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

Area of Science:

• Neurology
• Immunology
• Pathology

Background:

• Multiple sclerosis (MS) research traditionally relies on clinical groupings that overlook significant biologic heterogeneity.
• A unified mechanistic framework is needed to bridge the gap between understanding MS immunopathogenesis and clinical metrics.

Purpose of the Study:

• To explicate the spectrum of multiple sclerosis (MS) through a topographical model.
• To advance a cogent mechanistic framework for understanding MS heterogeneity and progression.

Main Methods:

• Review of contemporary evidence on MS pathobiology.
• Analysis of disease description across clinical and sub-clinical detection thresholds.
• Application of a topographical model to frame disease investigation.

Main Results:

• MS is viewed as a spectrum of disease with dynamic, interdependent pathobiological axes, not sequential phases.
• Inflammation and neurodegeneration occur early and continuously throughout the MS disease continuum.
• A gap exists between understanding immunopathologic processes and available measurement tools for MS.

Conclusions:

• A consistently applied mechanistic framework is crucial for research precision in MS.
• This framework will inform discussions on disability progression and patient care in MS.
• Advancing a unified model aids in prognostication and monitoring of treatment outcomes in MS.