The topographical model of MS: Empirical evaluation of the recapitulation hypothesis.

Objective: Using the topographical model of multiple sclerosis (MS) to evaluate a longitudinal cohort we (1) test the recapitulation hypothesis, positing that patients' "disease topography" predicts the clinical pattern of disability accumulation; and (2) identify leading indicators of progression.

Methods: 10 patients who transitioned from relapsing-remitting MS to secondary progressive MS (SPMS) were evaluated. Neurologic exams were analyzed from relapses, at time of SPMS diagnosis, and most recent visit. Functional systems (FS), location/laterality, and recovery were recorded. The pyramidal/motor system was the target FS assessing symptom laterality and severity at relapse and SPMS time-points. Each patient's clinical course was mapped using the topographical model software.

Results: Cohort was 80% female, age 31.6 ± 8.6 years at diagnosis, followed average 23.8 ± 8.8 years, mean 3.1 relapses before SPMS. 83.3 ± 0.2% of relapse symptoms were present at transition to SPMS, increasing to 91.0 ± 0.2% at most recent visit. This demonstrates concordance between the topographical distribution of relapse symptoms and deficits from subsequent progression. In the topographical model, progression became apparent 7.75 years earlier than SPMS was diagnosed in practice.

Conclusions: We demonstrate the model's utility in depicting patients' disease topography as the loci of clinical progression. This could allow for earlier recognition of progressive disease by identifying leading indicators of progression.