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

 965
  • Akiyuki Uzawa, Masahiro Mori, Shoichi Ito, Satoshi Kuwabara
    JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY 82(1) 85-86 2011年1月  査読有り
  • Setsu Sawai, Sonoko Misawa, Kazuaki Kanai, Sagiri Isose, Kazumoto Shibuya, Yuichi Noto, Yumi Fujimaki, Yukari Sekiguchi, Saiko Nasu, Fumio Nomura, Satoshi Kuwabara
    CLINICAL NEUROPHYSIOLOGY 122(1) 205-209 2011年1月  査読有り
    Objective: Juvenile muscular atrophy of distal upper extremity (Hirayama disease) is characterized by juvenile-onset of asymmetric amyotrophy, but the pathophysiology has not been fully clarified. "Cold paresis", aggravation of muscle weakness with exposure to cold, is a characteristic feature of this disease. The aim of this study was to investigate changes in axonal excitability properties in Hirayama disease. Methods: Threshold tracking was used to measure strength-duration time constant (SDTC), threshold electrotonus, refractoriness, and supernormality in median motor axons at the wrist of 14 patients and 10 age-matched normal controls. The measurements were performed at room temperature and after cooling. Results: Patients showed prolonged SDTC, fanning-out of threshold electrotonus curves, and increased refractoriness and supernormality. After cooling, there were similar changes in patients and normal subjects, compatible with axonal depolarization possibly due to paralysis of sodium-potassium pump. Conclusions: Motor axonal excitability in Hirayama disease were characterized by increased persistent sodium currents, and dysfunction of transient sodium and potassium channels possibly associated with prominent collateral sprouting in young individuals. Further studies will be required to elucidate mechanisms for cold paresis. Significance: Assessment of axonal excitability could provide characteristic features of ionic mechanisms in diseases with neurogenic amyotrophy such as Hirayama disease. (C) 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
  • Akiyuki Uzawa, Masahiro Mori, Saeko Masuda, Kazuhiko Aoe, Satoshi Kuwabara
    Case Reports in Medicine 2011 405837 2011年  査読有り
    Lidocaine unmasks silent symptoms and eases neuropathic pain in multiple sclerosis patients however, the effects of lidocaine in neuromyelitis optica have never been reported. We describe the case of a 59-year-old Japanese woman with neuromyelitis optica spectrum disorder who developed optic neuritis 1 day after intravenous lidocaine injection for treating allodynia. Her symptom seemed to result from a relapse of neuromyelitis optica induced by lidocaine administration, and not because of the transient effects of intravenous lidocaine administration. The possibility that lidocaine administration results in relapse of neuromyelitis optica due to its immunomodulating effects cannot be ruled out. Copyright © 2011 Akiyuki Uzawa et al.
  • Kazumoto Shibuya, Sonoko Misawa, Takuro Horikoshi, Kazuaki Kanai, Sagiri Isose, Saiko Nasu, Yukari Sekiguchi, Yu-ichi Noto, Yumi Fujimaki, Chiaki Nakaseko, Satoshi Kuwabara
    INTERNAL MEDICINE 50(13) 1393-1396 2011年  査読有り
    Objective To study the utility of CT for detection of small bone lesions in POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome. For patients with a solitary bone lesion, irradiation is a first-line treatment, whereas systemic chemotherapy is indicated for patients with multiple bone lesions. Therefore it is important to correctly identify the number of bone lesions. Methods We studied the sensitivity of chest/abdomen/pelvic CT to detect bone lesions in 28 patients with POEMS syndrome. 99mTc-HMDP bone scintigraphy was performed in 14 patients, and the results were compared with CT. Results CT showed multiple bone lesions in 68% of the 28 patients, and 71% of the lesions had a diameter < 10 mm. In 14 patients who underwent both CT and scintigraphy, bone lesions were detected in 57% by CT and in 79% by scintigraphy, but the location and nature of the identified lesions were considerably different; CT frequently showed small lesions (diameter < 10 mm) in the vertebrae and pelvis, which were not detected by scintigraphy, whereas scintigraphy could show lesions in the skull and long bones. Overall, by using both examinations, multiple bone lesions were found for 86% of patients. Conclusion CT is particularly useful to detect small bone lesions. CT and bone scintigraphy are complementary, and therefore both should be performed for bone survey in POEMS syndrome.
  • Satoshi Kuwabara
    Clinical Neurology 51(11) 1019 2011年  査読有り
  • T. Yamamoto, R. Sakakibara, T. Uchiyama, C. Yamaguchi, F. Nomura, T. Ito, M. Yanagisawa, M. Yano, Y. Awa, T. Yamanishi, T. Hattori, S. Kuwabara
    NEUROUROLOGY AND URODYNAMICS 30(1) 102-107 2011年  査読有り
    Aims: It is usually difficult to distinguish between idiopathic Parkinson's disease (PD) and parkinsonian-type multiple system atrophy (MSA-P) in the early stage. However, it is important to make a careful early-stage diagnosis. Therefore, we determined whether an examination of pelvic organ dysfunction would be helpful to distinguish between PD and MSA-P. Methods: We recruited 61 patients with PD and 54 patients with MSA-P who were examined at our neurology clinic. The mean ages of the patients with PD and MSA-P were 67 and 64 years, respectively. The mean disease duration of both groups was 3.2 years. We administered a questionnaire on pelvic organ dysfunction to the PD and MSA-P groups. The questionnaire had sections focusing on bladder, bowel, and sexual function. Dysfunction, as described in the responses, was evaluated as normal, mild (> once a month), moderate (> once a week), or severe (> once a day). The Mann-Whitney U-test was used for statistical analysis. Results: Compared with the PD group, the prevalence and severity of pelvic dysfunction in the MSA-P group was significantly higher for urinary urgency (MSA-P 76%, PD 58%, P<0.05), retardation in initiating urination (79%, 48%, P<0.05), prolongation in urination (79%, 72%, P<0.05), and constipation (58%, 31%, P<0.05). The quality-of-life index among pelvic organ dysfunctions indicated that urinary and bowel function was significantly more impaired in the MSA-P group than in the PD group. Conclusions: Urinary urgency, retardation in initiating urination, prolongation in urination, and constipation are more prevalent and severe in MSA-P compared to PD. Neurourol. Urodynam. 30: 102-107, 2011. (C) 2010 Wiley-Liss, Inc.
  • C. Yamaguchi, U. Tomoyuki, T. Yamamoto, M. Yanagisawa, K. Mamada, Y. Sawabe, Y. Awa, R. Sakakibara, T. Yamanishi, T. Hattori, S. Kuwabara, F. Nomura
    NEUROUROLOGY AND URODYNAMICS 30(6) 1117-1118 2011年  
  • Hitoshi Shimada, Shigeki Hirano, Hitoshi Shinotoh, Koichi Sato, Noriko Tanaka, Tsuneyoshi Ota, Masato Asahina, Akiyo Aotsuka, Hiroshi Ito, Kiyoshi Fukushi, Satoshi Kuwabara, Toshiaki Irie, Tetsuya Suhara
    NEUROSCIENCE RESEARCH 71 E187-E187 2011年  
  • Kazumoto Shibuya, Sonoko Misawa, Takeshi Fukushima, Tomoyuki Uchiyama, Kei Funakoshi, Satoshi Kuwabara
    Clinical Neurology 51(2) 141-144 2011年  査読有り
    Chronic inflammatory demyelinating polyneuropathy (CIDP) is classified into typical type that is characterized by proximal weakness and atypical type that include demyelinating acquired distal symmetric (DADS) type. DADS type CIDP is characterized by slowly progressive clinical course, motor and sensory involvement dominant in the leg and resistance to therapy. We report the case of a 72 year-old man with DADS type CIDP, who have dysesthesia and weakness dominant in distal of limbs. Disease progression was resistant to therapy for prednisolone and intravenous immunoglobulin, but slowly progressive for 4 years. Subacute exacerbation that was accompanied by proximal weakness was occurred at 4 years later from onset. Nerve conduction study revealed markedly prolonged distal latencies and slowing of conduction velocities. Double filtration plasmapheresis improved symptom, after oral prednisolone kept remission. This case had characteristic of DADS type CIDP at the onset, but changed into typical CIDP also for the therapy in the clinical course. This case indicate the multiplicity of CIDP.
  • Kazuaki Kanai, Kazumoto Shibuya, Satoshi Kuwabara
    Clinical Neurology 51(11) 1118-1119 2011年  査読有り
    Fasciculation is a characteristic feature of ALS. Nerve excitability studies have shown increased persistent sodium currents and reduced potassium currents in motor axons of ALS patients, both of which lead to axonal hyperexcitability and thereby generation of fasciculations. The present study was undertaken to investigate whether abnormal axonal excitability indices are correlated with survival in ALS patients. A total of 112 consecutive patients with sporadic ALS were followed-up until endpoint (death or tracheostomy). Univariate analyses revealed longer strength-duration time constant (SDTC) was associated with a shorter survival. In multivariate analyses using the Cox proportional hazard model, onset age&gt 60 years and longer SDTC were strong predictors of shorter survival. Assuming that SDTC depends on nodal persistent sodium conductances, our results showed that an increased persistent sodium current is strong and independent predictor for short survival of ALS patients. These findings support the hypothesis that membrane hyperexcitability would contribute to motor neuronal death in ALS.
  • Akiyuki Uzawa, Masahiro Mori, Kimihito Arai, Yasunori Sato, Sei Hayakawa, Saeko Masuda, Junko Taniguchi, Satoshi Kuwabara
    MULTIPLE SCLEROSIS 16(12) 1443-1452 2010年12月  査読有り
    Background: Neuromyelitis optica (NMO) is assumed to be immunologically distinct from multiple sclerosis (MS). Adequate studies about cytokines and chemokines in NMO have been lacking. Objective: To investigate the contribution of cytokines/chemokines in the pathogenesis of NMO. Methods: We measured 27 cytokines/chemokines and Th17 cell-associated cytokines in the cerebrospinal fluid (CSF) of 31 NMO, 29 MS and 18 other non-inflammatory neurological disorders patients. The serum levels of some cytokines/chemokines were also measured. The correlations between clinical characteristics/laboratory findings and levels of cytokines/chemokines in NMO were examined. Results: The CSF levels of interleukin (IL)-1 receptor antagonist, IL-6, IL-8, IL-13 and granulocyte colony-stimulating factor were significantly increased in NMO, while IL-9, fibroblast growth factor-basic, granulocyte macrophage colony-stimulating factor, macrophage inflammatory protein-1-beta and tumor necrosis factor-alpha were increased in MS. IL-10 and interferon-gamma-inducible protein-10 were elevated in NMO and MS. In serum analyses, only the IL-6 level showed significant elevation in NMO. The CSF IL-6 level had a significant correlation with the CSF glial fibrillary acidic protein level and CSF cells, and a weak correlation with anti-aquaporin-4 antibody titers. Conclusions: Different immunological status and pathophysiologies exist between NMO and MS, and IL-6 may play important roles in the pathogenesis of NMO.
  • Akiyuki Uzawa, Masahiro Mori, Sei Hayakawa, Saeko Masuda, Fumio Nomura, Satoshi Kuwabara
    BMC NEUROLOGY 10 113 2010年11月  査読有り
    Background: The role of different chemokine receptors in the pathogenesis of multiple sclerosis (MS) has been extensively investigated; however, little is known about the difference in the role of chemokine receptors between the pathogenesis of neuromyelitis optica (NMO) and MS. Therefore, we examined the expression of chemokine receptors on peripheral blood lymphocytes (PBL) in MS and NMO. Methods: We used flow cytometry to analyse lymphocyte subsets in 12 patients with relapsing NMO, 24 with relapsing-remitting MS during relapse, 3 with NMO and 5 with MS during remission. Results: Compared with healthy controls (HC), the percentage of lymphocytes in white blood cells was significantly lower in NMO and MS patients. The percentage of T cells expressing CD4(+)CD25(+) and CD4(+)CD45RO(+) was higher, while that of CD4(+)CC chemokine receptor (CCR)3(+) (T helper 2, Th2) was significantly lower in MS patients than in HC. The ratios of CD4(+)CXC chemokine receptors (CXCR)3(+)/CD4(+)CCR3(+) (Th1/Th2) and CD8(+)CXCR3(+)/CD8(+)CCR4(+) (T cytotoxic 1, Tc1/Tc2) were higher in MS patients than in HC. The percentage of CD8(+)CXCR3(+) T cell (Tc1) and CD4(+)CXCR3(+) T cell (Th1) decreased significantly during remission in MS patients (P <0.05). No significant differences were identified in the expression of the chemokine receptors on PBL in NMO patients compared with MS patients and HC. Conclusions: Th1 dominance of chemokine receptors on blood T cells and the correlation between CXCR3(+) T cell (Th1 and Tc1) and disease activity in MS patients were confirmed by analysing chemokines receptors on PBL. In contrast, deviation in the Th1/Th2 balance was not observed in NMO patients.
  • Miyashiro Ai, Matsui Naoko, Shimatani Yoshimitsu, Shibuta Yoshiko, Kuwabara Satoshi, Baba Masayuki, Komori Tetsuo, Sonoo Masahiro, Mezaki Takahiro, Kawamata Jun, Hitomi Takefumi, Kohara Nobuo, Arimura Kimiyoshi, Izumi Yuishin, Kusunoki Susumu, Kaji Ryuji
    JOURNAL OF NEUROIMMUNOLOGY 228(1-2) 30-30 2010年11月  
  • S. Kuwabara
    JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY 81(10) 1063-1063 2010年10月  
  • Satoshi Kuwabara
    Brain and Nerve 62(8) 885-891 2010年8月  
    It is essential to perform electromyography and nerve-conduction studies for diagnosis amyotrophic lateral sclerosis (ALS), but these conventional electrophysiologic methods cannot be used for studies on the mechanism underlying ALS. The recently developed nerve-excitability test can provide new insights into the pathophysiology of this disease. Fasciculation is one of the characteristic features of ALS. Ectopic firing of motor units originates usually from the motor nerve terminals and occasionally from the motor neurons, indicating a widespread abnormality in axonal excitability. ALS is a multifactorial disease in which some genetic abnormalities and environmental factors lead to cell death through a complex cascade, which includes oxidative stress, mitochondrial dysfunction, excitotoxicity, and impaired axonal transport. It is important to elucidate the pathophysiology of axonal excitability in ALS because increased axonal excitability enhances oxidative stress and excitotoxicity, ultimately contributing to motor neuron death. To date, 2 axonal ion channel abnormalities have been identified: (1) increased persistent sodium currents and (2) reduced potassium currents both abnormalities cause an increase in axonal excitability and are responsible for fasciculations. The results for excitability testing in such patients are characterized by the following features: (1) a prolonged strength-duration time constant, which suggests increased persistent sodium currents (2) greater threshold changes in depolarizing threshold electrotonus and (3) greater supernormality, which suggests impaired potassium channels. The altered axonal properties in patients with ALS may provide new insights into the pathophysiology of ALS and have implications for the development of ion channel modulators as therapeutic options for patients with ALS.
  • C. Yamaguchi, T. Uchiyama, T. Yamamoto, R. Sakakibara, M. Yanagisawa, M. Yano, Y. Awa, K. Mamada, Y. Sawabe, T. Yamanishi, S. Kuwabara, F. Nomura
    INTERNATIONAL UROGYNECOLOGY JOURNAL 21 S304-S305 2010年8月  
  • Satoshi Kuwabara
    CLINICAL NEUROPHYSIOLOGY 121(7) 994-995 2010年7月  査読有り
  • Shigeki Hirano, Hitoshi Shinotoh, Hitoshi Shimada, Akiyo Aotsuka, Noriko Tanaka, Tsuneyoshi Ota, Koichi Sato, Hiroshi Ito, Satoshi Kuwabara, Kiyoshi Fukushi, Toshiaki Irie, Tetsuya Suhara
    BRAIN 133(Pt 7) 2058-2068 2010年7月  査読有り
    Corticobasal syndrome, progressive supranuclear palsy and frontotemporal dementia are all part of a disease spectrum that includes common cognitive impairment and movement disorders. The aim of this study was to characterize brain cholinergic deficits in these disorders. We measured brain acetylcholinesterase activity by [(11)C] N-methylpiperidin-4-yl acetate and positron emission tomography in seven patients with corticobasal syndrome (67.6 +/- 5.9 years), 12 with progressive supranuclear palsy (68.5 +/- 4.1 years), eight with frontotemporal dementia (59.8 +/- 6.9 years) and 16 healthy controls (61.2 +/- 8.5 years). Two-tissue compartment three-parameter model and non-linear least squares analysis with arterial input function were performed. k(3) value, an index of acetylcholinesterase activity, was calculated voxel-by-voxel in the brain of each subject. The k(3) images in each disease group were compared with the control group by using Statistical Parametric Mapping 2. Volume of interest analysis was performed on spatially normalized k(3) images. The corticobasal syndrome group showed decreased acetylcholinesterase activity (k(3) values) in the paracentral region, frontal, parietal and occipital cortices (P < 0.05, cluster corrected). The group with progressive supranuclear palsy had reduced acetylcholinesterase activity in the paracentral region and thalamus (P < 0.05, cluster corrected). The frontotemporal dementia group showed no significant differences in acetylcholinesterase activity. Volume of interest analysis showed mean cortical acetylcholinesterase activity to be reduced by 17.5% in corticobasal syndrome (P < 0.001), 9.4% in progressive supranuclear palsy (P < 0.05) and 4.4% in frontotemporal dementia (non-significant), when compared with the control group. Thalamic acetylcholinesterase activity was reduced by 6.4% in corticobasal syndrome (non-significant), 24.0% in progressive supranuclear palsy (P < 0.03) and increased by 3.3% in frontotemporal dementia (non-significant). Both corticobasal syndrome and progressive supranuclear palsy showed brain cholinergic deficits, but their distribution differed somewhat. Significant brain cholinergic deficits were not seen in frontotemporal dementia, which may explain the unresponsiveness of this condition to cholinergic modulation therapy.
  • Satoshi Kuwabara
    JOURNAL OF PHYSIOLOGY-LONDON 588(14) 2523-2523 2010年7月  査読有り
  • S. Misawa, S. Hayakawa, K. Himuro, S. Sawai, Y. Akaogi, S. Ito, S. Kuwabara
    CLINICAL NEUROLOGY AND NEUROSURGERY 112(6) 527-529 2010年7月  
    We describe a 64-year-old woman who developed spinal myoclonus around the left scapula after long thoracic nerve injury by mastectomy. Involuntary muscle twitching was semi-rhythmic, and ultrasonography identified contraction of the serratus anterior, teres major, and rhomboid muscles. FDG-PET imaging revealed markedly increased glucose uptake only in the serratus anterior. Lidocaine injection into this muscle resulted in complete cessation of the involuntary movement, and then she was successfully treated with botulinum toxin type A. These findings raise the possibility that the myoclonus was primarily caused by ectopic firing of the injured long thoracic nerve, then spreading to adjacent muscles possibly via a central mechanism mediated by group la afferents. The new imaging tools, such as FDG-PET and ultrasonography, were useful to determine the therapeutic target muscle. (C) 2010 Published by Elsevier B.V.
  • Hirokatsu Takahashi, Naoki Kawaguchi, Shoichi Ito, Yuko Nemoto, Takamichi Hattori, Satoshi Kuwabara
    JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY 81(6) 701-702 2010年6月  査読有り
  • Sagiri Isose, Masahiro Mori, Sonoko Misawa, Kazumoto Shibuya, Satoshi Kuwabara
    JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM 15(2) 147-149 2010年6月  査読有り
  • Sagiri Isose, Sonoko Misawa, Kenichi Sakurai, Kazuaki Kanai, Kazumoto Shibuya, Yukari Sekiguchi, Saiko Nasu, Yuichi Noto, Yumi Fujimaki, Koutaro Yokote, Satoshi Kuwabara
    CLINICAL NEUROPHYSIOLOGY 121(5) 719-724 2010年5月  査読有り
    Objective: To investigate changes in axonal persistent Na(+) currents in patients with neuropathic pain and the effects of mexiletine, an analogue of lidocaine, on axonal excitability properties. Methods: The technique of latent addition was used to estimate nodal persistent Na(+) currents in superficial radial sensory axons of 17 patients with neuropathic pain/paresthesias before and after mexiletine treatment. Brief hyperpolarizing conditioning currents were delivered, and threshold change at the conditioning-test interval of 0.2 ms was measured as an indicator of the magnitude of persistent Na(+) currents. Results: Threshold changes at 0.2 ms in latent addition were greater in the neuropathic patients than in the normal controls (p < 0.001). After mexiletine treatment, there was a reduction in clinical pain scores (p < 0.001), associated with decreased threshold changes at 0.2 ms (p < 0.001). Conclusions: In patients with neuropathy, nodal persistent Na(+) currents in large sensory fibers increase, and the abnormal currents can be suppressed by mexiletine. Pain reduction after mexiletine treatment raises the possibility that excessive Na(+) currents are also suppressed in small fibers mediating neuropathic pain. Significance: Latent addition can be used for indirect in vivo monitoring of nodal Na(+) currents in large sensory fibers, and future studies using this approach in small fibers would provide new insights into the peripheral mechanism of neuropathic pain. (C) 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
  • A. Uzawa, M. Mori, S. Hayakawa, S. Masuda, S. Kuwabara
    EUROPEAN JOURNAL OF NEUROLOGY 17(5) 672-676 2010年5月  査読有り
    Background: Although the benefit of treatment for relapsing-remitting multiple sclerosis (MS) is firmly established, whether interferon beta-1b (IFNB-1b) therapy is efficacious for neuromyelitis optica (NMO) has been debated. Methods: We reviewed the responses to IFNB-1b treatment in 18 patients with relapsing NMO and compared the results with those from 38 patients with relapsing-remitting MS. We compared clinical characteristics, the annualized relapse rate (ARR) and the probability of being relapse free before and after IFNB-1b treatment in patients with NMO and MS. Results: The proportion of patients with more than 50% increase in the ARR after IFNB-1b treatment was much higher in NMO than in MS (P = 0.046). ARR was significantly lower in patients with MS after IFNB-1b administration than before (P = 0.015), but not in NMO. Kaplan-Meier and log-rank statistical analyses revealed that relapse-free rates were lower in NMO than MS after IFNB-1b treatment (P = 0.032). The analyses also showed lower relapse-free rates during the pre-IFNB-1b treatment period than the post-IFNB-1b treatment period in MS (P < 0.001), but not in NMO. Conclusion: IFNB-1b treatment does not appear to be effective for preventing relapse in NMO likely because of differences between the immune-pathogenesis of NMO and MS.
  • Masato Asahina, Akira Katagiri, Yoshitaka Yamanaka, Yuichi Akaogi, Takeshi Fukushima, Kazuaki Kanai, Satoshi Kuwabara
    AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL 154(1-2) 99-101 2010年4月  査読有り
    Objective: Tachycardia is a clinical feature of Machado-Joseph disease (MJD), and it may be attributable to cardiac autonomic dysfunction. We investigated heart rate variability in MJD patients to reveal heart rate dysregulation in MJD. Methods: Power spectral analysis of successive R-R intervals (300 beats) was performed in 10 genetically diagnosed MJD patients and 10 healthy control subjects to obtain frequency-domain measures, including high- (HF: 0.15-0.4 Hz) and low frequency power (LF; 0.04-0.15 Hz) and the ratio of LF to HF (LF/HF) of heart rate variability. In addition, the coefficient of R-R intervals (CV(R-R)) was calculated as a time-domain measure. Results: HF in the MJD patients (26.2 +/- 25.3 ms(2)) was lower than that in the controls (82.1 +/- 82.6 ms(2), p = 0.004). LF was also lower in the MJD patients (70.6 +/- 69.4 ms(2)) than in the controls (106.9 +/- 81.3 ms(2); p = 0.029). There was no significant difference in LF/HF or CV(R-R) between the groups. Conclusion: HF, which is modulated by parasympathetic vagal activity, was low in our MJD patients. The reduced parasympathetic activity may be a cause of tachycardia in MJD patients. (C) 2009 Elsevier B.V. All rights reserved.
  • Tatsuya Yamamoto, Ryuji Sakakibara, Ken Nakazawa, Tomoyuki Uchiyama, Eiji Shimizu, Takamichi Hattori, Satoshi Kuwabara
    NEUROSCIENCE LETTERS 473(1) 42-47 2010年3月  査読有り
    The forebrain is one of the important suprapontine micturition centres. Previous studies have shown that electrical stimulation of the frontal lobe and the anterior cingulate gyrus elicited either inhibition or facilitation of bladder contraction. Patients with frontal lobe tumours and aneurysms showed micturition disorders. Functional brain imaging studies showed that several parts of the forebrain are activated during bladder filling. We aimed to examine neuronal activities of forebrain structures with respect to bladder contraction in cats. In 14 adult male cats under ketamine anaesthesia in which a spontaneous isovolumetric bladder-contraction/relaxation cycle had been generated, we carried out extracellular single-unit recording in forebrain with respect to the contraction/relaxation cycles in the bladder. We recorded 112 neurons that were related to the bladder-contraction/relaxation cycles. Ninety-four neurons were found to be tonically activated during the bladder-relaxation phase, whereas the remaining 18 neurons were tonically activated during the bladder-contraction phase. Both types of neuron were widely distributed around the cruciate sulcus. Most were located medially (medial and superior frontal gyrus) and the rest were located laterally (middle and inferior frontal gyrus). Neurons recorded in forebrain structures were activated with respect to the contraction/relaxation cycles in the bladder. Forebrain structures may have a significant role in regulating bladder contraction in cats. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
  • Satoshi Kuwabara
    CLINICAL NEUROPHYSIOLOGY 121(1) 1-2 2010年1月  査読有り
  • Setsu Sawai, Hiroshi Umemura, Masahiro Mori, Mamoru Satoh, Sei Hayakawa, Yoshio Kodera, Takeshi Tomonaga, Satoshi Kuwabara, Fumio Nomura
    JOURNAL OF NEUROIMMUNOLOGY 218(1-2) 112-115 2010年1月  査読有り
    To detect serum biomarkers associated with disease activity in relapsing-remitting multiple sclerosis (MS). We Studied serum low-molecular peptide profiling of MS patients and normal controls comprehensively by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Serum level of 1741 Da peptide was increased at the time of clinical relapse in patients than in normal controls and returned toward normal during remission. Tandem mass spectrometry analysis revealed that the peptide was a fragment of complement C4 (NGFKSHALQLNNRQI). This fragment peptide could be a possible marker of disease activity. It may reflect complement activation in the pathogenesis of MS. (C) 2009 Elsevier B.V. All rights reserved.
  • Setsu Sawai, Sonoko Misawa, Makoto Kobayashi, Kazuaki Kanai, Sagiri Isose, Kazumoto Shibuya, Yukari Sekiguchi, Saiko Nasu, Yuichi Noto, Yumi Fujimaki, Shunsuke Koga, Ryohei Ohtani, Satoshi Kuwabara
    INTERNAL MEDICINE 49(5) 471-474 2010年  査読有り
    Peripheral neuropathy is a rare manifestation of sarcoidosis, and previous studies have shown axonal degeneration as the main pathology. We herein report three patients with sarcoidosis who presented with multiple mononeuropathy as the initial manifestation. Nerve conduction studies showed prominent multifocal conduction blocks in the intermediate nerve trunk. In all three patients, corticosteroid treatment resulted in a dramatic clinical improvement associated with rapid resolution of conduction blocks. The sequential electrodiagnostic findings suggest that demyelinative or ischemic-functional conduction block is responsible for their neuropathy. To date, only three cases of acute conduction block neuropathy associated with sarcoidosis have been reported, but it may occur more frequently than expected.
  • Tatsuya Yamamoto, Tomoyuki Uchiyama, Hirokatsu Takahashi, Keiichi Himuro, Kazuaki Kanai, Satoshi Kuwabara
    INTERNAL MEDICINE 49(7) 707-708 2010年  査読有り
    Although immunosuppressive effects of antiepileptic drug are well known, serious complications of antiepileptic drug are rare. We report a case of hypogammaglobulinemia associated with aplasia of B lymphocytes after carbamazepine treatment. Despite repeated intravenous immunoglobulin replacement therapy, this condition persisted for more than three months. The present case suggested that routine monitoring of the blood cell count and serum levels of immunoglobulin are important in patients treated with carbamazepine, and a lymphocyte subpopulation study is valuable in cases of hypogammaglobulinemia.
  • Satoshi Kuwabara
    Clinical Neurology 50(4) 219-224 2010年  査読有り
    There are significant advances in immune-modulating treatments for Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) in the past 20 years. GBS, however, is still a serious disease with a mortality rate of 8% and 20% of the patients being unable to walk independently a year after onset. For CIDP and related disorders such as multifocal motor neuropathy, and demyeinating neuropathy with antimyelin-associated-glycoprotein (MAG) antibody, treatments should be based on individual pathophysiology. Rituximab could be a promising agent for the subtypes of CIDP refractory to conventional immune treatments. Crow-Fukase syndrome is a rare cause of demyelinating neuropathy with multiorgan involvement. Overproduction of vascular endothelial growth factor (VEGF), probably mediated by monoclonal proliferation of plasma cells, is likely to be responsible for most of the characteristic symptoms. There is no established treatment regimen for Crow-Fukase syndrome. In appropriate candidates, high-dose chemotherapies with autologous peripheral blood stem cell transplantation is highly recommended, because this treatment could result in obvious improvement in neuropathy as well as other symptoms. Indication of this treatment has not yet been established, and long-term prognosis is unclear at present. Treatments that should be considered as future therapy against Crow-Fukase syndrome include thalidomide, and anti-VEGF monoclonal antibody (bevacizumab).
  • Akiyuki Hiraga, Masahiro Mori, Satoshi Kuwabara
    Autoimmune Diseases: Symptoms, Diagnosis and Treatment 265-278 2010年1月1日  
    Guillain–Barré syndrome is currently classified into 2 major forms based on pathologic and electrophysiologic criteria: (1) acute inflammatory demyelinating polyneuropathy (AIDP), by far the most common form in western countries and (2) acute motor axonal neuropathy (AMAN), which is more prevalent in East Asia (China and Japan). AMAN is characterized by electrophysiologic and pathologic evidence of axonal degeneration of the motor nerves as well as functional conduction failure or other pathophysiology. It is possibly associated with anti-ganglioside antibodies in particular, IgG antibodies to the gangliosides GM1, GM1b, GD1a and GalNAc-GD1a, which may be induced by particular infectious agents such as Campylobacter jejuni or Haemophilus influenza. Although AMAN appears to be similar to AIDP, there are important clinical differences. AMAN is a pure motor syndrome, with infrequent and mild involvement of the autonomic nervous system. When sensory fibres are also affected, this axonal subtype is called acute motor and sensory axonal neuropathy. Patients with AMAN often show hyperreflexia in the recovery phase. AMAN has a rapid progression in its early stage and has an earlier nadir than AIDP. AMAN has 2 patterns of clinical recovery, rapid and prolonged, in contrast to the relatively uniform recovery seen in AIDP. Electrophysiologic evidence of axonal degeneration is thought to be an indicator of poor prognosis. However, the most severely disabled AMAN patients are able to walk independently within a few years, indicating that electrodiagnosis of AMAN is not always a marker of poor recovery. This review provides an update on the clinical features, recovery pattern and long-term prognosis in AMAN patients.
  • Satoshi Kuwabara
    Clinical Neurology 50(11) 794-796 2010年  査読有り
    Crow-Fukase syndrome, also called POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome, is a rare cause of demyelinating and axonal mixed neuropathy with multiorgan involvement. The pathogenesis of Crow-Fukase syndrome is not well understood, but overproduction of vascular endothelial growth factor (VEGF), probably mediated by monoclonal proliferation of plasma cells, is likely to be responsible for most of the characteristic symptoms. There is no established treatment regimen. In appropriate candidates, high-dose chemotherapies with autologous peripheral blood stem cell transplantation is highly recommended, because this treatment could result in obvious improvement in neuropathy as well as other symptoms, with a significant decrease in serum VEGF levels. Indication of this treatment has not yet been established, and long-term prognosis is unclear at present. Thalidomide should be considered for patients who are not indicated for transplantation therapy. Treatments that should be considered as future therapy include lenalidomide, bortezomib, and anti-VEGF monoclonal antibody (bevacizumab).
  • C. Yamaguchi, T. Uchiyama, T. Yamamoto, R. Sakakibara, M. Yanagisawa, M. Yano, Y. Awa, K. Mamada, Y. Sawabe, T. Yamanishi, S. Kuwabara, F. Nomura
    NEUROUROLOGY AND URODYNAMICS 29(6) 1108-1109 2010年  
  • T. Uchiyama, R. Sakakibara, T. Yamamoto, T. Ito, C. Yamaguchi, M. Yanagisawa, M. Yano, Y. Awa, T. Yamanishi, T. Hattori, S. Kuwabara
    MOVEMENT DISORDERS 25(7) S336-S336 2010年  
  • Shunsuke Koga, Shunsuke Kojima, Takashi Kishimoto, Atsushi Yamaguchi, Satoshi Kuwabara
    NEUROSCIENCE RESEARCH 68 E207-E207 2010年  
  • Akiyuki Uzawa, Masahiro Mori, Michihiro Ito, Tomohiko Uchida, Sei Hayakawa, Saeko Masuda, Satoshi Kuwabara
    JOURNAL OF NEUROLOGY 256(12) 2082-2084 2009年12月  査読有り
    To investigate differences in helper T cell immune responses in cerebrospinal fluid (CSF) between neuromyelitis optica (NMO) and multiple sclerosis (MS), we measured CSF levels of interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-alpha and interferon-gamma at the time of relapse in 17 NMO patients and 21 MS patients using fluorescence-activated cell sorting. CSF IL-6 levels were significantly higher in NMO patients than in patients with MS (P = 0.001) and other neurological diseases (P = 0.001). The other cytokines tested were undetectable. Elevated CSF levels of IL-6 in only NMO supports the view of different pathophysiologies of NMO and MS. CSF IL-6 levels may be useful in the differential diagnosis of the two disorders.
  • Akiyuki Uzawa, Masahiro Mori, Yuhta Iwai, Makoto Kobayashi, Sei Hayakawa, Naoki Kawaguchi, Satoshi Kuwabara
    JOURNAL OF THE NEUROLOGICAL SCIENCES 287(1-2) 105-107 2009年12月  査読有り
    We describe 2 patients who developed anti-aquaporin-4 antibody-positive neuromyelitis optica (NMO) following the development of anti-acetylcholine receptor antibody-positive myasthenia gravis (MG). A literature review of 13 similar cases in addition to the present 2 cases of NMO with MG showed predominance among Asian women and frequent development of NMO following thymectomy for MG. Moreover, in one of our patients, serial assays of anti-aquaporin-4 antibody and anti-acetylcholine receptor antibody were performed. Accumulating evidence for the coexistence of NMO and MG suggests that a common immunopathogenesis of NMO and MG may exist, and the association of NMO with MG may be more frequent than hitherto believed. (C) 2009 Elsevier B.V. All rights reserved.
  • Akiyuki Uzawa, Masahiro Mori, Shigeyuki Kojima, Satsuki Mitsuma, Yukari Sekiguchi, Toshihide Kanesaka, Satoshi Kuwabara
    MOVEMENT DISORDERS 24(16) 2408-2411 2009年12月  査読有り
    Few cases of dopamine agonist-induced antecollis in Parkinson's disease (PD) have been reported. Literature review of 16 PD patients including our 3 cases with dopamine agonist-induced antecollis showed predominance of (1) Japanese, (2) women, and (3) Hoehn-Yahr stage of >= 3. We experienced three Japanese PD patients who subacutely exhibited antecollis following increased dopamine agonist dose that improved just after withdrawal of the agonist. One patient developed antecollis during increasing pramipexole dose in combination with cabergoline. Antecollis in another patient appeared during increasing pramipexole dose; it worsened after substituting pergolide for pramipexole, but improved after withdrawal of pergolide. Our cases indicate that there is no specific dopamine agonist causing antecollis, and it is possibly caused by a number of single dopamine agonists or a combination of them. Dopamine agonist-induced antecollis should be considered when encountering antecollis in PD patients being treated with dopamine agonists and withdrawal of the agonist can improve symptoms. (C) 2009 Movement Disorder Society
  • Tomoyuki Uchiyama, Ryuji Sakakibara, Tatsuya Yamamoto, Takashi Ito, Chiharu Yamaguchi, Yusuke Awa, Masashi Yano, Mitsuru Yanagisawa, Makoto Kobayashi, Yoshinori Higuchi, Tomohiko Ichikawa, Tomonori Yamanishi, Takamichi Hattori, Satoshi Kuwabara
    MOVEMENT DISORDERS 24(16) 2386-2390 2009年12月  査読有り
    To evaluate the effects of bromocriptine on bladder function in Parkinson's disease (PD) patients and compare these effects with those of (L-dopa). We recruited 8 patients with PD. Urodynamic study (UDS) was performed before and I hour after administering 100 mg L-dopa/decarboxylase inhibitor (DCI) and 2.5 hours after administering 7.5 mg bromocriptine. After the bromocriptine administration, urinary urgency aggravated. UDS revealed a decreased bladder volume at which detrusor overactivity (DO) was initiated, a decreased bladder volume at first sensation of bladder filling (FSV) (P < 0.05), an increased maximum Watts Factor value (WFmax) (detrusor contractility), a decreased Abrams-Griffiths (AG) number (urethral obstruction), and a decreased postvoid residual (PVR) (P < 0.01). Similarly, after the L-dopa administration, urinary urgency aggravated. UDS revealed an aggravated DO (P < 0.05), a decreased FSV and bladder capacity (P < 0.01, 0.05), an increased WFmax (P < 0.05), an increased AG number, and a decreased PVR (P < 0.01). A single dose of bromocriptine proved to exacerbate urinary urgency and DO in the storage phase, and improve bladder emptying through increased detrusor contractility and decreased bladder outlet obstruction, within hours. With the exception of bladder outlet obstruction, these effects of bromocriptine are similar to the effects of L-dopa, albeit slightly less pronounced. (C) 2009 Movement Disorder Society
  • Misawa S, Sakurai K, Shibuya K, Isose S, Kanai K, Ogino J, Ishikawa K, Kuwabara S
    Journal of the peripheral nervous system : JPNS 14(4) 279-284 2009年12月  査読有り
  • Junko Taniguchi, Setsu Sawai, Masahiro Mori, Takekazu Kubo, Kazuaki Kanai, Sonoko Misawa, Sagiri Isose, Toshihide Yamashita, Satoshi Kuwabara
    ANNALS OF NEUROLOGY 66(5) 694-697 2009年11月  査読有り
    Clinical course and prognosis are variable among patients with chronic inflammatory demyelinating polyneuropathy (CIDP), whereas the extent of axonal degeneration is the major prognostic factor. We studied the effects of sera from CIDP patients on axonal growth in cultured mouse dorsal root ganglion neurons. Compared with control sera, CIDP sera prominently Suppressed axonal Outgrowth of dorsal root ganglion neurons and shortened axonal length. The inhibitory activity was abolished by adding Y27632, a Rho-kinase inhibitor. These findings suggest that CIDP sera inhibit axonal elongation by Rho-kinase activation, and some serum factors may be responsible for development of axonal degeneration in CIDP.
  • Satoshi Kuwabara, Kazuaki Kanai, Sonoko Misawa, Chiaki Nakaseko
    19(10) 740-741 2009年10月  査読有り
  • K. Kanai, S. Yoshida, S. Hirose, H. Oguni, S. Kuwabara, S. Sawai, A. Hiraga, G. Fukuma, H. Iwasa, T. Kojima, S. Kaneko
    JOURNAL OF THE NEUROLOGICAL SCIENCES 285 S244-S244 2009年10月  
  • S. Kuwabara, S. Misawa, K. Kanai, C. Nakaseko
    NEUROLOGY 73(14) 1165-1166 2009年10月  
  • Satoshi Kuwabara, Kazuaki Kanai, Sonoko Misawa, Chiaki Nakaseko
    NEUROMUSCULAR DISORDERS 19(10) 740-740 2009年10月  
  • S. Misawa, S. Isose, K. Kanai, Y. Noto, S. Kuwabara
    JOURNAL OF THE NEUROLOGICAL SCIENCES 285 S148-S148 2009年10月  
  • Y. Fujimaki, K. Kanai, S. Misawa, S. Isose, K. Shibuya, Y. Noto, S. Nasu, Y. Sekiguchi, S. Kuwabara
    JOURNAL OF THE NEUROLOGICAL SCIENCES 285 S142-S142 2009年10月  
  • H. Shimada, K. Fukushi, K. Sato, H. Shinotoh, M. Miyoshi, S. Hirano, N. Tanaka, T. Ota, H. Ito, S. Kuwabara, T. Irie, T. Suhara
    JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM 29 S322-S322 2009年10月  
  • K. Kanai, S. Yoshida, S. Hirose, H. Oguni, S. Kuwabara, S. Sawai, A. Hiraga, G. Fukuma, H. Iwasa, T. Kojima, S. Kaneko
    JOURNAL OF MEDICAL GENETICS 46(10) 671-679 2009年10月  査読有り
    Background: Several different missense mutations in the voltage-gated sodium channel subunit gene SCN1A have been identified in epileptic patients with benign phenotype and patients with severe phenotype. However, the reason why similar missense mutations in SCN1A result in different phenotypes has not yet been fully clarified. Objective: To clarify the phenotype-genotype relationship in SCN1A, a meta-analysis was performed to quantitatively determine the effect of amino acid substitutions in SCN1A on epilepsy severity phenotype using physicochemical property indices of the amino acid, and to discuss in the context of the molecular evolution of the proteins. Methods: PubMed was searched for articles and information was extracted on localisation and types of SCN1A missense mutations in patients with benign and severe epileptic syndromes; detailed information was also extracted. Results: Meta-analysis quantitatively revealed that the physicochemical properties of several amino acids significantly affected epilepsy phenotype severity. It showed that missense mutations that decreased protein hydrophobicity were significantly associated with severe epilepsy phenotypes. It also showed that the phenotype severity of SCN1A missense mutations in the transmembrane domains of SCN1A (128/155; 82.6%)could be predicted with high sensitivity and positive predictive values using the physicochemical property changes, indicating the possibility of phenotype prediction for entirely new missense mutations using analytical methods. Conclusions: The results show that changes in the physicochemical properties of amino acids affected both the phenotype and clinical symptoms of patients with SCN1A missense mutations. This meta-analysis study provides new insights into SCN1A gene functions and a new strategy for genetic diagnosis, genetic counselling and epilepsy treatment.

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