Cognitive Impairment Worsens During Multiple Sclerosis Relapse


Patients with relapsing multiple sclerosis showed declining scores on tests of cognitive processing speeds from baseline to 3-month follow-up post-relapse.

Ralph H. Benedict, PhD

Ralph H. Benedict, PhD

Results from a study that examined patients with relapsing-remitting multiple sclerosis (MS) confirmed that cognitive impairment worsens during MS relapse, often without full recovery.1

The case-control study included 50 patients diagnosed with relapsing-remitting MS who were between 18 and 65 years, had an Expanded Disability Status Scale (EDSS) score of <7.0, relapsing remitting or active secondary progressive disease course, and NP testing within 4 years of study enrollment. To be included in the study, patients must have experienced a decline in Symbol Digit Modalities Test (SDMT) of at least 3 points to demonstrate cognitive decline. Each patient was evaluated at baseline, at the point of relapse, and at 3-month follow-up. Relapses were treated with a 5-day course of repository corticotrophin injection (HP Acthar Gel; Mallinkrodt).

At each time point, patients were evaluated on changes in cognitive processing speed, as measured by the SDMT, as well as measures of memory, ambulation, and manual dexterity. The investigators sought to identify any correlations between these changes and EDSS scores, magnetic resistance imaging (MRI), and cognitive reserve.

A regression model that predicted the change score on SDMT was computed (FU-RL) for each participant in the relapsing group. Within that model, the SDMT change score acted as the dependent variable, whereas other independent variables of the study included baseline demographics, volume and number of gadolinium-enhancing lesions at the relapse time-point, annualized relapse rate prior to enrollment, and baseline values for Depression Inventory Fast Screen (BDIFS), Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ), and Fatigue Severity Scale (FSS).

At time of relapse, patients saw an SDMT decline from 55.2 (SE = 2.6) to 44.6 (SE= 2.8; d= 0.7), recovering to 51.7 (SE = 2.8; d = 0.5) at 3-months post-relapse—all significant differences from stable controls (all P <.001). In addition, the investigators observed correlations between baseline and relapse (r = 0.81) and relapse and follow-up (r = 0.81), with between group differences significant for relapse (P = .001).

Notably, patients in the relapsing group experienced a significant slowing on the Timed 25-Foot Walk Test (P = .03), with significant change from baseline (5.4) to relapse (6.7; P = .003). The change recorded from relapse to 3-month follow-up was also significant (P = .005).

READ MORE: Cladribine Effectively Reduces Risk of Secondary Progressive Multiple Sclerosis

“Nevertheless, quantifying mental status changes during relapse remains an important endeavor and we believe the current data contribute to the mission of widening the scope of what can be easily ascertained about acute disease activity in people with MS,” the study authors concluded.

The findings contribute to a growing body of evidence about the long-term impact of relapses. Indeed, new research presented at ACTRIMS 2020 showed that incomplete recovery following an MS relapse may contribute to 10-year disability in patients with relapsing MS.2 That study, presented by Marinos Sotiropoulos, MD, of Brigham and Women’s Hospital, and colleagues, showed that there was a significant association between 10-year EDSS and the percentage of relapses with complete recovery (P <.001) and age at first symptom onset (P <.004).


1. Benedict RHB, Pol J, Yasin F, et al. Recovery of cognitive function after relapse in multiple sclerosis. Multiple Sclerosis Journal. Published online January 23, 2020. doi: 10.1177/1352458519898108

2. Sotiropoulos MG, Lokhande H, Rosso M, et al. The Contribution Of Relapse Recovery To Long-term Outcomes In MS. Presented at: 2020 ACTRIMS Forum. February 27-29, 2020; West Palm Beach, FL. Abstract LB317.

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