Abstract

Introduction: Late-onset Multiple Sclerosis (LOMS) constitutes a challenge considering the ageing population, differential diagnosis and increased prevalence of comorbidities. Its characterisation is essential to define the best therapeutic strategies for the future Objectives/Aims: To determine the frequency and relevant clinical characteristics of LOMS Methods: Longitudinal, observational, retrospective and prospective study including the registry of patients of the Programa de Esclerosis Multiple UC. We included patients who began with MS symptoms > 50 years old. Demographic and clinical variables were collected from 1995 until March 2024 Results: From a population of 949 patients, 55 (5.7%) were identified as having LOMS with median age at disease onset of 53 years (range: 50-75), 67.5% were female, median diagnostic delay of 1 year (range: 0-15), 14.5% reported a family history of MS, while 67% patients had a history of smoking. At the time of diagnosis, 51% presented with relapsing-remitting MS (RRMS) and 38% primary progressive MS (PPMS) phenotypes. The most common comorbidities included cardiovascular diseases (47%), mental health disorders (42%), other neurological diseases (33%), osteoarthritis (9%) and history of cancer (7%). In the first recorded neurological evaluation, the median EDSS score was 2.0 (range: 0-6.5) for RRMS and 3.0 (range: 1.0-6.0) for PPMS. The most prevalent first disease presentation was motor (47%), brainstem (22%) and sensory (13%) symptoms. Gadolinium-enhancing lesions were observed in 28% and 23% had spinal cord lesions, while 75% presented with positive oligoclonal bands (isoelectric focusing available since 2010). Regarding treatment, 51% of patients with LOMS started with a moderate-efficacy disease-modifying therapy (DMT), while 27% started with high-efficacy DMT. However, 24% were exposed to both during follow-up. Two patients (3.4%) developed cancer during follow-up (1 breast and 1 kidney). The annualized relapse rate (ARR) was 0.06 for the LOMS cohort during a median follow-up of 4 years Conclusion: This study provides valuable findings from a Latin American population with LOMS, with a higher frequency of PPMS and low ARR, consistent with other studies. We highlight the high percentage of comorbidities at disease onset, including cardiovascular disorders and cancer, considering that a high proportion of patients were candidates to receive DMT, this information should be taken into account when defining future treatments and prevention strategies in an ageing population