Japanese translation and validation of the 12-item Multiple Sclerosis Walking Scale version 2.

BACKGROUND: Disability in ambulation has a critical impact on activities of daily living in patients with multiple sclerosis (MS). The 12-item Multiple Sclerosis Walking Scale (MSWS-12) is a self-reported instrument developed to assess the impact of MS on walking. The scale's 12 items assess various aspects of walking-related tasks during the past 2 weeks. MSWS-12 has been used in multiple clinical studies and translated into several languages. In the present study, we translated the MSWS-12 into Japanese and evaluated its psychometric properties in a cross-sectional study. METHODS: The original English MSWS-12 version 2 (v2) was translated into Japanese through a standard procedure. Sixty consecutive Japanese MS patients completed the newly prepared Japanese MSWS-12v2 questionnaire and repeated the test 14 days later. Physical disability was assessed by the Expanded Disability Status Scale (EDSS), Timed 25-foot Walk (T25FW), and 9-hole Peg Test (9HPT). Cognitive performance was evaluated using the Processing Speed Test (PST). Fatigue and health-related quality of life were assessed using the Japanese versions of the Fatigue Severity Scale (FSS) and the Functional Assessment of MS (FAMS). RESULTS: The mean age of the patients was 42.5 years, with median disease duration of 10 years, and median EDSS of 2.0 (range 0, 6.5). Forty-seven patients (78.3 %) had relapsing-remitting, 9 (15.0 %) had secondary-progressive, and 4 (6.7 %) had primary-progressive phenotypes. The median score of the MSWS-12v2 was 5.95 (interquartile range 0, 50.6). Twenty-seven patients (45 %) scored the lowest possible score (0 points), while one (1.7 %) scored the highest possible score (100 points). Cronbach's alpha was 0.98 (95 % confidence interval [CI] 0.97, 0.98), and the test-retest intraclass correlation was 0.95 (95%CI 0.94, 0.96). MSWS-12v2 score was strongly correlated with EDSS (Spearman's ρ = 0.73 [95%CI 0.58, 0.83]), T25FW (ρ = 0.70 [95%CI 0.55, 0.81]), and total FAMS score (ρ = -0.80 [95%CI -0.88, -0.69]), and moderately correlated with 9HPT (ρ = 0.65 [95%CI 0.47, 0.77] for the dominant hand; ρ = 0.62 [95%CI 0.43, 0.75] for the non-dominant hand), PST (ρ = -0.65 [95%CI -0.78, -0.47]), and FSS (ρ = 0.68 [95%CI 0.52, 0.80]). Among the subcomponents of FAMS, the mobility subcomponent showed the most robust correlation with MSWS-12v2 score (ρ = -0.91 [95%CI -0.94, -0.81]). In patients with minimal or no objective disability (EDSS < 3.0, n = 40), only the mobility subcomponent of FAMS was strongly correlated with MSWS-12v2 score (ρ = -0.76 [95% CI -0.87, -0.58]). In contrast, correlations of MSWS-12v2 score with EDSS and T25FW were weak in this subgroup (ρ = 0.28 [95%CI -0.03, 0.55] for EDSS; ρ = 0.25 [95%CI -0.06, 0.52] for T25FW). Response patterns for the single items showed that 32.5 % of the patients with EDSS below 3.0 reported having problems with balance, followed by climbing stairs and standing while doing things (both 25 %). CONCLUSION: The Japanese version of the MSWS-12v2 developed in this study is reliable, valid, and helpful for screening walking disability in Japanese MS patients, including those with minimal objective disability.

[Thymoma-associated generalized myasthenia gravis complicated with anti-VGKC complex antibody-associated limbic encephalitis: a case report].

We present a case of a 54-year-old woman. She was attending our department for thymoma-associated generalized myasthenia gravis. While she was treated with intravenous immunoglobulins for the exacerbation of myasthenic symptoms, she suddenly lost her consciousness for the first time and continued to have mild disorientation along with anterograde and retrograde amnesia afterwards. The symptoms improved after steroid pulse therapy. After searching for autoantibodies, she was diagnosed with anti-VGKC complex antibody-associated limbic encephalitis. As one-third of cases are complicated by thymoma, anti-VGKC complex antibody-positive limbic encephalitis has the aspect of a paraneoplastic neurological syndrome. In this case, masses suspected to be a recurrence of thymoma were found. In cases of thymoma, involvement of anti-VGKC complex antibodies should be considered when central nervous system symptoms appear, and when anti-VGKC complex antibodies are positive, recurrence or exacerbation of thymoma should be considered.

Processing speed test: Results from a Japanese normative sample of healthy participants compared with a US normative sample.

BACKGROUND: The Processing Speed Test (PST), a validated iPad®-based cognitive screening test for MS, has been applied to the cognitive assessment of Japanese MS patients using US normative data. METHODS: To develop PST normative data from Japanese healthy volunteers and compare the PST score distribution between Japanese and US healthy volunteers, 254 healthy Japanese-speaking volunteers were enrolled and stratified by age (20-65 years). Potential participants with a Mini-Mental State Examination score < 27 were excluded. PST raw scores (total correct) were from the Japan cohort and compared with age-restricted US normative data and propensity score-matched data created by matching sex, age, and educational level from a published study of 428 healthy participants. PST score distributions and standardized z-scores were compared using t-test and Kolmogorov-Smirnov test statistics. RESULTS: The mean age of the Japan cohort was 44.1 years. The PST scores of Japanese volunteers were significantly different from those of the age-restricted (mean ± SD 61.8 ± 10.1 vs 53.7 ± 10.8; p < 0.001) and the propensity score-matched US cohort (62.1 ± 10.1 vs 53.3 ± 10.6; p < 0.001). CONCLUSION: Regression analyses centered on US normative data could underestimate disease severity in Japanese MS patients, suggesting that separate normative data should be considered for each population sample.

Immunotherapy for ocular myasthenia gravis: an observational study in Japan.

Background: Treatment for ocular myasthenia gravis (OMG) has not yet been well established. Few reports have been published on the clinical practice and outcomes of OMG. Objectives: We investigated treatment of OMG and its outcomes in Japan.We investigated treatment of OMG and its outcomes in Japan. Design: We performed a retrospective cross-sectional survey of OMG patients from eight hospitals in Japan. Methods: Clinical information, including sex, age at onset, initial symptoms, autoantibodies, clinical course, treatment history, complications, and outcomes, was obtained. In addition, we recorded the total number of patients with MG and OMG separately. Results: In total, 135 patients with OMG (67 men, 68 women) were included. Treatment of OMG was not simple and involved various immunotherapeutic strategies. Eight patients went into remission spontaneously without immunotherapy. A total of 117 patients showed improvements after treatment, whereas 10 patients showed refractory responses to treatment. Overall outcomes were good; however, symptoms persisted in 60.7% of patients even after treatment. Among 90 patients who received immunotherapy, only two showed a refractory response. Meanwhile, for 45 patients who did not receive immunotherapy, 8 were refractory. Thus, the rate of refractory disease in the group with immunotherapy was significantly lower (p = 0.001, u-test) than in the group without immunotherapy. The proportion of generalized MG patients among all MG cases was low in medical centers where immunotherapy for OMG was frequently performed. Conclusion: Although the overall prognosis for patients with OMG was good, symptoms remained in more than half of the patients. Immunotherapy, including corticosteroids, may be beneficial for patients with OMG. Plain language summary: Is immunosuppressive therapy beneficial for myasthenia gravis patients with ocular symptoms only? Patients with ocular myasthenia gravis (OMG) have only eye symptoms for more than 2 years. Whether this condition is an initial stage of the disease before eventually progressing to generalized myasthenia gravis (gMG) is still uncertain. Different from gMG, OMG is not life-threatening. But eye symptoms often cause troublesome problems in life. Doctors have treated OMG patients similarly to patients with gMG. There is no standard clinical practice for OMG. In this study, we examined how patients with OMG were treated at eight different specialist centers in Japan. In 135 patients with OMG, 8 patients became symptom free without treatment, 117 patients showed improvements after treatment, whereas 10 patients did not get well. Overall outcomes were good, but symptoms remained in 60.7% of patients even after treatment. Among 90 patients who received one or more immunotherapies, only 2 did not get well. Meanwhile, for 45 patients who did not receive immunotherapy, 8 remained ill. We found that treatment of OMG was not simple and often needed multiple immunotherapies. Administering immunotherapy, including corticosteroids, may be beneficial for patients with OMG.

The prevalence and incidence of multiple sclerosis over the past 20 years in northern Japan.

OBJECTIVES: The prevalence of multiple sclerosis (MS) in East Asia is thought to be lower than in Western countries. Globally, there is a trend of increasing MS prevalence. We investigated the changes in the prevalence and clinical phenotype of MS in the Tokachi province of Hokkaido in northern Japan, from 2001 to 2021. METHODS: Data processing sheets were sent to all related institutions inside and outside the Tokachi area of Hokkaido island in Japan and were collected from April to May 2021. The prevalence according to the Poser's diagnostic criteria for MS was determined on March 31, 2021. RESULTS: In 2021, the crude MS prevalence in northern Japan was 22.4/100,000 (95% confidence interval, 17.6-28.0). The prevalences of MS standardized by the Japanese national population in 2001, 2006, 2011, 2016, and 2021 were 6.9, 11.5, 15.3, 18.5, and 23.3, respectively. The female/male ratio was 4.0 in 2021, increased from 2.6 in 2001. We checked the prevalence using the 2017 revised McDonald criteria, and found only additional male patient who had not fulfilled Poser's criteria. The age- and sex-adjusted incidence of MS per 100,000 individuals increased from 0.09 in 1980-1984 to 0.99 in 2005-2009; since then, it has remained stable. The proportions of primary-progressive, relapsing-remitting, and secondary-progressive MS types in 2021 were 3%, 82%, and 15%, respectively. CONCLUSION: Our results demonstrated a consistent increase in the prevalence of MS among the northern Japanese over 20 years, particularly in females, and consistently lower rates of progressive MS in northern Japan than elsewhere in the world.

Health-related quality of life in Japanese patients with multiple sclerosis.

OBJECTIVES: Neurological disabilities, especially physical issues, can adversely affect the daily lives of people with multiple sclerosis (MS) and negatively impact their health-related quality of life (HRQOL). On the other hand, physical and psychiatric symptoms are variable in people with MS, and QOL can be influenced by cultural and educational background. This study aimed to evaluate the association of HRQOL with disabilities, fatigue, and depression in Japanese subjects with MS. METHODS: Evaluation of HRQOL, fatigue, and depression was performed in 184 Japanese individuals with MS, using the Functional Assessment of MS (FAMS), Fatigue Severity Scale (FSS), and Beck Depression Inventory-Second Edition (BDI-II), respectively. RESULTS: Multiple linear regression analysis demonstrated negative correlations of the Expanded Disability Status Scale (EDSS) with scores on the FAMS subscales of mobility, symptoms, thinking and fatigue, total FAMS, and additional concerns. The FSS score had negative correlations with mobility, symptoms, emotional well-being, thinking and fatigue, total FAMS, and additional concerns. There were negative correlations between BDI-II scores and all items of FAMS. CONCLUSIONS: HRQOL had relatively close correlations with disabilities and fatigue, and depression had an especially close relationship with HRQOL.

Smoking and younger age at onset in anti-acetylcholine receptor antibody-positive myasthenia gravis.

Smoking is a known risk factor for the development and progression of several autoimmune diseases. Previous studies have pointed out the association of smoking with the development and worsening of symptoms in myasthenia gravis (MG), but further investigation is necessary to confirm this association. Smoking history was investigated in a cross-sectional study of 139 patients with anti-acetylcholine receptor antibody-positive MG, and the association of smoking history with the age at the onset of MG was analyzed. Patients who had been smoking at the onset of MG were significantly younger compared with those who had never smoked or had quit before the onset of MG. A linear regression analysis adjusting for sex and the presence/absence of thymoma showed a significant association between smoking at onset and younger age at onset (regression coefficient -9.05; 95% confidence interval, -17.6, -0.51; p = 0.039). Among patients with smoking exposure within 10 years prior to or at the onset of MG, women were significantly younger at the onset of MG compared with men. Our results suggest that smoking is an independent risk factor for the earlier development of anti-acetylcholine receptor antibody-positive MG and further support the putative link between smoking and MG.

Stages of brain volume loss and performance in the Brief International Cognitive Assessment for Multiple Sclerosis.

BACKGROUND: Cognitive dysfunction occurs in a substantial proportion of patients with multiple sclerosis (MS), negatively affects their daily activities, and is associated with poor prognosis. Cognitive dysfunction in MS can extend across multiple cognitive domains, depending on the patterns and extent of the brain regions affected. Therefore, a combination of tests, including the Brief International Cognitive Assessment for MS (BICAMS), that assess different aspects of cognition is recommended to capture the full picture of cognitive impairment in each patient. However, the temporal relationships between the progression of the MS brain pathology and the performances in different cognitive tests remain unclear. METHODS: Global and regional brain volume data were obtained based on T1-weighted magnetic resonance imaging from 61 patients with MS, and hierarchical cluster analysis was performed using these brain volume data. Cognitive function was assessed using the three subcomponents of the BICAMS: the Symbol Digit Modalities Test (SDMT), California Verbal Learning Test Second Edition (CVLT2), and Brief Visuospatial Memory Test-Revised (BVMTR). Clinical characteristics, patterns of regional brain volume loss, and cognitive test scores were compared among clusters. RESULTS: Cluster analysis of the global and regional brain volume data classified patients into three clusters (Clusters 1, 2, and 3) in order of decreasing global brain volume. A comparison of the clinical profiles of the patients suggested that those in Clusters 1, 2, and 3 are in the early, intermediate, and advanced stages of MS, respectively. Pair-wise analysis of regional brain volume among the three clusters suggested brain regions where volume loss starts early and continues throughout the disease course, occurs preferentially at the early phase, or evolves relatively slowly. SDMT scores differed significantly among the three clusters, with a decrease from Clusters 1 to 3. BVMTR scores also declined in this order, whereas the CVLT2 was significantly impaired only in Cluster 3. CONCLUSION: Our results suggest that SDMT performance declines in conjunction with brain volume loss throughout the disease course of MS. Performance in the BVMTR also declines in line with the brain volume loss, but impairment in the CVLT2 becomes particularly apparent at the late phase of MS.

High-efficacy therapy reduces subcortical grey matter volume loss in Japanese patients with relapse-onset multiple sclerosis: A 2-year cohort study.

BACKGROUND: Different treatment strategies can have varying effects on disability and whole brain volume in patients with multiple sclerosis (MS). However, the association between regional brain volume and treatment efficacy is currently unclear. Our objective was to determine whether whole brain volume, as well as the regional volume of cortical and subcortical grey matter, differ with the administration of high-efficacy therapy (HET) versus low-efficacy therapy (LET). METHODS: We evaluated clinical data and change in regional brain volume in 44 patients with relapse-onset MS, who underwent HET (n = 19) or LET (n = 25). Regional brain volume was determined with three-dimensional T1-weighted magnetic resonance imaging using FreeSurfer. The association between volume change and treatment type was assessed via generalised linear mixed models (GLMMs). RESULTS: During the observation period (2.0 ± 0.16 years), the proportion of patients with a "no evidence of disease activity-3″ status was significantly greater in those who underwent HET versus LET (p = 0.012). HET was positively associated with volume changes in the cortex (ß = 0.64, p = 0.0499), left (ß = 0.98, p = 0.0033) and right (ß = 0.77, p = 0.019) caudate and right putamen (ß = 0.87, p = 0.0077), after adjusting for age, sex, and MS severity scores in the GLMMs. Further correction for multiple comparisons by false discovery rate revealed that HET was consistently associated with the volume changes of the left caudate (p = 0.049) and right putamen (p = 0.049). CONCLUSION: HET can improve the mid-term prognosis of Japanese patients with relapse-onset MS by reducing disease activity and regional brain volume loss.

[Therapeutic Strategy for Multiple Sclerosis Resistant to Standard Treatment: MS Cases When Relapses Cannot be Controlled with Standard Treatment].

Eight disease-modifying drugs have been approved for treating multiple sclerosis in Japan., The drugs show some differences in for the degree to which they prevent relapses; among them, natalizumab and ofatumumab are significantly effective in preventing relapses. If relapses are not suppressed when treated with natalizumab, the presence of anti-natalizumab antibodies should be investigated. When relapses cannot be suppressed with natalizumab, the patient should be treated with ofatumumab and vice versa. If relapses cannot be suppressed with both natalizumab and ofatumumab, then the diagnosis of multiple sclerosis should be thoroughly reassessed. In cases with atypical symptoms and/or exhibiting factors such as multiple sclerosis, oral steroids, and/or immunosuppressive agents can be administered to prevent relapses.

Correlation of the symbol digit modalities test with the quality of life and depression in Japanese patients with multiple sclerosis.

BACKGROUND: This study aimed to evaluate the association between cognitive impairment and health-related quality of life (HRQOL), fatigue, and depression in Japanese patients with multiple sclerosis (MS). METHODS: The Brief International Cognitive Assessment for MS (BICAMS) was performed in 184 Japanese patients with MS. The Functional Assessment of MS (FAMS), Fatigue Severity Scale (FSS), and Beck Depression Inventory-Second Edition (BDI-II) were used to evaluate HRQOL, fatigue, and depression, respectively. RESULTS: Multiple linear regression analysis demonstrated positive correlations of the Symbol Digit Modalities Test (SDMT) with the scores on the FAMS subscales of mobility, symptoms, emotional well-being, and additional concerns and with the total FAMS score even after controlling for the Expanded Disability Status Scale score, age at examination, and duration of education. The SDMT score in the BICAMS battery had negative correlations with the BDI-II score, as revealed by multiple linear regression analysis. None of the three tests in the BICAMS had any correlation with the FSS score. CONCLUSION: The SDMT has a significant relationship with HRQOL and depression in Japanese patients with MS.

Association of Smoking and Generalized Manifestations of Myasthenia Gravis.

Objective Smoking is a known risk factor for the development and progression of autoimmune diseases. Previous studies in ocular myasthenia gravis (MG) patients showed that smoking is associated with the severity of symptoms and progression to generalized MG. However, whether smoking affects MG symptoms in patients with a broader clinical spectrum of presentations is unknown. Therefore, in this study, the associations of smoking with the clinical characteristics of MG were analyzed in a cohort of patients including those with generalized, seronegative, and thymoma-associated MG. Methods The smoking history was investigated in a cross-sectional study of 187 patients with MG followed in a referral hospital for neurology. The association of smoking with MG-activities of daily living score at survey, the presence of generalized manifestations, and the age of onset was assessed using multiple regression models. Results Neither current nor prior smoking habit was associated with the MG-activities of daily living score at survey. However, smoking exposure after MG onset was significantly associated with the presence of generalized manifestations during the disease course (odds ratio, 3.57; 95% confidence interval, 1.04, 12.3). The smoking history before or at onset of MG was not associated with the age of onset. Conclusion Smoking exposure after the onset is associated with generalized manifestations of MG in our cohort of patients with a broad clinical spectrum of presentations.

B-cell depletion therapy for multiple sclerosis.

Since the initial observation of increased immunoglobulin concentrations in the cerebrospinal fluid of multiple sclerosis (MS) patients in the 1940s, B cells have been considered to participate in the pathology of MS through the production of autoantibodies reactive against central nervous system antigens. However, it is now recognized that B cells contribute to MS relapses via antibody-independent activities, including the presentation of antigens to T cells and the release of pro-inflammatory cytokines. In addition, the recent identification of B cell-rich follicle-like structures in the meninges of progressive MS patients suggests that the pathogenic roles of B cells also exist at the progressive phase of this disease. Recently, large-scale clinical trials have demonstrated the efficacy of B-cell depletion therapy using anti-CD20 antibodies in relapsing as well as primary progressive MS. B-cell depletion therapy has become an essential treatment option for MS based on its unique benefit to risk balance in relapsing MS, and because it is the only drug that has been shown to be effective in primary progressive MS to date.

Seasonal fluctuations in serum levels of vitamin D in Japanese patients with multiple sclerosis.

We explored the presence of seasonal fluctuations in serum vitamin D levels and potential relationship between vitamin D levels and disease severity or prognosis in patients with multiple sclerosis (MS) in northern Japan. Serum levels of 25(OH)D in spring were significantly lower than in summer and autumn, whereas no differences in 1,25(OH)2D levels were demonstrated among four seasons. Seasonal fluctuations in 25(OH)D were demonstrated in patients with EDSS ≤3.5, but not in those with EDSS≥4.0. Negative correlations between 25(OH)D and EDSS or MSSS were found in each season. Seasonal fluctuations in 25(OH)D levels may be affected by physical disabilities.

[Relapsing-Remitting Multiple Sclerosis].

Multiple sclerosis (MS) is an immune-mediated inflammatory demyelinating disease of the central nervous system. There are neither diagnostic tests nor markers for MS. Other causes must be excluded thoroughly before an MS diagnosis is considered definitive. The relapsing-remitting type is a major clinical course in MS. Most disease-modifying drugs (DMDs) target this clinical type. Many clinical studies have demonstrated that early intervention with DMDs may prevent disease progression and transition from relapsing-remitting MS to the secondary progressive type. There are windows of opportunity for DMDs. An adequate DMD should be used for the appropriate patient at the optimal time.

HLA genotype-clinical phenotype correlations in multiple sclerosis and neuromyelitis optica spectrum disorders based on Japan MS/NMOSD Biobank data.

HLA genotype-clinical phenotype correlations are not established for multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). We studied HLA-DRB1/DPB1 genotype-phenotype correlations in 528 MS and 165 NMOSD cases using Japan MS/NMOSD Biobank materials. HLA-DRB1*04:05, DRB1*15:01 and DPB1*03:01 correlated with MS susceptibility and DRB1*01:01, DRB1*09:01, DRB1*13:02 and DPB1*04:01 were protective against MS. HLA-DRB1*15:01 was associated with increased optic neuritis and cerebellar involvement and worsened visual and pyramidal functional scale (FS) scores, resulting in higher progression index values. HLA-DRB1*04:05 was associated with younger onset age, high visual FS scores, and a high tendency to develop optic neuritis. HLA-DPB1*03:01 increased brainstem and cerebellar FS scores. By contrast, HLA-DRB1*01:01 decreased spinal cord involvement and sensory FS scores, HLA-DRB1*09:01 decreased annualized relapse rate, brainstem involvement and bowel and bladder FS scores, and HLA-DRB1*13:02 decreased spinal cord and brainstem involvement. In NMOSD, HLA-DRB1*08:02 and DPB1*05:01 were associated with susceptibility and DRB1*09:01 was protective. Multivariable analysis revealed old onset age, long disease duration, and many relapses as independent disability risks in both MS and NMOSD, and HLA-DRB1*15:01 as an independent risk only in MS. Therefore, both susceptibility and protective alleles can influence the clinical manifestations in MS, while such genotype-phenotype correlations are unclear in NMOSD.

[Cognitive Impairment in Multiple Sclerosis].

Cognitive impairment is one of the major symptoms of multiple sclerosis (MS) and one that often remains unnoticed. An adequate battery should be used to evaluate cognitive function in patients with MS because cognitive impairment in MS typically involves specific deficits such as sustained attention and information processing speed rather than global cognitive decline. Cognitive impairment could influence patients' daily and social activities. It is not easy to improve cognitive impairment in patients with MS, and it is important to prevent the decline of function using disease-modifying drugs for MS.

Progressive Multifocal Leukoencephalopathy during Tocilizumab Treatment for Rheumatoid Arthritis.

A 61-year-old woman was diagnosed with rheumatoid arthritis 12 years ago and received multiple treatment regimens before achieving symptomatic stability with methotrexate plus tocilizumab, a humanized monoclonal antibody against the IL-6 receptor, about 2 years prior to the current presentation. Sixteen months after tocilizumab initiation, she exhibited dysarthria and disorientation; five months later, she was hospitalized with movement difficulties. Her neurological symptoms deteriorated thereafter, accompanied by enlarged cerebral white matter lesions on magnetic resonance imaging. A biopsy of the right frontal lesion confirmed progressive multifocal leukoencephalopathy (PML). While several therapeutic monoclonal antibodies have been linked to PML, this is the first case associated with tocilizumab.

Contribution of cortical lesions to cognitive impairment in Japanese patients with multiple sclerosis.

Cortical lesions (CLs) have a low prevalence and are associated with physical disabilities in Japanese patients with multiple sclerosis (MS). However, the contribution of CLs to cognitive impairment remains unclear in Asian MS. Sixty-one prospectively enrolled MS patients underwent three-dimensional double inversion recovery MR imaging, the Brief Repeatable Battery of Neuropsychological Tests (BRB-N), the Apathy Scale (AS), the Fatigue Questionnaire (FQ), and the Hospital Anxiety and Depression Scale (HADS) within a 1-week period. The cognitive impairment index (CII) score was calculated to measure patients' overall cognitive impairment. MS patients with CLs had poorer scores than those without CLs in most BRB-N tests, but scored comparably in the FQ, AS, and HADS. The number of CLs correlated negatively with all BRB-N test scores and positively with total CII scores. Leukocortical lesions were more extensively associated with cognitive dysfunction in various domains than intracortical lesions. Stepwise multiple regression analysis revealed that potential confounding factors for the highest quartile of CII score were the number of CLs (odds ratio 2.38, p = 0.0070) and the Expanded Disability Severity Scale score (odds ratio 2.13, p = 0.0003). Our results demonstrate that the presence and number of CLs are robustly associated with cognitive dysfunction in Asian MS patients.