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Introduction: It is generally recommended to avoid live attenuated vaccines in patients treated with high efficacy disease-modifying treatment (DMT). However, a delay in starting DMT in highly active or aggressive multiple sclerosis (MS) might lead to a significant disability., Objective: We aimed to report a case series of 16 highly active RRMS patients who received the live-attenuated varicella-zoster virus (VZV) vaccine during treatment with natalizumab., Methods: This retrospective case series was conducted between September 2015 and February 2022 at the MS Research Center of Sina and Qaem hospital, Tehran, Mashhad, Iran, to identify the outcome of highly active MS patients who received the live-attenuated VZV vaccine on natalizumab., Results: Two males and 14 females were included in this study, with a mean age of 25.5 ± 8.4-year-old. 10 patients were naïve cases of highly active MS, and six were escalated to natalizumab. The patients received two doses of live attenuated VZV vaccine after a mean of 6.72 cycles of natalizumab treatment. Except for the one who experienced mild chickenpox infection, no serious adverse event or disease activity was evident after vaccination., Conclusion: While our data do not confirm the safety of the live attenuated VZV vaccine in natalizumab recipients, it highlights the importance of case-by-case decision-making in MS management based on the risk-benefit assessment., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest, and no funding has been used for the manuscript., (Copyright © 2023. Published by Elsevier B.V.)

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.)