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Mahjong is one of the most popular Chinese tile games played in Japan. Mahjong-related seizures (MRS) are rare praxis-induced seizures. We identified three patients with MRS from February 2000 to February 2021. All cases were men, with a middle-age onset, generalized convulsive seizures, and lack of non-provoked, myoclonic, and absence seizures. All patients had no or non-specific neuroimaging or electroencephalogram abnormalities. They did not have features linked to idiopathic generalized epilepsy. All patients were seizure-free after behavioral adjustments, although one patient required anti-seizure medication and avoided long duration games. These changes may help other patients with MRS continue playing Mahjong.
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Epilepsia Generalizada , Jogos Recreativos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , População do Leste Asiático , Eletroencefalografia , Epilepsia Generalizada/diagnóstico , Epilepsia Generalizada/tratamento farmacológico , Epilepsia Generalizada/etiologia , Japão , Convulsões/etiologia , Fatores de Tempo , Jogos Recreativos/lesões , Jogos Recreativos/psicologiaRESUMO
OBJECTIVE: This study was aimed at assessing intraplaque neovessels, focusing on neovascularization from the vascular luminal side using contrast-enhanced ultrasound (CEUS) and determining that this contrast effect indicates that the neovessel is connected to the vessel lumen histopathologically. Whether plaque vulnerability can be assessed more accurately was also investigated. METHODS: We enrolled consecutive patients with internal carotid artery stenosis who underwent carotid endarterectomy (CEA) and pre-operative CEUS with perflubutane of the carotid arteries. We graded the contrast effect semi-quantitatively from the vascular luminal and adventitial sides. We compared the contrast effect with the pathological findings, especially the neovascularization of the CEA specimens. RESULTS: In total, 68 carotid arterial atheromatous plaques (47 symptomatic) were analyzed. Symptomatic plaques were significantly correlated with stronger contrast effects from the luminal side than from the adventitial side (p = 0.0095). Microbubbles from the luminal side appeared to flow mainly into the plaque shoulder. The contrast effect value for the plaque shoulder and neovessel density were significantly correlated (ρ = 0.35, p = 0.031). Neovessel density was significantly higher in symptomatic than in asymptomatic plaques (56.2 ± 43.7/mm2 and 18.1 ± 15.2/mm2, respectively, p < 0.0001). Serial histological sections of CEA specimens in a symptomatic plaque with a strong contrast effect from the luminal side revealed multiple neovessels fenestrated to the vessel lumen with endothelial cells, consistent with the CEUS findings. CONCLUSION: Contrast-enhanced ultrasound can be used to evaluate neovessels originating from the luminal side, histopathologically confirmed in serial sections. Symptomatic vulnerable plaque is correlated more significantly with intraplaque neovascularization from the luminal side than with neovascularization from the adventitia.
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Estenose das Carótidas , Endarterectomia das Carótidas , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/cirurgia , Placa Aterosclerótica/patologia , Células Endoteliais , Meios de Contraste , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/cirurgia , Artérias Carótidas/patologia , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Estenose das Carótidas/patologia , Ultrassonografia , Neovascularização Patológica/diagnóstico por imagemRESUMO
Proline-rich transmembrane protein 2 (PRRT2) was confirmed as the causative gene of paroxysmal kinesigenic dyskinesia (PKD) as shown by genome-wide linkage analyses. PRRT2 mutations are also associated with benign familial infantile seizures, infantile convulsions and choreoathetosis, and childhood absence epilepsy, but few reports have investigated adult-onset epilepsy. We describe here a rare presentation of adult-onset focal epilepsy with a PRRT2 mutation in a 31-year-old woman who showed cerebellar atrophy, familial paroxysmal kinesigenic dyskinesia, and paroxysmal non-kinesigenic dystonia. Video-electroencephalography (EEG) demonstrated focal impaired awareness seizures, in which ictal EEG changes showed left temporal onset with rhythmic theta activity over the left temporal region. Magnetic resonance imaging showed mild cerebellar atrophy. The administration of lamotrigine 50 mg/day resulted in freedom from her seizures and lamotrigine 150 mg/day reduced paroxysmal non-kinesigenic dystonia. Furthermore, she had a rare frameshift mutation, c.604_607del, p.Ser202fs of which the pathogenicity has been reported in ClinVar, but it has not been reported in Japan. Mutation of the PRRT2 gene can cause adult-onset epilepsy, paroxysmal non-kinesigenic movement disorder, and cerebellar atrophy, suggesting an expanding clinical phenotypic spectrum associated with PRRT2 mutations.
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Poststroke epilepsy is a major ischaemic/haemorrhagic stroke complication. Seizure recurrence risk estimation and early therapeutic intervention are critical, given the association of poststroke epilepsy with worse functional outcomes, quality of life and greater mortality. Several studies have reported risk factors for seizure recurrence; however, in poststroke epilepsy, the role of EEG in predicting the risk of seizures remains unclear. This multicentre observational study aimed to clarify whether EEG findings constitute a risk factor for seizure recurrence in patients with poststroke epilepsy. Patients with poststroke epilepsy were recruited from the PROgnosis of POst-Stroke Epilepsy study, an observational multicentre cohort study. The enrolled patients with poststroke epilepsy were those admitted at selected hospitals between November 2014 and June 2017. All patients underwent EEG during the interictal period during admission to each hospital and were monitored for seizure recurrence over 1 year. Board-certified neurologists or epileptologists evaluated all EEG findings. We investigated the relationship between EEG findings and seizure recurrence. Among 187 patients with poststroke epilepsy (65 were women with a median age of 75 years) admitted to the lead hospital, 48 (25.7%) had interictal epileptiform discharges on EEG. During the follow-up period (median, 397 days; interquartile range, 337-450 days), interictal epileptiform discharges were positively correlated with seizure recurrence (hazard ratio, 3.82; 95% confidence interval, 2.09-6.97; P < 0.01). The correlation remained significant even after adjusting for age, sex, severity of stroke, type of stroke and generation of antiseizure medications. We detected periodic discharges in 39 patients (20.9%), and spiky/sharp periodic discharges were marginally associated with seizure recurrence (hazard ratio, 1.85; 95% confidence interval, 0.93-3.69; P = 0.08). Analysis of a validation cohort comprising 187 patients with poststroke epilepsy from seven other hospitals corroborated the association between interictal epileptiform discharges and seizure recurrence. We verified that interictal epileptiform discharges are a risk factor for seizure recurrence in patients with poststroke epilepsy. Routine EEG may facilitate the estimation of seizure recurrence risk and the development of therapeutic regimens for poststroke epilepsy.
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BACKGROUND AND OBJECTIVES: The functional outcome and mortality of patients with poststroke epilepsy (PSE) have not been assessed in a prospective study. Previous reports have suggested that patients with PSE may suffer from prolonged functional deterioration after a seizure. In this study, we prospectively investigated the functional outcome and mortality of patients with PSE and analyzed the effect of seizure recurrence on the outcomes. METHODS: This is part of the Prognosis of Post-Stroke Epilepsy study, a multicenter, prospective observational cohort study, where 392 patients with PSE (at least 1 unprovoked seizure more than 7 days after the onset of the last symptomatic stroke) were followed for at least 1 year at 8 hospitals in Japan. This study included only PSE patients with a first-ever seizure and assessed their functional decline and mortality at 1 year. Functional decline was defined as an increase in modified Rankin Scale (mRS) score at 1 year compared with baseline, excluding death. The associations between the seizure recurrence and the outcomes were analyzed statistically. RESULTS: A total of 211 patients (median age of 75 years; median mRS score of 3) were identified. At 1 year, 50 patients (23.7%) experienced seizure recurrence. Regarding outcomes, 25 patients (11.8%) demonstrated functional decline and 20 (9.5%) had died. Most patients died of pneumonia or cardiac disease (7 patients each), and no known causes of death were directly related to recurrent seizures. Seizure recurrence was significantly associated with functional decline (odds ratio [OR] 2.96, 95% CI 1.25-7.03, p = 0.01), even after adjusting for potential confounders (adjusted OR 3.26, 95% CI 1.27-8.36, p = 0.01), but not with mortality (OR 0.79, 95% CI 0.25-2.48, p = 0.68). Moreover, there was a significant trend where patients with more recurrent seizures were more likely to have functional decline (8.7%, 20.6%, and 28.6% in none, 1, and 2 or more recurrent seizures, respectively; p = 0.006). DISCUSSION: One-year functional outcome and mortality of patients with PSE were poor. Seizure recurrence was significantly associated with functional outcome, but not with mortality. Further studies are needed to ascertain whether early and adequate antiseizure treatment can prevent the functional deterioration of patients with PSE.
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Epilepsia Generalizada , Epilepsia , Acidente Vascular Cerebral , Idoso , Epilepsia/complicações , Epilepsia Generalizada/complicações , Humanos , Estudos Prospectivos , Recidiva , Convulsões/complicações , Acidente Vascular Cerebral/complicaçõesRESUMO
A 36-year-old woman with neuromyelitis optica had been treated with steroids for the prevention of relapse. However, her treatment was not effective and she showed adverse effects such as diabetes mellitus, osteoporosis, compression fractures, and Pneumocystis carinii pneumonia. Therefore, we started her on mitoxantrone treatment. After five courses of mitoxantrone injection, she developed a herpes zoster infection in her thigh followed by aseptic meningitis. PCR for varicella zoster virus (VZV)-DNA was positive in the cerebrospinal fluid. The mechanisms that caused VZV reactivation by mitoxantrone are not known. Opportunistic herpes virus reactivation may occur easily with increasing use of immunosuppressive drugs for both neuromyelitis optica and multiple sclerosis. These drugs must be used under careful supervision.
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Herpes Zoster/etiologia , Meningite Viral/etiologia , Mitoxantrona/efeitos adversos , Neuromielite Óptica/tratamento farmacológico , Adulto , Feminino , Humanos , Neuromielite Óptica/complicações , Ativação ViralRESUMO
Polyneuropathy associated with antibodies directed against myelin-associated glycoprotein (MAG) is a chronic symmetric sensorimotor demyelinating neuropathy caused by monoclonal IgM against MAG (anti-MAG neuropathy). Intravenous immunoglobulin therapy (IVIg) has been partially successful in patients with anti-MAG neuropathy. A placebo-controlled trial of rituximab in patients with anti-MAG neuropathy has been reported. We report rapid improvement in a patient with anti-MAG neuropathy using rituximab. A 58-year-old man presented with abnormal sensation, weakness of the limbs, and unsteadiness. He was previously diagnosed with chronic inflammatory demyelinating neuropathy and was treated with steroid pulse therapy and IVIg. However, these treatments were not effective. On examination at our hospital, he showed areflexia in all limbs, mild weakness in distal portions of upper and lower extremities, sensory ataxia, and hypesthesia/hypalgesia except for his face. He showed high serum IgM levels (323mg/dl). He did not show M protein on immunoelectrophoresis; however, anti-MAG and anti-sulfoglucuronyl paragloboside (SGPG) antibodies were detected by immunoblot and enzyme-linked immunosorbent assay, respectively. He was diagnosed with anti MAG neuropathy and was administered four cycles of intravenous rituximab at a dose of 375mg/m(2)/week. After the first cycle of rituximab administration, he showed improvement in two-point discrimination of middle fingers (10/13 before therapy to 7/7mm after administration). Two-point discrimination and vibration markedly improved after four cycles of rituximab administration. Romberg sign became negative after 7 months. Anti-SGPG antibody titers reduced from 0.554 before rituximab administration to 0.307 (OD) at 1,600 dilution, 4 months after administration. We concluded that rituximab was effective for the treatment of anti-MAG neuropathy. We suggested that rapid and long-term improvement in our patient might be caused not only by preventing the formation of new antibody-secreting cells and antibody-titer reduction but also affecting the balance of proinflammatory cytokines and regulatory cytokines production.
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Anticorpos Monoclonais Murinos/uso terapêutico , Autoanticorpos/sangue , Doenças Desmielinizantes/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Glicoproteína Associada a Mielina/imunologia , Polineuropatias/tratamento farmacológico , Doenças Desmielinizantes/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Polineuropatias/imunologia , RituximabRESUMO
BACKGROUND AND PURPOSE: The management of post-stroke epilepsy (PSE) should ideally include prevention of both seizure and adverse effects; however, an optimal antiseizure medications (ASM) regimen has yet been established. The purpose of this study is to assess seizure recurrence, retention, and tolerability of older-generation and newer-generation ASM for PSE. METHODS: This prospective multicenter cohort study (PROgnosis of Post-Stroke Epilepsy [PROPOSE] study) was conducted from November 2014 to September 2019 at eight hospitals. A total of 372 patients admitted and treated with ASM at discharge were recruited. Due to the non-interventional nature of the study, ASM regimen was not adjusted and followed standard hospital practices. The primary outcome was seizure recurrence in patients receiving older-generation and newer-generation ASM. The secondary outcomes were the retention and tolerability of ASM regimens. RESULTS: Of the 372 PSE patients with ASM at discharge (median [IQR] age, 73 [64-81] years; 139 women [37.4%]), 36 were treated with older-generation, 286 with newer-generation, and 50 with mixed-generation ASM. In older- and newer-generation ASM groups (n = 322), 98 patients (30.4%) had recurrent seizures and 91 patients (28.3%) switched ASM regimen during the follow-up (371 [347-420] days). Seizure recurrence was lower in newer-generation, compared with the older-generation, ASM (hazard ratio [HR], 0.42, 95%CI 0.27-0.70; p = .0013). ASM regimen withdrawal and change of dosages were lower in newer-generation ASM (HR, 0.34, 95% CI 0.21-0.56, p < .0001). CONCLUSIONS: Newer-generation ASM possess advantages over older-generation ASM for secondary prophylaxis of post-stroke seizures in clinical practice.
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Anticonvulsivantes , Epilepsia , Idoso , Anticonvulsivantes/uso terapêutico , Estudos de Coortes , Epilepsia/tratamento farmacológico , Feminino , Humanos , Estudos Prospectivos , Convulsões/tratamento farmacológico , Convulsões/etiologiaRESUMO
A previously healthy, 10-year-old girl developed left optic neuritis that treated with oral prednisolon (PSL). During the following 8 months, the patient exhibited right optic neuritis 3 days after discontinuation of PSL therapy and three episodes of epileptic seizures 3 weeks after PSL withdrawal Cerebrospinal fluid (CSF) examination revealed pleocytosis (mononuclear cells), increased IgG index, and positive oligoclonal IgG expression. Brain MRI showed multiple cortical, subcortical, and leptomeningeal enhanced lesions. However, spinal cord MRI revealed no lesions. Neither autoantibodies to nuclear, thyroid, alpha-enolase, glutamic acid decarboxylase, nor aquaporin 4 was detected. However, anti-NMDA receptor antibodies (NMDAR-Ab) were present in her CSF. This patient is the second reported case of NMDAR-related encephalitis with recurrent optic neuritis. The possibility of seronegative neuromyelitis optica (NMO) could not be ruled out for the symptom of recurrent optic neuritis. However, the presence of NMDAR-Ab in the CSF together with increased IgG index and oligoclonal IgG bands, which are usually negative in NMO suggested that this patient is NMDAR-related encephalitis combined with rare symptom of optic neuritis for this type of encephalitis, though we need to wait larger number of patients' accumulation to conclude that the optic neuritis could be one of the features of NMDAR-related encephalitis.
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Autoanticorpos/sangue , Encefalite/complicações , Encefalite/imunologia , Epilepsia/etiologia , Neurite Óptica/etiologia , Receptores de N-Metil-D-Aspartato/imunologia , Criança , Feminino , Humanos , RecidivaRESUMO
Background We aimed to improve the assessment quality of plaque vulnerability with combined use of magnetic resonance imaging and contrast-enhanced ultrasound ( CEUS ). Methods and Results We prospectively enrolled 71 patients with internal carotid artery stenosis who underwent carotid endarterectomy and performed preoperative CEUS and magnetic resonance plaque imaging. We distinguished high-signal-intensity plaques ( HIP s) and non- HIP s based on magnetization-prepared rapid acquisition with gradient echo images. We graded them according to the CEUS contrast effect and compared the CEUS images with the carotid endarterectomy specimens. Among the 70 plaques, except 1 carotid endarterectomy tissue sample failure, 59 were classified as HIP s (43 symptomatic) and 11 were classified as non- HIP s (5 symptomatic). Although the magnetization-prepared rapid acquisition with gradient echo findings alone had no significant correlation with symptoms ( P=0.07), concomitant use of magnetization-prepared rapid acquisition with gradient echo and CEUS findings did show a significant correlation ( P<0.0001). CEUS showed that all 5 symptomatic non- HIP s had a high-contrast effect. These 5 plaques were histopathologically confirmed as vulnerable, with extensive neovascularization but only a small amount of intraplaque hemorrhage. Conclusions Complementary use of magnetic resonance imaging and CEUS to detect intraplaque hemorrhage and neovascularization in plaques can be useful for evaluating plaque vulnerability, consistent with the destabilization process associated with neovessel formation and subsequent intraplaque hemorrhage.
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Estenose das Carótidas/diagnóstico por imagem , Placa Aterosclerótica/diagnóstico por imagem , Idoso , Estenose das Carótidas/patologia , Estenose das Carótidas/cirurgia , Meios de Contraste , Endarterectomia das Carótidas , Feminino , Hemorragia/diagnóstico por imagem , Hemorragia/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Neovascularização Patológica/diagnóstico por imagem , Neovascularização Patológica/patologia , Placa Aterosclerótica/patologia , Placa Aterosclerótica/cirurgia , Medição de Risco , Índice de Gravidade de Doença , UltrassonografiaRESUMO
Mahjong, a game similar to bridge and chess in Western cultures, can cause reflex seizure. We report a case of Mahjong-induced seizures with the first documentation of ictal electroencephalography (EEG) findings, which showed secondarily generalized partial seizure of the right parietal origin.
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BACKGROUND: Seizure is a common complication after stroke (termed "post-stroke seizure," PSS). Although many studies have assessed outcomes and risk factors of PSS, no reliable predictors are currently available to determine PSS recurrence. We compared baseline clinical characteristics and post-stroke treatment regimens between recurrent and non-recurrent PSS patients to identify factors predictive of recurrence. METHODS: Consecutive PSS patients admitted to our stroke center between January 2011 and July 2013 were monitored until February 2014 (median 357 days; IQR, 160-552) and retrospectively evaluated for baseline clinical characteristics and PSS recurrence. Cumulative recurrence rates at 90, 180, and 360 days post-stroke were estimated by Kaplan-Meier analysis. Independent predictors of recurrent PSS were identified by Cox proportional-hazards analysis. RESULTS: A total of 104 patients (71 men; mean age, 72.1 ± 11.2 years) were analyzed. PSS recurred in 31 patients (30%) during the follow-up. Factors significantly associated with PSS recurrence by log-rank analysis included previous PSS, valproic acid (VPA) monotherapy, polytherapy with antiepileptic drugs (AEDs), frontal cortical lesion, and higher modified Rankin Scale score at discharge (all p < 0.05). Independent predictors of recurrent PSS were age <74 years (HR 2.38, 95% CI 1.02-5.90), VPA monotherapy (HR 3.86, 95% CI 1.30-12.62), and convulsions on admission (HR 3.87, 95% CI 1.35-12.76). CONCLUSIONS: Approximately one-third of PSS patients experienced seizure recurrence within one year. The predictors of recurrent PSS were younger age, presence of convulsions and VPA monotherapy. Our findings should be interpreted cautiously in countries where monotherapy with second-generation AEDs has been approved because this study was conducted while second-generation AEDs had not been officially approved for monotherapy in Japan.
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Convulsões/diagnóstico , Convulsões/etiologia , Acidente Vascular Cerebral/complicações , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Recidiva , Estudos Retrospectivos , Fatores de Risco , Convulsões/epidemiologiaRESUMO
OBJECTIVES: Month of birth has been associated with the environmental factors for multiple sclerosis (MS). This study aimed to investigate whether individuals with MS had significantly different frequencies of birth in a particular month of the year, and whether month-of-birth patterns were influenced by the longitudinally extensive spinal cord lesions (LESCL) status relative to the general population in the same Japanese birth cohort. METHODS: In this study, performed as a part of the fourth Japanese nationwide survey of MS, patients were divided into two groups according to the presence (n=307) or absence (n=906) of LESCLs that were diagnosed on the basis of magnetic resonance imaging findings. The number of births in every month was counted for both groups. Control data were obtained from birth records of the Japanese general population of the median years of birth of each group. Differences in the month-of-birth distributions between the patients and the general population were assessed using the chi-square test. RESULTS: In MS patients without LESCLs, significantly more patients were born in January and June, whereas significantly fewer patients were born in May, compared to the general population. The seasonal patterns of birth were not in association with those of ambient ultraviolet (UV) radiation. No significant differences were found for the month-of-birth distributions between MS patients with LESCLs and the general population. CONCLUSIONS: A different distribution of month of birth in Japanese MS patients without LESCLs from the general population, but not in those with LESCLs, suggests some role for environmental factors in the pathogenesis of the former group. Environmental factors other than UV radiation should be further elucidated in Japanese and other Asian MS cohorts.
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Esclerose Múltipla/epidemiologia , Esclerose Múltipla/patologia , Medula Espinal/patologia , Adulto , Idoso , Povo Asiático , Meio Ambiente , Feminino , Inquéritos Epidemiológicos , Humanos , Japão/epidemiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estações do Ano , Fatores Sexuais , Raios Ultravioleta , Adulto JovemAssuntos
Esclerose Lateral Amiotrófica/patologia , Demência/patologia , Transtornos Parkinsonianos/patologia , Medula Espinal/patologia , Fator de Transcrição TFIIIA/metabolismo , Idoso , Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/genética , Povo Asiático , Astrócitos/patologia , Proteínas de Ciclo Celular , Neurônios Colinérgicos/patologia , Demência/complicações , Demência/genética , Feminino , Humanos , Corpos de Inclusão/patologia , Japão , Masculino , Proteínas de Membrana Transportadoras , Pessoa de Meia-Idade , Mutação , Neurônios/patologia , Transtornos Parkinsonianos/complicações , Transtornos Parkinsonianos/genética , Fator de Transcrição TFIIIA/genéticaRESUMO
Treatment of patients with clinically isolated syndrome (CIS) with disease modifying drugs including interferon ß delays conversion to clinically definite multiple sclerosis (MS). However, CIS patients do not necessarily develop MS even after 20 years. Brain MRI lesions were required for CIS patients to include in clinical trials such as CHAMPS study and BENEFIT study. CIS patients with brain MRI lesions compatible to MS were considered as high risk to convert to MS in western countries. Previously we reported that asymptomatic enhancing brain lesions (AEBLs) were found in 9/23 (39.1%) of MS patients who had suffered at least one relapse in the preceding year or two relapses in the preceding 2 years, and the number of AEBLs per scan was 0.37, suggesting low disease activity of Japanese MS patients. We examined brain MRI findings in Japanese CIS patients and compared with those of Japanese MS patients at the first presentation. We reviewed brain MRI of 23 CIS visited our clinic from December 2007 to October 2010 who fulfilled the criteria proposed by Kappos et al. (2006) and Dalton et al (2002). Thirty two clinically definite MS (CDMS) patients fulfilled the first McDonald criteria (two or more attacks and objective clinical evidence of two or more lesions) proposed by Polman et al. (2005). Patients with neuromyelitis optica (NMO) and patients with NMO spectrum proposed by Wingerchuk et al. (2006) and Wingerchuk et al. (2007), respectively, were excluded. Patients with anti-aquaporin4 antibodies or with contiguous spinal cord lesion extending over three vertebral segments on MRI were also excluded. We could not obtain MRI of 11 patients with CDMS because of very long disease course, and 2 CIS and 13 CDMS patients had not been examined with MRI. So we examined 21 CIS and 8 CDMS patients at the first presentation using Paty criteria and Barkhof criteria. Eleven CIS patients did not meet any of the Barkhof criteria. Seven and 3 CIS patients met one and two of Barkhof criteria, respectively. No CIS patients showed fulfilled more than 3 of Barkhof criteria. Seven of eight CDMS patients at the first presentation showed more than one of the Barkhof criteria, however, only one CDMS patient at the onset fulfilled more than 3 of the Barkhof criteria. Japanese CIS patients seemed to show less brain lesions than those in western countries.