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Background and purpose: Preventing relapse by immunosuppressants (ISs) is critical for the prognosis of neuromyelitis optica spectrum disorder (NMOSD); however, the optimal duration of IS treatment is still under discussion. The objective was to explore the optimal duration of IS treatment and the risk of IS discontinuation for NMOSD. Method: This cohort study was conducted at a major neurological center that housed the largest NMOSD database in South China. Eligible participants were patients with NMOSD undergoing IS treatment. The main outcome measures were changes in relapse risk based on IS treatment duration, clinical outcomes and predictors of relapse following IS discontinuation. Results: In total, 343 patients were included in this study. The duration of IS treatment was strongly associated with a decrease in relapse risk (hazard ratio [HR] 0.53, p < 0.001). Continuous IS treatment resulted in decreased relapse HRs within 5 years of receiving IS medication, with a mild rebound starting at 5 years. Rituximab reduced the risk of NMOSD relapse to approximately zero within 3 years. The rate of relapse after IS withdrawal was high (77.5%). As opposed to other ISs, a delayed relapse following rituximab withdrawal was observed in this study. Longitudinal extensive transverse myelitis (HR = 2.023, p = 0.006) was associated with a higher risk of relapse after IS discontinuation. Conclusions: Long‐term IS medication for NMOSD is generally suitable. Patients with longitudinal extensive transverse myelitis had a higher risk of relapse after IS discontinuation. Future studies should explore individualized strategies of rituximab maintenance treatment. [ABSTRACT FROM AUTHOR]

Objective: Myelin oligodendrocyte glycoprotein-associated disorders (MOGADs) are a rare new neurological autoimmune disease with unclear pathogenesis. Since a linkage of the disease to the human leucocyte antigen (HLA) has not been shown, we here investigated whether MOGAD is associated with the HLA locus.Methods: HLA genotypes of 95 patients with MOGADs, assessed between 2016 and 2018 from three academic centres, were compared with 481 healthy Chinese Han individuals. Patients with MOGADs included 51 paediatric-onset and 44 adult-onset cases. All patients were seropositive for IgG targeting the myelin oligodendrocyte glycoprotein (MOG).Results: Paediatric-onset MOGAD was associated with the DQB1*05:02-DRB1*16:02 alleles (OR=2.43; OR=3.28) or haplotype (OR=2.84) of HLA class II genes. The prevalence of these genotypes in patients with paediatric-onset MOGAD was significantly higher than healthy controls (padj=0.0154; padj=0.0221; padj=0.0331). By contrast, adult-onset MOGAD was not associated with any HLA genotype. Clinically, patients with the DQB1*05:02-DRB1*16:02 haplotype exhibited significantly higher expanded disability status scale scores at onset (p=0.004) and were more likely to undergo a disease relapse (p=0.030). HLA-peptide binding prediction algorithms and computational docking analysis provided supporting evidence for the close relationship between the MOG peptide subunit and DQB1*05:02 allele. In vitro results indicated that site-specific mutations of the predicted target sequence reduced the antigen-antibody binding, especially in the paediatric-onset group with DQB1*05:02 allele.Conclusions: This study demonstrates a possible association between specific HLA class II alleles and paediatric-onset MOGAD, providing evidence for the conjecture that different aetiology and pathogenesis likely underlie paediatric-onset and adult-onset cases of MOGAD. [ABSTRACT FROM AUTHOR]

Abstract: To determine the diagnoses in a population of patients with presumed optic neuritis (ON) in China and compare the spectrum of etiologies with those in western countries, we studied a group of 204 patients referred to a teaching hospital with a presumptive diagnosis of ON. We conducted detailed medical and family history, thorough ophthalmologic and neurological examinations, and laboratory tests including neuroimaging. Patients were diagnosed using international diagnostic criteria. One hundred and thirteen patients (55.4%) met ON criteria, among whom 83 patients (73.5%) were diagnosed with idiopathic demyelinating optic neuritis (IDON). Brain MRI white matter lesions were found in 11 of 78 (14.1%) clinically “isolated” IDON patients. Tuberculosis meningitis was found in 2 patients and syphilis in 1 patient. The cause of ON in 26 patients (23.0%) remained uncertain, but it was still likely to be IDON accompanied by secondary axonal degeneration. Leber’s hereditary optic neuropathy (LHON) was found in 38 patients (18.6%), confirmed by mitochondrial DNA point mutation screening. Seventeen patients (8.3%) had ischemic optic neuropathy. A spectrum of other entities mimicked ON. Therefore, idiopathic demyelinating ON was the most common type of optic neuropathy in our group. Despite minor differences regarding the causes and prognosis, the etiology of ON in our population is similar to that reported in Western countries. [Copyright &y& Elsevier]

Background & Objective: Disease-modifying treatments (DMTs) for multiple sclerosis (MS) are widely used in Western countries. In China, however, the current treatment patterns of MS patients are not well characterized. This is to explore the gap between the current treatments in Guangzhou, Southern China and those given in Western countries. Methods: We performed a survey of MS patients at department of neurology, a tertiary MS referral centre in Guangzhou, concerning treatments of MS in Southern China. The clinical data in patients were collected. The initial treatment, drug withdrawal or switching profile, and therapeutic effect of existing treatments in MS patients were analyzed. Results: The ratio of MS patients who receive DMTs in Guangzhou China is extremely low. Among the 178 patients studied, only 28.09% received initial treatment with DMTs. MS patients who receive initial treatment with first-line DMTs have higher drug withdrawal rates (32.6%) and drug switching rates (30.43%) than those of western populations. The main reasons for withdrawal of first-line DMTs were doctor's advice (maintenance of remission) (40.00%), economic burden(20.00%), and no channels to buy drugs(13.33%). In MS patients initially treated with first-line DMTs who switched to other drugs, a gap between treatments was common (8/14; 57.14%). There were 18 patients with highly active MS receiving treatment with rituximab. Annual relapse rate after treatment significantly decreased than that before treatment (0.74 vs. 1.50, P < 0.001). Conclusions: DMTs for MS in Guangzhou, Southern China appear to lag behind those in Western countries. Much work is needed to improve drug accessibility and affordability of DMTs in China. Rituximab is an option for highly active MS in limited medical-resource countries. [ABSTRACT FROM AUTHOR]

Objective This study aimed to assess the effect of pregnancy on the course of neuromyelitis optica spectrum disorder (NMOSD), and the effect of this disease on pregnancy outcomes. Methods Consecutive patients with NMOSD were recruited between September 2015 and April 2016 at an outpatient clinic from four referral institutes in South China. Demographic, clinical, and pregnancy data were retrieved by questionnaires to analyze the association between NMOSD and pregnancy, as well as the potential risk factors for relapse. Results Among 249 patients with NMOSD, 55 had pregnancy-related attacks. The annual relapse rate in the first (3.20 ± 6.82) and second (3.25 ± 3.32) 3-month postpartum periods was marginally higher than that before pregnancy (1.44 ± 0.92, p = 0.682) and during pregnancy (1.23 ± 1.32, p = 0.758). The Kurtzke Expanded Disability Status Scale score increased from 1.55 ± 0.38 before pregnancy to 2.88 ± 2.14 at postpartum ( p < 0.001). NMOSD significantly increased the premature birth rate in patients after disease onset (8.33%) compared with before disease onset (1.95%, p = 0.025). Multivariate analysis showed that negative anti-aquaporin-4 IgG, concomitance with autoimmune diseases/antibodies, and no treatment in remission were risk factors of recurrence. Conclusion Our study shows a significant association between pregnancy and NMOSD in the Chinese population. Larger scale prospective studies are warranted in the future. [ABSTRACT FROM AUTHOR]

In this study, we included 461 NMOSD patients at our hospital from January 2016 to June 2019 and got some results. Eight (1.9%) originally AQP4-IgG-seronegative patients were retested as seropositive. 221 patients (47.9%) did not receive immunosuppressive treatment within 3 month. The adult/child distribution was significantly different (p = 0.001). Thirty-three patients (7.2%) had relapses after drug withdrawal, and fifteen of them had used drugs ≥3 years. The conclusion is that decision to treat with immunosuppression was made less often in children than in adults. Patients who took medication for a long time still need to be cautious of stopping using immunosuppression. [Display omitted] • AQP4-IgG seroconversion existed in 1.9% of originally seronegative patients and 4.2% of seropositive patients. • Nearly half of patients did not receive immunosuppressive treatment within 3 month. • The decision to treat with immunosuppression was made less often in children than in adults. • Patients who regularly take medication for 5 years or more still need to be cautious of stopping using immunosuppression. [ABSTRACT FROM AUTHOR]

Background: Familial clustering of neuromyelitis optica spectrum disorder (NMOSD) was present in Chinese. This study was to investigate the clinical characteristics and genetic background of familial NMOSD., Methods: Through questionnaires in four medical centres in 2016-2020, we identified 10 families with NMOSD aggregation. The statistical differences of clinical characteristics between familial and sporadic NMOSD (22 cases and 459 cases) were summarised. The whole-exome sequencing (WES) for seven families (13 cases and 13 controls) was analysed, compared with our previous WES data for sporadic NMOSD (228 cases and 1 400 controls). The family-based and population-based association and linkage analysis were conducted to identify the pathogenetic genes, the variant impacts were predicted., Results: The familial occurrence was 0.87% in Chinese. Familial patients had higher expanded disability status scale score than sporadic patients (p=0.03). The single-nucleotide polymorphism (SNP) rs2252257 in the promoter and enhancer of ubiquitin-specific peptidase USP18 was linked to familial NMOSD (p=7.8E-05, logarithm of the odds (LOD)=3.1), SNPs rs361553, rs2252257 and rs5746523 were related to sporadic NMOSD (p=1.29E-10, 3.45E-07 and 2.01E-09, respectively). Patients with the SNP rs361553 T/T genotype had higher recurrence rate than C/T or C/C genotype (1.22±0.85 vs 0.69±0.57 and 0.81±0.65, p=0.003 and 0.001, respectively). SNPs rs361553 and rs2252257 altered USP18 expression in brain and nerve tissues., Conclusion: Most clinical characteristics of familial NMOSD were indistinguishable from sporadic NMOSD except for the worst episodes severity. USP18 with impaired intronic regulatory function contributed to the pathogenesis of NMOSD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Serum neurofilament light chain (sNfL) is a promising biomarker for neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS), but there is limited validation data in specific ethnic and disease groups., Objective: To investigate the levels of sNfL in a cohort of Chinese patients with NMOSD and compare sNfL levels in patients with different disease courses and treatments., Methods: We analysed sNfL levels in 153 Chinese patients with NMOSD (n = 51) and MS (n = 102) using single-molecule array (Simoa) technology. The sNfL levels were compared with those of 71 healthy controls from two centres in southern China. For each disease, we assessed correlations between sNfL and disease phases and treatments., Results: Higher levels of sNfL were found in the patients with NMOSD [17.97 (10.55-27.94) pg/mL] and MS [15.83 (8.92-25.67) pg/mL] compared to healthy controls [10.09 (7.19-13.29) pg/mL, p < 0.001]. No significant differences were found between the AQP4-IgG-positive NMOSD group and OCB-positive MS group., Conclusions: sNfL measured by Simoa technology is a potential candidate blood biomarker for the diagnosis and disease monitoring of NMOSD in Chinese patients, warranting further prospective and multicentre studies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: Myelin oligodendrocyte glycoprotein-associated disorders (MOGADs) are a rare new neurological autoimmune disease with unclear pathogenesis. Since a linkage of the disease to the human leucocyte antigen (HLA) has not been shown, we here investigated whether MOGAD is associated with the HLA locus., Methods: HLA genotypes of 95 patients with MOGADs, assessed between 2016 and 2018 from three academic centres, were compared with 481 healthy Chinese Han individuals. Patients with MOGADs included 51 paediatric-onset and 44 adult-onset cases. All patients were seropositive for IgG targeting the myelin oligodendrocyte glycoprotein (MOG)., Results: Paediatric-onset MOGAD was associated with the DQB1*05:02-DRB1*16:02 alleles (OR=2.43; OR=3.28) or haplotype (OR=2.84) of HLA class II genes. The prevalence of these genotypes in patients with paediatric-onset MOGAD was significantly higher than healthy controls (p adj =0.0154; p adj =0.0221; p adj =0.0331). By contrast, adult-onset MOGAD was not associated with any HLA genotype. Clinically, patients with the DQB1*05:02-DRB1*16:02 haplotype exhibited significantly higher expanded disability status scale scores at onset (p=0.004) and were more likely to undergo a disease relapse (p=0.030). HLA-peptide binding prediction algorithms and computational docking analysis provided supporting evidence for the close relationship between the MOG peptide subunit and DQB1*05:02 allele. In vitro results indicated that site-specific mutations of the predicted target sequence reduced the antigen-antibody binding, especially in the paediatric-onset group with DQB1*05:02 allele., Conclusions: This study demonstrates a possible association between specific HLA class II alleles and paediatric-onset MOGAD, providing evidence for the conjecture that different aetiology and pathogenesis likely underlie paediatric-onset and adult-onset cases of MOGAD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The data for oligoclonal IgG bands (OCB) in cerebrospinal fluid and the association with clinical profiles of Chinese patients with multiple sclerosis (MS) is lacking. We aimed to investigate the positive OCB incidence, as well as the clinical and magnetic resonance imaging (MRI) features associated with positive OCB in MS patients in South China. Consecutive MS patients were recruited from two centers, located in Guangzhou city and Hong Kong in South China. MS was re-diagnosed by McDonald criteria 2017. OCB was tested using isoelectric focusing method. The difference in the clinical and MRI features between OCB-positive and OCB-negative MS patients was evaluated. Among 184 MS patients analyzed (102 from Guangzhou and 82 from Hong Kong), 110 (59.8%) patients were OCB-positive. Except for onset age (P = 0.019), there was no significant difference between MS patients with or without OCB in relation to the course of disease, symptoms of first attack, lesion distribution on MRI, relapse rates, or disability progression. Our results demonstrate no significant clinical differences between the OCB positive and negative MS patients in this MS cohort. Larger cohort in Chinese patients with MS is warranted., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

We investigated the efficacy of azathioprine (AZA) plus long-term low dose corticosteroids in Chinese patients with neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorders (NMOSD) at the Center for Demyelinating Diseases, South China. We prospectively enrolled patients between June 2010 and June 2014. Annualized relapse rate (ARR), expanded disability status scale (EDSS) score and modified Rankin Scale (mRS) were analyzed retrospectively. Of 77 patients with NMO/NMOSD (four males, 73 females; age range: 4-69 years), median disease duration before initiation of AZA was 32.0 months (range: 2.0-197.0). Median post-treatment follow-up was 23 months (range: 6-58) and 44 patients (57.1%) were relapse-free at median follow-up 19 months (range: 6-51). Pre-treatment ARR was 0.923, and post-treatment ARR was 0 (p < 0.0001). Survival analysis indicated a significantly lower risk of relapse (hazard ratio 0.522; 95% confidence interval 0.377-0.722; p < 0.0001). Significant improvements were shown in the EDSS (3.0 versus 1.0; p < 0.0001) and mRS (2.0 versus 1.0; p < 0.0001). Our study provides evidence supporting the use of AZA plus a low dose corticosteroid as an effective and safe strategy which is associated with a reduction in the risk of relapse in Chinese patients with NMO., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: The association of human leukocyte antigen (HLA) genes and multiple sclerosis (MS) has been extensively investigated in Caucasians, but less so in Oriental races such as Chinese., Objectives: To review studies on association of HLA class II alleles with MS in the Chinese population., Methods: An extensive search for published studies up to June 2010 was performed in the electronic databases. The meta-analysis facilities in the NCSS statistical package were utilized to analyze the findings in these studies. The odds ratios (ORs) of HLA-DR allele distributions in MS were analyzed against controls., Results: Eleven case-control studies were identified: nine genotyping and two serotyping studies. Six genotyping studies were suitable for HLA-DRB1 allele meta-analysis, which showed that HLA-DRB1*15 was associated with risk of MS in the combined group (308 cases and 407 controls; OR 1.39) while the HLA-DRB1*09 and HLA-DRB1*0901 alleles were protective. When the equivalent serotypes in these six studies were combined with the results from the two serotyping studies (431 cases and 652 controls) for a meta-analysis of HLA-DR serotypes, HLA-DR2 was a risk factor (OR 1.63) and HLA-DR9 was strongly protective in the combined group (OR 0.64)., Conclusions: Although limited data are available, our meta-analysis suggests that HLA-DR2/DRB1*15 are also associated with risk of MS in the Chinese population but less strongly so than in Western MS populations, whereas HLA-DR9 alleles appear to confer resistance in this population.

This was a retrospective review and descriptive analysis of the findings from the medical screening examinations conducted on the illegal migrants from Fujian Province of China (n = 589) who arrived on four boats on the West Coast of Canada between June 14 and September 9, 1999. The Canadian Navy conducted a screening medical exam of the illegal migrants, with Health Canada and Citizenship and Immigration Canada providing suggestions on the format of the exam. The illegal Chinese migrants were predominantly young, male adults. The most prevalent medical conditions detected were dermatological (55.2%), dental problems (25%), trauma (9.2%), urogenital (7.6%), and head/neck (6.6%). Recently induced trauma was more prevalent among females (20.5%) than males (6.5%). One case of community-acquired pneumonia was identified and later diagnosed as active pulmonary tuberculosis. Physicians dealing with illegal migrants should look for unusual physical findings and have a higher clinical suspicion regarding infectious diseases (tuberculosis, scabies) and abuse. Future encounters with illegal migrants should include standardized immigration screening exams, with adequate history taking and follow-up.