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Objective: The aim of this study is to investigate the unique features of seronegative neuromyelitis optica spectrum disorders (NMOSD) in Thailand. Background: It remains unknown whether seronegative NMOSD patients possess clinical and paraclinical features that are distinct from those with seropositivity. Methods: In a Thai cohort of idiopathic inflammatory CNS disorders (n =122), 52 patients fulfilled the Wingerchuk 2007 criteria for NMOSD. We determined anti-AQP4 antibody statuses using three different assays (an in-house cell-based assay [CBA], a commercially available CBA and a tissue-based indirect immunofluorescence [IIF] assay). Results: Among the NMOSD patients, the percentage of seropositive cases was 54.5% based on the in-house and commercial CBAs and 30.8% based on the IIF assay. Using the in-house CBA, seronegative NMOSD patients exhibited distinct features compared with seropositive patients, such as a lack of female preponderance (F/M=1.2 vs. 6.0), frequent simultaneous bilateral optic involvement (33.3% vs. 0.04%), a lower annual relapse rate (0.4±0.3 vs. 0.7±0.6), fewer spinal cord lesions (1.0±4.3 vs. 1.4±0.6), and lower CSF cell counts (20±72 vs. 80±285). Use of the commercial CBA yielded essentially similar results, but some of these differences were not significant using IIF. Conclusions: Sensitive anti-AQP4 antibody assays reveal features of seronegative NMOSD patients that differ from those of seropositive patients from Thailand. [ABSTRACT FROM AUTHOR]

The article presents a study which evaluates the effectiveness and adverse drug reactions of beta-interferon (IFN-β) treatment in Thai patients with demyelinating diseases. It says that the data of Thai patients with MS, neuromyelitis optica (NMO) and NMO spectrum disorders (NMOSDs) who participated the MS Clinic were retrospectively reviewed. Results show that IFN-β treatment was effective to reduce both annualized relapse rates (ARR) and disability progression in MS patients.

Background Patients with neuromyelitis optica spectrum disorder (NMOSD) are often seropositive for antibodies against aquaporin-4 (AQP4). The importance of MRI monitoring in this disease requires evaluation. Purpose To profile MRI features from a large international cohort with AQP4 immunoglobulin G (IgG)-seropositive NMOSD (from the Parallel MRI in NMOSD [PAMRINO] study) and to evaluate and confirm existing knowledge regarding the incidence, location, and longitudinal development of characteristic lesions in the central nervous system associated with AQP4-IgG-seropositive NMOSD. Materials and Methods In this retrospective study (from August 2016 to January 2019), MRI and clinical data were collected from 17 NMOSD expert sites in 11 countries across four continents. Clinical features and lesions identified at cross-sectional and longitudinal MRI were assessed. No formal statistical tests were used to compare observations; however, means, SDs, and 95% CIs are reported when evaluating lesion frequencies. Results Available T1-weighted and T2-weighted MRI scans in patients with AQP4-IgG-seropositive NMOSD ( n = 525) were read. Among the 525 patients, 320 underwent cerebral MRI examinations with T2-weighted hyperintense cerebral (264 of 320; 82.5%), cerebellar (44 of 320; 13.8%), and brainstem (158 of 321 [49.2%], including one lesion observed at cervical spinal cord [SC] MRI) lesions. Lesions in the optic nerves, analyzed from 152 MRI examinations, were mainly found in the central (81 of 92; 88%) and posterior (79 of 92; 86%) sections (bilaterally in 39 of 92; 42%). Longitudinally extensive transverse myelitis was the predominant SC lesion pattern (upper compartment from 322 MRI examinations, 133 of 210 [63.3%]; and lower compartment from 301 MRI examinations, 149 of 212 [70.3%]). However, nonlongitudinal extensive transverse myelitis lesions were also observed frequently (105 of 210; 50.0%) in the cervical SC. Clinical data ( n = 349; mean age, 44 years ± 14 [SD]; 202 female patients) and acute lesions at contrast-enhanced (CE) MRI ( n = 58, performed within 30 days of the last attack) were evaluated. CE lesions were detected in the cerebrum (eight of 13; 62%), optic nerves (14 of 19; 74%), or chiasm (three of four; 75%) within 15 days of any relapse. In the upper SC (29 of 44; 66%), CE lesions were frequently observed up to 20 days after a clinical myelitis event. Conclusion A high incidence of abnormal brain MRI examinations and nonlongitudinal extensive SC lesions was found in patients in PAMRINO with AQP4-IgG-seropositive NMOSD. © RSNA, 2024 Supplemental material is available for this article.

Objective: To evaluate the efficacy of rituximab (RTX) in stabilizing disability progression in secondary progressive multiple sclerosis (SPMS)., Methods: A systematic review was conducted, encompassing studies from inception to April 2023, utilizing the MEDLINE and EMBASE databases. Inclusion criteria comprised studies with a minimum of 3 SPMS patients receiving intravenous RTX in at least one infusion, with a follow-up duration of at least 6 months. Primary outcome measures included changes in Expanded Disability Status Scale (EDSS) scores. Mean differences in pre- and post-RTX EDSS scores were analyzed using a random-effects model. Meta-regression examined age at RTX initiation, pre-RTX EDSS scores, disease duration, and outcome reported time as variables. Secondary outcomes assessed changes in the annualized relapse rate (ARR)., Results: Thirteen studies, involving 604 SPMS patients, met the inclusion criteria. Following a mean follow-up of 2 years, the mean difference in EDSS scores (ΔEDSS = EDSS pre-RTX  - EDSS post-RTX ) was -0.21 (95% CI -0.51 to 0.08, p = 0.16), indicating no significant variation. Multivariable meta-regression identified significant associations between EDSS score mean difference and pre-RTX EDSS scores, disease duration at RTX initiation, and outcome reported time. However, age at RTX initiation showed no significant association. Pre- and post-RTX ARR data were available for 245 out of 604 SPMS patients across seven studies, revealing a mean difference in ARR (ΔARR = ARR pre-RTX  - ARR post-RTX ) of 0.74 (95% CI 0.19-1.29, p = 0.008)., Interpretation: RTX demonstrates efficacy in reducing relapse frequency and exhibits potential in stabilizing disability progression over a 2-year follow-up, particularly among individuals with shorter disease duration., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Objective: The first international consensus criteria for optic neuritis (ICON) were published in 2022. We applied these criteria to a prospective, global observational study of acute optic neuritis (ON)., Methods: We included 160 patients with a first-ever acute ON suggestive of a demyelinating CNS disease from the Acute Optic Neuritis Network (ACON). We applied the 2022 ICON to all participants and subsequently adjusted the ICON by replacing a missing relative afferent pupillary defect (RAPD) or dyschromatopsia if magnetic resonance imaging pathology of the optical nerve plus optical coherence tomography abnormalities or certain biomarkers are present., Results: According to the 2022 ICON, 80 (50%) patients were classified as definite ON, 12 (7%) patients were classified as possible ON, and 68 (43%) as not ON (NON). The main reasons for classification as NON were absent RAPD (52 patients, 76%) or dyschromatopsia (49 patients, 72%). Distribution of underlying ON etiologies was as follows: 78 (49%) patients had a single isolated ON, 41 (26%) patients were diagnosed with multiple sclerosis, 25 (16%) patients with myelin oligodendrocyte glycoprotein antibody-associated disease, and 15 (9%) with neuromyelitis optica spectrum disorder. The application of the adjusted ON criteria yielded a higher proportion of patients classified as ON (126 patients, 79%)., Interpretation: According to the 2022 ICON, almost half of the included patients in ACON did not fulfill the requirements for classification of definite or possible ON, particularly due to missing RAPD and dyschromatopsia. Thorough RAPD examination and formal color vision testing are critical to the application of the 2022 ICON., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

This study aimed to identify the prevalence, clinical and radiographic characteristics, and risk factors for cognitive dysfunction in patients with Neuromyelitis optica spectrum disorder (NMOSD). Eighty-three participants who were diagnosed with NMOSD were recruited. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and Frontal Assessment Battery (FAB). The mean age of the patients was 47.78 ± 13.14 years, with an average of 12.05 ± 4.62 years of formal education. The majority (54%) exhibited cognitive impairment, defined by a MoCA score < 25 (mean: 22.96 ± 3.82). Disease severity (evaluated by the Expanded Disability Status Scale) and lower formal education levels were associated with cognitive impairment (p = 0.011 and < 0.001, respectively). The annualized relapse rate, disease duration, and AQP4 antibody status were not associated with cognitive impairment. Interestingly, informant-reported cognitive decline was associated with poorer cognitive performance (p = 0.027). Radiographic findings of lesion location and severity were associated with MoCA-assessed cognitive performance, particularly for lesions in the right parietal lobes (p = 0.023). Hippocampal atrophy was negatively correlated with FAB scores. In conclusion, approximately half of the Thai patients with NMOSD exhibited cognitive impairment, which was associated with age, formal education level, disease severity, relative perception, and specific radiological findings. Further studies incorporating comprehensive neuropsychological tests and subjective cognitive complaints are warranted., (© 2024. The Author(s).)

Background: Despite the global availability of multiple sclerosis (MS) treatments, accessing and financing them in Southeast Asia (SEA) remains a challenge. This descriptive survey-based study aimed to describe the current state of MS treatment access and local access dynamics within this region., Methods: The survey questionnaire, comprising of 15 closed-ended and five open-ended questions, was developed by three neurologists with expertise in MS and routine MS patient management, or had training in neuroimmunology. Questionnaire development was guided by the recent Atlas of MS and in alignment with the Access to Treatment framework, focusing on MS diagnosis and treatment issues in SEA. Fifteen neurologists experienced in managing MS across the region were identified as key informants for this study., Results: All fifteen neurologists participated in the survey via email and videoconferencing between January 2020 and February 2023, which included the following countries: Brunei, Cambodia, Indonesia, Malaysia, Myanmar, Lao PDR, Philippines, Singapore, Thailand, Timor-Leste, and Vietnam. All had at least five years of experience in managing MS patients and six had previously completed a neuroimmunology fellowship programme. SEA countries showed disparities in healthcare financing, availability of neurologists, MS treatments, and investigative tools. Access to MS disease-modifying treatments (DMTs) is hindered by high cost, lack of MS specialists, and weak advocacy efforts. On-label DMTs are not listed as essential medicines regionally except for interferon beta1a and teriflunomide in Malaysia. On-label monoclonals are available only in Malaysia, Singapore, and Thailand. Generic on-label DMTs are unavailable due to lack of distributorship and expertise in using them. Off-label DMTs (azathioprine, methotrexate, and rituximab) predominate in most SEA countries. Other challenges include limited access to investigations, education, and knowledge about DMTs among general neurologists, and absence of registries and MS societies. Patient champions, communities, and MS organisations have limited influence on local governments and pharmaceutical companies. Despite its increasing prevalence, there is a lack of concerted priority setting due to MS being perceived as a rare, non-communicable disease., Conclusion: This study highlights the distinct dynamics, challenges, and research gaps within this region, and provides suggestions to improve MS diagnosis, education, and medicine access., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tianrong Yeo reports a relationship with Edanz Group Ltd that includes: consulting or advisory. Tianrong Yeo reports a relationship with Merck & Co Inc that includes: consulting or advisory and travel reimbursement. Tianrong Yeo reports a relationship with EUROIMMUN Medizinische Labordiagnostika AG that includes: consulting or advisory. Tianrong Yeo reports a relationship with Novartis that includes: consulting or advisory. Tianrong Yeo reports a relationship with Terumo BCT that includes: consulting or advisory. Tianrong Yeo reports a relationship with ASEAN Neurological Association that includes: consulting or advisory. Tianrong Yeo reports a relationship with National Medical Research Center that includes: funding grants. Tianrong Yeo reports a relationship with Roche that includes: funding grants. Joanna Laurson-Doube reports a relationship with Bristol Myers Squibb Co that includes: funding grants. Joanna Laurson-Doube reports a relationship with Sanofi that includes: funding grants. Joanna Laurson-Doube reports a relationship with Merck & Co Inc that includes: funding grants. Joanna Laurson-Doube reports a relationship with Viatris that includes: funding grants. Joanna Laurson-Doube reports a relationship with Novartis that includes: funding grants. Joanna Laurson-Doube reports a relationship with Biogen that includes: funding grants. Joanna Laurson-Doube reports a relationship with Roche that includes: funding grants., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Complementary and alternative medications (CAM) are common among patients with multiple sclerosis (MS) for physical and psychological support. However, there is insufficient data regarding the application of CAM in the different cultures and beliefs of each community as well as patient's status., Objective: To evaluate the prevalence and modalities of the use of CAM among patients with central nervous system idiopathic inflammatory demyelinating diseases (CNS-IIDD) in a tertiary care hospital., Methods: A cross-sectional study was conducted at Siriraj Hospital from June to December 2021 involving patients with MS, neuromyelitis optic spectrum disorders (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), idiopathic transverse myelitis (iTM), and optic neuritis (ON) to examine the prevalence and mode of CAM use and its correlation with patient characteristics., Results: There were 107 patients. The diagnoses were MS (38), NMOSD (55), MOGAD (5), iTM (7), and ON (2). Most of the patients were female (89.7%), and 61.7% were diagnosed over 5 years. The mean Expanded Disability Status Scale was 2.63 (S.D., 2.38), and the median ambulation index was 0 (range 0-8.5). There were 68 patients (63.6%) with a history of CAM use for at least 3 months, while those with current use decreased to 62 (58.5%). Vitamins and minerals were the most commonly used, particularly vitamin D (97.1%) and calcium (47.7%). Both treatments were primarily prescribed (95.3%) rather than self-administered (24.3%). The main reasons for the use of CAM were to strengthen their health (48.6%) and relieve existing symptoms (28.0%)., Conclusions: The use of CAM is common among patients with Thai CNS-IIDD. Further exploration of patient perspectives and preferences regarding CAM usage may contribute to a more comprehensive management approach for patients with CNS-IIDD., Competing Interests: There is no potential conflicts of interest or financial relationships that may be perceived as influencing the research presented in the manuscript titled “Use of Complementary and Alternative Medicine in Patients with Idiopathic Inflammatory Demyelinating Diseases of the Central Nervous System: A Cross-Sectional Study in Thailand.”, (© 2024 The Authors.)

In Thailand, resource limitations lead many multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) patients to use off-label immunosuppressants. This study assesses the efficacy and safety of rituximab (RTX) with a CD19-based reinfusion regimen among Thai MS and NMOSD patients. A retrospective review of patients at the Faculty of Medicine Siriraj Hospital from January 1994 to April 2023 was conducted. The primary outcome assessed was the change in annualized relapse rate (ARR) for patients using RTX for over a year. Secondary outcomes included changes in the Expanded Disability Status Scale (EDSS) scores, time to the first relapse after RTX initiation for patients using RTX for over a year, and an evaluation of the safety of RTX. The study encompassed 36 MS and 39 NMOSD patients. A majority of patients (91.7% of MS and 79.5% of NMOSD) experienced no relapses during a median follow-up of 30 months (Interquartile range [IQR] 20-46) and 31 months (IQR 23-41), respectively. The median ARR significantly decreased in both MS (from 0.77 [IQR 0.42-1.83] to 0 [IQR 0-0], p < 0.001) and NMOSD (from 0.92 [IQR 0.68-1.78] to 0 [IQR 0-0.17], p < 0.001) patients after switching to RTX, with no difference between those following a fixed 6-month time point regimen and a CD19-based reinfusion regimen. Median EDSS scores improved significantly at the last follow-up visit in both groups. The mean time to the first subsequent relapse was 8.3 ± 3.0 months in MS and 6.8 ± 1.7 months in NMOSD. Mild adverse drug reactions occurred in 44% of patients. RTX effectively prevents relapses in Thai MS and NMOSD patients, with no observed serious adverse drug reactions., (© 2024. The Author(s).)

Tumefactive demyelinating lesions (TDL), characterized by large (≥ 2 cm) demyelinating lesions mimicking tumors, are a rare manifestation of the central nervous system inflammatory demyelinating diseases (CNS-IDD). Distinguishing TDL from other brain lesions can be challenging, often necessitating biopsy or advanced diagnostics. The natural history of TDL varies among races. This study aimed to assess demographics, clinical and radiological features, laboratory findings, management, and outcomes of Thai patients with TDL. We retrospectively reviewed records of twenty-six patients with TDL from the Multiple Sclerosis and Related Disorders registry from two tertiary medical centers. Among 1102 CNS-IDD patients, 26 (2.4%) had TDL. The median age at TDLs onset was 34.5 years (range 17-75); 69.2% were female. Over 70% manifested TDL as their initial CNS-IDD presentation. Common presenting symptoms included motor deficits, sensory disturbances, and cognitive problems. About two-fifths exhibited multiple lesions, most frequently in the frontoparietal region (46.2%). Half of the patients showed an incomplete ring on post-contrast T1-weighted imaging, with peripheral diffusion-weighted imaging restriction in twenty-one patients. T2-hypointense rims were present in thirteen (56.5%) patients. Brain biopsy was performed in 12 cases (46.1%). Serum aquaporin-4 immunoglobulin was positive in 16.7% of tested (4/24) cases. Serum myelin oligodendrocyte glycoprotein immunoglobulin was negative in all thirteen patients tested. Twenty patients (76.9%) received intravenous corticosteroids for TDL attacks. After the median follow-up period of 48 months (range 6-300), 23.1% experienced CNS-IDD relapses. Median Expanded Disability Status Scale at TDL diagnosis was 4.3 (range 0.0-9.5), and improved to 3.0 (range 0.0-10.0) at the last follow-up. This study suggested that TDL were rare among Thai CNS-IDD patients, frequently presenting as a monophasic condition with a favorable outcome., (© 2024. The Author(s).)

Introduction: Therapeutic plasma exchange (TPE) for neuroimmunological disorders has played an important role in the Southeast Asian region. This study investigates the challenges of performing TPE within the region., Method: A questionnaire-based survey was conducted and launched to 15 South East Asian Therapeutic Plasma Exchange Consortium (SEATPEC) members from seven countries in January 2021. It included demographics, TPE techniques, indications, challenges, timing, outcome measurement, and access to laboratory testing in each local center., Results: A total of 15 neurologists from 12 participating centers were included. They usually perform five sessions of TPE (100.0%), with 1 to 1.5 plasma volume (93.3%), and exchanges via the central catheter (100.0%). Acute relapses of neuromyelitis optica spectrum disorder and myasthenia gravis are the most common indications. They used a combination of normal saline and 5% albumin (60.0%) as replacement fluid. Most (66.7%) used TPE as an add-on treatment in steroid-refractory cases or as first-line treatment for severe attacks. They suggested assessing the TPE efficacy of TPE by the interval to the next attack, post-TPE relapse rates, and TPE-related complications. The major challenges within our region are expense, reimbursibility, and access to TPE., Conclusion: Although countrywise differences exist, all share similarities regarding methods, indications, timing, obstacles, and challenges of TPE for neuroimmunological conditions. Regional collaboration will be essential to identify strategies to reduce these barriers to access to TPE in the future., (© 2023 Wiley Periodicals LLC.)

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system. The immunopathology of MS involves both T and B lymphocytes. Rituximab is one of the anti-CD20 monoclonal antibody therapies which deplete B-cells. Although some anti-CD20 therapies have been approved by the Food and Drug Administration for treatment of MS, rituximab is used off-label. Several studies have shown that rituximab has a good efficacy and safety in MS, including certain specific patient conditions such as treatment-naïve patients, treatment-switching patients, and the Asian population. However, there are still questions about the optimal dose and duration of rituximab in MS due to the different dosing regimens used in each study. Moreover, many biosimilars have become available at a lower cost with comparable physicochemical properties, pharmacokinetics, pharmacodynamics, efficacy, safety, and immunogenicity. Thus, rituximab may be considered as a potential therapeutic option for patients without access to standard treatment. This narrative review summarized the evidence of both original and biosimilars of rituximab in MS treatment including pharmacokinetics, pharmacodynamics, clinical efficacy, safety, and dosing regimen., 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 © 2023 Elsevier B.V. All rights reserved.)

Background: Neuromyelitis optica spectrum disorders (NMOSD) is considered a complex multifactorial disorder. Most cases are sporadic, and familial NMOSD is assumed as a rare occurrence. However, few studies reported familial aggregation of the disorder., Objectives: To report familial NMOSD cases in Thailand and conduct a systematic review of familial NMOSD., Methods: A retrospective chart review of familial NMOSD patients at the university hospital was performed. Articles related to "genetic" and "NMOSD" were systematically searched and reviewed. We included NMOSD patients whose one or more relatives were diagnosed with the same disease or multiple sclerosis (MS). Data regarding demographics, clinical features, disease outcomes, and genetic testing were collected and analyzed using descriptive statistics., Results: We identified 6 familial cases from 165 NMOSD cases (3.6%) at our hospital and gathered 77 cases from a systematic review, totaling 83 cases from 40 families. The mean (SD) age at onset was 37.2 (18.0) years. Familial NMOSD involved 1-2 generations with mainly 2 affected individuals. The most common kinship pattern was siblingship in 21 families (52.5%). Initial syndromes were mostly optic neuritis and transverse myelitis. Serum aquaporin-4 IgG was positive in 79.7% of cases. Median number of relapses was 3 (range 1-26). Median expanded disability status scale in the last visit was 2 (range 0-8). Reported human leukocyte antigens (HLA) alleles shared between familial cases were HLA-A*01 and HLA-DRB1*03., Conclusion: Familial clustering of NMOSD is more common than would be expected in the general population. The demographic, clinical, and outcome profiles of familial cases were not different from sporadic cases. Certain specific HLA haplotypes were shared among familial cases. Our systematic review highlighted complex genetic predisposition to NMOSD., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Optic neuritis (ON) often occurs at the presentation of multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD). The recommended treatment of high-dose corticosteroids for ON is based on a North American study population, which did not address treatment timing or antibody serostatus. The Acute Optic Neuritis Network (ACON) presents a global, prospective, observational study protocol primarily designed to investigate the effect of time to high-dose corticosteroid treatment on 6-month visual outcomes in ON. Patients presenting within 30 days of the inaugural ON will be enrolled. For the primary analysis, patients will subsequently be assigned into the MS-ON group, the aquapotin-4-IgG positive ON (AQP4-IgG+ON) group or the MOG-IgG positive ON (MOG-IgG+ON) group and then further sub-stratified according to the number of days from the onset of visual loss to high-dose corticosteroids ( days-to-Rx ). The primary outcome measure will be high-contrast best-corrected visual acuity (HC-BCVA) at 6 months. In addition, multimodal data will be collected in subjects with any ON (CIS-ON, MS-ON, AQP4-IgG+ON or MOG-IgG+ON, and seronegative non-MS-ON), excluding infectious and granulomatous ON. Secondary outcomes include low-contrast best-corrected visual acuity (LC-BCVA), optical coherence tomography (OCT), magnetic resonance imaging (MRI) measurements, serum and cerebrospinal fluid (CSF) biomarkers (AQP4-IgG and MOG-IgG levels, neurofilament, and glial fibrillary protein), and patient reported outcome measures (headache, visual function in daily routine, depression, and quality of life questionnaires) at presentation at 6-month and 12-month follow-up visits. Data will be collected from 28 academic hospitals from Africa, Asia, the Middle East, Europe, North America, South America, and Australia. Planned recruitment consists of 100 MS-ON, 50 AQP4-IgG+ON, and 50 MOG-IgG+ON. This prospective, multimodal data collection will assess the potential value of early high-dose corticosteroid treatment, investigate the interrelations between functional impairments and structural changes, and evaluate the diagnostic yield of laboratory biomarkers. This analysis has the ability to substantially improve treatment strategies and the accuracy of diagnostic stratification in acute demyelinating ON., Trial Registration: ClinicalTrials.gov, identifier: NCT05605951., Competing Interests: SA has received speaker honoraria from Alexion, Bayer, and Roche. JB reports payment for consultation from Horizon Therapeutics, Alexion, Antigenomycs, BeiGene, Chugai, Clene Nanomedicine, Genentech, Reistone Bio, Roche, Imcyse, and TG; grants from Alexion, Novartis, and the National Institutes of Health. In addition, JB has a patent on Compositions and methods for the treatment of neuromyelitis optica. YB has received speaker honoraria from Novartis, Roche, Genzyme-Sanofi, Merck, and Biogen. EC has received reimbursement for developing educational presentations, educational and research grants, consultation fees, and/or travel stipends from Biogen Argentina, Genzyme Argentina, Merck Argentina and LATAM, Roche Argentina and LATAM, Raffo, Novartis Argentina, LACTRIMS, and The Guthy-Jackson Charitable Foundation. JC has served on advisory boards for Horizon, Roche, and UCB. CC has received honoraria for speaking from Bayer and research funding from Novartis. JD has received royalties from Wolters Kluwer, Neurology—UpToDate and from Medlink Neurology as contributing author, from Athena Diagnostics for the use of Ma2 as an autoantibody test, and from Euroimmun for the use of NMDA-receptor, GABA(B)-receptor, GABA(A)-receptor, DPPX, and IgLON5 as autoantibody tests and has received research support from Advance Medical (allosteric modulation of NMDAR) SAGE Therapeutics, Instituto Carlos III/FEDER (FIS PI20/00197, CIBERER CB15/00010, Proyectos Integrados de Excelencia, PIE 16/00014 and AC18/00009), Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR), CERCA Programme Generalitat de Catalunya, ERA-NET NEURON, La Caixa Foundation Health Research Award, Pablove Foundation Childhood Cancer Grant, Safra Foundation, Sage therapeutics, Cellex Foundation, and La Caixa Health Foundation. EF has served on advisory boards for Alexion, Genentech, Horizon Therapeutics, and UCB. He has received speaker honoraria from Pharmacy Times. He received royalties from up-to-date. EF was a site primary investigator in a randomized clinical trial on Inebilizumab in neuromyelitis optica spectrum disorder run by Medimmune/Viela-Bio/Horizon Therapeutics. EF has received funding from the NIH (R01NS113828). EF is a member of the medical advisory board of the MOG project. EF is an editorial board member of the Journal of the Neurological Sciences and Neuroimmunology Reports. A patent has been submitted on DACH1-IgG as a biomarker of paraneoplastic autoimmunity. CF participates in a regional medical board advisory of Alexion. CG-A has received grants from Biogen Colombia. JH reports grants for OCT research from the Friedrich-Baur-Stiftung and Merck, personal fees, and non-financial support from Celgene, Janssen, Bayer, Merck, Alexion, Horizon, Novartis, Roche, Biogen, and non-financial support of the Guthy-Jackson Charitable Foundation, all outside the submitted work. JH was partially funded by the German Federal Ministry of Education and Research [(DIFUTURE), Grant Numbers 01ZZ1603[A-D] and 01ZZ1804[A-H]]. HK has received a grant from the National Research Foundation of Korea; consultancy/speaker fees or research support from Alexion, Aprilbio, Altos Biologics, Biogen, Celltrion, Daewoong, Eisai, GC Pharma, HanAll BioPharma, Handok, Horizon Therapeutics (formerly Viela Bio), Kolon Life Science, MDimune, Mitsubishi Tanabe Pharma, Merck Serono, Novartis, Roche, Sanofi Genzyme, Teva-Handok, and UCB; and is a coeditor for the Multiple Sclerosis Journal and an associated editor for the Journal of Clinical Neurology. CLM reports consultancy fees for Chiesi Farmaceutici, Regulatory PharmaNet, and Thenewway Srl and received speaker honoraria and/or travel support for meetings from Santhera Pharmaceuticals, Chiesi Farmaceutici, Regulatory Pharma Net, Thenewway Srl, First Class Srl, and Biologix. ML-P has received funding for travel and speaker honoraria from Novartis, Biogen, and Roche. MLei was funded by NHS (Myasthenia and Related Disorders Service and National Specialized Commissioning Group for Neuromyelitis Optica, UK) and by the University of Oxford, UK. She has been awarded research grants from the UK association for patients with myasthenia—Myaware and the University of Oxford. She has received speaker honoraria or travel grants from Biogen Idec, Novartis, Argenx, UCB, and the Guthy–Jackson Charitable Foundation. MLei serves on scientific or educational advisory boards for UCB Pharma, Argenx, and Viela/Horizon. SL has received consulting fees and speaker honoraria from Biogen, Novartis, TEVA, Genzyme, Sanofy, and Merck. PL has received reimbursement for developing educational presentations, educational and research grants, consultation fees, and/or travel stipends from Biogen Argentina and LATAM, Genzyme Argentina, Merck Argentina, Roche Argentina, Novartis Argentina, and LACTRIMS. AL has served as a Biogen, Bristol Myers Squibb, Merck Serono, Novartis, Roche, Sanofi/Genzyme, and Teva Advisory Board Member, has received congress and travel/accommodation expense compensations, or speaker honoraria from Biogen, Merck Serono, Mylan, Novartis, Roche, Sanofi/Genzyme, Teva, and Fondazione Italiana Sclerosi Multipla (FISM), her institutions received research grants from Novartis and Sanofi/Genzyme. SMo reports consultancy fees (Invex Therapeutics); advisory board fees (Invex therapeutics, Gensight); and speaker fees (Heidelberg engineering, Chugai-Roche Ltd., Allergan, Santen, Chiesi, and Santhera), all outside the submitted work. RM serves on scientific advisory boards for Alexion, Horizon Therapeutics, Roche, and UCB has received speaker honoraria from Alexion, Biogen, Horizon Therapeutics, Novartis, Roche, and Sanofi Genzyme, has received support for attending scientific meetings by Merck and Euroimmun, has received speaker honoraria from Biogen and Novartis. SMa received speaker honoraria for presenting at scientific meetings by Novartis and Biogen. SMo reports consultancy fees (Invex Therapeutics); advisory board fees (Invex therapeutics, Gensight); and speaker fees (Heidelberg engineering, Chugai-Roche Ltd., Allergan, Santen, Chiesi, and Santhera). All outside the submitted work. FC receives ongoing research support from the National Multiple Sclerosis Society (NMSS), the American Academy of Neurology (AAN), and Deutsche Gesellschaft für Neurologie (DGN). JPa has received support for scientific meetings and honorariums for advisory work from Merck Serono, Novartis, Chugai, Alexion, Roche, Medimmune, Argenx, UCB, Mitsubishi, Amplo, Janssen, and Sanofi. Grants from Alexion, Roche, Medimmune, UCB, and Amplo biotechnology. Patent ref P37347WO and license agreement Numares multimarker MS diagnostics Shares in AstraZeneca. Acknowledges Partial funding by Highly specialized services NHS England. SP is a named inventor on filed patents that relate to functional AQP4/NMO-IgG assays and NMO-IgG as a cancer marker, was consulted for Alexion and MedImmune, has received research support from Grifols, MedImmune, and Alexion, all compensation for consulting activities is paid directly to Mayo Clinic. SR has received research funding from the National Health and Medical Research Council (Australia), the Petre Foundation, the Brain Foundation (Australia), the Royal Australasian College of Physicians, and the University of Sydney. She was supported by an NHMRC Investigator Grant (GNT2008339). She serves as a consultant on an advisory board for UCB and Limbic Neurology and has been an invited speaker for Biogen, Excemed, and Limbic Neurology. AS received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merck-Serono, Sanofi, Biogen, Roche, Novartis, Alexion, Janssen, and Horizon Therapeutics. DS received a grant from the National Multiple Sclerosis Society and serves on several advisory committees for the Multiple Sclerosis International Federation in unpaid roles. MS received speaker honoraria from Teva Pharmaceuticals and has received funding from the German Research Foundation, Federal Ministry of Education and Research and Federal Ministry for Economic Affairs and Energy, Volkswagen Stiftung, and Berlin Institute of Health. He is holding patents for the 3D printing of computed tomography models and is a shareholder of PhantomX and MSC3D. All unrelated to this work. PSu has served on advisory boards for Horizon Therapeutics, Viridian Therapeutics, Invex Therapeutics, Kriya Therapeutics, and GenSight Biologics. He receives research support from the NIH, DOD, Horizon, Invex, and Viridian. AM has received a grant for Biopas Laboratories and reports speaking fees from Chiesi. HZ received research grants from Novartis and speaking fees from Bayer Healthcare, unrelated to this project. FP served on the scientific advisory boards of Novartis and MedImmune; received travel funding and/or speaker honoraria from Bayer, Novartis, Biogen, Teva, Sanofi-Aventis/Genzyme, Merck Serono, Alexion, Chugai, MedImmune, and Shire; is an associate editor of Neurology: Neuroimmunology & Neuroinflammation; is an academic editor of PLoS ONE; consulted for Sanofi Genzyme, Biogen, MedImmune, Shire, and Alexion; received research support from Bayer, Novartis, Biogen, Teva, Sanofi-Aventis/Geynzme, Alexion, and Merck Serono; and received research support from the German Research Council, Werth Stiftung of the City of Cologne, German Ministry of Education and Research, Arthur Arnstein Stiftung Berlin, EU FP7 Framework Program, Arthur Arnstein Foundation Berlin, Guthy-Jackson Charitable Foundation, and NMSS. HS-K received speaker honoraria from Roche. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Asseyer, Asgari, Bennett, Bialer, Blanco, Bosello, Camos-Carreras, Carnero Contentti, Carta, Chen, Chien, Chomba, Dale, Dalmau, Feldmann, Flanagan, Froment Tilikete, Garcia-Alfonso, Havla, Hellmann, Kim, Klyscz, Konietschke, La Morgia, Lana-Peixoto, Leite, Levin, Levy, Llufriu, Lopez, Lotan, Lugaresi, Marignier, Mariotto, Mollan, Ocampo, Cosima Oertel, Olszewska, Palace, Pandit, Peralta Uribe, Pittock, Ramanathan, Rattanathamsakul, Saiz, Samadzadeh, Sanchez-Dalmau, Saylor, Scheel, Schmitz-Hübsch, Shifa, Siritho, Sperber, Subramanian, Tiosano, Vaknin-Dembinsky, Mejia Vergara, Wilf-Yarkoni, Zarco, Zimmermann, Paul and Stiebel-Kalish.)

Background: Central nervous system inflammatory demyelinating diseases (CNSIDDs) have notable interracial heterogeneity. The epidemiology of CNSIDDs in Thailand, a mainland Southeast Asian country, is unknown., Objectives: To determine the cumulative incidence, point prevalence, and disease burden of neuromyelitis optica spectrum disorder (NMOSD) and other CNSIDDs in Thailand using population-based data of Chumphon., Methods: Searching for CNSIDD patients at a public secondary care hospital in Chumphon, the only neurology center in the province, from January 2016 to December 2021 was implemented using relevant ICD-10-CM codes. All diagnoses were individually ascertained by a retrospective chart review. Cumulative incidence, point prevalence, attack rate, mortality rate, and disability-adjusted life years (DALYs) were calculated., Results: Aquaporin 4-IgG-positive NMOSD was the most prevalent CNSIDD in the Thai population at 3.08 (1.76-5.38) per 100,000 persons. The prevalence of multiple sclerosis (MS) followed at 0.77 (0.26-2.26) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) at 0.51(0.14-1.87) per 100,000 adults. In the pediatric population, the incidence of acute disseminated encephalomyelitis was 0.28 (0.08-1.02) per 100,000 persons/year. Among other idiopathic demyelinating diseases, idiopathic optic neuritis had the highest incidence at 0.58 (0.24-0.92) per 100,000 persons/year, followed by acute transverse myelitis at 0.44 (0.14-0.74). Idiopathic demyelinating brainstem syndrome was also observed at 0.04 (0.01-0.25) per 100,000 persons/year. Although most had a fair recovery, disability was worst among NMOSD patients with DALYs of 3.61 (3.00-4.36) years per 100,000 persons. Mortality rate was the highest in NMOSD as well., Conclusion: CNSIDDs are rare diseases in Thailand. The prevalence is comparable to that of East Asian populations. A nationwide CNSIDDs registry would better elaborate the epidemiology of these diseases., Competing Interests: Declaration of Competing Interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: An increasing number of reports on associations between neoplasms and neuromyelitis optica spectrum disorder (NMOSD) have been published over the past decade. However, types of neoplasms and temporal relationships have not been widely studied., Objective: To report cases and determine the associations between neoplasms and NMOSD., Method: A retrospective chart review of possible paraneoplastic NMOSD patients at a university hospital was performed. Articles related to "neoplasm" and "NMOSD" were systematically searched and reviewed. We included aquaporin-4 (AQP4)-IgG-seropositive NMOSD patients whose onset of NMOSD and cancer diagnosis or recurrence were within 24 months of one another. Temporal relationship, types of neoplasms involved, treatments, and outcomes of both NMOSD and neoplasms were determined. The subgroup analysis was based on the AQP4 expression of neoplasm histology., Results: We identified 3 cases (1.3%) from a cohort of 224 AQP4-IgG-seropositive NMOSD at our hospital and retrieved 68 cases from a systematic review, totaling 71 cases of possible paraneoplastic NMOSD. The median age at onset of NMOSD was 55 (IQR 41-64) years. Eighty percent were female. The most frequently identified types of neoplasms were lung and breast, accounting for 21.1% and 18.3%, respectively. The other tumor types were ovarian tumors and hematologic malignancy, both at 12.7%. The most commonly identified tissue histology was adenocarcinoma (52.1%). We also reported the first case of melanoma in an NMOSD patient. Twenty-eight patients (39.4%) were diagnosed with cancer before the onset of NMOSD with a median duration of 9.5 (range 1-24) months. Of those, eight patients had NMOSD after surgical removal of neoplasms, and one patient had NMOSD after radiotherapy of prostate adenocarcinoma. Twenty-three patients (32.4%) had NMOSD before cancer diagnosis by a median of 3 (range 1-24) months, and the rest were diagnosed concurrently during the same admission. Three cases were diagnosed with NMOSD around the time of tumor recurrence. Tumor tissue expressed AQP4 in 82.4%., Conclusion: A small proportion of AQP4-IgG-positive NMOSD is associated with malignancy. In newly diagnosed NMOSD patients without symptoms of neoplasms, screening for age- and risk-appropriate cancer should be recommended, similar to the general population. The occurrence of NMOSD in cancer patients might suggest tumor recurrence., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Neuromyelitis optica spectrum disorder (NMOSD) often leaves patients with a residual disability after each attack. Several studies have demonstrated that mycophenolate mofetil (MMF) effectively prevents relapse in NMOSD. So far, there has been no data on the effectiveness, dosage, and safety of MMF in the Thai population., Objectives: To analyze the efficacy and safety of MMF in Thai NMOSD patients., Materials and Methods: We performed a retrospective review of NMOSD patients at Siriraj Hospital from January 1994 to December 2020. The primary outcomes were changes in annualized relapse rate (ARR) and time to relapse after MMF. Pre- and post-MMF Expanded Disability Status Scale (EDSS) scores and visual functional system scores were also compared., Results: Fifty-eight NMOSD patients taking MMF were included. The median dose required was 1,250 (IQR 1,000 - 1,500) mg/day or 23.1 (IQR 17.6-30.8) mg/kg/day. Thirty-five patients (65.5%) were relapse-free after MMF with a median follow-up period of 46.8 months (IQR 24.0-60.9). The median ARR was reduced from 0.80 (IQR 0.45-1.39) to 0 (IQR 0-0.31) after MMF treatment (p < 0.001). Over 90% had either stabilized or improved EDSS. The median EDSS score decreased from 3.5 (IQR 3-6) to 3 (IQR 2-6) (p = 0.004). Nine patients experienced adverse events from MMF, with lymphopenia and infection observed in 8.6% and 5.1% of the cohort, respectively. No serious adverse events were observed. A subgroup analysis of 25 patients switching to MMF after azathioprine failure showed a significant ARR and EDSS reduction., Conclusions: MMF is effective for relapse prevention in Thai NMOSD patients and has a low risk of adverse events. It could be a salvage therapy for patients with azathioprine failure., (Copyright © 2022. Published by Elsevier B.V.)

Background: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating astrocytopathy with a high relapse-related disability. This is the largest long-term study of Thai NMOSD patients., Objectives: To compare characteristics and outcomes of aquaporin 4 (AQP4)-IgG-positive and AQP4-IgG-negative patients., Methods: A retrospective review of NMOSD patients at a university hospital was performed from January 1994 to July 2021., Results: From 165 NMSOD patients, the overall female-to-male ratio was 14:1. The mean onset age was 37.5 ± 14.3 years, and the median disease duration was 10.2 years. Transverse myelitis (46.1%) and optic neuritis (39.4%) were the most common presentations. Around 60% remained fully ambulatory at the last follow-up. Severe visual loss and ambulation aids were comparable in both groups, but the AQP4-IgG-positive had severe bowel and/or bladder dysfunction more often than the AQP4-IgG-negative (p = 0.026). The mortality rate was 6.7%, mainly from infection. Multivariate analysis showed that longer time-to-diagnosis and higher disability scores were associated with death. Diagnosis within one year yielded better visual and motor outcomes and lower annualized relapse rate., Conclusions: Thai AQP4-IgG-positive and AQP4-IgG-negative NMOSD patients had similar baseline characteristics. Relapse and mortality rates were comparable to global NMOSD patients. Diagnosis within one year promises better outcomes., (Copyright © 2022. Published by Elsevier B.V.)

Background: Despite rigorous confirmation with reliable assays, some individuals showing the neuromyelitis optica spectrum disorder (NMOSD) phenotype remain negative for both aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) antibodies., Objective: We aimed to investigate whether double seronegative NMOSD (DN-NMOSD) and NMOSD with AQP4 antibody (AQP4-NMOSD) share the same pathophysiological basis, astrocytopathy, by measurement of cerebrospinal fluid (CSF) glial fibrillary acidic protein (GFAP) levels as a marker of astrocyte damage., Methods: Seventeen participants who (1) satisfied the 2015 diagnostic criteria for NMOSD, and (2) tested negative for AQP4 and MOG antibodies confirmed with repeated cell-based assays, and (3) had available CSF samples obtained at the point of clinical attacks, were enrolled from 4 medical centers (South Korea, Germany, Thailand, and Denmark). Thirty age-matched participants with AQP4-NMOSD, 17 participants with MOG antibody associated disease (MOGAD), and 15 participants with other neurological disorders (OND) were included as controls. The concentration of CSF GFAP was measured using enzyme-linked immunosorbent assay., Results: CSF GFAP levels in the DN-NMOSD group were significantly lower than those in the AQP4-NMOSD group (median: 0.49 versus 102.9 ng/mL; p < 0.001), but similar to those in the OND (0.25 ng/mL) and MOGAD (0.39 ng/mL) control groups. The majority (90% (27/30)) of participants in the AQP4-NMOSD group showed significantly higher CSF GFAP levels than the highest level measured in the OND group, while no participant in the DN-NMOSD and MOGAD groups did., Conclusions: These results suggest that DN-NMOSD has a different underlying pathogenesis other than astrocytopathy, distinct from AQP4-NMOSD., (© 2022. The Author(s).)

Background: Spasticity is a common and disabling problem in multiple sclerosis (MS), but its effect in other CNS inflammatory demyelinating diseases (CNSIDDs), such as neuromyelitis optica spectrum disorder (NMOSD) is not widely studied. This study aims to compare subjective and objective measurements of spasticity in NMOSD patients and determine associated factors., Methods: A prospective cross-sectional study was performed on CNSIDD patients attending the Multiple Sclerosis and Related Disorders Clinic at Siriraj Hospital, a tertiary hospital in Thailand, from June to November 2020 was performed. MS, NMOSD, and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) patients were included. Patients' self-rated Numeric Rating Scale (NRS) for spasticity and clinician-evaluated Modified Ashworth Scale (MAS) scores on the same visit were compared and assessed for correlations. Data on characteristics of patients including demographics, number of transverse myelitis (TM) attacks, disease duration, and Expanded Disability Status Scale (EDSS) score were collected., Results: Seventy-nine CNSIDD patients were included with 25 MS, 53 NMOSD, and 1 MOGAD. There was a statistically significant correlation between NRS and MAS scores (r = 0.934, p < 0.001). Spasticity was more commonly observed in NMOSD patients compared to MS (34% vs 8%, p = 0.016). Clinical characteristics strongly associated with spasticity were higher number of TM attacks (p < 0.001), severe TM attacks (p < 0.001), longitudinally extensive transverse myelitis attacks (p < 0.001), longer disease duration (p = 0.025), higher EDSS (p < 0.001), and pyramidal Functional System Scale scores (p = 0.001)., Conclusions: Patients' self-reported NRS score had a good correlation with clinician-evaluated MAS score for spasticity assessment in NMOSD and CNSIDD patients overall. Number and severity of TM attacks were associated with spasticity. Spastic patients had more disability measured by EDSS., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: The pathogenesis of neuromyelitis optica spectrum disorder (NMOSD) has been vigorously illustrated, but triggers of the disease remain unclear. Viral infection and vaccination have been observed to precede certain cases of NMOSD. Amidst the Coronavirus disease 2019 (COVID-19) pandemic, mass vaccination takes place across the globe. We report two cases of newly diagnosed NMOSD following COVID-19 vaccination and systematically review previous reports., Method: Searching of Ovid MEDLINE and EMBASE databases was done using predefined search terms related to NMOSD and vaccination. Duplicates were removed. Newly diagnosed NMOSD cases fulfilling the 2015 International Panel for NMO Diagnosis criteria with symptoms presenting between 2-30 days after vaccination were included. Data on age, sex, comorbidity, vaccine name, type, and dose number, duration from vaccination to symptom onset, clinical phenotype(s), MRI findings, CSF profiles, severity of attack, initial and maintenance treatment, number of relapses after vaccination, and clinical outcomes were extracted using a standardized table and compared., Result: Ten cases of postvaccination NMOSD were identified. Patients aged between 15-46 years old. Nine patients (90%) presented with transverse myelitis and 3 (30%) with optic neuritis. The mean duration from vaccination to clinical onset was 8.2 days (median 9 days). Five patients (50%) tested positive for aquaporin 4 (AQP4) antibody. One patient had a family history of NMOSD. Three-fourths of AQP4-IgG seropositive patients with myelopathy had short transverse myelitis. The reported vaccines included CoronaVac, ChAdOx1 nCoV-19, yellow fever, quadrivalent influenza, H1N1 influenza, quadrivalent human papillomavirus, Japanese encephalitis, rabies, and recombinant hepatitis B virus together with tetanus-diphtheria-pertussis vaccines. All patients received high-dose steroids for initial treatment and 2 received additional therapeutic plasma exchange. Maintenance therapy was given in 4 patients. Five patients (50%) experienced no subsequent relapses within the follow-up period ranging between 3-34 months. Almost all patients returned to baseline functional status., Discussion: The temporal relationship between vaccination and onset of symptoms suggests that vaccine might be a trigger of NMOSD. Genetic predisposition could be a risk factor for postvaccination NMOSD as there are evidences of family history and presence of an associated HLA allele. The prevalence of short-segment transverse myelitis seems to be higher than in typical cases of NMOSD, but the natural history is otherwise similar. All patients received acute treatment with high-dose corticosteroids, most with excellent response. Long-term immunomodulation therapy should be initiated for relapse prevention. Limitations of this study are lack of some relevant data, precision of temporal relationship, and the small number of reports., Conclusion: Postvaccination NMOSD is a rare condition that can occur with various types of vaccines. The short temporal relationship between vaccination and onset of NMOSD and the history of NMOSD in one patient's sibling indicate that vaccine might be a trigger for genetically predisposed individuals., (Copyright © 2021. Published by Elsevier B.V.)

Background: Patients with anti-aquaporin-4 antibody seropositive (AQP4-IgG+) neuromyelitis optica spectrum disorders (NMOSDs) frequently suffer from optic neuritis (ON) leading to severe retinal neuroaxonal damage. Further, the relationship of this retinal damage to a primary astrocytopathy in NMOSD is uncertain. Primary astrocytopathy has been suggested to cause ON-independent retinal damage and contribute to changes particularly in the outer plexiform layer (OPL) and outer nuclear layer (ONL), as reported in some earlier studies. However, these were limited in their sample size and contradictory as to the localisation. This study assesses outer retinal layer changes using optical coherence tomography (OCT) in a multicentre cross-sectional cohort., Method: 197 patients who were AQP4-IgG+ and 32 myelin-oligodendrocyte-glycoprotein antibody seropositive (MOG-IgG+) patients were enrolled in this study along with 75 healthy controls. Participants underwent neurological examination and OCT with central postprocessing conducted at a single site., Results: No significant thinning of OPL (25.02±2.03 µm) or ONL (61.63±7.04 µm) were observed in patients who were AQP4-IgG+ compared with patients who were MOG-IgG+ with comparable neuroaxonal damage (OPL: 25.10±2.00 µm; ONL: 64.71±7.87 µm) or healthy controls (OPL: 24.58±1.64 µm; ONL: 63.59±5.78 µm). Eyes of patients who were AQP4-IgG+ (19.84±5.09 µm, p=0.027) and MOG-IgG+ (19.82±4.78 µm, p=0.004) with a history of ON showed parafoveal OPL thinning compared with healthy controls (20.99±5.14 µm); this was not observed elsewhere., Conclusion: The results suggest that outer retinal layer loss is not a consistent component of retinal astrocytic damage in AQP4-IgG+ NMOSD. Longitudinal studies are necessary to determine if OPL and ONL are damaged in late disease due to retrograde trans-synaptic axonal degeneration and whether outer retinal dysfunction occurs despite any measurable structural correlates., Competing Interests: Competing interests: HZ reports grants from Novartis and speaking honoraria from Bayer Healthcare, unrelated to this study. EHM-L received funding from the Instituto de Salud Carlos III (Spain) and Fondo Europeo de Desarrollo Regional (FEDER-JR16/00006), Grant for MS Innovation, Fundació Privada Cellex and Marató TV3 Charitable Foundation and is a researcher in the OCTIMS study, an observational study (that involves no specific drugs) to validate SD-OCT as a biomarker for MS, sponsored by Novartis and has received honoraria and travel support for international and national meetings over the last 3 years from from Biogen, Novartis, Roche, Genzyme. She is a member of the working committee of International Multiple Sclerosis Visual System (IMSVISUAL) Consortium. MAL-P has received funding for travel and speaker honoraria from Novartis, Sanofi- Genzyme and Roche. MAF has nothing to disclose. Jacqueline Palace has received support for scientific meetings and honorariums for advisory work From Merck Serono, Novartis, Chugai, Alexion, Roche, Medimmune, Argenx, UCB, Mitsubishi, Amplo, Janssen. Grants from Alexion, Amplo biotechnology. Shares in AstraZenica. Acknowledges Partial funding by Highly specialised services NHS England. MIL reported being involved in aquaporin 4 testing, receiving salary from the National Health Service National Highly Specialised Commissioning Group for Neuromyelitis Optica, UK, being supported by the National Institute for Health Research Oxford Biomedical Research Centre, UK, and receiving speaking honoraria and travel grants from Biogen Idec, and travel grant from Novartis. SMS has nothing to disclose. AR-F is sponsored by Abide Therapeutic outside of the submitted work and reports no potential conflicts of interest. SSiritho received funding for travel and speaker honoraria from Merck Serono, Pacific Healthcare (Thailand), Menarini (Thailand), Biogen Idec, UCB (Thailand), and Novartis. AA reports personal fees from received honoraria for giving educational presentations on multiple sclerosis and neuroimmunology at several national congresses or symposia from Teva Turkey, Merck-Serono, Biogen Idec-Gen Pharma of Turkey, Roche, Novartis, Bayer, Sanofi-Genzyme. She has received travel and registration coverage for attending several national and international congresses or symposia from Merck-Serono, Biogen Idec-Gen Pharma of Turkey, Roche, Sanofi-Genzyme and Bayer. AJ has received compensation for advisory board, consulting, meeting attendance and speaking from Biogen, Terumo-BCT, Genentech, Shire and Chugai Pharmaceuticals. SH has received funding from the NMO Spectrum-UK charity and was previously funded by an MGA/Watney/NIHR Oxford Biomedical research grant. RM serves on scientific advisory board for MedImmune and has received funding for travel and honoraria from Biogen, Merck Serono, Novartis, Sanofi- Genzyme, Roche and Teva. EN has nothing to disclose. ACC received funding from the Instituto de Salud Carlos III (Spain) JR19/00007 unrelated to this manuscript. DB has received speaking/consulting honoraria from Bayer Health Care, Biogen Idec, Merck, Sanofi-Genzyme, TEVA and Roche and had travel expenses to scientific meetings sponsored by Bayer Health Care, Merck Serono, TEVA and Roche. JH reports grants for OCT research from the Friedrich-Baur-Stiftung and Merck, personal fees and non-financial support from Celgene, Merck, Alexion, Novartis, Roche, Santhera, Biogen, Heidelberg Engineering, Sanofi Genzyme and non-financial support of the Guthy-Jackson Charitable Foundation, all outside the submitted work. JH is partially funded by the German Federal Ministry of Education and Research (DIFUTURE), Grant Numbers 01ZZ1603[A-D] and 01ZZ1804[A-H]. LL received honoraria for consulting services from Merck, Roche, Biogen and for speaking activities from Teva; research support from Merck, Biogen, Novartis; travel support from Merck, Roche, Biogen, Almirall. MP has nothing to disclose. OA has received honoraria for speaking/consultation and travel grants from Bayer Healthcare, Biogen Idec, Chugai, Novartis, Medimmune, Merck Serono, and Teva and research grants from Bayer Healthcare, Biogen Idec, Novartis, and Teva. MR received speaker honoraria from Novartis, Bayer, Roche, Alexion and Ipsen and travel reimbursement from Bayer, Biogen, Merz, Genzyme, Teva, Roche and Merck, none related to this study. PA reports grants, personal fees and non-financial support from Allergan, Biogen, Ipsen, Merz Pharmaceuticals, Novartis, and Roche, personal fees and non-financial support from Bayer Healthcare, and Merck, and non-financial support from Sanofi-Aventis/Genzyme. HJK reports speaking and/or consulting: Bayer Schering Pharma, Biogen, Celltrion, Eisai, HanAll BioPharma, MedImmune, Merck Serono, Novartis, Sanofi Genzyme, Teva-Handok, and UCB; research support: Ministry of Science & ICT, Sanofi Genzyme, Teva-Handok, and UCB; steering committee member: MedImmune; co-editor/associated editor: MS Journal-Experimental, Translational and Clinical; and Journal of Clinical Neurology. J-WH has received a grant from the National Research Foundation of Korea. YM-D has served as a consultant and/or received grant support from: Acorda, Bayer Pharmaceutical, Biogen Idec, Celgene, EMD Serono, Genzyme, Novartis, Questor, Chugai, and Teva Neuroscience and is currently supported by grants from NIH NIAID Autoimmune Center of Excellence: UM1-AI110557; NIH NINDS R01-NS080821. HSK has nothing to disclose. IK served on scientific advisory board for Biogen Idec and Genentech and received research support from Guthy-Jackson Charitable Foundation, National Multiple Sclerosis Society, Biogen-Idec,Serono, Genzyme and Novartis. ZR has nothing to disclose. AR has nothing to disclose. MRY is founder and a shareholder of NovaDigm Therapeutics, Inc; he receives funding from the United States National Institutes of Health and United States Department of Defense; he holds US and international patents on immunotherapeutic and anti-infective technologies, is a member of the Genentech-Roche Scientific Advisory Committee and adviser to The Guthy-Jackson Charitable Foundation. TJS was issued US patents covering the therapeutic targeting of IGF-I receptor in autoimmune diseases. He is a paid consultant for Horizon Thera and Immunovant and is a scientific advisor to the Guthy-Jackson Charitable Foundation. He receives research funding from the National Institutes of Health. AP is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Moorfields Eye Hospital National Health Service (NHS) Foundation Trust and University College London Institute of Ophthalmology. AB is cofounder and shareholder of Motognosis and Nocturne. He is named as inventor on several patent applications regarding MS serum biomarkers, OCT image analysis and perceptive visual computing. FP reports research grants and speaker honoraria from Bayer, Teva, Genzyme, Merck, Novartis, MedImmune and is member of the steering committee of the OCTIMS study (Novartis), all unrelated to this work. FCO was employee of Nocturne GmbH and receives research support by the American Academy of Neurology and National Multiple Sclerosis Society (US), unrelated to this work as well as funding by the German Association of Neurology (Deutsche Gesellschaft für Neurologie) in context of this project.CC has received a speaking honorarium from Bayer and research funding from Novartis unrelated to this publication. All other authors have nothing to disclose., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Therapeutic plasma exchanges (TPE) has been recommended for neuromyelitis optica spectrum disorders (NMOSD) as a rescue therapy after nonresponding from the high-dose steroid and as an early therapy in severe attacks. We performed a systematic review to evaluate whether therapeutic plasma exchange (TPE) is better than conventional intravenous methylprednisolone (IVMP) in neuromyelitis optica spectrum disorders (NMOSD) patients., Methods: Systematic search was conducted in five databases: PubMed, Embase, Scopus, Web of Science, and CENTRAL for randomized controlled trials and observational studies of TPE compared to intravenous steroid in NMOSD patients with neurological or visual outcomes in English without publication date restriction. Quality assessment was performed using ROB2 and ROBINS-I. The meta-analysis was done using a random-effects model. Pooled risk ratio (RR) or mean difference with a 95% CIs of efficacy outcomes included the Expanded Disability Status Scale (EDSS), visual acuity, and LogMAR were measured., Results: Of 3439 potential studies, seven were included in the systematic review (1211 attacks; 433 patients) and three studies were included in the meta-analysis. Compared to high dose steroid alone, the add-on TPE increases a chance for the returning of EDSS to baseline at discharge (RR 3.02, 95% CI 1.34-6.81) and last follow-up (RR 1.68, 95% CI 1.01-2.79) as well as improves visual acuity at last follow-up., Conclusion: TPE as an add-on therapy to high-dose steroid injection during an acute attack in NMOSD patients is associated with returning to baseline EDSS at discharge and last follow-up, and a trend to have a lower disability at 6-12 months., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Therapeutic plasma exchange (TPE) for neuroimmunological disorders has played an increasingly important role within the Southeast Asian (SEA) region. The South East Asian Therapeutic Plasma exchange Consortium (SEATPEC) was formed in 2018 to promote education and research on TPE within the region. The advent of the Covid-19 pandemic has produced challenges for the development and expansion of this service., Methodology: A qualitative and semi-quantitative questionnaire-based survey was conducted by SEATPEC member countries from January to June 2020 (Phase 1) and then from July 2020 to January 2021 in (Phase 2) to assess the impact of Covid-19 on regional TPE., Objectives: The study's main objectives were to explore the challenges experienced and adaptations/adjustments taken by SEATPEC countries in order to continue safe and efficient TPE during the Covid-19 pandemic., Results: The pandemic was found to disrupt the delivery of TPE services in all SEATPEC countries. Contributing factors were multifactorial due to overstretched medical services, staff shortages, quarantines and redeployments, fear of acquiring Covid-19, movement restriction orders, and patient's psychological fear of attending hospitals/testing for Covid-19. All SEATPEC countries practiced careful stratification of cases for TPE (electives vs emergencies, Covid-19 vs non-Covid-19 cases). SEATPEC countries had to modify TPE treatment protocols to include careful preprocedure screening of patient's for Covid-19, use of personal protective equipment (PPE) and post-TPE sanitization of machines and TPE suites., Conclusion: Based on the responses of the survey, SEATPEC countries produced a consensus statement with five recommendations for safe and effective TPE within the region., (© 2021 Wiley Periodicals LLC.)

Therapeutic plasma exchange (TPE) is an effective and affordable treatment option in most parts of Southeast Asia (SEA). In 2018, the SEA TPE Consortium (SEATPEC) was established, consisting of regional neurologists working to improve outcome of various autoimmune neurological diseases. We proposed an immunotherapeutic guideline prioritizing TPE for this region. We reviewed disease burden, evidence-based treatment options, and major guidelines for common autoimmune neurological disorders seen in SEA. A modified treatment algorithm based on consensus agreement by key-opinion leaders was proposed. Autoimmune antibody diagnostic testing through collaboration with accredited laboratories was established. Choice of first-line immunotherapies (IVIg/corticosteroid/TPE) is based on available evidence, clinicians' experience, contraindications, local availability, and affordability. TPE could be chosen as first-line therapy for GBS, CIDP, MG (acute/short term), IgG, A paraproteinemic neuropathy, and NMDAR encephalitis. Treatment is stopped for acute monophasic conditions such as GBS and ADEM following satisfactory outcome. For chronic immune disorders, a therapy taper or long-term maintenance therapy is recommended depending on the defined clinical state. TPE as second-line treatment is indicated for IVIg or corticosteroids refractory cases of ADEM, NMOSD (acute), MG, and NMDAR/LGI1/CASPR2/Hashimoto's encephalitis. With better diagnosis, treatment initiation with TPE is a sustainable and effective immunotherapy for autoimmune neurological diseases in SEA., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Background and Objectives: To determine optic nerve and retinal damage in aquaporin-4 antibody (AQP4-IgG)-seropositive neuromyelitis optica spectrum disorders (NMOSD) in a large international cohort after previous studies have been limited by small and heterogeneous cohorts., Methods: The cross-sectional Collaborative Retrospective Study on retinal optical coherence tomography (OCT) in neuromyelitis optica collected retrospective data from 22 centers. Of 653 screened participants, we included 283 AQP4-IgG-seropositive patients with NMOSD and 72 healthy controls (HCs). Participants underwent OCT with central reading including quality control and intraretinal segmentation. The primary outcome was thickness of combined ganglion cell and inner plexiform (GCIP) layer; secondary outcomes were thickness of peripapillary retinal nerve fiber layer (pRNFL) and visual acuity (VA)., Results: Eyes with ON (NMOSD-ON, N = 260) or without ON (NMOSD-NON, N = 241) were assessed compared with HCs (N = 136). In NMOSD-ON, GCIP layer (57.4 ± 12.2 μm) was reduced compared with HC (GCIP layer: 81.4 ± 5.7 μm, p < 0.001). GCIP layer loss (-22.7 μm) after the first ON was higher than after the next (-3.5 μm) and subsequent episodes. pRNFL observations were similar. NMOSD-NON exhibited reduced GCIP layer but not pRNFL compared with HC. VA was greatly reduced in NMOSD-ON compared with HC eyes, but did not differ between NMOSD-NON and HC., Discussion: Our results emphasize that attack prevention is key to avoid severe neuroaxonal damage and vision loss caused by ON in NMOSD. Therapies ameliorating attack-related damage, especially during a first attack, are an unmet clinical need. Mild signs of neuroaxonal changes without apparent vision loss in ON-unaffected eyes might be solely due to contralateral ON attacks and do not suggest clinically relevant progression but need further investigation., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy characterized by aquaporin-4 antibodies, whose prognosis is influenced by onset age, race, environmental exposures and immunosuppression. Distinguishing the contribution of environment from genetics is challenging. We aimed to compare neuromyelitis optica spectrum disorder (NMOSD) patient outcomes according to self-identified racial group and place of residence., Methods: This retrospective analysis of prospectively collected data included non-white anti-aquaporin-4 antibody positive NMOSD patients under follow-up from 15 centers [United Kingdom, France, Germany, Denmark, Martinique, United States of America, Japan, South Korea, Singapore, Thailand, China (including Hong Kong) and India]. Racial groups were designated: African/Caribbean; South Asian; East Asian (including Southeast Asia). Patients from these racial groups residing outside Africa/Caribbean or Asia were compared with those living in the Caribbean or the Asian areas. Kaplan-Meier survival curves and Cox models were generated using time to sustained Expanded Disability Status Scale≥6.0 or death; time to sustained Kurtzke Visual Function Score≥3.0 or a composite endpoint of all three., Results: Among 821 patients, African/Caribbean patients (n = 206) had the shortest time to immunosuppression and higher visual disability at onset. South Asian patients (n = 65) were younger, had lower visual disability at onset and higher mortality rate. East Asians (n = 550) had the lowest relapse rate and lowest accrued motor disability. Survival analysis of African/Caribbean outside Africa/Caribbean vs those in the Caribbean showed a significant difference in the composite endpoint (p = 0.024,log-rank test), not apparently related to treatment differences. No significant differences between native and those residing outside Asia were found for other racial groups., Conclusion: This NMOSD study reports the effects of place of residence on the outcomes in different races. Place of residence may not be a significant driver of disability among Asian patients, while it may influence African/Caribbean patient outcomes. Validating these findings could help distinguish between genetic causes and potentially modifiable environmental factors., (Copyright © 2021. Published by Elsevier B.V.)

Objective: To conduct systematic review and meta-analysis for the efficacy of therapeutic plasma exchange (TPE) for neuromyelitis optica spectrum disorder (NMOSD) with an acute attack., Methods: Systematic review was performed using EMBASE and OVID/Medline database. The eligible studies must be the studies of NMOSD patients treated with TPE during the acute phase. They must report treatment outcomes using either Expanded Disability Status Scale (EDSS) or visual acuity (VA) before and after the therapy. Pooled mean difference (MD) was then calculated by combining MDs of each study using the random-effects model., Results: Fifteen studies were identified; eleven with 241 NMOSD patients reported EDSS outcome and four studies with 103 NMOSD reported visual outcomes. The meta-analysis demonstrated a significantly decreased in EDSS after TPE treatment for NMOSD with an acute attack with the pooled MD of 0.83 (95% CI, 0.26-1.40; I 2 69%) comparing pretreatment to immediate posttreatment and 2.13 (95% CI, 1.55-2.70; I 2 31%) comparing pretreatment to posttreatment at 6 months to 1-year follow-up. Unfortunately, only one of the four studies evaluating visual outcomes reported standard deviation in association with mean LogMAR; therefore, the meta-analysis cannot be conducted. Nonetheless, all studies consistently demonstrated the benefit of TPE with improved VA and/or LogMAR after treatment., Interpretation: This systematic review and meta-analysis showed the benefit of TPE during the NMOSD attack with a significantly improved disability status immediately after treatment and during follow-up., (© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Purpose: Optical coherence tomography (OCT) captures retinal damage in neuromyelitis optica spectrum disorders (NMOSD). Previous studies investigating OCT in NMOSD have been limited by the rareness and heterogeneity of the disease. The goal of this study was to establish an image repository platform, which will facilitate neuroimaging studies in NMOSD. Here we summarise the profile of the Collaborative OCT in NMOSD repository as the initial effort in establishing this platform. This repository should prove invaluable for studies using OCT to investigate NMOSD., Participants: The current cohort includes data from 539 patients with NMOSD and 114 healthy controls. These were collected at 22 participating centres from North and South America, Asia and Europe. The dataset consists of demographic details, diagnosis, antibody status, clinical disability, visual function, history of optic neuritis and other NMOSD defining attacks, and OCT source data from three different OCT devices., Findings to Date: The cohort informs similar demographic and clinical characteristics as those of previously published NMOSD cohorts. The image repository platform and centre network continue to be available for future prospective neuroimaging studies in NMOSD. For the conduct of the study, we have refined OCT image quality criteria and developed a cross-device intraretinal segmentation pipeline., Future Plans: We are pursuing several scientific projects based on the repository, such as analysing retinal layer thickness measurements, in this cohort in an attempt to identify differences between distinct disease phenotypes, demographics and ethnicities. The dataset will be available for further projects to interested, qualified parties, such as those using specialised image analysis or artificial intelligence applications., (© 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.)

Mycophenolate mofetil (MMF) is an immunosuppressive agent (IS) which is widely prescribed in neuromyelitis optica spectrum disorder (NMOSD) patients. We aim to assess the efficacy and safety of MMF in controlling relapse and disease severity. Eligible studies obtained from the EMBASE and Ovid MEDLINE databases were studies of NMOSD patients treated with MMF, which reported treatment outcomes as Annualized Relapse Rate (ARR) or Expanded Disability Status Scale (EDSS) before and after treatment. Fifteen studies included 1047 patients, of whom 915 (87.4%) were aquaporin-4 immunoglobulin seropositive. The total number of patients that received MMF was 799. A meta-analysis on ARR was conducted in 200 patients from 4 studies and on EDSS in 158 patients from 3 studies. The result showed a significant improvement with a mean reduction of 1.13 [95% confidence interval (CI) 0.60-1.65] in ARR, and a mean reduction of 0.85 (95% CI 0.36-1.34) in EDSS after MMF therapy. Adverse events occurred in 106 (17.8%) of 594 patients during MMF therapy. This systematic review and meta-analysis showed that using MMF as a preventive therapy in NMOSD patients can significantly reduce relapse rates and improve disease severity with acceptable tolerability.

Painful tonic spasm (PTS) is a common yet debilitating symptom in patients with neuromyelitis optica spectrum disorder (NMOSD), especially those with longitudinally extensive transverse myelitis. Although carbamazepine is an effective treatment, it poses the risk of severe adverse reactions, such as Steven-Johnson syndrome (SJS). In this case report, we describe an NMOSD patient with severe PTS suffering from carbamazepine-induced SJS who responded well to cannabis extract. Since cannabinoids can ameliorate spasticity in an experimental autoimmune encephalomyelitis model through cannabinoid 1 (CB1) receptor activation, cannabis extract which includes delta-9-tetrahydrocannabinol (THC) is a potential treatment option for PTS in NMOSD patients., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Intravenous methylprednisolone (IVMP) is an initially recommended therapy for an acute attack of neuromyelitis optica spectrum disorder (NMOSD). For those who do not respond to steroid treatment, plasma exchange (PLEX) is generally added-on. We evaluated adverse events of an acute treatment in NMOSD patients in a university-based hospital during January 2009 and December 2017. Ninety-seven patients with 177 attacks were collected. The therapy included IVMP alone (123 events, 62.4%), IVMP followed by PLEX (46 events, 23.4%) and, PLEX alone (8 events, 4.5%). Adverse events occurred in 36.7% of the IVMP group and 61.1% of the PLEX group. The most common adverse event was hyperglycemia (43.5%) followed by infection (29%) in the former and hypocalcemia (63.6%) followed by hypofibrinogen (42.4%), hypotension (30.3%), and infection (21.2%) in the latter. One severe adverse event was documented in the IVMP group and 13 events in the PLEX groups, nevertheless, all were manageable., (© 2019 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Background: The 2015 International Panel for Neuromyelitis Optica (NMO) Diagnosis (IPND) criteria was revised using systematic literature reviews and consensus from the experts. It facilitates NMOSD diagnosis and is applicable in an Asian population., Objective: To compare the utility of the 2015 IPND criteria and the 2006 NMO diagnostic criteria for the diagnosis of NMO/SD., Methods: We retrospectively reviewed the electronic medical records 5 of patients with NMOSD who attended Multiple Sclerosis and Related Disorders Clinic between January 2010 and December 2016. Two independent investigators applied the 2006 revised diagnostic criteria for NMO in patients who fulfilled the 2015 IPND criteria., Results: Of all 70 cases who had an NMOSD diagnosis according to 2015 criteria, 56 cases (80.0%) were positive for aquaporin-4 immunoglobulin (AQP4-IgG). Nineteen patients (27.1%) fulfilled the 2006 NMO diagnostic criteria. The 2015 IPND criteria identified 51 more NMOSD cases, increasing the diagnostic yield by 268%, compared to the 2006 criteria. The median time from onset to diagnosis by using the 2015 IPND criteria was shorter than those identified by the 2006 criteria (128 vs. 547 days, p=0.002). The 2015 IPND also provides for lesser attacks occurring before achieving diagnosis (1.7 vs. 2.7, p<0.001). In the absence of known AQP4-IgG serostatus, the 2015 criteria still indicated NMOSD patients by a 124% increase in detection rate (p<0.001); however, time to diagnosis was not statistically significant between the two criteria (258 vs. 604 days, p=0.081)., Conclusions: Compared to the 2006 criteria, the 2015 IPND criteria increased diagnostic yield for NMOSD regardless of AQP4-IgG status and shortened the time from onset to diagnosis in patients with NMOSD with known AQP4-IgG serostatus., Competing Interests: Competing Declaration of Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Our previous retrospective study demonstrated that NMOSD patients with an acute attack who did not respond to IVMP alone, however, showed further significant improvement after treatment with PLEX at 6 month-follow-up., Objective: To compare the efficacy between treatments with intravenous methylprednisolone (IVMP) with subsequent add-on plasma exchange (PLEX) and a combination of simultaneous IVMP and PLEX in neuromyelitis optica spectrum disorders (NMOSD) patients with a severe acute attack., Method: We conducted a prospective, randomized, controlled, pilot study of the treatments for a severe acute attack in NMOSD patients., Results: There were eleven AQP4-positive NMOSD patients in the study. One received only IVMP, five received IVMP with subsequent add-on PLEX treatment, and the other five received simultaneous IVMP and PLEX treatment. The attacks comprised myelitis (57.1%) and optic neuritis (42.9%). Both treatments with IVMP followed by subsequent add-on PLEX when needed (not-respond to IVMP treatment) and a combination treatment of simultaneous IVMP+PLEX from the outset showed clinical improvement measured by EDSS at 6 months follow-up, compared to those at the attacks (p-value = 0.07 in IVMP add-on PLEX group and p-value = 0.05 in IVMP+PLEX group), respectively. Although, a trend of a better outcome stratified by EDSS toward early PLEX initiation with IVMP+PLEX treatment was observed at 6 months follow-up, however not significantly., Conclusion: Early treatment with PLEX should be encouraged especially in NMOSD with a severe acute attack., Competing Interests: Declaration of Competing Interest Dr. Songthammawat has nothing to disclose. Dr. Srisupa - Olan has nothing to disclose. Dr. Siritho has received funding for travel and speaker honoraria from Merck Serono, Pacific Healthcare (Thailand), Menarini (Thailand), Biogen Idec, UCB (Thailand), Eisai Inc, Sanofi-Aventis and Novartis. Dr. Kittisares has nothing to disclose. Dr. Jitprapaikulsan has received funding for travel and speaker honoraria from Novartis, Thailand, Bayer Schering Pharma, Easai Inc, Merck Serono, Thailand, Pfizer Pharamaceutical company, Sanofi-Aventis, outside the submitted work; Dr. Satukijchai: has received funding for travel and received speaker honoraria from Merck Serono, Eisai Inc, Sanofi-Aventis and Novartis. Dr. Prayoonwiwat has received funding for travel and received speaker honoraria from Bayer Schering Pharma, Eisai Inc, UCB, Thailand, Merck Serono, Pfizer Pharmaceutical Company Limited, Novartis, Sanofi-Aventis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In conjunction with the third regional Southeast Asian (SEA) therapeutic plasma exchange (TPE) conference in Kuala Lumpur, Malaysia, 25 clinicians and researchers from SEA and South Asian countries attended the inaugural strategy meeting for the establishment of a regional TPE consortium for neurological disorders. The primary objective was to establish regional collaboration to improve delivery of TPE services in SEA. A pre-meeting survey was conducted to gather insights on disease spectrum, contextual practice challenges, and the need for a regional TPE consensus. Challenges identified include limited healthcare funding in support of diagnostic workup, TPE therapy, as well as development of clinical infrastructure and expertise capacity building. There was favorable interest in developing a working plan contextualized to this region. Strategies to overcome challenges were discussed. This included the need for a comprehensive referral system and network of regional TPE centers suited to local needs, supported by innovative TPE delivery programs., (© 2019 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Objective: We aimed to evaluate racial differences in the clinical features of neuromyelitis optica spectrum disorder., Methods: This retrospective review included 603 patients (304 Asian, 207 Caucasian, and 92 Afro-American/Afro-European), who were seropositive for anti-aquaporin-4 antibody, from 6 centers in Denmark, Germany, South Korea, United Kingdom, United States, and Thailand., Results: Median disease duration at last follow-up was 8 years (range 0.3-38.4 years). Asian and Afro-American/Afro-European patients had a younger onset age than Caucasian patients (mean 36, 33, and 44 years, respectively; p < 0.001). During the disease course, Caucasian patients (23%) had a lower incidence of brain/brainstem involvement than Asian (42%) and Afro-American/Afro-European patients (38%) ( p < 0.001). Severe attacks (visual acuity ≤0.1 in at least one eye or Expanded Disability Status Scale score ≥6.0 at nadir) at onset occurred more frequently in Afro-American/Afro-European (58%) than in Asian (46%) and Caucasian (38%) patients ( p = 0.005). In the multivariable analysis, older age at onset, higher number of attacks before and after immunosuppressive treatment, but not race, were independent predictors of severe motor disabilities at last follow-up., Conclusion: A review of a large international cohort revealed that race affected the clinical phenotype, age at onset, and severity of attacks, but the overall outcome was most dependent on early and effective immunosuppressive treatment., (© 2018 American Academy of Neurology.)

Aim: To compare the thickness of the peripapillary retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) among patients with various forms of optic neuritis (ON) and to identify whether any particular parameters or their thinning pattern can be used to distinguish the type of ON., Methods: This prospective study was conducted at the Department of Ophthalmology, Faculty of Medicine, Siriraj Hospital, Thailand, between January, 2015 and December, 2016. We enlisted patients over 18 years of age with history of ON and categorized patients into 4 groups: 1) aquaporin 4 antibodies (AQP4-IgG) positive; 2) multiple sclerosis (MS); 3) myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) positive; 4) idiopathic-ON patients. Healthy controls were also included during the same study period. All patients underwent complete ophthalmological examination and spectral domain optical coherence tomography (OCT) imaging to analyze RNFL and GCIPL thickness after at least 3mo since the last episode of acute ON. The generalized estimating equation (GEE) models were used to compare the data amongst ON groups., Results: Among 87 previous ON eyes from 57 patients (43 AQP4-IgG+ON, 17 MS-ON, 8 MOG-IgG+ON, and 19 idiopathic-ON), mean logMAR visual acuity of AQP4-IgG+ON, MS-ON, MOG-IgG+ON, and idiopathic-ON groups was 0.76±0.88, 0.12±0.25, 0.39±0.31, and 0.75±1.08, respectively. Average, superior, and inferior RNFL were significantly reduced in AQP4-IgG+ON, MOG-IgG+ON and idiopathic-ON eyes, relative to those of MS-ON. Differences were not statistically significant for RNFL or GCIPL between the AQP4-IgG+ON and MOG-IgG+ON groups, whereas visual acuity in MOG-IgG+ON was slightly, but not significantly, better (0.39 vs 0.76). Although RNFL thickness in MOG-IgG+ON was significantly reduced as compared to MS-ON, mean visual acuity and GCIPL were not different., Conclusion: Thinning of superior and inferior quadrants of RNFL are more commonly seen in MOG-IgG+ON and AQP4-IgG+ON. Long term visual acuity in MOG-IgG+ON is often better than AQP4-IgG+ON, whereas the structural change from OCT is comparable.

Purpose: To investigate the correlation between visual function and thinning of the retinal nerve fiber layer (RNFL) and the macular ganglion cell-inner plexiform layer (GCIPL) as measured by optical coherence tomography (OCT) in eyes with aquaporin-4 IgG-positive optic neuritis (AQP4-IgG-positive ON)., Study Design: Prospective study., Methods: Patients with a history of ON were categorized into 2 groups: the AQP4-IgG-positive group and the AQP4-IgG-negative group. Patients with multiple sclerosis were excluded. All patients underwent ophthalmologic examination and OCT imaging at least 6 months after the last episode of acute ON. Visual function and inner retinal structure correlations were analyzed using Pearson correlation and regression analyses., Results: Thirty-one previous ON eyes of 17 AQP4-IgG-positive patients and 21 previous ON eyes of 15 AQP4-IgG-negative patients were registered. Visual function, especially the visual field, was better correlated with RNFL than with macular GCIPL. The best correlation between visual function and RNFL was the linear model, whereas the best correlation between visual function and GCIPL was the nonlinear model (inverse regression). Regression models revealed worse visual function in AQP4-IgG-positive ON than in AQP4-IgG-negative ON, whereas no differences in RNFL and GCIPL were found between the 2 groups., Conclusions: RNFL measured by OCT can be a useful retinal structure for estimating and monitoring visual field loss in AQP4-IgG-positive ON patients, particularly in patients whose visual field cannot be quantitated. The correlation between visual function and the inner retinal structure of eyes with AQP4-IgG is unique and differs from that of eyes without AQP4-IgG.