Abstract
Multiple sclerosis is now diagnosed and treated earlier than in previous therapeutic eras, but the clinical value of this shift depends on whether earlier recognition leads to prevention of irreversible disability rather than simply earlier labeling of disease. This narrative review examines the relationship among contemporary diagnostic criteria, timing and selection of disease-modifying therapies, and disability accumulation. PubMed/MEDLINE was searched in 2026 using combinations of terms related to the McDonald criteria, magnetic resonance imaging biomarkers, high-efficacy treatment, escalation strategies, relapse-associated worsening, progression independent of relapse activity, and pivotal disease-modifying therapy trials. The evidence indicates that the 2024 McDonald criteria can shorten diagnostic delay by incorporating the optic nerve and selected imaging and cerebrospinal fluid biomarkers, while requiring careful exclusion of mimics. Randomized trials establish strong control of relapses and magnetic resonance imaging activity with several high-efficacy therapies, whereas registry studies and meta-analyses increasingly associate early intensive treatment with more favorable long-term disability trajectories than delayed escalation. However, progression independent of relapse activity remains a major source of disability and is incompletely prevented by current therapies. Optimal care therefore requires diagnostic specificity, timely treatment matched to prognostic risk, safety-aware sequencing, and longitudinal monitoring that extends beyond relapse counts.