Is a motor phenotype at the first relapse associated with greater disability in multiple sclerosis?

Abstract

Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system characterized by marked clinical heterogeneity. The phenotype of the first relapse has been investigated as a potential prognostic marker, particularly whether initial motor manifestations are associated with worse functional outcomes; however, findings remain inconsistent. Objective: To investigate whether a motor phenotype at the first relapse is associated with greater functional disability. Methods: This cross-sectional study included patients diagnosed with Multiple Sclerosis according to the McDonald Criteria for Multiple Sclerosis Diagnosis. Clinical and demographic data were collected through patient interviews and medical record review at a neuroimmunology referral center in Bahia, Brazil. The level of functional disability was determined by the Expanded Disability Status Scale (EDSS), and the phenotype of the first relapse was classified as motor or non-motor. The primary outcome was neurological disability measured by EDSS, analyzed using clinically relevant cutoffs (≥3, ≥4, and ≥6). Multivariable logistic regression models were used to assess associations, adjusting for age at diagnosis, sex, educational level, diagnostic delay, clinical disease course, spinal cord or infratentorial involvement, vascular risk factors, and the number of syndromes at the first relapse. Results: A total of 416 patients with multiple sclerosis were included. In descriptive analyses stratified by first relapse phenotype, no significant differences were observed between motor and non-motor groups regarding age at first relapse, age at diagnosis, sex, progressive disease form, vascular risk factors, or spinal and infratentorial lesion involvement. Patients with non-motor onset presented a higher number of clinical syndromes at the first event. In multivariable logistic regression analysis, motor first relapse was not associated with higher disability and showed a trend toward a protective effect for EDSS ≥3 (OR = 0.56; 95% CI: 0.32–0.97; p = 0.039). Progressive disease form was strongly associated with greater disability (OR = 7.03; 95% CI: 3.16–17.5; p < 0.001), as well as diagnostic delay of 12–36 months (OR = 2.35; 95% CI: 1.40–3.96; p = 0.001) and >36 months (OR = 4.02; 95% CI: 2.33–7.05; p < 0.001). A higher number of clinical syndromes at the first relapse was also independently associated with disability (OR = 1.38; 95% CI: 1.17–1.64; p < 0.001). Conclusion: Motor first relapse was not associated with worse disability and showed a modest protective association. However, long-term disability in multiple sclerosis appears to be more closely related to the overall clinical inflammatory burden at the first relapse and diagnostic delay than to the specific anatomical system initially involved, suggesting that the extent of clinical involvement in the first event may be a more relevant prognostic marker of future disability.