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The Multiple Sclerosis Performance Test (MSPT): An iPad-Based Disability Assessment Tool
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Evidence for a two-stage disability progression in multiple sclerosis.

Emmanuelle Leray1, Jacqueline Yaouanq, Emmanuelle Le Page

  • 1Service d'épidémiologie et santé publique, Centre Hospitalier Universitaire, Rennes, France.

Brain : a Journal of Neurology
|April 29, 2010
PubMed
Summary

Multiple sclerosis (MS) disability progression occurs in two distinct stages. Early focal inflammation drives the first stage, while later disability accumulation appears independent of current inflammation, suggesting new therapeutic targets for MS.

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Area of Science:

  • Neuroscience
  • Immunology
  • Neurology

Background:

  • Disability accumulation in multiple sclerosis (MS) is linked to axonal injury and inflammation.
  • The interplay between focal inflammation, diffuse inflammation, neurodegeneration, and clinical deficits in MS is not fully understood.
  • A two-stage disease model for MS is hypothesized, with early focal inflammation as a potential trigger.

Purpose of the Study:

  • To define and analyze two distinct phases of MS disability progression: Phase 1 (onset to irreversible Kurtzke Disability Status Scale [DSS] 3) and Phase 2 (irreversible DSS 3 to irreversible DSS 6).
  • To investigate the relationship between disability progression in Phase 1 and Phase 2.
  • To identify early clinical markers predictive of disability progression.

Main Methods:

  • Analysis of the Rennes MS database (2054 patients, 26,273 patient-years).
  • Defined two phases of MS based on Kurtzke Disability Status Scale milestones.
  • Utilized Kaplan-Meier estimates and Cox models to assess outcomes and predictive factors.
  • Stratified analysis by phenotype at onset (relapsing vs. progressive).

Main Results:

  • Disability progression in Phase 2 was independent of Phase 1 duration.
  • Median Phase 2 duration remained consistent (6-9 years) regardless of Phase 1 length across the entire cohort and both phenotypes.
  • In relapsing-onset MS, gender, age at onset, initial residual deficit, and early relapses predicted Phase 1 progression but not Phase 2.

Conclusions:

  • MS disability progression follows a two-stage process.
  • Phase 1 is likely influenced by focal inflammation, while Phase 2 appears independent of current focal inflammation.
  • This two-stage model has significant implications for developing future therapeutic strategies in MS.