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Background Few epidemiological studies have explored the effects of soil pollution on multiple sclerosis ( MS) risk in Asia. Method Based on catchment areas, Isfahan province is divided into five regions (Central, North, East, West, and South), and Soil sampling performed in catchment area with the highest range of MS prevalence and incidence. Samples were analyzed for cobalt (Co), lead (Pb), cadmium (Cd), copper (Cu), zinc (Zn), and absorbable forms of Pb, Cd, and Co. Linear regression is used to examine the association of soil heavy metals with prevalence of MS in central part of Isfahan province. Result Multiple sclerosis prevalence ranged from 5.62 to 156.65 in different townships. Based on regression analysis, in case of considering fixed amounts for the rest of elements, a one ( SD) increase of absorbable Pb and absorbable Cd are associated with 0.385 ( SD) ( P < 0.0001) increase and 0.209 ( SD) ( P < 0.007) decrease in MS prevalence, respectively. Conclusion This study documented a significant association between exposure to absorbable Pb and Cd in soil with prevalence of MS in Isfahan. Further work is warranted to confirm this association and if validated, to understand the mechanisms behind the association. [ABSTRACT FROM AUTHOR]

Background and Objectives Multiple sclerosis (MS) is an autoimmune neurodegenerative disease in which the body's natural defense system attacks myelin on neuronal cells. One of the most important immune system cells involved in MS is Th17 which is one of the main cells involved in most of autoimmune diseases. Recently, microRNAs (miRNAs) have been remarkably used in treating many kinds of diseases. MicroRNAs are endogenous 22-25 nt RNAs playing an important regulatory roles in cellular and developmental processes. Materials and Methods The goal of this article is to determine miRNAs which possibly have the most effect in the pathway of differentiation to Th17 cells by using miRWalk database and candidate microRNAs that can suppress this pathway and limit the disease's symptoms. Our in-silico studies identified the possible role of several miRNAs in differentiation of naïve CD4+ cells to Th17 cells. Results miR-93,miR-20a/b are probably applicable to inhibit the differentiation of naïve T cells into Th17 cells to reduce the progress of MS and also to be used as markers of diagnosis of MS in early stages. Conclusions According to our results miR-20a/b&miR-93 can possibly be the key miRNAs, inhibiting the progression of MS by preventing the differentiation to Th17 cells. [ABSTRACT FROM AUTHOR]

Cytokines are implicated in the immunopathogenesis of multiple sclerosis (MS). Interleukin (IL)-33, one of the recently discovered members of the IL-1 superfamily, is a dual functional cytokine involved in various autoimmune disorders. In a case-control study, venous blood was collected from healthy subjects categorized as control group (n=44) and MS patients (n=44). All recruited patients were clinically diagnosed with relapsing-remitting MS (RRMS), including patients without treatment (new identified cases, n=16) and those treated with interferon beta (IFN-β) (n=28). The plasma levels of IL-33 in subjects were measured with ELISA. Significantly elevated IL-33 plasma levels were observed in RRMS patients (p=0.005). Furthermore, IFN-β-treated MS patients had lower levels of IL-33 compared to the untreated patients (p

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) syndrome is a rare central nervous system inflammatory disorder with an unknown pathophysiology. We present the case of a 51-year-old female exhibiting clinical and radiological features consistent with CLIPPERS syndrome. She manifested diplopia, vertigo, gait ataxia, and lower limb asthenia, accompanied by impaired tandem gait, right sixth nerve palsy, and coarse horizontal nystagmus during the physical examination. Magnetic resonance imaging (MRI) revealed punctate and curvilinear lesions centered in the pons. Treatment with glucocorticoids resulted in significant clinical improvement, and the patient was discharged with a maintenance dose of prednisolone. Throughout a four-year follow-up period, the patient remained symptom-free without any relapses using the low-dose corticosteroid. The CLIPPERS syndrome diagnosis remains challenging, but recent evidence supports an autoimmune pathogenesis. Although corticosteroid treatment has shown significant clinical improvement, there are no established guidelines or clinical trials on the optimal therapeutic regimen. Despite its rarity, clinicians should consider CLIPPERS syndrome in patients with compatible clinical and radiological features to prevent irreversible neurological damage., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Background: Pediatric-onset multiple sclerosis (POMS) cases, defined as multiple sclerosis (MS) with onset before the age of 18, represent between 3 and 5 % of all MS patients. Anti-CD20 drugs mainly rituximab, ocrelizumab, and ofatumumab are being widely used in adult-onset MS. Their use in POMS is also being increasingly considered by experts., Objective: to review the latest evidence on safety and efficacy of the use of anti-CD20 therapies in POMS., Methods: An extensive search was performed in PubMed, Scopus, and Web of Science databases until the end of July 1st, 2024. Two independent reviewers screened the articles, and collected data. 832 studies were screened using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines., Results: 12 studies on rituximab (328 patients) and 6 studies on ocrelizumab (106 patients) were synthesized. Using monoclonal antibodies in POMS patients has a noteworthy effect on reducing relapses and lesions and achieving no evidence of disease activity especially in highly active POMS patients. However, anti-CD20 therapies in MS are associated with potential adverse events (AEs). Additional data is required on the effect of anti-CD20 therapy on disability accrual., Conclusion: Although anti-CD20 therapy is associated with some AEs, it can be provided in several circumstances, especially to patients with highly active disease, or ones resistant to platform therapies., Competing Interests: Declaration of competing interest The author declares no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Primary Hemifacial Spasm (pHFS) is a disorder caused by compression of vessels on the root of the facial nerve. There has been conflicting evidence regarding the side of the face that is more frequently affected. Moreover, it has been found in several studies that women are afflicted by approximately twice as many as men., Objectives: We reviewed the literature to explain HFS tendencies from an anatomical aspect. We wanted to see whether there are anatomical variations that can increase the risk of developing HFS or underlie its tendency to a specific gender and side of the face., Methods and Material: A PubMed search was done for the articles on "Hemifacial Spasm" published in English literature, and we selected the articles regarding the significant anatomical differences in HFS patients., Results: AICA proximal branching pattern, highly originated PICA, VA dominancy, and VA deviation are among the predisposing anatomical variances. Overall, both sides of the face are equally affected in HFS. However, there are side preferences based on the causative vessels, which may be due to differences in the anatomical features of the left and right side vessels., Conclusions: Various anatomical variations regarding posterior circulation can increase the risk of HFS. Recent evidence suggests whether there is no side dominance or a tendency exists toward the left side. There is no comprehensive explanation for precise reasons underlying the tendency of HFS to affect women. Evidence regarding anatomical variations of the posterior circulation comparing men and women with HFS is scarce, and further studies are required., (© 2024. The Author(s) under exclusive licence to Belgian Neurological Society.)

Introduction: Neuromyelitis Optica Spectrum Disorders (NMOSD) is a neuroinflammatory condition characterized by optic neuritis and transverse myelitis. While the current approach to NMOSD focuses on relapse-associated worsening (RAW), recent evidence indicates Relapse-Independent Disease Activity (RIDA) in patients., Method: Databases including Embase, PubMed, Scopus, and Web of Sciences were systematically searched up to December 2023. No restrictions were applied. Inclusion criteria focused on studies reporting evidence of RIDA in NMOSD patients. Data extraction involved details such as study title, author, participant characteristics, treatment, evaluation methods, positive findings according to RIDA, and prevalence of findings in NMOSD patients. This study is conducted following the PRISMA guidelines with a registered protocol on PROSPERO (ID = CRD42023492352)., Result: Of 802 studies, 38 were included in the systematic review, covering 1881 NMOSD patients. AQP4-IGg status was positive in 90.6 % of the patients. Ocular findings indicative of RIDA were reported in 23 studies, including thinning of GCIPL, RNFL, GCC, and GCL layers, foveal and macular shape and volume abnormalities, vessel loss, and visual evoked potentials (VEPs) abnormalities. MRI findings supporting the RIDA were reported in 13 studies, including new lesion incidence and brain and spinal cord atrophy. Serum and CSF RIDA-supporting findings were reported in five studies, including elevation in sGFAP and sNFL. Biopsies and autopsies suggested inflammatory processes in relapse-free patients in 2 studies. The predominant manifestation of RIDA in NMOSD was identified in the visual system, suggesting the impaired retinal glial cells like Müller cells during the relapse-free period in NMOSD., Interpretation: Our systematic review provides valuable insights into RIDA in NMOSD. Establishing guidelines for the diagnosis and treatment of RIDA is crucial. Further studies are needed to provide robust evidence on RIDA in NMOSD patients., 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 © 2024 Elsevier B.V. All rights reserved.)

Background: Since data is limited on radiologically isolated syndrome (RIS) subjects in certain regions like the Middle East, we aimed to further explore the replicability and generalizability of previously suggested predictors among a cohort of Iranian RIS subjects and report the long-term clinically definite MS (CDMS) conversion rate in this cohort., Methods: We conducted a prospective 10-year cohort on our RIS participants, during which we collected the MRI, paraclinical, and demographic data of the subjects, and identified those who converted to CDMS., Results: Out of 35 participants, 10 (28.5 %) developed CDMS during an average of 5.58 ± 3.08 years (range: 4 months to 10.33 years). OCB positivity was the only definitive predictor for conversion to CDMS in this cohort (P-value = 0.006), but other previously reported risk factors such as spinal cord lesions or age lacked statistical significance (P-values > 0.05). We also reported the median survival time as 114 months, the proportion surviving after 14 months as 96.9 % ± 3.1 %, and the overall conversion rate as 0.05 cases per year., Conclusion: Our results highlight OCB as an important predictive factor of clinical conversion in RIS. The prominence of OCB suggests a need for routine CSF analysis in RIS subjects and could guide clinicians in deciding which RIS subjects benefit from DMTs., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Neuromyelitis optica spectrum disorder (NMOSD) can be categorised into aquaporin-4 antibody (AQP4-IgG) NMOSD or seronegative NMOSD. While our knowledge of AQP4-IgG NMOSD has evolved significantly in the past decade, seronegative NMOSD remains less understood. This study aimed to evaluate the predictors of relapses and treatment responses in AQP4-IgG NMOSD and seronegative NMOSD., Methods: This was a multicentre, international, retrospective cohort study using the MSBase registry. Recurrent relapse risk was assessed using an Andersen-Gill model and risk of first relapse was evaluated using a Cox proportional hazards model. Covariates that putatively influence relapse risk included demographic factors, clinical characteristics and immunosuppressive therapies; the latter was assessed as a time-varying covariate., Results: A total of 398 patients (246 AQP4-IgG NMOSD and 152 seronegative NMOSD) were included. The AQP4-IgG NMOSD and seronegative NMOSD patients did not significantly differ by age at disease onset, ethnicity or annualised relapse rate. Both low-efficacy and high-efficacy immunosuppressive therapies were associated with significant reductions in recurrent relapse risk, with notably greater protection conferred by high-efficacy therapies in both AQP4-IgG NMOSD (HR 0.27, 95% CI 0.15 to 0.49, p<0.001) and seronegative NMOSD (HR 0.21, 95% CI 0.08 to 0.51, p<0.001). Longer disease duration (HR 0.97, 95% CI 0.95 to 0.99, p<0.001) and male sex (HR 0.52, 95% CI 0.34 to 0.84, p=0.007) were additional protective variables in reducing the recurrent relapse risk for the AQP4-IgG NMOSD group., Conclusion: Although further studies are needed to improve our understanding of seronegative NMOSD, our findings underscore the importance of aggressive treatment with high-efficacy immunotherapies in both NMOSD subtypes, regardless of serostatus., Competing Interests: Competing interests: The author(s) would like to disclose the following. PSiriratnam has received travel support from Novartis and Biogen; AvdW has received travel support and served on advisory boards for Novartis, Biogen, Merck Serono, Roche and Teva, she receives grant support from the National Health and Medical Research Council of Australia; HB served on scientific advisory boards for Biogen, Novartis and Sanofi-Aventis and received conference travel support from Novartis, Biogen and Sanofi Aventis, he serves on steering committees for trials conducted by Biogen and Novartis and received research support from Merck, Novartis and Biogen, Medical Research Council and MS Research Australia; YCF has received travel support from Roche and Biogen, he receives grant support from Australian National Health Medical Research Council, Australia and New Zealand Association of Neurologists, AVANT foundation and MS Research Australia; WZY has received speaker honoraria from Merck and Novartis; CZ receives fellowship from the Trish Multiple Sclerosis Research Foundation; VJ receives fellowship and research support from the National Health and Medical Research Council of Australia, she also receives research grant support form F.Hoffmann La-Roche and the International Progressive MS Alliance; SH receives research support from academic entity - National Institute for Health Research (NIHR304529): Research funding; MM has served on advisory board for Merck, and Novartis and has received speaker honoraria from Merck, Biogen and Novartis, her institution receives funding from Merck, Australian National Health; TK served on scientific advisory boards for MS International Federation and WHO, BMS, Roche, Janssen, Sanofi Genzyme, Novartis, Merck and Biogen, steering committee for Brain Atrophy Initiative by Sanofi Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Eisai, Novartis, Biogen, Roche, Sanofi-Genzyme, Teva, BioCSL and Merck and received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene and Merck; SJK received compensation for scientific advisory board activity from Merck and Roche, and received compensation for serving on the IDMC for Biogen; TC received speaker honoraria/conference travel support from Biogen, Merck, Novartis, Roche, Sanofi-Aventis and Teva; BW received honoraria for acting as a member of Scientific Advisory Boards/Consultancy for Alexion, Almirall, Biogen, Celgene/BMS, Merck, Janssen, Novartis, Roche, Sandoz, Sanofi-Genzyme and speaker honoraria and travel support from Biogen, Celgene/BMS, Merck, Novartis, Roche, Sanofi-Genzyme, research and/or patient support grants from Biogen, Janssen, Merck, Sanofi-Genzyme, Roche, Honoraria and grants were paid to UZA/UZA Foundation, further, B.W. received research funding from FWO-TBM, Belgian Charcot Foundation, Start2Cure Foundation, Queen Elisabeth Medical Foundation for Neurosciences and the National MS Society USA; PN received speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck, Roche, Jannsen, Astra Zeneca and financial support for research activities from Roche and Merck, the work of PN was supported by Ministry of Health of the Czech Republic, grant nr. NU23-05-00462; AA received speaker honoraria from Novartis and Alexion; AA-A received personal compensation for serving as a Scientific Advisory or speaker/moderator for Novartis, Biogen, Roche, Sanofi-Genzyme, and Merck; BY received honoraria as a speaker and member of scientific advisory boards from Sanofi, Bayer, Biogen, Merck, Janssen, Novartis, Roche and Aspen; GL received travel and/or consultancy compensation from Sanofi-Genzyme, Roche, Teva, Merck, Novartis, Celgene, Biogen; FP received personal compensation for serving on advisory board by Almirall, Alexion, Biogen, Bristol, Janssen, Merck, Novartis and Roche, he further received research grant by Alexion, Almirall, Biogen, Bristol, Merck, Novartis and Roche and by FISM, Reload Association (Onlus), Italian Health Minister and University of Catania. Magdolna Simo received speaker honoraria from Novartis, Biogen, Bayer Schering, Sanofi, Merck, Roche, congress/travel compensation from Teva, Biogen, Merck, Bayer Schering Novartis, Roche; MF received travel and meeting attendance support from Novartis, Biogen, Roche, Sanofi-Genzyme and Merck; ASoysal received travel and meeting attendance support from Novartis, Biogen, Roche, Merck, Bristol, Sanofi-Genzyme, Almirall, Piam; PAM received honoraria and consulting fees from Novartis, Bayer Schering and Sanofi and travel grants from Novartis, Biogen and Bayer Schering; RA received honoraria as a speaker and for serving on scientific advisory boards from Bayer, Biogen, GSK, Merck, Novartis, Roche and Sanofi-Genzyme; JLS-M, accepted travel compensation from Novartis, Merck and Biogen, speaking honoraria from Biogen, Novartis, Sanofi, Merck, Almirall, Bayer and Teva and has participated in clinical trials by Biogen, Merck and Roche; JLS received travel compensation from Novartis, Biogen, Roche and Merck, her institution receives the honoraria for talks and advisory board commitment as well as research grants from Biogen, Merck, Roche, TEVA and Novartis., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The COVID-19 pandemic raised concern amongst clinicians that disease-modifying therapies (DMT), particularly anti-CD20 monoclonal antibodies (mAb) and fingolimod, could worsen COVID-19 in people with multiple sclerosis (pwMS). This study aimed to examine DMT prescribing trends pre- and post-pandemic onset., Methods: A multi-centre longitudinal study with 8,771 participants from MSBase was conducted. Two time periods were defined: pre-pandemic (March 11 2018-March 10 2020) and post-pandemic onset (March 11 2020-11 March 2022). The association between time and prescribing trends was analysed using multivariable mixed-effects logistic regression. DMT initiation refers to first initiation of any DMT, whilst DMT switches indicate changing regimen within 6 months of last use., Results: Post-pandemic onset, there was a significant increase in DMT initiation/switching to natalizumab and cladribine [(Natalizumab-initiation: OR 1.72, 95% CI 1.39-2.13; switching: OR 1.66, 95% CI 1.40-1.98), (Cladribine-initiation: OR 1.43, 95% CI 1.09-1.87; switching: OR 1.67, 95% CI 1.41-1.98)]. Anti-CD20mAb initiation/switching decreased in the year of the pandemic, but recovered in the second year, such that overall odds increased slightly post-pandemic (initiation: OR 1.26, 95% CI 1.06-1.49; Switching: OR 1.15, 95% CI 1.02-1.29. Initiation/switching of fingolimod, interferon-beta, and alemtuzumab significantly decreased [(Fingolimod-initiation: OR 0.55, 95% CI 0.41-0.73; switching: OR 0.49, 95% CI 0.41-0.58), (Interferon-gamma-initiation: OR 0.48, 95% CI 0.41-0.57; switching: OR 0.78, 95% CI 0.62-0.99), (Alemtuzumab-initiation: OR 0.27, 95% CI 0.15-0.48; switching: OR 0.27, 95% CI 0.17-0.44)]., Conclusions: Post-pandemic onset, clinicians preferentially prescribed natalizumab and cladribine over anti-CD20 mAbs and fingolimod, likely to preserve efficacy but reduce perceived immunosuppressive risks. This could have implications for disease progression in pwMS. Our findings highlight the significance of equitable DMT access globally, and the importance of evidence-based decision-making in global health challenges., (© 2024. The Author(s).)

Background: Recent literature describes a condition similar to multiple sclerosis (MS) but with demyelinating lesions limited to the spinal cord. This condition, referred to as "pure spinal" MS, might benefit from disease-modifying treatment (DMT)., Methods: We screened the medical records of approximately 8000 patients with demyelinating diseases at the Isfahan MS clinic in Iran. Criteria for inclusion in the case series were adults with a demyelinating disease limited to the spinal cord, positive oligoclonal IgG bands in cerebrospinal fluid (CSF), and negative results for other potential diagnoses., Results: Seven people with pure spinal MS were identified (all women, mean age [SD]: 40.14 [6.17] years at the first visit, mean follow-up duration [SD]: 98 [39.41] months). Two had a family history of conventional MS in their siblings. All patients exhibited lower limb weakness and tested negative for anti-MOG and anti-AQP4 antibodies. They experienced relapsing-remitting partial myelitis, with new spinal cord lesions on MRI but no extraspinal CNS lesions. DMT significantly reduced relapse rates in all patients, and two showed no increase in EDSS scores., Conclusion: Pure spinal MS might be an atypical form of MS. Those affected may benefit from DMT; therefore, further investigation and consideration in the upcoming revisions of the McDonald criteria are recommended., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Characteristics of livers and spleens of people with multiple sclerosis (pwMS) could constitute good biomarkers of MS-related characteristics such as the disability status. To test the hypothesis "the gross anatomical features of livers and spleens, are not similar between pwMS with different disease characteristics" a cross-sectional study was conducted on pwMS seen at the Isfahan MS clinic, Iran, from February until December 2023. Definitive, otherwise-healthy, pwMS were enrolled after an initial laboratory evaluation. Presence/absence and grading of non-alcoholic fatty liver disease (NAFLD) and the span of spleen were determined by a radiologist using high-resolution abdominopelvic ultrasonography. 193 pwMS (160 women) were enrolled. Of whom, 143 (74.1%) were receiving first-line disease-modifying therapies (DMTs), 24 (12.4%) fingolimod, and 26 (13.5%) rituximab. The span of spleen was negatively associated with EDSS (adjusted β [SE] - 4.08 [1.52], p < 0.01), as well as 6 m-CDW (adjusted β [SE] - 6.94 [3.56], p = 0.05), unlike age, DMTs, and MS duration (all with p > 0.05). Receiver operating characteristic analysis showed, spleen span performs significant but poor in discrimination of EDSS > 1 from EDSS = 1 (area under curve [AUC] 0.62, SE 0.05, p < 0.01), yet, significant and fair in discrimination of presence from absence of 6 m-CDW (AUC 0.72, SE 0.06, p < 0.01). Other findings were unremarkable. Further longitudinal, prospective studies are warranted to confirm whether smaller spleens are predictive of higher disability accrual rate in pwMS. Particularly, findings require further validation in untreated/treatment-naïve pwMS, and ones with higher EDSS scores., (© 2024. The Author(s).)