研究者業績

桑原 聡

クワバラ サトシ  (Satoshi Kuwabara)

基本情報

所属
千葉大学 大学院医学研究院脳神経内科学 教授 (教授)
学位
医学博士(1993年3月 千葉大学)

J-GLOBAL ID
200901033727459280
researchmap会員ID
1000200574

論文

 964
  • Merkies ISJ, van Schaik IN, L?ger JM, Bril V, van Geloven N, Hartung HP, Lewis RA, Sobue G, Lawo JP, Durn BL, Cornblath DR, De Bleecker JL, Sommer C, Robberecht W, Saarela M, Kamienowski J, Stelmasiak Z, Tackenberg B, Mielke O, PRIMA Trial Investigators, the PATH StudyGroup
    Journal of the peripheral nervous system : JPNS. 24(1) 48-55 2019年3月  査読有り
  • Kuwabara S, Misawa S, Mori M
    Journal of Neurology, Neurosurgery & Psychiatry 90(2) 121-121 2019年2月  
  • Atsuhiko Sugiyama, Yukari Sekiguchi, Minako Beppu, Takayuki Ishige, Kazuyuki Matsushita, Satoshi Kuwabara
    Internal medicine (Tokyo, Japan) 58(1) 119-122 2019年1月1日  査読有り
    Peripheral neuropathy is a common extracerebellar manifestation of spinocerebellar ataxia type 3 (SCA3). However, to date, only a few SCA3 case reports have described the development of neuropathy before the emergence of apparent cerebellar signs. We herein report a case of very late-onset SCA3 in which preceding peripheral neuropathy seemingly concealed cerebellar signs, with seven years lapsing from the onset to the diagnosis. Horizontal gaze-evoked nystagmus and brain magnetic resonance imaging (MRI) findings prompted genetic testing, which confirmed the diagnosis of SCA3. A careful follow-up of neurological findings, such as nystagmus, and brain MRI are imperative for such cases.
  • Kanai T, Uzawa A, Kawaguchi N, Oda F, Ozawa Y, Himuro K, Kuwabara S
    Journal of the neurological sciences 396 8-11 2019年1月  査読有り
  • Yamashita T, Ueda M, Misawa S, Inoue Y, Masuda T, Misumi Y, Takamatsu K, Obayashi K, Kuwabara S, Ando Y
    Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis 26(sup1) 9-10 2019年  査読有り
  • Ogino M, Nakanishi Y, Mitsuhashi T, Hatanaka Y, Amano T, Marukawa K, Nitta T, Ueno T, Ono M, Kuwabara S, Yamada T, Hirano S
    Histopathology 74(6) 861-872 2019年1月  査読有り
  • Kuwabara S, Misawa S
    Advances in experimental medicine and biology 1190 333-343 2019年  査読有り
  • Ryosuke Oki, Yuishin Izumi, Hiroyuki Nodera, Yasutaka Sato, Hiroshi Nokihara, Kazuaki Kanai, Masahiro Sonoo, Makoto Urushitani, Kazuto Nishinaka, Naoki Atsuta, Nobuo Kohara, Toshio Shimizu, Hitoshi Kikuchi, Masaya Oda, Ken Ikeda, Makiko Nagai, Kiyonobu Komai, Yasuhiro Kojima, Daisuke Kuzume, Sagiri Isose, Shun Shimohama, Koji Abe, Hidefumi Ito, Kazuyuki Noda, Tomohiko Ishihara, Mitsuya Morita, Takayoshi Shimohata, Satoshi Teramukai, Tatsuo Kagimura, Kensuke Noma, Hiroaki Yanagawa, Satoshi Kuwabara, Ryuji Kaji
    JMIR research protocols 7(12) e12046 2018年12月21日  査読有り
    BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects the upper and lower motor neurons. Currently, only riluzole and edaravone are approved as drugs to treat ALS and new agents with larger effect sizes are warranted. Exploratory analyses in our previous study (study ID #E0302-J081-761) have suggested that high-dose methylcobalamin (E0302) prolonged the overall survival of ALS patients and suppressed ALS progression in patients with a disease duration of less than 12 months. OBJECTIVE: This clinical trial aims to evaluate the efficacy and safety of E0302 for treatment of ALS patients within one year of onset. METHODS: The Japanese early-stage trial of high-dose methylcobalamin for ALS (JETALS) is a prospective, multicenter, placebo-controlled, double-blind, randomized phase III study conducted at 24 tertiary neurology centers and is funded by the Japan Agency for Medical Research and Development. A total of 128 ALS patients within one year of onset were randomized at a 1:1 ratio to receive intramuscular injection with E0302 50 mg or placebo twice a week for 16 weeks. The primary endpoint is changes in the ALS Functional Rating Scale-Revised (ALSFRS-R) total score at 16 weeks. If patients wish to receive E0302 50 mg after the double-blind administration period, E0302 will be provided to them until March 2020 during the continuous administration period. RESULTS: This study began in October 2017 and is being conducted at 24 participating institutions in Japan. The study is in progress and the patient enrollment period is scheduled to end in August 2019, with follow-up scheduled to end in March 2020. CONCLUSIONS: This study is being performed to revalidate the efficacy and safety of E0302 in patients with early-stage ALS in the first year of symptom onset. If positive results are obtained, the aim is to apply for E0302 approval as a new drug for the treatment of ALS. TRIAL REGISTRATION: ClinicalTrials.gov NCT03548311; https://clinicaltrials.gov/ct2/show/NCT03548311 (Archived by WebCite at http://www.webcitation.org/74Fw3rDzb). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/12046.
  • Sugimoto K, Hiwasa T, Shibuya K, Hirano S, Beppu M, Isose S, Arai K, Takiguchi M, Kuwabara S, Mori M
    Journal of neuroimmunology 325 54-60 2018年12月  査読有り
  • Uncini A, Kuwabara S
    Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology 129(12) 2586-2593 2018年12月  
  • Yamamoto T, Uchiyama T, Asahina M, Yamanaka Y, Hirano S, Higuchi Y, Kuwabara S
    Brain and behavior 8(12) e01164 2018年12月  査読有り
  • Sonoko Misawa, Yasunori Sato, Kanako Katayama, Kengo Nagashima, Yukari Sekiguchi, Hiroshi Amino, Tomoki Suichi, Satoshi Kuwabara
    JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM 23(4) 265-265 2018年12月  
  • Oki R, Izumi Y, Nodera H, Sato Y, Nokihara H, Kanai K, Sonoo M, Urushitani M, Nishinaka K, Atsuta N, Kohara N, Shimizu T, Kikuchi H, Oda M, Ikeda K, Nagai M, Komai K, Kojima Y, Kuzume D, Isose S, Shimohama S, Abe K, Ito H, Noda K, Ishihara T, Morita M, Shimohata T, Teramukai S, Kagimura T, Noma K, Yanagawa H, Kuwabara S, Kaji R, JETALS Collabolators
    JMIR Research Protocols in press(12) e12046 2018年12月  査読有り
  • Tsuneyama Atsuko, Shibuya Kazumoto, Misawa Sonoko, Sekiguchi Yukari, Amino Hiroshi, Suichi Tomoki, Suzuki Youichi, Kuwabara Satoshi
    JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM 23(4) 294-294 2018年12月  査読有り
  • Amino Hiroshi, Shibuya Kazumoto, Misawa Sonoko, Sekiguchi Yukari, Suichi Tomoki, Suzuki Youichi, Tsuneyama Atsuko, Kuwabara Satoshi
    JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM 23(4) 381-381 2018年12月  査読有り
  • Suichi Tomoki, Misawa Sonoko, Sekiguchi Yukari, Shibuya Kazumoto, Amino Hiroshi, Tsuneyama Atsuko, Suzuki Youichi, Kuwabara Satoshi
    JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM 23(4) 292-292 2018年12月  査読有り
  • Soichiro Kitamura, Hitoshi Shimada, Fumitoshi Niwa, Hironobu Endo, Hitoshi Shinotoh, Keisuke Takahata, Manabu Kubota, Yuhei Takado, Shigeki Hirano, Yasuyuki Kimura, Ming-Rong Zhang, Satoshi Kuwabara, Tetsuya Suhara, Makoto Higuchi
    Journal of neurology, neurosurgery, and psychiatry 89(11) 1208-1214 2018年11月  査読有り
    OBJECTIVE: Apathy is a common neuropsychological symptom in Alzheimer's disease (AD), and previous studies demonstrated that neuronal loss and network disruption in some brain regions play pivotal roles in the pathogenesis of apathy. However, contributions of tau and amyloid-β (Aβ) depositions, pathological hallmarks of AD, to the manifestation of apathy remain elusive. METHODS: Seventeen patients with AD underwent positron emission tomography (PET) with 11C-pyridinyl-butadienyl-benzothiazole 3 (11C-PBB3) and 11C-Pittsburgh compound-B (11C-PiB) to estimate tau and Aβ accumulations using standardised uptake value ratio (SUVR) images. 11C-PBB3 and 11C-PiB SUVR were compared between AD patients with high and low Apathy Scale (AS) scores. Additionally, volumetric and diffusion tensor MRI was performed in those areas where any significant difference was observed in PET analyses. Correlation and path analyses among AS and estimated imaging parameters were also conducted. RESULTS: AD patients with high AS scores showed higher 11C-PBB3 SUVR in the orbitofrontal cortex (OFC) than those with low AS scores, while 11C-PiB SUVR in any brain regions did not differ between them. Elevated 11C-PBB3 SUVR in OFC, decreased OFC thickness and decreased fractional anisotropy (FA) in the uncinate fasciculus (UNC), which is structurally connected to OFC, correlated significantly with increased scores of the AS. Path analysis indicated that increased 11C-PBB3 SUVR in OFC affects apathy directly and through reduction of OFC thickness and subsequent decrease of FA in UNC. CONCLUSIONS: The present findings suggested that tau pathology in OFC may provoke focal neurotoxicity in OFC and the following disruption of the OFC-UNC network, leading to the emergence and progression of apathy in AD.
  • Nakamura K, Yamanaka Y, Higuchi Y, Hirano S, Kuroiwa R, Abe M, Murata A, Iwadate Y, Kuwabara S, Yamamoto T
    Neurology and Clinical Neuroscience 1-6 2018年11月  査読有り
  • Daisuke Sawada, Katsunori Fujii, Sonoko Misawa, Tadashi Shiohama, Tomoyuki Fukuhara, Mayuko Fujita, Satoshi Kuwabara, Naoki Shimojo
    Brain and Development 40(9) 830-832 2018年10月  査読有り
  • Doets AY, Verboon C, van den Berg B, Harbo T, Cornblath DR, Willison HJ, Islam Z, Attarian S, Barroso FA, Bateman K, Benedetti L, van den Bergh P, Casasnovas C, Cavaletti G, Chavada G, Claeys KG, Dardiotis E, Davidson A, van Doorn PA, Feasby TE, Galassi G, Gorson KC, Hartung HP, Hsieh ST, Hughes RAC, Illa I, Islam B, Kusunoki S, Kuwabara S, Lehmann HC, Miller JAL, Mohammad QD, Monges S, Nobile Orazio E, Pardo J, Pereon Y, Rinaldi S, Querol L, Reddel SW, Reisin RC, Shahrizaila N, Sindrup SH, Waqar W, Jacobs BC, IGOS Consortium
    Brain : a journal of neurology 141(10) 2866-2877 2018年10月  査読有り
  • Aoyama S, Mori M, Uzawa A, Uchida T, Masuda H, Ohtani R, Kuwabara S
    Multiple sclerosis (Houndmills, Basingstoke, England) 26(1) 1352458518808473-129 2018年10月  査読有り
  • Suichi T, Misawa S, Sato Y, Beppu M, Sakaida E, Sekiguchi Y, Shibuya K, Watanabe K, Amino H, Kuwabara S
    Journal of Neurology, Neurosurgery & Psychiatry 90(2) 133-137 2018年10月  査読有り
  • Kishin Koh, Hiroyuki Ishiura, Minako Beppu, Haruo Shimazaki, Yuta Ichinose, Jun Mitsui, Satoshi Kuwabara, Shoji Tsuji, Yoshihisa Takiyama
    Journal of human genetics 63(9) 1009-1013 2018年9月  査読有り
    Hereditary spastic paraplegias (HSPs) are characterized by various inherited disorders in which weakness and spasticity of the lower extremities are the predominant symptoms. Recently, HSP caused by ALDH18A1 mutations has been reported as SPG9 with autosomal dominant (SPG9A) and autosomal recessive (SPG9B) transmission. In this study, we obtained clinical and genetic findings in two Japanese families with SPG9B. One family had a novel compound heterozygous mutation (c.1321 C > T/c.1994G > A) in the ALDH18A1 gene. The other family had a homozygous mutation (c.383 G > A/c.383 G > A) in the ALDH18A1 gene. To date, only two SPG9B families with ALDH18A1 mutations have been reported. This is the first report of SPG9 in non-Caucasians. Furthermore, we found cerebellar ataxia in one family, although cerebellar ataxia has not been reported in SPG9B so far. SPG9B might involve a complicated HSP including cerebellar ataxia and cognitive impairment. This study expands the clinical and genetic spectrum of ALDH18A1-related disorders.
  • Kawajiri-Manako C, Mimura N, Fukuyo M, Namba H, Rahmutulla B, Nagao Y, Togasaki E, Shimizu R, Oshima-Hasegawa N, Tsukamoto S, Mitsukawa S, Takeda Y, Ohwada C, Takeuchi M, Iseki T, Misawa S, Yokote K, Tsuiji M, Kuwabara S, Sakaida E, Kaneda A, Nakaseko C
    American journal of hematology 93(9) 1161-1168 2018年9月  査読有り
  • Keisuke Suzuki, Yasuyuki Okuma, Tomoyuki Uchiyama, Masayuki Miyamoto, Ryuji Sakakibara, Yasushi Shimo, Nobutaka Hattori, Satoshi Kuwabara, Toshimasa Yamamoto, Yoshiaki Kaji, Shigeki Hirano, Shiho Suzuki, Yasuo Haruyama, Gen Kobashi, Koichi Hirata
    CEPHALALGIA 38(9) 1535-1544 2018年8月  査読有り
    Background Previous studies have reported a lower migraine prevalence in Parkinson's disease (PD) patients and improvements in migraine headaches after PD onset, but the clinical association of migraines with PD is unclear.Methods We analysed headache and migraine prevalence and clinical correlates in 436 PD patients (mean age, 69.37.8 years) and 401 age- and sex-matched controls (mean age, 69.28.6 years) in a case-controlled, multicentre study. Migraines were diagnosed by a questionnaire developed according to the International Classification of Headache Disorders, second edition. We evaluated changes in headache intensity, frequency and severity over several years around the onset of PD among PD patients with headaches or migraines, and over the past several years among control subjects with headaches or migraines.Results PD patients had lower lifetime (9.6% vs. 18.0%) and 1-year (6.7% vs. 11.0%) migraine prevalences than controls. However, lifetime (38.5% vs. 38.9%) and 1-year (26.1% vs. 26.2%) headache prevalence did not differ between PD patients and controls. After adjusting for gender, timing of the evaluation of headache changes, and recall period, PD patients with headaches or migraines exhibited a pronounced reduction in the intensity, frequency and overall severity of their headaches and migraines after the onset of PD compared with controls with headaches or migraines. PD patients with migraines exhibited a higher rate of depression and higher Pittsburgh Sleep Quality Index and PD sleep scale-2 scores than those without headaches.Conclusion While overall headache and migraine severity reduced after PD onset, the presence of migraines was associated with sleep disturbances and depression in PD patients.
  • Akiyuki Hiraga, Satoshi Kuwabara
    Journal of the Neurological Sciences 390 261-264 2018年7月15日  査読有り
    Background: Meningitis-retention syndrome (MRS) is a peculiar combination of aseptic meningitis (AM) and acute urinary retention without other neurological symptoms. MRS has not been well recognised, and the prevalence of MRS in patients with AM is unknown. Objective: To investigate the frequency and clinical features of MRS. Methods: Clinical and laboratory features of patients with MRS who were consecutively admitted to the Chiba Rosai Hospital between 2009 and 2017. Results: Of the 37 patients with AM, MRS was observed in three (8%). In MRS patients, the mean latency between the onset of meningeal symptoms (headache and/or fever) and the three clinical course milestones (the onset of voiding difficulty, urinary retention and recovery of no residual urine volume) were 8, 9.3 and 18 days, respectively. Patients with MRS frequently showed elevated cerebrospinal fluid adenosine deaminase levels and decreased cerebrospinal fluid/serum glucose ratios. All patients with MRS recovered without a specific treatment, and the mean hospital stay was 18 days. Conclusions: MRS may be more common than is generally considered. The long-term prognosis of MRS was good, and it was a self-limiting condition. However, it is likely to be underreported or misdiagnosed. Therefore, it is important to recognise that patients with AM may have MRS.
  • Hiroshi Matsuda, Miho Murata, Yohei Mukai, Kazuya Sako, Hidetoshi Ono, Hiroshi Toyama, Yoshitaka Inui, Yasuyuki Taki, Hideo Shimomura, Hiroshi Nagayama, Amane Tateno, Kenjiro Ono, Hidetomo Murakami, Atsushi Kono, Shigeki Hirano, Satoshi Kuwabara, Norihide Maikusa, Masayo Ogawa, Etsuko Imabayashi, Noriko Sato, Harumasa Takano, Jun Hatazawa, Ryosuke Takahashi
    European journal of nuclear medicine and molecular imaging 45(8) 1405-1416 2018年7月  査読有り
    PURPOSE: The aim of this multicenter trial was to generate a [123I]FP-CIT SPECT database of healthy controls from the common SPECT systems available in Japan. METHODS: This study included 510 sets of SPECT data from 256 healthy controls (116 men and 140 women; age range, 30-83 years) acquired from eight different centers. Images were reconstructed without attenuation or scatter correction (NOACNOSC), with only attenuation correction using the Chang method (ChangACNOSC) or X-ray CT (CTACNOSC), and with both scatter and attenuation correction using the Chang method (ChangACSC) or X-ray CT (CTACSC). These SPECT images were analyzed using the Southampton method. The outcome measure was the specific binding ratio (SBR) in the striatum. These striatal SBRs were calibrated from prior experiments using a striatal phantom. RESULTS: The original SBRs gradually decreased in the order of ChangACSC, CTACSC, ChangACNOSC, CTACNOSC, and NOACNOSC. The SBRs for NOACNOSC were 46% lower than those for ChangACSC. In contrast, the calibrated SBRs were almost equal under no scatter correction (NOSC) conditions. A significant effect of age was found, with an SBR decline rate of 6.3% per decade. In the 30-39 age group, SBRs were 12.2% higher in women than in men, but this increase declined with age and was absent in the 70-79 age group. CONCLUSIONS: This study provided a large-scale quantitative database of [123I]FP-CIT SPECT scans from different scanners in healthy controls across a wide age range and with balanced sex representation. The phantom calibration effectively harmonizes SPECT data from different SPECT systems under NOSC conditions. The data collected in this study may serve as a reference database.
  • Uzawa A, Furuya T, Ohtori S, Kuwabara S
    Neurology 91(1) 45-46 2018年7月  査読有り
  • Sugiyama A, Beppu M, Kuwabara S
    Neurology 91(2) e185-e186 2018年7月  査読有り
  • Uzawa A, Mori M, Masuda H, Ohtani R, Uchida T, Kuwabara S
    Clinical and experimental immunology 193(1) 47-54 2018年7月  査読有り
  • Akiyuki Uzawa, Masahiro Mori, Satoshi Kuwabara
    Journal of Neurology, Neurosurgery and Psychiatry 89(9) 900 2018年6月5日  
  • Satoshi Kuwabara, Sonoko Misawa, Masahiro Mori, Yuta Iwai, Kazuhide Ochi, Hidekazu Suzuki, Hiroyuki Nodera, Akira Tamaoka, Masahiro Iijima, Tatsushi Toda, Hiroo Yoshikawa, Takashi Kanda, Ko Sakamoto, Susumu Kusunoki, Gen Sobue, Ryuji Kaji, Satoshi Kuwabara, Masahiro Mori, Sonoko Misawa, Yuta Iwai, Kazuhide Ochi, Susumu Kusunoki, Hidekazu Suzuki, Ryuji Kaji, Hiroyuki Nodera, N. Matsui, Akira Tamaoka, A. Ishi, Gen Sobue, Masahiro Iijima, Tatsushi Toda, K. Sekiguchi, Hiroo Yoshikawa, A. Yamamoto, Takashi Kanda, T. Maeda, M. Tahara, M. Nakagawa, T. Mizuno, on behalf of the Glovenin-I MMN Study Group
    Journal of the Peripheral Nervous System 23(2) 115-119 2018年6月1日  査読有り
    Intravenous immunoglobulin (IVIg) therapy is currently the only established treatment in patients with multifocal motor neuropathy (MMN), and many patients have an IVIg-dependent fluctuation. We aimed to investigate the efficacy and safety of every 3 week IVIg (1.0 g/kg) for 52 weeks. This study was an open-label phase 3 clinical trial, enrolling 13 MMN patients. After an induction IVIg therapy (0.4 g/kg/d for 5 consecutive days), maintenance dose (1.0 g/kg) was given every 3 weeks for 52 weeks. The major outcome measures were the Medical Research Council (MRC) sum score and hand-grip strength at week 52. This trial is registered with ClinicalTrials.gov, number NCT01827072. At week 52, 11 of the 13 patients completed the study, and all 11 had a sustained improvement. The mean (SD) MRC sum score was 85.6 (8.7) at the baseline, and 90.6 (12.8) at week 52. The mean grip strength was 39.2 (30.0) kPa at the baseline and 45.2 (32.8) kPa at week 52. Two patients dropped out because of adverse event (dysphagia) and decision of an investigator, respectively. Three patients developed coronary spasm, dysphagia, or inguinal herniation, reported as the serious adverse events, but considered not related with the study drug. The other adverse effects were mild and resolved by the end of the study period. Our results show that maintenance treatment with 1.0 g/kg IVIg every 3 week is safe and efficacious for MMN patients up to 52 weeks. Further studies are required to investigate optimal dose and duration of maintenance IVIg for MMN.
  • Misawa S, Kuwabara S, Sato Y, Yamaguchi N, Nagashima K, Katayama K, Sekiguchi Y, Iwai Y, Amino H, Suichi T, Yokota T, Nishida Y, Kanouchi T, Kohara N, Kawamoto M, Ishii J, Kuwahara M, Suzuki H, Hirata K, Kokubun N, Masuda R, Kaneko J, Yabe I, Sasaki H, Kaida KI, Takazaki H, Suzuki N, Suzuki S, Nodera H, Matsui N, Tsuji S, Koike H, Yamasaki R, Kusunoki S, Japanese Eculizumab Trial for GBS, JET-GBS, Study Group
    The Lancet. Neurology 17(6) 519-529 2018年6月  査読有り
  • Tanaka TD, Misawa S, Yoshimura M, Kuwabara S
    European heart journal. Case reports 2(2) yty051 2018年6月  査読有り
  • Masahiro Mori, Satoshi Kuwabara, Friedemann Paul
    Journal of Neurology, Neurosurgery & Psychiatry 89(6) 555-556 2018年6月  
  • Kazumoto Shibuya, Sonoko Misawa, Yukari Sekiguchi, Minako Beppu, Hiroshi Amino, Tomoki Suichi, Yo-Ichi Suzuki, Atsuko Tsuneyama, Satoshi Kuwabara
    Journal of Neurology, Neurosurgery and Psychiatry 90(2) 242-243 2018年5月18日  査読有り
  • Chikako Ohwada, Emiko Sakaida, Chika Kawajiri-Manako, Yuhei Nagao, Nagisa Oshima-Hasegawa, Emi Togasaki, Tomoya Muto, Shokichi Tsukamoto, Shio Mitsukawa, Yusuke Takeda, Naoya Mimura, Masahiro Takeuchi, Naomi Shimizu, Sonoko Misawa, Tohru Iseki, Satoshi Kuwabara, Chiaki Nakaseko
    Blood 131(19) 2173-2176 2018年5月10日  査読有り
  • Shinji Aoyama, Masahiro Mori, Akiyuki Uzawa, Tomohiko Uchida, Hiroki Masuda, Ryohei Ohtani, Satoshi Kuwabara
    Journal of Neurology 265(5) 1145-1150 2018年5月1日  査読有り
    Background: The risk of developing progressive multifocal leukoencephalopathy in natalizumab-treated multiple sclerosis (MS) patients is related to serum anti-JCV antibody (JCVAb) index. However, the correlation of JCVAb index with other disease-modifying treatments (DMTs) is not well understood. Objective: In this study, we investigated the JCVAb seropositivity rate/JCVAb indexes and its correlation with clinical profiles in Japanese MS patients, and the relationship between JCVAb indexes and DMTs. Methods: JCVAb indexes were measured in 149 serum samples from 105 patients with MS. JCVAb indexes and seropositivity, and their correlation with age, sex, disease duration, Kurtzke expanded disability status scale and the duration of the DMTs were evaluated in each patient. Results: JCVAb was positive in 73 of 105 MS patients. Within 40 fingolimod-treated patients, 27 were positive for JCVAb and JCVAb indexes were positively correlated with the duration of fingolimod treatment. No significant relation was found between JCVAb indexes and the duration of treatment for the other disease-modifying drugs. Conclusion: JCVAb seropositivity was comparatively high in Japanese MS patients. Fingolimod treatment is likely to increase serum JCVAb index, possibly leading to the development of PML. Therefore, it is advised that JCVAb index should be serially monitored during fingolimod treatment to decrease PML risk.
  • Kuwabara S
    Clinical Neurophysiology 129(5) e19 2018年5月  
  • van Schaik IN, Mielke O, PATH study group
    The Lancet. Neurology 17(5) 393-394 2018年5月  査読有り
  • Misawa Sonoko, Kuwabara Satoshi, Sato Yasunori, Yamaguchi Nobuko, Nagashima Kengo, Katayama Kanako, Sekiguchi Yukari, Iwai Yuta, Amino Hiroshi, Suichi Tomoki, Yokota Takanori, Nishida Yoichiro, Kanouchi Tadashi, Kohara Nobuo, Kawamoto Michi, Ishii Junko, Kuwabara Motoi, Suzuki Hidekazu, Hirata Koichi, Kokubun Norito, Masuda Ray, Kaneko Juntaro, Yabe Ichiro, Sasaki Hidenao, Kaida Ken-ichi, Takazaki Hiroshi, Suzuki Norihiro, Suzuki Shigeaki, Hiroyuki Nodera, Naoko Matsui, Tsuji Shoji, Koike Haruki, Yamasaki Ryo, Kusunki Susumu
    The Lancet Neurology Vol.17(No.6) 519-529 2018年4月21日  査読有り
    Despite the introduction of plasmapheresis and immunoglobulin therapy, many patients with Guillain-Barr? syndrome still have an incomplete recovery. Evidence from pathogenesis studies suggests the involvement of complement-mediated peripheral nerve damage. We aimed to investigate the safety and efficacy of eculizumab, a humanised monoclonal antibody against the complement protein C5, in patients with severe Guillain-Barr? syndrome. This study was a 24 week, multicentre, double-blind, placebo-controlled, randomised phase 2 trial done at 13 hospitals in Japan. Eligible patients with Guillain-Barr? syndrome were aged 18 years or older and could not walk independently (Guillain-Barr? syndrome functional grade 3-5). Patients were randomly assigned (2:1) to receive 4 weeks of intravenous immunoglobulin plus either eculizumab (900 mg) or placebo; randomisation was done via a computer-generated process and web response system with minimisation for functional grade and age. The study had a parallel non-comparative single-arm outcome measure. The primary outcomes were efficacy (the proportion of patients with restored ability to walk independently [functional grade ?2] at week 4) in the eculizumab group and safety in the full analysis set. For the efficacy endpoint, we predefined a response rate threshold of the lower 90% CI boundary exceeding 50%. This trial is registered with ClinicalTrials.gov, number, NCT02493725. Between Aug 10, 2015, and April 21, 2016, 34 patients were assigned to receive either eculizumab (n=23) or placebo (n=11). At week 4, the proportion of the patients able to walk independently (functional grade ?2) was 61% (90% CI 42-78; n=14) in the eculizumab group, and 45% (20-73; n=5) in the placebo group. Adverse events occurred in all 34 patients. Three patients had serious adverse events: two in the eculizumab group (anaphylaxis in one patient and intracranial haemorrhage and abscess in another patient) and one in the placebo group (depression). The possibility that anaphylaxis and intracranial abscess were related to eculizumab could not be excluded. No deaths or meningococcal infections occurred. The primary outcome measure did not reach the predefined response rate. However, because this is a small study without statistical comparison with the placebo group, the efficacy and safety of eculizumab could be investigated in larger, randomised controlled trials. The Japan Agency for Medical Research and Development, Ministry of Health, Labor and Welfare, and Alexion Pharmaceuticals.
  • Keisuke Watanabe, Shigeki Hirano, Kazuho Kojima, Kengo Nagashima, Hiroki Mukai, Takatoshi Sato, Minoru Takemoto, Koji Matsumoto, Takashi Iimori, Sagiri Isose, Shigeki Omori, Kazumoto Shibuya, Yukari Sekiguchi, Minako Beppu, Hiroshi Amino, Tomoki Suichi, Koutaro Yokote, Takashi Uno, Satoshi Kuwabara, Sonoko Misawa
    Journal of Neurology, Neurosurgery and Psychiatry 89(10) 1082-1087 2018年4月7日  査読有り
    Objective: To assess the cerebral blood flow (CBF) in patients with diabetic neuropathic pain, and its changes after duloxetine therapy. Methods: Using iodine-123-N-isopropyl-p-iodoamphetamine single-photon emission computed tomography (IMP-SPECT), we performed a cross-sectional study of 44 patients with diabetes, and compared CBF in those with (n = 24) and without neuropathic pain (n = 20). In patients with neuropathic pain, we also longitudinally assessed changes in CBF 3 months after treatment with duloxetine. Results: IMP-SPECT with voxel-based analyses showed a significant increase in cerebral blood flow in the right anterior cingulate cortex and a decrease in the left ventral striatum in patients with neuropathic pain, compared with those without pain. After duloxetine treatment, volume of interest analyses revealed a decrease in cerebral blood flow in the anterior cingulate cortex in patients with significant pain relief but not in non-responders. Furthermore, voxel-based whole brain correlation analyses demonstrated that greater baseline CBF in the anterior cingulate cortex was associated with better pain relief on the numerical rating scale. Conclusions: Our results suggest that the development of neuropathic pain is associated with increased activity in the anterior cingulate cortex, and greater baseline activation of this region may predict treatment responsiveness to pharmacological intervention. Trial registration number: UMIN000017130 Results.
  • Genki Tohnai, Ryoichi Nakamura, Jun Sone, Masahiro Nakatochi, Daichi Yokoi, Masahisa Katsuno, Hazuki Watanabe, Hirohisa Watanabe, Mizuki Ito, Yuanzhe Li, Yuishin Izumi, Mitsuya Morita, Akira Taniguchi, Osamu Kano, Masaya Oda, Satoshi Kuwabara, Koji Abe, Ikuko Aiba, Koichi Okamoto, Kouichi Mizoguchi, Kazuko Hasegawa, Masashi Aoki, Nobutaka Hattori, Osamu Onodera, Hiroya Naruse, Jun Mitsui, Yuji Takahashi, Jun Goto, Hiroyuki Ishiura, Shinichi Morishita, Jun Yoshimura, Koichiro Doi, Shoji Tsuji, Kenji Nakashima, Ryuji Kaji, Naoki Atsuta, Gen Sobue
    Neurobiology of aging 64 158.e15-158.e19-158.e19 2018年4月  査読有り
    Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease, and the etiology of sporadic ALS is generally unknown. The TANK-binding kinase 1 (TBK1) gene was identified as an ALS gene contributing to a predisposition toward ALS. To reveal the frequency and characteristics of variants of the TBK1 gene in sporadic ALS patients in Japan, we analyzed the TBK1 gene by exome sequencing in a large Japanese cohort of 713 sporadic ALS patients and 800 controls. We identified known or potentially toxic rare variants of TBK1 gene in 9 patients (1.26%) with sporadic ALS, including 4 novel missense variants (p.V23I, p.H322R, p.R358C, and p.T478I) and 3 loss-of-function variants (p.R357X, p.P378_I379del, and p.T419_G420del). The odds ratio between sporadic ALS patients and controls was 10.2 (p = 0.008, 95% confidence interval = 1.67-62.47). These findings support the contribution of TBK1 to the etiology of sporadic ALS in Japanese patients.
  • 木内 友紀, 仲野 義和, 鵜沢 顕之, 杉山 淳比古, 常山 篤子, 桑原 聡
    千葉医学雑誌 94(2) 85-85 2018年4月  
  • Kawaguchi N, Nakatani K, Uzawa A, Nemoto Y, Himuro K, Kuwabara S
    Journal of Pharmacovigilance 6(2) 1.00E+06 2018年4月  査読有り
  • Hiroki Masuda, Masahiro Mori, Kenta Umehara, Tomomi Furihata, Tomohiko Uchida, Akiyuki Uzawa, Satoshi Kuwabara
    Journal of neuroimmunology 316 117-120 2018年3月15日  査読有り
    Serum soluble CD40 ligand (sCD40L) has been reported to positively correlate with the albumin quotient, a marker of blood-brain barrier (BBB) breakdown, in patients with multiple sclerosis (MS). To clarify the mechanisms of sCD40L in MS pathophysiology, sCD40L was administered to experimental autoimmune encephalomyelitis (EAE) mice and a human brain microvascular endothelial cell (HBMEC)-based BBB model. The high-dose sCD40L group showed a worse EAE score than the low-dose and control groups. BBB permeability was increased by administering sCD40L in a HBMEC-based BBB model. Thus, sCD40L induces more severe inflammation in the central nervous system by disrupting the BBB.
  • Akiyuki Hiraga, Reiji Aoki, Keigo Nakamura, Satoshi Kuwabara
    Neurological Sciences 39(3) 577-579 2018年3月1日  査読有り
  • Sugiyama A, Sato N, Kimura Y, Ota M, Maekawa T, Sone D, Enokizono M, Murata M, Matsuda H, Kuwabara S
    Parkinsonism & related disorders 48 10-16 2018年3月  査読有り
  • Kappos, Bar-Or, Cree BA, Fox R, Giovannoni, Gold R, Vermersch P, Arnold DL, Arnould S, Scherz T, Wolf C, Wallstr?m E, Dahlke F, EXPAND Clinical Investigators
    Lancet 391(10127) 1263-1273 2018年3月  査読有り
  • Akiyuki Hiraga, Reiji Aoki, Marie Morooka, Hiroki Kano, Satoshi Kuwabara
    Neurological Sciences 39(7) 1-2 2018年2月28日  査読有り

MISC

 1029

書籍等出版物

 77

講演・口頭発表等

 84

担当経験のある科目(授業)

 3

共同研究・競争的資金等の研究課題

 64