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Mohammad-Ali Abtahi1–3, Seyed-Hossein Abtahi1,3,4, Farhad Fazel2,3, Peyman Roomizadeh1,4, Masoud Etemadifar5, Keivan Jenab2,3, Mojtaba Akbari11Medical School, Isfahan University of Medical Sciences, 2Ophthalmology Ward, Feiz Hospital, Isfahan University of Medical Sciences, 3Isfahan Eye Research Center (IERC), Feiz Hospital, Isfahan University of Medical Sciences, 4Isfahan Medical Students Research Center (IMSRC), Isfahan University of Medical Sciences, 5Department of Neurology, Medical School, Isfahan University of Medical Sciences, Isfahan, IranBackground and purpose: Topiramate (TPM) is a sulfa-derivative monosaccharide that is used mainly for treating epilepsy and preventing migraine. Within the gamut of side effects attributable to this drug, ophthalmologic manifestations are of crucial importance. In this study, for the first time, the aim was to provide a systematic literature review regarding this issue.Methods: For the time period 1996–2011, a PubMed search was made for the studies concerning the adverse/beneficial effects of TPM on vision. Overall, 404 citations out of a total of 2756 TPM-related studies were examined for relevance.Results: A total of 74 relevant studies were reviewed, 65 of which comprise small observational studies describing the ophthalmic side effects of TPM in 84 patients. Of these patients, 66 were affected by ciliochoroidal effusion syndrome as the cardinal ocular side effect of TPM (17 cases of myopic shift and 49 cases of angle closure glaucoma). A comprehensive statistical analysis is provided on these 66 subjects. Other rare side effects of TPM on the vision were also reviewed, including massive choroidal effusion, ocular inflammatory reactions, visual field defects, probable effects on retina, cornea, and sclera, and neuroophthalmologic complications. In addition, a framework is provided to classify these results.Discussion: Due to the expanding spectrum of indications for the administration of TPM, neurologists and psychiatrists should be aware of its diverse ocular side effects. In conclusion, ocular complications following this drug should be taken seriously and be subjected to ophthalmic counseling.Keywords: topiramate, eye, vision, ophthalmology, side effect, review

Background: Investigations have shown that some factors like stress can increase the recurrence and severity of multiple sclerosis (MS). Considering the direct influences of depression and anxiety on our body immunity system, and also the relation between stress and factors, such as Insulin Growth Factor (IGF-1), involved in neurogenesis and myelin repairing, it is an essential issue to identify the most common method used in relieving stress by such patients. Objective: To identify the type of common coping methods for stressful situation. Materials and Methods: This case-control study was performed on 50 patients of both the genders with MS in Esfahan (Esfahan MS Association). The data were collected and then analyzed using analysis of variance (ANOVA) method with the help of SPSS software version 15. P value less than 0.05 was considered as statistically significant. Results: In our study, coping method for stressful situation was significantly different in MS patients versus the healthy group (P=0.02). Descriptive indices showed that these patients use avoidant method more commonly than the control group (mean=45.01, SD=8.9 vs. mean=40.8, SD=11.8, respectively). Conclusion: Due to the different methods used by MS patients to cope with stressful situation in comparison with the healthy ones, more appropriate techniques can be introduced to modify them, and hence, less stress-induced side effects could be expected in this population.

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]

Introduction: This study aimed at investigating these models through evaluation of one psychological variable correlation (pain self efficacy) with pain intensity in M.S. Method: In this study, 249 patients were selected through convenient sampling. They were selected among those who referred to M.S assembly of Isfahan. The data were analyzed through Pearson product moment correlation, regression analysis, and MANOVA. Results: There is a significant negative correlation between pain self-efficacy and perceived intensity in M.S patients. The results of MANOVA also indicate that the highest correlation was reported to be between the highest rate of pain and the lowest rate of pain self-efficacy among the patients. Conclusion: This study provided empirical evidence supporting bio-psycho-social model and shows that psychological factors influence the perception and experience of pain intensity. [ABSTRACT FROM AUTHOR]

Introduction Co-occurrence of multiple sclerosis (MS) and neurofibromatosis type 1 (NF1) is rare. Case reports In this study, we describe the clinical and neuroimaging features of seven patients with NF1 and MS. In our patients, six patients with MS were women, in all of them history of NF1 existed. Three of our patients had primary progressive, one had secondary progressive MS, and three relapsing-remitting MS. Optic neuritis as presenting symptoms was seen in three patients, and motor manifestation as presenting symptom was observed in three patients. The risk of having both NF1 and MS seemed to be higher than would be expected based on the prevalence rates of the two diseases in the general population. Conclusion The findings of this study suggest a possible casual relationship between MS and NF1, indicating higher risk of MS among patients with NF1. [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

There is an overall increase in the worldwide prevalence and incidence of multiple sclerosis (MS). Studies from several countries also demonstrated an increase of female/male ratio over time denoting an increase in the incidence of MS particularly in women. In this study we sought to assess the trends in MS incidence and prevalence in males and females over recent decades in Isfahan, Iran, which differs from other regions in terms of environmental and lifestyle changes. We determined female/male ratio by year of birth (YOB) in 1584 patients with MS registered with Isfahan Multiple Sclerosis Society (IMSS) from April 2003 to August 2007. A comparison of sex ratio of MS patients by YOB showed a significant, progressive, gradual increase, with an apparent interruption in the late 1960s. In this study year of birth is a significant predictor for sex ratio (p<0.001, χ2=17.130, Spearman's rank correlation r=0.893). Our findings show that there is a significant increase in the incidence of MS among females for the the last decades in the Isfahan province of Iran. This rapid increase may be related to changes in environmental interactions rather than genetic factors, and among them vitamin D insufficiency, enhanced diagnosis, and lifestyle changes appear to be more plausible causative factors. [ABSTRACT FROM AUTHOR]

Conjugal multiple sclerosis (MS) is a rare form of MS in which both spouses are affected, and at least one is affected after marriage. Among 1606 definite MS patients, 1076 were in marital relationship, among whom we identified six conjugal pairs, giving the conjugal rate of 0.5%. This rate is 12.5 times higher than the estimated risk of MS for the general population (0.04%). The observed conjugal rate suggests an increased risk of developing MS for MS patients' spouses, this could be due to transmission or, more likely, to the same environmental factors shared in adult life. [ABSTRACT FROM AUTHOR]

Abstract Objectives This review summarizes recent developments in platelet biology relevant to neuroinflammatory disorders. Multiple sclerosis (MS) is taken as the "Poster Child" of these disorders but the implications are wide. The role of platelets in inflammation is well appreciated in the cardiovascular and cancer research communities but appears to be relatively neglected in neurological research. Organization After a brief introduction to platelets, topics covered include the matrix metalloproteinases, platelet chemokines, cytokines and growth factors, the recent finding of platelet PPAR receptors and Toll-like receptors, complement, bioactive lipids, and other agents/functions likely to be relevant in neuroinflammatory diseases. Each section cites literature linking the topic to areas of active research in MS or other disorders, including especially Alzheimer's disease. Conclusion The final section summarizes evidence of platelet involvement in MS. The general conclusion is that platelets may be key players in MS and related disorders, and warrant more attention in neurological research.

Abstract Objectives This is a critical review of anti-phospholipid antibodies (aPL). Most prior reviews focus on the aPL syndrome (APS), a thrombotic condition often marked by neurological disturbance. We bring to attention recent evidence that aPL may be equally relevant to non-thrombotic autoimmune conditions, notably, multiple sclerosis and ITP. Organization After a brief history, the recent proliferation of aPL target antigens is reviewed. The implication is that many more exist. Theories of aPL in thrombosis are then reviewed, concluding that all have merit but that aPL may have more diverse pathological consequences than now recognized. Next, conflicting results are explained by methodological differences. The lupus anticoagulant (LA) is then discussed. LA is the best predictor of thrombosis, but why this is true is not settled. Finally, aPL in non-thrombotic disorders is reviewed. Conclusion The current paradigm of aPL holds that they are important in thrombosis, but they may have much wider clinical significance, possibly of special interest in neurology.

In this article the author discusses the development of oropharyngeal dysphagia in multiple sclerosis (MS) patients. The author mentions that the study made use of 101 MS patients wherein 32% of patients were found to be infected with dysphagia. The author adds that the study give unclear result regarding the impact of dysphagia to MS patients whether it increases the risk of pneumonia or made the patients to be impaired while suggesting its use as a reminder for early detection of dysphagia.

Objectives: This review summarizes recent developments in platelet biology relevant to neuroinflammatory disorders. Multiple sclerosis (MS) is taken as the "Poster Child" of these disorders but the implications are wide. The role of platelets in inflammation is well appreciated in the cardiovascular and cancer research communities but appears to be relatively neglected in neurological research.Organization: After a brief introduction to platelets, topics covered include the matrix metalloproteinases, platelet chemokines, cytokines and growth factors, the recent finding of platelet PPAR receptors and Toll-like receptors, complement, bioactive lipids, and other agents/functions likely to be relevant in neuroinflammatory diseases. Each section cites literature linking the topic to areas of active research in MS or other disorders, including especially Alzheimer's disease.Conclusion: The final section summarizes evidence of platelet involvement in MS. The general conclusion is that platelets may be key players in MS and related disorders, and warrant more attention in neurological research. [ABSTRACT FROM AUTHOR]

Objectives: This is a critical review of anti-phospholipid antibodies (aPL). Most prior reviews focus on the aPL syndrome (APS), a thrombotic condition often marked by neurological disturbance. We bring to attention recent evidence that aPL may be equally relevant to non-thrombotic autoimmune conditions, notably, multiple sclerosis and ITP.Organization: After a brief history, the recent proliferation of aPL target antigens is reviewed. The implication is that many more exist. Theories of aPL in thrombosis are then reviewed, concluding that all have merit but that aPL may have more diverse pathological consequences than now recognized. Next, conflicting results are explained by methodological differences. The lupus anticoagulant (LA) is then discussed. LA is the best predictor of thrombosis, but why this is true is not settled. Finally, aPL in non-thrombotic disorders is reviewed.Conclusion: The current paradigm of aPL holds that they are important in thrombosis, but they may have much wider clinical significance, possibly of special interest in neurology. [ABSTRACT FROM AUTHOR]

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).)

Objectives: In aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-IgG NMOSD), disability accrual is mostly attributed to relapses. This study aimed to assess the prevalence of progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) in AQP4-IgG NMOSD., Methods: This was a retrospective cohort study of patients with AQP4-IgG NMOSD enrolled in the MSBase international data registry. Patients required a minimum of 3 recorded Expanded Disability Status Scale (EDSS) scores: baseline, event, and a 6-month confirmation score. Presence and absence of relapses between the baseline and event EDSS scores determined RAW and PIRA, respectively. Descriptive statistics were used to present the results., Results: A total of 181 patients followed for a median of 4.5 years (Q1 1.7, Q3 7.8) were included. Most patients were female (88.4%), and the median age at disease onset was 38.1 years. Overall, 4 patients (2.2%) developed 5 incidences of PIRA and 13 patients developed RAW (7.2%)., Discussion: This multicenter study highlights that PIRA is very rare in AQP4-IgG NMOSD. Limitations of this study include the sole focus of overall EDSS to measure disability, lack of requirement for a second EDSS score to confirm baseline EDSS, and the absence of magnetic resonance imaging information for all patients.

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).)