural electroencephalography (EEG) activity at the possible seizure onset zone (SOZ) where electrodes are placed and responds with electrical stimulation when a pre-defined epileptic activity is detected. The controlled clinical trials in the United States have demonstrated long-term utility and safety of the RNS System. Seizure reduction rates have continued to improve over time, reaching 75% over 9 years of treatment. The incidence of implant-site infection, the most frequent device-related adverse event, is similar to those of other neuromodulation devices. The RNS System has shown favorable efficacy for both mesial temporal lobe epilepsy (TLE) and neocortical epilepsy of the eloquent cortex. Another unique advantage of the RNS System is its ability to provide chronic monitoring of ambulatory electrocorticography (ECoG). Valuable information obtained from ECoG monitoring provides a better understanding of the state of epilepsy in each patient and improves clinical management. This article reviews the developmental history, structure, and clinical utility of the RNS System, and discusses its indications as a novel palliative option for drug-resistant epilepsy.
  • Yuiko Kimura, Toshihiro Mashiko, Eiju Watanabe, Kensuke Kawai
    Surgical neurology international 12 70 - 70 2021年 
    Background: In recent years, young neurosurgeons have had few opportunities to gain experience with clipping surgeries. The first author was sometimes surprised that she could not predict the anatomical relationships between the aneurysm and vessels during actual surgery. This study investigated the differences between the expected and actual operative findings during clipping surgery for aneurysms of the middle cerebral artery. Methods: Medical records for 15 patients who underwent rotational three-dimensional (3D) digital subtraction angiography (3D-DSA) before the clipping surgery were analyzed after the surgery. The anatomical relationships between the aneurysm and parent arteries were defined by the intraoperative findings just before clipping. The viewing direction to obtain this definitive perspective (virtual viewing direction) was measured. The angle between this viewing direction and the coordinate axis was denoted as the "virtual angle for clipping (VAC)." Results: The VAC between the X-axis and viewing direction on the XY-plane (VAC-XY) ranged from -43° to +73° (mean, +27°), and the angle between the XY-plane and viewing direction (VAC-Z) ranged from +25° to -34° (mean, 5.5°). The difference between the VAC-XY and mean angle was significantly larger in cases with hidden branches behind the aneurysm. In these cases, the virtual viewing direction visualized the neck of the aneurysm. There is no correlation between M1 length and VAC-XY or VAC-Z discrepancy. Conclusion: 3D-DSA or 3D computed tomography angiography images visualizing the neck of the aneurysm should be obtained in combination with images obtained from the standard oblique angle.
  • Rintaro Kuroda, Kaoru Tominaga, Katsumi Kasashima, Kenji Kuroiwa, Eiji Sakashita, Hiroko Hayakawa, Tom Kouki, Nobuhiko Ohno, Kensuke Kawai, Hitoshi Endo
    PloS one 16 7 e0255355  2021年 
    Mitochondrial dysfunction is significantly associated with neurological deficits and age-related neurological diseases. While mitochondria are dynamically regulated and properly maintained during neurogenesis, the manner in which mitochondrial activities are controlled and contribute to these processes is not fully understood. Mitochondrial transcription factor A (TFAM) contributes to mitochondrial function by maintaining mitochondrial DNA (mtDNA). To clarify how mitochondrial dysfunction affects neurogenesis, we induced mitochondrial dysfunction specifically in murine neural stem cells (NSCs) by inactivating Tfam. Tfam inactivation in NSCs resulted in mitochondrial dysfunction by reducing respiratory chain activities and causing a severe deficit in neural differentiation and maturation both in vivo and in vitro. Brain tissue from Tfam-deficient mice exhibited neuronal cell death primarily at layer V and microglia were activated prior to cell death. Cultured Tfam-deficient NSCs showed a reduction in reactive oxygen species produced by the mitochondria. Tfam inactivation during neurogenesis resulted in the accumulation of ATF4 and activation of target gene expression. Therefore, we propose that the integrated stress response (ISR) induced by mitochondrial dysfunction in neurogenesis is activated to protect the progression of neurodegenerative diseases.
  • Yoshiyuki Onuki, Sayaka Ono, Takeshi Nakajima, Karin Kojima, Naoyuki Taga, Takahiro Ikeda, Mari Kuwajima, Yoshie Kurokawa, Mitsuhiro Kato, Kensuke Kawai, Hitoshi Osaka, Toshihiko Sato, Shin-Ichi Muramatsu, Takanori Yamagata
    Brain communications 3 3 fcab078  2021年 
    Aromatic l-amino acid decarboxylase (AADC) is an essential dopamine-synthesizing enzyme. In children with AADC deficiency, the gene delivery of AADC into the putamen, which functionally interacts with cortical regions, was found to improve motor function and ameliorate dystonia. However, how the restoration of dopamine in the putamen in association with cortico-putaminal networks leads to therapeutic effects remains unclear. Here, we examined neuroimaging data of eight patients with AADC deficiency (five males and three females, age range 4-19 years) who received the AADC gene therapy of the bilateral putamen in an open-label phase 1/2 study. Using high-resolution positron emission tomography with a specific AADC tracer, 6-[18F]fluoro-l-m-tyrosine (FMT), we showed that FMT uptake increased in the broad area of the putamen over the years. Then, with the structural connectivity-based parcellation of the putaminal area, we found that motor improvement is associated with dopaminergic restoration of the putaminal area that belongs to the prefrontal cortico-putaminal network. The prefrontal area dominantly belongs to the frontoparietal control network, which contributes to cognitive-motor control function, including motor initiation and planning. The results suggest that putaminal dopamine promotes the development of an immature motor control system, particularly in the human prefrontal cortex that is primarily affected by AADC deficiency.
  • Naoto Kunii, Tomoyuki Koizumi, Kensuke Kawai, Seijiro Shimada, Nobuhito Saito
    Frontiers in human neuroscience 15 726087 - 726087 2021年 
    Background: Vagus nerve stimulation (VNS) is an established palliative surgical treatment for refractory epilepsy. Recently, pairing VNS with rehabilitation received growing attention for their joint effect on neural plasticity. However, objective biological measurements proving the interaction between VNS effects and cortical recruitment are lacking. Studies reported that VNS induced little blood flow increase in the cerebral cortex. Objective: This study tested the hypothesis that pairing VNS with a cognitive task amplifies task-induced cerebral blood flow (CBF). Methods: This study included 21 patients implanted with vagus nerve stimulator to treat refractory epilepsy. Near-infrared spectroscopy (NIRS) with sensors on the forehead measured CBF changes in the frontal cortices in response to VNS. Cerebral blood flow was measured when VNS was delivered during a resting state or a verbal fluency task. We analyzed the VNS effect on CBF in relation to stimulation intensity and clinical responsiveness. Results: We observed no CBF change when VNS was delivered during rest, irrespective of stimulation intensity or responsiveness. Cerebral blood flow changed significantly when a verbal fluency task was paired with VNS in a stimulation intensity-dependent manner. Cerebral blood flow changes in the non-responders showed no intensity-dependency. Conclusion: Our results could be an important biological proof of the interaction between VNS effects and cortical recruitment, supporting the validity of pairing VNS with rehabilitation.
  • Hirokazu Takahashi, Ali Emami, Takashi Shinozaki, Naoto Kunii, Takeshi Matsuo, Kensuke Kawai
    Computers in biology and medicine 125 104016 - 104016 2020年10月 
    OBJECTIVE: In long-term video-monitoring, automatic seizure detection holds great promise as a means to reduce the workload of the epileptologist. A convolutional neural network (CNN) designed to process images of EEG plots demonstrated high performance for seizure detection, but still has room for reducing the false-positive alarm rate. METHODS: We combined a CNN that processed images of EEG plots with patient-specific autoencoders (AE) of EEG signals to reduce the false alarms during seizure detection. The AE automatically logged abnormalities, i.e., both seizures and artifacts. Based on seizure logs compiled by expert epileptologists and errors made by AE, we constructed a CNN with 3 output classes: seizure, non-seizure-but-abnormal, and non-seizure. The accumulative measure of number of consecutive seizure labels was used to issue a seizure alarm. RESULTS: The second-by-second classification performance of AE-CNN was comparable to that of the original CNN. False-positive seizure labels in AE-CNN were more likely interleaved with "non-seizure-but-abnormal" labels than with true-positive seizure labels. Consequently, "non-seizure-but-abnormal" labels interrupted runs of false-positive seizure labels before triggering an alarm. The median false alarm rate with the AE-CNN was reduced to 0.034 h-1, which was one-fifth of that of the original CNN (0.17 h-1). CONCLUSIONS: A label of "non-seizure-but-abnormal" offers practical benefits for seizure detection. The modification of a CNN with an AE is worth considering because AEs can automatically assign "non-seizure-but-abnormal" labels in an unsupervised manner with no additional demands on the time of the epileptologist.
  • Kensuke Kawai
    No shinkei geka. Neurological surgery 48 9 866 - 876 2020年09月
  • Hirokazu Takahashi, Tomoyo I Shiramatsu, Rie Hitsuyu, Kenji Ibayashi, Kensuke Kawai
    Scientific reports 10 1 8932 - 8932 2020年06月 
    Neuromodulation achieved by vagus nerve stimulation (VNS) induces various neuropsychiatric effects whose underlying mechanisms of action remain poorly understood. Innervation of neuromodulators and a microcircuit structure in the cerebral cortex informed the hypothesis that VNS exerts layer-specific modulation in the sensory cortex and alters the balance between feedforward and feedback pathways. To test this hypothesis, we characterized laminar profiles of auditory-evoked potentials (AEPs) in the primary auditory cortex (A1) of anesthetized rats with an array of microelectrodes and investigated the effects of VNS on AEPs and stimulus specific adaptation (SSA). VNS predominantly increased the amplitudes of AEPs in superficial layers, but this effect diminished with depth. In addition, VNS exerted a stronger modulation of the neural responses to repeated stimuli than to deviant stimuli, resulting in decreased SSA across all layers of the A1. These results may provide new insights that the VNS-induced neuropsychiatric effects may be attributable to a sensory gain mechanism: VNS strengthens the ascending input in the sensory cortex and creates an imbalance in the strength of activities between superficial and deep cortical layers, where the feedfoward and feedback pathways predominantly originate, respectively.
  • Takuji Nishida, Kensuke Kawai, Hisateru Tachimori
    Seizure 76 110 - 115 2020年02月 
    PURPOSE: The Japanese authorities require a 2-year seizure-free period for a driver's license in people with epilepsy. To evaluate the stringency of the criteria, we calculated the risk of fatal traffic crashes by epileptic seizure and compared that to the risk of fatal traffic crashes among the general population. METHODS: Nation-wide questionnaire surveys to physicians and their patients with epilepsy were conducted to determine the rate of seizure recurrence after given seizure-free periods, average driving time and the rate of traffic crashes by epileptic seizures. The risk of fatal traffic crashes by epileptic seizures was calculated using the method proposed by the Driving License Committee of the EU. The risk of fatal traffic crashes among subgroups of the general population was calculated using the national statistics available. RESULTS: Valid answers were obtained from a total of 548 patients of 138 epilepsy-specialists and 102 non epilepsy-specialist physicians. The relative risks of fatal traffic crashes in people with epilepsy with 1-year and 2-year seizure-free periods were 1.22 and 1.15, compared to the general population, while the ones in males in their twenties, people aged 60 and over, people aged 65 and over, and people aged 75 and over among the general population were 1.71, 1.31, 1.52 and 2.69, respectively. CONCLUSION: The risk of fatal traffic crashes in people with epilepsy for 1-year and 2-year seizure-free periods was estimated to be lower than that of some age groups in the general population. The increased risk in 1-year seizure freedom from that in 2-year seizure freedom was relatively small.
  • Tomoaki Ban, Yohei Ishishita, Masayuki Tetsuka, Taku Uchiyama, Keisuke Ohtani, Kensuke Kawai
    Epilepsy & behavior reports 13 100356 - 100356 2020年 
    An epileptic seizure during the course of driving can result in a serious car accident. However, basic data on how epileptic seizures actually affect driving performance is significantly lacking. To understand the relationship, it is crucial to conduct not only behavioral but also electroencephalogram (EEG) analysis during epileptic seizures. Therefore, we developed a mobile driving simulator which makes it possible to record driving-related parameters time-lined with video-EEG. We report a case in which behavioral and EEG changes were successfully recorded during ictal periods of focal impaired awareness seizure in a patient engaged with the system. With the current lack of objective data describing how seizures impair driving performance, such an accumulation of information could improve personalized medical management, influence legal adjudication and assist in the development of driving support systems for people with epilepsy.
  • Tadashi Ozawa, Ryota Tanaka, Risa Nagaoka, Yuhei Anan, Younhee Kim, Kosuke Matsuzono, Takafumi Mashiko, Reiji Koide, Haruo Shimazaki, Keisuke Ohtani, Yusuke Amano, Kensuke Kawai, Shigeru Fujimoto
    Data in brief 27 104648 - 104648 2019年12月 [査読有り][通常論文]
    Data presented in this article are related to our article entitled "Unilateral posterior reversible encephalopathy syndrome: A case report" [1]. Cases of Posterior Reversible Encephalopathy Syndrome (PRES) involving unilateral lesions are very rare. We searched the PubMed database using keywords such as PRES, unilateral, and asymmetric and found a small number of cases to include in our review. We summarized the characteristics of these reported cases of unilateral PRES, including our case.
  • Makoto Satoh, Takeshi Nakajima, Takashi Yamaguchi, Eiju Watanabe, Kensuke Kawai
    Neurologia medico-chirurgica 59 11 444 - 447 2019年11月 
    Both frame-based stereotaxy and frameless stereotaxy are established surgical procedures. However, they each have their respective disadvantages when used in the biopsy of a deep-seated lesion. To overcome the drawbacks associated with these procedures, we evaluated the feasibility of applying augmented reality (AR) to stereotactic biopsy. We applied our trans-visible navigator (TVN) to frame-based stereotactic biopsy in five cases of deep-seated lesions. This navigation system uses the AR concept, allowing surgeons to view three-dimensional virtual models of anatomical structures superimposed over the surgical field on a tablet personal computer. Using TVN, we could easily confirm a clear trajectory avoiding the important structures as well as the target point's location in the lesion. Use of the stereotactic apparatus allowed the surgeon to easily advance the biopsy probe to the target point. Consequently, a satisfactory histopathological diagnosis without complication was achieved in all cases. In conclusion, applying AR to stereotactic biopsy is feasible and may improve the safety of the procedure.
  • Kensuke Kawai
    No shinkei geka. Neurological surgery 47 10 1021 - 1036 2019年10月
  • Tadashi Ozawa, Ryota Tanaka, Risa Nagaoka, Yuhei Anan, Younhee Kim, Kosuke Matsuzono, Takafumi Mashiko, Reiji Koide, Haruo Shimazaki, Keisuke Ohtani, Yusuke Amano, Kensuke Kawai, Shigeru Fujimoto
    Clinical neurology and neurosurgery 185 105493 - 105493 2019年10月 [査読有り][通常論文]
  • ミニブタ皮質脳波測定による軟膜下皮質多切術の安全性の検討
    石下 洋平, 庭山 雅嗣, 齋藤 敏之, 大貫 良幸, 内山 拓, 横田 英典, 渡辺 英寿, 川合 謙介
    てんかん研究 37 2 532 - 532 (一社)日本てんかん学会 2019年09月 [査読有り][通常論文]
  • RNS(Responsive Neurostimulation)
    稲次 基希, 山本 貴道, 川合 謙介, 前原 健寿, Doyle Werner
    てんかん研究 37 2 448 - 448 (一社)日本てんかん学会 2019年09月 [査読無し][通常論文]
  • Miyata S, Tominaga K, Sakashita E, Urabe M, Onuki Y, Gomi A, Yamaguchi T, Mieno M, Mizukami H, Kume A, Ozawa K, Watanabe E, Kawai K, Endo H
    Scientific reports 9 1 9787 - 9787 2019年07月 [査読有り][通常論文]
    Gliomas with Isocitrate dehydrogenase 1 (IDH1) mutation have alterations in several enzyme activities, resulting in various metabolic changes. The aim of this study was to determine a mechanism for the better prognosis of gliomas with IDH mutation by performing metabolomic analysis. To understand the metabolic state of human gliomas, we analyzed clinical samples obtained from surgical resection of glioma patients (grades II-IV) with or without the IDH1 mutation, and compared the results with U87 glioblastoma cells overexpressing IDH1 or IDH1R132H. In clinical samples of gliomas with IDH1 mutation, levels of D-2-hydroxyglutarate (D-2HG) were increased significantly compared with gliomas without IDH mutation. Gliomas with IDH mutation also showed decreased intermediates in the tricarboxylic acid cycle and pathways involved in the production of energy, amino acids, and nucleic acids. The marked difference in the metabolic profile in IDH mutant clinical glioma samples compared with that of mutant IDH expressing cells includes a decrease in β-oxidation due to acyl-carnitine and carnitine deficiencies. These metabolic changes may explain the lower cell division rate observed in IDH mutant gliomas and may provide a better prognosis in IDH mutant gliomas.
  • Ali Emami, Naoto Kunii, Takeshi Matsuo, Takashi Shinozaki, Kensuke Kawai, Hirokazu Takahashi
    Computers in biology and medicine 110 227 - 233 2019年07月 [査読有り][通常論文]
    INTRODUCTION: Epileptologists could benefit from a diagnosis support system that automatically detects seizures because visual inspection of long-term electroencephalograms (EEGs) is extremely time-consuming. However, the diversity of seizures among patients makes it difficult to develop universal features that are applicable for automatic seizure detection in all cases, and the rarity of seizures results in a lack of sufficient training data for classifiers. METHODS: To overcome these problems, we utilized an autoencoder (AE), which is often used for anomaly detection in the field of machine learning, to perform seizure detection. We hypothesized that multichannel EEG signals are compressible by AE owing to their spatio-temporal coupling and that the AE should be able to detect seizures as anomalous events from an interictal EEG. RESULTS: Through experiments, we found that the AE error was able to classify seizure and nonseizure states with a sensitivity of 100% in 22 out of 24 available test subjects and that the AE was better than the commercially available software BESA and Persyst for half of the test subjects. CONCLUSIONS: These results suggest that the AE error is a feasible candidate for a universal seizure detection feature.
  • Shimazaki K, Kobari T, Oguro K, Yokota H, Kasahara Y, Murashima Y, Watanabe E, Kawai K, Okada T
    Molecular therapy. Methods & clinical development 13 180 - 186 2019年06月 [査読有り][通常論文]
    © 2019 The Author(s) Gene therapy has been employed as a therapeutic approach for intractable focal epilepsies. Considering the potential of focal GABAergic neuromodulation in regulating epileptogenesis, the GABA-producing enzyme, γ-aminobutyric acid decarboxylase 67 (GAD67), is highly suitable for epilepsy therapy. The EL/Suz (EL) mouse is a model of multifactorial temporal lobe epilepsy. In the present study, we examined focal gene transduction in epileptic EL mice using recombinant adeno-associated virus serotype 8 (rAAV8) expressing human GAD67 to enhance GABA-mediated neural inhibition. Eight-week-old mice were bilaterally injected with rAAV8-GFP or rAAV8-GAD67 in the hippocampal CA3 region. After four weeks, the GAD67-transduced EL mice, but not the rAAV-GFP-treated EL mice, exhibited a significant reduction in seizure generation. The GAD67-mediated depression became stable after 14 weeks. The excitability of the CA3 region was markedly reduced in the GAD67-transduced EL mice, consistent with the results of the Ca 2+ imaging using hippocampal slices. In addition, downregulation of c-Fos expression was observed in GAD67-transduced hippocampi. Our findings showed that rAAV8-GAD67 induced significant changes in the GABAergic system in the EL hippocampus. Thus, rAAV8-mediated GAD67 gene transfer is a promising therapeutic strategy for the treatment of epilepsies.
  • Takeshi Sakurada, Aya Goto, Masayuki Tetsuka, Takeshi Nakajima, Mitsuya Morita, Shin-Ichiroh Yamamoto, Masahiro Hirai, Kensuke Kawai
    Neurophotonics 6 2 025012 - 025012 2019年04月 [査読有り][通常論文]
    Directing attention to movement outcomes (external focus; EF), not body movements (internal focus; IF), is a better cognitive strategy for motor performance. However, EF is not effective in some healthy individuals or stroke patients. We aimed to identify the neurological basis reflecting the individual optimal attentional strategy using functional near-infrared spectroscopy. Sixty-four participants (23 healthy young, 23 healthy elderly, and 18 acute stroke) performed a reaching movement task under IF and EF conditions. Of these, 13 healthy young participants, 11 healthy elderly participants, and 6 stroke patients showed better motor performance under EF conditions (EF-dominant), whereas the others showed IF-dominance. We then measured prefrontal activity during rhythmic hand movements under both attentional conditions. IF-dominant participants showed significantly higher left prefrontal activity than EF-dominant participants under IF condition. In addition, receiver operating characteristic analysis supported that the higher activity in the left frontopolar and dorsolateral prefrontal cortices could detect IF-dominance as an individual's optimal attentional strategy for preventing motor performance decline. Taken together, these results suggest that prefrontal activity during motor tasks reflects an individual's ability to process internal body information, thereby conferring IF-dominance. These findings could be applied for the development of individually optimized rehabilitation programs.
  • Yohei Ishishita, Naoto Kunii, Seijiro Shimada, Kenji Ibayashi, Mariko Tada, Kenji Kirihara, Kensuke Kawai, Takanori Uka, Kiyoto Kasai, Nobuhito Saito
    Human brain mapping 40 4 1184 - 1194 2019年03月 [査読有り][通常論文]
    Auditory contextual processing has been assumed to be based on a hierarchical structure consisting of the primary auditory cortex, superior temporal gyrus (STG), and frontal lobe. Recent invasive studies on mismatch negativity (MMN) have revealed functional segregation for auditory contextual processing such as neural adaptation in the primary auditory cortex and prediction in the frontal lobe. However, the role of the STG remains unclear. We obtained induced activity in the high gamma band as mismatch response (MMR), an electrocorticographic (ECoG) counterpart to scalp MMN, and the components of MMR by analyzing ECoG data from patients with refractory epilepsy in an auditory oddball task paradigm. We found that MMR localized mainly in the bilateral posterior STGs, and that deviance detection largely accounted for MMR. Furthermore, adaptation was identified in a limited number of electrodes on the superior temporal plane. Our findings reveal a mixed contribution of deviance detection and adaptation depending on location in the STG. Such spatial considerations could lead to further understanding of the pathophysiology of relevant psychiatric disorders.
  • Kimura T, Ochiai C, Kawai K, Morita A, Saito N
    Journal of neurosurgery 1 - 6 2019年03月 [査読有り][通常論文]
    OBJECTIVE: To investigate the risk of bleeding from unruptured cerebral aneurysms (UCAs), previous studies have used Kaplan-Meier analyses without treating the definitive treatment as a competing risk event, which may underestimate the rupture rate. The authors analyzed the survival of patients with UCAs alongside the occurrence of aneurysm bleeding and its competing risk events. METHODS: A retrospective analysis was conducted on 722 patients diagnosed with UCAs in the period from 2000 to 2009 using an institution's electronic medical records and telephone interviews. The cumulative incidence of aneurysm rupture was examined, and factors contributing to rupture were assessed using regression analyses. RESULTS: By 2014, 19 patients had experienced aneurysm rupture, with an overall rupture rate of 0.57% per year over 3320.8 person-years. However, cumulative incidence analysis indicated that 1.3% of all patients had a rupture within 2 years after aneurysm identification, and 38.4% of the patients underwent definitive treatment in the same period. Among the patients who experienced rupture, regression analysis revealed that an aneurysm size greater than 5 mm, a location in the anterior or posterior communicating arteries, and an irregular shape contributed to aneurysm rupture, with HRs of 4.4 (95% CI 1.2-15.7), 3.5 (95% CI 1.4-8.7), and 2.1 (95% CI 0.7-6.0), respectively. CONCLUSIONS: Rupture rate analyses using the person-year or standard Kaplan-Meier method are not as informative without consideration of the competing risks. The incidence of aneurysm rupture should be presented clearly with those of competing risks.
  • Namba K, Higaki A, Kaneko N, Nemoto S, Kawai K
    Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences 1591019918824012  2019年02月 [査読有り][通常論文]
  • Emami A, Kunii N, Matsuo T, Shinozaki T, Kawai K, Takahashi H
    NeuroImage. Clinical 22 101684  2019年01月 [査読有り][通常論文]
  • Yoshihide Sehara, Toshiki Inaba, Takao Urabe, Fumio Kurosaki, Masashi Urabe, Naoki Kaneko, Kuniko Shimazaki, Kensuke Kawai, Hiroaki Mizukami
    The European journal of neuroscience 48 12 3466 - 3476 2018年12月 [査読有り][通常論文]
    Survivin, a member of the inhibitors of apoptosis protein gene family, inhibits the activity of caspase, leading to a halt of the apoptotic process. Our study focused on the neuroprotective effect of survivin after transient middle cerebral artery occlusion (MCAO) with intraparenchymal administration of an adeno-associated virus (AAV) vector. His-tagged survivin was cloned and packaged into the AAV-rh10 vector. Four-week-old Sprague-Dawley rats were injected with 4 × 109  vg of AAV-GFP or AAV-His-survivin into the right striatum and were treated 3 weeks later with transient MCAO for 90 min. Twenty-four hours after MCAO, functional and histological analyses of the rats were performed. The result showed that rats that had been treated with AAV-green fluorescent protein (GFP) and those that had been treated with AAV-His-survivin did not show a significant difference in neurological scores 24 hr after MCAO, however, infarction volume was significantly reduced in the AAV-His-survivin group compared to that in the AAV-GFP group. Although the neutrophil marker myeloperoxidase did not show a significant difference in the ischemic boundary zone, cells positive for active caspase-3 and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling were significantly decreased in the AAV-His-survivin group. In conclusion, survivin overexpression in the ischemic boundary zone induced by using an AAV vector has the potential for amelioration of ischemic damage via an antiapoptotic mechanism.
  • 聴覚ミスマッチ課題により誘発される高周波脳律動の解析
    石下 洋平, 國井 尚人, 嶋田 勢二郎, 井林 賢志, 多田 真理子, 切原 賢治, 宇賀 貴紀, 川合 謙介, 笠井 清登, 斉藤 延人
    てんかん研究 36 2 426 - 426 (一社)日本てんかん学会 2018年09月
  • てんかん外科の世界的趨勢と日本における今後の展開 てんかん外科におけるRNSの可能性と課題
    稲次 基希, 山本 貴道, 川合 謙介, 前原 健寿, Doyle Werner
    てんかん研究 36 2 314 - 315 (一社)日本てんかん学会 2018年09月 [査読有り][通常論文]
  • Yoshihide Sehara, Kuniko Shimazaki, Fumio Kurosaki, Naoki Kaneko, Ryosuke Uchibori, Masashi Urabe, Kensuke Kawai, Hiroaki Mizukami
    Neuroscience letters 682 27 - 31 2018年08月 [査読有り][通常論文]
    Adeno-associated virus (AAV) is an ideal vector for gene transduction into the central nervous system because of its safety and efficiency. While it is currently widely used for clinical trials and is expected to become more widespread, the appropriate combination of viral serotypes and promoters have not been fully investigated. In this study, we compared the transduced gene expression of AAVrh10 to AAV5 in gerbil hippocampus using three different promoters, including cytomegalovirus (CMV), chicken β-actin promoter with the CMV immediate-early enhancer (CAG), and the Synapsin 1 (Syn1) promoter. Four-week-old male gerbils underwent stereotaxic injection with 1 × 1010 viral genome of AAV carrying green fluorescent protein (GFP). Quantification of the GFP-positive areas 3 weeks after injection showed that AAVrh10-CMV and AAVrh10-CAG were the most efficient (p < 0.001, compared with the control) and AAVrh10-Syn1 and AAV5-CMV were the next most efficient (p < 0.05, compared with the control). On the other hand, AAV5-Syn1 showed little expression, which was only observed at the injected site. In conclusion, we should note that some combinations of viral capsids and promoters can result in failure of gene delivery, while most of them will work appropriately in the transgene expression in the brain.
  • Toshikazu Kimura, Kenji Ibayashi, Kensuke Kawai
    World Neurosurgery 113 e650 - e653 2018年05月 [査読有り][通常論文]
    Background: In superficial temporal artery−middle cerebral artery (STA-MCA) anastomosis, there is a certain risk of intraoperative acute occlusion of the bypass that can cause operative complications. Objective: We sought to assess the efficacy of resuturing at the same site after intraoperative acute occlusion of the bypass. Methods: In total, 129 STA-MCA anastomosis operations were performed on 125 patients at our institution. The electronic medical records of each patient were reviewed to gather information regarding intraoperative occlusion events, and the operative videos and postoperative radiologic images were also reviewed. Results: Twelve intraoperative acute occlusions were identified. In each case, resuturing was performed after cutting all knots, flushing the thrombus, and trimming the edges of the STAs. In 11 cases, indocyanine green videoangiography and/or Doppler sonography revealed patency during the operation, which was confirmed by postoperative magnetic resonance angiography. None of the 12 cases exhibited high-signal intensities in the MCA area on diffusion-weighted images. Conclusion: If intraoperative acute occlusion of STA-MCA anastomosis occurs, reanastomosis at the site should be the first option.
  • Kenji Ibayashi, Naoto Kunii, Takeshi Matsuo, Yohei Ishishita, Seijiro Shimada, Kensuke Kawai, Nobuhito Saito
    Frontiers in Neuroscience 12 221  2018年04月 [査読有り][通常論文]
    Restoration of speech communication for locked-in patients by means of brain computer interfaces (BCIs) is currently an important area of active research. Among the neural signals obtained from intracranial recordings, single/multi-unit activity (SUA/MUA), local field potential (LFP), and electrocorticography (ECoG) are good candidates for an input signal for BCIs. However, the question of which signal or which combination of the three signal modalities is best suited for decoding speech production remains unverified. In order to record SUA, LFP, and ECoG simultaneously from a highly localized area of human ventral sensorimotor cortex (vSMC), we fabricated an electrode the size of which was 7 by 13 mm containing sparsely arranged microneedle and conventional macro contacts. We determined which signal modality is the most capable of decoding speech production, and tested if the combination of these signals could improve the decoding accuracy of spoken phonemes. Feature vectors were constructed from spike frequency obtained from SUAs and event-related spectral perturbation derived from ECoG and LFP signals, then input to the decoder. The results showed that the decoding accuracy for five spoken vowels was highest when features from multiple signals were combined and optimized for each subject, and reached 59% when averaged across all six subjects. This result suggests that multi-scale signals convey complementary information for speech articulation. The current study demonstrated that simultaneous recording of multi-scale neuronal activities could raise decoding accuracy even though the recording area is limited to a small portion of cortex, which is advantageous for future implementation of speech-assisting BCIs.
  • 機能的脳神経外科最新の動向 難治性てんかんに対する発作感知型デバイスによる新たな治療選択肢 AspireSR & RNS System
    山本 貴道, 稲次 基希, 前原 健寿, 川合 謙介, Doyle Werner K
    Neurological Surgery 46 3 247 - 262 (株)医学書院 2018年03月 [査読有り][通常論文]
    <文献概要>I.はじめに 難治性てんかんに対してさまざまな刺激療法が行われてきたが,現在,普及し拡大を続けている植込み型デバイスは,迷走神経刺激療法(vagus nerve stimulation:VNS)のシステム(VNS Therapy System. LivaNova USA, Inc., Houston, TX, USA)である.1980年代から基礎研究が進められ,欧州では1994年,米国では1997年に正式に認可された.VNSの治験は本邦においても1993〜1997年にかけて行われ,認可申請されたが,承認を得るには時間を要した.2006年10月から始まった厚生労働省の「医療ニーズの高い医療機器等の早期導入に関する検討会」の第2回会合(2007年2月)でVNSが取り上げられ,これによって本邦においてもようやく日の目を見ることとなった.2010年1月に薬事法承認,同年7月に保険適用となったことで保険償還が可能となり,急速に普及していった.VNSのデバイスは,本邦での治験の頃はNeuroCybernetic Prosthesis(Model 100)というプロトタイプであったが,2010年から実際に使われ始めたのは小型化されたDemipulse(Model 103)で
  • Naoki Kaneko, Toshihiro Mashiko, Katsunari Namba, Satoshi Tateshima, Eiju Watanabe, Kensuke Kawai
    Journal of NeuroInterventional Surgery 10 3 306 - 309 2018年03月 [査読有り][通常論文]
    Objectives To develop an in vitro model for studying the biological effect of complex-flow stress on endothelial cells in three-dimensional (3D) patient-specific vascular geometry. Materials and methods A vessel replica was fabricated with polydimethylsiloxanes using 3D printing technology from vascular image data acquired by rotational angiography. The vascular model was coated with fibronectin and immersed in a tube filled with a cell suspension of endothelium, and then cultured while being slowly rotated in three dimensions. Culture medium with viscosity was perfused in the circulation with the endothelialized vascular model. A computational fluid dynamics (CFD) study was conducted using perfusion conditions used in the flow experiment. The morphology of endothelial cells was observed under a confocal microscope. Results The CFD study showed low wall shear stress and circulating flow in the apex of the basilar tip aneurysm, with linear flow in the parent artery. Confocal imaging demonstrated that the inner surface of the vascular model was evenly covered with monolayer endothelial cells. After 24 h of flow circulation, endothelial cells in the parent artery exhibited a spindle shape and aligned with the flow direction. In contrast, endothelial cells in the aneurysmal apex were irregular in shape and size. Conclusions A geometrically realistic intracranial aneurysm model with live endothelial lining was successfully developed. This in vitro model enables a new research approach combining study of the biological impact of complex flow on endothelial cells with CFD analysis and patient information, including the presence of aneurysmal growth or rupture.
  • Yamamoto T, Inaji M, Maehara T, Kawai K, Doyle WK
    No shinkei geka. Neurological surgery 46 3 247 - 262 2018年03月 [査読有り][通常論文]
  • Tomoaki Ban, Kensuke Kawai, Kyojiro Nambu, Hiroshi Iseki, Ken Masamune
    Epilepsy and Seizure 10 1 1 - 10 2018年 [査読有り][通常論文]
    Purpose: Proper judgement of the aptitude of people with epilepsy (PWE) for driving is a critical issue, both medically and socially. One thus far reported approach is a quantitative comparison of the risk of fatal traffic accidents caused by PWE drivers and that by subgroups of drivers in the general population. We propose a new approach that compares the risk posed by PWE drivers and that by sud-den death of occupational drivers, and the maximum driving time for PWE based on that comparison. Method: The risk of fatal traffic accidents was estimated using four variables. The value assigned to each variable was determined using reports and statistics. Results: The risk of fatal traffic accidents caused by sudden death of occupational drivers was estimated to be 7.6×10-5/year, 4.9×10-5/year, and 1.7×10-5/year for large-sized, mid-sized and normal-sized vehicles. The risk of fatal traffic accidents caused by PWE drivers was estimated to be 5.3×10-5/year and 3.2×10-5/year for PWE with seizure-free periods of 1 year and 2 years, respectively. The maxi-mum acceptable driving time for PWE having a 2-year seizure-free period at the equivalent risk caused by sudden death of occupational drivers of mid-sized vehicles was estimated to be 304 min/week. Conclusion: The risk of fatal traffic accidents caused by PWE drivers can be evaluated by com-paring to that caused by sudden death of occupational drivers. Such risk posed by PWE drivers having a 2-year seizure-free period was less than that caused by sudden death of occupational drivers of mid-sized vehicles. Assuming that the society accepts the latter risk, PWE may be permitted to drive for an estimated maximum time at the equivalent risk of causing a fatal accident.
  • Toshihiro Mashiko, Hirohumi Oguma, Takehiko Konno, Akira Gomi, Takashi Yamaguchi, Rie Nagayama, Makoto Sato, Ryo Iwase, Kensuke Kawai
    World Neurosurgery 109 e298 - e304 2018年01月 [査読有り][通常論文]
    Introduction Self-made devices composed of agar and gelatin gel were used for resident training in intra-axial brain tumor resection. The mixture gel of agar and gelatin is retractable and can be suctioned. Hardness of the gel depends on the concentration of the solution. Therefore, by changing the concentration, it is easy to make gels of various hardness. Methods In this study, a mass of gel that looked like a tumor was placed into another gel that looked like the brain. A part of the “brain” was regarded as the eloquent area. Three types of “tumor” were prepared: hard, moderately hard, and soft tumors. Residents tried to remove the tumor entirely with minimal brain invasion. The training was repeated with 3 types of gel. After resection, the weight of the residual tumor, resected normal brain, and resected eloquent area were measured, and the time taken for removal was recorded. Results These data were compared between residents and neurosurgeons. We also analyzed how these data improved with repeated practice. In most cases, residual tumor, resected normal brain, resected eloquent area, and time taken for removal were less in neurosurgeons than in residents. Repeated training made residents more skillful. The responses of the trainees were almost all favorable. Conclusions Our devices with “tumors” of various hardness appear to be suitable for resident training in each surgical skill. For the next step of this study, we will attempt to fabricate more practical 3-dimensional gel models for presurgical simulation.
  • Takeshi Matsuo, Kensuke Kawai, Kenji Ibayashi, Ichiro Shirouzu, Miki Sato
    World Neurosurgery 116 e577 - e587 2018年 [査読有り][通常論文]
    Background: The lesionectomy is a general surgical procedure for treating focal epilepsy resulting from a structural abnormality, but a favorable outcome cannot be achieved in some patients, especially patients whose symptomatogenic zone is located in remote regions. Herein we propose the surgical disconnection of the seizure propagation pathway, which consists of short and long associating fibers linking the epileptogenic zone to the remote symptomatogenic zone, as an effective method of achieving favorable seizure outcomes in patients with posterior cortex epilepsy. Methods: Three patients with intractable epilepsy showing a structural abnormality in the medial posterior cortex participated in this study. Their habitual seizures were complex partial seizures stemming from remote symptomatogenic zones. Seizure propagation-related fibers were assumed by non-invasive examination and semiology. Results: Cingulum and superior/inferior longitudinal fasciculus were considered to form main seizure propagation pathway. Based on the preoperative assumption and the intraoperative intracranial electroencephalogram findings, a lesionectomy and corticectomy were performed for 2 patients while a clusterectomy and corticectomy were performed for the remaining patient. The resection area was extended in the direction of the association fibers to disconnect the remote symptomatogenic zone completely from the epileptogenic zone. Engel class I was achieved in all the patients. Conclusion: The current study suggested that assuming the presence of association fibers was an important factor for achieving a favorable outcome in the surgical treatment of posterior cortex epilepsy. Though further study is required, disconnection surgery is recommended as a treatment option for cases in which the epileptogenic zone is located in an eloquent area.
  • Kenji Ibayashi, Naoto Kunii, Kensuke Kawai, Nobuhito Saito
    WORLD NEUROSURGERY 108 325 - 327 2017年12月 [査読有り][通常論文]
    BACKGROUND: Safe entry to the inferior horn is required for a selective approach to the medial temporal region. This can be challenging sometimes for inexperienced surgeons. Our objective was to verify the usefulness of the deep medullary vein (DMV) as an intraoperative landmark for safely entering the inferior horn during the transsylvian selective approach to the mesial temporal region. METHODS: Videos of 8 cases of transsylvian selective amygdalohippocampectomies performed at the University of Tokyo Hospital from 2013 to 2015 were reviewed. Consistency of the DMV and time required to open the inferior horn via the temporal stem through the inferior limiting sulcus were retrospectively evaluated. RESULTS: DMVs were identified in all cases; the average number identified was 2.5 +/- 0.3 (mean +/- SE). The inferior horn was opened without disorientation in all cases, with mean dissecting time of 7.0 minutes +/- 1.1. No complications were caused by disorientation within the temporal stem white matter. CONCLUSIONS: Consideration of the venous system within the white matter and following the DMV could reduce the risk of disorientation and enable the surgeon to reach the inferior horn in a straightforward manner without accidental white matter damage.
  • Naoki Kaneko, Mayumi Tsunoda, Masatsugu Mitsuhashi, Keisuke Okubo, Taro Takeshima, Yoshihide Sehara, Mutsumi Nagai, Kensuke Kawai
    JOURNAL OF ULTRASOUND IN MEDICINE 36 10 2071 - 2077 2017年10月 [査読有り][通常論文]
    ObjectivesThe purpose of this study was to examine the feasibility of an optical see-through head-mounted display (OST-HMD) to improve ergonomics during ultrasound-guided fine-needle aspiration (FNA) in the neck region. MethodsThis randomized controlled study compared an OST-HMD with a normal ultrasound monitor during an ultrasound-guided FNA in the neck region. Patients with a neck tumor were recruited and randomized into one of two groups. Two practitioners performed ultrasound-guided FNA with or without the HMD, as indicated. An independent researcher measured the procedure time, the number and time of head movements, as well as the number of needle redirections. In addition, practitioners completed questionnaires after performing the FNA on each patient. ResultsIn 93% of the sessions with the OST-HMD, practitioners performed ultrasound-guided FNA without turning the patients' heads. There was no difference in procedural time and number of needle redirections between the two groups. Results from the questionnaire revealed not only good wearability and low fatigue, but also the practitioners' preference for the HMD. ConclusionsThe OST-HMD improved the practitioners' ergonomics and can be adopted for performing ultrasound-guided interventional procedures in clinical settings.
  • Kensuke Kawai, Tatsuya Tanaka, Hiroshi Baba, Mark Bunker, Akio Ikeda, Yushi Inoue, Shigeki Kameyama, Sunao Kaneko, Amami Kato, Taneyoshi Nozawa, Eiji Maruoka, Makiko Osawa, Taisuke Otsuki, Sadatoshi Tsuji, Eiju Watanabe, Takamichi Yamamoto
    EPILEPTIC DISORDERS 19 3 327 - 338 2017年09月 [査読有り][通常論文]
    Aims. Vagus nerve stimulation (VNS) is an established option of adjunctive treatment for patients with drug-resistant epilepsy, however, evidence for long-term efficacy is still limited. Studies on clinical outcomes of VNS in Asia are also limited. We report the overall outcome of a national, prospective registry that included all patients implanted in Japan.Methods. The registry included patients of all ages with all seizure types who underwent VNS implantation for drug-resistant epilepsy in the first three years after approval of VNS in 2010. The registry excluded patients who were expected to benefit from resective surgery. Efficacy analysis was assessed based on the change in frequency of all seizure types and the rate of responders. Changes in cognitive, behavioural and social status, quality of life (QOL), antiepileptic drug (AED) use, and overall AED burden were analysed as other efficacy indices.Results. A total of 385 patients were initially registered. Efficacy analyses included data from 362 patients. Age range at the time of VNS implantation was 12 months to 72 years; 21.5% of patients were under 12 years of age and 49.7% had prior epilepsy surgery. Follow-up rate was >90%, even at 36 months. Seizure control improved over time with median seizure reduction of 25.0%, 40.9%, 53.3%, 60.0%, and 66.2%, and responder rates of 38.9%, 46.8%, 55.8%, 57.7%, and 58.8% at three, six, 12, 24, and 36 months of VNS therapy, respectively. There were no substantial changes in other indices throughout the three years of the study, except for self/family-accessed QOL which improved over time. No new safety issues were identified.Conclusions. Although this was not a controlled comparative study, this prospective national registry of Japanese patients with drug-resistant epilepsy, with >90% follow-up rate, indicates long-term efficacy of VNS therapy which increased over time, over a period of up to three years. The limits of such trials, in terms of AED modifications and during follow-up and difficulties in seizure counting are also discussed.
  • 大槻 泰介, 久保田 有一, 川合 謙介, 島 由季子, 尾関 宏文, 井上 有史
    臨床医薬 33 8 645 - 654 (株)臨床医薬研究協会 2017年08月 
  • Rie Hitsuyu, Tomoyo Isoguchi Shiramatsu, Takahiro Noda, Ryohei Kanzaki, Takeshi Uno, Kensuke Kawai, Hirokazu Takahashi
    ELECTRONICS AND COMMUNICATIONS IN JAPAN 100 5 34 - 43 2017年05月 [査読有り][通常論文]
    Vagus nerve stimulation (VNS) causes neuromodulatory effects in the cerebral cortex, which are useful not only for therapy on intractable epilepsy but also for enhancement of higher brain functions such as cognition and memory. Recently, it has been reported that VNS may also affect auditory-evoked neutral activities. However, it remains to be elucidated how and where VNS modulates neutral activities in the auditory cortex. Here, we examined effects of VNS on adaptation of neutral activities in response to repeated stimuli in the rat auditory cortex. Both a surface and depth microelectrode array recorded auditory-evoked potentials in response to click train and oddball stimuli. We quantified a repetition rate transfer function and common stimulus-specific adaptation (SSA) index from the amplitude of middle-latency response (PI). Consequently, VNS affected temporal response property and increased SSA in the layer 1 and 5/6 of auditory cortex. This result suggests that VNS strengthens adaptation in the auditory cortex in a layer-specific manner. (C) 2017 Wiley Periodicals, Inc.
  • Akito Oshima, Toshikazu Kimura, Atsuya Akabane, Kensuke Kawai
    JOURNAL OF CLINICAL NEUROSCIENCE 39 199 - 202 2017年05月 [査読有り][通常論文]
    Introduction: Although Ommaya reservoir implantation is effective in reducing the target volume of cystic brain metastases preceding stereotactic radiosurgery, adequate volume reduction cannot be achieved in some cases, and the factors leading to failure in volume reduction have not been clearly identified. In this study, we investigated the factors leading to failure in volume reduction after use of the Ommaya reservoir. Materials and methods: Between December 2007 and February 2015, 38 consecutive patients with 40 cystic metastases underwent Ommaya reservoir implantation at our institution. The patient characteristics, treatment parameters, and all available clinical and neuroimaging follow-ups were analyzed retrospectively. Results: The rate of volume reduction was significantly related to the location of the tube tip inside the cyst. By placing the tip at or near the center, 58.7% reduction was achieved, whereas reduction of 42.6% and 7.7% occurred with deep and shallow tip placement, respectively (p = 0.011). Although there was no additional surgery in the center placement group, additional surgeries were performed in 5 out of the 23 deep and shallow cases due to inadequate volume reduction. No other factors were correlated with successful volume reduction. Conclusion: For adequate volume reduction using the Ommaya reservoir in the treatment of cystic brain metastases prior to stereotactic radiosurgery, the tip of the reservoir tube should be placed at the center of the cyst. (C) 2016 Elsevier Ltd. All rights reserved.
  • Seijiro Shimada, Naoto Kunii, Kensuke Kawai, Takeshi Matsuo, Yohei Ishishita, Kenji Ibayashi, Nobuhito Saito
    CLINICAL NEUROPHYSIOLOGY 128 4 549 - 557 2017年04月 [査読有り][通常論文]
    Objective: Cortico-cortical evoked potential (CCEP) has been utilized to evaluate connectivity between cortices. However, previous reports have rarely referred to the impact of volume-conducted potential (VCP) which must be a confounding factor of large potential around the stimulation site. To address this issue, we challenged the null hypothesis that VCP accounts for the majority of the recorded potential, particularly around the stimulation site. Methods: CCEP was recorded with high-density intracranial electrodes in 8 patients with intractable epilepsy. First, we performed regression analysis for describing the relationship between the distance and potential of each electrode. Second, we performed principal component analysis (PCA) to reveal the temporal features of recorded waveforms. Results: The regression curve, declining by the inverse square of the distance, fitted tightly to the plots (R-2: 0.878-0.991) with outliers. PCA suggested the responses around the stimulation site had the same temporal features. We also observed the continuous declination over the anatomical gap and the phase reversal phenomena around the stimulation site. Conclusions: These results were consistent with the null hypothesis. Significance: This study highlighted the risk of misinterpreting CCEP mapping, and proposed mathematical removal of VCP, which could lead to more reliable mapping based on CCEP. (C) 2017 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
  • 桐山 健司, 鎌田 恭輔
    脳卒中の外科 45 5 398 - 402 一般社団法人 日本脳卒中の外科学会 2017年 
    An 89-year-old man presented to our hospital with a pulsatile mass in his neck. Based on magnetic resonance imaging (MRI) and blood tests, he was diagnosed as having an infected aneurysm of the right carotid artery bifurcation. Conservative therapy with antibiotic use was initiated. However, the aneurysm was found to rapidly increase in size. We decided to repair the culprit vessel walls because of the risk of lethal rupture. The aneurysm extended between the common carotid artery (CCA) and internal carotid artery (ICA). Strong adhesions were noted between the walls of the aneurysm and surrounding structures. The wall was difficult to dissect and showed leakage of blood, indicating vascular injury. Thus, resection of the CCA, ICA and external carotid artery (ECA) was performed, followed by reconstruction using a synthetic graft. The patient demonstrated no neurological deficit postoperatively, and postoperative magnetic resonance angiography (MRA) and MRI revealed a patent graft and no new ischemic lesion. Conservative therapy maintained his general condition without any vascular event. Extracranial aneurysms of the carotid artery without any associated history of traumatic events are rare. We discuss the treatment strategy for this condition based on previous reports.
  • Alief Dhuha, Takehiko Konno, Hidenori Yokota, Keiji Oguro, Eiju Watanabe, Kensuke Kawai
    Epilepsy and Seizure 9 1 1 - 10 2017年 [査読有り][通常論文]
    Purpose: The purpose of this study was to determine the optimal duration of long-term videoEEG monitoring (VEEG) in patients with epilepsy. The response time of medical staff to seizures was also evaluated from the viewpoint of safety of the monitoring. Methods: We estimated the optimal duration of VEEG from the seizure onset pattern. We retrospectively investigated all VEEG sessions performed in our department during the period between June 2005 and July 2016. Sessions with no seizures and with only non-epileptic seizures were excluded. Using 91 sessions from 69 patients, information on the onset time and response time of medical staff to seizures was collected. Results: The median duration from the start of VEEG to the first seizure was 2 days. Seventy-seven percent of first seizures occurred within 3 days of VEEG. The median duration from the first seizure to the third seizure was 2 days. Eighty percent of third seizures occurred within 3 days of the first seizure. There was no significant diurnal distribution of seizure occurrence. Medical staff did not respond to 20% of generalized seizures and 69% of focal seizures. The overlooking of generalized seizures occurred mainly during the hours of 1-2 pm and 8-9 pm but there was no significant diurnal pattern in overlooking generalized and focal seizures. Conclusion Based on these findings, we suggest that VEEG can be terminated when no seizure occurs within 4 days after onset. In our VEEG protocol, in which all antiepileptic drugs were discontinued before the start of a session, there was no diurnal pattern of seizure occurrence. This is the first study investigating the diurnal pattern of overlooking seizures by medical staff during VEEG. Since there was no diurnal pattern to the overlooking, medical staff should pay equal, 24- hour attention to patients on VEEG.
  • 脳卒中患者の認知運動機能連関に関する個人差とその神経基盤
    櫻田武, 後藤彩, 中嶋剛, 森田光哉, 平井真洋, 山本紳一郎, 渡辺英寿, 川合謙介
    機能的脳神経外科 56 62 - 67 2017年 [査読無し][招待有り]
  • Naoki Kaneko, Toshihiro Mashiko, Taihei Ohnishi, Makoto Ohta, Katsunari Namba, Eiju Watanabe, Kensuke Kawai
    SCIENTIFIC REPORTS 6 39168  2016年12月 [査読有り][通常論文]
    Patient-specific vascular replicas are essential to the simulation of endovascular treatment or for vascular research. The inside of silicone replica is required to be smooth for manipulating interventional devices without resistance. In this report, we demonstrate the fabrication of patient-specific silicone vessels with a low-cost desktop 3D printer. We show that the surface of an acrylonitrile butadiene styrene (ABS) model printed by the 3D printer can be smoothed by a single dipping in ABS solvent in a time-dependent manner, where a short dip has less effect on the shape of the model. The vascular mold is coated with transparent silicone and then the ABS mold is dissolved after the silicone is cured. Interventional devices can pass through the inside of the smoothed silicone vessel with lower pushing force compared to the vessel without smoothing. The material cost and time required to fabricate the silicone vessel is about USD $2 and 24 h, which is much lower than the current fabrication methods. This fast and low-cost method offers the possibility of testing strategies before attempting particularly difficult cases, while improving the training of endovascular therapy, enabling the trialing of new devices, and broadening the scope of vascular research.
  • Yumiko Yamaoka, Mitsuaki Bandoh, Kensuke Kawai
    NEUROCASE 22 4 387 - 391 2016年08月 [査読有り][通常論文]
    We report two extremely rare cases involving the development of transient selective retrograde amnesia for simple machine operation lasting for several hours. A 61-year-old male taxi driver suddenly became unable to operate a taximeter, and a 66-year-old female janitor suddenly became unable to use a fax machine. They could precisely recount their episodes to others both during and after the attacks, and their memories during their attacks corresponded to the memory of the witness and the medical records of the doctor, respectively. Therefore, it appears that these individuals remained alert and did not develop anterograde amnesia during their attacks. On day 4, they underwent high-resolution magnetic resonance imaging (MRI), and diffusion-weighted MRI with 2-mm section thickness revealed small high-intensity signal lesions in the left hippocampal cornu ammonis area 1 (CA1) region. However, these lesions disappeared during the chronic phase. This is the first report describing lesions detected by MRI in patients with transient selective amnesia without anterograde amnesia. Reversible damage to the hippocampal CA1 region may cause transient selective amnesia by impairing the retrieval of relevant memories.
  • Kenichi Usami, Mayumi Kubota, Kensuke Kawai, Naoto Kunii, Takeshi Matsuo, Kenji Ibayashi, Miwako Takahashi, Kyousuke Kamada, Toshimitsu Momose, Shigeki Aoki, Nobuhito Saito
    EPILEPSIA 57 6 931 - 940 2016年06月 [査読有り][通常論文]
    Objective: Multiple hippocampal transection (MHT) is a surgical procedure developed to avoid postoperative memory decline. Its efficacy has been documented in only a few small series with relatively short observation periods. We prospectively evaluated the long-term seizure and cognitive outcomes of MHT combined with multiple subpial transection or lesionectomy (MHT + MST/L). Moreover, we quantitatively evaluated the structural and metabolic neuroradiologic changes after the procedure to elucidate the anatomofunctional correlates of memory preservation. Methods: Twenty-four patients underwent MHT + MST/L for treatment of drug-resistant mesial temporal lobe epilepsy (mTLE) and were followed for more than 5 years. Indications for the procedure were the following: (1) verbally dominant-sided surgery in patients with a radiologically normal hippocampus or normal/near normal memory, and (2) surgery for patients with concomitant epileptic activity on the contralateral side, that is, when the surgery was considered a high risk for severe postoperative memory decline. Seizure outcome was evaluated using Engel's classification 1, 2, and 3 years after surgery, and at the last visit (LV). Three subgroups were evaluated as well: magnetic resonance imaging (MRI) negative (MN), hippocampal sclerosis (HS), and normal hippocampus with extrahippocampal lesion (NHEL). The long-term cognitive outcome was followed through to LV in patients who underwent verbally dominant-sided surgery. Hippocampal volume (HV), diffusion tensor parameters (DTP), and glucose utilization (GU) were determined from MRI and fluorodeoxyglucose-positron emission tomography (FDG-PET) studies performed before and >6 months after surgery. Results: Whereas the rate of Engel class I as a whole was 71% at 1 year and 67% at LV, the rates in the MN, HS, and NHEL groups were 60%, 67%, and 100% at 1 year, respectively, and 70%, 56%, and 80% at LV, respectively. Memory indices after verbally dominant-sided surgery transiently declined at 1 month but recovered to and remained at the preoperative level through LV. The HV, DTP of the fornix, and GU of the temporal lobe on the treated side showed pathologic changes even when the transiently declined memory indices had recovered to the preoperative level. Significance: The long-termoutcome for complex partial seizures afterMHT + MST/L was comparable to that seen after anterior temporal lobectomy. The long-term cognitive outcome was favorable, even for patients with a high risk of severe postoperative memory decline. MHT + MST/L may be a treatment option for mTLE in which resective surgery carries a risk of postoperative memory decline, particularly in patients without MRI lesion. A discrepancy between the preserved memory and the pathologic neuroradiologic changes indicates the necessity for further studies including functional MRI.
  • Keisuke Takai, Hiroki Kurita, Takayuki Hara, Kensuke Kawai, Makoto Taniguchi
    NEUROSURGICAL FOCUS 40 3 E10  2016年03月 [査読有り][通常論文]
    OBJECTIVE The microvascular anatomy of spinal perimedullary arteriovenous fistulas (AVFs) is more complicated than that of dural AVFs, and occlusion rates of AVF after open microsurgery or endovascular embolization are lower in patients with perimedullary AVFs (29%-70%) than they are in those with dural AVF (97%-98%). Reports of intraoperative blood flow assessment using indocyanine green (ICG) video angiography in spinal arteriovenous lesions have mostly been for spinal dural AVFs. No detailed reports on spinal perimedullary AVFs are available. METHODS Participants were 11 patients with spinal perimedullary AVFs (Type IVa in 5 patients, Type VIb in 4, and Type IVc in 2). Intraoperative ICG video angiography was assessed by measuring the number of cases in which this modality was judged essential by the surgeon to correctly occlude the fistula. RESULTS In all patients, arterial feeders were identified and intravenous ICG video angiography was performed before and after blocking the feeders. In one patient, selective intraarterial ICG video angiography was also performed. The findings provided by ICG video angiography significantly changed the surgical procedure in 4 of 11 patients (36%). Post-operatively, complete occlusion of the AVF was achieved in 10 of the 11 patients (91%). CONCLUSIONS Intraoperative ICG video angiography can have a significant impact on deciding surgical strategy in the microsurgical treatment of spinal perimedullary AVF.
  • Mizuho Yoshida, Toshihiro Hayashi, Kurumi Fujii, Kensuke Kawai, Shoji Tsuji, Atsushi Iwata
    NEUROLOGY 86 8 790 - + 2016年02月 [査読有り][通常論文]
    A 45-year-old woman had a 6-month history of progressive amnesia and diplopia. At age 34, a pineal germinoma was diagnosed; whole-brain radiation induced tumor regression for 10 years. The tumor had recurred and at surgery it was detached from the fornix and resected through an occipital transtentorial approach (figure 1). The fornix was decompressed and amnesia was remarkably recovered (figure 2A).
  • Japanese registry and outcome of vagus nerve stimulation for drug-resistant epilepsy: A prospective, observational, all-comers registry of first three years.
    Kawai K, Tanaka T, Baba H, Bunker M, Ikeda A, Inoue Y, Kameyama S, Kaneko S, Kato A, Nozawa T, Maruoka, Osawa M, Otsuki T, Tsuji S, Watanabe E, Yamamoto T
    Epil Disord in press in press in press - in press 2016年 [査読有り][通常論文]
  • Tomoyo I. Shiramatsu, Rie Hitsuyu, Kenji Ibayashi, Ryohei Kanzaki, Kensuke Kawai, Hirokazu Takahashi
    Vagus nerve stimulation (VNS) is a therapy on medically refractory epilepsy, and recently reported to improve cognitive function including learning and memory. The thalamo-cortical system may underlie such VNS-induced cognitive improvements. Thus, the present study targeted the auditory cortex and thalamus in rats, and investigated whether and how VNS modulates stimulus-specific adaptation (SSA) of the neural activity in these nuclei. A depth electrode array recorded auditory evoked potentials from the auditory thalamus and cortex under an oddball paradigm either with or without VNS. Consequently, VNS weakened SSA in the cortex, but did not affect that in the thalamus, indicating that VNS has neuromodulatory effects on the cortical inhibitory system and the thalamo-cortical projections, but not on the feedforward projections from the auditory periphery up to thalamus.
  • Kouhei Kamiya, Shiori Amemiya, Yuichi Suzuki, Naoto Kunii, Kensuke Kawai, Harushi Mori, Akira Kunimatsu, Nobuhito Saito, Shigeki Aoki, Kuni Ohtomo
    MAGNETIC RESONANCE IN MEDICAL SCIENCES 15 1 121 - 129 2016年 [査読有り][通常論文]
    Background and Purpose: We analyzed the ability of a machine learning approach that uses diffusion tensor imaging (DTI) structural connectomes to determine lateralization of epileptogenicity in temporal lobe epilepsy (TLE). Materials and Methods: We analyzed diffusion tensor and 3-dimensional (3D) T-1-weighted images of 44 patients with TLE (right, 15, left, 29; mean age, 33.0 +/- 11.6 years) and 14 age-matched controls. We constructed a whole brain structural connectome for each subject, calculated graph theoretical network measures, and used a support vector machine (SVM) for classification among 3 groups (right TLE versus controls, left TLE versus controls, and right TLE versus left TLE) following a feature reduction process with sparse linear regression. Results: In left TLE, we found a significant decrease in local efficiency and the clustering coefficient in several brain regions, including the left posterior cingulate gyrus, left cuneus, and both hippocampi. In right TLE, the right hippocampus showed reduced nodal degree, clustering coefficient, and local efficiency. With use of the leave-one-out cross-validation strategy, the SVM classifier achieved accuracy of 75.9 to 89.7% for right TLE versus controls, 74.4 to 86.0% for left TLE versus controls, and 72.7 to 86.4% for left TLE versus right TLE. Conclusion: Machine learning of graph theoretical measures from the DTI structural connectome may give support to lateralization of the TLE focus. The present good discrimination between left and right TLE suggests that, with further refinement, the classifier should improve presurgical diagnostic confidence.
  • Seijiro Shimada, Naoto Kunii, Kensuke Kawai, Kenichi Usami, Takeshi Matsuo, Takeshi Uno, Tomoyuki Koizumi, Nobuhito Saito
    WORLD NEUROSURGERY 84 3 867.e1 - 6 2015年09月 [査読有り][通常論文]
    BACKGROUND: Refractory temporal lobe epilepsy due to spontaneous temporal pole encephalocele is a rare but increasingly recognized condition. Optimal surgical management is complicated by the lack of knowledge regarding both the extent of the epileptogenic area and the need for repair of the encephalocele. CASE DESCRIPTION: We report two cases that add significant information to these issues. In Case 1, with a 5-year history of refractory seizures, implantation of diagnostic subdural electrodes into the anterior temporal base happened to abolish the seizures completely. No structural changes were evident on postoperative magnetic resonance imaging. In Case 2, with a large encephalocele and a 5-year history of refractory seizures, surgical disconnection of the temporal pole successfully abolished seizures without any need for encephalocele repair. CONCLUSIONS: These two cases support the view that the epileptogenic area is confined to within the temporal pole for spontaneous temporal pole encephalocele. Temporopolar disconnection represents one surgical option for this entity that achieves seizure cessation without requiring extra repair procedures.
  • Toshikazu Kimura, Naoya Kidani, Kenji Ibayashi, Kensuke Kawai
    BRITISH JOURNAL OF NEUROSURGERY 29 5 726 - 727 2015年09月 [査読有り][通常論文]
    Background. ICG videoangiography (ICG-VAG) is widely used in neurovascular surgery. In carotid artery disease, it has been used to assess the extent of the plaque and to confirm the removal of the plaque and patency of the artery. We introduce a novel usage of the ICG-VAG to confirm the patency of the external carotid artery (ECA) and superior thyroid artery (STA), which should work as a drainage system of possible debris in the lumen. Method. Consecutive 27 patients with severe internal carotid artery stenosis were employed. Carotid endarterectomy (CEA) was done in the usual fashion. After suturing the arteriotomy, ICG was injected intravenously before reperfusion. Before declamping procedure, ICG-VAG mode was started. As the declamping procedure went on, the assistant judged whether the STA and the ECA were patent by watching the ICG flow on the monitor. After confirming the patency of the ECA-CCA system, the ICA was reperfused. Result. The back flow from the STA was not confirmed in two cases. The back flow from the ECA was confirmed in all 27 cases. In four cases, the ICG-VAG showed air bubbles in the lumen; these bubbles were washed away to the ECA or STA. Conclusion. Using ICG-VAG during the reperfusion procedure of CEA, the patency of the ECA and the STA can be confirmed. It may contribute to reduce embolic complication during reperfusion procedure.
  • Kenichi Usami, Ryuji Kano, Kensuke Kawai, Takahiro Noda, Tomoyo Isoguchi Shiramatsu, Nobuhito Saito, Hirokazu Takahashi
    ELECTRONICS AND COMMUNICATIONS IN JAPAN 98 6 44 - 50 2015年06月 [査読有り][通常論文]
    Vagus nerve stimulation (VNS) is a palliative treatment for intractable epilepsy. Therapeutic mechanisms of VNS have not been elucidated. In this study, we measured the local field potential (LFP) with high-spatial resolution using a microelectrode array in adult rats, and analyzed VNS-induced phase modulation at a local network level. Eight adult Wistar rats (270-330 g) were used. Each rat underwent implantation of a VNS system under 1.5% isoflurane anesthesia. One week after implantation, right temporal craniotomy was performed under the same anesthesia as previously. Subsequently, a microelectrode array was placed in the temporal lobe cortex, and the LFP was recorded with a sampling rate of 1000 Hz. Phase-locking values (PLV) between all pairs of electrodes in varied frequency bands were calculated in order to evaluate the effect of VNS in terms of synchrony of neuronal activities. The PLV was calculated both in a normal state and in an epileptic state induced by kainic acid. VNS increased the PLV in a normal state, particularly in the high- band. In an epileptic state, on the other hand, VNS increased the PLV in the high- band and decreased the PLV in the and low- bands. These results suggest that VNS modulates neural activities in a band-specific and state-dependent manner so as to keep cortical synchrony within the optimal state. (C) 2015 Wiley Periodicals, Inc.
  • Toshio Yamauchi, Kosuke Kanemoto, Kensuke Kawai, Shigenobu Ishida, Mayumi Yamada, Takaki Tokumasu, Hirokazu Shirai, Kayo Yamamura
    Brain and Nerve 67 6 749 - 758 2015年06月 [査読有り][通常論文]
    This prospective, nationwide, specified drug use-results survey investigated the effects of levetiracetam (LEV) in elderly individuals with partial-onset seizures of advanced-age onset in a practical setting. Participants comprised LEV-naïve patients with onset of focal epilepsy at ≥50 years old and management by at least one antiepileptic drug. Efficacy measures were the physician-rated global improvement scale (GIS), and proportions of patients showing 50% and 100% seizure reduction by comparing seizure frequency during the 4-week pre-treatment period and the last 4 weeks of the 25-week treatment period. Adverse drug reactions (ADRs) and retention rate were also evaluated. Data for safety, GIS evaluation, and seizure frequency analyses were available from 105, 78, and 76, respectively, of 116 enrolled patients, 83 (71.55%) of whom were enrolled by neurosurgeons. Improvement rate (improved or markedly improved) as determined by GIS was 98.72% (77/78). Seventy-four (97.37%) and 64 patients (84.21%) showed 50% and 100% seizure reduction, respectively. Incidence of ADRs was 12.38%, including one serious ADR (mania). LEV retention rate remained high at the end of the 25-week treatment period (96.00%). LEV appears efficacious and well-tolerated in elderly patients with focal epilepsy. Including LEV in the treatment regimen may allow elderly patients to achieve freedom from seizures.
  • Takeshi Matsuo, Keisuke Kawasaki, Kensuke Kawai, Kei Majima, Hiroshi Masuda, Hiroatsu Murakami, Naoto Kunii, Yukiyasu Kamitani, Shigeki Kameyama, Nobuhito Saito, Isao Hasegawa
    CEREBRAL CORTEX 25 5 1265 - 1277 2015年05月 [査読有り][通常論文]
    Recognition of faces and written words is associated with category-specific brain activation in the ventral occipitotemporal cortex (vOT). However, topological and functional relationships between face-selective and word-selective vOT regions remain unclear. In this study, we collected data from patients with intractable epilepsy who underwent high-density recording of surface field potentials in the vOT. "Faces" and "letterstrings" induced outstanding category-selective responses among the 24 visual categories tested, particularly in high-gamma band powers. Strikingly, within-hemispheric analysis revealed alternation of face-selective and letterstring-selective zones within the vOT. Two distinct face-selective zones located anterior and posterior portions of the mid-fusiform sulcus whereas letterstring-selective zones alternated between and outside of these 2 face-selective zones. Further, a classification analysis indicated that activity patterns of these zones mostly represent dedicated categories. Functional connectivity analysis using Granger causality indicated asymmetrically directed causal influences from face-selective to letterstring-selective regions. These results challenge the prevailing view that different categories are represented in distinct contiguous regions in the vOT.
  • Kensuke Kawai
    NEUROLOGIA MEDICO-CHIRURGICA 55 5 357 - 366 2015年05月 [査読有り][通常論文]
    This article reviews the current status of surgical treatment of epilepsy and introduces the ongoing challenges. Seizure outcome of resective surgery for focal seizures associated with focal lesions is satisfactory. Particularly for mesial temporal lobe epilepsy, surgical treatment should be considered from the earlier stage of the disease. Meanwhile, surgical outcome in nonlesional extratemporal lobe epilepsy is still to be improved using various approaches. Disconnective surgeries reduce surgical complications of extensive resections while achieving equivalent or better seizure outcomes. Multiple subpial transection is still being modified expecting a better outcome by transection to the vertical cortices along the sulci- and multi-directional transection from a single entry point. Hippocampal transection is expected to preserve memory function while interrupting the abnormal epileptic synchronization. Proper selection or combination of subdural and depth electrodes and a wide-band analysis of electroencephalography may improve the accurate localization of epileptogenic region. Patients for whom curative resective surgery is not indicated because of generalized or bilateral multiple nature of their epilepsies, neuromodulation therapies are options of treatment which palliate their seizures.
  • Ryuji Kano, Kenichi Usami, Takahiro Noda, Tomoyo I. Shiramatsu, Ryohei Kanzaki, Kensuke Kawai, Hirokazu Takahashi
    ELECTRONICS AND COMMUNICATIONS IN JAPAN 98 3 47 - 56 2015年03月 [査読有り][通常論文]
    Vagus nerve stimulation (VNS) is a surgical treatment for intractable epilepsy. Although VNS has been used to treat more than 60,000 patients, the precise therapeutic mechanism of action has not been elucidated. Here, we hypothesize that VNS modulates the local synchronization of cortical activities and thus inhibits seizures. In order to verify this hypothesis, we mapped local field potentials (LFPs) with high-spatial resolution using a microelectrode array from the temporal cortices of adult rats and analyzed VNS-induced phase modulation at the local network level. VNS significantly increased the phase locking value (PLV), an index of synchronization, specifically at the gamma band. The optimal stimulation pulse of VNS was 0.5 mA delivered at 10 Hz. This PLV modulation was most effective when the interelectrode distance was about 1.6 mm. Gamma-band PLVs within the auditory cortex increased more significantly than those between the auditory and nonauditory cortices, while alpha- and low-beta PLV exhibited more synchronization between the auditory and nonauditory cortices. These results demonstrate that VNS modulates cortical synchronization in a band specific manner, and has some implications for the mechanism of action of VNS.
  • Takeshi Uno, Kensuke Kawai, Katsuyuki Sakai, Toshihiro Wakebe, Takuya Ibaraki, Naoto Kunii, Takeshi Matsuo, Nobuhito Saito
    PLOS ONE 10 3 e0122580  2015年03月 [査読有り][通常論文]
    Visual inputs can distort auditory perception, and accurate auditory processing requires the ability to detect and ignore visual input that is simultaneous and incongruent with auditory information. However, the neural basis of this auditory selection from audiovisual information is unknown, whereas integration process of audiovisual inputs is intensively researched. Here, we tested the hypothesis that the inferior frontal gyrus (IFG) and superior temporal sulcus (STS) are involved in top-down and bottom-up processing, respectively, of target auditory information from audiovisual inputs. We recorded high gamma activity (HGA), which is associated with neuronal firing in local brain regions, using electrocorticography while patients with epilepsy judged the syllable spoken by a voice while looking at a voice-congruent or -incongruent lip movement from the speaker. The STS exhibited stronger HGA if the patient was presented with information of large audiovisual incongruence than of small incongruence, especially if the auditory information was correctly identified. On the other hand, the IFG exhibited stronger HGA in trials with small audiovisual incongruence when patients correctly perceived the auditory information than when patients incorrectly perceived the auditory information due to the mismatched visual information. These results indicate that the IFG and STS have dissociated roles in selective auditory processing, and suggest that the neural basis of selective auditory processing changes dynamically in accordance with the degree of incongruity between auditory and visual information.
  • Hirotsugu Hashimoto, Atsushi Kurata, Tamaki Nashiro, Shigeru Inoue, Tomonori Ushijima, Koji Fujita, Toshikazu Kimura, Kensuke Kawai, Hajime Horiuchi, Masahiko Kuroda
    Although immaturity of neointimal smooth muscle cells (SMCs) in coronary arteries has recently been demonstrated to be associated with acute coronary syndrome, the carotid arterial counterpart has not been investigated. We hypothesized that the same investigation of carotid endarterectomy specimens might contribute to living patients. Carotid endarterectomy specimens from 33 Asian males who underwent a 5-year follow-up were examined. Age, atherosclerotic risk factors, and percentage stenosis were investigated. Histologically, the fibrous cap/lipid core ratio was measured. Maturation of SMCs was assessed by the h-caldesmon/smooth muscle actin (SMA) ratio by immunohistochemistry in 3 different regions (luminal, medial, and opposite side of lipid core) in the neointima. Associations of these factors with preoperative symptoms along with postoperative systemic atherogenic cardiovascular events were analyzed. It was revealed that fibrous cap/lipid core ratio was significantly lower in symptomatic than in asymptomatic patients, while the h-caldesmon/SMA ratio was significantly lower in patients with than without postoperative systemic atherogenic cardiovascular events by the Student's t-test (P<0.05). Logistic regression model demonstrated that younger age and a lower h-caldesmon/SMA ratio were associated with postoperative systemic atherogenic cardiovascular events (P<0.05). This result was not different when 3 different regions were each analyzed instead. Immaturity of neointimal SMCs shown by a lower h-caldesmon/SMA ratio by immunohistochemistry was associated with systemic atherogenic cardiovascular events. Thus, this finding may be predictive of these events after carotid endarterectomy. Uniform results among different neointimal regions suggest that immaturity of neointimal SMCs causes plaque instability and does not occur secondarily to plaque instability.
  • Toshikazu Kimura, Daichi Nakagawa, Kensuke Kawai
    Neurosurgical Focus 38 VideoSuppl1 Video17  2015年 [査読有り][通常論文]
    A large basilar trunk aneurysm was incidentally found in a 77-year-old woman in examination for headache. Though it was asymptomatic, high signal intensity was noticed in the brainstem around the aneurysm on FLAIR image of MRI. As she was otherwise healthy, surgical clipping was performed through anterior temporal approach.
  • Naoto Kunii, Kensuke Kawai, Kyousuke Kamada, Takahiro Ota, Nobuhito Saito
    EPILEPSIA 55 10 1594 - 1601 2014年10月 [査読有り][通常論文]
    ObjectiveResective surgery for mesial temporal lobe epilepsy (MTLE) with a correspondent lesion has been established as an effective and safe procedure. Surgery for temporal lobe epilepsies with bilateral hippocampal sclerosis or without correspondent lesions, however, carries a higher risk of devastating memory decline, underscoring the importance of establishing the memory-dominant side preoperatively and adopting the most appropriate procedure. In this study, we focused on high gamma activities (HGAs) in the parahippocampal gyri and investigated the relationship between memory-related HGAs and memory outcomes after hippocampal transection (HT), a hippocampal counterpart to neocortical multiple subpial transection. The transient nature of memory worsening after HT provided us with a rare opportunity to compare HGAs and clinical outcomes without risking permanent memory disorders. MethodsWe recorded electrocorticography from parahippocampal gyri of 18 patients with temporal lobe epilepsy while they executed picture naming and recognition tasks. Memory-related HGA was quantified by calculating differences in power amplification of electrocorticography signals in a high gamma range (60-120Hz) between the two tasks. We compared memory-related HGAs from correctly recognized and rejected trials (hit-HGA and reject-HGA). Using hit-HGA, we determined HGA-dominant sides and compared them with memory outcomes after HT performed on seven patients. ResultsWe observed memory-related HGA mainly between 500 and 600msec poststimulus. Hit-HGA was significantly higher than reject-HGA. Three patients who had surgery on the HGA-dominant side experienced transient memory worsening postoperatively. The postoperative memory functions of the other four patients remained unchanged. SignificanceParahippocampal HGA was indicated to reflect different memory processes and be compatible with the outcomes of HT, suggesting that HGA could provide predictive information on whether the mesial temporal lobe can be resected without causing memory worsening. This preliminary study suggests a refined surgical strategy for atypical MTLE based on reliable memory lateralization.
  • Kawai K
    No shinkei geka. Neurological surgery 42 9 807 - 816 2014年09月 [査読有り][通常論文]
  • Rie Hitsuyu, Takeshi Uno, Hiroyuki Nagata, Kazusa Takahashi, Takahiro Noda, Tomoyo Shiramatsu-Isoguchi, Ryohei Kanzaki, Kensuke Kawai, Hirokazu Takahashi
    Transactions of Japanese Society for Medical and Biological Engineering 52 371 - O-372 2014年08月 [査読有り][通常論文]
    Vagus nerve stimulation (VNS) reduces intractable epileptic seizures. VNS is also likely to improve higher brain functions such as cognition and memory, although the mechanisms of action remain speculative. In this study, we examined the effects of VNS on auditory perception. Using a depth microelectrode array, we investigated neural activities in the auditory cortex and thalamus of anesthetized rats in terms of reproducibility and temporal resolution of sound evoked responses. Consequently, we found that, in the auditory cortex, VNS improved reproducibility of neural activities in response to characteristic-frequency tones and strengthened adaptation to repetitive clicks. On the other hand, in the thalamus, VNS had no significant effect on reproducibility and temporal resolution of sound evoked responses. Thus, VNS may affect auditory perception.
  • Kawai K
    Nihon rinsho. Japanese journal of clinical medicine 72 5 881 - 886 2014年05月 [査読有り][通常論文]
  • Kei Majima, Takeshi Matsuo, Keisuke Kawasaki, Kensuke Kawai, Nokihito Saito, Isao Hasegawa, Yukiyasu Kamitani
    NEUROIMAGE 90 74 - 83 2014年04月 [査読有り][通常論文]
    How visual object categories are represented in the brain is one of the key questions in neuroscience. Studies on low-level visual features have shown that relative timings or phases of neural activity between multiple brain locations encode information. However, whether such temporal patterns of neural activity are used in the representation of visual objects is unknown. Here, we examined whether and how visual object categories could be predicted (or decoded) from temporal patterns of electrocorticographic (ECoG) signals from the temporal cortex in five patients with epilepsy. We used temporal correlations between electrodes as input features, and compared the decoding performance with features defined by spectral power and phase from individual electrodes. While using power or phase alone, the decoding accuracy was significantly better than chance, correlations alone or those combined with power outperformed other features. Decoding performance with correlations was degraded by shuffling the order of trials of the same category in each electrode, indicating that the relative time series between electrodes in each trial is critical. Analysis using a sliding time window revealed that decoding performance with correlations began to rise earlier than that with power. This earlier increase in performance was replicated by a model using phase differences to encode categories. These results suggest that activity patterns arising from interactions between multiple neuronal units carry additional information on visual object categories. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.
  • Kensuke Kawai, Michiharu Morino, Masaki Iwasaki
    BRAIN & DEVELOPMENT 36 2 124 - 129 2014年02月 [査読有り][通常論文]
    Delalande's vertical hemispherotomy is an innovative evolution of hemispherectomy in minimizing brain resection. We report our modification for this surgical procedure. We modified the original procedure in two aspects for the purpose of less brain resection and confirmation of the complete disconnection. Firstly, all procedures were done via an interhemispheric route instead of a transcortical route. Secondly, we set the anterior disconnection plane as the one that connects the anterior end of the choroidal fissure to the anterior end of the foramen of Monro, instead of the former to the subcallosal area. We applied this modified vertical hemispherotomy to 7 cases. Four cases were children with hemimegalencephaly and other 3 were adults with ulegyric hemisphere. Surgical procedure was completed without complication in all cases. There was no case that required CSF shunting. Seizure outcome was Engel's class I in 6 and class IV in 1. Postoperative MRI revealed complete disconnection of the affected hemisphere in all patients. We reported our modification of vertical hemispherotomy. Although these are minor modifications, they further minimized brain resection and may serve for less invasiveness of procedure and improvement in completeness of disconnection and its confirmation during surgery. (C) 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
  • Kenichi Usami, Ryuji Kano, Kensuke Kawai, Takahiro Noda, Tomoyo Isoguchi Shiramatsu, Nobuhito Saito, Hirokazu Takahashi
    IEEJ Transactions on Electronics, Information and Systems 134 3 332 - 337 2014年 [査読有り][通常論文]
    Vagus nerve stimulation (VNS) is a palliative treatment for intractable epilepsy. Therapeutic mechanisms of VNS have not been elucidated. In this study, we measured the local field potential (LFP) with high-spatial resolution using a microelectrode array in adult rats, and analyzed VNS-induced phase modulation at a local network level. Eight adult Wistar rats (270 - 330 g) were used. Each rat underwent implantation of VNS system under 1.5% isoflurane anesthesia. One week after implantation, right temporal craniotomy was performed under the same as previous anesthesia. Subsequently, a microelectrode array was placed in the temporal lobe cortex, and LFP was recorded with sampling rate of 1000 Hz. Phase-locking values (PLV) between all pairs of electrodes in varied frequency bands were calculated in order to evaluate the effect of VNS in terms of synchrony of neuronal activities. PLV was calculated both in a normal state and in an epileptic state induced by kainic acid. VNS increased PLV in a normal state, particularly in the high-? band. In an epileptic state, on the other hand, VNS increased PLV in high-? band, and decreased PLV in the d and low-β bands. These results suggest that VNS modulates neural activities in a band-specific and state-dependent manner so as to keep cortical synchrony within the optimal state. ©2014 The Institute of Electrical Engineers of Japan.
  • Takeshi Matsuo, Kensuke Kawai, Takeshi Uno, Naoto Kunii, Naohisa Miyakawa, Kenichi Usami, Keisuke Kawasaki, Isao Hasegawa, Nobuhito Saito
    NEUROSURGERY 73 2 Suppl Operative 146 - 154 2013年12月 [査読有り][通常論文]
    BACKGROUND: There has been growing interest in clinical single-neuron recording to better understand epileptogenicity and brain function. It is crucial to compare this new information, single-neuronal activity, with that obtained from conventional intracranial electroencephalography during simultaneous recording. However, it is difficult to implant microwires and subdural electrodes during a single surgical operation because the stereotactic frame hampers flexible craniotomy. OBJECTIVE: To describe newly designed electrodes and surgical techniques for implanting them with subdural electrodes that enable simultaneous recording from hippocampal neurons and broad areas of the cortical surface. METHODS: We designed a depth electrode that does not protrude into the dura and pulsates naturally with the brain. The length and tract of the depth electrode were determined preoperatively between the lateral subiculum and the lateral surface of the temporal lobe. A frameless navigation system was used to insert the depth electrode. Surface grids and ventral strips were placed before and after the insertion of the depth electrodes, respectively. Finally, a microwire bundle was inserted into the lumen of the depth electrode. We evaluated the precision of implantation, the recording stability, and the recording rate with microwire electrodes. RESULTS: Depth-microwire electrodes were placed with a precision of 3.6 mm. The mean successful recording rate of single-or multiple-unit activity was 14.8%, which was maintained throughout the entire recording period. CONCLUSION: We achieved simultaneous implantation of microwires, depth electrodes, and broad-area subdural electrodes. Our method enabled simultaneous and stable recording of hippocampal single-neuron activities and multichannel intracranial electroencephalography.
  • Yuta Fukushima, Soichi Oya, Hirofumi Nakatomi, Junji Shibahara, Shunya Hanakita, Shota Tanaka, Masahiro Shin, Kensuke Kawai, Masashi Fukayama, Nobuhito Saito
    JOURNAL OF NEUROSURGERY 119 6 1373 - 1379 2013年12月 [査読有り][通常論文]
    Object. Meningiomas treated by subtotal or partial resection are associated with significantly shorter recurrence-free survival than those treated by gross-total resection. The Simpson grading system classifies incomplete resections into a single category, namely Simpson Grade IV, with wide variations in the volume and location of residual tumors, making it complicated to evaluate the achievement of surgical goals and predict the prognosis of these tumors. Authors of the present study investigated the factors related to necessity of retreatment and tried to identify any surgical nuances achievable with the aid of modern neurosurgical techniques for meningiomas treated using Simpson Grade IV resection. Methods. This retrospective analysis included patients with WHO Grade I meningiomas treated using Simpson Grade IV resection as the initial therapy at the University of Tokyo Hospital between January 1995 and April 2010. Retreatment was defined as reresection or stereotactic radiosurgery due to postoperative tumor growth. Results. A total of 38 patients were included in this study. Regrowth of residual tumor was observed in 22 patients with a mean follow-up period of 6.1 years. Retreatment was performed for 20 of these 22 tumors with regrowth. Risk factors related to significantly shorter retreatment-free survival were age younger than 50 years (p = 0.006), postresection tumor volume of 4 cm(3) or more (p = 0.016), no dural detachment (p = 0.001), and skull base location (p = 0.016). Multivariate analysis revealed that no dural detachment (hazard ratio [BR] 6.42,95% CI 1.41-45.0; p = 0.02) and skull base location (HR 11.6, 95% CI 2.18-218; p = 0.002) were independent risk factors for the necessity of early retreatment, whereas postresection tumor volume of 4 cm(3) or more was not a statistically significant risk factor. Conclusions. Compared with Simpson Grade I, II, and III resections, Simpson Grade IV resection includes highly heterogeneous tumors in terms of resection rate and location of the residual mass. Despite the difficulty in analyzing such diverse data, these results draw attention to the favorable effect of dural detachment (instead of maximizing the resection rate) on long-term tumor control. Surgical strategy with an emphasis on detaching the tumor from the affected dura might be another important option in resection of high-risk meningiomas not amenable to gross-total resection.
  • 小川 博司, 國井 尚人, 広島 覚, 佐藤 正夫, 安栄 良悟, 鎌田 恭輔
    脳神経外科ジャーナル = Japanese journal of neurosurgery 22 10 786 - 790 The Japanese Congress of Neurological Surgeons 2013年10月 
    脳腫瘍摘出では機能の温存が重要であり, その機能マッピングには覚醒下手術, 頭蓋内電極による脳皮質電気刺激 (ECS) がある. しかし, ECSは痙攣誘発のリスクや痛みなどを伴う. 近年は脳皮質電位 (ECoG) による機能マッピングの報告があり, 特に高周波律動に注目が集まっている. 今回われわれは, 言語野近傍の脳腫瘍患者において, 頭蓋内電極によりECSマッピングとECoG計測を行った. ECoGは60∼120Hzの高周波律動であるhigh Gamma activity (HGA) に着目した. 文字読み課題で約600msec付近に誘発されたHGAはECSマッピングの側頭葉言語野と一致していた. また, HGAは後頭葉から側頭葉-前頭葉言語関連機能ダイナミクスを表していた. 本症例で施行した認知課題ECoGはECSに代わる脳機能マッピング法となる.
  • Kenichi Usami, Kensuke Kawai, Masahiro Sonoo, Nobuhito Saito
    BRAIN STIMULATION 6 4 615 - 623 2013年07月 [査読有り][通常論文]
    Background: Vagus nerve stimulation (VNS) is a palliative treatment for drug resistant epilepsy for which the efficacy and safety are well established. Accumulating evidence suggests that ascending vagal signals modulate abnormal cortical excitability via various pathways. However, there is no direct evidence for an ascending conduction of neural impulses in a clinical case of VNS. Objective: We recorded and analyzed the short-latency components of the vagus nerve (VN) evoked potential (EP) from the viewpoint of determining whether or not it is a marker for the ascending neural conduction. Methods: EPs within 20 ms were prospectively recorded simultaneously from a surgical wound in the neck and at multiple scalp sites during implantation surgery in 25 patients with drug-resistant epilepsy. Electrical stimulation was delivered using the clinical VNS Therapy system. A recording was made before and after a muscle relaxant was administered, when changing the rostrocaudal position of stimulation, or when stimulating the ansa cervicalis instead of the VN. Results: The short-latency components consisted of four peaks. The early component around 3 ms, which was most prominent in A1-Cz, remained unchanged after muscle relaxation while the later peaks disappeared. Rostral transition of the stimulation resulted in an earlier shift of the early component. The estimated conduction velocity was 27.4 +/- 10.2 m/s. Stimulation of the ansa cervicalis induced no EP. Conclusions: The early component was regarded as directly resulting from ascending neural conduction of A fibers of the VN, probably originating around the jugular foramen. Recording of VN-EP might document the cause of treatment failure in some patients. (C) 2013 Elsevier Inc. All rights reserved.
  • Ryuji Kano, Kenichi Usami, Takahiro Noda, Tomoyo I. Shiramatsu, Ryohei Kanzaki, Kensuke Kawai, Hirokazu Takahashi
    IEEJ Transactions on Electronics, Information and Systems 133 8 11 - 1500 2013年 [査読有り][通常論文]
    Vagus Nerve Stimulation (VNS) is a surgical treatment for intractable epilepsy. Although VNS has treated more than 60,000 patients, the precise therapeutic mechanism of action have not been elucidated. Here we hypothesize that VNS modulates the local synchronization of cortical activities and thus inhibits a seizure. In order to verify this hypothesis, we mapped local field potentials (LFPs) with high-spatial resolution using a microelectrode array from the temporal cortices of adult rats and analyzed VNS-induced phase modulation at a local network level. VNS significantly increased phase locking value (PLV), an index of synchronization, specifically at the gamma band. The optimal stimulation pulse of VNS was 0.5 mA and delivered at 10 Hz. This PLV modulation was most effective when the inter-electrode distance was about 1.6 mm. Gamma-band PLVs within the auditory cortex increased more significantly than those between the auditory and non-auditory cortices, while alpha- and low-beta PLV exhibited more synchronization between the auditory and non-auditory cortices. These results demonstrate that VNS modulates cortical synchronization in a band specific manner, and have some implications for the mechanism of action of VNS. © 2013 The Institute of Electrical Engineers of Japan.
  • Naoto Kunii, Kyousuke Kamada, Takahiro Ota, Richard E. Greenblatt, Kensuke Kawai, Nobuhito Saito
    CLINICAL NEUROPHYSIOLOGY 124 1 91 - 100 2013年01月 [査読有り][通常論文]
    Objective: We developed a novel technique of spatial normalization of subdural electrode positions across subjects and assessed the spatial-temporal dynamics of high-gamma activity (HGA) in the dominant hemisphere elicited by three distinct language tasks. Methods: The normalization process was applied to 1512 subdural electrodes implanted in 21 patients with intractable epilepsy. We projected each task-related HGA profile onto a normalized brain. Results: The word interpretation task initially elicited HGA augmentation in the bilateral fusiform gyri at 100 ms after stimulus onsets, subsequently in the left posterior middle temporal gyrus, in the left ventral premotor cortex at 200 ms and in the left middle and left inferior frontal gyri at 300 ms and after. The picture naming task elicited HGA augmentation in few sites in the left frontal lobe. The verb generation task elicited HGA in the left superior temporal gyrus at 100-600 ms. Common HGA augmentation elicited by all three tasks was noted in the left posterior-middle temporal and left ventral premotor cortices. Conclusions: The spatial-temporal dynamics of language-related HGA were demonstrated on a spatially normalized brain template. Significance: This study externally validated the spatial and temporal dynamics of language processing suggested by previous neuroimaging and electrophysiological studies. (C) 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
  • Naoto Kunii, Kyousuke Kamada, Takahiro Ota, Kensuke Kawai, Nobuhito Saito
    NEUROIMAGE 65 242 - 249 2013年01月 [査読有り][通常論文]
    High gamma activity (HGA) has been shown to be positively correlated with blood oxygenation level-dependent (BOLD) responses in the primary cortices with simple tasks. It is, however, an open question whether the correlation is simply applied to the association areas related to higher cognitive functions. The aim of this study is to investigate quantitative correlation between HGA and BOLD and their spatial and temporal profiles during semantic processing. Thirteen patients with intractable epilepsy underwent fMRI and electrocorticography (ECoG) with a word interpretation task to evoke language-related responses. Percent signal change of BOLD was calculated at each site of ECoG electrode, which has power amplification of high gamma band (60-120 Hz) activity. We transformed locations of individual electrodes and brains to a universal coordination using SPM8 and made the quantitative comparisons on a template brain. HGAs were increased in several language-related areas such as the inferior frontal and middle temporal gyri and were positively correlated with BOLD responses. The most striking finding was different temporal dynamics of HGAs in the different brain regions. Whereas the frontal lobe showed longer-lasting HGA, the HGA-intensity on the temporal lobe quickly declined. The different temporal dynamics of HGA might explain why routine language-fMRI hardly detected BOLD in the temporal lobe. This study clarified different neural oscillation and BOLD response in various brain regions during semantic processing and will facilitate practical utilization of fMRI for evaluating higher-order cognitive functions not only in basic neuroscience, but also in clinical practice. (C) 2012 Elsevier Inc. All rights reserved.
  • Kenichi Usami, Ryuji Kano, Kensuke Kawai, Takahiro Noda, Tomoyo I. Shiramatsu, Nobuhito Saito, Hirokazu Takahashi
    Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS 2013 5348 - 5351 2013年 [査読有り][通常論文]
    Vagus nerve stimulation (VNS) is a palliative treatment for intractable epilepsy. Therapeutic mechanisms of VNS have not been elucidated. In this study, we measured the local field potential (LFP) with high-spatial resolution using a microelectrode array in adult rats, and analyzed VNS-evoked phase modulation at a local network level. Eight adult Wistar rats (270 - 330 g) were used. Each rat underwent implantation of VNS system (Cyberonics, Houston, TX., USA) under 1.5% isoflurane anesthesia. One week after implantation, right temporal craniotomy was performed under the same as previous anesthesia. Subsequently, a microelectrode array was placed in the temporal lobe cortex, and LFP was recorded with sampling rate of 1000 Hz. Phase-locking value (PLV) between all pairs of electrodes in varied frequency bands was calculated in order to evaluate the effect of VNS in terms of synchrony of neuronal activities. PLV was calculated both in a normal state and in an epileptic state induced by kainic acid. VNS increased PLV in a normal state, particularly in high-γ band. In an epileptic state, VNS increased PLV in high-γ band, and decreased in d and low-β bands. VNS modulates synchrony in a band-specific and state-dependent manner. VNS might keep cortical synchrony within the optimal state. © 2013 IEEE.
  • Hirokazu Takahashi, Shuhei Takahashi, Ryohei Kanzaki, Kensuke Kawai
    NEUROLOGICAL SCIENCES 33 6 1355 - 1364 2012年12月 [査読有り][通常論文]
    Accurate prediction of epileptic seizures will open novel therapeutic possibilities for patients with intractable epilepsy. We attempted to identify precursors of seizures in the functional networks of electrocorticograms by applying graph theory. Long-term electrocorticograms for periods of 39-76 h from three patients with temporal lobe epilepsy were investigated using pair-wise cross-correlations. Time-varying network properties suggested that there were several distinct brain states. Although functional networks during seizures could be characterized as having a regular topography, no consistent characteristics of functional networks were found immediately prior to seizure onsets. However, it was found that seizures under an identical state were followed by similar transients of the network properties. These results suggest that network properties themselves could not serve as reliable predictors of seizure onset. Yet, some significant pre-seizure changes in the parameters tested appear likely to depend on the brain state. To predict seizures, it may be necessary to take into consideration the states of the brain. In addition to stationary network properties we characterized in the present study, dynamic interactions of epileptic activities with the network might be taken into account to predict the spread of a seizure.
  • Kouhei Kamiya, Harushi Mori, Akira Kunimatsu, Kensuke Kawai, Kenichi Usami, Kuni Ohtomo
    JOURNAL OF NEURORADIOLOGY 39 5 360 - 363 2012年12月 [査読有り][通常論文]
    This is a report of two cases of spontaneous temporal encephalocele: one was anteroinferior and presented with epilepsy; the other was posteroinferior and presented with facial neuritis and labyrinthitis. Spontaneous temporal encephalocele is relatively rare and apparently not familiar to a majority of primary physicians. It may present with a variety of symptoms according to its anatomical location, including cerebrospinal fluid fistulas, recurrent meningitis, chronic otitis media, hearing loss, facial nerve palsy and medically intractable epilepsy. Attention should be paid to this disease entity, as it is easily overlooked in imaging studies and can leave serious neurological deficits. (C) 2012 Elsevier Masson SAS. All rights reserved.
  • Yuta Fukushima, Takahiro Ota, Akitake Mukasa, Hiroshi Uozaki, Kensuke Kawai, Nobuhito Saito
    WORLD NEUROSURGERY 78 5 553.e9 - 553.e13 2012年11月 [査読有り][通常論文]
    BACKGROUND: Tumor-to-tumor metastasis is a rare but well-known phenomenon. Among the more than 100 intracranial tumors reported, meningiomas are the most common type, whereas schwannoma is extremely rare. CASE DESCRIPTION: We describe a 75-year-old woman with a lung adenocarcinoma that metastasized to a vestibular schwannoma. Tumor-to-tumor metastasis was indicated by preoperative [F-18]-fluorodeoxyglucose positron emission tomography. CONCLUSIONS: [F-18]-fluorodeoxyglucose positron emission tomography is effective in the preoperative diagnosis of rapidly growing cerebellopontine angle tumors in patients with a history of malignancy.
  • Miwako Takahashi, Tsutomu Soma, Kensuke Kawai, Keitraro Koyama, Kuni Ohtomo, Toshimitsu Momose
    ANNALS OF NUCLEAR MEDICINE 26 9 698 - 706 2012年11月 [査読有り][通常論文]
    This study aims to elucidate differences in preoperative cerebral glucose metabolism between patients who did and did not become seizure free after unilateral mesial temporal lobe epilepsy (mTLE) surgery. We hypothesized that regional glucose metabolism on preoperative fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with seizure-free outcomes differed from that in patients who were not seizure free after appropriate epilepsy surgery for unilateral mTLE. In this study, we compared preoperative FDG-PET findings between these two patient groups by applying a statistical analysis approach, with a voxel-based Asymmetry index (AI), to improve sensitivity for the detection of hypometabolism. FDG-PET scans of 28 patients with medically refractory mTLE, of whom 17 achieved a seizure-free outcome (Engel class 1 a-b) during a postoperative follow-up period of at least 2 years, were analyzed retrospectively. Voxel values were adjusted by the AI method as well as the global normalization (GN) method. Two types of statistical analysis were performed. One was a voxel severity analysis with comparison of voxel values at the same coordinate, and the other was extent analysis with comparison of the number of significant voxels in the anatomical areas predefined with Talairach's atlas. In the voxel severity analysis, significant hypometabolism restricted to the ipsilateral temporal tip and hippocampal area was detected in the postoperative seizure-free outcome group as compared to controls. No significant area was detected in the non-seizure-free group as compared to controls (family-wise error corrected, p < 0.05). With extent analysis using a low threshold, the extents of hypometabolism in the ipsilateral hippocampal, frontal and thalamic areas were larger in the seizure-free than in the non-seizure-free group (p = 0.01, 0.03 and 0.01, respectively.) On the other hand, in the contralateral frontal and thalamic areas, extents of hypometabolism were smaller in the seizure-free than in the non-seizure-free group (p = 0.01 and 0.01). We found the preoperative distribution of hypometabolism to differ between the two patient groups. Severe hypometabolism restricted to the unilateral temporal lobe, with ipsilateral dominant hypometabolism including mild decreases, may support the existence of an epileptogenic focus in the unilateral temporal lobe and a favorable seizure outcome after mTLE surgery.
  • Takuya Iida, Makoto Mihara, Hidehiko Yoshimatsu, Hisako Hara, Isao Koshima, Kensuke Kawai, Tsukasa Tsuchiya, Takahiro Asakage
    MICROSURGERY 32 8 622 - 626 2012年11月 [査読有り][通常論文]
    Despite the recent advances in microsurgical techniques, reconstruction of extensive skull base defects using free flaps in pediatric patients presents a surgical challenge, and reports on skull base reconstruction in infants is quite limited. We present a case of reconstruction of an extensive anterior skull base defect using a rectus abdominis (RA) myocutaneous flap in a 1 year-old (14 months) infant. Sufficient coverage of the intracranial contents, good aesthetic results, and minimal growth disturbance at the donor site were achieved by the muscle-sparing RA flap transfer. To the best of our knowledge, this was among the youngest case of skull base reconstruction using a free flap. The feasibility of free flap transfer and flap selection in pediatric skull base reconstruction is discussed. (c) 2012 Wiley Periodicals, Inc.
  • Shunya Hanakita, Kensuke Kawai, Junichi Shibahara, Nobutaka Kawahara, Nobuhito Saito
    NEUROLOGIA MEDICO-CHIRURGICA 52 10 747 - 750 2012年10月 [査読有り][通常論文]
    A 20-year-old woman presented with a rare case of intraorbital mesenchymal chondrosarcoma manifesting as a 6-month history of progressive ptosis and exophthalmos of her left eye. Computed tomography and magnetic resonance imaging revealed a partially calcified round mass occupying the postbulbar space. Partial removal of the tumor via a left fronto-orbital approach was performed. The histological diagnosis was mesenchymal chondrosarcoma, and additional intraorbital exenteration was performed. Neither chemotherapy nor radiotherapy was performed. She was free from tumor recurrence at the 6-year follow-up examination. Radical resection, including exenteration if possible, is recommended for intraorbital mesenchymal chondrosarcoma.
  • Kyousuke Kamada, Naoto Kunii, Satoru Hiroshima, Takahiro Ota, Kensuke Kawai, Nobuhito Saito
    Brain and Nerve 64 9 1001 - 1012 2012年09月 [査読有り][通常論文]
    We compared electrocorticography (ECoG) with invasive intracranial noninvasive functional MRI using language-related tasks. Twenty patients underwent bilateral implantation of subdural electrodes (more than 80 channels) for diagnosing intractable epilepsy. Before implantation of the electrodes, language-related fMRI was performed, and the fMR images were superimposed on individual brain images. Brain mapping with electrocortical stimulation was performed on the basis of the fused fMR and brain MR images, and the specificity and sensitivity of language-related fMRI was calculated. For careful interpretation of spatial and temporal ECoG changes with semantic tasks, we developed a software to visualize semantic-ECoG dynamics in the brain. Semantic-ECoG was recorded during word, figure, and face recognition as well as memory tasks. The raw ECoG data were processed by averaging and time-frequency analysis, and the functional profiles were projected onto the individual brain surface. Acquired ECoG was classified using Support Vector Machine and Sparse Logistic Regression to decode brain signals. Because of variations in electrode locations, we normalized the ECoG electrodes by using SPM8. Although fMRI has 90% sensitivity, its specificity is only up to 50%. The basal temporal-occipital cortex was activated within 250 ms after visual object presentation. Compared to other stimuli, face stimulation evoked significantly higher ECoG amplitudes. Among different brain regions, the hippocampus was predominantly activated during the memory task. The prediction rate of ECoG classification was 90%, which was sufficient for clinical use. Semantic-ECoG is a powerful technique to detect and decode human brain functions.
  • Kensuke Kawai
    Brain and Nerve 64 9 1013 - 1022 2012年09月 [査読有り][通常論文]
    Functional neuroimaging is one of the most progressing fields in neuroscience and clinical neurological practice. It has also been contributing to the diagnosis and treatment of epilepsy. Intracranial electroencephalography (iEEG) is the gold standard for the diagnostic localization of the epileptogenic zone in the surgical treatment of epilepsy. Currently, no other modalities, including novel functional neuroimaging modalities, are superior to ¡EEG in sensitivity and spatial resolution. However, iEEG is an invasive procedure and its clinical usefulness is dependent on appropriate coverage of the epileptogenic zone. In this review article, the author discusses the principles of decision making in surgical indication and procedures by presenting clinical cases and evaluating the significance of functional neuroimaging in these processes the review focuses on magnetoencephalography, 2-deoxy-2-[ 18F] fluoro-D-glucose positron emission tomography, and single photon emission computed tomography. The characteristics, advantages, and disadvantages of each modality are summarized. In some cases, but not all, functional neuroimaging modalities help avoid invasive iEEG without worsening surgical outcome and aid in determining the coverage area of iEEG, thereby resulting in better outcome and less complication.
  • Soichi Oya, Kensuke Kawai, Hirofumi Nakatomi, Nobuhito Saito
    JOURNAL OF NEUROSURGERY 117 1 121 - 128 2012年07月 [査読有り][通常論文]
    Object. Techniques for the surgical treatment of meningioma have undergone many improvements since Simpson established the neurosurgical dogma for meningioma surgery in his seminal paper published in 1957. This study aims to assess the clinical significance and limitations of the Simpson grading system in relation to modern surgery for WHO Grade I benign meningiomas and to explore the potential of the cell proliferation index to complement the limitations in predicting their recurrence. Methods. The surgical records of patients who underwent resection of intracranial meningiomas at the University of Tokyo Hospital between January 1995 and August 2010 were retrospectively analyzed. The authors investigated the relationships between recurrence-free survival (RFS) and Simpson grade or MIB-1 labeling index value. Results. A total of 240 patients harboring 248 benign meningiomas were included in this study. Simpson Grade IV resection was associated with a significantly shorter RFS than Simpson Grade I, II, or III resection (p < 0.001), while no statistically significant difference was noted in RFS between Simpson Grades I, II, and III. Among meningiomas treated by Simpson Grade II and III resections, however, multivariate analysis revealed that an MIB-1 index of 3% or higher was associated with a significantly shorter time to recurrence. Conclusions. The clinical significance of the different management strategies related to Simpson Grade I-III resection may have been diluted in the modern surgical era. The MIB-1 index can differentiate tumors with a high risk of recurrence, which could be beneficial for planning tailored optimal follow-up strategies. The results of this study appear to provide a significant backing for the recent shift in meningioma surgery from attempting aggressive resection to valuing the quality of the patient's life. (http://thejns.org/doi/abs/10.3171/2012.3.JNS111945)
  • Kenichi Usami, Kensuke Kawai, Tomoyuki Koga, Masahiro Shin, Hiroki Kurita, Ichiro Suzuki, Nobuhito Saito
    JOURNAL OF NEUROSURGERY 116 6 1221 - 1225 2012年06月 [査読有り][通常論文]
    Object. Despite the controversy over the clinical significance of Gamma Knife surgery (GKS) for refractory mesial temporal lobe epilepsy (MTLE), the modality has attracted attention because it is less invasive than resection. The authors report long-term outcomes for 7 patients, focusing in particular on the long-term complications. Methods. Between 1996 and 1999,7 patients with MTLE underwent GKS. The 50% marginal dose covering the medial temporal structures was 18 Gy in 2 patients and 25 Gy in the remaining 5 patients. Results. High-dose treatment abolished the seizures in 2 patients and significantly reduced them in 2 others. One patient in this group was lost to follow-up. However, 2 patients presented with symptomatic radiation necrosis (SRN) necessitating resection after 5 and 10 years. One patient who did not need necrotomy continued to show radiation necrosis on MRI after ID years. One patient died of drowning while swimming in the sea 1 year after GKS, before seizures had disappeared completely. Conclusions. High-dose treatment resulted in sufficient seizure control but carried a significant risk of SRN after several years. Excessive target volume was considered as a reason for delayed necrosis. Drawbacks such as a delay in seizure control and the risk of SRN should be considered when the clinical significance of this treatment is evaluated. (http://thejns.org/doi/abs/10.3171/2012.2.JNS111296)
  • Takato Morioka, Tetsuro Sayama, Takashi Shimogawa, Takeshi Hamamura, Kimiaki Hashiguchi, Kensuke Kawai, Nobutaka Mukae, Nobuya Murakami, Tomio Sasaki
    Brain and Nerve 64 6 681 - 687 2012年06月 [査読有り][通常論文]
    Vagus nerve Stimulation (VNS) is a palliative treatment for medically intractable epilepsy and has been covered by public health insurance in Japan since July 1, 2010. The frequency of the use of VNS during the first year of insurance coverage was determined by assessing the number of cases for which VNS was performed in Kyushu Rosai Hospital, the number of registered cases, and the questionnaire survey filled by 68 surgeons who are board certified as both epileptologists and neurosurgeons. VNS devices were placed in 98 patients from July 2010 to June 2011. These devices were placed in an average of 4.4 patients per month from July 2010 to November 2010 and in an average of 10.9 patients from December 2010 to June 2011. However, we did not observe an increasing trend. Almost all of the surgeries were performed in the Kanto (56 patients in 8 institutes) and Tokai (24 patients in 2 institutes) areas. VNS was not performed in many institutes primarily because VNS was not indicated for any of the patients. The questionnaire survey indicated that the use of VNS was likely to increase with an increase in the number of neurologists who decide on performing VNS preoperatively and regulate the conditions of the vagus nerve stimulator postoperatively. In conclusion, VNS is currently being applied in a limited number of institutes in the Kanto and Tokai areas, and a close association between the epileptologists and neurologists during preoperative and postoperative periods will increase the use of VNS.
  • Mori H, Kunimatsu A, Abe O, Sasaki H, Takao H, Nojo T, Kawai K, Saito N, Ohtomo K
    The neuroradiology journal 25 2 163 - 171 2012年05月 [査読有り][通常論文]
  • Tsutomu Soma, Toshimitsu Momose, Miwako Takahashi, Keitraro Koyama, Kensuke Kawai, Kenya Murase, Kuni Ohtomo
    ANNALS OF NUCLEAR MEDICINE 26 4 319 - 326 2012年05月 [査読有り][通常論文]
    Inter-ictal F-18-2-fluoro-deoxy--glucose-positron emission tomography (FDG-PET) is widely used for preoperative evaluation to identify epileptogenic zones in patients with temporal lobe epilepsy. In this study, we combined statistical parametric mapping (SPM) with the asymmetry index and volume-of-interest (VOI) based extent analysis employing preoperative FDG-PET in unilateral mesial temporal lobe epilepsy (MTLE) patients. We also evaluated the detection utility of these techniques for automated identification of abnormalities in the unilateral hippocampal area later confirmed to be epileptogenic zones by surgical treatment and subsequent good seizure control. FDG-PET scans of 17 patients (9 males, mean age 35 years, age range 16-60 years) were retrospectively analyzed. All patients had been preoperatively diagnosed with unilateral MTLE. The surgical outcomes of all patients were Engel class 1A or 1B with postoperative follow-up of 2 years. FDG-PET images were spatially normalized and smoothed. After two voxel-value adjustments, one employing the asymmetry index and the other global normalization, had been applied to the images separately, voxel-based statistical comparisons were performed with 20 controls. Peak analysis and extent analysis in the VOI in the parahippocampal gyrus were conducted for SPM. For the extent analysis, a receiver operating characteristic (ROC) curve was devised to calculate the area under the curve and to determine the optimal threshold of extent. The accuracy of the method employing the asymmetry index was better than that of the global normalization method for both the peak and the extent analysis. The ROC analysis results, for the extent analysis, yielded an area under the curve of 0.971, such that the accuracy and optimal extent threshold of judgment were 92 and 32.9%, respectively. Statistical -score mapping with the asymmetry index was more sensitive for detecting regional glucose hypometabolism and more accurate for identifying the side harboring the epileptogenic zone using inter-ictal FDG-PET in unilateral MTLE than -score mapping with global normalization. Moreover, the automated determination of the side with the epileptogenic zone in unilateral MTLE showed improved accuracy when the combination of SPM with the asymmetry index and extent analysis was applied based on the VOI in the parahippocampal gyrus.
  • Takuya Iida, Makoto Mihara, Mitsunaga Narushima, Isao Koshima, T. Asakage, K. Kawai
    Annals of Plastic Surgery 68 1 49 - 51 2012年01月 [査読有り][通常論文]
    Malignant change in fibrous dysplasia (FD) is a well-described phenomenon in the literature. When rapid enlargement is observed in an FD lesion, malignant change should be considered first. We present a case with McCune-Albright syndrome in which a rapidly enlarging orbital tumor developed in a facial FD lesion, which was subsequently proven to be a metastasis from an incidental esophageal carcinoma. Although metastasis of a malignant tumor to an FD lesion is quite rare and has been neglected as a differential diagnosis in the literature, it should be included in the important differential diagnosis because hematogenous metastasis could readily occur in FD due to its abundant blood flow. The importance of systemic examinations, such as positron emission tomography, is also emphasized. © 2012 by Lippincott Williams & Wilkins.
  • Naoto Kunii, Kyousuke Kamada, Takahiro Ota, Kensuke Kawai, Nobuhito Saito
    NEUROSURGERY 69 3 590 - 596 2011年09月 [査読有り][通常論文]
    BACKGROUND: Functional magnetic resonance imaging (fMRI) is a less invasive way of mapping brain functions. The reliability of fMRI for localizing language-related function is yet to be determined. OBJECTIVE: We performed a detailed analysis of language fMRI reliability by comparing the results of 3-T fMRI with maps determined by extraoperative electrocortical stimulation (ECS). METHODS: This study was performed on 8 epileptic patients who underwent subdural electrode placement. The tasks performed during fMRI included verb generation, abstract/concrete categorization, and picture naming. We focused on the frontal lobe, which was effectively activated by these tasks. In extraoperative ECS, 4 tasks were combined to determine the eloquent areas: spontaneous speech, picture naming, reading, and comprehension. We calculated the sensitivity and specificity with different Z score thresholds for each task and appropriate matching criteria. For further analysis, we divided the frontal lobe into 5 areas and investigated intergyrus variations in sensitivity and specificity. RESULTS: The abstract/concrete categorization task was the most sensitive and specific task in fMRI, whereas the picture naming task detected eloquent areas most efficiently in ECS. The combination of the abstract/concrete categorization task and a 3-mm matching criterion gave the best tradeoff (sensitivity, 83%; specificity, 61%) when the Z score was 2.24. As for intergyrus variation, the posterior inferior frontal gyrus showed the best tradeoff (sensitivity, 91%; specificity, 59%), whereas the anterior middle frontal gyrus had low specificity. CONCLUSION: Despite different tasks for fMRI and extraoperative ECS, the relatively low specificity might be caused by a fundamental discrepancy between the 2 techniques. Reliability of language fMRI activation might differ, depending on the brain region.
  • HANAKITA Shunya, IIJIMA Akira, ISHIKAWA Osamu, KAMADA Kyousuke, SAITO Nobuhito
    Neurologia medico-chirurgica = 神経外科 51 8 588 - 591 The Japan Neurosurgical Society 2011年08月 
    A 62-year-old man presented with rupture of a pseudoaneurysm of the left common carotid artery (CCA) that was induced after radiation therapy and neck surgery. The initial treatment was an endovascular procedure to obliterate the aneurysm with coils, and a covered stent was placed in the parent artery. However, the patient presented with subsequent coil migration, wound infection, and left CCA stenosis. Direct surgical procedures were then performed, including resection of the pseudoaneurysm with coils and stent; replacement of the carotid artery with a saphenous vein graft; and operative wound reinforcement with a pedicle flap. Endovascular treatments may be chosen for vascular diseases after irradiation, because of the low risk of wound infection and fragility of the vessels, but the long-term outcomes of intravascular treatments are still unclear. In direct surgery, dissection of the adhesive tissue and adequate wound healing are difficult. Musculocutaneous flaps with vascular pedicles can achieve good results.
  • Satoshi Koizumi, Kensuke Kawai, Shuichiro Asano, Keisuke Ueki, Ichiro Suzuki, Nobuhito Saito
    NEUROLOGIA MEDICO-CHIRURGICA 51 8 604 - 610 2011年08月 [査読有り][通常論文]
    Documentation of familial epilepsy is of paramount importance for identification of epilepsy-associated genes, elucidation of pathomechanisms of epilepsy, and development of treatment of epilepsy. We report a Japanese family with 5 members with lateral temporal lobe epilepsy beginning around the second decade of life. All seizures were intractable to medical treatment, and four patients underwent surgical treatment following long-term monitoring by intracranial electroencephalography with subdural electrodes, which revealed neocortical origins for the seizure. These four patients were successfully treated with surgery. The clinical features of this familial temporal lobe epilepsy seem to be different from those of previously reported types of familial temporal lobe epilepsy.
  • Kenya Kobayashi, Kazunari Nakao, Kensuke Kawai, Ken Ito, Seiji Hukumoto, Takahiro Asakage, Satoshi Oota, Ryo Motoi
    Background. Tumor-induced osteomalacia (TIO) is a rare clinical entity in which secondary osteomalacia is induced by tumor-related products. Fibroblast growth factor 23 (FGF-23) mRNA is overexpressed in the tumor tissue, leading to impaired reabsorption of phosphorus in the renal tubules and hypophosphatemia. Curative treatment is considered to be total resection of the tumor. Methods and Results. A 53-year-old woman had experienced systemic bone pain and muscle weakness for several years. She had refractory hypophosphatemia and marked elevation of serum FGF-23 level. Whole body imaging eventually revealed a hypervascular mass in the right temporal bone, leading to a diagnosis of TIO. She underwent skull-base surgery after embolization of the tumor. After the en bloc resection, FGF-23 became undetectable, phosphate reabsorption normalized, and all symptoms resolved. Conclusions. We discuss the clinical features and treatment options for this rare disease. (C) 2010 Wiley Periodicals, Inc. Head Neck 33: 1072-1075, 2011
  • Takeshi Uno, Kensuke Kawai, Naoto Kunii, Seiji Fukumoto, Junji Shibahara, Toru Motoi, Nobuhito Saito
    NEUROSURGERY 69 1 E239 - E244 2011年07月 [査読有り][通常論文]
    BACKGROUND AND IMPORTANCE: Tumor-induced osteomalacia (TIO) is an uncommon paraneoplastic syndrome rarely encountered in neurosurgical practice. We report on 2 cases of TIO caused by skull base tumors. Although the diagnosis of TIO is difficult to make and often is delayed because of the insidious nature of the symptoms, mostly systemic pain and weakness, it is curable once it is diagnosed and properly treated. CLINICAL PRESENTATION: Both patients presented with severe pain developing in the lower extremities and moving out to the entire body, as well as difficulty moving. They were diagnosed with TIO several years after onset. A high level of serum FGF23 was confirmed, and whole-body imaging studies demonstrated tumors in the middle and anterior cranial base, respectively. The patient with the anterior cranial base tumor had a history of hemorrhage into the frontal lobe and partial resection. En bloc resection of tumor with surrounding skull bone was performed. The histological diagnosis for both cases was phosphaturic mesenchymal tumor, mixed connective tissue variant. CONCLUSION: The level of FGF23 normalized immediately after surgery. Both patients experienced a dramatic relief of pain and recovery of muscle power. Although reports of osteomalacia caused by tumors in the neurosurgical field are extremely rare in the literature, its true incidence is unknown. We emphasize the importance of recognition of this syndrome and recommend total resection of tumors when possible.
  • Takeshi Matsuo, Keisuke Kawasaki, Takahiro Osada, Hirohito Sawahata, Takafumi Suzuki, Masahiro Shibata, Naohisa Miyakawa, Kiyoshi Nakahara, Atsuhiko Iijima, Noboru Sato, Kensuke Kawai, Nobuhito Saito, Isao Hasegawa
    Frontiers in Systems Neuroscience 5 2011 34  2011年05月 [査読有り][通常論文]
    Electrocorticography (ECoG), multichannel brain-surface recording and stimulation with probe electrode arrays, has become a potent methodology not only for clinical neurosurgery but also for basic neuroscience using animal models. The highly evolved primate's brain has deep cerebral sulci, and both gyral and intrasulcal cortical regions have been implicated in important functional processes. However, direct experimental access is typically limited to gyral regions, since placing probes into sulci is difficult without damaging the surrounding tissues. Here we describe a novel methodology for intrasulcal ECoG in macaque monkeys. We designed and fabricated ultra-thin flexible probes for macaques with micro-electro-mechanical systems (MEMS) technology. We developed minimally invasive operative protocols to implant the probes by introducing cutting edge devices for human neurosurgery. To evaluate the feasibility of intrasulcal ECoG, we conducted electrophysiological recording and stimulation experiments. First, we inserted parts of the Parylene-C-based probe into the superior temporal sulcus to compare visually evoked ECoG responses from the ventral bank of the sulcus with those from the surface of the inferior temporal cortex. Analyses of power spectral density and signal-to-noise ratio revealed that the quality of the ECoG signal was comparable inside and outside of the sulcus. Histological examination revealed no obvious physical damage in the implanted areas. Second, we placed a modified silicone ECoG probe into the central sulcus and also on the surface of the precentral gyrus for stimulation. Thresholds for muscle twitching were significantly lower during intrasulcal stimulation compared to gyral stimulation. These results demonstrate the feasibility of intrasulcal ECoG in macaques. The novel methodology proposed here opens up a new frontier in neuroscience research, enabling the direct measurement and manipulation of electrical activity in the whole brain. © 2011 Matsuo, Kawasaki, Osada, Sawahata, Suzuki, Shibata, Miyakawa, Nakahara, Iijima, Sato, Kawai, Saito and Hasegawa.
  • Takahiro Ota, Kyousuke Kamada, Kensuke Kawai, Masato Yumoto, Shigeki Aoki, Nobuhito Saito
    BRITISH JOURNAL OF NEUROSURGERY 25 2 197 - 202 2011年04月 [査読有り][通常論文]
    Objective. The determination of language lateralisation is important for patients with medically intractable epilepsy or a brain tumour near the language areas to avoid the risk of post-surgical language deficits. The aim of this study was to evaluate the clinical usefulness of near-infrared spectroscopy (NIRS) to identify language lateralisation compared with functional MRI (fMRI) and magnetoencephalography (MEG) in multiple language tasks. Methods. We investigated 28 patients whose language dominance was evaluated by the Wada test. fMRI, MEG and NIRS were performed to investigate language representation. All patients were as'ked to read three-letter words silently for fMRI and MEG (Kana reading) and to write words beginning with a visually presented letter (word generation) for NIRS. The laterality index was calculated to assess language lateralisation in each investigation. Results. In 24 cases (85.7%), of which two investigations showed the same laterality, the results had perfect concordance with the Wada test. In patients with left dominance, the sensitivity and specificity of fMRI, MEG and NIRS was 95.0% and 62.5%, 100% and 87.5%, 75.0% and 87.5%, respectively. In three patients with right lateralization, only NIRS showed a significant increase of oxygenated-haemoglobin in the right inferior frontal region, indicating right dominance. Conclusion. We established a method to determine language lateralisation by co-utilising fMRI, MEG and NIRS with high reliability. NIRS recognised atypical language representation, in addition to fMRI and MEG. While fMRI, MEG and NIRS are not currently as accurate as the Wada test in determining language lateralisation, this non-invasive and repeatable method has great potential as an alternative to the Wada test in time following further research and refinement of these techniques.
  • Kensuke Kawai
    Brain and Nerve 63 4 331 - 346 2011年04月 [査読有り][通常論文]
    Vagus nerve stimulation is a palliative treatment for medically intractable epilepsy. This treatment reduces the frequency and severity of seizures refractory to antiepileptic drugs. Implanted generator and helical electrodes electrically stimulate the left vagus nerve at the neck chronically and intermittently. This was the first electrostimulation therapy clinically introduced for epilepsy. This treatment approach is supported by randomized double-blind trials even though the anti-seizure effect of vagus nerve stimulation is palliative and not curative. In Western countries, particularly the United States, this therapy has become an important alternative treatment for a subpopulation of patients with drug-resistant seizures who are not good candidates for craniotomy. In Japan, vagus nerve stimulation therapy was finally approved in January 2010 and has been covered by public health insurance since July 2010. Here, the author reviews the history, efficacy, and safety of this treatment, surgical anatomy and physiology of the vagus nerve, and the putative mechanisms underlying inhibition of epileptic seizures and accompanying effect on the central nervous system. Further experimental and clinical studies regarding this treatment approach are required to elucidate the detailed mechanism of action, to clarify the predicting factors of favorable outcome, and to scientifically confirm the anti-seizure effect in children and in generalized seizures and the efficacy in improvement of cognitive function, development, and quality of life.
  • Kawasaki Keisuke, Matsuo Takeshi, Osada Takahiro, Sawahata Hirohito, Suzuki Takafumi, Shibata Masahiro, Miyakawa Naohisa, Nakahara Kiyoshi, Sato Noboru, Kawai Kensuke, Saito Nobuhito, Hasegawa Isao
    NEUROSCIENCE RESEARCH 71 E413 - E414 2011年 [査読有り][通常論文]
  • Kensuke Kawai, Kenichi Usami, Nobuhito Saito
    Clinical Neurology 51 11 990 - 992 2011年 [査読有り][通常論文]
    Vagus nerve stimulation is the first electrical stimulation therapy for epilepsy. While its clinical use was approved by the European Union in 1994 and by the United States in 1997, it was approved last year and coverage by public insurance started last July in Japan. Owing to less invasiveness and broad indication, it is expected that vagus nerve stimulation will be increasingly used in Japan as well. Its efficacy for refractory partial seizures in patients older than 13 years was validated by two randomized control trials. Although it has been used for children and generalized seizures broadly, the efficacy for these subpopulations of patients has not been validated by randomized control trials, necessitating those studies in the near future. Afferent neural impulses generated by vagus nerve stimulation transmit to the solitary tract nucleus, then via multiple pathways including the monoamine system, vagus nerve stimulation affects the excitability of the cortical neurons. It likely exerts the anti-epileptic and anti-seizure effects using these pathways, but the detailed mechanisms underlying the effect remains to be elucidated further in future.
  • Takahiro Ota, Kensuke Kawai, Kyousuke Kamada, Taichi Kin, Nobuhito Saito
    JOURNAL OF NEUROSURGERY 112 2 285 - 294 2010年02月 [査読有り][通常論文]
    Object. Intraoperative monitoring of visual evoked potentials (VEPs) has been regarded as having limited significance for the preservation Of Visual function during neurosurgical procedures, mainly due to its poor spatial resolution and signal-to-noise ratio. The authors evaluated the usefulness of cortically recorded VEPs, instead of the usual scalp VEPs, as intraoperative monitoring focusing on the posterior Visual pathway. Methods. In 17 consecutive patients who underwent microsurgical procedures for lesions near the posterior visual pathway, cortical responses were recorded using 1-Hz flashing light-emitting diodes and subdural strip electrodes after induction of general anesthesia with sevoflurane or propofol. The detectability and waveform of the initial response, stability, and changes during microsurgical manipulations were analyzed in association with the position of electrodes and postoperative changes in Visual function. Results. Initial VEPs were detected in 82% of all patients. The VEPs were detected in 94% of patients without total hemianopia in whom electrodes were placed sufficiently near the occipital pole; in these cases the recordings were not significantly affected by anesthesia. The detectability rates of the negative peak before 100 msec (NI), positive peak similar to 100 msec (P100), and negative peak after 100 msec (N2) were 36, 50, and 100%, respectively. The mean latencies and amplitudes of N1, P100, and N2 were 90.0 +/- 15.9 msec and 61.0 +/- 64.0 mu V, 103.9 +/- 13.5 msec and 34.3 +/- 38.6 mu V, and 125.7 +/- 12.2 msec and 44.9 +/- 48.9 mu V, respectively, showing great variability. In 11 patients, the initial waveforms of VEP remained stable during microsurgical procedures, and the visual status did not change postoperatively, while it disappeared in 2 patients who presented with postoperative hemianopia. Conclusions. Direct recording from the visual cortices under general anesthesia achieved satisfactory detectability of the visual response to a light-emitting diode flashing light. Although the initial waveforms varied greatly among patients, they were stable during microsurgical procedures, and the changes were consistent with postoperative visual function. Intraoperative cortical VEP monitoring is a potentially useful procedure to monitor the functional integrity of the posterior Visual pathway. (DOI: 10.3171/2009.6.JNS081272)
  • Matsuo Takeshi, Kawasaki Keisuke, Kawai Kensuke, Masuda Hiroshi, Kunii Naoto, Murakami Hiroatu, Majima Kei, Kamada Kyousuke, Kamitani Yukiyasu, Kameyama Shigeki, Saito Nobuhito, Hasegawa Isao
    NEUROSCIENCE RESEARCH 68 E99  2010年 [査読有り][通常論文]
  • Majima Kei, Matsuo Takeshi, Kawasaki Keisuke, Kawai Kensuke, Masuda Hiroshi, Kunii Naoto, Murakami Hiroatsu, Kamada Kyousuke, Kameyama Shigeki, Saito Nobuhito, Hasegawa Isao, Kamitani Yukiyasu
    NEUROSCIENCE RESEARCH 68 E381 - E382 2010年 [査読有り][通常論文]
  • Kyousuke Kamada, Tomoki Todo, Takahiro Ota, Kenji Ino, Yoshitaka Masutani, Shigeki Aoki, Fumiya Takeuchi, Kensuke Kawai, Nobuhito Saito
    JOURNAL OF NEUROSURGERY 111 4 785 - 795 2009年10月 [査読有り][通常論文]
    Object. To validate the corticospinal tract (CST) illustrated by diffusion tensor imaging, the authors used tractography-integrated neuronavigation and direct fiber stimulation with monopolar electric currents. Methods. Forty patients with brain lesions adjacent to the CST were studied. During the operation, the motor responses (motor evoked potential [MEP]) elicited at the hand by the cortical stimulation to the hand motor area were continuously monitored, maintaining the consistent stimulus intensity (mean 15.1 +/- 2.21 mA). During lesion resection, direct fiber stimulation was applied to elicit MEP (referred to as fiber MEP) to identify the CST functionally. The threshold intensity for the fiber MEP was determined by searching for the best stimulus point and changing the stimulus intensity. The minimum distance between the resection border and illustrated CST was measured on postoperative isotropic images. Results. Direct fiber stimulation demonstrated that tractography accurately reflected anatomical CST functioning. There were strong correlations between stimulus intensity for the fiber MEP and the distance between the CST and the stimulus points. The results indicate that the minimum stimulus intensity of 20, 15, 10, and 5 mA had stimulus points similar to 16, 13.2, 9.6, and 4.8 mm from the CST, respectively. The convergent calculation formulated 1.8 mA as the electrical threshold of the CST for the fiber MEP, which was much smaller than that of the hand motor area. Conclusions. The investigators found that diffusion tensor imaging-based tractography is a reliable way to map the white matter connections in the entire brain in clinical and basic neuroscience applications. By combining these techniques, investigating the cortical-subcortical connections in the human CNS could contribute to elucidating the neural networks of the human brain and shed light on higher brain functions. (DOI: 10.3171/2008.9.JNS08414)
  • Masaya Kubota, Keiji Goishi, Sachiko Takemura, Kensuke Kawai, Nobutaka Arai
    EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY 12 6 516 - 520 2008年11月 [査読有り][通常論文]
    we present a patient with multilobar cortical dysplasia who underwent hemispherotomy, a modified functional hemispherectomy, at the age of 2 months because of intractable seizures and report the clinical-neurophysiological findings including EEG and somatosensory evoked potentials (SEP). After hemispherotomy, the seizures and EEG abnormality disappeared completely and postoperative SEP showed an ipsilateral cortical response at the unaffected hemisphere, suggesting a reorganization process, which was possibly facilitated more intensively after surgery. Furthermore, developmental catch-up was observed. our patient's clinical course and neurophysiological data suggested that very early hemispherotomy resulted in not only the control of seizures but also a better developmental outcome. (C) 2008 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
  • Kensuke Kawai
    NEUROLOGICAL SURGERY 36 11 979 - 989 2008年11月 [査読有り][通常論文]
  • Kensuke Kawai
    Brain and Nerve 59 4 299 - 311 2007年04月 [査読有り][通常論文]
    Vagus nerve stimulation (VNS) and stereotactic radiosurgery (SRS) represent novel and less invasive therapeutics for medically intractable epilepsy. VNS ushered in the recent advancement in clinical application of electrical stimulation therapy for epilepsy. Chronic stimulation of the left vagus nerve with implanted generator and electrodes inhibits seizure susceptibility of the cerebral cortices. Its efficacy and safety have been established by randomized clinical trials in 1990s in the Western countries and it has been widely accepted as a treatment option for patients with medically intractable epilepsy for whom brain surgery is not indicated or failed. Although the effect on seizures is not so dramatic, the less invasiveness and a wide range of indication have made VNS indispensable for comprehensive care of epilepsy. Since the devices are not approved for clinical use in Japan, there exist barriers to provide VNS to patients at present. Use of SRS for intractable epilepsy started in mid 90s as gamma knife surgery for mesial temporal lobe epilepsy. The marginal dose of 25 Gy to the medial temporal structures has been confirmed to be effective for seizure control, but there seems to be an unignorable risk of brain edema and radiation necrosis. It is still controversial whether the therapy is more effective and less invasive than brain surgery. A randomized clinical trial using the dose of 20 or 24 Gy is ongoing in the United States. SRS for intractable epilepsy associated with hypothalamic hamartoma has been advocated because of a high surgical morbidity, but further study is needed for standardization of the treatment. Substitute use of SRS for other surgical technique like callosotomy or disconnection of epileptic focus seems to be another direction worth pursuing.
  • Kawai K
    Brain and nerve = Shinkei kenkyu no shinpo 59 4 299 - 311 2007年04月 [査読有り][通常論文]
  • Kyousuke Kamada, Yutaka Sawamura, Fumiya Takeuchi, Shinya Kuriki, Kensuke Kawai, Akio Morita, Tomoki Todo
    NEUROSURGERY 60 2 296 - 305 2007年02月 [査読有り][通常論文]
    OBJECTIVE: It is known that functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) are sensitive to the frontal and temporal language function, respectively. Therefore, we established combined use of fMRI and MEG to make reliable identification of the global language dominance in pathological brain conditions. METHODS: We investigated 117 patients with brain lesions whose language dominance was successfully confirmed by the Wada test. All patients were asked to generate verbs related to acoustically presented nouns (verb generation) for fMRI and to read three-letter words for fMRI and MEG. RESULTS: fMRI typically showed prominent activations in the inferior and middle frontal gyri, whereas calculated dipoles on MEG typically clustered in the superior temporal region and the fusiform gyrus of the dominant hemisphere. A total of 87 patients were further analyzed using useful data from both the combined method and the Wada test. Remarkably, we observed a 100% match of the combined method results with the results of the Wada test, including two patients who showed expressive and receptive language areas dissociated into bilateral hemispheres. CONCLUSION: The results demonstrate that this non-invasive and repeatable method is not only highly reliable in determining language dominance, but can also locate the expressive and receptive language areas separately. The method may be a potent alternative to invasive procedures of the Wada test and useful in treating patients with brain lesions.
  • H Shimizu, K Kawai, S Sunaga, H Sugano, T Yamada
    JOURNAL OF CLINICAL NEUROSCIENCE 13 3 322 - 328 2006年04月 [査読有り][通常論文]
    Despite good seizure outcome with temporal lobectomy, postoperative impairment of verbal memory remains unsolved. To address this problem we developed a new method, applying the rationale of multiple subpial transection (MST) to the hippocampus. The inferior ventricle is accessed without disrupting the neuronal pathways related to verbal memory. Intraoperative electrocorticography is recorded over the hippocampus and amygdala. After the extent of the epileptic area is determined, multiple transections of the pyramidal layer under the alveus is performed using specially designed ring transectors. After this procedure, epileptic discharges from the hippocampus can be completely abolished. Of 21 cases undergoing this operation, 12 left-sided and nine right-sided, 17 were followed up for more than one year. Fourteen (82%) are seizure free, two (12%) have rare seizures, and one (6%) has significantly improved. Of eight patients who underwent a battery of neuropsychometric tests both before and after left hippocampal transection, postoperative verbal memory was completely preserved in seven cases, and one transiently worsened patient recovered within 6 months. However, these results are still preliminary as the number of patients is small and the follow-up time short. The accumulation of cases and follow-up of greater duration will be necessary to precisely confirm the efficacy of this new technique. (C) 2006 Elsevier Ltd. All rights reserved.
  • K Kamada, T Todo, A Morita, Y Masutani, S Aoki, K Ino, K Kawai, T Kirino
    NEUROSURGERY 57 1 121 - 126 2005年07月 [査読有り][通常論文]
    OBJECTIVE: It has been difficult to obtain anatomic and functional information about the visual pathway during neurosurgical operations. The aim of this study was to combine the information of the visual evoked potentials (VEPs) and the anatomic navigation of the optic radiation by diffusion tensor imaging-based tractography for functional monitoring of the visual pathway. METHODS: The subjects were two patients with brain lesions adjacent to the visual pathway. Diffusion tensor imaging-based tractography of the optic radiation was performed by selecting appropriate regions of interest and by fractional anisotropy. During surgery, cortical VEPs were recorded continuously under general anesthesia with sevoflurane. In Patient 2, the results of optic radiation tractography were imported to a neuronavigation system to better understand the spatial relationships between the lesions and the visual pathway (functional neuronavigation). RESULTS: In Patient 1, the lesion did not seem to be attached to the optic radiation, and VEP profiles remained stable during resection. In Patient 2, who had a lesion adjacent to the posterior horn of the lateral ventricle, VEPs suddenly diminished when resection reached the optic radiation as illustrated on the neuronavigation system. AS a result, complete left hemianopia developed after surgery in Patient 2. CONCLUSION: We confirmed functional correlations of the results of diffusion tensor imaging-based tractography by monitoring intraoperative VEPs. The combination of continuous VEP and optic-radiation tractography is reliable to monitor the visual function and is helpful in performing neurosurgical planning near the visual pathway.
  • M Nishida, S Uchida, N Hirai, F Miwakeichi, T Maehara, K Kawai, H Shimizu, S Kato
    NEUROSCIENCE LETTERS 379 2 110 - 115 2005年05月 [査読有り][通常論文]
    We recorded human orbitofrontal electrocorticogram during wakefulness and sleep in epileptic patients using subdural electrodes. During wakefulness and rapid eye movement (REM) sleep, we observed beta activity in the raw orbitofrontal signals. Power spectral analysis demonstrated beta enhancement during wakefulness and REM sleep when compared to slow wave sleep (SWS). During the phasic REM periods, the beta power was significantly lower than during the tonic REM periods. Gamma enhancement manifested itself in four out of six subjects during the phasic periods. This study is the first that has focused on electrical activity in the human orbitofrontal cortex. Although the role of the orbitofrontal cortex during sleep still remains unclear, high frequency activities give us important suggestions in elucidating the human sleep mechanism. (c) 2004 Elsevier Ireland Ltd. All rights reserved.
  • M Nishida, N Hirai, F Miwakeichi, T Maehara, K Kawai, H Shimizu, S Uchida
    NEUROSCIENCE RESEARCH 50 3 331 - 341 2004年11月 [査読有り][通常論文]
    Ten epileptic patients each with subdural electrodes surgically attached to the anterior cingulate cortex (ACC; two cases), the orbitofrontal cortex (OFC: seven cases), or both (one case) were included in this study. We recorded each patient's ACC or OFC electrocorticogram (ECoG) during the time period that the patient was awake and naturally asleep. We performed a Fast Fourier Transformation (FFT) power spectral analysis on each ECoG to examine its frequency component. We found that the ACC showed regular and continuous theta oscillation (5-7Hz) during wakefulness and rapid eye movement (REM) sleep, but not during slow wave sleep. Theta waves observed in REM sleep were not as distinct as those found in wakefulness. We also discovered that the orbitofrontal signals represented spectral peaks in the theta band only during wakefulness. This suggests the coexistence of theta oscillation in the ACC. Considering our previous observations of gamma and beta oscillations in the human hippocampus, we hypothesize that the human limbic system manifests two oscillatory activities. The results obtained in this study suggest that electrophysiological activity in the ACC could be related to particular psychological functions in wakefulness and in REM sleep. These results are useful in elucidating the human brain mechanism. (C) 2004 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
  • Hiroyuki Shimizu, Kensuke Kawai, Shigeki Sunaga, Toshitaka Yamada
    Clinical Neurology 44 11 868 - 870 2004年11月 [査読有り][通常論文]
    Temporal lobe epilepsy is frequently drug-resistant in adult epilepsy. However, its surgical treatment is very effective and about 70% of operated patients become seizure-free. As preoperative evaluation, analysis of seizure characteristics, scalp EEG with sphenoidal lead, and neuroimaging are most important. When these noninvasive examinations are concordant in focus localization, surgical treatment without prolonged recording by intracranial electrodes become feasible. In spite of good seizure outcome after temporal lobectomy, postoperative impairment of verbal memory has remained to be a long-standing problem. To cope with this ominous complication, we developed a new surgical method of hippocampal transection, based on the principle of multiple subpial transection (MST). Placing a small corticotomy on the anterior part of superior temporal gyrus, the inferior ventricle is opened through suctioning the temporal stem. Intraoperative electrocorticography (ECoG) is recorded over the hippocampus. After the extent of the epileptic area is determined, the alveus is cut with microscissors and the pyramidal layer is transected in parallel with neuronal fibers by a specially designed ring transector. With this procedure, epileptic discharges from the hippocampus can be completely abolished. In all 7 cases undergoing left hippocampal transection, postoperative verbal memory was preserved with excellent seizure outcome.
  • F Miwakeichi, A Galka, S Uchida, H Arakaki, N Hirai, M Nishida, T Maehara, K Kawai, S Sunaga, H Shimizu
    EPILEPSY RESEARCH 61 1-3 73 - 87 2004年09月 [査読有り][通常論文]
    The purpose of this study is to propose and investigate a new approach for discriminating between focal and non-focal hemispheres in intractable temporal lobe epilepsy, based on applying multivariate time series analysis to the discharge-free background brain activity observed in nocturnal electrocorticogram (ECoG) time series. Five unilateral focal patients and one bilateral focal patient were studied. In order to detect the location of epileptic foci, linear multivariate autoregressive (MAR) models were fitted to the ECoG data; as a new approach for the purpose of summarizing these models in a single relevant parameter, the behaviour of the corresponding impulse response functions was studied and described by an attenuation coefficient. In the majority of unilateral focal patients, the averaged attenuation coefficient was found to be almost always significantly larger in the focal hemisphere, as compared to the non-focal hemisphere. Also the amplitude of the fluctuations of the attenuation coefficient was significantly larger in the focal hemisphere. Moreover, in one patient showing a typical regular sleep cycle, the attenuation coefficient in the focal hemisphere tended to be larger during REM sleep and smaller during Non-REM sleep. In the bilateral focal patient, no statistically significant distinction between the hemispheres was found. This study provides encouraging results for new investigations of brain dynamics by multivariate parametric modeling. It opens up the possibility of relating diseases like epilepsy to the properties of inconspicuous background brain dynamics, without the need to record and analyze epileptic seizures or other evidently pathological waveforms. (C) 2004 Elsevier B.V. All rights reserved.
  • K Kawai, H Shimizu, A Yagishita, T Maehara, K Tamagawa
    JOURNAL OF NEUROSURGERY 101 1 7 - 15 2004年08月 [査読有り][通常論文]
    Object. Epilepsy in patients with bihemispheric malformations of cortical development (MCD) is typically medically intractable. Focal resection has been reported to be ineffective. Corpus callosotomy has been advocated as a treatment option, but the results have been reported only in several case reports. The authors describe a series of 10 patients with biltemispheric MCDs who underwent total corpus callosotomy. Methods. The MCDs in these patients included lissencephaly, band heterotopia, perisylvian polymicrogyria, and tuberous sclerosis. Preoperatively all patients suffered disabling drop attacks or intense head drop seizures that caused frequent physical injuries. The follow-up period ranged from 1.4 to 5.8 years (median 3.2 years). Seizure outcome, parental assessment of daily function, and parental satisfaction with outcome were assessed postoperatively. Drop attacks disappeared completely during the entire follow-up period in eight patients and decreased to less than 10% of baseline in one. Other types of seizures were resolved completely in one patient and decreased in seven. Overall daily function improved and parents were satisfied with the surgery-related results in all patients except one who experienced a recurrence of drop attacks. There were no signs of significant and persistent neurological deficits in any case. Conclusions. Results of total corpus callosotomy in patients with bihemispheric MCDs were favorable in most cases. The procedure was particularly effective against drop attacks causing physical injuries and impaired quality of life in these patients.
  • T Maehara, T Nariai, N Arai, K Kawai, H Shimizu, K Ishii, K Ishiwata, K Ohno
    EPILEPSIA 45 1 41 - 45 2004年01月 [査読有り][通常論文]
    Purpose: We assessed the diagnostic value of [C-11]methionine (MET) positron emission tomography (PET) in the differential diagnosis of dysembryoplastic neuroepithelial tumors (DNETs) among benign tumors associated with temporal lobe epilepsy (TLE). Methods: This series consisted of seven TLE patients with benign tumors in the temporal lobe. After MET-PET study, all seven patients underwent tumor resection along with focus excision. The uptake of tracers was evaluated by the lesion-to-contralateral ratio (L/C ratio) and the standardized uptake value (SUV). We also assessed the relation between MET uptake and proliferation capacity observed in the surgical specimens. Results: Whereas four patients with DNETs did not show high MET uptake visually, the ganglioglioma and gliomas of the remaining three patients were identified as high-MET-uptake lesions. In the DNETs, the SUV ranged from 1.03 to 1.41, and the L/C ratio ranged from 0.99 to 1.14. MET uptake was significantly lower in the patients with DNETs than in the patients with ganglioglioma and brain gliomas (SUV, p=0.045; L/C ratio, p=0.0079). The Ki-67 labeling index was 4% in one patient with DNET and 5% in one patient with pleomorphic xanthoastrocytoma (higher labeling index). The higher labeling index was not related to high MET uptake based on the SUV (p=0.91) and L/C ratio (p=0.38). Conclusions: Negative MET uptake in benign temporal lobe tumors with TLE is consistent with a preoperative diagnosis of DNET.
  • K Furuya, N Kawahara, K Kawai, T Toyoda, K Maeda, T Kirino
    JOURNAL OF NEUROSURGERY 100 1 97 - 105 2004年01月 [査読有り][通常論文]
    Object. The intraluminal suture model for focal cerebral ischemia is increasingly used, but not without problems. It causes hypothalamic injury, subarachnoid hemorrhage, and inadvertent premature reperfusion. The patency of the posterior communicating artery (PCoA) potentially affects the size of the infarct. In addition, survival at I week is unstable. The authors operated on C57Black6 mice to produce proximal middle cerebral artery occlusion (MCAO) so that drawbacks with the suture model could be Circumvented. Methods. The MCA segment just proximal to the olfactory branch was occluded either permanently or temporarily. After I hour of MCAO the infarct volume was significantly smaller than that found after 2 hours or in instances of permanent MCAO. The differences were assessed at 24 hours and 7 days after surgery (p < 0.05 and p < 0.001, respectively). The patency of the PCoA, as visualized using carbon black solution, did not correlate with the infarct size. Neurologically, the 1 - and 2-hour MCAO groups displayed significantly less severe deficits than the permanent MCAO group on Days 1, 4, and 7 (p < 0.005 and p < 0.01, respectively). Although the infarct size, neurological deficits, and body weight loss were more severe in the permanent MCAO group, the survival rate at Day 7 was 80%. Conclusions. This model provides not only a robust infarct size (which is not affected by the patency of the PCoA), but also a better survival rate.
  • Sunao Uchida, Taketoshi Maehara, Nobuhide Hirai, Kensuke Kawai, Hiroyuki Shimizu
    J Clin Neurosci 10 3 371 - 374 2003年05月 [査読有り][通常論文]
    In previous studies we observed gamma (30-150 Hz) and beta-1 (10-20 Hz) oscillations in the medial temporal lobe (MTL) using subdural electrodes. The beta-1 was present during wake and REM sleep while gamma was present in all states. Recently we studied a patient (35 years M) with electrodes attached to the anterior cingulate cortex (ACC). This structure showed regular theta (5-6 Hz) oscillations. In the first recording, electrodes were attached to the MTL, that demonstrated the beta-1 and gamma oscillations. Two months later, electrodes were placed on orbitofrontal and ACC and an all night sleep recording was carried out. The ACC exhibited a highly regular and continuous theta oscillation during wakefulness and REM sleep, but not during NREM sleep. Since this same subject showed beta-1 oscillations in the MTL, it is probable that the theta in the ACC is independent of beta-1 in the MTL. This single case suggests the existence of two different frequency oscillators in the human limbic system. Elucidating their functional roles will be an interesting challenge for future studies.
  • S Uchida, T Maehara, N Hirai, K Kawai, H Shimizu
    JOURNAL OF CLINICAL NEUROSCIENCE 10 3 371 - 374 2003年05月 [査読有り][通常論文]
    In previous studies we observed gamma (30-150 Hz) and beta-1 (10-20 Hz) oscillations in the medial temporal lobe (MTL) using subdural electrodes. The beta-1 was present during wake and REM sleep while gamma was present in all states. Recently we studied a patient (35 years M) with electrodes attached to the anterior cingulate cortex (ACC). This structure showed regular theta (5-6 Hz) oscillations. In the first recording, electrodes were attached to the MTL, that demonstrated the beta-1 and gamma oscillations. Two months later, electrodes were placed on orbitofrontal and ACC and an all night sleep recording was carried out. The ACC exhibited a highly regular and continuous theta oscillation during wakefulness and REM sleep, but not during NREM sleep. Since this same subject showed beta-1 oscillations in the MTL, it is probable that the theta in the ACC is independent of beta-1 in the MTL. This single case suggests the existence of two different frequency oscillators in the human limbic system. Elucidating their functional roles will be an interesting challenge for future studies. (C) 2003 Elsevier Science Ltd. All rights reserved.
  • M Nakamura, S Uchida, T Maehara, K Kawai, N Hirai, T Nakabayashi, H Arakaki, Y Okubo, T Nishikawa, H Shimizu
    NEUROSCIENCE RESEARCH 45 4 419 - 427 2003年04月 [査読有り][通常論文]
    To investigate the sleep spindle activity of the human prefrontal cortex (PFC), we simultaneously recorded whole nights of polysomnographic and electrocorticographic (ECoG) activities during the natural sleep of epileptic patients. Subjects were nine patients with intractable epilepsy who had subdural electrodes surgically attached to the orbital (seven cases), medial (three cases), or dorsolateral (two cases) PFC, and in one case to the frontal pole. To examine spindle frequencies, fast Fourier transformation (FFT) and auto-correlation analyses were performed on the PFC ECoG and Cz EEG data, primarily on epochs of stage 2 sleep. Lower sigma band ECoG oscillations of about 12 Hz were widely distributed across all prefrontal cortical areas including the frontal limbic regions, but none of the PFC sigma frequency peaks coincided with the faster (about 14 Hz) Cz EEG sleep spindles. Combining our results with anatomical and electrophysiological facts, it is suggested that the thalamofrontal circuit involving the rostral reticular and the mediodorsal nucleus of the thalamus is responsible for the generation of 12 Hz frontal spindles in humans. (C) 2003 Elsevier Science Ireland Ltd. and the Japan Neuroscience Society. All rights reserved.
  • K Kawai, H Shimizu, T Maehara, H Murakami
    NEUROLOGIA MEDICO-CHIRURGICA 42 11 481 - 489 2002年11月 [査読有り][通常論文]
    The outcome of long-term vagus nerve stimulation (VNS) was evaluated in 13 Japanese patients with intractable epilepsy, all followed up for more than 4 years (48-91 months, median 56 months). VNS achieved a long-lasting and cumulative seizure-control effect in nine of 13 patients. The mean reduction of seizure frequency in the 1st to 4th year was 28%, 47%, 54%, and 63%, respectively. The percentage of patients with >60% seizure reduction in the 1st to 4th year was 15%, 46%, 54%, and 69%, respectively. One patient did not respond to the treatment at all. No patient became completely free from seizure or free from medication, but the number and/or dosage of antiepileptic drugs was reduced in five patients. Ten patients underwent exchange of the generator and continued treatment, and two patients underwent removal of the generator because of the unsatisfactory result. VNS controlled more disabling seizures earlier and more efficiently than less disabling seizures in seven patients. The cumulative reduction of seizures was partly associated with changes in the device setting toward increased stimulation. These effects were similar in patients with or without previous resective surgery. Long-term VNS therapy achieved a favorable outcome in a significant proportion of patients with intractable epilepsy.
  • H Uesugi, H Shimizu, N Arai, T Maehara, T Mizutani, K Kawai, H Nakayama
    PSYCHIATRY AND CLINICAL NEUROSCIENCES 56 5 557 - 559 2002年10月 [査読有り][通常論文]
    The cause of Ammon's horn sclerosis in temporal lobe epilepsy has not yet been clarified. In the present study, the pathological effect of epileptic seizures on the hippocampus was investigated in surgically treated patients with brain tumor-induced temporal lobe epilepsy. Tumors involving the hippocampus were identified as the foci of epilepsy in 13 patients (seven male and six female) and resected after epileptic discharges were found at the hippocampus on intraoperative electrocorticogram. The mean age at operation was 29.8 +/- 11.5 years and the mean age of seizure onset was 19.9 +/- 10.8 years. Because only three of the 13 patients who underwent temporal lobectomy for brain tumors involving the hippocampus had Ammon's horn sclerosis pathologically, it was concluded that it was very unlikely that the Ammon's horn sclerosis was produced by the epileptic seizures. Two of the three patients with pathological signs of Ammon's horn sclerosis had episodes of coma, covulsion, high fever and cyanosis in their past histories that might have portended the appearance of Ammon's horn sclerosis later in their lives.
  • S. Uchida, N. Hirai, N. Watanabe, F. Miwakeichi, T. Maehara, K. Kawai, H. Shimizu
    International Congress Series 1232 C 827 - 835 2002年04月 [査読有り][通常論文]
    The medial temporal lobe (MTL) is known to play important roles in learning and memory in both humans and animals. Some investigators have proposed that the rhythmic slow activity (RSA) or theta that can be recorded in an animal hippocampus is related to learning and memory. It is unclear whether the human hippocampus displays a similar activity. In the past few years, we have studied electrophysiological properties of the human medial temporal lobe (MTL) during wake and all-night sleep. In this paper, we will summarize our results in the electrophysiology of the human medial temporal lobe during sleep and wake and discuss their physiological significances. Electrocorticograms (ECoG) during wake, slow wave sleep (SWS) and rapid eye movement (REM) sleep were subjected to fast Fourier transformation (FFT) analysis. During wake, two peaks, beta-1 (10–20 Hz) and gamma (30–150 Hz) were consistently observed across the subjects. In SWS, the beta-1 peak disappeared but gamma remained although slightly reduced. During REM sleep, beta-1 appeared again, but the peak frequency was slightly lower than that during wake. The gamma peak was also present in REM sleep. These results indicate similarities in the human MTL gamma and beta-1 when compared to animal gamma and RSA in the hippocampus. Thus, this suggests the functional significances of these two MTL oscillations in relation to learning and memory throughout wake and sleep. © 2001 Elsevier Science B.V.
  • T Maehara, H Shimizu, K Kawai, R Shigetomo, K Tamagawa, T Yamada, M Inoue
    BRAIN & DEVELOPMENT 24 3 155 - 160 2002年04月 [査読有り][通常論文]
    We studied the postoperative development of 14 children with cortical dysgenesis who underwent modified functional hemispherectomy (hemispherotomy) at the age of 6 years or younger. At follow-up of 24-72 months (median of 47 months), six (43%) were seizure-free, six achieved > 90% reduction, one achieved 50-90% reduction, and one achieved 0-50% reduction in seizure frequency. At the preoperative and final postoperative examinations, mean scores of developmental quotient (DQ) were as follows: 25.5 and 31.9 in total DQ, 26.0 and 33.7 in intellectual DQ, and 27.4 and 22.9 in motor DQ. Children scoring > 50 points in preoperative intellectual DQ score obtained near-normal intellectual DQ postoperatively, while, those scoring < 10 DQ preoperatively remained at a low developmental level. Among children with DQ scores in the range from 10 to 50. two children who obtained seizure-free outcome and were operated upon in the first 3 years of life achieved marked developmental progress. The present study indicated that high preoperative intellectual DQ and cessation of seizures seem to be associated with better postoperative intellectual development. However, long-term observation of postoperative development and an accumulation of more cases will be needed before we can reach a firm conclusion. (C) 2002 Elsevier Science B.V. All rights reserved.
  • N Kawahara, K Kawai, T Toyoda, H Nakatomi, K Furuya, T Kirino
    NEUROSCIENCE LETTERS 322 2 91 - 94 2002年04月 [査読有り][通常論文]
    Global cerebra ischemia models for genetically engineered mice are of particular importance for the study of delayed neuronal death, but have been complicated by variability of vascular anatomy. Here we developed a 5-min cardiac arrest model that was not affected by vascular anatomy, and evaluated the hippocampal neuronal injury in BL/6 and SV129 mice. Despite prolonged anoxic depolarization for approximately 7 min, however, no consistent ischemic neuronal injury was noted in the CA1 sector of the hippocampus in both strains. Thus, our observations suggested that murine hippocampal neurons are relatively resistant to ischemia compared with those in other rodents. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
    Neuroscience Research 44 4 421 - 427 2002年 [査読無し][通常論文]
  • K Kawai, Suzuki, I, H Kurita, M Shin, N Arai, T Kirino
    JOURNAL OF NEUROSURGERY 95 5 883 - 887 2001年11月 [査読有り][通常論文]
    Radiosurgical treatment of intractable epilepsy has emerged as a noninvasive alternative to resection. Although gamma knife surgery (GKS) reportedly is effective when the radiation dose is sufficient to cause a destructive reaction in the targeted medial temporal lobe, the optimal target area and dose distribution are largely unknown. Some investigators have suggested that focused irradiation from a nondestructive dose is also effective. In this article the authors report two cases of medial temporal lobe epilepsy in which the patients underwent GKS performed using a 50% marginal dose of 18 Gy covering the amygdala hippocampal head and body, and parahippocampal gyrus. In both cases this procedure failed to control seizures. Both patients became seizure free after undergoing anterior temporal lobectomy 30 and 16 months, respectively, after radiosurgery.
  • H. Kurita, I. Suzuki, M. Shin, K. Kawai, M. Tago, T. Momose, T. Kirino
    Minimally Invasive Neurosurgery 44 1 43 - 46 2001年03月 [査読有り][通常論文]
    We report a case of successful radiosurgical treatment of lesional epilepsy of mesial temporal origin. A patient presented with a 2-year history of medically intractable complex partial seizures associated with a mesial temporal angioma. Interictal scalp EEG and MEG showed focal epileptiform activity around the lesion. 99mTc-HMPAO-SPECT and 18F-FDG-PET demonstrated depressed blood flow and glucose metabolism in the corresponding temporal lobe. The patient underwent gamma knife radiosurgery for the causative lesion with a low marginal dose of 18 Gy. After treatment, the partial attack ceased without shrinkage of the lesion or peri-lesional parenchymal radiation injury.
  • Kensuke Kawai, Koichi Nonaka, Hiromasa Suzuki, Takaaki Kirino, Akira Tamura
    Neurologia Medico-Chirurgica 41 5 229 - 236 2001年 [査読有り][通常論文]
    Conflicting findings of the effect of climate on onset of subarachnoid hemorrhage (SAH) may result from the influence of strenuous activities which can trigger aneurysmal rupture independent of climatological factors. The effect of climate and patient activities on onset of SAH were analyzed. The clinical records of 786 consecutive patients with aneurysmal SAH admitted to our hospital for 10 years were reviewed. Activities at onset were categorized according to the intensity of strain at onset. Seasonal variation, circannual cyclic trend, and association with 90 meteorological factors were examined in each category and the results were compared between categories. Bimonthly occurrence in the light strain group showed a significant seasonal variation and cyclic trend with two peaks in early spring and fall, whereas no significant trend was detected in the overall patients and in the heavy strain group. The significant meteorological factors were global solar radiation, sunshine hours, changes in mean and minimum temperature and mean vapor pressure from the previous day, and minimum pressure in the previous 7 days. Lower global solar radiation in the light strain group was associated with onset with the lowest p value (p = 0.0046). No factors were significant in the heavy strain group. There is some evidence of the possible influence of climatological factors on onset of SAH without strenuous activity. Strenuous activity seems to affect onset more strongly, which masks any effect of climate.
  • Kiyoshi Takagi, Akira Tamura, Tadayoshi Nakagomi, Hitoshi Nakayama, Osamu Gotoh, Kensuke Kawai, Mamoru Taneda, Nobuyuki Yasui, Hiromu Hadeishi, Keui Sano
    Journal of Neurosurgery 90 4 680 - 687 1999年 [査読有り][通常論文]
    Object. The purpose of this study was to present a combinatorial approach used to develop a subarachnoid hemorrhage (SAH) grading scale based on the patient's preoperative Glasgow Coma Scale (GCS) score. Methods. There are 4094 different combinations that can be used to compress the 13 scores of the GCS into two to 12 grades. Break points, the positions in the scale in which two adjacent scores connote a significantly different outcome, are obtained by a direct comparison of the GCS and the Glasgow Outcome Scale (GOS). Guided by the break points, the number of combinations to be considered can be limited. All possible combinations are statistically analyzed with respect to intergrade differences in outcome. Single combinations, with the maximum number of grades having maximum intergrade outcome differences for each corresponding set of adjacent grades, must be selected. The authors verified the validity of this combinatorial approach by retrospectively analyzing 1398 consecutive patients with aneurysmal SAH who underwent surgery within 7 days of the last hemorrhage episode. The patients' GCS scores were assessed just before surgery and their GOS scores were estimated 6 months post-SAH. The combinatorial approach yields only one acceptable grading scale: I (GCS Score 15) II (GCS Scores 11-14) III (GCS Scores 8-10) IV (GCS Scores 4-7) and V (GCS Score 3). Conclusions. The combinatorial approach, guided by the break points, is so simple and systematic that it can be used again in the future when revision of the grading scale becomes necessary after development of new and effective treatment modalities that improve patients' overall outcome.
  • Nobutaka Kawahara, Takafumi Ide, Nobuhito Saito, Kensuke Kawai, Takaaki Kirino
    Journal of Cerebral Blood Flow and Metabolism 18 5 472 - 475 1998年 [査読有り][通常論文]
    The effect of propentofylline, an adenosine uptake inhibitor, on ischemic tolerance was investigated in the gerbil global ischemia model. Propentofylline was administered 24 hours after short preconditioning ischemia, and animals were subjected to 5-minute ischemia 24 hours thereafter. Propentofylline at a dose of 20 mg/kg intraperitoneally, but not at a dose of 10 mg/kg, significantly potentiated the protective effect of preconditioning ischemia in the CA1 hippocampal neurons. This effect was completely abolished by simultaneous administration of theophylline (20 mg/kg), an adenosine receptor blocker. This finding suggests the involvement of adenosine receptor for the development of ischemic tolerance.
  • Kensuke Kawai, Tadayoshi Nakagomi, Takaaki Kirino, Akira Tamura, Nobufumi Kawai
    Journal of Cerebral Blood Flow and Metabolism 18 3 288 - 296 1998年 [査読有り][通常論文]
    Preconditioning with sublethal ischemia induces tolerance to subsequent lethal ischemia in neurons. We investigated electrophysiologic aspects of the ischemic tolerance phenomenon in the gerbil hippocampus. Gerbils were subjected to 2 minutes of forebrain ischemia (preconditioning ischemia). Some of them were subjected to a subsequent 5 minutes of forebrain ischemia 2 to 3 days after the preconditioning ischemia (double ischemia). Hippocampal slices were prepared from these gerbils subjected to the preconditioning or double ischemia, and field excitatory postsynaptic potentials were recorded from CA1 pyramidal neurons. Capacity for long-term potentiation triggered by tetanic stimulation (tetanic LTP) was transiently inhibited 1 to 2 days after the double ischemia but then recovered. Latency of anoxic depolarization was not significantly different between slices from preconditioned gerbils and those from sham-operated gerbils when these slices were subjected to in vitro anoxia. Postanoxic potentiation of N-methyl-D-aspartate (NMDA) receptor- mediated transmission (anoxic LTP) was inhibited in slices from gerbils 2 to 3 days after the preconditioning ischemia, whereas it was observed in slices from sham-operated gerbils and gerbils 9 days after the preconditioning ischemia. These results suggest that protection by induced tolerance is (1) not only morphologic but also functional and (2) expressed in inhibiting postischemic overactivation of NMDA receptor-mediated synaptic responses.
  • Melvyn P. Heyes, Kuniaki Saito, Cai Y. Chen, Margit G. Proescholdt, Thaddeus S. Nowak Jr., Ju Li, Karen E. Beagles, Martin A. Proescholdt, Mark A. Zito, Kensuke Kawai, Sanford P. Markey
    Journal of Neurochemistry 69 4 1519 - 1529 1997年10月 [査読有り][通常論文]
    Quinolinic acid is an excitotoxic kynurenine pathway metabolite, the concentration of which increases in human brain during immune activation. The present study compared quinolinate responses to systemic and brain immune activation in gerbils and rats. Global cerebral ischemia in gerbils, but not rats increased hippocampus indoleamine-2,3-dioxygenase activity and quinolinate levels 4 days postinjury. In a rat focal ischemia model, small increases in quinolinate concentrations occurred in infarcted regions on days 1,3, and 7, although concentrations remained below serum values. In gerbils, systemic immune activation by an intraperitoneal injection of endotoxin (1 mg/kg of body weight)increased quinolinate levels in brain, blood, lung, liver, and spleen, with proportional increases in lung indoleamine-2,3- dioxygenase activity at 24 h postinjection. In rats, however, no significant quinolinate content changes occurred, whereas lung indoleamine-2,3- dioxygenase activity increased slightly. Gerbil, but not rat, brain microglia and peritoneal monocytes produced large quantities of [13C6]quinolinate from L-[13C6]tryptophan. Gerbil astrocytes produced relatively small quantities of quinolinate, whereas rat astrocytes produced no detectable amounts. These results demonstrate that the limited capacity of rats to replicate elevations in brain and blood quinolinic acid levels in response to immune activation is attributable to blunted increases in local indoleamine- 2,3-dioxygenase activity and a low capacity of microglia, astrocytes, and macrophages to convert L-tryptophan to quinolinate.
  • Kensuke Kawai, Koji Narita, Hitoshi Nakayama, Akira Tamura
    Neurologia Medico-Chirurgica 37 2 184 - 187 1997年02月 [査読有り][通常論文]
    A 19-year-old male presented with intraventricular hemorrhage manifesting as sudden onset of headache. Angiography showed mild stenotic changes in the distal internal carotid artery and proximal anterior cerebral artery only on the right. The anterior choroidal artery and lenticulostriate arteries appeared dilated, and an aneurysm-like shadow was seen in the distal right anterior choroidal artery. He was discharged without treatment. Eighteen months later, he presented with a second intraventricular hemorrhage manifesting as sudden occipitalgia, vomiting, and nausea. He had hyperreflexia of the left extremities and paresthesia of the left upper extremity. Angiography showed marked progression of the vascular abnormalities bilaterally. Moyamoya vessels were also present. He received bilateral encephalo-duro-arterio-myo-synangiosis with good results. Moyamoya disease may cause hemorrhage even at an early stage.
  • Kensuke Kawai, Hiroshi Nagashima, Kohji Narita, Tadayoshi Nakagomi, Hitoshi Nakayama, Akira Tamura, Keiji Sano
    Neurological Research 19 6 649 - 653 1997年 [査読有り][通常論文]
    We retrospectively evaluated efficacy and risk of external ventricular drainage which was performed in early management of high grade subarachnoid hemorrhage. Acute ventricular drainage was performed on 36.6% of 93 patients with grade V subarachnoid hemorrhage. The percentages of patients whose GCS improved following ventricular drainage were 14.3% from GCS 3, 61.5% from GCS 4, 42.9% from GCS 5 and 42.9% from GCS 6. The occurrence rate of rebleeding was approximately three-fold higher in patients who underwent ventricular drainage than in patients who did not. Aneurysmal surgery performed after ventricular drainage, compared with acute aneurysmal surgery, resulted in the smaller percentage of patients who became persistently vegetative and in the larger percentage of patients who became severely disabled, while it did not change the percentage of patients who resulted in favorable outcome and death. These results of retrospective study suggested that ventricular drainage performed on grade V subarachnoid hemorrhage increased the risk of rebleeding and did not increase the percentage of patients who resulted in favorable outcome although it reduced the percentage of patients who resulted in persistent vegetative state.
  • Kazuhide Furuya, Kensuke Kawai, Akio Asai, Akira Tamura
    Neurological Research 19 2 160 - 164 1997年 [査読有り][通常論文]
    We first detected growth-associated protein (GAP-43) immunoreactivity in the neuronal somata following middle cerebral artery occlusion in the rat. Four days after the middle cerebral artery occlusion, GAP-43 immunoreactivity was detected in some cortical neurons of the ischemic penumbra at the level of the hippocampus.
  • Kensuke Kawai, Hitoshi Nakayama, Akira Tamura
    Journal of Cerebral Blood Flow and Metabolism 17 5 543 - 552 1997年 [査読有り][通常論文]
    We investigated the protective effect of hypothermia on ultra-early- type ischemic injury in the thalamic reticular nucleus of the rat. Cerebral ischemia was produced by 5 min of cardiac arrest followed by resuscitation. Rectal and cranial temperature during and after cardiac arrest was maintained at 37-38°C in the normothermic group and at 32-33°C in the hypothermic group. In the postischemic hypothermic group, temperature was maintained at 32-33°C starting 15 min after normothermic ischemia. Histological damage was evaluated quantitatively. While after 5 min of recirculation there was no difference in morphological changes in terms of neuronal halo formation, intraischemic hypothermia reduced the severity of the degenerative changes represented by vacuolated or dark neurons by 15 min. Postischemic hypothermia failed to show any evidence of protection by 30 min. The protective effect of intraischemic hypothermia remained significant when evaluated at 14 days after ischemia by volumetry of the lesion and neuronal density analysis, whereas postischemic hypothermia had no clear protective effect. These results suggest that the protective effect of intraischemic hypothermia applies to neurons susceptible to ultra-early-type injury, but the effect of postischemic hypothermia is limited because normothermic ischemia results in extensive degeneration in these neurons by 15 min.
  • Kensuke Kawai, Thaddeus S. Nowak Jr., Igor Klatzo
    Acta Neuropathologica 89 3 262 - 269 1995年03月 [査読有り][通常論文]
    The thalamic reticular nucleus (NRT) is one of the most vulnerable structures to selective neuronal damage both in human cardiac arrest patients and in experimental rodent global cerebral ischemia models. The detailed distribution of neuronal injury within the NRT was examined following 10-min cardiac arrest in the rat with conventional Nissl staining, 45Ca autoradiography and immunocytochemistry of the calcium binding proteins parvalbumin (PV) and calretinin (CR). While Nissl staining was almost unable to show the exact boundary of the nucleus and of the lesion, immunocytochemistry of PV proved to be the most useful index of the exact location and extent of neuronal loss in the NRT after ischemia. Calcium autoradiography was a sensitive method for detecting the lesion, and showed a similar distribution to the loss of PV staining, but did not give optimal spatial resolution. Quantitative analysis of PV staining at 7 days of recirculation demonstrated cell loss restricted to the lateral aspect of the middle segment of the NRT, identical with the distribution of large fusiform neurons in the somatosensory component of the nucleus. CR-positive neurons in the NRT were completely spared, although not all surviving neurons contained CR. These studies provide the first detailed characterization of the distribution of vulnerable neurons within the NRT after experimental ischemia and suggest that immunocytochemistry of PV is a useful tool for quantitative analysis of the lesion for use in further experiments to elucidate the mechanisms of selective vulnerability of the NRT. © 1995 Springer-Verlag.
  • T. Toyoda, M. Matsutani, K. Kawai, Y. Iwasaki, T. Kirino
    Radiation Medicine - Medical Imaging and Radiation Oncology 13 6 315 - 317 1995年 [査読有り][通常論文]
    Astrocytoma arising from the rectum of the mesencephalon is an unusual tumor that is different from other brain stem tumors in clinical features. We describe two patients with tectal low-grade astrocytoma. Each patient underwent CSF diversion and biopsy followed by radiation therapy. A review of the literature on the clinical, radiographic, and pathological findings and the management of rectal tumor is presented.
  • K. Kawai, M. Aoki, H. Nakayama, K. Kobayashi, K. Sano, A. Tamura
    Journal of Neurosurgery 83 2 368 - 371 1995年 [査読有り][通常論文]
    A 28-year old man presented with diabetes insipidus (DI) 10 days after basilar skull fracture without brain injury. Magnetic resonance (MR) imaging revealed a hematoma in the posterior lobe of the pituitary gland but no lesions in the hypothalamus or pituitary stalk. The patient's DI continued for 2 months at which time transsphenoidal surgery was performed to decompress the cystic hematoma with persistent mass effect. The DI attenuated shortly after the surgery and the patient became completely free from DI 5 months later. Although hemorrhage into the posterior lobe is one of the frequent pathological changes in fatal head-injury victims and secondary DI in these cases has usually been thought to be acute and transient, the true incidence and natural course of the posterior pituitary hemorrhage and subsequent DI in nonfatal head-injury patients are totally unknown. In this article, the authors present the first demonstration on MR imaging of a posterior pituitary hematoma in a patient with head injury. The authors propose that serial MR imaging is an important diagnostic tool in patients with posttraumatic DI because some of them may harbor pituitary hematoma and because decompression surgery may prevent transition to permanent DI, especially in cases when the mass effect is persistent due to a cystic change in the hematoma.
  • Kensuke Kawai, Tomio Sasaki, Akira Yanai, Akira Teraoka
    Neurologia Medico-Chirurgica 35 3 165 - 167 1995年 [査読有り][通常論文]
    A 42-year-old male presented with a high cervical chordoma detected at an early stage and manifesting only as neck pains. Serial cervical roentgenograms over 8 years confirmed the slow growth character of this malignant tumor. Computed tomography and magnetic resonance imaging provided clear visualization of the tumor localized in the anterior aspect of the C-2 vertebral body. The tumor was totally removed through a transoral approach. Early diagnosis of vertebral chordoma is difficult due to the slow growth character and insidiousness of initial symptoms, but meticulous examination of serial roentgenograms, followed by neuroimaging, can achieve early detection of cervical chordoma. © 1995, The Japan Neurosurgical Society. All rights reserved.
  • Kensuke Kawai, LaRoy P. Penix, Nobutaka Kawahara, Christi A. Ruetzler, Igor Klatzo
    Journal of Cerebral Blood Flow and Metabolism 15 2 248 - 258 1995年 [査読有り][通常論文]
    Susceptibility to audiogenic seizures (AGS) was investigated in Sprague- Dawley rats subjected to cardiac arrest cerebral ischemia (CACI), produced by compression of the major cardiac vessels. The onset of AGS was regularly observed 1 day after CACI of > 5 min duration. The duration of postischemic susceptibility to AGS was directly related to the density of cerebral ischemia, with 50% of more severely ischemic animals still showing AGS susceptibility 8 weeks after CACI. Lesioning of the inferior colliculi (IC) abolished the onset of AGS no such effect was observed after lesioning the medial geniculate (MG). Glutamic acid decarboxylase (GAD) immunochemistry revealed ~50% loss of GAD-positive neurons in the IC, which was similar in animals with various durations of AGS susceptibility. Otherwise, there was a conspicuous sprouting of γ-aminobutyric acid (GABA)-ergic terminals in the ventral thalamic nuclei, which peaked ~1 month after the CACI. Evaluation of GABA-A inhibitory function in the hippocampus by the paired pulse stimulation revealed changes indicating loss of GABA-A inhibition coinciding with the onset of AGS, and its return in animals tested 2 months after CACI. Our observations suggest a potential role of GABA-ergic dysfunction in the postischemic development of AGS.



  • 大谷 啓介, 川合 謙介, 五味 玲, 佐藤 信, 内山 拓, 大貫 良幸, 石下 洋平, 日本てんかん学会てんかん専門医療施設(センター)検討委員会 てんかん研究 37 (3) 766 -778 2020年01月 [査読無し][通常論文]
  • 宮田 五月, 難波 克成, 檜垣 鮎帆, 大貫 良幸, 山口 崇, 川合 謙介 脳神経外科と漢方 5 48 -52 2019年10月 [査読無し][通常論文]
    69歳、女性。進行する動眼神経麻痺で発症した脳底動脈・上小脳動脈分岐部動脈瘤に対してBioactive coilを用いて脳動脈瘤コイル塞栓術を施行した。術後、脳動脈瘤周囲に浮腫性変化を認めたため、ステロイド治療を開始した。しかし治療効果を認めず、脳浮腫の増悪、水頭症も合併した。五苓散を追加投与することで、脳浮腫および水頭症は改善した。ステロイド難治例に対する治療の選択肢の一つとなる可能性がある。(著者抄録)
  • ミニブタ皮質脳波測定による軟膜下皮質多切術の安全性の検討
    石下 洋平, 庭山 雅嗣, 齋藤 敏之, 大貫 良幸, 内山 拓, 横田 英典, 渡辺 英寿, 川合 謙介 てんかん研究 37 (2) 532 -532 2019年09月 [査読無し][通常論文]
  • 救急医療情報を活用したてんかんに起因する交通事故の後向き観察研究
    伴 知晃, 手塚 正幸, 大貫 良幸, 内山 拓, 大谷 啓介, 石下 洋平, 米川 力, 中嶋 剛, 川合 謙介 日本交通科学学会誌 19 (Suppl.) 91 -91 2019年06月 [査読無し][通常論文]
  • DNTの病理学的特徴を持つ、播種した側頭葉腫瘍の1例
    内山 拓, 永山 理恵, 柴原 純二, 福嶋 敬宜, 松原 大祐, 川合 謙介, 五味 玲 Brain Tumor Pathology 36 (Suppl.) 124 -124 2019年05月 [査読有り][通常論文]
  • 急性期脳卒中患者の前頭前野ニューロフィードバック訓練効果差
    手塚正幸, 松本万由子, 櫻田武, 中嶋剛, 森田光哉, 川合謙介 第33回 日本ニューロモデュレーション学会 2019年05月 [査読無し][通常論文]
  • 急性期脳卒中患者のワーキングメモリ機能個人差とfNIRSによる前頭前野ニューロフィードバック訓練効果
    手塚正幸, 松本万由子, 櫻田武, 中嶋剛, 森田光哉, 川合謙介 第44回 日本脳卒中学会学術集会 2019年03月 [査読無し][通常論文]
  • Isolated hand palsyを呈した脳梗塞 機能的MRIによる機能局在解析の検討
    古谷 浩平, 小澤 忠嗣, 大貫 良幸, 金 蓮姫, 横瀬 美里, 鈴木 雅之, 松薗 構佑, 益子 貴史, 嶋崎 晴雄, 小出 玲爾, 松浦 徹, 川合 謙介, 藤本 茂 臨床神経学 58 (Suppl.) S279 -S279 2018年12月 [査読無し][通常論文]
  • 急性期脳卒中患者におけるワーキングメモリ機能個人差に応じた前頭前野ニューロモジュレーション効果
    手塚正幸, 川合謙介, 松本万由子, 櫻田武 第5回 脳神経外科BMI研究会 2018年11月 [査読無し][通常論文]
  • fNIRSニューロフィードバックによる急性期脳卒中患者の前頭前野活動修飾と運動機能への影響
    手塚正幸, 松本万由子, 櫻田武, 川合謙介 第77回 日本神経脳外科学会 2018年10月 [査読無し][通常論文]
  • 運動中のワーキングメモリ機能差に依存したニューロフィードバック訓練効果
    松本万由子, 櫻田武, 手塚正幸, 中嶋剛, 森田光哉, 平井真洋, 藤本茂, 川合謙介, 山本紳一郎 第12回 Motor Control研究会 2018年08月 [査読無し][通常論文]
  • テイラーメード・ニューロフィードバック系構築に向けた運動学習中のワーキングメモリの個人差を反映する神経基盤の同定
    松本万由子, 櫻田武, 手塚正幸, 中嶋剛, 森田光哉, 平井真洋, 山本紳一郎, 藤本茂, 川合謙介 第41回 日本神経科学大会 2018年07月 [査読無し][通常論文]
  • Taku Uchiyama, Rie Nagayama, Junji Shibahara, Noriyoshi Fukushima, Daisuke Matsubara, Kensuke Kawai, Akira Gomi NEURO-ONCOLOGY 20 146 -146 2018年06月 [査読無し][通常論文]
  • 運動機能障害リハビリテーションの効果促進を目的としたfNIRSを使ったニューロフィードバックによる前頭前野の脳活動修飾訓練
    手塚正幸, 松本万由子, 櫻田武, 川合謙介 第76回 日本神経脳外科学会 2017年10月 [査読無し][通常論文]
  • 運動学習中の最適注意戦略個人差に関する健常者・脳卒中患者の共通神経基盤
    櫻田武, 後藤彩, 手塚正幸, 中嶋剛, 森田光哉, 山本紳一郎, 平井真洋, 川合謙介 第20回日本光脳機能イメージング学会 2017年07月 [査読無し][通常論文]
  • 運動学習中における最適な注意の向け方を決定する前頭前野活動個人差
    後藤彩, 櫻田武, 手塚正幸, 中嶋剛, 森田光哉, 山本紳一郎, 平井真洋, 川合謙介 第40回 日本神経科学大会 2017年07月 [査読無し][通常論文]
  • 國井尚人, 川合謙介 診断と治療 105 (7) 883‐887 2017年07月 [査読無し][通常論文]
  • 運動機能障害リハビリテーションにおけるニューロモジュレーションのための認知-運動機能連関に関する個人差とその神経基盤
    櫻田武, 後藤彩, 中嶋剛, 平井真洋, 森田光哉, 山本紳一郎, 渡辺英寿, 川合謙介 第56回 日本定位・機能神経外科学会 2017年01月 [査読無し][通常論文]
  • 川合謙介, 荒木敦, 石田重信, 久保田英幹, 菅野秀宣, 太組一朗, 西田拓司, 平田幸一, 前垣義弘, 松浦雅人 てんかん研究 34 (3) 637‐644 2017年 [査読無し][通常論文]
  • 皮質脳波によるmismatch negativityの局在解析とcomponentの分離
    石下 洋平, 國井 尚人, 多田 真理子, 宇賀 貴紀, 井林 賢志, 嶋田 勢二郎, 切原 賢治, 川合 謙介, 笠井 清登, 齊藤 延人 てんかん研究 34 (2) 487 -487 2016年09月 [査読無し][通常論文]
  • 白松(磯口) 知世, 日露 理英, 井林 賢志, 神崎 亮平, 川合 謙介, 高橋 宏知 聴覚研究会資料 = Proceedings of the auditory research meeting 46 (3) 163 -168 2016年05月
  • 亀山 茂樹, 川合 謙介, 井上 有史 Epilepsy : てんかんの総合学術誌 9 (2) 85 -94 2015年11月 [査読無し][通常論文]
  • 【てんかん診療入門-患者100万人のありふれた神経疾患を知る】 てんかん診療のmultidisciplinarity 各科のエキスパートが教える最新知識
    加藤 天美, 宇川 義一, 兼本 浩祐, 川合 謙介, 須貝 研司 脳神経外科速報 25 (10) 1051 -1060 2015年10月 [査読無し][通常論文]
  • クリニカルパスの運用のための看護師と臨床検査技師の連携
    佐藤 泰史, 高工 愛美, 芳村 旺美, 山田 由美, 宮崎 由紀, 山川 憲文, 三田村 靖子, 川合 謙介, 松尾 健 日本クリニカルパス学会誌 17 (4) 590 -590 2015年10月 [査読無し][通常論文]
  • てんかんの治療・検査クリニカルパス作成
    畑山 勝彦, 平野 翔, 山田 由美, 宮崎 由紀, 松尾 健, 川合 謙介 日本クリニカルパス学会誌 17 (4) 606 -606 2015年10月 [査読無し][通常論文]
  • 【てんかん】 ピンポイント小児医療 てんかんの治療 小児における迷走神経刺激療法
    國井 尚人, 川合 謙介 小児内科 47 (9) 1517 -1519 2015年09月 [査読無し][通常論文]
    <Key Points>(1)VNSは確立された緩和的外科治療であり、小児においても成人と同等の発作抑制効果がある。(2)VNSの安全性は小児においても十分確認されている。(3)VNSによる認知機能やQOLの改善効果、費用効果も示されてきている。(著者抄録)
  • VNS導入後5年 VNS市販後調査の臨床転帰 治療2年間の成績(Two-year outcome of VNS for refractory epilepsy in Japan PMS study)
    川合 謙介, 田中 達也, Bunker Mark, 丸岡 英二, VNS資格認定委員会 てんかん研究 33 (2) 384 -384 2015年09月 [査読無し][通常論文]
  • Non-lesional MTLEに対する外科治療の成績と課題
    國井 尚人, 川合 謙介, 嶋田 勢二郎, 井林 賢志, 石下 洋平, 小泉 友幸, 松尾 健, 齊藤 延人 てんかん研究 33 (2) 483 -483 2015年09月 [査読無し][通常論文]
  • 当院における頭蓋内電極留置術の成績と術中手技の工夫について
    石下 洋平, 國井 尚人, 井林 賢志, 嶋田 勢二郎, 小泉 友幸, 松尾 健, 川合 謙介, 齊藤 延人 てんかん研究 33 (2) 485 -485 2015年09月 [査読無し][通常論文]
  • 側頭葉てんかんの外科治療 微小解剖に留意した側脳室下角到達の工夫
    井林 賢志, 國井 尚人, 川合 謙介, 石下 洋平, 嶋田 勢二郎, 小泉 友幸, 齊藤 延人 てんかん研究 33 (2) 485 -485 2015年09月 [査読無し][通常論文]
  • 言語野周辺での根治的焦点切除と機能温存 慢性頭蓋内電極と覚醒下手術の併用
    嶋田 勢二郎, 國井 尚人, 川合 謙介, 小泉 友幸, 石下 洋平, 井林 賢志, 齊藤 延人 てんかん研究 33 (2) 489 -489 2015年09月 [査読無し][通常論文]
  • 【抗てんかん薬と精神科臨床】 新しい静注製剤(fosphenytoin・phenobarbital)
    井林 賢志, 川合 謙介 精神科治療学 30 (8) 1045 -1052 2015年08月 [査読無し][通常論文]
  • 「平成26年度警察庁委託調査研究報告書:てんかんにかかっている者と運転免許に関する調査研究」の解説と検討
    川合 謙介, 西田 拓司, 荒木 敦, 久保田 英幹, 菅野 秀宣, 太組 一朗, 平田 幸一, 前垣 義弘, 松浦 雅人, 日本てんかん学会法的問題検討委員会 てんかん研究 33 (1) 147 -158 2015年06月 [査読無し][通常論文]
  • 実臨床下での日本人高齢発症部分てんかん患者に対するレベチラセタムの併用療法
    山内 俊雄, 兼本 浩祐, 川合 謙介, 石田 重信, 山田 真由美, 徳増 孝樹, 白井 大和, 山村 佳代 BRAIN and NERVE: 神経研究の進歩 67 (6) 749 -758 2015年06月 [査読無し][通常論文]
  • 川合 謙介, 西田 拓司, 荒木 敦, 久保田 英幹, 菅野 秀宣, 太組 一朗, 平田 幸一, 前垣 義弘, 松浦 雅人, 日本てんかん学会法的問題検討委員会 てんかん研究 33 (1) 147 -158 2015年06月 [査読無し][通常論文]
  • MEGはVNSの治療効果予測因子となり得るか
    國井 尚人, 川合 謙介, 湯本 真人, 小泉 友幸, 嶋田 勢二郎, 斉藤 延人 日本生体磁気学会誌 28 (1) 76 -77 2015年06月 [査読無し][通常論文]
  • 今後のてんかんの作業療法にむけて 重複した障害をもつてんかん患者への取り組み
    村木 慈, 稲川 利光, 川合 謙介 日本作業療法学会抄録集 49回 O1032 -O1032 2015年06月 [査読無し][通常論文]
  • 【精神疾患・向精神薬と運転】 てんかんと自動車運転
    川合 謙介 臨床精神薬理 18 (5) 537 -544 2015年05月 [査読無し][通常論文]
  • てんかん最前線 海馬多切術
    川合 謙介 Epilepsy: てんかんの総合学術誌 9 (1) 39 -45 2015年05月 [査読無し][通常論文]
  • 【症候性てんかんと自動車運転-最新の道路交通法改正も踏まえて-】 抗てんかん薬服用中の自動車運転
    川合 謙介 MEDICAL REHABILITATION (184) 47 -52 2015年05月 [査読無し][通常論文]
  • 【難治性けいれん重積】 てんかんの外科的治療
    松尾 健, 川合 謙介 ICUとCCU 39 (5) 309 -313 2015年05月 [査読無し][通常論文]
  • 症候性てんかんと自動車運転
    川合 謙介 The Japanese Journal of Rehabilitation Medicine 52 (Suppl.) S113 -S113 2015年05月 [査読無し][通常論文]
  • てんかんと自動車運転 押さえておきたい基本的知識と日本てんかん学会の提言
    川合 謙介 Journal of Clinical Rehabilitation 24 (4) 395 -400 2015年04月 [査読無し][通常論文]
  • T. Matsuo, K. Kawai, N. Kunii, K. Ibayashi, N. Saito EPILEPSIA 56 161 -162 2015年02月 [査読無し][通常論文]
  • Rie Hitsuyu, Tomoyo Isoguchi Shiramatsu, Takahiro Noda, Ryohei Kanzaki, Takeshi Uno, Kensuke Kawai, Hirokazu Takahashi IEEJ Transactions on Electronics, Information and Systems 135 (9) 1112 -1119 2015年 [査読無し][通常論文]
    Vagus nerve stimulation (VNS) causes neuromodulatory effects in the cerebral cortex, which are useful not only for therapy on intractable epilepsy but also for enhancement of higher brain functions such as cognition and memory. Recently, it has been reported that VNS may also affect auditory-evoked neural activities. However, it remains to be elucidated how and where VNS modulates neural activities in the auditory cortex. Here we examined effects of VNS on adaptation of neural activities in response to repeated stimuli in the rat auditory cortex. Both a surface and depth microelectrode array recorded auditory evoked potentials in response to click trains and oddball stimuli. We quantified a repetition rate transfer function (RRTF) and common stimulus-specific adaptation (SSA) index (CSI) from the amplitude of middle-latency response (P1). Consequently, VNS affected temporal response property and increased SSA in the layer 1 and 5/6 of auditory cortex. This result suggests that VNS strengthens adaptation in the auditory cortex in a layer-specific manner.
  • 【電気刺激による神経・精神疾患治療】 てんかんに対する迷走神経刺激療法
    松尾 健, 川合 謙介 脳21 18 (1) 23 -27 2015年01月 [査読無し][通常論文]
  • 側頭葉てんかん術後の視野欠損と一過性の幻視 シャルル・ボネ症候群
    嶋田 勢二郎, 國井 尚人, 川合 謙介, 寺西 裕, 小泉 友幸, 宇野 健志, 松尾 健, 斉藤 延人 てんかん研究 32 (3) 596 -596 2015年01月 [査読無し][通常論文]
  • 脳炎後難治性てんかんに対する迷走神経刺激療法の治療成績 成人6例の検討
    小泉 友幸, 國井 尚人, 嶋田 勢二郎, 宇野 健志, 宇佐美 憲一, 松尾 健, 川合 謙介, 斉藤 延人 てんかん研究 32 (3) 604 -604 2015年01月 [査読無し][通常論文]
  • 迷走神経刺激の即時的効果に対する電気生理学的検討
    宇野 健志, 國井 尚人, 嶋田 勢二郎, 小泉 友幸, 宇佐美 憲一, 松尾 健, 川合 謙介, 斉藤 延人 てんかん研究 32 (3) 607 -607 2015年01月 [査読無し][通常論文]
  • 抗てんかん薬単剤療法下の部分てんかん患者に対するlevetiracetamの付加投与 実臨床下における有効性と安全性の検討
    山内 俊雄, 兼本 浩祐, 川合 謙介, 石田 重信, 山田 真由美, 徳増 孝樹, 白井 大和, 山村 佳代 臨床精神薬理 17 (12) 1671 -1686 2014年12月 [査読無し][通常論文]
  • パッと見てサッと押さえる!科別で覚える診る看るカンタン手術イラスト 脳神経外科
    川合 謙介, 庄野 直之 オペナーシング 29 (9) 795 -798 2014年09月 [査読無し][通常論文]
  • 専門医に求められる最新の知識 機能外科 てんかん外科における言語機能マッピング
    國井 尚人, 川合 謙介 脳神経外科速報 24 (9) 1008 -1014 2014年09月 [査読無し][通常論文]
  • 難治性てんかんのパラダイムシフト 緩和的治療の存在意義と迷走神経刺激療法
    川合 謙介 Neurological Surgery 42 (9) 807 -816 2014年09月 [査読無し][通常論文]
  • てんかん発作と不随意運動発作をめぐって 術前の神経心理検査は頭蓋内脳波による焦点・機能局在をどの程度予見し得るか
    國井 尚人, 川合 謙介, 鎌田 恭輔, 太田 貴裕, 宇野 健志, 小泉 友幸, 嶋田 勢二郎, 宇佐美 憲一, 松尾 健, 斉藤 延人 てんかん研究 32 (2) 306 -306 2014年09月 [査読無し][通常論文]
  • 内側側頭葉てんかん 手術時期に関するPros and Cons 海馬切除のpros and cons
    川合 謙介, 松尾 健, 國井 尚人 てんかん研究 32 (2) 313 -313 2014年09月 [査読無し][通常論文]
  • 側頭葉てんかん画像診断におけるピットフォール 中頭蓋窩脳瘤の2症例
    嶋田 勢二郎, 國井 尚人, 川合 謙介, 小泉 友幸, 宇野 健志, 松尾 健, 宇佐美 憲一, 斉藤 延人 てんかん研究 32 (2) 424 -424 2014年09月 [査読無し][通常論文]
  • 迷走神経刺激療法におけるマグネットの使用状況と効果
    小泉 友幸, 國井 尚人, 嶋田 勢二郎, 宇野 健志, 松尾 健, 川合 謙介, 斉藤 延人 てんかん研究 32 (2) 426 -426 2014年09月 [査読無し][通常論文]
  • 頸動脈超音波検査による回旋性椎骨動脈閉塞の検出は、アトラスループ(V3部)の動脈解離の検出と経過観察に有用である
    山岡 由美子, 市川 靖充, 森田 明夫, 川合 謙介 Neurosonology 27 (増刊) 88 -88 2014年06月 [査読無し][通常論文]
  • 運転中の急病と交通事故 てんかんと自動車運転をめぐる諸問題
    川合 謙介 日本交通科学学会誌 14 (1) 39 -39 2014年06月 [査読無し][通常論文]
  • 吉田 瑞, 林 俊宏, 藤井 くるみ, 川合 謙介, 岩田 淳, 辻 省次 認知神経科学 16 (2) 121 -121 2014年06月 [査読無し][通常論文]
  • 【てんかん-基礎・臨床研究の最新知見-】 てんかんの治療 てんかんの外科治療における最新知見
    川合 謙介 日本臨床 72 (5) 881 -886 2014年05月 [査読無し][通常論文]
  • 【小児の治療指針】 神経・筋 水頭症、Dandy-Walker症候群
    川合 謙介 小児科診療 77 (増刊) 793 -795 2014年04月 [査読無し][通常論文]
  • てんかんと法・制度
    川合 謙介 てんかん研究 31 (3) 533 -534 2014年01月 [査読無し][通常論文]
  • 脳炎後の難治性てんかんに外科治療を行った一成人例
    小泉 友幸, 國井 尚人, 宇野 健志, 川合 謙介, 斉藤 延人 てんかん研究 31 (3) 539 -539 2014年01月 [査読無し][通常論文]
  • 鎌田 恭輔, 広島 覚, 小川 博司, 國井 尚人, 川合 謙介, 安栄 良悟, 斉藤 延人 脳神経外科ジャーナル 23 (4) 296 -305 2014年 [査読無し][通常論文]
  • 川合 謙介 脳神経外科ジャーナル 23 (8) 627 -634 2014年 [査読無し][通常論文]
  • 【海馬とその周辺】 疾患とその病態 側頭葉てんかんの外科治療
    川合 謙介 Clinical Neuroscience 31 (12) 1428 -1430 2013年12月 [査読無し][通常論文]
  • 【徹底解説!小児のてんかん-多様な事例からエキスパートの「観察眼」を身につける-】 てんかんの治療 てんかんの内科的治療の限界と外科治療のポイント
    宇佐美 憲一, 川合 謙介 小児科学レクチャー 3 (6) 1476 -1483 2013年11月 [査読無し][通常論文]
  • 頭蓋内電極による脳機能検査の新展開 皮質脳波による短時間・高精度脳機能マッピングの可能性
    國井 尚人, 川合 謙介, 鎌田 恭輔, 宇野 健志, 小泉 友幸, 松尾 健, 宇佐美 憲一, 斉藤 延人 臨床神経生理学 41 (5) 323 -323 2013年10月 [査読無し][通常論文]
  • Quadripulse transcranial magnetic stimulation(QPS)の難治性てんかんに対する影響
    榎本 雪, 花島 律子, 濱田 雅, 松本 英之, 町井 克行, 寺尾 安生, 川合 謙介, 管 るみ子, 丹羽 慎一, 榎本 博之, 宇川 義一 臨床神経生理学 41 (5) 492 -492 2013年10月 [査読無し][通常論文]
  • Intractable epilepsy; Cut or stimulate? 難治性てんかんに対する電気刺激療法の論拠
    川合 謙介 てんかん研究 31 (2) 305 -306 2013年09月 [査読無し][通常論文]
  • 記憶課題による海馬誘発電位と海馬傍回高周波脳律動活動の比較 側頭葉てんかんの記憶優位側同定に向けて
    國井 尚人, 川合 謙介, 鎌田 恭輔, 太田 貴裕, ファリアス・フェリペ, 宇野 健志, 宇佐美 憲一, 松尾 健, 斉藤 延人 てんかん研究 31 (2) 366 -366 2013年09月 [査読無し][通常論文]
  • 迷走神経刺激による大脳皮質神経活動の同期度変化
    宇佐美 憲一, 川合 謙介, 高橋 宏知, 狩野 竜示, 野田 貴大, 白松 知世, 國井 尚人, 斉藤 延人 てんかん研究 31 (2) 371 -371 2013年09月 [査読無し][通常論文]
  • 脳梁離断術後の部分発作に対する迷走神経刺激療法の効果
    村上 秀喜, 清水 弘之, 川合 謙介, 森野 道晴 てんかん研究 31 (2) 433 -433 2013年09月 [査読無し][通常論文]
  • 國井尚人, 鎌田恭輔, 太田貴裕, 川合謙介, 斉藤延人 てんかん治療研究振興財団研究年報 24 95 -102 2013年08月 [査読無し][通常論文]
  • N. Kunii, K. Kawai, K. Kamada, T. Ota, N. Saito EPILEPSIA 54 259 -259 2013年06月 [査読無し][通常論文]
  • 【てんかんの新治療戦略と課題】 電気刺激デバイスを用いたてんかん治療
    宇佐美 憲一, 川合 謙介 医薬ジャーナル 49 (5) 1289 -1293 2013年05月 [査読無し][通常論文]
  • 宇佐美 憲一, 川合 謙介 医薬ジャーナル 49 (5) 1289 -1293 2013年05月 [査読無し][通常論文]
  • 鎌田恭輔, 國井尚人, 川合謙介, 斉藤延人 脳神経外科ジャーナル 22 (Supplement) 71 2013年04月 [査読無し][通常論文]
  • 小児難治性てんかんに対する迷走神経刺激療法の有効性
    宇佐美 憲一, 川合 謙介, 斉藤 延人 小児の脳神経 38 (1) 108 -108 2013年04月 [査読無し][通常論文]
  • 鎌田 恭輔, 國井 尚人, 太田 貴裕, 川合 謙介, 斉藤 延人 脳神経外科ジャーナル 22 (3) 178 -184 2013年03月 [査読無し][通常論文]
  • 狩野 竜示, 宇佐美 憲一, 野田 貴大, 白松 磯口 知世, 神崎 亮平, 川合 謙介, 高橋 宏知 電気学会研究会資料. MBE, 医用・生体工学研究会 2013 (25) 65 -70 2013年03月
  • 基本をマスター 脳神経外科手術のスタンダード 側頭葉内側腫瘍の手術
    川合 謙介 脳神経外科速報 23 (3) 246 -252 2013年03月 [査読無し][通常論文]
  • てんかんの診断から最新の治療まで 見過ごしていないか? 日常診療に潜むてんかんを考える 古くて新しい疾患「てんかん」を考える 成人てんかんの病因、診断と治療
    川合 謙介 東京都医師会雑誌 66 (1) 25 -30 2013年01月 [査読無し][通常論文]
  • 興味深い発作症候を呈した小児前頭葉てんかんの1手術例
    長谷川 義仁, 井林 賢志, 川合 謙介, 斎藤 延人, 松浦 隆樹, 浜野 晋一郎 てんかん研究 30 (3) 530 -530 2013年01月 [査読無し][通常論文]
  • 松尾健, 川合謙介, 宇野健志, 國井尚人, 川嵜圭祐, 宮川尚久, 長谷川功, 斉藤延人 日本てんかん外科学会プログラム・抄録集 36th 50 2012年12月 [査読無し][通常論文]
  • 【いま知っておくべきてんかん 診る・治す・フォローする-てんかん診療の新展開】 てんかんの外科適応
    宇佐美 憲一, 川合 謙介, 斉藤 延人 Mebio 29 (11) 99 -106 2012年11月 [査読無し][通常論文]
  • 前頭葉言語野におけるfMRIの信頼度の検証 皮質電気刺激マッピングとの比較
    國井 尚人, 鎌田 恭輔, 太田 貴裕, 川合 謙介, 斉藤 延人 脳循環代謝 24 (1) 163 -163 2012年11月 [査読無し][通常論文]
  • 顔認知の神経生理学 ECoGによる顔-文字-図形認知ダイナミクス
    鎌田 恭輔, 國井 尚人, 広島 覚, 川合 謙介, 斉藤 延人 臨床神経生理学 40 (5) 385 -385 2012年10月 [査読無し][通常論文]
  • 鎌田恭輔, 國井尚人, 太田貴裕, 川合謙介, 斉藤延人 てんかん治療研究振興財団研究年報 23 47 -55 2012年09月 [査読無し][通常論文]
  • 【高次脳機能イメージングの脳科学への新展開】 脳皮質電位と機能的MRIによる言語・記憶機能ダイナミクス
    鎌田 恭輔, 國井 尚人, 広島 覚, 太田 貴裕, 川合 謙介, 斉藤 延人 BRAIN and NERVE: 神経研究の進歩 64 (9) 1001 -1012 2012年09月 [査読無し][通常論文]
  • てんかんのニューロモデュレーション VNSとニューロモデュレーション
    川合 謙介, 宇佐美 憲一, 高橋 宏知, 斉藤 延人 てんかん研究 30 (2) 253 -254 2012年09月 [査読無し][通常論文]
  • 海馬傍回high gamma activityによる記憶優位側の同定
    國井 尚人, 鎌田 恭輔, 太田 貴裕, ファリアス・フェリペ, 宇野 健志, 宇佐美 憲一, 松尾 健, 川合 謙介, 斉藤 延人 てんかん研究 30 (2) 367 -367 2012年09月 [査読無し][通常論文]
  • 成人大脳半球離断術の全般性起始発作に対する効果
    宇野 健志, 川合 謙介, 宇佐美 憲一, 松尾 健, 國井 尚人, ファリアス・フェリペ, 斉藤 延人 てんかん研究 30 (2) 369 -369 2012年09月 [査読無し][通常論文]
  • 成人大脳半球離断術の適応判断における運動機能予測
    Farias Felipe, 川合 謙介, 宇野 健志, 國井 尚人, 宇佐美 憲一, 松尾 健, 斉藤 延人, 寺尾 安生, 花島 律子 てんかん研究 30 (2) 372 -372 2012年09月 [査読無し][通常論文]
  • 側頭葉てんかんに対する海馬多切術の長期成績 発作抑制と記憶・認知機能について
    宇佐美 憲一, 川合 謙介, 久保田 真由美, 斉藤 延人 てんかん研究 30 (2) 373 -373 2012年09月 [査読無し][通常論文]
  • 【高次脳機能イメージングの脳科学への新展開】 てんかん外科治療における高次脳機能イメージングの役割
    川合 謙介 BRAIN and NERVE: 神経研究の進歩 64 (9) 1013 -1022 2012年09月 [査読無し][通常論文]
  • 川合 謙介, 斉藤 延人 脳神経外科ジャーナル 21 (8) 594 -603 2012年08月 [査読無し][通常論文]
  • Soichi Oya, Hirofumi Nakatomi, Kensuke Kawai, Nobuhito Saito JOURNAL OF NEUROSURGERY 117 (2) A440 -A441 2012年08月 [査読無し][通常論文]
  • 川合 謙介, 斉藤 延人 脳神経外科ジャーナル 21 (8) 594 -603 2012年08月 [査読無し][通常論文]
  • 川合 謙介, 須貝 研司, 赤松 直樹, 岡崎 光俊, 亀山 茂樹, 笹川 睦男, 辻 貞俊, 前原 健寿, 山本 仁 てんかん研究 = Journal of the Japan Epilepsy Society 30 (1) 68 -72 2012年06月 [査読無し][通常論文]
  • Kenichi Usami, Masahiro Shin, Kensuke Kawai Journal of Neurosurgery 116 (6) 1220 2012年06月 [査読無し][通常論文]
  • Kenichi Usami, Masahiro Shin, Kensuke Kawai JOURNAL OF NEUROSURGERY 116 (6) 1220 -1220 2012年06月 [査読無し][通常論文]
  • 難治てんかんに対する迷走神経刺激療法導入1年後の状況 九州労災病院と全国における状況
    森岡 隆人, 佐山 徹郎, 下川 能史, 濱村 威, 橋口 公章, 川合 謙介, 迎 伸孝, 村上 信哉, 佐々木 富男 BRAIN and NERVE: 神経研究の進歩 64 (6) 681 -687 2012年06月 [査読無し][通常論文]
  • 【小児・思春期診療 最新マニュアル】(4章)よくみられる疾患・見逃せない疾患の診療 神経系疾患 水頭症
    川合 謙介 日本医師会雑誌 141 (特別1) S232 -S233 2012年06月 [査読無し][通常論文]
  • 【小児・思春期診療 最新マニュアル】(4章)よくみられる疾患・見逃せない疾患の診療 神経系疾患 脳腫瘍
    川合 謙介, 武笠 晃丈 日本医師会雑誌 141 (特別1) S233 -S235 2012年06月 [査読無し][通常論文]
  • 【子どもの突然死】 てんかんに関連した突然死
    川合 謙介 小児科 53 (6) 675 -679 2012年06月 [査読無し][通常論文]
  • てんかんのある人における運転免許の現状と問題点 道路交通法改正8年後の公安委員会・医師へのアンケート調査
    松浦 雅人, 川合 謙介, 久保田 英幹, 西田 拓司, 杉本 健郎, 平田 幸一, 日本てんかん学会法的問題検討委員会 てんかん研究 30 (1) 60 -67 2012年06月 [査読無し][通常論文]
  • 川合 謙介 小児科 53 (6) 675 -679 2012年06月 [査読無し][通常論文]
  • 症候・疾患と検査・診断 てんかんの治療 特に外科的治療について
    川合 謙介 小児神経学の進歩 41 57 -68 2012年05月 [査読無し][通常論文]
  • 頭蓋底悪性腫瘍手術例における予後因子に関する検討
    朝蔭 孝宏, 蝦原 康宏, 齊藤 祐毅, 小村 豪, 川合 謙介, 飯田 拓也, 山本 健太郎 頭頸部癌 38 (2) 141 -141 2012年05月 [査読無し][通常論文]
  • 鎌田 恭輔, 國井 尚人, 川合 謙介, 斉藤 延人 脳神経外科ジャーナル 21 (0) 2012年04月 [査読無し][通常論文]
  • 脳神経疾患に伴うてんかんの治療戦略 QOLに着目した薬物治療の実践
    川合 謙介, 卜部 貴夫, 藤本 礼尚, 太組 一朗 Pharma Medica 30 (4) 123 -128 2012年04月 [査読無し][通常論文]
  • 【脳室と髄液腔の最新情報】 小児の水頭症と奇形 脳室病変とてんかん
    川合 謙介 Clinical Neuroscience 30 (4) 447 -449 2012年04月 [査読無し][通常論文]
  • 高橋 長久, 内野 俊平, 水野 葉子, 岩崎 博之, 高橋 寛, 武笠 晃丈, 川合 謙介, 小林 敏之, 樋野 興夫, 大澤 麻記, 斎藤 真木子, 水口 雅 脳と発達 44 (2) 156 -156 2012年03月 [査読無し][通常論文]
  • 迷走神経刺激装置植込術の術中モニタリング法
    宇佐美 憲一, 川合 謙介, 斉藤 延人 てんかん研究 29 (3) 509 -510 2012年01月 [査読無し][通常論文]
  • 【小児医療における診断・治療の進歩】 治療技術 てんかんに対する迷走神経刺激療法
    川合 謙介, 宇佐美 憲一 小児科 52 (12) 1689 -1695 2011年11月 [査読無し][通常論文]
  • 川合 謙介, 宇佐美 憲一 小児科 52 (12) 1689 -1695 2011年11月 [査読無し][通常論文]
  • 迷走神経刺激療法の現状 迷走神経刺激療法の臨床神経生理学的側面
    宇佐美 憲一, 川合 謙介 臨床神経生理学 39 (5) 329 -329 2011年10月 [査読無し][通常論文]
  • 症例検討会 先生ならどうするか クモ膜嚢胞に伴う小児難治性てんかんの1例
    宇佐美 憲一, 川合 謙介, 石下 洋平, 齊藤 延人 てんかん研究 29 (2) 249 -249 2011年09月 [査読無し][通常論文]
  • 言語課題における皮質電気刺激と高周波ガンマ帯活動の比較(A comparative study between electrocortical stimulation and high-frequency gamma activity during language tasks)
    國井 尚人, 鎌田 恭輔, 宇佐美 憲一, 松尾 健, ファリアス・フェリペ, 太田 貴裕, 川合 謙介, 齊藤 延人 てんかん研究 29 (2) 314 -314 2011年09月 [査読無し][通常論文]
  • 迷走神経刺激療法における迷走神経誘発電位の測定とその意義
    宇佐美 憲一, 川合 謙介, 園生 雅弘, 松尾 健, 國井 尚人, 齊藤 延人 てんかん研究 29 (2) 314 -314 2011年09月 [査読無し][通常論文]
  • 電極間相関を考慮にいれたてんかん焦点診断(Localization of epileptogenic zone from electrocorticogram using causal connectivity)
    松尾 健, 川合 謙介, 宇佐美 憲一, 國井 尚人, 齊藤 延人 てんかん研究 29 (2) 334 -334 2011年09月 [査読無し][通常論文]
  • てんかん術前モニタリングにおける単一ニューロン記録電極の開発と皮質脳波同時記録の試み
    川合 謙介, 松尾 健, 宇佐美 憲一, 國井 尚人, 宮川 尚久, 長谷川 功, 齊藤 延人 てんかん研究 29 (2) 335 -335 2011年09月 [査読無し][通常論文]
  • 内側型側頭葉てんかん症例の発作間欠期画像におけるAsymmetry解析法の術後予後予測における有用性
    高橋 美和子, 相馬 努, 古山 桂太郎, 川合 謙介, 大友 邦, 百瀬 敏光 核医学 48 (3) S285 -S286 2011年09月 [査読無し][通常論文]
  • 脳外科領域で用いられる機器最前線 迷走神経刺激装置 植込み型迷走神経刺激装置
    宇佐美 憲一, 川合 謙介 脳神経外科速報 21 (8) 904 -909 2011年08月 [査読無し][通常論文]
  • 小児難治てんかんに対する迷走神経刺激療法の効果 本邦における7例の臨床経過と予後
    若井 周治, 川合 謙介, 長尾 雅悦, 小野村 章 てんかん研究 29 (1) 82 -82 2011年06月 [査読無し][通常論文]
  • 検査からみる神経疾患 高FGF23血症による骨軟化症
    宇野 健志, 川合 謙介, 福本 誠二, 齊藤 延人 Clinical Neuroscience 29 (6) 714 -715 2011年06月 [査読無し][通常論文]
  • 【医療現場におけるてんかん診療の現状と展望】 てんかん外科の種類と適応 どのような患者をいつどこに紹介するか
    川合 謙介 医薬ジャーナル 47 (5) 1465 -1469 2011年05月 [査読無し][通常論文]
    てんかん治療において外科治療は強力な選択肢の一つである。限局性MRI(magnetic resonance imaging)病変に対する焦点切除術の発作消失率は70〜80%に上り、抗てんかん薬投与を終了できる可能性もある。一方、MRI病変を欠く場合やてんかん焦点が広範囲に及ぶ場合の発作消失率は50%未満で、適応判断には専門施設での詳細な術前検査による有効性と合併症の評価が必要である。根治的な開頭手術の適応とならない全般性てんかんや両側多焦点でも、迷走神経刺激療法や脳梁離断など緩和的治療が選択肢となり得るので、適切な薬剤治療に関わらず、生活上支障の大きい発作が持続する場合には、外科的治療を念頭において、まずてんかん専門医へ紹介することが勧められる。(著者抄録)
  • 【てんかんの新しい治療】 てんかんに対する迷走神経刺激療法
    川合 謙介 BRAIN and NERVE: 神経研究の進歩 63 (4) 331 -346 2011年04月 [査読無し][通常論文]
  • 【最新の治療デバイス】 刺激・微量注入デバイス 迷走神経刺激療法(Vagus nerve stimulation)
    宇佐美 憲一, 川合 謙介 Clinical Neuroscience 29 (4) 422 -425 2011年04月 [査読無し][通常論文]
  • Kyousuke Kamada, Naoto Kunii, Kensuke Kawai, Nobuhito Saito NEUROSCIENCE RESEARCH 71 E91 -E91 2011年 [査読無し][通常論文]
  • 【てんかん治療 New Standards】 その他のポイント 迷走神経刺激療法
    川合 謙介 Clinical Neuroscience 29 (1) 76 -77 2011年01月 [査読無し][通常論文]
  • 各種疾患 機能性疾患 難治性てんかんに対する迷走神経刺激療法
    川合 謙介 Annual Review神経 2011 366 -373 2011年01月 [査読無し][通常論文]
  • 難治性てんかんに対する迷走神経刺激療法
    川合 謙介 てんかん研究 28 (3) 466 -466 2011年01月 [査読無し][通常論文]
  • 興味深い経過をたどったくも膜下嚢胞に伴う小児てんかんの1手術例
    石下 洋平, 小泉 友幸, 國井 尚人, 宇佐美 憲一, 川合 謙介, 斎藤 延人 てんかん研究 28 (3) 489 -489 2011年01月 [査読無し][通常論文]
  • 小児難治てんかんに対する迷走神経刺激療法の効果 本邦における7例の臨床経過と予後
    若井 周治, 川合 謙介, 長尾 雅悦, 小野村 章 てんかん研究 28 (3) 506 -506 2011年01月 [査読無し][通常論文]
  • 川合 謙介, 宇佐美 憲一, 斎藤 延人 臨床神経学 51 (11) 990 -992 2011年 [査読無し][通常論文]
    Vagus nerve stimulation is the first electrical stimulation therapy for epilepsy. While its clinical use was approved by the European Union in 1994 and by the United States in 1997, it was approved last year and coverage by public insurance started last July in Japan. Owing to less invasiveness and broad indication, it is expected that vagus nerve stimulation will be increasingly used in Japan as well. Its efficacy for refractory partial seizures in patients older than 13 years was validated by two randomized control trials. Although it has been used for children and generalized seizures broadly, the efficacy for these subpopulations of patients has not been validated by randomized control trials, necessitating those studies in the near future. Afferent neural impulses generated by vagus nerve stimulation transmit to the solitary tract nucleus, then via multiple pathways including the monoamine system, vagus nerve stimulation affects the excitability of the cortical neurons. It likely exerts the anti-epileptic and anti-seizure effects using these pathways, but the detailed mechanisms underlying the effect remains to be elucidated further in future.
  • 【新時代の脳腫瘍学 診断・治療の最前線】 脳腫瘍の治療 脳腫瘍の外科療法 脳腫瘍摘出に用いる術中モニタリング
    鎌田 恭輔, 川合 謙介, 斉藤 延人 日本臨床 68 (増刊10 新時代の脳腫瘍学) 344 -348 2010年12月 [査読無し][通常論文]
  • 鎌田 恭輔, 川合 謙介, 斉藤 延人 日本臨床 68 (0) 344 -348 2010年12月 [査読無し][通常論文]
  • 【てんかん 最近の話題】 てんかんの外科治療の進歩 成人てんかん
    川合 謙介 MEDICO 41 (11) 377 -381 2010年11月 [査読無し][通常論文]
  • 【てんかん 最近の話題】 成人てんかんの診断と治療 最近の話題
    亀山 茂樹, 岡田 元宏, 池田 昭夫, 川合 謙介 MEDICO 41 (11) 382 -392 2010年11月 [査読無し][通常論文]
  • 【大脳機能局在はここまで分かった】 側頭葉 側頭葉の解剖と機能概説 臨床的視点から
    川合 謙介 Clinical Neuroscience 28 (10) 1131 -1134 2010年10月 [査読無し][通常論文]
  • 脳神経外科からみたてんかんの新たな薬物治療戦略
    中里 信和, 兼本 浩祐, 三國 信啓, 川合 謙介 Pharma Medica 28 (10) 141 -146 2010年10月 [査読無し][通常論文]
  • 【神経疾患に対するもう一つのEBM-Engineering Based Medicine】 難治性てんかんに対する迷走神経刺激療法
    川合 謙介 Brain Medical 22 (3) 215 -221 2010年09月 [査読無し][通常論文]
  • 小児難治性てんかんに対する迷走神経刺激療法の効果 本邦における7例の臨床経過と予後
    若井 周治, 川合 謙介, 長尾 雅悦, 小野村 章 てんかん研究 28 (2) 255 -255 2010年09月 [査読無し][通常論文]
  • 3T-fMRIによる言語機能局在の実用化にむけての現状と課題
    國井 尚人, 鎌田 恭輔, 太田 貴裕, 宇佐美 憲一, 川合 謙介, 斉藤 延人 てんかん研究 28 (2) 266 -266 2010年09月 [査読無し][通常論文]
  • 迷走神経刺激時皮質脳波の時間周波数解析
    宇佐美 憲一, 國井 尚人, 川合 謙介, 斉藤 延人 てんかん研究 28 (2) 312 -312 2010年09月 [査読無し][通常論文]
  • 一般病棟でターミナルケアを行った新生児頭蓋内未熟奇形腫の1例
    設楽 佳彦, 井田 孔明, 大久保 淳, 伊藤 直樹, 細井 洋平, 安井 孝二郎, 五石 圭司, 本村 あい, 滝田 順子, 菊地 陽, 五十嵐 隆, 辛 正廣, 川合 謙介 日本小児科学会雑誌 114 (8) 1241 -1241 2010年08月 [査読無し][通常論文]
  • てんかんの外科治療 最近の進歩
    川合 謙介 Current Insights in Neurological Science 18 (2) 2 -4 2010年08月 [査読無し][通常論文]
  • 皮質脳波を用いた側頭葉視覚領野の機能マッピング(Electrocorticographic mapping of human ventral visual areas)
    松尾 健, 川嵜 圭祐, 川合 謙介, 増田 浩, 國井 尚人, 村上 博淳, 間島 慶, 鎌田 恭輔, 神谷 之康, 亀山 茂樹, 齋藤 延人, 長谷川 功 神経化学 49 (2-3) 508 -508 2010年08月 [査読無し][通常論文]
  • 皮質脳波の時間的パターンを用いた視覚物体カテゴリーのデコーディング(Neural decoding of visual object categories using temporal patterns of ECoG signals)
    間島 慶, 松尾 健, 川嵜 圭祐, 川合 謙介, 増田 浩, 國井 尚人, 村上 博淳, 鎌田 恭輔, 亀山 茂樹, 斉藤 延人, 長谷川 功, 神谷 之康 神経化学 49 (2-3) 724 -724 2010年08月 [査読無し][通常論文]
  • 言語ネットワークの画像化と電気刺激マッピングによる検証(Visualization of language network and its validation by electrical stimulation)
    鎌田 恭輔, 川合 謙介, 國井 尚人, 斉藤 延人 神経化学 49 (2-3) 743 -743 2010年08月 [査読無し][通常論文]
  • 鎌田 恭輔, 太田 貴裕, 國井 尚人, 青木 茂樹, 増谷 佳孝, 川合 謙介, 斉藤 延人 脳神経外科ジャーナル 19 (0) 2010年04月 [査読無し][通常論文]
  • 【小児の治療指針】 神経・筋 水頭症・Dandy-Walker症候群
    川合 謙介 小児科診療 73 (増刊) 737 -739 2010年04月 [査読無し][通常論文]
  • 小児てんかんの外科治療
    川合 謙介 日本小児科学会雑誌 114 (4) 749 -749 2010年04月 [査読無し][通常論文]
  • 【島皮質は何をしているか】 島皮質の疾患 島領域の腫瘍
    川合 謙介 Clinical Neuroscience 28 (4) 422 -426 2010年04月 [査読無し][通常論文]
  • 宇佐美 憲一, 川合 謙介 医学のあゆみ 232 (10) 998 -1002 2010年03月 [査読無し][通常論文]
  • 【てんかん治療Update 研究と臨床の最前線】 最新・外科治療動向 難治性てんかんに対する迷走神経刺激療法
    宇佐美 憲一, 川合 謙介 医学のあゆみ 232 (10) 998 -1002 2010年03月 [査読無し][通常論文]
  • 【てんかんのトピックス】 難治性部分てんかんと迷走神経刺激療法
    川合 謙介 神経内科 72 (3) 262 -269 2010年03月 [査読無し][通常論文]
  • Kyousuke Kamada, Kensuke Kawai, Naoto Kunii, Nobuhito Saito NEUROSCIENCE RESEARCH 68 E405 -E405 2010年 [査読無し][通常論文]
  • 鎌田 恭輔, 太田 貴裕, 川合 謙介, 安栄 良悟, 斉藤 延人 脳神経外科ジャーナル 19 (12) 916 -922 2010年 [査読無し][通常論文]
    グリオーマ手術をより安全に施行するため、非侵襲的脳機能マッピング法による脳皮質-白質情報を脳神経外科手術navigation systemに転送する機能的手術ナビゲーション法を確立し、実際の臨床応用について報告した。運動野近傍に病変を有する30例において、機能的MRIと脳磁図による中心溝同定成功率はそれぞれ76.7%、93.3%であったが、連続した白質線維の画像化(tractography)を用いることで全例で運動野を同定することができた。また、皮質脊髄路(CST)傍病変40例において、白質電気刺激により脳磁図(MEP)が誘発されたのは17例で、43%でCSTの白質マッピングを行うことができた。皮質刺激MEPの平均刺激強度は15.6mAであったのに対し、白質刺激MEPが出現した症例では9.4mAと有意差を認めた。白質電気刺激によりMEPを誘発する因子としては、刺激部位とCSTまでの距離が重要であると考えられた。
  • 川合 謙介 小児科診療 73 (0) 737 -739 2010年 [査読無し][通常論文]
  • 鎌田 恭輔, 太田 貴裕, 川合 謙介, 安栄 良悟, 斉藤 延人 脳神経外科ジャーナル 19 (12) 916 -922 2010年 [査読無し][通常論文]
    脳機能画像と電気生理学的モニタリングを融合してグリオーマ手術に応用した.運動野および皮質脊髄路(CST)と病変の関係を明らかにするために,finger tapping課題によるfMRI,CST-tractographyを組み合わせてニューロナビゲーション上に表示した.電気生理学的モニタリングは,運動野の皮質-白質電気刺激によるMEPの持続モニタリングを行った.Fucntional neuronavigation上の運動野,CST近傍の電気刺激によりMEPが誘発された.Functional neuronavigationは,グリオーマ手術における運動機能温存に関してきわめて有用であった.
  • 川合 謙介 Epilepsy 3 (2) 129 -133 2009年11月 [査読無し][通常論文]
  • 久保田 真由美, 川合 謙介, 太田 貴裕 臨床脳波 51 (10) 620 -625 2009年10月 [査読無し][通常論文]
  • 鎌田 恭輔, 太田 貴裕, 川合 謙介, 斉藤 延人 臨床検査 53 (9) 1027 -1033 2009年09月 [査読無し][通常論文]
    本稿では脳磁図(MEG)と機能MRI(fMRI)という機序の異なる機能画像の組み合わせにより,信頼性の高い言語機能マッピング法を確立した.対象は頭蓋内疾患を有する138症例である.文字読みMEGは単語を黙読して計測し,単一ダイポールモデルを用いて側頭葉内の文字認知ダイポール数を比較した.語想起課題fMRIでは有意なfMRI信号変化を示すピクセル数の比較を行った.文字読みMEGは上側頭回近傍部と紡錘回に認知ダイポールの集積を認め,その成功率は86.5%であった.語想起課題fMRIは優位側の上・中前頭回に強い活動を認め,82.0%の成功率であった.MEGとfMRIの併用により優位半球の同定成功率は95%となり,Wada testと比較して十分臨床応用が可能と考えられた.本法が確立することにより言語機能局在を詳細に把握することができ,脳神経外科手術計画立案に大きく貢献するものと期待できる.(著者抄録)
  • 難治性てんかんに対する外科的治療における核医学検査の有用性の検討
    高橋 美和子, 百瀬 敏光, 古山 桂太郎, 川合 謙介, 大友 邦 核医学 46 (3) 313 -313 2009年09月 [査読無し][通常論文]
  • 内側側頭葉てんかんに対するガンマナイフ治療の長期成績 特に長期経過後の合併症について(Long-term outcome of gamma knife surgery for mesial temporal lobe epilepsy)
    宇佐美 憲一, 川合 謙介, 甲賀 智之, 辛 正廣, 栗田 浩樹, 鈴木 一郎, 斉藤 延人 てんかん研究 27 (2) 243 -243 2009年09月 [査読無し][通常論文]
  • 発作時MEG-ECoG同時記録の臨床的意義(The clinical impact of simultaneous recording of MEG and ECoG in ictal state)
    國井 尚人, 鎌田 恭輔, 太田 貴裕, 川合 謙介, 斉藤 延人 てんかん研究 27 (2) 274 -274 2009年09月 [査読無し][通常論文]
  • 脳皮質電位によるてんかん焦点活動の時間-周波数変化と発作Semiology(Time-frequency ECoG changes of epileptogenic activity and seizure semiology)
    鎌田 恭輔, 川合 謙介, 太田 貴裕, 國井 尚人, 斉藤 延人 てんかん研究 27 (2) 275 -275 2009年09月 [査読無し][通常論文]
  • 難治性てんかんに対する迷走神経刺激療法後の発作予後の予測因子(Predictive factors of seizure outcome in vagus nerve stimulation for intractable epilepsy)
    川合 謙介, 宇佐美 憲一, 鎌田 恭輔, 斉藤 延人 てんかん研究 27 (2) 285 -285 2009年09月 [査読無し][通常論文]
  • 鎌田 恭輔, 太田 貴裕, 川合 謙介 臨床検査 53 (9) 1027 -1033 2009年09月 [査読無し][通常論文]
  • 【てんかん外科】 機能温存的てんかん外科とニューロネットワーク
    川合 謙介, 鎌田 恭輔, 太田 貴裕, 斎藤 延人 臨床脳波 51 (7) 389 -396 2009年07月 [査読無し][通常論文]
  • 川合 謙介, 鎌田 恭輔, 太田 貴裕 臨床脳波 51 (7) 389 -396 2009年07月 [査読無し][通常論文]
  • 全身の骨痛及び、筋力低下で発症した側頭骨腫瘍性骨軟化症の1例
    小林 謙也, 中尾 一成, 朝蔭 孝宏, 山岨 達也, 福本 誠二, 川合 謙介, 大田 聡, 元井 亨 頭頸部癌 35 (2) 198 -198 2009年05月 [査読無し][通常論文]
  • 久保田 真由美, 川合 謙介, 荻原 英樹, 太田 貴裕, 鎌田 恭輔, 斉藤 延人 てんかん研究 26 (3) 463 -464 2009年01月 [査読無し][通常論文]
  • Takahiro Ota, Kyousuke Kamada, Kensuke Kawai, Nobuhito Saito NEUROSCIENCE RESEARCH 65 S34 -S34 2009年 [査読無し][通常論文]
  • Kyousuke Kamada, Takahiro Ota, Kensuke Kawai, Nobuhito Saito NEUROSCIENCE RESEARCH 65 S32 -S32 2009年 [査読無し][通常論文]
  • 興味深い画像所見を呈した前頭葉てんかんの一例
    久保田 真由美, 川合 謙介, 荻原 英樹, 太田 貴裕, 鎌田 恭輔, 斉藤 延人 てんかん研究 26 (3) 463 -464 2009年01月 [査読無し][通常論文]
  • 川合 謙介, 鎌田 恭輔, 太田 貴裕, 斉藤 延人 脳神経外科ジャーナル 18 (8) 586 -595 2009年 [査読無し][通常論文]
    Intractable epilepsy associated with organic lesions in MRI is generally a good candidate for surgical treatment. Meticulous localization of the epileptic focus is required even in patients with MRI lesions when surgical treatment is considered for abolishment of the seizures. Initial noninvasive evaluation includes recording of seizures and analysis of semiology, interictal and ictal electroencephalography (EEG), magnetoencephalography, and nuclear medicine studies. The final determination of epileptic focus is made in principle by intracranial EEG, particularly when noninvasive examinations do not lead to a decisive result and when a high spatial resolution is required for tailored resection of the epileptic focus. While intracranial EEG is presently the most useful method and a gold standard for localization of epileptic focus, it is unignorably invasive for patients. Further identification of patients in whom intracranial EEG can be skipped and development of a novel approach in localization and treatment of epileptic focus are urgently required.
  • 川合 謙介, 鎌田 恭輔, 太田 貴裕, 斉藤 延人 脳神経外科ジャーナル 18 (8) 586 -595 2009年 [査読無し][通常論文]
  • 解剖を中心とした脳神経手術手技 難治性てんかんに対する迷走神経刺激療法 刺激装置の埋込術
    川合 謙介 Neurological Surgery 36 (11) 979 -989 2008年11月 [査読無し][通常論文]
  • 側頭葉てんかん研究・治療の進歩 側頭葉てんかんに対する海馬多切術後の記銘力
    川合 謙介, 久保田 真由美, 太田 貴裕, 鎌田 恭輔, 百瀬 敏光, 青木 茂樹, 川島 明子, 斎藤 延人 臨床神経生理学 36 (5) 466 -466 2008年10月 [査読無し][通常論文]
  • 脳皮質電位によるヒト高次脳機能ネットワークの解明
    鎌田 恭輔, 川合 謙介, 太田 貴裕, 斉藤 延人 日本脳神経外科学会総会CD-ROM抄録集 67回 2D -O07 2008年10月 [査読無し][通常論文]
  • 鎌田 恭輔, 川合 謙介, 太田 貴裕, 増谷 佳孝, 青木 茂樹, 斉藤 延人 てんかん研究 26 (2) 2008年09月 [査読無し][通常論文]
  • 久保田 真由美, 川合 謙介, 鎌田 恭輔, 太田 貴裕, 青木 茂樹, 百瀬 敏光, 川島 明子, 斉藤 延人 てんかん研究 26 (2) 2008年09月 [査読無し][通常論文]
  • てんかんの最先端医療 日本のTractography最新情報 Tractographyと電気生理モニタリング融合によるeloquent networkの画像化
    鎌田 恭輔, 川合 謙介, 太田 貴裕, 増谷 佳孝, 青木 茂樹, 斉藤 延人 てんかん研究 26 (2) 254 -254 2008年09月 [査読無し][通常論文]
  • 多点皮質脳波におけるてんかん発作の予測・検出の試み
    藤原 正道, 川合 謙介, 神崎 亮平, 高橋 宏知 てんかん研究 26 (2) 257 -257 2008年09月 [査読無し][通常論文]
  • 海馬多切術後の記憶温存とPapez's circuit 海馬容積・糖代謝・白質線維の変化
    久保田 真由美, 川合 謙介, 鎌田 恭輔, 太田 貴裕, 青木 茂樹, 百瀬 敏光, 川島 明子, 斉藤 延人 てんかん研究 26 (2) 277 -277 2008年09月 [査読無し][通常論文]
  • 鎌田 恭輔, 川合 謙介, 太田 貴裕, 斉藤 延人 まぐね = Magnetics Japan 3 (2) 73 -81 2008年02月 [査読無し][通常論文]
  • Kyousuke Kamada, Takahiro Ota, Kensuke Kawai, Nobuhito Saito NEUROSCIENCE RESEARCH 61 S10 -S10 2008年 [査読無し][通常論文]
  • Kensuke Kawai, K. Kamada, T. Ohta, N. Saito EPILEPSIA 49 281 -281 2008年 [査読無し][通常論文]
  • Kyousuke Kamada, Kensuke Kawai, Takahiro Ota, Shigeki Aoki, Nobuhito Saito NEUROSCIENCE RESEARCH 61 S33 -S33 2008年 [査読無し][通常論文]
  • 【てんかん What's new?】 てんかんの治療 てんかんの外科治療
    川合 謙介 Clinical Neuroscience 26 (1) 83 -86 2008年01月 [査読無し][通常論文]
  • 頭蓋内くも膜嚢胞
    川合 謙介 Current Insights in Neurological Science 16 (1) 5 -5 2008年01月 [査読無し][通常論文]
  • 鎌田 恭輔, 太田 貴裕, 川合 謙介, 藤堂 具紀, 川原 信隆, 森田 明夫, 斉藤 延人 脳神経外科ジャーナル 17 (1) 4 -12 2008年 [査読無し][通常論文]
    非侵襲的脳機能マッピング法としての皮質電気刺激マッピング、機能MRI(fMRI)及び脳磁図(MEG)の原理を解説し、臨床応用においてこれらの手法を融合した時の有用性を提示した。頭蓋内疾患を有する117例を対象としてfMRIとMEGを実施し、このうち97例ではWada testで言語優位半球を同定した。fMRIでは前頭葉のブローカ領、MEGでは側頭葉後半部のウェルニッケ領の言語機能を局在でき、言語機能の画像化成功率は各々90%と82%であったが、両者の融合により成功率は95%に達した。また、両手法の所見が一致した症例では、Wada testで同定した言語優位半球の結果と100%一致した。一方、fMRIは脳血管性反応性に障害がある症例には不適であり、MEGは脳組織状態より患者の脳機能低下により検査の成功率が低下した。両手法の融合により、術前に言語機能局在を把握することが可能になった。
  • 鎌田 恭輔, 太田 貴裕, 川合 謙介, 藤堂 具紀, 川原 信隆, 森田 明夫, 斉藤 延人 脳神経外科ジャーナル 17 (1) 4 -12 2008年 [査読無し][通常論文]
    非侵襲的脳機能マッピング法としては,機能MRI(fMRI),脳磁図(MEG)などが挙げられる.この両者を融合することで,言語優位半球の同定を行った.言語機能画像の課題は,語想起,文字読み課題とした.fMRIでは前頭葉のブローカ領を,MEGでは側頭葉後半部のウェルニッケ領の言語機能を局在できた.fMRIとMEGによる言語機能の画像化の成功率は90%と82%であったが,両者を併用することで95%に達した.また,fMRIとMEGの所見が一致した症例では,Wada testで同定した言語優位半球の結果と100%一致した.fMRIは脳血管性反応性が障害される症例(脳浮腫を伴う脳腫瘍,脳動静脈奇形など)には不適であった.一方,MEGは,脳組織状態よりは患者の脳機能低下(精神発達遅滞,痴呆,失語)により,検査の成功率が低下していた.fMRIとMEGを融合することで術前に患者個々の言語機能局在を把握することが可能となった.
  • 脳手術におけるNIRSの応用 言語優位半球同定においてNIRSはfMRIをこえられるか? 42例の経験から
    太田 貴裕, 鎌田 恭輔, 川合 謙介, 湯本 真人, 青木 茂樹, 斉藤 延人 臨床神経生理学 35 (5) 307 -308 2007年10月 [査読無し][通常論文]
  • てんかん外科とニューロネットワーク 機能温存的てんかん外科とニューロネットワーク
    川合 謙介 臨床神経生理学 35 (5) 353 -353 2007年10月 [査読無し][通常論文]
  • Eloquent fiber tractographyとマルチ電気生理学モニタリングによる白質マッピングの検証と課題
    鎌田 恭輔, 川合 謙介, 藤堂 具紀, 太田 貴裕, 増谷 佳孝, 青木 茂樹, 斉藤 延人 日本脳神経外科学会総会CD-ROM抄録集 66回 1D -S04 2007年10月 [査読無し][通常論文]
  • 術中Diffusion Tensor Tractographyが可能なニューロナビゲーション装置の開発とその臨床応用
    金 太一, 鎌田 恭輔, 太田 貴裕, 増谷 佳孝, 青木 茂樹, 川合 謙介, 藤堂 具紀, 斉藤 延人 日本脳神経外科学会総会CD-ROM抄録集 66回 2J -O27 2007年10月 [査読無し][通常論文]
  • 非侵襲的言語優位半球同定法の検討
    太田 貴裕, 鎌田 恭輔, 川合 謙介, 青木 茂樹, 斎藤 延人 日本脳神経外科学会総会CD-ROM抄録集 66回 3A -S21 2007年10月 [査読無し][通常論文]
  • MST・海馬多切を中心としたnon-lesional TLEの外科治療
    川合 謙介, 太田 貴裕, 鎌田 恭輔, 斎藤 延人 日本脳神経外科学会総会CD-ROM抄録集 66回 3G -O50 2007年10月 [査読無し][通常論文]
  • 川合 謙介, 清水 弘之, 若井 周二, 太田 貴裕, 鎌田 恭輔, 斎藤 延人 てんかん研究 25 (3) 2007年09月 [査読無し][通常論文]
  • 脳皮質電位計測による言語関連脳機能とてんかん焦点活動の時間 周波数変化とネットワークの画像化
    鎌田 恭輔, 川合 謙介, 太田 貴裕, 青木 茂樹, 斉藤 延人 てんかん研究 25 (3) 245 -245 2007年09月 [査読無し][通常論文]
  • 未承認状況下での迷走神経刺激療法の治療適応
    川合 謙介, 清水 弘之, 若井 周二, 太田 貴裕, 鎌田 恭輔, 斎藤 延人 てんかん研究 25 (3) 275 -275 2007年09月 [査読無し][通常論文]
  • 黒岩 正文, 宮本 伸哉, 太田 貴裕, 鎌田 恭輔, 川合 謙介, 斎藤 延人 てんかん研究 25 (2) 2007年08月 [査読無し][通常論文]
  • 外科治療方針決定に難渋した複雑身振り自動症の1例
    黒岩 正文, 宮本 伸哉, 太田 貴裕, 鎌田 恭輔, 川合 謙介, 斎藤 延人 てんかん研究 25 (2) 131 -131 2007年08月 [査読無し][通常論文]
  • Masaki Nishida, Nobuhide Hirai, Fumikazu Miwakeichi, Taketoshi Maehara, Kensuke Kawai, Hiroyuki Shimizu, Sunao Uchida NEUROSCIENCE RESEARCH 58 (2) 215 -217 2007年06月 [査読無し][通常論文]
  • 【脳腫瘍の診断と治療 グリオーマにおける画像診断の役割を中心に】 Fiber trackingの脳腫瘍手術ナビゲーションへの応用
    鎌田 恭輔, 青木 茂樹, 増谷 佳孝, 井野 賢二, 藤堂 具紀, 川合 謙介, 太田 貴裕, 斉藤 延人 臨床放射線 52 (6) 759 -765 2007年06月 [査読無し][通常論文]
  • 適応の破綻と修復 脳機能可塑性の画像化と脳神経疾患の治療戦略
    鎌田 恭輔, 太田 貴裕, 川合 謙介, 斉藤 延人 適応医学 11 (1) 19 -19 2007年05月 [査読無し][通常論文]
  • 鎌田 恭輔, 川合 謙介, 藤堂 具紀, 川原 信隆, 斉藤 延人 脳神経外科ジャーナル 16 (4) 2007年04月 [査読無し][通常論文]
  • 【てんかん外科 てんかん治療の現状と将来】 代替療法 難治性てんかんに対する迷走神経刺激療法の現状
    川合 謙介 カレントテラピー 25 (4) 309 -313 2007年04月 [査読無し][通常論文]
  • 【最近注目される脳神経疾患治療の研究】 難治性てんかんに対する低侵襲治療 迷走神経刺激療法と定位的放射線治療
    川合 謙介 BRAIN and NERVE: 神経研究の進歩 59 (4) 299 -311 2007年04月 [査読無し][通常論文]
  • 神経機能局在と脳神経外科手術 皮質・白質機能の局在と温存 機能MRI/MEGを用いた術前言語関連脳機能局在診断とその検証
    鎌田 恭輔, 川合 謙介, 藤堂 具紀, 川原 信隆, 斉藤 延人 脳神経外科ジャーナル 16 (4) 308 -308 2007年04月 [査読無し][通常論文]
  • 川合 謙介 脳神経外科ジャーナル = Japanese journal of neurosurgery 16 (3) 194 -202 2007年03月 [査読無し][通常論文]
  • 川合 謙介, 清水 弘之 脳神経外科ジャーナル 16 (3) 184 -193 2007年03月 [査読無し][通常論文]
  • 川合 謙介 脳神経外科ジャーナル 16 (3) 194 -202 2007年03月 [査読無し][通常論文]
  • 川合 謙介, 清水 弘之 脳神経外科ジャーナル = Japanese journal of neurosurgery 16 (3) 184 -193 2007年 [査読無し][通常論文]
    Hemispherectomy and its modifications are the most effective treatment for intractable epilepsy with hemispheric foci. In this article, those procedures were historically overviewed, and then the anatomical background and surgical techniques of the latest modification, hemispherotomy, were illustrated along with our refinements. The major anatomical components to be disconnected in hemispherotomy are the corpus callosum and the projection fibers. For each, we compared the approaches we adopted. The interhemispheric callosotomy enabled more reliable disconnection of the callosal fibers than transventricular callosotomy and was especially advantageous for anomalous and asymmetric callosum frequently found in hemimegalencephaly. Transopercular disconnection of the projection fibers overcame the problems encountered in periinsular disconnection but resulted in a higher occurrence of impaired CSF circulation. Reviewing these results we recently adopted vertical hemispherotomy for use with our modification.
  • 川合 謙介, 清水 弘之 脳神経外科ジャーナル 16 (3) 184 -193 2007年 [査読無し][通常論文]
  • 川合 謙介 脳神経外科ジャーナル 16 (3) 194 -202 2007年 [査読無し][通常論文]
  • 鎌田 恭輔, 森田 明夫, 藤堂 具紀, 川合 謙介, 太田 貴裕, 川原 信隆, 斉藤 延人 脳神経外科ジャーナル 16 (3) 206 -214 2007年 [査読無し][通常論文]
    非侵襲的脳機能マッピング法としては,機能MRI (fMRI),脳磁図(MEG)などが挙げられる.また,電気生理学的モニタリング装置の進歩も目覚ましく,さまざまな術中電気生理学的モニタリングを行えるようになった.本稿ではまず,近年臨床に応用されている脳機能画像・モニタリングについて解説する.さらに臨床において,上述した技術を融合することの重要性と,より確実な脳機能温存を目指した頭蓋内病変の切除手術の実際について述べる.われわれの提案したfunctional neuronavigationを用いることで,皮賢-白質機能を把握し,それらの機能を温存しながら頭蓋内病変切除,機能再建にも応用できるものと期待される.
  • 放射線壊死
    川合 謙介 Current Insights in Neurological Science 14 (3) 5 -5 2006年10月 [査読無し][通常論文]
  • 鎌田 恭輔, 川合 謙介, 太田 貴裕, 斉藤 延人 てんかん研究 24 (3) 2006年08月 [査読無し][通常論文]
  • 太田 貴裕, 川合 謙介, 鎌田 恭輔, 斎藤 延人 てんかん研究 24 (3) 2006年08月 [査読無し][通常論文]
  • 川合 謙介, 鎌田 恭輔, 太田 貴裕, 百瀬 敏光, 青木 茂樹, 斎藤 延人 てんかん研究 24 (3) 2006年08月 [査読無し][通常論文]
  • 脳機能画像と慢性硬膜下電極による皮質電気刺激、皮質電位計測結果の比較検討
    鎌田 恭輔, 川合 謙介, 太田 貴裕, 斉藤 延人 てんかん研究 24 (3) 185 -185 2006年08月 [査読無し][通常論文]
  • non-lesional Frontal Lobe epilepsyに対して外科治療をおこなった4例
    太田 貴裕, 川合 謙介, 鎌田 恭輔, 斎藤 延人 てんかん研究 24 (3) 200 -200 2006年08月 [査読無し][通常論文]
  • 側頭葉てんかんに対する海馬多切術後の高次脳機能
    川合 謙介, 鎌田 恭輔, 太田 貴裕, 百瀬 敏光, 青木 茂樹, 斎藤 延人 てんかん研究 24 (3) 219 -219 2006年08月 [査読無し][通常論文]
  • 【術中の皮質脳波】 てんかん外科における術中皮質脳波の有用性
    川合 謙介 臨床脳波 48 (5) 267 -274 2006年05月 [査読無し][通常論文]
    1)てんかん焦点に対する裁断的治療には,高空間解像度の頭蓋内脳波が必要であり,頭蓋内脳波記録法には慢性皮質脳波と術中皮質脳波がある. 2)セボフルレン麻酔下での術中皮質脳波における棘波発射領域は,慢性皮質脳波の発作起始領域を含んでおり,治療対象領域を過大評価する可能性があるが,軟膜下皮質多切など機能温存的手技と併用することにより,幅広い患者を対象として機能を犠牲にせずに高い発作抑制率が期待できる. 3)各々の頭蓋内脳波測定法の長所と短所をふまえて,個々の患者で最適と考えられる取捨選択や組み合わせを行う(著者抄録)
  • 川合 謙介 臨床脳波 48 (5) 267 -274 2006年05月 [査読無し][通常論文]
  • てんかん外科の温故創新 半球切除術から半球離断術まで
    川合 謙介 脳神経外科ジャーナル 15 (4) 319 -319 2006年04月 [査読無し][通常論文]
  • Kensuke Kawai, Kyosuke Kamada, Takahiro Ohta, Toshimitsu Momose, Shigeki Aoki, Akiko Kawashima, Nobuhito Saito EPILEPSIA 47 12 -13 2006年 [査読無し][通常論文]
  • 側頭葉てんかん
    川合 謙介 Current Insights in Neurological Science 14 (1) 6 -6 2006年01月 [査読無し][通常論文]
  • 川合 謙介 脳神経外科ジャーナル 15 (1) 27 -35 2006年 [査読無し][通常論文]
    難治性の側頭葉てんかんに対する標準的前側頭葉切除は, その有効性と安全性から, すでに確立された推奬治療となった.良好な術後成績をもたらす有力な術前因子は限局した画像病変の存在であるが, さらに発作成績を向上させるためには海馬外焦点の同定とその処置が必要となる.新皮質切除を少なくして側頭葉内側に到達するためにいろいろな方法が提唱されているが, 発作成績や術後認知機能についてある術式が他よりも優れているという証拠は今のところない.側頭葉内側構造の安全で確実な切除のためには, (1)側脳室下角への確実な到達, (2)隣接する大脳脚や周回槽内血管への障害回避, 特に海馬溝に入る動静脈の処理, の2点がポイントとなる.
  • 川合 謙介 神経研究の進歩 49 (5) 809 -823 2005年10月 [査読無し][通常論文]
  • 川合 謙介 神経研究の進歩 49 (5) 809 -823 2005年10月 [査読無し][通常論文]
  • 専門医に求められる最新の知識 脳腫瘍 Tractographyと白質マッピング融合型functional neuronavigation
    鎌田 恭輔, 藤堂 具紀, 川原 信隆, 川合 謙介, 森田 明夫, 桐野 高明 脳神経外科速報 15 (8) 751 -759 2005年08月 [査読無し][通常論文]
  • 結節性硬化症のてんかんと認知発達障害
    川合 謙介 Current Insights in Neurological Science 13 (2) 6 -6 2005年08月 [査読無し][通常論文]
  • 【脳神経疾患病棟で起こるけいれんと看護】 けいれんの原因疾患とその病態
    川合 謙介 Brain Nursing 21 (6) 579 -585 2005年06月 [査読無し][通常論文]
  • 川合 謙介 ブレインナーシング 21 (6) 579 -585 2005年06月 [査読無し][通常論文]
  • 川合 謙介 脳神経外科ジャーナル 14 (4) 2005年04月 [査読無し][通常論文]
  • てんかんの外科治療 適応とpitfall回避法 側頭葉切除術
    川合 謙介 脳神経外科ジャーナル 14 (4) 236 -236 2005年04月 [査読無し][通常論文]
  • 機能MRIを用いた言語関連脳領域の局在と皮質刺激による結果の検証
    鎌田 恭輔, 川合 謙介, 増谷 佳孝, 青木 茂樹, 桐野 高明 てんかん研究 23 (1) 44 -45 2005年02月 [査読無し][通常論文]
  • S Sunaga, H Shimizu, K Kawai EPILEPSIA 46 7 -7 2005年 [査読無し][通常論文]
  • H Shimizu, K Kawai, S Sunaga EPILEPSIA 46 21 -21 2005年 [査読無し][通常論文]
  • K Kawai, H Shimizu EPILEPSIA 46 82 -82 2005年 [査読無し][通常論文]
  • T Maehara, T Nariai, N Arai, K Kawai, H Shimizu, K Ishii, K Ishiwata, K Ohno EPILEPSIA 46 76 -77 2005年 [査読無し][通常論文]
  • N Arai, J Mizutani, T Maehara, K Kawai, H Shimizu EPILEPSIA 46 22 -23 2005年 [査読無し][通常論文]
  • 【機能的脳神経外科の最前線】 難治性てんかん 特異な病態に対する外科治療 大脳皮質形成異常
    川合 謙介 Clinical Neuroscience 22 (11) 1273 -1275 2004年11月 [査読無し][通常論文]
  • てんかんの基礎と臨床 側頭葉てんかんの外科的治療と術後記銘力障害
    清水 弘之, 川合 謙介, 須永 茂樹, 山田 俊隆 臨床神経学 44 (11) 868 -870 2004年11月 [査読無し][通常論文]
  • 術中皮質脳波の応用 てんかん外科における術中皮質脳波の有用性 特に側頭葉外てんかんについて
    川合 謙介 臨床神経生理学 32 (5) 431 -432 2004年10月 [査読無し][通常論文]
  • Optic radiation tractographyと皮質VEPモニタリング融合によるFunctional Neuronavigation
    鎌田 恭輔, 藤堂 具紀, 川合 謙介, 青木 茂樹, 増谷 佳孝, 森田 明夫, 桐野 高明 臨床神経生理学 32 (5) 566 -566 2004年10月 [査読無し][通常論文]
  • 片側巨脳症・水頭症を認め日齢71で機能的半球離断術を施行された一例
    竹村 祥子, 五石 圭司, 久保田 雅也, 川合 謙介 脳と発達 36 (Suppl.) S299 -S299 2004年06月 [査読無し][通常論文]
  • 小児の機能的疾患の手術適応・外科的治療 大脳半球離断を施行したスタージウエーバー症候群の2例
    中西 肇, 新井 一, 菅野 秀宣, 川合 謙介, 清水 弘之 小児の脳神経 29 (2) 201 -201 2004年04月 [査読無し][通常論文]
  • 難治性てんかん焦点部における微小形成不全 同一施設における焦点切除全532例の解析
    新井 信隆, 前原 健寿, 川合 謙介, 清水 弘之 てんかん研究 22 (1) 28 -28 2004年02月 [査読無し][通常論文]
  • 難治性てんかんに対する半球離断術式の比較と新しい工夫
    川合 謙介, 清水 弘之, Delalande Olivier てんかん研究 22 (1) 37 -37 2004年02月 [査読無し][通常論文]
  • 異なる機序に由来すると思われる転倒発作を伴う側頭葉てんかんの2症例
    須永 茂樹, 清水 弘之, 川合 謙介 てんかん研究 22 (1) 41 -41 2004年02月 [査読無し][通常論文]
  • Hippocampal transectionによる左側頭葉てんかんの外科的治療と言語性記銘力の温存
    清水 弘之, 川合 謙介, 須永 茂樹 てんかん研究 22 (1) 45 -45 2004年02月 [査読無し][通常論文]
  • 新井 信隆, 水谷 俊雄, 前原 健寿, 川合 謙介, 清水 弘之 日本てんかん学会プログラム・予稿集 (37) 2003年10月 [査読無し][通常論文]
  • 川合 謙介, 清水 弘之, Delalande Olivier 日本てんかん学会プログラム・予稿集 (37) 2003年10月 [査読無し][通常論文]
  • 須永 茂樹, 清水 弘之, 川合 謙介 日本てんかん学会プログラム・予稿集 (37) 2003年10月 [査読無し][通常論文]
  • 清水 弘之, 川合 謙介, 須永 茂樹 日本てんかん学会プログラム・予稿集 (37) 2003年10月 [査読無し][通常論文]
  • 【てんかんの神経生理】 前頭葉てんかん手術後の脳機能
    清水 弘之, 川合 謙介 臨床脳波 45 (8) 475 -479 2003年08月 [査読無し][通常論文]
    MRI上器質的疾患を有さない前頭葉てんかん9例を対象に前頭葉眼窩面切除術を行い,術後の大脳機能変化をWisconsinカードソーティングテスト(WCST),Modified Stroop Test,聴覚性言語学習テストを用いて解析した.その結果,言語優位半球左側の眼窩面切除例5例では,いずれも手術直後からWCSTの悪化やModified Stroop Testの変化を認めなかった.また,聴覚性言語学習テストでは1例を除き,全く変化を示さないか軽度の改善を示した.一方,両側前頭葉眼窩切除例4例中3例では,手術直後にWCSTおよびModified Stroop Test成績の低下を認めたが,半年から一年の経過で全例ほぼ術前レベルかやや改善傾向を示した.また,聴覚性言語学習テストでは術後著変した例はなく,半年〜1年後の経過で全例術前よりも改善傾向を示した
  • 清水 弘之, 川合 謙介 臨床脳波 = Clinical electroencephalography : 脳波・筋電図と臨床神経生理 45 (8) 475 -479 2003年08月 [査読無し][通常論文]
  • 左側脳室三角部近傍腫瘍の一例
    永井 正一, 上山 浩永, 栗本 昌紀, 平島 豊, 遠藤 俊郎, 川合 謙介 Brain Tumor Pathology 20 (Suppl.) 52 -52 2003年05月 [査読無し][通常論文]
  • てんかん外科病理における形成異常と脳腫瘍
    新井 信隆, 小森 隆司, 水谷 俊雄, 川合 謙介, 清水 弘之 Brain Tumor Pathology 20 (Suppl.) 82 -82 2003年05月 [査読無し][通常論文]
  • 両側広範な大脳皮質形成異常に伴う難治性てんかんに対する全脳梁離断術の効果
    川合 謙介, 清水 弘之, 前原 健寿, 玉川 公子 脳と発達 35 (Suppl.) S184 -S184 2003年05月 [査読無し][通常論文]
  • 新井 信隆, 前原 健寿, 川合 謙介, 水谷 俊雄, 村上 秀喜, 田邊 豊, 清水 弘之 Neuropathology : official journal the Japanese Society of Neuropathology 23 2003年05月 [査読無し][通常論文]
  • 良性脳腫瘍を伴う側頭葉てんかん患者におけるメチオニンPETの有用性
    前原 健寿, 成相 直, 新井 信隆, 川合 謙介, 清水 弘之, 石井 賢二, 大野 喜久郎 てんかん研究 21 (1) 50 -51 2003年02月 [査読無し][通常論文]
  • 側頭葉前底部に焦点を有する側頭葉てんかんの診断と外科治療
    川合 謙介, 清水 弘之 てんかん研究 21 (1) 59 -60 2003年02月 [査読無し][通常論文]
  • 三分一 史和, 内田 直, 荒垣 宏, 平井 伸英, 前原 健寿, 川合 謙介, 清水 博之 日本統計学会誌 32 (3) 2002年12月 [査読無し][通常論文]
  • 直達手術によるマウス中大脳動脈近位閉塞モデルの開発とその特性の検討
    古屋 一英, 川原 信隆, 川合 謙介, 豊田 富勝, 前田 佳一郎, 桐野 高明 脳循環代謝 14 (3) 230 -231 2002年09月 [査読無し][通常論文]
  • 【Radiosurgeryの最前線 現況と展望】 Radiosurgeryに望むこと てんかん治療におけるradiosurgeryの展望 てんかん外科の立場から
    川合 謙介 医学のあゆみ 別冊 (Radiosurgeryの最前線-現況と展望) 121 -125 2002年09月 [査読無し][通常論文]
  • 三分一 史和, 内田 直, 荒垣 宏, 平井 伸英, 前原 健寿, 川合 謙介, 清水 博之 日本統計学会講演報告集 70 303 -304 2002年09月 [査読無し][通常論文]
  • 【てんかん update】 てんかんの外科療法 難治性てんかんに対するガンマナイフ治療
    川合 謙介 Clinical Neuroscience 20 (7) 828 -829 2002年07月 [査読無し][通常論文]
  • 両側広汎な大脳形成異常に伴う難治性てんかんに対する脳梁離断術の効果
    川合 謙介, 清水 弘之, 前原 健寿, 村上 秀喜, 玉川 公子, 柳下 章 脳と発達 34 (Suppl.) S105 -S105 2002年06月 [査読無し][通常論文]
  • 脳波・筋電図の臨床 ヒトの辺縁系における覚醒睡眠時の脳波律動
    内田 直, 西多 昌規, 平井 伸英, 川合 謙介, 清水 弘之, 前原 健寿 臨床脳波 44 (6) 361 -366 2002年06月 [査読無し][通常論文]
  • 新井 信隆, 清水 弘之, 川合 謙介, 玉川 公子, 水谷 俊雄, 永田 仁郎, 倉田 清子, 海津 怜子, 林 雅晴, 小森 隆司, 森松 義雄 Neuropathology : official journal the Japanese Society of Neuropathology 22 2002年05月 [査読無し][通常論文]
  • クリニカルテクニック 難治性てんかんに対する迷走神経刺激療法
    川合 謙介 Clinical Neuroscience 20 (2) 234 -235 2002年02月 [査読無し][通常論文]
  • 結節性硬化症に伴う難治性てんかんの外科的治療戦略
    川合 謙介, 清水 弘之, 前原 健寿, 村上 秀喜, 新井 信隆, 柳下 章, 繁友 律子, 玉川 公子 てんかん研究 20 (1) 63 -63 2002年02月 [査読無し][通常論文]
  • 軟膜下皮質多切術(multiple subpial transection)の処置巣の形態学的,免疫組織学的解析
    新井 信隆, 川合 謙介, 村上 秀喜, 前原 健寿, 水谷 俊雄, 清水 弘之 てんかん研究 20 (1) 66 -66 2002年02月 [査読無し][通常論文]
  • 内側側頭葉てんかんの外科治療における非発作時[18F]FDG-PETの有効性
    浅野 修一郎, 川合 謙介, 鈴木 一郎, 百瀬 敏光, 川原 信隆, 森田 明夫, 桐野 高明 てんかん研究 20 (1) 59 -60 2002年02月 [査読無し][通常論文]
  • 側頭葉てんかんに対するガンマナイフ治療の至適線量分布 低線量照射が無効であった症例の病理学的検討
    川合 謙介, 鈴木 一郎, 新井 信隆, 栗田 浩樹, 辛 正廣, 桐野 高明 てんかん研究 20 (1) 63 -64 2002年02月 [査読無し][通常論文]
  • 外科的治療が奏効した両側前頭葉眼窩面起始の複雑部分発作の1例
    村上 秀喜, 川合 謙介, 清水 弘之 てんかん研究 20 (1) 64 -64 2002年02月 [査読無し][通常論文]
  • マウス一過性心停止モデルにおける海馬の虚血性神経細胞死 マウス海馬は虚血抵抗性か?
    川原 信隆, 川合 謙介, 豊田 富勝, 古屋 一英, 斎藤 延人, 中冨 浩文, 桐野 高明 脳循環代謝 13 (4) 239 -240 2001年12月 [査読無し][通常論文]
  • 【難治性てんかんの治療】 難治性てんかんの外科的適応
    川合 謙介 脳の科学 23 (11) 941 -950 2001年11月 [査読無し][通常論文]
  • 難治性てんかんに対する迷走神経刺激療法の長期成績
    川合 謙介, 清水 弘之 臨床神経学 41 (11) 960 -960 2001年11月 [査読無し][通常論文]
  • 川合 謙介, 清水 弘之, 前原 健寿, 村上 秀喜, 新井 信隆, 柳下 章, 繁友 律子, 玉川 公子 日本てんかん学会プログラム・予稿集 (35) 2001年09月 [査読無し][通常論文]
  • 川合 謙介, 鈴木 一郎, 新井 信隆, 栗田 浩樹, 辛 正廣, 桐野 高明 日本てんかん学会プログラム・予稿集 (35) 2001年09月 [査読無し][通常論文]
  • 新井 信隆, 川合 謙介, 村上 秀喜, 前原 健寿, 水谷 俊雄, 清水 弘之 日本てんかん学会プログラム・予稿集 (35) 2001年09月 [査読無し][通常論文]
  • 浅野 修一郎, 川合 謙介, 鈴木 一郎, 百瀬 敏光, 川原 信隆, 森田 明夫, 桐野 高明 日本てんかん学会プログラム・予稿集 (35) 2001年09月 [査読無し][通常論文]
  • 村上 秀喜, 川合 謙介, 清水 弘之 日本てんかん学会プログラム・予稿集 (35) 2001年09月 [査読無し][通常論文]
  • 【脳波のGamma activity】 ヒトの後頭葉皮質におけるガンマオシレーション
    平井 伸英, 内田 直, 前原 健寿, 川合 謙介, 清水 弘之 臨床脳波 43 (8) 479 -484 2001年08月 [査読無し][通常論文]
  • 難治性てんかんに対する迷走神経刺激療法の長期成績
    川合 謙介, 清水 弘之, 前原 健寿, 村上 秀喜 東京都医師会雑誌 54 (5) 589 -591 2001年06月 [査読無し][通常論文]
    難治性局在関連癲癇15例に対して迷走神経刺激療法(VNS)を行った.全経過中全く無効であった1例を除くと治療開始前に対する発作頻度はVNSにより減少しその後は安定する傾向がみられた.又,全般発作や複雑部分発作は単純部分発住より早期に減少する傾向がみられた.両側前頭葉に癲癇性脳波異常を有し,atypical absenceやnonconvulsive status epilepticusを呈する患者にも有効であった.又,disablingな発作ほど早期に減少する傾向は難治性癲癇の患者にとって利点の一つに挙げられた.VNSでは根治的外科治療と異なり,発作を完全に消失させることは不可能であるが,根治的外科治療が不可能又は無効な例では,低侵襲な代替治療として大いに期待される
  • 小児難治性てんかんに対する半球離断術後の大脳形態成長と精神運動発達
    川合 謙介, 清水 弘之, 前原 健寿, 村上 秀喜 脳と発達 33 (Suppl.) S256 -S256 2001年05月 [査読無し][通常論文]
  • 側頭葉てんかんの成因としての人ヘルペス6(HHV-6)脳炎(軽症)について
    上杉 秀二, 南 成祐, 清水 弘之, 川合 謙介, 水谷 俊雄, 中山 宏, 新井 信隆 臨床神経生理学 29 (2) 199 -199 2001年04月 [査読無し][通常論文]
  • 難治性てんかんに対する迷走神経刺激療法の長期成績
    川合 謙介, 清水 弘之, 前原 健寿, 村上 秀喜 てんかん研究 19 (1) 59 -59 2001年02月 [査読無し][通常論文]
  • 脳腫瘍に起因する側頭葉てんかんと海馬病理所見 てんかん発作の海馬への影響
    上杉 秀二, 清水 弘之, 新井 信隆, 前原 健寿, 水谷 俊雄, 川合 謙介, 中山 宏 てんかん研究 19 (1) 58 -59 2001年02月 [査読無し][通常論文]
  • 外科手術著効例から検討した非器質性前頭葉性複雑部分発作の解析
    前原 健寿, 清水 弘之, 川合 謙介, 村上 秀喜 てんかん研究 19 (1) 57 -58 2001年02月 [査読無し][通常論文]
  • マウス心停止モデルにおける海馬の虚血性神経細胞死 マウス海馬は虚血抵抗性か?
    川原 信隆, 川合 謙介, 豊田 富勝, 斎藤 延人, 中冨 浩文, 桐野 高明 日本脳神経外科学会総会抄録集 59回 192 -192 2000年10月 [査読無し][通常論文]
  • 難治性てんかんに対する迷走神経刺激療法の手技と長期成績
    川合 謙介, 清水 弘之, 前原 健寿, 村上 秀喜 日本脳神経外科学会総会抄録集 59回 43 -43 2000年10月 [査読無し][通常論文]
  • 非器質性の前頭葉前部難治てんかんの外科治療
    前原 健寿, 清水 弘之, 川合 謙介, 村上 秀喜 日本脳神経外科学会総会抄録集 59回 54 -54 2000年10月 [査読無し][通常論文]
  • 前原 健寿, 清水 弘之, 川合 謙介, 村上 秀喜 日本てんかん学会プログラム・予稿集 (34) 2000年09月 [査読無し][通常論文]
  • 上杉 秀二, 清水 弘之, 新井 信隆, 前原 健寿, 水谷 俊雄, 川合 謙介, 中山 宏 日本てんかん学会プログラム・予稿集 (34) 2000年09月 [査読無し][通常論文]
  • 川合 謙介, 清水 弘之, 前原 健寿, 村上 秀喜 日本てんかん学会プログラム・予稿集 (34) 2000年09月 [査読無し][通常論文]
  • 側頭葉てんかんの診断におけるMRIの有用性と限界
    川合 謙介, 鈴木 一郎, 桐野 高明 脳神経外科速報 9 (11) 939 -940 1999年11月 [査読無し][通常論文]
  • 虚血性脳障害におけるグルタミン酸トランスポーターの役割に関する実験的研究
    川合 謙介 臨床成人病 29 (10) 1376 -1377 1999年10月 [査読無し][通常論文]
  • 脳虚血 アポトーシス抑制蛋白質XIAPの成長期及び虚血ラット脳における発現
    斉藤 延人, 川原 信隆, 川合 謙介, 淺井 昭雄, 桐野 高明 日本脳神経外科学会総会抄録集 58回 72 -72 1999年10月 [査読無し][通常論文]
  • 脳神経外科疾患と細胞死研究の最前線 calcineurin発現による神経細胞脆弱性の増加と細胞死誘導
    淺井 昭雄, 秋 建華, 篠浦 伸禎, 成田 善孝, 斎藤 延人, 川合 謙介, 川原 信隆, 桐野 高明 日本脳神経外科学会総会抄録集 58回 293 -293 1999年10月 [査読無し][通常論文]
  • 海馬CA1の虚血性遅発性神経細胞死におけるGluR2仮説の検証
    川合 謙介, 川原 信隆, 斉藤 延人, 中富 浩文, 桐野 高明 日本脳神経外科学会総会抄録集 58回 365 -365 1999年10月 [査読無し][通常論文]
  • 虚血耐性 Adenosine受容体を介する虚血耐性増強効果
    川原 信隆, 井手 隆文, 斉藤 延人, 川合 謙介, 桐野 高明 脳循環代謝 11 (1) 12 -13 1999年07月 [査読無し][通常論文]
    propentofylline(PPF)が,虚血耐性に及ぼす影響を検討した.2分虚血により虚血耐性を誘導し,その48時間後に5分虚血を行う砂ネズミ一過性前脳虚血モデルを用いた.薬剤は,2分虚血24時間後にvehicle,PPF10mg/kg,PPF20mg/kgを腹腔内投与し,更にnon-selective adenosine receptor antagonistであるtheophyllineを同時投与した.又,PPF20mg/kgを5分単独虚血24時間前に投与して,その影響を検討した.vehicle群では,preconditioning ischemiaによる海馬CA1錘体細胞死への保護効果が認められ,PPF10mg/kgでも同様であった.しかし,PPF20mg/kg投与群ではこれら2群に対し有意にCA1錐体細胞障害が軽く,虚血耐性増強効果が確認された.更に,この増強効果はtheophyllineの同時投与によって消失した
  • Proapoptotic factor Bak及びBadのラット脳での発現と一過性前脳虚血後の変化
    川原 信隆, 川合 謙介, 斎藤 延人, 中富 浩文, 伊地 俊介, 桐野 高明 脳卒中 21 (1) 180 -180 1999年03月 [査読無し][通常論文]
  • 側頭葉焦点に対するガンマナイフ治療の効果
    川合 謙介, 鈴木 一郎, 栗田 浩樹, 辛 正廣, 桐野 高明 てんかん研究 17 (1) 58 -58 1999年02月 [査読無し][通常論文]
  • 【神経細胞制御】 遺伝的要因と環境因子の相互作用 グルタミン酸興奮毒性と虚血性神経細胞死
    川合 謙介, 桐野 高明 医学のあゆみ 別冊 (神経細胞死制御) 85 -89 1998年11月 [査読無し][通常論文]
  • 川合 謙介, 鈴木 一郎, 栗田 浩樹, 辛 正廣, 桐野 高明 日本てんかん学会プログラム・予稿集 (32) 1998年10月 [査読無し][通常論文]
  • 虚血耐性現象の電気生理学的検討
    川合 謙介, 中込 忠好, 桐野 高明, 田村 晃, 川合 述史 神経化学 37 (3) 475 -475 1998年09月 [査読無し][通常論文]
  • in vivo前負荷虚血は海馬スライスにおけるanoxic LTPを抑制する
    川合 謙介, 中込 忠好, 桐野 高明, 田村 晃, 川合 述史 脳循環代謝 10 (2) 236 -237 1998年09月 [査読無し][通常論文]
  • 釣田 義一郎, 上野 照剛, 名川 弘一, 武藤 徹一郎, 川合 謙介, 桐野 高明, 多氣 昌生 日本応用磁気学会学術講演概要集 = Digest of ... annual conference on magnetics in Japan 22 1998年09月 [査読無し][通常論文]
  • 斉藤 延人, 川原 信隆, 川合 謙介, 桐野 高明 神経組織の成長・再生・移植 10 (1) 39 -40 1998年06月 [査読無し][通常論文]
  • 難治てんかんに対する定位的放射線治療
    鈴木 一郎, 栗田 浩樹, 川合 謙介, 佐々木 富男, 桐野 高明 日本脳神経外科学会総会抄録集 56回 44 -44 1997年10月 [査読無し][通常論文]
  • クモ膜下出血発症に気象要因は本当に関係しているのか?
    川合 謙介, 野中 浩一, 成田 孝而, 中込 忠好, 中山 比登志, 桐野 高明, 田村 晃 日本脳神経外科学会総会抄録集 56回 291 -291 1997年10月 [査読無し][通常論文]
  • くも膜下出血の予後について 過去15年に経験した症例の検討
    高木 清, 田村 晃, 中込 忠好, 永島 博, 古屋 一英, 西原 哲浩, 川合 謙介 脳血管攣縮 12 344 -347 1997年07月 [査読無し][通常論文]
  • 川合 謙介, 佐々木 富男, 藤巻 高光, 石田 剛, 桐野 高明 Neuropathology : official journal the Japanese Society of Neuropathology 17 (Suppl.) 279 -279 1997年05月 [査読無し][通常論文]
  • 石田 剛, 佐々木 富男, 藤巻 高光, 三島 一彦, 川合 謙介, 桐野 高明, 町並 陸生 Neuropathology : official journal the Japanese Society of Neuropathology 17 (Suppl.) 295 -295 1997年05月 [査読無し][通常論文]
  • 脳低体温療法 その基礎と臨床 前脳虚血モデルにおける低脳温の効果
    川合 謙介, 桐野 高明 集中治療 9 (6) 627 -634 1997年05月 [査読無し][通常論文]
  • 頭蓋底骨折に伴う外傷性下垂体損傷の検討
    川合 謙介 日本脳神経外科学会総会抄録集 53回 155 -155 1994年10月 [査読無し][通常論文]
  • ラット一過性全脳虚血における視床網様核の選択的脆弱性
    川合 謙介 脳循環代謝 5 (1) 130 -130 1993年11月 [査読無し][通常論文]
  • ラット一過性全脳虚血後に認められるangiogenic seizure susceptibility
    川合 謙介 脳循環代謝 5 (1) 62 -62 1993年11月 [査読無し][通常論文]
  • 医師に必要とされる放射線防護の基本的知識
    吉沢 康雄, 草間 朋子, 川合 謙介 日本医事新報 (3265) 43 -47 1986年11月 [査読無し][通常論文]


  • 1999年 日本脳卒中学会草野賞
  • 1993年 日本脳神経外科学会ガレヌス賞


  • てんかんと記憶に関わる脳内機能的結合性の特性抽出と外科的及び電気刺激による介入
    研究期間 : 2017年04月 -2020年03月 
    代表者 : 川合 謙介
  • 文部科学省:科学研究費補助金(基盤研究(C))
    研究期間 : 2014年 -2016年 
    代表者 : 川合 謙介
  • 文部科学省:科学研究費補助金(基盤研究(B))
    研究期間 : 2012年 -2015年 
    代表者 : 鎌田 恭輔, 川合 謙介, 竹内 文也
    ヒト脳機能解読に頭蓋内電極から得られる認知関連機能脳表電位(ECoG)は、最も髙い信号/雑音(S/N)比を有するため注目を集めている。本申請では複数の言語、記憶課題を組み合わせて、認知ECoGを検討し、言語・記憶ネットワークを解明する。さらに計測症例のECoGを標準脳変換することで脳全体を広範囲、かつ高密度に電極で覆うことが可能となる (標準化ECoG)。本法により言語・記憶などの複雑な脳機能の典型ダイナミクスが明らかとなる。この解読結果を出力系デバイスと融合してリアルタイム処理Brain-machine interface (BMI)開発を目指す。またECoG周波数等の変化を同様の課題機能MRI(fMRI)とTractographyを個人・標準脳間で比較することで、fMRIの生理学的意味、臨床応用へのフィードバック、脳内ネットワークの解釈、適切なBMI用硬膜下電極位置、数を決定することができる。BMIによる出力目標は、意志疎通のための文字提示、音声提示法の確立とする。標準化した認知ECoGのテンプレートを課題毎に作成する。課題は1、単純なストライプ視覚認知、2、単純図形認知, 3, ひらがな一文字;音読、3, 黙読、4,1音節(文字)想起を基礎実験とする。 いずれもわずかなECoG反応変化を捉えるため、前述した機能テンプレートを用いることで解読精度の向上が期待できる。一台のコンピュータから直接視覚、聴覚刺激提示、およびデータ保存、解析を行う。コンピュータの高速化によりリアルタイムに脳皮質電位の周波数解析、抽出、表示を可能とした。これにより従来の電気刺激を行わずにベッドサイドでヒト運動・言語・記憶機能を抽出することに成功した。さらに本システムを手術室内に持ち込み、覚醒下手術に応用した。覚醒下の患者脳表面に留置した硬膜下電極から脳皮質電位を計測することができた。また、リアルタイム周波数解析により、覚醒下手術における脳機能マッピングができることが検証できた。
  • 文部科学省:科学研究費補助金(基盤研究(A))
    研究期間 : 2011年 -2014年 
    代表者 : 神保 泰彦, 川合 謙介, 佐久間 一郎, 湯ノ口 万友
    平成25年度の研究実施計画として設定した検討課題に対して以下の成果を得た.(1)脳幹神経核から採取した細胞群の培養海馬,大脳皮質等上位の中枢神経系に広範囲調節系として作用し,かつその同期活動(同期活動制御が正常な範囲を逸脱した場合にてんかん様の活動が発生すると考えるのが本研究の立場である)制御に本質的な役割を担うと考えられる背側縫線核 (dorsal raphe nucleus; DRN, セロトニン作動性)の細胞群採取とその培養手法確立を重点的に進めた(ノルアドレナリン作動性青斑核; LCについてはH24年度に実施).今回,ラット新生児から採取した脳幹細胞群を分散培養し,5-Tryptophan Hydroxylaseを指標とする免疫化学染色による評価を実施した.高効率に当該部位を摘出,採取するプロセスを確立することができた.また,微小電極アレイ基板(MicroElectrode Array; MEA)上で培養した細胞群から培養13日目の時点で自発電気活動を計測することに成功した.(2)海馬培養神経回路の同期電気活動に対する神経調節物質の効果ノルアドレナリン(NE)投与の効果につき,同期活動の指標であるネットワークバーストに焦点を絞って計測・解析した.スパイク数,バースト数,バースト持続時間,バースト活動の空間的な広がり,のいずれにおいてもNE投与による抑制効果が観測され,NE作動性神経核活動の抗てんかん効果を示唆する結果となった.同時にこの効果が培養神経回路の発達段階に依存して変化する可能性が示唆され,培養開始後2,3,4週間の試料に対するNE投与の効果を系統的に調べた.発生するバースト数が減少する傾向は全ての試料に共通であったが,1バーストの持続時間と含まれるスパイク数,バースト活動の空間的な広がりについては3週間までとそれ以降で異なる傾向を示すことがわかった.
  • 文部科学省:科学研究費補助金(基盤研究(B))
    研究期間 : 2009年 -2012年 
    代表者 : 川合 謙介, 鎌田 恭輔, 辛 正廣, 鎌田 恭輔
  • 文部科学省:科学研究費補助金(基盤研究(C))
    研究期間 : 2004年 -2006年 
    代表者 : 川合 謙介, 鎌田 恭輔
  • 文部科学省:科学研究費補助金(基盤研究(B))
    研究期間 : 1999年 -2001年 
    代表者 : 鈴木 一郎, 豊田 富勝, 川合 謙介, 辛 正廣, 杉下 守弘, 浅野 修一郎
    難治性側頭葉てんかんに対して一般的には選択的海馬扁桃体切除術が行われているが、我々はこの方法を一歩前進させる方法として1996年よりガンマナイフによる海馬扁桃体の定位的放射線照射を行った。本研究に登録された症例は男2例、女5例の計7例。このうち2例(男1例、女1例)では低線量(18Gy 50%照射線量)ガンマナイフ治療を施行、他の5例(男1例、女4例)では高線量(25Gy 50%照射線量)ガンマナイフ治療を施行した。各症例ともガンマナイフ治療の前後で高次機能検査を施行した。またictal-SPECT, PET, functional MRIも可能な症例において施行した。2例の低線量ガンマナイフ治療群ではそれぞれ30ヶ月、16ヶ月の追跡でも発作頻度に変化はなく治療の有効な結果が得られず、最終的には両症例とも外科的手術を施行しててんかん発作の消失をみた。またMRIにて組織反応は出現せず、高次機能検査においてもガンマナイフ治療前後で変化は認められなかった。切除標本の病理像は、通常の海馬硬化所見に加え反応性星細胞の増殖、変性神経細胞の存在など明らかな放射線照射に対する組織反応が見られたが壊死巣は小さいかもしくは見られずこの程度の組織変化では補佐速成にはつながらず、非組織障害性の照射線量で発作を抑制できる可能性は低いと考えられた。一方、高線量治療群においてガンマナイフ照射後にMRIにて海馬の組織変化及び広範な脳浮腫が認められたがいずれの症例においても発作頻度の有意な減少は認められなかった。以上の結果と文献での報告から、発作抑制には側頭葉内側構造の大部分に壊死巣を形成するほどの線量が必要と考えられる。しかし高線量では低侵襲とはいい難い脳のダメージがあり、真の有効性や至適線量分布に関しては未確定と言わざるを得ない。小壊死巣であっても至適部分であれば発作を抑制できる可能性は残されており、照射体積を減らすことで脳浮腫の軽減をはかることができると期待できる。
  • 文部科学省:科学研究費補助金(基盤研究(C))
    研究期間 : 1999年 -2000年 
    代表者 : 斉藤 延人, 川合 謙介
    神経細胞におけるXIAPの発現を確認し、脳虚血後の神経細胞の生存にXIAPの発現が関与するのかを明らかにし、さらにXIAPの過剰発現により、神経細胞のアポトーシス、及び虚血性神経細胞死が制御できるのかどうかを明らかすることを本研究の目的とした。脳虚血はラットの4血管閉塞モデルで作成し、海馬、大脳皮質におけるXIAPの発現をwestern blottingで解析した。前年度に明らかにした虚血後のXIAP mRNAの発現増加に反し、XIAPの発現は蛋白レベルでは変化がなかった。この結果より、おそらく蛋白合成障害によるXIAP蛋白の合成不全が遅発性神経細胞死の一因となっている可能性が考えられた。次いでラットXIAP c DNAをアデノウィルスベクターにいれ、ラットIAPを大量発現するアデノウィルスを作成し、神経系細胞のアポトーシスを抑制できるかどうかを検討した。NGF存在化に神経細胞に分化したPC12細胞でラットXIAPをアデノウィルスベクターにより大量発現させた。NGF除去によりアポトーシスを誘導すると、コントロールのlacZでは細胞死が起こったが、XIAPを高発現させたPC12細胞ではアポトーシスが抑制された。これらの結果から、XIAPは神経細胞のアポトーシスを防ぐ能力があり、虚血後の神経細胞ではXIAPが必要とされているが、おそらく蛋白合成障害によるXIAP蛋白の合成不全があり神経細胞死がおこる可能性が考えられた。XIAPの機能不全が遅発性神経細胞死の一因となっている可能性が考えられたが、虚血神経細胞保護効果に関してはさらに検討が必要である。
  • 文部科学省:科学研究費補助金(基盤研究(B))
    研究期間 : 1999年 -2000年 
    代表者 : 桐野 高明, 川合 謙介, 川原 信隆
    虚血性細胞死におけるグルタミン酸濃度の異常上昇の引き金となるのがグルタミン酸トランスポーターの逆転による、という仮説に立脚し、グルタミン酸トランスポーターを阻害した状態での細胞外グルタミン酸濃度や虚血性神経細胞死の変化を捉えるべく、平成12年度はin vivoモデルにおいて、以下の実験を行った。(1)グルタミン酸トランスポーター阻害薬の脳内微小透析法による灌流投与砂ネズミ海馬にグルタミン酸トランスポーター阻害薬であるグルタミン酸アナログ(tPDC)を脳内微小透析法にて投与し、一過性全脳虚血を加えた。(a)tPDC灌流により細胞外グルタミン酸濃度の上昇が確認された。(b)tPDC前投与した砂ネズミに一過性全脳虚血を加えたが、vehicleと同様のCA1細胞死が認められ、明らかな保護効果は認められなかった。(2)グルタミン酸トランスポーターノックアウトマウスを使った脳梗塞作成Homoマウスの収穫率が悪く、ヘテロ同志から回収されるのはわずか5%であった。痙攣発作による早期死亡が報告されているが、バルプロ酸投与にてこれは防止された。HomoとWildとを局所脳虚血(中大脳動脈永久閉塞)に供し脳梗塞体積の比較を行った。(a)梗塞体積はwildが12.6±10.3mm^3,homoが12.6±6.8mm^3)と有意差を認めなかった。平成13年度は(2)を進め、弱い虚血、つまり1時間での虚血再灌流を行って脳梗塞体積の比較を行っている。すでにこのモデルも当教室にて確立している。
  • 文部科学省:科学研究費補助金(基盤研究(C))
    研究期間 : 1999年 -2000年 
    代表者 : 川合 謙介, 斉藤 延人
    最近、虚血後にAMPA型受容体のサブユニット構成が変化することによりAMPA型受容体がカルシウム透過性を持つようになり,遅発性神経細胞死を引き起こす可能性が示唆されたが(GluR2仮説),in vivoでの直接的証拠はいまだ無い.本研究は,GluR2仮説をin vivoで直接的に検証することを目的とする.すなわち,カルシウム非透過性を決定するサブユニットGluR2を持たないAMPA型受容体を選択的に阻害する薬剤を脳虚血動物モデルに投与することにより,海馬CA1細胞の虚血性神経細胞死を抑制することが可能かどうかを検討した.虚血モデルには砂ネズミの両側総頚動脈5分間閉塞モデルを用い,カルシウム透過型AMPA型グルタミン酸受容体の選択的阻害薬である1-naphythyl-acetyl spermin(Nasp)を人工髄液に溶解し様々な濃度および時間で左側脳室内投与した.動物は虚血後7日で潅流固定しCA1の残存細胞数を計測した.mini-osmotic pumpを用い,8ul/hで虚血後2〜7時間から24時間連続投与した場合,わずかな保護効果が認められたが,その効果は僅少であった。lul/hで虚血前日から7日間連続投与した場合(1,5,10,50mM),25mMを2.5ul/10minで1回投与した場合(虚血後1時間,24時間)には有意の保護効果は認められなかった.砂ネズミ一過性前脳虚血による海馬CA1遅発性神経細胞死ではGluR2仮説で提唱された虚血後のAMPA型受容体を介したカルシウム流入は,その細胞死進行の機構において大きな役割を担っているとは考えにくいことが示唆された.平成12年度には,視床網様核ニューロンなど海馬CA1ニューロン以外の神経細胞における虚血性神経細胞死でのGluR2仮説の検証を行う予定である.
  • 文部科学省:科学研究費補助金(基盤研究(C))
    研究期間 : 1997年 -1998年 
    代表者 : 井手 隆文, 川合 謙介, 藤巻 高光, 井手 隆文
    リン脂質のひとつであるsphingosine-1-phosphate(Sph-1-P)が、単にsphingosineの代謝産物ではなく、細胞内の重要な情報伝達物質であり細胞内Ca貯蔵庫より細胞内にCaを放出させる作用を有し脳に豊富に存在するが、本研究は砂ネズミ海馬CA1神経細胞の遅発性神経細胞死に至る過程とSph-1-Pとの関連を明らかにすることにある。平成10年度は、本年度は、Sph-1-P測定系の確立と砂ネズミのnormal controlにおける脳の部位別のSph-1-Pの定量を施行した。砂ネズミの海馬、大脳皮質、小脳からice cold chloroform/methanol(1:2)3mlにてSph-1-Pを抽出し、HPLCにて定量測定した。海馬と大脳皮質からはSph-1-Pは検出されなかったが、小脳からは検出された。この測定法自体の感度に問題があることも予想されたが、部位特異的にSph-1-Pが分布していることも示唆された。上記の結果に基づいて同様のsampleにてSph-1-Pをradioimmunoassay法にて定量した。検出感度はHPLCよりも高いとされている測定方法である。海馬、大脳皮質、小脳はそれぞれ5.42±1.90,0.84±0.21,4.29±1.67 nmol/mg(mean±SEM,n=5)であった。以上より、Sph-1-Pは部位によって含有量に差があり、部位特異的な細胞機能を担っていることが示唆された。平成11年度には、一過性前脳虚血によるSph-1-Pの変動を解析した。砂ネズミ(雄性60-80g)にハロセン麻酔を施行し、頚部正中皮膚切開後に両側総頚動脈を露出し、動脈瘤用クリップを用いて5分間の前脳虚血を負荷した。この間、heatlampとブランケットを用いて側頭筋温と直腸温を37.5℃に維持した。虚血前と再潅流後6,12,24,48時間で麻酔下に断頭して、直ちに、海馬、大脳皮質、小脳をそれぞれ取り出し、前述の方法のうちradioimmunoassay法を用いてSph-1-Pを定量した。各々、正常対照群、虚血6時間後、虚血24時間後、虚血48時間後の値を示す。海馬:5.42±1.90,4.63±1.24,4.62±1.55,4.89±1.73(nmol/mg,mean±SEM,n=5)大脳皮質:0.84±0.21,0.67±0.19,0.72±0.12,0.63±0.15(nmol/mg,mean±SEM,n=5)小脳:4.29±1.67,4.56±1.71,6.04±1.37,6.34±2.26(nmol/mg,mean±SEM,n=5)すなわち、どの部位においても虚血前後の時間経過による有意の差は認められなかった。以上により、少なくとも現行の測定系による限りSph-1-P含有量の虚血後変動は認められず、また海馬Sph-1-P含有量の虚血後上昇は認められなかった。このことは、海馬CA1領域にみられる遅発性神経細胞死の機構にはSph-1-Pが直接関与していない可能性を示唆する。しかし、今回確立した測定系は、必ずしも細胞特異的、または細胞内微小領域特異的に測定しているわけではなく、細胞内における局所的なSph-1-Pの変動が遅発性神経細胞死の機構に関与している可能性は否定できない。
  • 文部科学省:科学研究費補助金(基盤研究(B))
    研究期間 : 1996年 -1998年 
    代表者 : 鈴木 一郎, 栗田 浩樹, 杉下 守弘, 川合 謙介
    てんかん焦点切除術を行う場合には、焦点の空間的広がりや焦点部位固有の脳機能を正確に解析する必要がある。皮質焦点てんかんの場合、焦点の中心領域は比較的容易に決定できるが、焦点周囲の正常脳との境界を決定することは困難である。従来の方法では、焦点内の異常波と軸索投射や電気緊張性に拡散した二次的異常波とを鑑別することが困難であった。この様な観点から、大脳皮質に対する外科治療を行う前に、一過性、可逆的かつ部分的な大脳皮質冷却を行い機能的な皮質切除が可能になれば、手術効果ならびにその危険性の判定が術前に確実に行える様になるものと期待される。上に述べた背景に基づいて、てんかん焦点の可逆的でかつ機能的な切除法を検討した。方法としてはラットならびにマウスのてんかんモデルを作製した上で(ラットはNoda epileptic rat(NER)、マウスはEL mouse)、実験を行った。しかし、ラットやマウスの脳容積が小さく、脳血流が豊富なためか安定した局所脳冷却もしくは全脳冷却は困難であった。また冷却範囲の安定したコントロールも困難であった。このため、関連研究として全脳放射線照射の効果を検討した。その結果、NER rat群で放射線照射によるてんかん原性抑制効果が示唆された。さらに、臨床的に術中に局所冷却法を行いてんかん性発作波の抑制効果を検討した。
  • 文部科学省:科学研究費補助金(一般研究(A), 基盤研究(A))
    研究期間 : 1994年 -1997年 
    代表者 : 田村 晃, 戸向 則子, 川合 謙介, 中山 比登志, 金光 秀晃, 中込 忠好, 古屋 一英, 長島 正, 松野 彰
    (1)虚血による神経細胞死には、視床網様核にみられるような超早発性の神経細胞死、脳梗塞モデルで認められるような急性神経細胞死、蛋白代謝障害や遺伝子発現を伴った遅発性神経細胞死のようなアポートーシス類似神経細胞死、脳梗塞における遠隔部の緩徐な神経細胞死などの病態があることを明らかにした。(2)脳梗塞モデルでは虚血早期より蛋白代謝の低下がみられ、遠隔部では視床では変化が認められないが黒質では蛋白代謝の亢進が認められこと、MRIの観察で視床と黒質でintensityの違いが認められることこと等から両者の機序に違いがあることが明らかとなった。(3)脳梗塞モデルでアポトーシス関連遺伝子の発現を検討し、c-myc mRNAが虚血部で時間依存性に発現し、c-fos mRNAも同じ部位で発現するが、N-myc,s-myc,bcl-2のmRNAsの発現は見られないことが明らかとなった。(4)apoptosisのsecond messenger として注目されているセラミドとその関連物質のsphingolipidsと虚血性神経細胞死との関連を検討した。脳梗塞モデルではsphingomyelinは2時間後より減少しセラミドは6時間後より増加し両者の構成脂肪酸も一致した。また、前脳虚血後の海馬では虚血直後にsphingomyelinaseによるsphingomyelinの加水分解が起こり、虚血後のsphingomyelinaseの活性化にアラキドン酸の関与が推定された。セラミドは虚血30分後に有意な上昇を示したが90分後には対照値に戻り24時間後に再び有意に上昇した。この結果、スフインゴミエリン・サイクルが、虚血性神経細胞死に関与している可能性が示唆された。(5)記憶および神経再生への関与が推定されるアセチルコリンおよびアセチルコリン合成酵素および分解酵素の測定をラット脳梗塞モデルで行った。3者とも梗塞中心部・辺縁部での有意の低下が認められた。また再生に関与するGAP43の免疫染色を行い虚血辺縁部の神経細胞に淡白の存在が認められた。
  • 文部科学省:科学研究費補助金(一般研究(C), 基盤研究(C))
    研究期間 : 1994年 -1996年 
    代表者 : 金光 秀晃, 川合 謙介, 田村 晃
    虚血性神経細胞損傷には酸化的損傷が深く関係している。遷移金属は水酸化鉄のような細胞傷害用のあるフリーラジカルを発生する。従って、虚血性神経細胞損傷には遷移金属、とりわけ鉄が大きな役割を演じている可能性が極めて高い。一方、その鉄は鉄運搬蛋白であるトランスフェリンにより運ばれ、トランスフェリン受容体を介して細胞内に取込まれる。この際クラスリンが重要な役割を演じる。細胞内の余った鉄はフェリチンの形で貯蔵される。またこの系で細胞内に取込まれた鉄は、虚血性神経細胞損傷で新たに注目されている神経伝達物質CO(一酸化炭素)と関連するヘムオキシゲナーゼの産生、活性化と密接な関係を有している。従って、虚血脳における脳内の鉄の分布、代謝を追究することは虚血性神経細胞損傷の仕組を少なからず明らかにできる可能性があるので、ラットの局所脳虚血ならびに全脳虚血モデル、砂ネズミの前脳虚血モデルを使用し、虚血性神経細胞死に鉄がいかなる役割を演じているかに注目し各種の実験を行なった。ラット局所脳虚血(MCA閉塞)モデル、ラット心停止モデル、砂ネズミの両総頚動脈閉塞モデルによる脳虚血モデルでの鉄染色、免疫組織化学法によるクラスリン、トランスフェリン、トランスフェリン受容体、in site hybridization又はin situ RT-PCR hybridizationによるヘムオキシゲナーゼ1とヘムオキシゲナーゼ2の両mRNAなどの虚血脳における脳内の鉄の分布、代謝を検討したがコントロールと比較していずれも顕著な差が観察できなかった。これらの結果より鉄沈着、鉄代謝は我々が観察した期間では、神経細胞死に直接関与していないことが考えられる。
  • 文部科学省:科学研究費補助金(一般研究(C))
    研究期間 : 1994年 -1996年 
    代表者 : 川合 謙介, 中山 比登志
    (1)破壊実験による痙攣焦点の同定心停止・蘇生を加える7日前にラットをペントバルビタール麻酔下に定位脳手術装置に固定し、下丘または内側膝状体に電気凝固病変を作成した。この操作そのものではラットに行動上の変化は認められなかった。病変作成の7日後に心停止・蘇生による一過性全脳虚血を加えた。両側内側膝状体を破壊したラットは全て、誘発音に反応して聴原性痙攣を示した。一方、両側下丘を破壊したラットでは、聴原性痙攣が誘発されなかった。心停止・蘇生の7日後にラットを潅流固定して破壊病変の広がりを確認したが、下丘に不十分な病変しか作成されなかった動物では、不完全なwild runningが認められただけで、典型的な聴原性痙攣(robust wild runningからtonic-clonic seizureに移行する型)は認められなかった。したがって、一過性全脳虚血後にラットで誘発される易痙攣性も、遺伝的痙攣ラット(GEPR)と同様、上行性聴覚伝導路のうち下丘がその焦点となっていることが示唆された。(2)下丘の形態学的変化古典的染色法では一過性全脳虚血後の下丘では、梗塞巣や著明なニューロンの脱落などは認められず、正常対照ラットと差異はなかった。しかし、抗glutamic acid decarboxylase抗体によるGABA陽性細胞の免疫染色では、下丘中心核の特に腹外側部でGABA陽性細胞が50%以上脱落していた。正常ラット下丘には小型と大型のGAD陽性細胞が認められたが、虚血後動物での脱落は特に小型細胞に強かった。GEPRでは、おそらく代償的な機構によって、下丘中心核腹外側部のGAD陽性細胞数が増加していると報告されているが、虚血後ラットでは下丘の抑制性ニューロンそのものの脱落が、易痙攣性誘導に関与している可能性が示唆された。
  • 文部科学省:科学研究費補助金(一般研究(C))
    研究期間 : 1994年 -1995年 
    代表者 : 川嵜 良明, 川合 謙介, 土井 勝美
    I.1)内耳の蝸牛軸動脈からコイル状細動脈にはエンドセリンBレセプターが発現している。2)蝸牛内に直接エンドセリンを導入すると、蝸牛電位は急速に低下する。3)エンドセリンによる蝸牛電位の低下は、エンドセリンBレセプターの選択的アンタゴニストにより抑制される。4)虚血性内耳障害の一つの病態である突発性難聴症例では、その発症時に血清中エンドセリン値は高値を示す。5)虚血性内耳障害による感音性難聴の発症機構の一つの因子として、エンドセリンおよびそり受容体による内耳血流低下が考慮される。II.1)蝸牛血管条には、ATP-dependent potassium channelの一つであるKAB-2チャネルが発現しており、一過性内耳虚血による血管条でのATR量の変化は、同チャネルの生理機能に影響を与える。2)ATP-dependent potassium channelの阻害剤であるBa^<2+>を蝸牛動脈内に投与すると、蝸牛電位は可逆的な低下を示す。3)虚血性内耳障害による感音性難聴の発症機構の一つの因子として、虚血時の血管条におけるATP量の変化を原因とするATP-dependent potassium channelの機能異常が考慮される。III.1)内耳前庭系の有毛細胞と1次ニューロン間の神経伝達も、グルタミン酸受容体のAMPA型レセプターを介して行われる。2)前庭および蝸牛系において、虚血性変化として、AMPA型レセプターのGluR2サブユニットの変化が示唆される。蝸牛有毛細胞に発現するMAP-2は、一過性虚血に対して鋭敏な反応を示し、中枢神経系の発生初期段階に発現するMAP-2cの発現増加が認められる。4)これらの2つの分子は内耳の虚血性変化を示す良いマーカーと考えられる。
  • 難治性てんかんに対する新しい治療法の開発、記憶のfMRIの臨床応用、頭蓋内脳波解析


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