The natural history of brain volume loss among patients with multiple sclerosis: a systematic literature review and meta-analysis

Background: Multiple sclerosis has been associated with progressive brain volume loss.

Objective: We aimed to systematically summarize reported rates of brain volume loss in multiple sclerosis and explore associations between brain volume loss and markers of disease severity.

Methods: A systematic literature search (2003-2013) was conducted to identify studies with ≥12months of follow-up, reported brain volume measurement algorithms, and changes in brain volume. Meta-analysis random-effects models were applied. Associations between brain volume change, changes in lesion volume and disease duration were examined in pre-specified meta-regression models.

Results: We identified 38 studies. For the meta-analysis, 12 studies that reported annualized percentage brain volume change (PBVC), specified first-generation disease-modifying treatments (e.g., interferon-beta or glatiramer acetate) and used Structural Image Evaluation of Normalized Atrophy algorithm were analyzed. The annualized PBVC ranged from -1.34% to -0.46% per year. The pooled PBVC was -0.69% (95% CI=-0.87% to -0.50%) in study arms receiving first-generation disease-modifying treatments (N=6 studies) and -0.71% (95% CI=-0.81% to -0.61%) in untreated study arms (N=6 studies).

Conclusions: In this study, the average multiple sclerosis patient receiving first-generation disease-modifying treatment or no disease-modifying treatment lost approximately 0.7% of brain volume/year, well above rates associated with normal aging (0.1%-0.3% of brain volume/year).