Cognitive Relapse in Multiple Sclerosis: New Findings and Directions for Future Research

Multiple sclerosis (MS) is a chronic inflammatory, demyelinating disease of the central nervous system, often presenting with brain atrophy and cognitive impairment (CI). In the relapsing-remitting phenotype, cognitive performance is increasingly recognized to decline acutely during MS relapse, with varying degrees of recovery afterwards. Therefore, CI in MS may result from incomplete recovery from episodes of so-called "cognitive relapse", gradual neurodegeneration, or both. Among a variety of validated measures of cognitive performance, the Symbol Digit Modalities Test (SDMT) represents the most sensitive measure of cognitive decline and is easily translated to clinical practice. In fact, cognitive relapse identified using the SDMT has been reported in clinically relapsing cohorts as well as in individuals with no other neurological signs, suggesting that routine cognitive assessment may be necessary to fully appreciate the extent of a patient's disease activity. The aim of this narrative review is as follows: (1) to provide the historical context for neuropsychological assessment in MS, (2) to provide a summation of key studies describing the cognitive relapse phenomenon, and (3) to discuss current gaps in our knowledge and highlight avenues for future research.