Early determinants of long-term outcomes in multiple sclerosis

Abstract

Background

Multiple sclerosis (MS) exhibits remarkable heterogeneity in its clinical course, yet the determinants of long-term disability progression remain incompletely understood. Identifying demographic and clinical predictors of unfavorable trajectories is essential for individualized management.

Objective

To investigate demographic, clinical, and laboratory factors influencing disability progression and relapse dynamics in a large Turkish MS cohort with over two decades of follow-up.

Methods

This retrospective study included 1580 patients diagnosed with MS according to the 2017 McDonald criteria and followed between 1980 and 2020. Data on demographic, clinical, and laboratory parameters were analyzed. Survival analyses assessed time to expanded disability status scale (EDSS) 3 and 6 milestones, and logistic regression identified predictors of progressive disease.

Results

The cohort comprised 1092 females and 488 males (mean follow-up: 7.5 ± 5.7 years). Male sex and lower educational attainment were associated with faster disability accumulation (log-rank, p < 0.005 and p < 0.001, respectively). Motor, cerebellar, and spinal onset were significant predictors of a progressive phenotype, while optic neuritis, sensory, and brainstem onset indicated a relapsing–remitting course. Neither smoking, family history, nor oligoclonal band (OCB) positivity influenced disability progression. Inter-relapse intervals shortened until the fifth relapse, thereafter stabilizing, marking a potential inflection point in inflammatory activity.

Conclusion

This long-term cohort highlights distinct demographic and clinical predictors of MS progression. Early disability accumulation, particularly before reaching EDSS 3, appears critical in determining long-term outcomes. These findings emphasize the importance of early, aggressive therapeutic intervention within the initial disease phase to alter the trajectory of MS progression.