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Background and Objectives: Women with multiple sclerosis (MS) are at risk of disease reactivation in the early postpartum period. Ocrelizumab (OCR) is an anti-CD20 therapy highly effective at reducing MS disease activity. Data remain limited regarding use of disease-modifying therapies (DMTs), including OCR, and disease activity during peripregnancy periods., Methods: We performed a retrospective cohort study using data from the MSBase Registry including pregnancies conceived after December 31, 2010, from women aged 18 years and older, with relapsing-remitting MS or clinically isolated syndrome. Women were classified by preconception exposure to DMTs, including OCR, rituximab (RTX), natalizumab (NAT), stratified into active (NAT-A; continued ≥28 weeks of gestation, restarted ≤1 month postpartum) or conservative (NAT-C; continued ≤4 weeks of gestation, restarted >1 month postpartum) strategies, dimethyl fumarate (DMF) or low-efficacy DMTs (interferon-beta, glatiramer acetate). Annualized relapse rates (ARRs) were calculated for 12-month prepregnancy, pregnancy, and 6-month postpartum periods., Results: A total of 2,009 live births from 1,744 women were analyzed, including 73 live births from 69 women treated with preconception OCR. For OCR, no within-pregnancy relapse was observed and 3 women (4.1%) experienced 1 relapse in the postpartum period (ARR 0.09 [95% CI 0.02-0.27]). For NAT-A, 3 (3.7%) of 82 women relapsed during pregnancy (0.05 [0.01-0.15]) and 4 (4.9%) relapsed during postpartum (0.10 [0.03-0.26]). However, for NAT-C, 13 (15.9%) of 82 women relapsed within pregnancy (0.32 [0.20-0.51]) and 25 (30.5%) relapsed during postpartum (0.74 [0.50-1.06]). In the low-efficacy DMT group, 101 (7.6%) of 1,329 women experienced within-pregnancy relapse (0.12 [0.10-0.14]), followed by an increase in postpartum relapse activity with 234 women (17.6%) relapsing (0.43 [0.38-0.48]). This was similarly seen in the DMF group with 13 (7.9%) of 164 women experiencing within-pregnancy relapse (0.12 [0.06-0.20]) and 25 (15.2%) of 164 relapsing postpartum (0.39 [0.26-0.57]). Our RTX cohort had 0 of 24 women experiencing within-pregnancy relapse and 3 (12.5%) of 24 experiencing postpartum relapse., Discussion: Women treated with OCR or NAT-A were observed to have low relapse rates during pregnancy and postpartum. NAT-C was associated with increased risk of relapses. There was no within-pregnancy relapse in our RTX cohort, although we caution overinterpretation due to our sample size. An effective DMT strategy with a favorable safety profile for the mother and infant should be discussed and implemented well in advance of planning a family., Classification of Evidence: This study provides Class III evidence that for women with relapsing-remitting MS or clinically isolated syndrome who become pregnant, ocrelizumab, rituximab, and natalizumab (continued ≥28 weeks of gestation and restarted ≤1 month postpartum) were associated with reduced risk of relapses, compared with other therapeutic strategies.

Multiple sclerosis is an inflammatory demyelinating disease and represents a global health concern. Ocrelizumab, a humanized IgG monoclonal antibody, selectively targets CD20 on B cells and CD20-expressing T cells. This study aimed to compare the efficacy and safety of the biosimilar ocrelizumab candidate (Xacrel) to the originator product (Ocrevus) in Relapsing Multiple Sclerosis (RMS) patients. In this randomized trial, patients received either Xacrel or Ocrevus for 96 weeks. The primary endpoint was the equivalency of the medications in reducing the annualized relapse rate (ARR) at week 48. The secondary endpoints included time to the onset of disability progression confirmed at 12 and 24 weeks, the proportion of relapse-free patients, magnetic resonance imaging (MRI) evaluations, safety assessments, and immunogenicity over 96 weeks. A total of 170 patients were randomized (1:1 ratio). In the per protocol analysis, the upper and lower limits of 95% two-sided confidence intervals of difference between treatments in the 48-week ARR rate were in the predefined margin of - 0.2 to 0.2 (- 0.002; 95% CI - 0.080 to 0.075). The two products were also comparable in terms of other efficacy parameters, safety, and immunogenicity. The results confirmed that Xacrel is equivalent to Ocrevus in terms of 48-week ARR in RMS patients, with no considerable difference in other efficacy parameters and the safety profile during the 96 weeks. The trial was registered in Iranian registry of clinical trials (IRCT) on 10/06/2019 with the registration number of IRCT20150303021315N13 and in Clinicaltrials.gov on 19/07/2021 with the registration code of NCT04966338., (© 2024. The Author(s).)

Background: Multiple sclerosis (MS) is a prevalent, disabling, inflammatory, neurodegenerative disease that typically manifests during a highly productive stage of life. Interferon beta-1a was among the first approved disease-modifying therapies for MS and remains among the first-line treatment options. Pegylation of the interferon beta-1a molecule prolongs its half-life while maintaining its efficacy and safety profile. In PEGINTEGRITY study, we aimed to compare peginterferon beta-1a with interferon beta-1a in terms of efficacy and safety in relapsing-remitting multiple sclerosis (RRMS) patients., Methods: This study was a randomized, active-controlled, parallel-group, multi-center Phase 3 trial conducted in Iran in participants with RRMS. Participants received 125 µg of subcutaneous peginterferon beta-1a every two weeks or 30 µg of intramuscular interferon beta-1a once a week for up to 96 weeks. The primary outcome was the non-inferiority of peginterferon beta-1a to interferon beta-1a in reducing annualized relapse rate (ARR). Other outcomes included the number of patients with 12-week confirmed disability progression, the number of new or newly-enlarging T2 hyperintense lesions, the number of gadolinium-enhancing lesions, the number of new T1 hypointense lesions, the volume of new or newly-enlarging T2 hyperintense lesions, changes in brain volume, immunogenicity, and safety assessments., Results: A total of 168 patients who met the eligibility criteria were enrolled and assigned to two arms of the study, each consisting of 84 participants. Totally, 41 participants (24 patients in the peginterferon beta-1a group and 17 patients in the interferon beta-1a group) were withdrawn from the study. The withdrawn patients were included in the per-protocol analysis for the period of time they were in the study. In 96 weeks, in the per-protocol population, the ARR was 0.05 in the peginterferon beta-1a group versus 0.11 in the interferon beta-1a group, which does not reflect a statistically significant difference (p=0.09; 95 % CI, 0.18-1.14). Considering the upper limit of the one-sided 95 % CI of the rate ratio of peginterferon beta-1a compared to interferon beta-1a, as well as the non-inferiority margin, it can be concluded that the primary outcome was met. The results were also comparable for other efficacy and safety outcomes., Conclusion: The results demonstrate the non-inferiority of peginterferon beta-1a to interferon beta-1a with similar efficacy in 96-week ARR in RRMS patients. Both arms were also comparable in other efficacy outcomes and safety profiles with no statistically significant differences. These findings support considering peginterferon beta-1a as a safe and efficient option in patients with RRMS. This study was registered on Iranian Registry of Clinical Trials (IRCT201612306135N8) and clinicaltrials.gov (NCT05242133)., Competing Interests: Declaration of competing interest Amirreza Azimi Saeen has received consulting and/or lecture fee from CinnaGen, Zistdaru, Cobel Darou, Biologix, Merck Serono, Roche, Actoverco, and Byer Schering. He also has received travel grant from CinnaGen, Zistdaru, Biologix, Zahravi, Cobel Darou, and Sanofi Genzyme. Vahid Shaygannejad, Fereshteh Ashtari, Morteza Saeidi, and Seyed Mohammad Baghbanian have received educational, research grants, lecture honorarium, travel supports to attend scientific meetings from Biogen, Merck, Bayer, Roche, Novartis, CinnaGen, Osveh, Zistdaru, Zahravi, Nanoalvand, and Genzyme. Hamidreza Ghalyanchi Langroodi has received educational, lecture honorarium, travel supports to attend scientific meetings from Biogen, Merck, Bayer, Roche, CinnaGen, Zistdaru, Zahravi, Nanoalvand, and Genzyme. Roya Abolfazli has received support for scientific meetings and honorarium for advisory board from CinnaGen, Merck, Roche, Zistdaru, Nanoalvand, Zahravi, Cobel Darou, and Actoverco. Hormoz Ayromlou has received educational, research grants, lecture honorarium, travel supports to attend scientific meetings from Biogen, Merck, Bayer, Novartis, CinnaGen, Zistdaru, Zahravi, and Nanoalvand. Nahid Beladi Moghadam and Masoud Ghiasian declared no conflict of interest regarding to this article. Elnaz Asadollahzadeh has received payment from CinnaGen for the interpretation of MRI scans. Hamidreza Kafi is the head of the medical department of Orchid Pharmed Company; the CinnaGen Company partner in conducting clinical trials. Araz Sabzvari is a member of CinnaGen medical biotechnology research center, which collaborates with universities and researchers all over the world with regards to research and development of medications and health issues., (Copyright © 2024. Published by Elsevier B.V.)

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: 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., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Sharareh Eskandarieh reports financial support was provided by 10.13039/501100004484Tehran University of Medical Sciences. Sharareh Eskandarieh reports a relationship with 10.13039/501100004484Tehran University of Medical Sciences that includes: consulting or advisory, employment, equity or stocks, and funding grants. Sharareh Eskandarieh has patent licensed to NMSRI. None If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Support for the Reported Work: Tehran University of Medical Sciences. Relevant support: advisory positions, consulting fees. Intellectual Property: National multiple sclerosis registry system of Iran (NMSRI). Other Activities: None. The entire data of the study has been sent to the journal in Excel file format. If needed, it will be provided by contacting the website https://nmsri.ir/or by email., (© 2024 The Authors.)

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., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: The time to diagnosis of multiple sclerosis (MS) is of great importance for early treatment, thereby reducing the disability and burden of the disease. The purpose of this study was to determine the time from the onset of clinical symptoms to the diagnosis of MS and to evaluate the factors associated with a late diagnosis in Iranian MS patients., Methods: The present cross-sectional study was conducted on patients with MS who were registered in the National MS Registry System of Iran (NMSRI)., Results: Overall, 23291 MS patients registered in 18 provinces of Iran were included in this study. The mean (standard deviation) interval between the onset of the disease and diagnosis of MS was 13.42 (32.40) months, and the median was one month. The diagnostic interval of 41.6% of patients was less than one month, and 14.8% of them had a one-month time to diagnosis. Patients with an age of onset below 18 years and those diagnosed after the age of 50 years had a longer time to diagnosis (P<0.001). Patients with primary progressive MS (PPMS) had the longest time to diagnose and those with relapsing-remitting MS (RRMS) had the shortest time (P<0.001). The results of negative binominal regression showed that the average rate of delay in diagnosis in women was 12% less than that in men. The average delay in diagnosis in patients with a positive family history of MS was 23% more than that in others. The rate of delay in the diagnosis of patients with PPMS and secondary progressive MS was 2.22 and 1.66 times higher, respectively, compared with RRMS., Conclusion: The findings of the present study revealed that more than half of the MS patients were diagnosed within a one-month interval from the symptom onset, which is an acceptable period. More attention should be paid to patients' access to medical facilities and MS specialists., (Copyright © 2024. Published by Elsevier B.V.)

Background: Ocrelizumab is a humanized antiCD20, thought to be a highly effective disease-modifying therapy (DMT). Its most frequent adverse effects are infusion-related reactions (IRRs). To reduce these reactions, the first dose of ocrelizumab is administered as two 300 mg infusions separated by two weeks. However, in the phase II trial of ocrelizumab, severe IRRs were not significantly different between two doses of 600 mg dose (two separate 300 mg doses) and 2000 mg dose (two separate 1000 mg doses). We compared the IRRs in undivided full (one 600 mg) and divided (two 300 mg) doses of ocrelizumab which is the standard protocol., Methods: MS patients (relapsing or primary progressive MS) who are selected to receive ocrelizumab by neurologist or MS fellowship were enrolled in an open-label randomized controlled trial. Iranian biosimilar of the drug (Xacrel ® by Cinnagen, approved by the Iranian Food and Drug Administration in 2021) was used. The participants received the first dose of ocrelizumab as either one 600 mg dose in one session or two 300 mg doses in two weeks apart. IRRs during or in the first 24 h after infusion were recorded., Results: Of 332 participants, 150 received two 300 mg doses, and 182 received one 600 mg dose (by random selection). Life-threatening adverse effects were not observed in both groups. Overnight admission or permanent drug discontinuation was not needed. Temporary drug discontinuation was significantly higher in the one 600 mg dose group (p-value < 0.001). During the infusions, malaise (p-value: 0.003), skin reactions (p-value: 0.04), throat swelling (p-value: 0.03), and dyspnea (p-value: 0.01) were significantly increased in the intervention group. However, in the first 24 h, there was no significant difference between two different treatment protocols (one 600 mg dose or two 300 mg doses) in the onset of IRRS (p-value: 0.12)., Conclusion: These findings suggest one 600 mg dose of ocrelizumab administration for the first dose is relatively safe. With some protocol modifications, it could lead to fewer patient referrals, saving time and cost and improvement the access for patients., (© 2023. The Author(s) under exclusive licence to Belgian Neurological Society.)

Background: Optic neuritis (ON) is one of the main neuro-ophthalmic presentations of multiple sclerosis (MS), and it causes optic nerve atrophy and axonal loss. However, so far, there is no effective treatment to improve long-term outcomes., Methods: In a double-blind placebo-controlled randomized clinical trial, 50 patients with MS-related ON were allocated into two arms (24 in the control group and 26 in the intervention group) receiving either 25000IU retinyl palmitate or an identical placebo for six months. Visual evoked potential (VEP), visual acuity, and the retinal nerve fiber layer (RNFL) thickness were evaluated and compared before and after the treatment., Results: RNFL thickness reduction in the affected eyes at sixth month compared to the baseline were 14.81 and 19.46 μm, in the intervention and control groups, respectively (P=0.017). However, VitA therapy did not affect visual acuity and VEP., Conclusion: Vitamin A supplementation in the patients with acute ON in MS could lessen optic nerve axonal loss., Competing Interests: The authors declare there is no conflict of interest.

Background: Every patient diagnosed with definite multiple sclerosis (MS) should begin disease modifying therapies. Cinnomer ® contains 40 mg glatiramer acetate (GA) and is available in prefilled syringes and autoinjector devices., Methods: A phase IV multicenter study was conducted to explore the safety and effectiveness of Cinnomer ® in the treatment of MS. Study-related data were collected for 14 months., Results: Totally, 368 Iranian relapsing-remitting MS patients in nine cities were enrolled. The patients were either treatment naïve (n=191) or switchers (n=177). Cinnomer ® treatment was associated with a significant reduction in annual relapse rate (ARR) (RR: 0.65, 95% CI: 0.43, 0.98). Final mean Expanded Disability Status Scale (EDSS) scores showed improvement from baseline (difference: -0.21, 95% confidence interval (CI): -0.34, -0.08). There was a significant decrease in gad-enhancing lesions during treatment (difference: -0.38, 95% CI: -0.64, -0.12). The mean score for the depression measure (21-item BDI-II questionnaire) significantly improved (difference: -2.39, 95% CI: -3.74, -1.03). There was a significant change in the "psychological well-being" dimension ( P =0.02) (in line with BDI-II scores) and "rejection" MusiQoL dimensions ( P =0.04). The adverse events documented throughout the study were not unexpected for GA and were principally not serious., Conclusion: Safety measures were in line with the known profiles of GA. The results suggest that Cinnomer ® is effective with respect to clinical outcomes and from the patient's perspective and in reducing MRI-measured MS activity., (© 2023 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Patients with multiple sclerosis (MS) experience various physical symptoms and psychosocial problems that disrupt their normal life, and adapting to these conditions is vital for them. Many factors that serve as facilitators of and barriers to achieving adjustment should be identified to be able to help the patients. This study was conducted to explain the experiences of patients with MS regarding the facilitators of and barriers to adjustment using conventional content analysis. The participants consisted of 18 patients, one nurse, one physician, and one patient companion, who were selected from the Multiple Sclerosis Clinic of BouAli, northern Iran, through purposive sampling. Data were collected through individual, in-depth, and semi-structured interviews and analyzed using the method recommended by Elo and Kyngäs (2008). The data analysis generated five subcategories as facilitators and five subcategories as barriers. The subcategories of facilitators included family's appropriate behavior with the patient, occupation, studying and information gathering, religious beliefs, and turning attitude into disease simplification and optimism. The subcategories of barriers were concerns about the uncertain future of the disease, physicians' poor communication and behavior, society's poor attitude, economic problems, and unsatisfactory support by the government and insurance companies. The results showed that a set of individual, environmental, and social factors serves as facilitators of or barriers to the process of adjustment to MS in patients. Gaining knowledge about these factors in congruence with the sociocultural context of the society, as derived from people's real experiences, can help healthcare staff and the family of these patients provide more efficient assistance to the patients for achieving adjustment earlier., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Multiple sclerosis (MS) may be affected by socioeconomic status (SES). This study aims to explore the determinants of SES among Iranian patients with MS and examine how these factors relate to disability and disease progression., Methods: All patients with MS listed in the nationwide MS registry of Iran (NMSRI) until January 8, 2022, were included in this population-based study., Results: Among the 5153 patients, most were female (74.5%), married (70.8%), and did not hold an academic degree (53.8%). Unemployment (OR: 3.75) and being unmarried (OR: 2.60) were significantly associated with Expanded Disability Status Scale (EDSS)≥6, and the time to progression was shorter in the unemployed group ( P value: 0.03). There was also a significant negative correlation between the time to progression and the age at disease onset., Conclusion: The study suggests that providing financial and social support to MS patients and their families through investment could reduce both individual and societal burdens., (© 2023 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

This project sought to explore the potential association between medical history and the development of multiple sclerosis (MS) by conducting a retrospective study. This population-based case-control study included 200 MS cases and 2 control groups of 200 patients and healthy individuals each. Data was collected through face-to-face interviews, medical file reviews, and an electronic checklist. Multivariable analysis was used to calculate odds ratios and 95% confidence intervals to estimate the risk of each medical history on MS occurrences. Of 600 participants, 381 (63.5%) individuals were female. The mean age of the participants was 36.5 ± 11.9 years. The adjusted risks of MS were 4.40; 95% CI: 1.73 to 11.1 for measles and 4.75; 95% CI: 2.05 to 11 for amoxicillin consumption. The adjusted MS odds for autoimmune disease including 4.63; 95% CI: 0.35 to 60.6 for psoriasis and 7.15; 95% CI: 1.87 to 27.2 for myasthenia gravis. On the other hand, the calculated adjusted odds of MS occurrence were 0.14; 95% CI: 0.03 to 0.69 for seizure and 0.17; 95% CI: 0.02 to 1.49 for epilepsy. This study suggested that individuals with autoimmune diseases should be monitored more closely, as they may be at an increased risk of developing other autoimmune conditions, particularly MS., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear., Objective: To determine whether early non-disabling relapses predict disability accumulation in RRMS., Methods: We redefined mild relapses in MSBase as 'non-disabling', and moderate or severe relapses as 'disabling'. We used mixed-effects Cox models to compare 90-day confirmed disability accumulation events in people with exclusively non-disabling relapses within 2 years of RRMS diagnosis to those with no early relapses; and any early disabling relapses. Analyses were stratified by disease-modifying therapy (DMT) efficacy during follow-up., Results: People who experienced non-disabling relapses within 2 years of RRMS diagnosis accumulated more disability than those with no early relapses if they were untreated ( n  = 285 vs 4717; hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.00-1.68) or given platform DMTs ( n  = 1074 vs 7262; HR = 1.33, 95% CI = 1.15-1.54), but not if given high-efficacy DMTs ( n  = 572 vs 3534; HR = 0.90, 95% CI = 0.71-1.13) during follow-up. Differences in disability accumulation between those with early non-disabling relapses and those with early disabling relapses were not confirmed statistically., Conclusion: This study suggests that early non-disabling relapses are associated with a higher risk of disability accumulation than no early relapses in RRMS. This risk may be mitigated by high-efficacy DMTs. Therefore, non-disabling relapses should be considered when making treatment decisions.

Background: It may take a long time to diagnose multiple sclerosis (MS) since the emergence of primary symptoms. This study aimed to use count regression models to compare their fit and to identify factors affecting delay in the diagnosis of MS. Methods: Data were collected from the Nationwide MS Registry of Iran (NMSRI) for Mazandaran Province, Iran, using census sampling until April 2022. The four models of Poisson regression, negative binomial (NB) regression, zero-inflated Poisson (ZIP) regression, and zero-inflated negative binomial (ZINB) regression were used in this study. Results: In this study on 2894 patients, 74.0% were women, and 8.5% had a family history of MS. The mean ± standard deviation (SD) of the patients' age was 34.96 ± 9.41 years, and the mean delay in diagnosis was 12.32 ± 33.26 months, with a median of 0 (Q1-Q3: 0-9). The NB regression model showed the best performance, and factors, including a history of hospitalization and the year of symptom onset, had significant effects on a delayed diagnosis. Besides, the Expanded Disability Status Scale (EDSS) score was significantly different before and after 2017; it was also associated with sex, type of MS, and history of hospitalization. Conclusion: The mean diagnostic delay and the mean age of MS diagnosis are critical in Mazandaran Province. Patients with MS develop the disease at an early age and are diagnosed with a long delay. The time of symptom onset is a significant factor in the diagnosis of MS, and in recent years, there have been improvements in the diagnostic process., Competing Interests: The authors declare no conflict of interest in this study., (Copyright © 2023 Iranian Neurological Association, and Tehran University of Medical Sciences Published by Tehran University of Medical Sciences.)

Background: Data on perioperative risk stratification in patients with multiple sclerosis (MS) are limited. In this regard, the present study was conducted to investigate Iranian specialists' approach to surgical counseling for patients with MS (PwMS). Methods: 21 MS specialists were asked about 11 case scenarios with different MS disease statuses, disease-modifying therapies (DMTs), and urgency of the operation. The reasons for refusing surgery or factors that have to be considered before surgery were studied. Results: Overall, Fleiss Kappa was estimated to be 0.091 [95% confidence interval (CI): 0.090-0.093, P < 0.001] indicating a very poor level of agreement among responders. Conclusion: PwMS face surgery for various reasons. Risk assessment of surgery, the effect of various drugs such as anesthetics and DMT on patients, as well as many other aspects of MS are issues challenging the practitioners. Clarifying the various dimensions of these issues requires further research., Competing Interests: The authors declare no conflict of interest in this study., (Copyright © 2023 Iranian Neurological Association, and Tehran University of Medical Sciences Published by Tehran University of Medical Sciences.)

Background: Today, it is estimated that around 5% of multiple sclerosis (MS) patients are in the late-onset category (age at disease onset ≥ 50). Diagnosis and treatment in this group could be challenging. Here, we report the latest update on the characteristics of Iranian patients with late-onset MS (LOMS)., Methods: This cross-sectional study used the information provided by the nationwide MS registry of Iran (NMSRI). The registrars from 14 provinces entered data of patients with a confirmed diagnosis of MS by neurologists. Patients with disease onset at or later than 50 years of age were considered LOMS., Results: Of 20,036 records, the late-onset category included 321 patients (1.6%). The age-standardized LOMS prevalence was around 75 per 100,000 people. 215 patients (67%) were female. Median Expanded Disability Status Scale (EDSS) was 3 (interquartile range: 1.5-5). The majority of the cases (56%) suffered from relapsing-remitting (RR) course while 20% were diagnosed with primary progressive (PP) MS. Significantly higher proportion of male sex, PPMS, and higher EDSS were seen in the late-onset group compared with early-onset and adult-onset cases (p-value < 0.05). Seventy-five (23%) patients did not receive any disease-modifying treatment., Discussion: The more prominent degenerative pathology of LOMS may be the underlying mechanism of the observed differences in comparison to non-LOMS., Conclusion: There are substantial differences and knowledge gaps regarding LOMS which could be the subject of further research., Competing Interests: Declarations of Competing Interests None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: People with multiple sclerosis ‎(MS) and their physicians recognize cognitive retention as an important desired outcome of disease-modifying therapies (DMTs). In this study, we attempted to gather the opinions of Iranian MS experts regarding the treatment approach toward clinical cases with different physical and cognitive conditions. Methods: Opinions of 20 MS specialists regarding the best approach to 6 case scenarios (with different clinical, cognitive, and imaging characteristics) were gathered via a form. Results: The estimated kappa of 0.16 [95% confidence interval (CI): 0.159-0.163; P < 0.001] suggested a poor degree of agreement on the treatment choice among the professionals. Conclusion: Although most specialists agreed with treatment escalation in cases with cognitive impairment, there was no general agreement. Furthermore, there was not enough clinical evidence in the literature to develop consensus guidelines on the matter., Competing Interests: The authors declare no conflict of interest in this study., (Copyright © 2023 Iranian Neurological Association, and Tehran University of Medical Sciences Published by Tehran University of Medical Sciences.)

Background: Sexual dysfunction (SD) is one of the most common complications of multiple sclerosis (MS). The aim of this study was to evaluate the effects of bupropion on SD among female patients with MS., Methods: This double-blind placebo-control randomized clinical trial was conducted on MS patients with SD complaint. Diagnosis was based on the secondary SD subscale scores of the Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19). Accordingly, individuals scoring above 27 based on this scale were diagnosed with SD. The subjects were randomly assigned to the bupropion and placebo groups. Bupropion was administered 75 mg twice daily for twelve weeks. As for the study outcomes, besides MSISQ-19, quality of life (Multiple Sclerosis Quality Of Life-54 (MSQOL-54)), fatigue (Multidimensional Fatigue Inventory (MFI)), depression and anxiety (Hospital Anxiety and Depression Scale), and bupropion tolerability were assessed at baseline as well as at weeks 6 and 12., Results: From 84 patients who met the inclusion criteria, 64 patients completed the trial and were analyzed. Demographics and baseline clinical characteristics were not significantly differed between the two groups. The results showed the mean score of MSISQ-19 from baseline to the end of the study period significantly improved in the bupropion group compared with the placebo (week 6: P: 0.03; week 12: P: 0.03). Similarly, MFI scores showed significant improvement in the bupropion group compared with the placebo group (P: 0.001). Both anxiety and depression scores showed significant alterations at study interval between the two groups (Anxiety: weeks 6 and 12: P:0.04; depression: week 6: 0.01, week 12: 0.02). However, there was no significant change in the MSQOL-54 score between the two groups., Conclusion: The results of the study substantiated that bupropion can be an effective agent for SD improvement in female patients with MS. Further clinical trials with larger sample sizes can more accurately evaluate the observed findings., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Fatigue is a common complication associated with multiple sclerosis (MS). The aim of this study was to evaluate the impact of dalfampridine and amantadine on fatigue in patients with MS. Methods: This was a randomized, double-blind, clinical trial on patients with MS. The recruited patients were adults (≥ 18 years old) diagnosed with MS; their Expanded Disability Status Scale (EDSS) was between 0.0 and 5.5, and their fatigue was confirmed by the Modified Fatigue Impact Scale (MFIS). They were randomly assigned to the amantadine (100 mg twice daily) and dalfampridine (10 mg twice daily) for eight weeks. The primary outcome was the improvement of fatigue score, and the secondary outcome was assessment of quality of life by the Short-Form Health Survey (SF-36) and any reported side effects. Results: A total of 69 patients were recruited, and 54 of them were analyzed. The mean MFIS significantly improved in both groups after one and two months compared to baseline: amantadine: first month: 40.63 ± 14.35 (P = 0.040), second month: 36.56 ± 17.12 (P = 0.010); dalfampridine: first month: 38.29 ± 15.23 (P = 0.001), second month: 34.26 ± 18.30 (P = 0.001). However, the amount of changes from baseline was not significantly different (amantadine, P = 0.090; dalfampridine, P = 0.130). The amount of changes in quality of life showed no significant improvement (P = 0.210). Conclusion: The results showed that dalfampridine was not different with amantadine in improving fatigue in patients with MS; besides, it showed an acceptable safety profile. Therefore, it can be considered as a possible beneficial therapeutic agent in MS fatigue., Competing Interests: The authors declare no conflict of interest in this study., (Copyright © 2022 Iranian Neurological Association, and Tehran University of Medical Sciences.)

Background: Multiple Sclerosis (MS) patients experience a variety of disease caused disabilities that makes them more vulnerable to the effects of disasters. This study aimed to review all existed studies about disasters and related disaster management planning about MS patients., Methods: The PubMed, Google Scholar, Scopus, and Web of Science, ProQuest, science direct , and grey literature databases were searched up to the mid of 2021. All obtained titles were assessed by the inclusion criteria. Abstracts of the relevant titles were reviewed and eligible articles/documents were included for full text review and data abstraction., Results: From 24616 Articles/documents, finally 15 documents (13 articles, and 2 books) were selected. In 8 articles (53%) specifically, focused on MS patients and, in the rest focused on them as a member of people with disabilities. Most studies (10, 71.4%), emphasized on the disaster induced stress effect on MS patients. In two books/book sections, the disaster preparedness plan for all types of disabilities was presented in general, and MS patients were mentioned as a member of the group of patients with disabilities., Conclusion: Despite the importance of planning in response to disasters to address specific problems of MS patients, there is a lack of proper planning. This is very important and there is an urgent need to develop appropriate planning protocols for addressing the special conditions of MS patients in response to disasters., (Copyright © 2022 HabibiSaravi et al. Published by Tehran University of Medical Sciences.)

Objective: The objective of this study was to evaluate how COVID-19 affects patients with acute ischemic or hemorrhagic stroke outcome., Materials and Methods: This retrospective study was performed on adult patients (> 18 years old) with stroke (ischemic or hemorrhagic) who were admitted to hospital with or without COVID-19. The primary outcome was stroke-related disability, which was measured by mRS at baseline and discharge. Hospital duration, intensive care unit (ICU) admission, and mortality were considered the secondary outcomes., Results: From February 2019 until August 2020, we recruited and analyzed 151 patients, 42 of whom had COVID-19 based on RT-PCR tests or lung CT scan findings. COVID-19 positive patients had higher baseline and final mRS scores than the control group (4.46 ± 0.67 vs 4.79 ± 0.61, P: 0.001, 3.83 ± 1.22 vs 4.46 ± 0.67, P: 0.001). Moreover, stroke patients with COVID-19 experienced a more severe disease and required a higher rate of ICU admission (17 vs 0, P:0.001) and longer hospitalization compared to those without COVID-19 (8.50 ± 7.86 vs 7.5 ± 11.20, P: 0.021). Also, mortality was higher in the COVID-19 group (19 vs 13, P:0.001). There was not any significant differences between the two groups in terms of the involvement of cerebral arteries and type of stroke. Male sex, COVID-19, and ICU admission were the main independent risk factors for death., Conclusion: The results of the study showed stroke patients (ischemic or hemorrhagic) with COVID-19 can have more disabilities and incur more hospital complications and mortality than non-COVID-19 patients., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Iran, as a middle income country, is one of the places with high and rising prevalence of multiple sclerosis (MS). Regarding the substantial economic burden, reviewing the trend in prescribed disease modifying treatments (DMTs) could be of help. Here we studied the DMT information of nearly 14000 MS cases and its trends change for 30 years to improve health services to patients., Methods: The population base of this descriptive-analytical (cross-sectional) study consisted of all MS patients in the nationwide MS registry of Iran (NMSRI), up to August 1, 2021. Registrars from 15 provinces, 24 cities, 13 hospitals,8 MS associations, 16 private offices, and 7 clinics had entered the data., Results: Overall, 14316 cases were enrolled. The majority (76.1%) were female. The youngest and eldest patients were 5 and 78 years old, respectively. Diagnosis delay was under one year in most cases (median: 0, IQR: 0 - 1). Most (61.4%) had RRMS. Generally, platform injectables (IFN beta, glatiramer acetate) were the most used DMTs until 2010. It seems that introduction of newer agents (antiCD20s and oral DMTs) resulted in a decrease in the use of former drugs since around 2015. Some unusual practices are prominent such as using not approved DMTs for PPMS over the years, or administering high efficacy drugs like natalizumab for CIS. The results indicate the remaining popularity of first line injectable DMTs in female and pediatric patients., Discussion: Mean age (SD) at onset in our study (29 ± 8.8) is near the statistics in Asia and Oceania (28 ± 0.7). Concerns about COVID-19 had a noticeable impact on administering high efficacy drugs like rituximab and fingolimod. However, in male patients this approach has not been the case. It may be related to more aggressive disease course in this group. The other possible explanation could be planning for pregnancy in female cases. The popularity of platform injectable drugs in pediatric MS may be related to its favorable safety profile over the years. Another point in this group, is the superiority of rituximab over other highly efficient medications., (Copyright © 2022. Published by Elsevier B.V.)

Background: Admittedly, little is known about the epidemiological signatures of familial multiple sclerosis (FMS) in different geographical regions of Iran., Objective: To determine the epidemiology and the risk of FMS incidence in several provinces of Iran with a different ethnic population including, Fars, Tehran, Isfahan (Persians), and Mazandaran (Mazanis), Kermanshah (Kurds), and Chaharmahal and Bakhtiari (Lors)., Methods: This cross-sectional registry-based study was performed on nationwide MS registry of Iran (NMSRI) data collected from 2018 to 2021. This system, registers baseline characteristics, clinical presentations and symptoms, diagnostic and treatments at regional and national levels., Results: A total of 9200 patients including, 7003 (76.1%) female and 2197 (23.9%) male, were participated. About 19% of patients reported a family history of MS; the order from highest to lowest FMS prevalence was as follows: Fars (26.5%), Chaharmahal and Bakhtiari (21.1%), Tehran (20.5%), Isfahan (20.3%), Mazandaran (18.0%), and Kermanshah (12.5%). Of all FMS cases, 74.7% (1308 cases) were female and 25.3% (442 cases) were male. FMS occurrence was much more common in females than males (P-value = 0.001). Further, the mean age at onset was 30 years among FMS cases. A substantially higher probability of relapsing-remitting MS and secondary-progressive MS was found among FMS cases than sporadic MS (SMS) (P&#95;value = 0.001). There was no significant difference in Expanded Disability Status Scale (EDSS) scores between FMS and SMS. The majority of FMS cases were observed among first-degree relatives, with the highest rate in siblings. There was a significant association between MS risk and positive familial history in both maternal and paternal aunt/uncle (P&#95;value = 0.043 and P&#95;value = 0.019, respectively). Multiple sclerosis occurrence among offspring of females was higher than males (P&#95;value = 0.027)., Conclusions: In summary, our findings imply a noteworthy upward trend of FMS in Iran, even more than the global prevalence, which suggests a unique Atlas of FMS prevalence in this multi-ethnic population. Despite the highest rate of FMS within Persian and Lor ethnicities, no statistically significant difference was observed among the provinces., (© 2022. The Author(s).)

This study aimed to investigate the association between serum levels and polymorphic variants of IL-35 with susceptibility, clinical features, and disease severity in multiple sclerosis (MS) patients.This case-control study recruited 186 MS patients and 195 sex- and age-matched healthy controls. Serum levels and polymorphic variants of IL-35 were determined by ELISA and restriction fragment length polymorphism (RFLP)-PCR or high resolution melting (HRM) analysis methods, respectively. In addition, by in silico analysis, we evaluated the location and function of the polymorphism.Serum levels of IL-35 were significantly lower in the patients than those of healthy controls (49.3 ± 3.7 vs. 69.5 ± 7.8, p = 0.009). EBI3 rs4740 polymorphism of IL-35 was associated with 2.2-fold increased risk of MS susceptibility (95% CI, 1.3-3.9, p = 0.005). However, there were no differences in the genotype distribution and allele frequencies of IL-35 rs568408 between the patients and controls (p > 0.05). In silico results showed that variation in IL-12A and EBI3 may affect on protein pathways of the cells and different components of the immune system such as NF-κB and INF-γ.The results show that IL-35 polymorphisms might be a genetic risk factor for the development of MS., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Regarding the high prevalence of multiple sclerosis (MS) and COVID-19 in Iran, a multicenter study of COVID-19 in Iranian MS patients with is carried out to address the concerns of this population., Methods: Data on MS patients with COVID-19 from nine provinces of Iran were entered in a web-based registry system, between July 2020 and March 2021. Among the COVID-19 symptoms, dyspnea, altered mental status, or those resulting in hospital admission were considered severe., Results: A total of 397 eligible patients were identified. In addition, 310 (78%) were female. The mean age was 36.5 ± 9.5. 294 (74%) patients had relapsing- remitting form. Also, four patients (1%) expired due to COVID-19 infection. The mean duration of admission in hospitalized patients was 9 (± 5.3) days. MRI was performed on 111 (28%) patients after developing COVID-19. MRI changes were observed in 27 (24%) of these cases. MS drug was changed in 26 (6%) patients. Steroid use in the past three months (OR: 2.43, 95% CI: 1.003-5.88) (p value: 0.049) and antiCD20s (OR: 4.03, 95% CI: 2.41-6.68) (p value < 0.001) showed significant association with severe COVID-19 symptoms., Conclusion: The death rate of COVID-19 among MS patients (1%) is lower than the overall death rate of the pandemic in Iran (3%). Those who received steroid in the past three months may be at increased risk of more severe forms of COVID-19. There are still doubts about the effect of anti CD20s on COVID-19 severity., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: There is limited evidence about the neurological manifestations of COVID-19 in infected patients. In this report, we describe three patients with ischemic stroke associated with COVID-19 infection., Methods: We report 3 cases of adult patients with ischemic stroke and novel coronavirus 2019 infection. Case 1 is an 88-year-old female with acute left hemiplegia and right peripheral facial paresis that she had a fever along with stroke symptoms. Case 2 is an 85-year-old female with left hemiplegia and drowsiness who had a weakness, asthenia, and dry cough 3 days before appearing stroke signs. Case 3 is a 55-year-old male with acute Broca's aphasia and right hemiplegia who experience fever and respiratory problems 3 days after admission., Results: The clinical symptoms of infected patients with COVID-19 have been associated with severe symptoms of ischemic stroke. Two patients were admitted to the ICU. RT-PCR of the oropharyngeal sample was positive in three cases. All patients had the involvement of large cerebral arteries., Conclusion: The mechanism by which COVID-19 causes ischemic stroke is unknown but it is likely by production inflammatory cytokines or direct infection of cerebral arteries. Therefore, regarding the current situation of the COVID-19 pandemic, it is indispensable that the possible diagnosis of COVID-19 vasculopathy is considered in all ischemic strokes of unclear etiology.

Cerebrotendinous xanthomatosis is a rare autosomal recessive lipid storage syndrome defined clinically by the triad of progressive neurodegeneration, juvenile cataracts and tendon xanthomas in adults. It is treatable, and a prompt diagnosis can improve outcomes. We describe a patient with this condition who presented with progressive ataxia., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Multiple sclerosis (MS) is a chronic inflammatory disease leading to demyelination and axonal loss in the central nervous system that causes focal lesions of gray and white matter. However, the functional impairments of brain networks in this disease are still unspecified and need to be clearer. Materials and Methods: In the present study, we investigate the resting-state brain network impairments for MS participants in comparison to a normal group using electroencephalography (EEG) and graph theoretical analysis with a source localization method. Thirty-four age- and gender-matched participants from each MS group and normal group participated in this study. We recorded 5 min of EEG in the resting-state eyes open condition for each participant. One min (15 equal 4-sec artifact-free segments) of the EEG signals were selected for each participant, and the Low-Resolution Electromagnetic Tomography software was employed to calculate the functional connectivity among whole cortical regions in six frequency bands (delta, theta, alpha, beta1, beta2, and beta3). Graph theoretical analysis was used to calculate the clustering coefficient ( CL ), betweenness centrality ( BC ), shortest path length ( SPL ), and small-world propensity ( SWP ) for weighted connectivity matrices. Nonparametric permutation tests were utilized to compare these measures between groups. Results: Significant differences between the MS group and the normal group in the average of BC and SWP were found in the alpha band. The significant differences in the BC were spread over all lobes. Conclusion: These results suggest that the resting-state brain network for the MS group is disrupted in local and global scales, and EEG has the capability of revealing these impairments.

Background: Fingolimod was the first oral therapy approved for treating relapsing-remitting multiple sclerosis (RRMS) in 2010. This open-label study evaluated the safety and efficacy of fingolide R , 0.5 mg in Iranian MS patients during one-year follow-up., Methods: A multicenter, open-label, longitudinal was designed to evaluate the safety and efficacy of fingolide R , 0.5 mg over a one-year follow-up period across 11 centers. The patients were visited by their neurologists every two months to evaluate possible adverse events and clinical disease activity considered by recording Kurtzke's Expanded Disability Status Scale (EDSS)., Results: A total of 252 patients with the mean treatment duration of 343±45.70 days were. 20 patients experienced adverse events (AEs) and serious adverse events (SAEs) such as resistant urinary tract infection (UTI), premature atrial contraction (PAC), skin allergic reaction, macular edema, chicken pox, zona, panic attacks, and exacerbations associated with steroids treatment, all of which led to Fingolide R discontinuation. The mean EDSS decreased from (2.15±1.29, 95%CI: 1.99to2.32) at baseline to (1.85±1.22, 95%CI: 1.68to2.02) at 12th month (final visit) while a p-value revealed significant differences comparing baseline and final EDSS (p<0.001). Mean annualized relapse rate (ARR) of the patients in one year prior to the study was (0.006±0.016, 95%CI: 0.004to0.008) which changed to (0.005±0.016, 95%CI: 0.003to0.007) at the end of the study period. Patients with a 12-month period of fingolide R treatment experienced sustained ARR and disease progression (p<0.001)., Conclusion: The obtained findings suggest that the administration of Fingolide R , 0.5 mg (Fingolimod, Osvahpharma, Tehran, Iran) is safe and efficient for Iranian MS patients., (Copyright © 2020, Babol University of Medical Sciences.)

Discharges of dyes-containing wastewater from industries have created global concern. Removal of these substances from aqueous solution is very important and essential. Magnetic chitosan coated with ZIF-8 was prepared successfully and used to eliminate cationic dye malachite green in various conditions. To find the effectiveness of ZIF-8 towards malachite green removal, their surface interaction was investigated using density functional theory (DFT) calculations for the first time which the results show physisorption of malachite green on ZIF-8. The characteristics of adsorbent synthesized were evaluated using XRD, FTIR, FE-SEM, TEM and TGA analysis. In addition, the influence of different parameters on malachite green removal was investigated. The results showed that pH = 7, 40 mg of adsorbent dosage, 10 mg/L initial concentration, 40 min contact time and temperature of 25 °C were obtained as an optimum values for Fe 3 O 4 @chitosan@ZIF-8. The equilibrium data were in good agreement with the Langmuir model having maximum capacity (q m ) value of 3.282 mg/g. The experimental data revealed that the adsorption process obeyed to pseudo-second order kinetic model. It was concluded that Fe 3 O 4 @chitosan@ZIF-8 can be utilized as an efficient and effective adsorbent for removal of toxic malachite green dye from aqueous solution., (Copyright © 2020. Published by Elsevier B.V.)

The first treatment for multiple sclerosis exacerbation is usually short-term intravenous methylprednisolone (IVMP), with or without a regimen of oral prednisone taper (OPT). This study aims to evaluate the effects of IVMP and OPT in comparison with IVMP alone in raising the risk of urinary tract infection (UTI) and posttreatment improvement of urinary tract symptoms in patients with relapsing-remitting multiple sclerosis. This double-blind randomized clinical trial was conducted on 56 people with multiple sclerosis relapse who had undergone methylprednisolone for 5 days. Patients were randomly split into two groups: oral prednisolone and placebo (tapering for 20 days). Demographic data, duration of multiple sclerosis, urinary tract symptoms, the Expanded Disability Status Scale (EDSS) score, and urine data were analyzed. The incidence of UTI in the intervention and control groups did not differ significantly ( p =560). However, the improvement of urinary tract symptoms in the intervention group was significantly more favorable than in the control group ( p ≤ 0.001). Furthermore, administering OPT after IVMP did not increase the risk of UTI occurrence in patients with multiple sclerosis exacerbation. The urine analysis results did not show any differences at baseline and after the corticosteroid tapering regimen. Due to the risk of infection by corticosteroids, it is no longer necessary to do further urinary screening in this group of patients., Competing Interests: The authors declare that they have no conflict of interests., (Copyright © 2021 Aliyeh Bazi et al.)

Background: Relapse is one of the main features of multiple sclerosis (MS). Corticosteroids are the first line of management during MS relapse. Since tapering or non-tapering prednisolone after corticosteroid pulse has been a controversial issue, this clinical trial is designed to evaluate the efficacy and safety of the tapering regimen., Methods: Having been treated by intravenous methylprednisolone (IVMP) pulse, sixty-six patients with MS-relapse were randomly assigned to receive oral prednisolone tapering (OPT) or placebo. The regimen was administered in line with the study protocol and the dose was tapered over 20 days. Demographics and symptoms, impact on activities of daily living (ADL), and management procedures were recorded according to Assessing Relapse in Multiple Sclerosis (ARMS) Questionnaire. The incidence of adverse events was assessed using the same questionnaire. Patients' disability improvement was assessed using the Extended Disability Scale (EDSS) during relapse, and over the first, third, sixth months following treatment., Results: As shown by the results of the questionnaire, 75% reported that their ADL was not or minimally affected by OPT and there was no significant difference in terms of ADL after treatment between the two groups (p=0.3). The effect of treatment on return to the previous state of health (RSH) showed that there were no differences between the two groups of the study (p=0.5). The improvement of disability in the two groups of oral prednisolone and placebo did not indicate a difference in terms of EDSS in the first and third and six months (p = 0.5, p = 0.9, p=0.3, respectively). Also, the occurrence of some side effects such as weight gain (p = 0.000) and increased appetite (p = 0.004) was higher in the OPT group., Conclusion: The findings of this study revealed that the efficacy of an OPT after a corticosteroid pulse is non-superior to IVMP plus only in case the safety and tolerability profile are comparable., (Copyright © 2020. Published by Elsevier B.V.)

Introduction: The incidence rate of MS is a valuable indicator of the recent changes in the risk of this disease, and it is widely implicated for health planning purposes., Objectives: This study aims to determine the MS incidence over the past eleven years in Mazandaran province and to compare it with the other parts of Iran and the world., Materials and Methods: This retrospective study is conducted in Mazandaran province by using registered data in the files of the patients with their consent. The yearly crude incidence rates, age, and sex-specific incidence rates and directly standardized incidence rates of this population are calculated, and the temporal changes in the incidence rates are analyzed., Results: 662 (26%) male patients with the mean (SD) age of 32.6 (9.48) and 1884 (74%) female patients with the mean (SD) age of 31.9 (9.15) are studied. The direct standardized incidence rate of MS was 3.28 in 100.000 in 2008 and reached 4.17 in 100.000 in 2018, and this increase was significant (p<0.05). Also, the yearly prevalence of MS increased from 24.4 to 72.5 in this period., Conclusions: The MS incidence has increased in Mazandaran. The potential role of some genetic or environmental factors needs further investigation., Competing Interests: The authors have declared that no competing interests exist.

Background: Information of Previous studies on the prevalence of MS, including our study conducted 12 years ago, used to shape global prevalence map of MS. According to those results, Iran placed in medium-prevalence MS region in the world Atlas of MS 2013.This study aimed to investigate the prevalence of MS in Mazandaran province after 12 years and the need for possible changes in the global map of the prevalence of MS., Methods: We included all MS patients living in Mazandaran province in 2018 in this descriptive cross-sectional study. We updated our pre-existing registration questionnaires which included demographic information and medical data of MS patients by interview. We obtained the demographic profile of Mazandaran province from the most recent census in 2016 and the National Civil Registry of the Mazandaran province for calculating prevalence of MS., Results: The total number of MS patients in Mazandaran was 2418 (25.8% male and 74.2% female) with a female to male ratio of 2.9. Based on the local population of 3,332,556, (50.4% male and 49.6% female), this study showed a prevalence of 72.5 per 100,000 for MS in this region. The prevalence of this disease by gender was 37.1 per 100,000 for men and 108.5 per 100,000 for women. The mean (SD) age of the patients at the time of the study was 38.5 (10.1) years with a minimum of 15 and a maximum of 75 years. The most common type of MS was Relapsing-Remitting MS with 86%., Conclusions: All recent studies showed significant upward trend in the prevalence of MS around the world. Based on the results of our study and many other studies in Iran, the Atlas of MS prevalence map needs to be update. Iran's status should be changed to the high-prevalence of MS in the new Atlas. Due to the increasing prevalence of MS, we suggest an adjustment in the Global MS Prevalence Scale.

Competing Interests: The authors declare that there are no conflicts of interests of this paper.

This report is about a female child born to a multiple sclerosis mother who continued fingolimod during her first trimester of pregnancy. The child was born with normal full-term delivery but showed neurodevelopmental retardation in the following years. it is recommended that multiple sclerosis patients undergoing treatment with fingolimod use contraceptive methods for at least two months after discontinuation of the medication., (Copyright © 2019. Published by Elsevier B.V.)

Background: As the prevalence and incidence of Multiple Sclerosis (MS) are increasing remarkably in Iran, gathering standardized information regarding the individual's diagnosis, care, and outcomes through a uniform registry system would enable policy-makers to systematically plan for care quality improvements., Objective: To design a valid and reliable Persian version of a minimum data set to be utilized and integrated into the national MS registry system of Iran., Method: The minimum data set consisted of six domains including patient identification, family history of MS, diagnosis, disease course, disability status, and medications. The content validity was assessed based on 27 experts' opinions. Item-Content Validity Index (I-CVI) and Scale-Content Validity Index (S-CVI) were used to assess the questions and their validities. Reliability was evaluated using the intra-class correlation coefficient (ICC) of the test-retest results., Results: For validity appraisal, 27 experts reviewed the developed minimum data set. All the items had I-CVI values higher than the critical value of 0.78 in terms of relevance, clarity, and simplicity, except for "medication start date" and "medication end date" in relevance (I-CVI = 0.75 and 0.73, respectively) and "MS type" in simplicity (I-CVI = 0.76). The total S-CVI scores for relevance, clarity, and simplicity were higher than 0.9. In reliability assessment, 27 patients (out of 74 interviewed patients) were re-interviewed to assess the test-retest reliability. All ICCs were higher than the critical value of 0.7 (in 14 items out of 16), except for "progression to secondary-progressive MS" with the ICC = 0.68 and "the reason for medication discontinuance" with the ICC = 0.64., Conclusion: The use of standardized validated minimum data set has the potential to enable the researchers and policy-makers to systematically compare and analyze patient information. The Persian version of the minimum data set found to be valid and reliable in Iran., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: Cooccurrence of a seizure in a patient with multiple sclerosis (MS) may complicate the management process. Questions, which may complicate the management process of a patient with MS and seizure, include "how should we approach to the patient", "how should we treat the patient", "how should we modify the patient's MS treatment strategy", etc. METHODS: We searched the electronic database PubMed on March 30, 2018 for articles in English that included the following search terms: "epilepsy" AND "multiple sclerosis" or "seizure" AND "multiple sclerosis" since 2013, to obtain the best recent relevant scientific evidence on the topic. A working group of 6 epilepsy and 5 MS experts took part in two consensus workshops in Tehran, Iran, in 2018. The final consensus manuscript was prepared and approved by all participants., Results: The search with words "seizure" and "multiple sclerosis" yielded 121 entries; 10 were relevant to the topic. The search with words "epilepsy" and "multiple sclerosis" yielded 400 entries; 7 were relevant to the topic. We reviewed these 17 articles and also some other references, derived from these articles or relevant to the topic, for the purpose of our review., Conclusion: Cooccurrence of a seizure in a patient with MS may complicate the management process. In this review, we tried to provide answers to the frequently asked questions, considering the best available scientific evidence and expert opinion., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: The characteristics of paediatric neuromyelitis optica spectrum disorder (NMOSD) may indicate the degree of disability and identify factors that predict the response to treatment., Materials & Methods: Among 114 NMOSD patients in an acquired demyelinating syndromes registry at the Sina Hospital, in Tehran, Iran, 10 paediatric NMOSD patients with longitudinal follow-up from 2005 to 2016 were retrospectively identified. The median time between disease onset and diagnosis was 18 months (range 1-108 months)., Results: All patients had a relapsing course, which resulted in disability in six with severe visual impairment and functional blindness in one and impaired ambulation in five patients during follow-up. Azathioprine (AZA) was first drug of choice for prophylaxis, but in five patients new attacks occurred and therapy was switched to rituximab (RTX) with no further relapses after median two years (range 1-3 y) follow-up., Conclusion: Paediatric onset of NMOSD was associated with severe attacks and poor response in 50 % of cases to AZA, RTX seemed to decrease the relapse rate., Competing Interests: The authors declare that there is no conflict of interests.

Background: Mesenchymal stem cells (MSCs) are a potential therapy for various diseases. Here, the results of intrathecal injection of MSCs in multiple sclerosis (MS) patients are reported., Materials and Methods: Four patients were enrolled in the study. Three were male and one was female. There were three secondary-progressive MS patients and one relapsing-remitting MS patient. An amount of 50-80 ml of bone marrow was collected from the patients. MSC cultures were collected for each microbiological examination at each change of medium and passage as well as at the time of sample injection. Then, MSCs were injected into the patients by the intrathecal method. In two patients, the injection was replicated in 1 year., Results: All the patients were followed up for 2 years. Three patients who had secondary progression did not show disease progress after the injection, and the disease entered a stable state. A degree of recovery was observed in two patients. The relapsing-remitting patient suffered an attack that led to corticosteroid injection. None of the patients reported side effects. In terms of magnetic resonance imaging, there were no new plaques or enhanced plaques., Conclusion: This study suggests that injection of MSC can be a suitable method, especially for secondary-progressive patients. It seems that reinjection of these stem cells can be safe and sustaining it positively increases the effects of this therapeutic approach.