Prevalence of cognitive impairment (CI) in patients with multiple sclerosis (MS): A systematic review and meta-analysis.

Background: One of the complications of multiple sclerosis (MS) is cognitive impairment (CI). The prevalence of CI is reported variously in previous studies. The goal of this systematic review and meta-analysis to estimate pooled prevalence of CI in patients with MS and also the prevalence of CI based on the type of applied test. Methods: Two independent researchers systematically searched PubMed, Scopus, EMBASE, Web of Science, and google scholar as well as gray literature (conference abstracts, references of the references) which were published before up January 2022. Results: We found 4089 articles by literature search, after deleting duplicates 3174 remained. Ninety articles remained for meta-analysis. The pooled prevalence of CI using all types of tests was 41% (95% CI: 38-44%) (I2=91.7%, p<0.001). The pooled prevalence of CI using BRB test was 39% (95%CI: 36-42%) (I2=89%, p<0.001). The pooled prevalence of CI using BICAMS was 44% (95%CI: 37-51%, I2=95.4%, p<0.001). The pooled prevalence of CI using MACFIMS was 44% (95% CI: 36-53%) (I2=89.3%, p<0.001). Conclusions: The pooled prevalence of cognitive impairment in patients with MS is estimated as 41%, so CI it should be considered by clinicians.

Consanguineous marriage among familial multiple sclerosis subjects: A national registry-based study.

Background: The rising prevalence of familial multiple sclerosis (MS) in Iran has spurred interest in the potential impact of parental consanguinity on the risk of developing the disease. This study aims to aggregate current knowledge on parental consanguinity and its possible effect on MS risk, particularly among familial MS patients from various regions and ethnicities in Iran. The objective is to enhance the understanding of MS genetics and encourage further research in this field. Materials and methods: A cross-sectional study was conducted on clinically definite familial MS (FMS) patients registered in the nationwide MS registry of Iran (NMSRI). Data were extracted and supplemented with structured telephone follow-ups to gather detailed histories of MS in relatives and the familial relationships of the patients' parents. A family penetration score was proposed. Descriptive statistics and inferential statistical tests were used to analyze the data at a significance level of 0.05, adhering to ethical guidelines. Results: Out of 19,911 individuals registered in the NMSRI, 2307 FMS patients across 13 provinces were included in the final analysis. Among these, 385 (19.3 %) reported parental consanguinity, with 283 (14.2 %) having parents who were cousins and 102 (5.1 %) having parents who were distant relatives. The data showed no significant association between parental kinship and variables such as MS phenotype, number of affected relatives with MS, hospitalization rates, and expanded disability status scale score. Similarly, MS severity did not differ based on parental consanguinity (P-value >0.05). While the rate of consanguineous marriage was higher among patients with an onset age less than 18 years, there was no statistically significant difference in disease onset age based on parental consanguinity status. Conclusion: Our study highlights the complexity of factors influencing MS development, including genetic and environmental components. These results highlight the need for further research to achieve a more comprehensive understanding of MS etiology.

Protocol of a prospective multicenter study on comorbidity impact on multiple sclerosis and antibody-mediated diseases of the central nervous system (COMMIT).

Comorbidities in patients with multiple sclerosis (MS) and antibody-mediated diseases of the central nervous system (CNS) including neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein (MOG)-antibody-associated disease (MOGAD) are common and may influence the course of their neurological disease. Comorbidity may contribute to neuronal injury and therefore limit recovery from attacks, accelerate disease progression, and increase disability. This study aims to explore the impact of comorbidity, particularly vascular comorbidity, and related risk factors on clinical and paraclinical parameters of MS, NMOSD and MOGAD. We propose COMMIT, a prospective multicenter study with longitudinal follow-up of patients with MS, NMOSD, and MOGAD, with or without comorbidities, as well as healthy subjects as controls. Subjects will be stratified by age, sex and ethnicity. In consecutive samples we will analyze levels of inflammation and neurodegeneration markers in both fluid and cellular compartments of the peripheral blood and cerebrospinal fluid (CSF) using multiple state-of-the-art technologies, including untargeted proteomics and targeted ultrasensitive ELISA assays and quantitative reverse transcription polymerase chain reaction (RT-qPCR) as well as high-dimensional single-cell technologies i.e., mass cytometry and single-cell RNA sequencing. Algorithm-based data analyses will be used to unravel the relationship between these markers, optical coherence tomography (OCT) and magnetic resonance imaging (MRI), and clinical outcomes including frequency and severity of relapses, long-term disability, and quality of life. The goal is to evaluate the impact of comorbidities on MS, NMOSD, and MOGAD which may lead to development of treatment approaches to improve outcomes of inflammatory demyelinating diseases of the CNS.

Neurological efficacy and safety of mesenchymal stem cells (MSCs) therapy in people with multiple sclerosis (pwMS): An updated systematic review and meta-analysis.

BACKGROUND: Current therapeutic strategies for multiple sclerosis (MS) aim to suppress the immune response and reduce relapse rates. As alternative treatments, mesenchymal stem cells (MSCs) are being explored. MSCs show promise in repairing nerve tissue and reducing autoimmune responses in people with MS (pwMS). OBJECTIVE: This review delves into the literature on the efficacy and safety of MSC therapy for pwMS. METHODS: A comprehensive search strategy was employed to identify relevant articles from five databases until January 2024. The inclusion criteria encompassed interventional studies. Efficacy and safety data concerning MSC therapy in relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS) groups were extracted and analyzed. RESULTS: A comprehensive analysis encompassing 30 studies revealed that individuals who underwent intrathecal (IT) protocol-based transplantation of MSCs experienced a noteworthy improvement in their expanded disability status scale (EDSS) compared to the placebo group. Weighted mean difference (WMD) was -0.28; 95 % CI -0.53 to -0.03, I2 = 0 %, p-value = 0.028); however, the intravenous (IV) group did not show significant changes in EDSS scores. The annualized relapse rate (ARR) did not significantly decrease among pwMS (WMD = -0.34; 95 % CI -1.05 to 0.38, I2 = 98 %, p-value = 0.357). Favorable results were observed in magnetic resonance imaging (MRI), with only 19.11 % of pwMS showing contrast-enhanced lesions (CEL) in the short term and no long-term MRI activity. The most common complications in both short-term and long-term follow-ups were infection, back pain, and gastrointestinal symptoms. CONCLUSIONS: The study highlights the safety potential of MSC therapy for pwMS. While MRI-based neural regeneration shows significant treatment potential, the effectiveness of MSC therapy remains uncertain due to study limitations and ineffective outcome measures. Further research is needed to establish efficacy and optimize evaluation methods for MSC therapy on pwMS.

Comparing the consequences of COVID-19 vaccination between central nervous system (CNS) demyelinating diseases and other neurological disorders.

BACKGROUND: Vaccination constitutes a crucial preventive measure against COVID-19 infection. Concerns have been raised regarding the efficacy of vaccines in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) patients due to various immunomodulatory medications and potential adverse events that may impact neurological function. This study aimed to explore the implications of COVID-19 vaccination within MS and NMSOD patients and compare it with other neurological disorders (OND). METHOD: In this cross-sectional study conducted in Isfahan, Iran, baseline data and information on COVID-19 infections and vaccinations were collected from MS, NMOSD, and OND patients between September 2021 and September 2022. The predominant neurological disorders identified among OND patients encompassed headache, epilepsy, and Parkinson's disease. Logistic regression analysis was employed to compare COVID-19 vaccination outcomes among different patient groups, presenting odds ratios (OR) with 95% confidence intervals (CI). RESULTS: The study included 1,307 participants, with 738 having MS, 96 having NMOSD, 76 having clinically isolated syndrome (CIS), and 397 having OND. Significantly higher odds of post-vaccination COVID-19 infection were detected in MS (OR = 3.86, p < 0.001) NMOSD (OR = 2.77, p = 0.015) patients than OND patients. The prior history of COVID-19 infection and the type of vaccine administered did not demonstrate significant associations with the likelihood of post-vaccination COVID-19 infection in MS and NMOSD patients (p > 0.05 for all). There were no significant differences in the rates of adverse events in MS, NMOSD, and OND patients, except the second dose, where NMOSD patients had lower odds than OND patients (OR = 0.55, p = 0.019). CONCLUSION: Although the safety profile of COVID-19 vaccination in MS and NMOSD was similar to that in OND, the rates of post-vaccination COVID-19 infection in MS and NMOSD seem higher than OND. These findings highlight the importance of regular serological monitoring and the potential advantages of supplementary vaccine doses in MS and NMOSD patients.

The association between dietary inflammatory index and risk of neuromyelitis optica spectrum disorder: a case-control study.

BACKGROUND AND AIM: Neuromyelitis optica spectrum disorder (NMOSD) is a severe and rare inflammatory disease affecting the central nervous system through optic neuritis and transverse myelitis. Present study aimed to investigate the association between dietary inflammatory index (DII) and risk of NMOSD. METHODS: In this case-control study, 30 NMOSD cases and 90 aged matched healthy individuals were recruited. Habitual dietary intakes were assessed by a validated 168-item food frequency questionnaire to calculate the DII score. A multiple adjusted regression was used to determine the odd ratio (OR) of NMOSD across DII tertiles. The Residual method was applied to adjust the energy intake. RESULTS: Participants in the top of DII tertile were more likely to have NMOSD in the crude model compared to those with the lowest one (OR: 4.18; 95%CI: 1.43-12.21). It was the case when multivariable confounders were considered in adjustment model I (OR: 3.98; 95%CI: 1.34-11.82) and II (OR: 4.43; 95%CI: 1.36-14.38), such that, individuals with a greater DII score had 3.98 and 4.43-time higher risk of NMOSD in model I and II, respectively. CONCLUSION: The Present study suggests that greater adherence to a pro-inflammatory diet may be associated with an increased risk of NMOSD.

Early clinical response and complications of therapeutic plasma exchange in central nervous system demyelinating diseases.

Background: Appropriate treatment reduces the severity and duration of relapses in demyelinating diseases of Central Nervous System (CNS). If high-dose corticosteroids treatment fails, therapeutic plasma exchange (TPE) is considered as a rescue treatment. Objectives: This study aimed to investigate early clinical response and complications of TPE and prognostic factors in CNS demyelinating relapses. Design: This prospective observational study was designed in a tertiary center during one year. Methods: All adult patients diagnosed corticosteroid-resistant Multiple Sclerosis (MS), NeuroMyelitis Optica Spectrum Disorder (NMOSD), idiotypic Transverse Myelitis or Clinical Isolated Syndrome relapses, were eligible. Clinical response is defined based on Expanded Disability Status Scale (EDSS) at discharge. Clinical and laboratory complications recorded. Results: Seventy-two patients were analyzed which 58.3% patients were female. MS was diagnosed for 61.1% of cases. Thirty-five patients (48.6%) responded and the mean differences of EDSS significantly decreased 0.60 score (CI95%:0.44-.77). Electrolyte imbalances and thrombocytopenia occurred in 80.6% and 55.6% of cases respectively and 40.3% of patients had systemic reactions. However, 26.4% patients experienced moderate to severe complications. In patients with moderate to severe disability, responders were younger (MD: 8.42 years, CI95%: 1.67-15.17) and had lower EDSS score at admission (median:6, IQR: 5.5-6 against 7.5 IQR: 6.5-8). The risk of failure was higher in active progressive MS patients compared with RRMS patients (OR: 6.06, CI 95%:1.37-26.76). Patients with thrombocytopenia were hospitalized more than others (MD: 1.5 days, CI 95%: 0-3). Females were more prone to hypokalemia and systemic reactions (OR: 3.11, CI 95%:1.17-8.24 and OR: 6.67, CI 95%:2.14-20.81 respectively). Conclusion: The most common indication of TPE was corticosteroid-resistant severe MS relapses. About half of the patients presented an early clinical response. Lower disability, younger age and RRMS diagnosis are prognostic factors of better response. One out of four patients experienced moderate to severe complications, mainly electrolyte imbalances and systemic reactions. Appropriate interventions against these complications should be considered during TPE, especially in females.

Dysphagia in neuromyelitis optica spectrum disorder and multiple sclerosis: A comparison of frequency, severity, and effects on quality of life.

OVERVIEW: Dysphagia has been previously discussed as a potential life-threatening condition secondary to chronic neurological diseases such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). However, its impact on the quality of life (QoL) of patients with NMOSD has never been studied before. This study aims to determine the frequency of dysphagia and its impact on QoL in NMOSD patients in comparison with MS people and healthy individuals. METHODS: Seventy-five MS and sixty-five NMOSD patients with an expanded disability status scale (EDSS) score ≥ 3.5 in addition to 106 healthy controls were enrolled in this cross-sectional study. All the participants completed the self-report dysphagia in MS (DYMUS) and 36-item short-form health survey (SF-36) questionnaires. In case of positive answers to at least one of the questions in DYMUS, they were asked to fill out the dysphagia handicap index (DHI) questionnaire. RESULTS: The frequency of dysphagia in NMOSD, MS, and control groups was 61.54 %, 72.97 %, and 27 %, respectively. Patients with swallowing problems had reduced scores across different swallowing-related QoL domains compared to non-dysphagic patients (p < 0.05). NMOSD (1, IQR [0-3.5]) and MS patients (2, IQR [0-4]) had a significantly higher median total DYMUS score than control (0, IQR [0-1]) (p < 0.01). However, there was no discernible difference between the two patient groups. NMOSD had the highest mean total DHI score (21.22 ± 21), followed by MS (15.25 ± 18.94) and control (7.08 ± 5.12). A significant correlation was seen in the NMOSD group between the DHI total score and the SF-36 total score (r = 0.62, p < 0.05). The DHI and SF-36 subscales showed a strong association as well. The overall SF-36 scores in both the control and MS groups was not significantly correlated with DHI. The generalized linear model analysis showed that the NMOSD group's age (p-value = 0.005), EDSS (p-value < 0.001), and total DYMUS score (p-value = 0.018) significantly affected overall health status. CONCLUSION: The presence of dysphagia significantly impacts the QoL in NMOSD patients, particularly in aspects related to swallowing. These findings underscore the critical need for diligent dysphagia screening and emphasize the importance of educating both caregivers and NMOSD patients about managing this challenging symptom.

Comparative effectiveness of dimethyl fumarate versus non-specific immunosuppressants: Real-world evidence from MSBase.

Background: The use of non-specific immunosuppressants (NSIS) to treat multiple sclerosis (MS) remains prevalent in certain geographies despite safety concerns, likely due to resource limitations. Objective: To use MSBase registry data to compare real-world outcomes in adults with relapsing-remitting MS (RRMS) treated with dimethyl fumarate (DMF) or NSIS (azathioprine, cyclosporine, cyclophosphamide, methotrexate, mitoxantrone or mycophenolate mofetil) between January 1, 2014 and April 1, 2022. Methods: Treatment outcomes were compared using inverse probability of treatment weighting (IPTW) Cox regression. Outcomes were annualized relapse rates (ARRs), time to discontinuation, time to first relapse (TTFR) and time to 24-week confirmed disability progression (CDP) or 24-week confirmed disability improvement (CDI; in patients with baseline Expanded Disability Status Scale [EDSS] score ≥2). Results: After IPTW, ARR was similar for DMF (0.13) and NSIS (0.16; p = 0.29). There was no difference in TTFR between cohorts (hazard ratio [HR]: 0.98; p = 0.84). The DMF cohort experienced longer times to discontinuation (HR: 0.75; p = 0.001) and CDP (HR: 0.53; p = 0.001), and shorter time to CDI (HR: 1.99; p < 0.008), versus the NSIS cohort. Conclusion: This analysis supports the use of DMF to treat patients with relapsing forms of MS, and may have implications for MS practices in countries where NSIS are commonly used to treat RRMS.

Onabotulinum toxin A improves neurogenic detrusor overactivity following spinal cord injury: a systematic review and meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES: The current study aimed to assess the efficacy and safety of Onabotulinum toxin A (OBTX-A) treatment for neurogenic detrusor overactivity (NDO) in spinal cord injury (SCI) patients. SETTING: Iran. METHODS: All relevant articles of clinical trials and cohort studies indexed in PubMed/MEDLINE, Embase, Scopus, and Web of Science databases up to September 6, 2022, that addressed OBTX-A treatment for NDO following SCI were included. The quality of eligible studies was evaluated using Cochrane criteria. Also, the weighted mean difference (WMD) was measured with a random-effect model. RESULTS: Regarding the overall efficacy after OBTX-A treatment in the short term, volume per void (VV) (WMD = 118.8, 95% CI: 90.9-146.7, p < 0.01), incontinence-quality of life (IQoL) (WMD = 24.3, 95% CI: 15.8-32.8, p < 0.01), and maximum cystometric capacity (MCC) (WMD = 144.5, 95% CI: 132.3 to 156.7, p < 0.01) significantly increased, while maximum detrusor pressure during storage (MDP) (WMD = -30.5, 95% CI: -35.9 to -25.1, p < 0.01) showed a significant decrease. Furthermore, compared to the placebo group at the 200-unit dose, there was a significant increase in MCC (WMD = 113.5, 95% CI: 84.7 to 142.3, p < 0.01) and a significant decrease in MDP (WMD = -27.2, 95% CI: -39.2 to -15.1, p < 0.01). Urinary tract infection (UTI), hematuria, and autonomic dysreflexia were the most common side effects, occurring at rates of 29.6%, 14.8%, and 13.4%, respectively. CONCLUSION: Our findings highlighted the effectiveness and safety of OBTX-A as a promising treatment of NDO following SCI.

Comparative Effectiveness of Natalizumab, Fingolimod, and Injectable Therapies in Pediatric-Onset Multiple Sclerosis: A Registry-Based Study.

BACKGROUND AND OBJECTIVES: Patients with pediatric-onset multiple sclerosis (POMS) typically experience higher levels of inflammation with more frequent relapses, and though patients with POMS usually recover from relapses better than adults, patients with POMS reach irreversible disability at a younger age than adult-onset patients. There have been few randomized, placebo-controlled clinical trials of multiple sclerosis (MS) disease-modifying therapies (DMTs) in patients with POMS, and most available data are based on observational studies of off-label use of DMTs approved for adults. We assessed the effectiveness of natalizumab compared with fingolimod using injectable platform therapies as a reference in pediatric patients in the global MSBase registry. METHODS: This retrospective study included patients with POMS who initiated treatment with an injectable DMT, natalizumab, or fingolimod between January 1, 2006, and May 3, 2021. Patients were matched using inverse probability treatment weighting. The primary outcome was time to first relapse from index therapy initiation. Secondary study outcomes included annualized relapse rate; proportions of relapse-free patients at 1, 2, and 5 years; time to treatment discontinuation; and times to 24-week confirmed disability worsening and confirmed disability improvement. RESULTS: A total of 1,218 patients with POMS were included in this analysis. Patients treated with fingolimod had a significantly lower risk of relapse than patients treated with injectable DMTs (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.29-0.83; p = 0.008). After adjustment for prior DMT experience in the unmatched sample, patients treated with natalizumab had a significantly lower risk of relapse than patients treated either with injectable DMTs (HR, 0.15; 95% CI 0.07-0.31; p < 0.001) or fingolimod (HR, 0.37; 95% CI 0.14-1.00; p = 0.049). The adjusted secondary study outcomes were generally consistent with the primary outcome or with previous observations. The findings in the inverse probability treatment weighting-adjusted patient populations were confirmed in multiple sensitivity analyses. DISCUSSION: Our analyses of relapse risk suggest that natalizumab is more effective than fingolimod in the control of relapses in this population with high rates of new inflammatory activity, consistent with previous studies of natalizumab and fingolimod in adult-onset patients and POMS. In addition, both fingolimod and natalizumab were more effective than first-line injectable therapies. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that patients with POMS treated with natalizumab had a lower risk of relapse than those with fingolimod.

Multiple sclerosis and personality traits: associations with depression and anxiety.

BACKGROUND: Depression and anxiety are commonly observed in people with multiple sclerosis (pwMS). There is a growing body of literature supporting the hypothesis that personality traits can influence the mood disorders. This study aimed to investigate the personality traits and their relationships with depression and anxiety among pwMS. METHODS: 234 pwMS were involved in this cross-sectional study. Personality traits, depression, and anxiety were assessed using the NEO Five-Factor Inventory (NEO-FFI) and Hospital Anxiety and Depression Scale (HADS), respectively. Pearson's correlation coefficient and generalized linear model were employed to evaluate the relationships between demographic and clinical characteristics, NEO-FFI, and HADS subscales. RESULTS: In pwMS, longer disease duration was significantly associated with lower level of conscientiousness (ß = - 0.23, p = 0.008) and agreeableness (ß = - 0.2, p = 0.01). Moreover, higher expanded disability status scale (EDSS) of pwMS had a significant relationship with higher level of neuroticism (ß = 0.89, p = 0.01). Increased level of neuroticism was significantly correlated with lower level of extraversion (r = - 0.28, p < 0.001), openness (r = - 0.37, p < 0.001), agreeableness (r = - 0.31, p < 0.001), and conscientiousness (r = - 0.45, p < 0.001). PwMS with higher level of conscientiousness showed more extraversion (r = 0.23, p < 0.001), openness (r = 0.61, p < 0.001), and agreeableness (r = 0.41, p < 0.001). Elevated level of neuroticism was significantly associated with higher level of anxiety (ß = 0.47, p < 0.001) and depression (ß = 0.11, p < 0.001) among pwMS. CONCLUSION: The co-occurrence of depression and anxiety is probably associated with neuroticism among pwMS. Additionally, the impact of personality traits extends to influencing key disease aspects such as physical disability and disease duration in MS.

Asthma and chronic obstructive pulmonary disease (COPD) in people with multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Studies have found that multiple sclerosis (MS) has an impact on the initiation or the course of asthma and chronic obstructive pulmonary disease (COPD). This review amied to investigate the prevalence and odds of asthma and COPD among people with MS (pwMS). METHOD: PubMed, Embase, Scopus, and Web of Science were systemically searched from inception to May 2023. R version 4.3.2 and random-effect model were used to calculate the pooled prevalence and odds ratio (OR), with their 95 % confidence interval (CI), in pwMS. RESULTS: A total of 40 studies consisting of 287,702 pwMS were included. 37 studies indicated that the pooled prevalences of asthma and COPD among pwMS were 5.97 % (95 % CI: 4.62 %-7.69 %, I2=99 %) and 3.03 % (95 % CI: 1.82 %-5.00 %, I2=99 %), respectively. 24 studies on 236,469 pwMS and 85,328,673 healthy controls revealed that the overall odds of asthma and COPD in MS were 1.14 (95 % CI: 0.76-1.71, p-value=0.53, I2=97 %) and 1.28 (95 % CI: 1.11-1.47, p-value<0.01, I2=70 %), respectively. CONCLUSION: MS can increased the risk of developing COPD, while asthma does not exhibit a significant relationship with MS. Our study highlights the importance of identifying pwMS who face greater risks of respiratory issues to monitor efficiently and initiate suitable preventative actions.

A national registry-based study of ethnic differences in people with multiple sclerosis in Iran.

OBJECTIVE: The relationship between MS and ethnicity has been understudied in the Middle East compared to the United States and Europe. As Iran as the highest prevalence of MS in the Middle East, we decided to investigate the demographic and clinical differences in people with MS (pwMS) from major ethnicities Iran. METHODS: In a cross-sectional study using data from National Multiple Sclerosis Registry in Iran. PwMS from six provinces were chosen and interviewed for determining their ethnicity. Persians (Fars), Kurds, Lurs, Azeris and Arabs with a clear ethnic background were included. Recorded data from the registry was used to compare the demographic and clinical features. RESULTS: A total of 4015 pwMS (74.2% female) were included in the study with an average age of 36.76 ± 9.68 years. Persians and Kurds had the highest percentage of pwMS in youngest and oldest age groups, respectively, with 2.9% and 5.7% (p<0.01). The highest average age of onset was seen in Persians (29.47 ± 8.89) and the lowest observed in Mazandaranis (26.82 ± 7.68, p<0.01). Azeris and Kurds had the highest proportions of pwMS diagnosed <18 and >55, at rates of 12% and 1.6%, respectively (p<0.01). There were statistically significant differences in distribution of phenotypes (p<0.01) and time to progression to secondary progressive MS (p<0.01) such that Persians had the highest rate of clinically isolated syndrome (CIS) at 19.3% and Arabs had highest rates of relapsing-remitting MS (86.2%) and secondary progressive MS (16.4%). Lurs, Azeris and Mazandaranis had significantly more patients progressing to secondary-progressive MS <5 years from diagnosis (p<0.01). There was a significant difference in number of relapses between the ethnicities (p<0.01) with Lurs having the highest proportion of participants reporting >4 relapses with 23.0% and Azeris having the highest percentage of pwMS reporting no relapse (53.0%). Kurds had the highest Expanded Disability Status Scale (EDSS) average at 2.93 ± 1.99 and Lurs had the lowest with 1.28 ± 1.25 (p<0.01). The differences in prevalence of positive family history for the whole cohort between ethnicities were significant (P=0.02), ranging from 12.8% in Kurds to 19.6% in Persians. CONCLUSION: We found Persians to have higher rates of pediatric MS and higher rates of CIS. Kurds and Lurs had higher and lower EDSS scores, respectively. Lurs and Persian had higher annual relapse rates. We also found lower rates of SPMS among Arabs and earlier progression to SPMS in Lurs, Azeris and Mazandaranis. Such differences highlight the importance of the potential role of ethnicities in diagnosis and prognosis of MS, especially considering their observation within the geographical limits of a single country.

Concurrent glioma and multiple sclerosis: A systematic review of case reports.

BACKGROUND: It is uncommon for individuals with demyelinating disease, notably multiple sclerosis (MS), to be diagnosed with intracranial gliomas. It has been debated whether or not the concurrence of these two disorders is accidental. Clinically, it may be challenging to diagnose someone who has MS and an intracranial tumor simultaneously. We conducted this systematic review to evaluate the glioma patients following MS. METHODS: We collected 63 studies from 1672 databases from January 1990 to February 2023, and our inclusion criteria involved peer-reviewed case reports/series studies reporting concurrent MS and glioma in patients, considering various types of gliomas. RESULTS: We included 145 cases, 51% were women and 49 % were men, with an average age of 47.4 years. Common symptoms of glioma at admission included seizures (31.2 %), hemiparesis (15.6 %), and headache (14.3 %). 75 % of patients had primarily with relapsing-remitting MS (RRMS). MS treatments included interferon(IFN)-ß (44.6 %), glatiramer acetate (GA) (21.4 %), fingolimod (19.6 %), and natalizumab (19.6 %). The average time between MS and glioma diagnosis was 12.1 years, with various timeframes. Among the 59 reported cases, 45.8 % led to patient fatalities, while the remaining 54.2 % managed to survive. CONCLUSION: This co-occurrence, though rare, suggests potential underlying shared mechanisms or vulnerabilities, possibly at a genetic or environmental level. An interdisciplinary approach, combining the expertise of neurologists, oncologists, radiologists, and pathologists, is vital to ensure accurate diagnosis and optimal management of affected individuals. Nonetheless, there is still a significant lack of information regarding this phenomenon, necessitating large-scale population-based studies and experimental research.

Fulminant multiple sclerosis versus autoimmune encephalitis: A case report.

Key Clinical Message: This case highlights the importance of early diagnosis and treatment in prognosis of fulminant multiple sclerosis, and its similar management with autoimmune encephalitis in some clinical settings, in which these diseases are indistinguishable. This case also supports the use of rituximab in these patients with an adequate response to plasmapheresis. Abstract: Early diagnosis and treatment of fulminant multiple sclerosis (MS), also known as Marburg' or malignant variant of MS (MVMS), is of great value in reducing morbidity and mortality. Seronegative autoimmune encephalitis (AIE) is very similar to, and sometimes indistinguishable from, fulminant MS. However, the acute and long-term management of the two diseases is often the same. This article describes the clinical course of a patient suspected of having MVMS or AIE and the challenges of their differential diagnosis and management.

Insights into the interplay between Epstein-Barr virus (EBV) and multiple sclerosis (MS): A state-of-the-art review and implications for vaccine development.

Background and Aims: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS). MS results from an inflammatory process leading to the loss of neural tissue and increased disability over time. The role of Epstein Barr Virus (EBV), as one of the most common global viruses, in MS development has been the subject of several studies. However, many related questions are still unanswered. This study aimed to review the connection between MS and EBV and provide a quick outline of MS prevention using EBV vaccination. Methods: For this narrative review, an extensive literature search using specific terms was conducted across online databases, including PubMed/Medline, Scopus, Web of Science, and Google Scholar, to identify pertinent studies. Results: Several studies proved that almost 100% of people with MS showed a history of EBV infection, and there was an association between high titers of EBV antibodies and an increased risk of MS development. Various hypotheses are proposed for how EBV may contribute to MS directly and indirectly: (1) Molecular Mimicry, (2) Mistaken Self, (3) Bystander Damage, and (4) Autoreactive B cells infected with EBV. Conclusion: Given the infectious nature of EBV and its ability to elude the immune system, EBV emerges as a strong candidate for being the underlying cause of MS. The development of an EBV vaccine holds promise for preventing MS; however, overcoming the challenge of creating a safe and efficacious vaccine presents a significant obstacle.

Prevalence and incidence of multiple sclerosis in Isfahan, Iran between 1996 and 2021: A population-based study.

BACKGROUND: There has been no recent comprehensive epidemiological study on a large and stable population of multiple sclerosis (MS) in Isfahan. Therefore, we conducted this study to estimate the incidence and prevalence of MS in Isfahan province from 1996 to 2021. METHOD: In this population-based study, we utilized the dataset from the Vice-Chancellor's Office of Isfahan University of Medical Sciences, which registers all people diagnosed with MS (PDWM) in Isfahan province, excluding those residing in Kashan city. We measured crude incidence and prevalence of MS, separated by sex, and based on age of MS onset, as well as changes in age of MS onset during observation. RESULTS: A total of 9,909 PDWM were included in our study. The incidence during the time period of 1996-2000 was 5.4/100,000 (1.1/100,000 per year), which subsequently increased to 14.1 (2.8/100,000 per years) and 31.1 per 100,000 (6.2/100,000 per year) during 2001-2005 and 2006-2010, respectively. There was a further increase to 70.9/100,000 (14.2/100,000 per year) in 2011-2015, but it remained stable at 71.8/100,000 (12/100,000 per year) during the period of 2016-2021. In 2016, the age-standardized incidence rates of pediatric-onset, adult-onset, and late-onset MS were 1.8/100,000, 31.4/100,000, and 17.5/100,000, respectively. The prevalence of MS in 2021 was 183.9/100,000. The female/male new case ratio was 4.5 during 1996-2000, decreasing to 4.0, 3.9, 3.9, and 2.9 in the subsequent four five-year periods. The mean age of RRMS onset was 26.3 ± 8.1 between 1990 and 1999, 28.5 ± 8.3 during 2000-2009, and increased to 32.8 ± 9.6 in 2010-2019. CONCLUSION: This study shows that Isfahan has one of the highest incidence rate and prevalence ratio of MS in the region. We observed an increase in the incidence rate during the first decade, followed by stability in the last two five- and six-year periods. Further studies are needed to identify the reasons behind the change in incidence of MS in Iran.

Validity and reliability of the Persian version of Recce stigma scale in people with multiple sclerosis and its impact on quality of life.

BACKGROUND: There is often a fear of social stigma experienced by people with multiple sclerosis (pwMS), which negatively impacts the quality of their lives (QoL). Currently, no Persian-validated questionnaire is available to assess this issue in pwMS. This study aimed to assess the validaty and reliability of the Persian version of Reece Stigma Scale Multiple Sclerosis (RSS-MS) questionnaire for pwMS. METHOD: This cross-sectional was conducted between January and February 2023 in Isfahan, Iran. The demographic and clinical information and the RSS-MS and Multiple Sclerosis Impact Scale-29 (MSIS-29) questionnaires were recorded from pwMS. The content validity index (CVI) and content validity ratio (CVR) have been used to evaluate validity. To identify the factors supporting the MS-related stigma, an exploratory factor analysis (EFA) was conducted. RESULTS: The present study recruited 194 pwMS. Based on factor analysis, only two factors had eigenvalues ≥ 1.0 and exhibited high internal consistency. The Cronbach's α coefficient for internal consistency of the RSS-MS scale was 0.822. More evidence for the construct validity suggested that having higher levels of stigma is significantly correlated with psychological (r = 0.468, p-value < 0.001) and physical dimensions (r = 0.585, p-value < 0.001) of MSIS-29. Expanded Disability Status Scale, disease duration, and treatment duration did not show a significant correlation with stigma (p-value > 0.05). CONCLUSION: This study indicated that the modified version of the RSS-MS scale in the Persian language showed acceptable validity and reliability for evaluating the stigma among Persian pwMS. Furthermore, this study emphasizes the cruciality of monitoring and addressing stigma among pwMS, as it can potentially enhance medical, psychological, physical, and QoL outcomes.

Examining the environmental risk factors of progressive-onset and relapsing-onset multiple sclerosis: recruitment challenges, potential bias, and statistical strategies.

It is unknown whether the currently known risk factors of multiple sclerosis reflect the etiology of progressive-onset multiple sclerosis (POMS) as observational studies rarely included analysis by type of onset. We designed a case-control study to examine associations between environmental factors and POMS and compared effect sizes to relapse-onset MS (ROMS), which will offer insights into the etiology of POMS and potentially contribute to prevention and intervention practice. This study utilizes data from the Primary Progressive Multiple Sclerosis (PPMS) Study and the Australian Multi-center Study of Environment and Immune Function (the AusImmune Study). This report outlines the conduct of the PPMS Study, whether the POMS sample is representative, and the planned analysis methods. The study includes 155 POMS, 204 ROMS, and 558 controls. The distributions of the POMS were largely similar to Australian POMS patients in the MSBase Study, with 54.8% female, 85.8% POMS born before 1970, mean age of onset of 41.44 ± 8.38 years old, and 67.1% living between 28.9 and 39.4° S. The POMS were representative of the Australian POMS population. There are some differences between POMS and ROMS/controls (mean age at interview: POMS 55 years vs. controls 40 years; sex: POMS 53% female vs. controls 78% female; location of residence: 14.3% of POMS at a latitude ≤ 28.9°S vs. 32.8% in controls), which will be taken into account in the analysis. We discuss the methodological issues considered in the study design, including prevalence-incidence bias, cohort effects, interview bias and recall bias, and present strategies to account for it. Associations between exposures of interest and POMS/ROMS will be presented in subsequent publications.