Predicting disability worsening in relapsing and progressive multiple sclerosis

Multiple sclerosis (MS) is a clinically heterogeneous disease, which complicates expectant management as well as treatment decisions. This review provides an overview of both well established and emerging predictors of disability worsening, including clinical factors, imaging factors, biomarkers and treatment strategies.

In addition to well known clinical predictors (age, male sex, clinical presentation, relapse behaviour), smoking, obesity, vascular and psychiatric comorbidities are associated with subsequent disability worsening in persons with MS. A number of imaging features are predictive of disability worsening and are present to varying degrees in relapsing and progressive forms of MS. These include brain volumes, spinal cord atrophy, lesion volumes and optical coherence tomography features. Cerebrospinal and more recently blood biomarkers including neurofilament light show promise as more easily attainable biomarkers of future disability accumulation. Importantly, recent observational studies suggest that initiation of early-intensive therapy, as opposed to escalation based on breakthrough disease, is associated with decreased accumulation of disability overall, although randomized controlled trials investigating this question are underway.

Understanding risk factors associated with disability progression can help to both counsel patients and enhance the clinician's availability to provide evidence-based treatment recommendations.