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Updated: Jul 20, 2026

Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
[The natural history of multiple sclerosis]
Christian Confavreux1, Sandra Vukusic
1Service de neurologie A, centre de coordination Edmus et Inserm U433, hôpital neurologique Pierre-Wertheimer, 69677 Lyon, Bron. christian.confavreux@chu-lyon.fr
Abstract:
The course of multiple sclerosis (MS) results from the interplay of two clinical processes, relapses and progression. Three main clinical forms may be identified as relapsing-remitting, secondary progressive and primary progressive. The disease appears on average at the age of 30 and follows a remitting or a progressive course in 85% and 15% of the cases, respectively. Initial symptoms are related to an isolated or combined disturbance(s) of the long tracts of the central nervous system, of the brainstem, or of the optic nerve in 70%, 20% and 25% of the cases, respectively. The relapse rate is one relapse on average every other year. After an exacerbating-remitting onset of MS, secondary progression appears after 19 years on average. The median time to reach the landmarks of irreversible disability are 8 years regarding limitation of ambulation, 20 years for walking with a stick, and 30 years for wheel-chair dependency. In fact, MS prognosis is highly variable depending on individuals. All the intermediate types do exist between malignant forms, possibly lethal, and benign forms (circa 30% of the cases) that allow normal daily life. The clinical and paraclinical predictive factors identified so far have been acknowledged statistically. They provide little help however, if any, when an individual is concerned. Recent research has showed that relapses have only a marginal effect, relatively to progression, on the accumulation of irreversible neurological disability. Furthermore, the age when reaching the landmarks of irreversible disability is essentially similar whatever the mode of onset of MS, be it exacerbating-remitting or progressive. In spite of the outstanding clinical polymorphism of MS, a unifying concept of the disease ("complexity vs heterogeneity") can be put forward.
Insights
Multiple sclerosis (MS) prognosis is highly variable, with progression, not relapses, significantly impacting irreversible neurological disability accumulation. Understanding MS complexity is key despite its heterogeneity.
Area of Science:
- Neurology
- Clinical Neuroscience
Context:
- Multiple sclerosis (MS) is characterized by relapses and progression, with three main clinical forms: relapsing-remitting, secondary progressive, and primary progressive.
- The disease typically manifests around age 30, affecting 85% of patients with a remitting course and 15% with a progressive course.
- Initial symptoms often involve disturbances in the central nervous system's long tracts, brainstem, or optic nerve.
Purpose:
- To analyze the interplay of relapses and progression in multiple sclerosis (MS) and their impact on disease course and prognosis.
- To evaluate the effectiveness of clinical and paraclinical factors in predicting individual MS prognosis.
- To explore a unifying concept for understanding the complexity and heterogeneity of MS.
Summary:
- MS prognosis is highly variable, ranging from benign to malignant forms, with significant individual differences.
- Progression, rather than relapses, is the primary driver of irreversible neurological disability accumulation in MS.
- The age at which irreversible disability landmarks are reached is similar regardless of the initial disease onset (relapsing-remitting or progressive).
Impact:
- Highlights that clinical and paraclinical predictive factors offer limited individual prognostic value in MS.
- Suggests that focusing on progression, rather than just relapses, is crucial for understanding MS disability.
- Proposes a unifying concept of "complexity vs heterogeneity" to conceptualize the diverse clinical presentations of MS.
Related Concept Videos
Multiple Sclerosis l: Introduction
Myasthenia Gravis ll: Pathophysiology

