Time to Rebaseline Cognitive Performance in People with Multiple Sclerosis?

Abstract

We read with great interest the article by McKay et al analyzing Swedish registry data on the changes observed in cognitive processing speed around a relapse in relapsing-remitting multiple sclerosis. 1 They showed that Symbol Digit Modalities Test scores were depressed in the 30 days preceding a relapse and remained significantly lowered for 30 days afterward. The results of this study are in accordance with previous studies demonstrating that a decline in cognitive function may be observed during inflammatory activity. 2 According to all these studies, processing speed is expected to recover during a postrelapse period of at least 3 months in those people with multiple sclerosis (MS) experiencing a cognitive or more extensive relapse.Although agents used in MS are expected to prevent, at least partially, further cognitive decline, by reducing inflammatory activity and relapse rates, their ability to improve cognitive function is less certain. Numerous observational studies, with several methodological limitations, have presented evidence to support an improvement of cognitive function after initiating a therapeutic agent, 3 and recent and ongoing phase 3 clinical trials of new disease-modifying therapies (DMTs), with more robust designs, have included cognitive function as an outcome measure, with participants undergoing periodic cognitive assessments. 4 The concept of rebaselining has been implemented in the radiological monitoring of the disease, to capture precisely the DMT's therapeutic action and to avoid pseudoatrophy phenomena when applying volumetric measures. Similarly, reassessing the Expanded Disability Status Scale score in the months following a relapse may be needed, because incomplete recovery is considered a poor prognostic factor for future disability. 5 We propose that information about relapses should be kept with the patient's cognitive profile and incorporated into the interpretation of test scores. Algorithms with confidence limits could be calculated from registry or other large datasets to monitor recovery. This could extend the rebaselining concept to cognitive assessment, in both clinical practice and research. Neuropsychological testing should be performed at least 3 months following inflammatory activity (identified via magnetic resonance imaging or clinical examination), as a new baseline, to document the patients' cognitive status. In the era of telehealth and digital self-monitoring, this might be feasible in clinical practice and could enable the optimal detection of individuals in need of cognitive rehabilitation. With regard to clinical trials and other longitudinal datasets, further subanalyses using this concept could further characterize cognitive recovery trajectory after relapses and provide more robust data regarding the impact of DMTs on cognition.