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

Abstract

ObjectiveUsing 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.Methods10 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.ResultsCohort 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.ConclusionsWe 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.

Menopause does not modify disability trajectories in a longitudinal cohort of women with clinically isolated syndrome and multiple sclerosis followed from disease onset

“…It has been suggested that the loss of ovarian estrogen after menopause could lead to a decrease in brain repair, which would promote accelerated neurodegeneration and the subsequent disability progression [11]. However, this effect attributed to hormones in menopause could be mainly driven by the effect of age and disease duration, which are known to have a clear impact on disability accumulation [19][20][21].…”

Understanding multiple sclerosis as a disease spectrum: above and below the clinical threshold

“…2 ). Importantly, this model incorporates the role of lesion localization (disease topography) and the extent of compensatory functional reserve, two increasingly recognized drivers of disability accrual [ 8 , 9 ] that were previously absent from traditional clinical course depictions.…”