Clinical acute manifestations in the multiple sclerosis onset associated with worse functional outcomes

Background: Multiple sclerosis (MS) is a chronic autoimmune disease with a wide variability of neurological manifestations in the first acute episode. Some symptoms may be associated with long term neurological dysfunction and functional dependence in the patient’s daily activities. The Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC) are complementary and aim to quantify the degree of disability of patients with MS. In this sense, data regarding the incidence and liability implications of the first acute manifestation are still lacking. This knowledge may help re-evaluate therapeutic protocols in MS. Objective: To identify the clinical syndromes in MS onset that are associated with worse functional outcomes. Methods: This study is a cross-sectional design with patients diagnosed with MS, according to the McDonald 2017 criteria, who were followed up at a neuroimmunology reference center in Bahia, from January 2019 to May 2024. This study is part of an ongoing cohort study that evaluates the clinical features of patients followed in this reference center. The clinical manifestations of the first acute episode were collected through a clinical interview and compiled into seven major syndromes: visual, motor, sensory, ataxic, postrema area, cranial nerves and autonomic. Functional outcomes were assessed using the EDSS (assessed by neurologists and/or neurology residents) and the MSFC (assessed by trained researchers).Patients with MS and a relapse in the last three months were excluded. The Mann-Whitney test was used to assess the association of the first clinical syndrome and worse functional outcomes. Linear regression was performed to address the effect of each clinical syndrome in both functional scales, considering only syndromes that were associated in univariate analysis with worse functional outcome. Results: A total of 274 patients were included in the study, of whom the majority were female (71.5%), non-white (71.9%) and complete secondary education (79.6%). Our sample’s mean age was 42 (SD±13) with a median length of disease of 8 years (4-13), a median EDSS of 2 (0-4.5), a global MSFC of -0,6 (-1.6 to 0.0), and relapsing-remitting clinical form as the most common (87.6%). Worse EDSS and global MSFC scores were identified in those patients who presented motor (p< 0.01), ataxic (p<0.01), and autonomic syndrome (p<0.01) in the first acute episode.In multivariate analysis considering EDSS as the dependent variable, motor and autonomic syndrome remained associated with worse functional outcome (p<0.001, B=0.373; p0,05, B=0.163, respectively). Regarding MSFC, we found that motor, ataxic, and autonomic syndromes remained associated (p<0.05, B=-0.206; p<0.05, B=-0.188; p<0.05, B=-0.156). Conclusion: Among the possible symptoms in the first acute episodes of patients with Multiple Sclerosis, motor, ataxia and dysautonomic symptoms may be associated with worse functional status.