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Learn more: PMC Disclaimer | PMC Copyright Notice BMJ Open . 2026 Jan 8;16(1):e099386. doi: 10.1136/bmjopen-2025-099386 Search in PMC Search in PubMed View in NLM Catalog Add to search Chinese neuroimmunological disease (NIDBase) cohort study: cohort profile Mengyao Zhang Mengyao Zhang 1 Department of Neurology, Xuanwu Hospital Capital Medical University, National Center for Neurological Disorders, Beijing, China Find articles by Mengyao Zhang 1, 0 , Jinming Han Jinming Han 1 Department of Neurology, Xuanwu Hospital Capital Medical University, National Center for Neurological Disorders, Beijing, China Find articles by Jinming Han 1, 0 , Jiangwei Xia Jiangwei Xia 1 Department of Neurology, Xuanwu Hospital Capital Medical University, National Center for Neurological Disorders, Beijing, China Find articles by Jiangwei Xia 1, 0 , Ming Lin Ming Lin 1 Department of Neurology, Xuanwu Hospital Capital Medical University, National Center for Neurological Disorders, Beijing, China Find articles by Ming Lin 1 , Teng Chen Teng Chen 1 Department of Neurology, Xuanwu Hospital Capital Medical University, National Center for Neurological Disorders, Beijing, China Find articles by Teng Chen 1 , Shishuang Ruan Shishuang Ruan 1 Department of Neurology, Xuanwu Hospital Capital Medical University, National Center for Neurological Disorders, Beijing, China Find articles by Shishuang Ruan 1 , Qiujia Wang Qiujia Wang 1 Department of Neurology, Xuanwu Hospital Capital Medical University, National Center for Neurological Disorders, Beijing, China Find articles by Qiujia Wang 1 , Yi Men Yi Men 1 Department of Neurology, Xuanwu Hospital Capital Medical University, National Center for Neurological Disorders, Beijing, China Find articles by Yi Men 1 , Ruiping Gao Ruiping Gao 1 Department of Neurology, Xuanwu Hospital Capital Medical University, National Center for Neurological Disorders, Beijing, China Find articles by Ruiping Gao 1 , Hanyue Zheng Hanyue Zheng 1 Department of Neurology, Xuanwu Hospital Capital Medical University, National Center for Neurological Disorders, Beijing, China Find articles by Hanyue Zheng 1 , Jiajian Li Jiajian Li 1 Department of Neurology, Xuanwu Hospital Capital Medical University, National Center for Neurological Disorders, Beijing, China Find articles by Jiajian Li 1 , Yuan Qi Yuan Qi 1 Department of Neurology, Xuanwu Hospital Capital Medical University, National Center for Neurological Disorders, Beijing, China Find articles by Yuan Qi 1 , Siqi Chen Siqi Chen 1 Department of Neurology, Xuanwu Hospital Capital Medical University, National Center for Neurological Disorders, Beijing, China Find articles by Siqi Chen 1 , Yingtao Wang Yingtao Wang 1 Department of Neurology, Xuanwu Hospital Capital Medical University, National Center for Neurological Disorders, Beijing, China Find articles by Yingtao Wang 1 , Yuqi Tang Yuqi Tang 1 Department of Neurology, Xuanwu Hospital Capital Medical University, National Center for Neurological Disorders, Beijing, China Find articles by Yuqi Tang 1 , Dawei Li Dawei Li 1 Department of Neurology, Xuanwu Hospital Capital Medical University, National Center for Neurological Disorders, Beijing, China Find articles by Dawei Li 1 , Xixi Yang Xixi Yang 1 Department of Neurology, Xuanwu Hospital Capital Medical University, National Center for Neurological Disorders, Beijing, China Find articles by Xixi Yang 1 , Zhandong Qiu Zhandong Qiu 1 Department of Neurology, Xuanwu Hospital Capital Medical University, National Center for Neurological Disorders, Beijing, China Find articles by Zhandong Qiu 1 , Zheng Liu Zheng Liu 1 Department of Neurology, Xuanwu Hospital Capital Medical University, National Center for Neurological Disorders, Beijing, China Find articles by Zheng Liu 1 , Huiqing Dong Huiqing Dong 1 Department of Neurology, Xuanwu Hospital Capital Medical University, National Center for Neurological Disorders, Beijing, China Find articles by Huiqing Dong 1 , Yinan Zhao Yinan Zhao 1 Department of Neurology, Xuanwu Hospital Capital Medical University, National Center for Neurological Disorders, Beijing, China Find articles by Yinan Zhao 1, * , Junwei Hao Junwei Hao 1 Department of Neurology, Xuanwu Hospital Capital Medical University, National Center for Neurological Disorders, Beijing, China 2 Beijing Municipal Geriatric Medical Research Center, Beijing, China 3 Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, China Find articles by Junwei Hao 1, 2, 3, ✉ Author information Article notes Copyright and License information 1 Department of Neurology, Xuanwu Hospital Capital Medical University, National Center for Neurological Disorders, Beijing, China 2 Beijing Municipal Geriatric Medical Research Center, Beijing, China 3 Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, China Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise. None declared. ✉ Dr Junwei Hao; [email protected] * Yinan Zhao; [email protected] 0 MZ, JH and JX contributed equally. Received 2025 Feb 17; Accepted 2025 Dec 11; Collection date 2026. Copyright © Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: https://creativecommons.org/licenses/by-nc/4.0/ . PMC Copyright notice PMCID: PMC13059851 PMID: 41506767 Abstract Abstract Purpose The Chinese neuroimmunological disease database (NIDBase) cohort was established to explore genetic and environmental risk factors, clinical features, multi-omics data and prognostic biomarkers. The aim is to enhance our understanding of central nervous system (CNS) demyelinating diseases. Additionally, the establishment of this cohort will address the critical issue of the lack of comprehensive genetic data and biological samples for precision diagnosis and treatment research related to neuroimmunological diseases in China. Participants 56 hospitals in various regions of China were selected to participate in this study. The patients diagnosed with CNS demyelinating diseases were recruited, including clinically isolated syndrome (CIS), multiple sclerosis (MS), neuromyelitis optica spectrum disease (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A). Finding to date At the time of patient enrolment, the clinical information is designated as baseline data. The collected baseline data include demographic information, disease history, clinical features of each demyelinating event, treatment records, standardised scales, questionnaire assessments and laboratory test results. Furthermore, biological samples, MRI and high-density electroencephalography (hd-EEG) data will be collected at baseline. All patients will be followed up at 3 months and 6 months and annually thereafter. As of December 2024, 3866 patients with CNS demyelinating diseases have been enrolled, including 84 CIS, 282 MOGAD, 1405 MS and 2095 NMOSD. Our findings indicate that CNS demyelinating diseases, particularly NMOSD, are more prevalent in women in China, with significant age differences observed among NMOSD patients compared with those with CIS, MS and MOGAD. Future plans In future, all patients in our cohort will be followed up at 3 months and 6 months and then annually. By the end of December 2024, the database has been locked and is now being processed and analysed, while our data continue to be updated and expanded for further analysis. Both prospective and retrospective observations will be included in this study. Subsequent publications will emerge from this multicentre cohort, encompassing genomics, clinical cohort studies, hd-EEG biomarkers, imaging-based radiomics and electrical stimulation therapies. Trail registration number NCT06443333 . Keywords: Multiple sclerosis, Neurology, IMMUNOLOGY STRENGTHS AND LIMITATIONS OF THIS STUDY. The Chinese neuroimmunological disease database (NIDBase) includes the data on neuroimmunological diseases collected from 56 subcentres nationwide across China. The cohort not only collects demographic characteristics and clinical information from patients but also conducts multi-omics studies including genomics and radiomics. The cohort has regular follow-ups and a higher rate of active participants, which facilitates our prospective study. The cohort may encounter limitations in the management and data cleaning processes for data from subcentres. Introduction Neuroimmunological diseases are a group of disease conditions including central and peripheral nervous system immune diseases. Central nervous system (CNS) demyelinating diseases, the most prevalent type of CNS immune disease, are characterised by multifocal and inflammatory demyelination, including clinically isolated syndrome (CIS), multiple sclerosis (MS), neuromyelitis optica spectrum disease (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A). 1 , 7 These diseases may lead to vision loss, movement disorders, paraesthesia, cognitive impairment and urine and faecal disorders, affecting young adults and posing a heavy burden on the family and society. Previous studies have indicated a rising incidence and prevalence of CNS demyelinating diseases, which may be partly explained by the increased awareness of these diseases and the application of cell-based assay (CBA) detection method. 8 9 Identifying potential prodromes and risk factors, initiating early treatment to prevent recurrence and adopting comprehensive management are important for these patients with CNS demyelinating diseases. 10 , 15 Both environmental and genetic factors play crucial roles in the development of CNS demyelinating diseases. The genetic architecture of MS has been mapped by the International Multiple Sclerosis Genetics Consortium (IMSGC), with changes in the HLA-DRB1 gene identified as the strongest genetic risk factors for developing MS. 16 A common promoter single-nucleotide polymorphism in CYP7A1 was associated with the risk of NMOSD in Korean patients, while not verified in European ancestry. 17 Furthermore, previous whole-genome sequencing studies indicated genetic variants in the major histocompatibility complex region associated with NMOSD susceptibility in European ancestry. 18 Importantly, environmental factors also contribute to the risk of CNS demyelinating disease. For example, smoking, vitamin D deficiency, Epstein-Barr virus infection and higher latitude are associated with the development of CNS demyelinating diseases. 19 Genetic factors and environmental factors can be accumulated gradually, reaching a biological threshold and causing diseases. Unlike genetic risk factors, environmental and lifestyle factors can be modified, offering potential avenues for disease prevention. 20 Significant heterogeneity of CNS demyelinating diseases was noted between Eastern and Western populations. Multidimensional clinical cohort resources have been established in several Western countries. For instance, the Swiss Multiple Sclerosis Cohort 21 integrates detailed data from over 1600 patients across eight centres in Switzerland, documenting 1000 MS relapse events and 8000 standardised MRI assessments. On the genetic front, two international MS genetic consortia, the IMSGC and the Multiple Sclerosis Alliance, have collected genetic data from more than 40 000 MS patients, significantly advancing the identification of genetic factors associated with MS. 16 22 It is important to note that previous genomic studies focusing on CNS demyelinating diseases have primarily concentrated on European populations, 18 23 while evidence from large disease cohorts in China remains limited. Furthermore, electroencephalography (EEG) patterns can serve as diagnostic biomarkers, reflecting alterations of brain connectivity and evaluating the MS-related sensorimotor disorders. 24 25 Personalised neuromodulation has been shown to improve the symptoms of MS, such as fatigue. 26 In NMOSD, the resting-state EEG features are associated with fatigue, anxiety and depression, which can help us evaluate the patients’ conditions and provide a credible evidence base for personalised neuromodulation therapy. 27 High-density electroencephalography (hd-EEG) uses a greater number of electrodes, enabling the capture of subtle, localised neural activity and yielding superior spatial resolution. As a non-invasive source-imaging technique, hd-EEG offers millisecond-level temporal precision, allowing for the detection of functional impairment earlier than conventional neurophysiological methods. However, only a limited number of studies have employed hd-EEG to investigate CNS demyelinating diseases, and large-sample investigations are particularly scarce. 28 , 30 In recent years, China has significantly enhanced its awareness and capability in establishing specialised disease databases, such as those for MS and NMOSD. 8 31 32 Current Chinese cohort studies of CNS demyelinating diseases face several challenges, including a lack of comprehensive clinical database that incorporates genetic information and a limited sample size with few disease types represented. Therefore, the establishment of a large-scale, multimodal database for CNS demyelinating diseases in the Chinese population, integrating clinical, genetic, imaging and electrophysiological data, is crucial. It may facilitate our understanding of the aetiology of CNS demyelinating diseases, accelerate the discovery of biomarkers, optimise disease management and provide robust data support for the development of personalised treatment regimens. Cohort description The cohort was originally established based on the synthesis and investigation of neuroimmunological diseases by clinical experts. A foundational cohort was constructed using clinical information of CNS demyelinating diseases. In 2020, a national multicentre neuroimmunology database in China was established with the support of the National Key R&D Program ‘Neurological Disease Cohort Study’, including clinical information and biological samples. Subsequently, we integrated the hd-EEG database in 2021 and neuroimaging database in 2024, which are now collectively referred to as the Chinese neuroimmunological disease database (NIDBase). NIDBase is a multicentre cohort, approved by the ethical committees of Xuanwu Hospital, Capital Medical University, China. The primary objective of the cohort is to identify genetic and environmental risk factors, evaluate the geographic and socioeconomic status and explore biomarkers for early disease detection, relapse risks and disability progress. Additionally, the cohort can assess the safety and efficiency of various drugs for CNS demyelinating diseases. Considering the diversity of Chinese medical centres in this study, we simplified the information needs collected for our subcentres to facilitate easier integration and management. To avoid duplicate patients in the database, we used the identity card number as a unique identifier. Each subcentre will have its own independent login identification (ID) and password. The NIDBase has a safety and integrity quality control system. Data cleaning and verification will be conducted regularly. Patient and public involvement Patients or the public were not involved in the planning or design, recruitment or conduction of the study. Patient recruitment Patients diagnosed with CNS demyelinating diseases in 56 Chinese medical centres were enrolled in this study. All patients agreed and signed informed consents. MS was diagnosed based on the 2017 Revised McDonald Criteria. 33 Patients with NMOSD met the 2015 diagnosis criteria established by the International Panel for Neuromyelitis Optica Diagnosis. 34 MOGAD patients were diagnosed according to the proposed criteria from the 2023 international MOGAD panel. 35 GFAP-A was diagnosed when the GFAP-IgG was positive in serum or cerebrospinal fluid (CSF) and the clinical features were consistent with GFAP-A, while excluding other potential aetiologies. 5 Once patients meet the inclusion criteria, the enrolment process will be initiated. Baseline data, biological samples, MRI scans and hd-EEG will be collected by face-to-face interviews. Neurologists will conduct regular follow-ups either in the outpatient department or via telephone (summarised in figure 1 ). Figure 1. The flowchart depicting enrolment and follow-up of patients with CNS demyelinating diseases in the NIDBase. CNS, central nervous system; Hd-EEG, high-density electroencephalography; NIDBase, Chinese neuroimmunological disease database. Open in a new tab Data collection According to clinical features of recurrent episodes of CNS demyelinating diseases, baseline data include basic information, scale assessments, details of each demyelinating event and therapeutic records. Related information will be collected through face-to-face follow-ups. Basic information includes sociodemographics, economic status, lifestyle, family history, disease history, medical records and the summary of all attacks. Baseline scale assessment contains standardised scale assessment (activities of daily living assessment, cognitive function assessment, anxious and depression assessment) and standardised questionnaire assessment (eating habit scale and physical activity). Records for each demyelinating event will include a summary of all attacks: clinical symptoms and signs, examinations at the time of attack, diagnosis and recovery. Regarding therapeutic records, the medications used during acute and remission phases for each patient will be collected. Potential side effects and instances of switching drugs will also be recorded (shown in online supplemental table 1 ). Laboratory test results will be recorded after enrolment, including systemic immunology, blood routine, blood biochemistry, thyroid function, CSF examinations, flow cytometry of lymphocytes and demyelinating antibody detection. The demyelinating antibodies were detected by CBA (positivity threshold: titer ≥1:10). Additional biological samples will be collected for genetics, proteomics and single-cell sequencing. All biological samples will be collected by research nurses. Then, samples will be prepared and stored at −80°C. The sample numbers of each patient are shown in table 1 . Table 1. Biological sample collection in the NIDBase. Sample Number of cryotubes Volume (mL) Plasma 1 1.5 Serum 1 1.5 Whole blood 1 1.5 Open in a new tab NIDBase, Chinese neuroimmunological disease database. Comprehensive neuroimaging assessment and hd-EEG will be conducted (as summarised in table 2 ). Due to spatial and temporal characteristics of demyelination, brain and spinal cord MRI will be performed on each patient. During follow-up, MRI data from patients will also be collected regularly. Baseline hd-EEG data will be collected for each patient with demyelinating diseases. Based on the patients’ symptoms and baseline data, individualised clinical trials for neuromodulation will be designed and conducted. Original MRI and hd-EEG data of all subcentres will be stored at Xuanwu Hospital to explore brain functional connectivity and construct deep learning models. Table 2. The parameter of MRI and high-density electroencephalography (hd-EEG). Parameter MRI T1WI, T2WI, T2 fluid-attenuated inversion recovery (FLAIR), Sag bravo, diffusion tensor imaging (DTI), blood oxygenation level dependent (BOLD) hd-EEG 30 min (baseline) in resting state Open in a new tab Follow-up schedule After enrolment, all patients will be followed up according to the planned time: at 3 months and 6 months and then annually. Face-to-face follow-ups will be conducted if patients are hospitalised due to recurrence or if they visit the outpatient clinic. Otherwise, we will conduct follow-ups via phone calls and WeChat (social media) communications. During the follow-up periods, disease condition and outcome, therapeutic adverse events, standardised scale and questionnaire assessments will be recorded. Biological samples, MRI and hd-EEG will be collected during face-to-face appointments. All-cause mortality is defined as our follow-up endpoint. Currently, the follow-up rate of this study is approximately 70%. Annual recurrence rate, confirmed disability progression (CDP) and cognitive scale assessment are main outcome variables in this study. The first attack is defined as the first episode of inflammatory demyelinating diseases. The first occurrence is defined as the second episode after disease onset. CDP is defined as disease progression from baseline in clinical disability dysfunction. It is usually measured by an increase in the Expanded Disability Status Scale (EDSS) at 3 or 6 months (an increase of ≥1.0 points for baseline EDSS ≤5.5 points; or an increase of ≥0.5 points for baseline EDSS >5.5 points). Symbol Digit Modalities Test ≤55 is defined as cognitive impairment. 36 37 Finding to date Up to December 2024, there are 3866 CNS demyelinating diseases (84 CIS, 282 MOGAD, 1405 MS and 2095 NMOSD) in the NIDBase. As shown in figure 2 , 56 subcentres are located across 21 provinces in China, covering most regions of the country. Figure 2. The regional distribution and proportion of CNS demyelinating diseases in the NIDBase. CIS, clinically isolated syndrome; MOGAD, myelin oligodendrocyte glycoprotein antibody-associated disease; MS, multiple sclerosis; NIDBase, Chinese neuroimmunological disease database; NMOSD, neuromyelitis optica spectrum disease. Open in a new tab The baseline information is shown in table 3 . Consistent with previous studies, CNS demyelinating diseases are more common in women, with a particularly significant prevalence in NMOSD ( figure 3A ). In our study, the gender ratio (female/male) is 1.4 in CIS, 2.12 in MS, 6.73 in NMOSD and 1.1 in MOGAD, reflecting the real-world data on CNS demyelinating diseases in China ( table 3 ). The age range of NMOSD patients is relatively broad, with the 50–60 age group being most commonly affected. In contrast, MS is more prevalent among individuals in the 30–40 age group ( figure 3B ). There are significant differences in the ages of NMOSD patients compared with those with CIS, MS and MOGAD (p<0.001) ( figure 3C ). Table 3. Baseline characteristics of the participants in the NIDBase. Baseline characteristics All (n=3866) CIS (n=84) MS (n=1405) NMOSD (n=2095) MOGAD (n=282) Gender, n (%) Female 2976 (77%) 49 (58.3%) 955 (68%) 1824 (87.1%) 148 (52.5%) Male 890 (23%) 35 (41.7%) 450 (32%) 271 (12.9%) 134 (47.5%) Ages (years) <10 1 0 0 1 0 10–20 114 9 49 31 25 20–30 526 10 254 205 57 30–40 1070 27 544 428 71 40–50 768 29 295 392 52 50–60 856 7 191 615 43 60–70 387 2 55 303 27 70–80 128 0 16 107 5 80–90 14 0 0 12 2 >90 2 0 1 1 0 Open in a new tab CIS, clinically isolated syndrome; MOGAD, myelin oligodendrocyte glycoprotein antibody-associated disease; MS, multiple sclerosis; NIDBase, Chinese neuroimmunological disease database; NMOSD, neuromyelitis optica spectrum disease. Figure 3. A The numbers of patients with CIS, MS, MOGAD and NMOSD stratified by gender. B Patient numbers for different age groups with various CNS demyelinating diseases. C Boxplot showing the distribution of age grouped by gender in patients with different CNS demyelinating diseases. ***p<0.001. CIS, clinically isolated syndrome; MS, multiple sclerosis; MOGAD, myelin oligodendrocyte glycoprotein antibody-associated disease; NMOSD, neuromyelitis optica spectrum disease. Open in a new tab Strengths and limitations In this protocol, a comprehensive NIDBase will be established, including clinical information, biological samples, imaging and hd-EEG databases. All patients will be followed up regularly. This is the largest multimodal cohort study on CNS demyelinating diseases in China. Due to the challenging nature of diagnosis and treatment, as well as the observed racial disparities, patients with CNS demyelinating disease face numerous obstacles. A multicentre disease cohort will be used to explore the risk factors and disease characteristics for the application of diagnosis and treatment in this study. Additionally, our cohort, with its relatively long-term follow-up of patients, ensures comprehensive management while simultaneously gathering precise and dependable real-world data on CNS demyelinating patients. There are some limitations in our cohort. Data were contributed by multiple participating centres. Although staff received uniform training, medical record templates, laboratory reference ranges and data interpretation remained heterogeneous. Adopting a common minimum dataset, harmonising reference intervals across sites and implementing automated validation rules would reduce this variability. Patient and public involvement was not integrated into the design or conduct of the present study. There are plans to involve patients and public: (1) presenting the key findings to our patients and codeveloping a dissemination strategy with patient partners and (2) updating the protocol after 12 months to incorporate their feedback on future analyses and data-sharing policies. Furthermore, in our study, we diagnosed MS using the 2017 revised McDonald Criteria. We will update and revise our data according to the latest 2024 diagnostic criteria. Additionally, we will re-evaluate and compare the data for patients diagnosed using the 2017 criteria to ensure the accuracy and reliability of our results. Collaboration We warmly embrace potential collaborations with other researchers. Presently, only our research team has access to the data. Researchers interested in collaboration are welcome to contact our corresponding author, Professor Hao ([email protected]). Supplementary material online supplemental file 1 bmjopen-16-1-s001.docx (22.1KB, docx) DOI: 10.1136/bmjopen-2025-099386 Acknowledgements We thank the Chinese Institute for Brain Research (Beijing) for their assistance. We also thank other subcentres, including Affiliated Hospital of Zunyi Medical University, Baoding No 1 Central Hospital, Beijing Fengtai You'anmen Hospital, Bishan Hospital of Chongqing Medical University, Central Hospital of Dalian University of Technology, Changde First People's Hospital, China-Japan Union Hospital of Jilin University, Daping Hospital, Third Military Medical University, First Hospital of Shanxi Medical University, Guangzhou First People's Hospital, South China University of Technology, Guizhou Provincial People's Hospital, Inner Mongolia People's Hospital, Lanzhou University Second Hospital, Liuzhou Workers Hospital, the Fourth Affiliated Hospital of Guangxi Medical University, Ningbo No 2 Hospital, No 1 Traditional Chinese Medicine Hospital in Changde, Ordos Central Hospital, Peking University People's Hospital, Peking University Third Hospital, Qilu Hospital of Shandong University (Qingdao), Qilu Hospital of Shandong University, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Renmin Hospital of Wuhan University, Rizhao Center Hospital, Second Affiliated Hospital of Army Medical University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shanxi Provincial People's Hospital, Tangdu Hospital, Air Force Medical University, The Affiliated Hospital of Qingdao University, The Affiliated Hospital of Xuzhou Medical University, The Eighth Medical Center of PLA General Hospital, The First Affiliated Hospital of Chongqing Medical University, The First Affiliated Hospital of Guangxi Medical University, The First Affiliated Hospital of Harbin Medical University, The First Affiliated Hospital of Kunming Medical University, The First Affiliated Hospital of Nanjing Medical University, The First Affiliated Hospital of Soochow University, The First Affiliated Hospital of Wenzhou Medical University, The First Affiliated Hospital of Zhengzhou University, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, The First Affiliated Hospital, Sun Yat-sen University, The First Affiliated Hospital, Zhejiang University School of Medicine, The First Hospital of China Medical University, The First Hospital of Hebei Medical University, The First Hospital of Jilin University, The First Hospital of Shijiazhuang, The People's Hospital of Liaoning Province, The Second Affiliated Hospital of Anhui Medical University, The Second Affiliated Hospital of Harbin Medical University, The Second Affiliated Hospital of Soochow University, The Second Affiliated Hospital of Xinjiang Medical University, The Second Hospital of Hebei Medical Hospital, West China Hospital, Sichuan University, Xiangya Hospital, Central South University, Zhengzhou University People's Hospital, Zhengzhou University. Footnotes Funding: This work was supported by Beijing Research Ward Excellence Program (BRWEP2024W022010101), the Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes (JYY2023-7), the grant from the Chinese Institutes for Medical Research, Beijing (CX23YZ15), Youth Beijing Scholar (NO.020), the Project for Innovation and Development of Beijing Municipal Geriatric Medical Research Center (11000023T000002041657). Prepublication history and additional supplemental material for this paper are available online. To view these files, please visit the journal online ( https://doi.org/10.1136/bmjopen-2025-099386 ). Provenance and peer review: Not commissioned; externally peer reviewed. Patient consent for publication: Not applicable. Ethics approval: This study involves human participants. The cohort study was approved by the ethical committees of Xuanwu Hospital, Capital Medical University, China (2021-017-002). All patients agreed and signed informed consents. Participants gave informed consent to participate in the study before taking part. Data availability free text: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Map disclaimer: The depiction of boundaries on this map does not imply the expression of any opinion whatsoever on the part of BMJ (or any member of its group) concerning the legal status of any country, territory, jurisdiction or area or of its authorities. This map is provided without any warranty of any kind, either express or implied. Patient and public involvement: Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research. Data availability statement Data are available upon reasonable request. References 1. Miller DH, Chard DT, Ciccarelli O. Clinically isolated syndromes. Lancet Neurol. 2012;11:157–69. doi: 10.1016/S1474-4422(11)70274-5. 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