Quantifying cognition and fatigue to enhance the sensitivity of the EDSS during relapses.

BACKGROUND: Cognition is affected by relapses in persons with multiple sclerosis (PwMS), yet the Expanded Disability Status Scale (EDSS) does not readily detect cognitive changes. OBJECTIVE: The objective of this study is to improve the detection of cognitive decline during relapses, by incorporating the Symbol Digit Modalities Test (SDMT) into the cerebral Functional System Score (CFSS) of the EDSS. METHODS: This prospective study recruited PwMS from three dedicated MS centers. All subjects had EDSS, SDMT, and Fatigue Severity Scale (FSS) administered. Subjects experiencing a relapse were assigned to the relapse group (RG). Matched controls from the larger cohort were assigned to the stable group (SG). RG and SG subjects underwent the same evaluation at relapse and 3 months later. Our main outcomes were a modified CFSS (m-CFSS) and modified EDSS (m-EDSS), incorporating SDMT and FSS, accounting for cognitive performance and fatigue rating, during relapse. RESULTS: The full cohort included 592 subjects; 80 qualified for RG and 72 were matched to the SG. The m-CFSS was significantly higher than CFSS at baseline (median = 2 vs. median = 0, p < 0.001) and relapse (median = 2 vs. median = 1, p < 0.001). The m-EDSS was higher than EDSS (median 3.0 vs. 2.5, p = 0.02) at relapse, where 35 RG subjects (43.8%) had higher m-EDSS than EDSS at relapse. CONCLUSION: This study demonstrates that incorporating the SDMT and FSS improves the accuracy of the EDSS, by accounting for cognitive changes, during relapse activity.

Recovery of cognitive function after relapse in multiple sclerosis.

BACKGROUND: Cognitive impairment is common in multiple sclerosis (MS) but its manifestation as acute disease activity is underappreciated. OBJECTIVE: The aim of this study is to examine recovery after MS relapse on multiple tests of cognitive and motor function and explore correlates of change with Expanded Disability Status Scale (EDSS), magnetic resonance imaging (MRI), and cognitive reserve. METHODS: Fifty relapsing group (RG) and matched stable participants were examined at baseline, during relapse, and at 3-month follow-up. Tests of cognitive processing speed (Symbol Digit Modalities Test (SDMT)) and consensus opinion measures of memory, ambulation, and manual dexterity were administered. All RG patients were treated with a 5-day course of Acthar Gel (5 mL/80 IU). RESULTS: In RG patients, SDMT declined from 55.2 to 44.6 at relapse and recovered to 51.7, a slope differing from stable controls (p = 0.001). A statistical trend (p = 0.07) for the same effect was observed for verbal memory and was significant for ambulation (p = 0.03). The Cerebral Function Score from the EDSS also changed in the RG and recovered incompletely relative to controls (p = 0.006). CONCLUSION: These results replicate earlier reports of cognitive worsening during relapse in MS. Clinically meaningful improvements followed relapse on SDMT and ambulation. Cognitive decline during relapse can be appreciated on neurological exam but not patient-reported outcomes.

Trait Conscientiousness predicts rate of longitudinal SDMT decline in multiple sclerosis.

BACKGROUND: Many people with multiple sclerosis (MS) exhibit cognitive decline over several years. Baseline differences may put people at greater risk for such decline. OBJECTIVE: To characterize rates of longitudinal cognitive decline and investigate baseline clinical predictors. METHODS: We report a retrospective analysis of 531 MS patients whose data were gleaned from a multi-study database, aggregated over 16 years. Linear mixed effects modeling was applied to estimate the average rate of decline on Symbol Digit Modalities Test (SDMT) performance and to predict rates of decline using baseline clinical variables. RESULTS: Participants exhibited an average estimated decline of 0.22 SDMT raw-score points/year (95% confidence interval (CI) (-0.32, -0.12)). We observed a significant main effect of time from baseline (t = -2.78, p = 0.006), test form (t = 2.13, p = 0.034), disease course (t = 2.91, p = 0.004), age (t = -2.76, p = 0.006), sex (t = -2.71, p = 0.007), subjective cognitive impairment (t = -2.00, p = 0.046), premorbid verbal intelligence (t = 5.14, p < 0.001), and trait Conscientiousness (t = 2.69, p = 0.008). A significant interaction emerged for Conscientiousness and time from baseline (t = 2.57, p = 0.011). CONCLUSION: Higher baseline trait Conscientiousness predicts slower rates of longitudinal cognitive decline in MS. This relationship, the average rate of decline, and practice effects can inform future research and clinical treatment decisions.

Necessity of technicians for computerized neuropsychological assessment devices in multiple sclerosis.

OBJECTIVE: Determine the influence of technician supervision on computer-administered cognitive tests in multiple sclerosis (MS). METHODS: Eighty MS patients underwent assessment using the CogState Brief Battery (CSBB) and the Cleveland Clinic Cognitive Battery (C3B). Each was administered twice, once with a technician guiding assessment, and once with technician-absent. Twenty-eight healthy controls were also evaluated. RESULTS: The influence of technician guidance was not statistically significant for group means on either test. For CSBB, administration problems were more common in the technician-absent condition. CONCLUSION: In this MS sample, reliable and valid test results were obtained from computer-assisted cognitive testing without technician guidance.

Response heterogeneity to home-based restorative cognitive rehabilitation in multiple sclerosis: An exploratory study.

BACKGROUND: Growing evidence supports the efficacy of restorative cognitive training in people with multiple sclerosis (PwMS), but the effects vary across individuals. Differences in treatment efficacy may be related to baseline individual differences. We investigated clinical characteristics and MRI variables to predict response to a previously validated approach to home-based restorative cognitive training. METHODS: In a single-arm repeated measures study, 51 PwMS completed a 12-week at-home restorative cognitive training program called BrainHQ, shown to be effective in a placebo-controlled clinical trial. Baseline demographic, clinical, neuropsychological, and brain MRI factors were captured and the effects of treatment were quantified with Symbol Digit Modalities Test (SDMT). Also measured were indices of treatment compliance. Regression modeling was employed to identify the factors associated with greatest SDMT improvement. RESULTS: As a group, patients improved significantly after training: mean SDMT improving from 49.6 ±â€¯14.7 to 52.6 ±â€¯15.6 (t = 3.91, p<0.001). Greater SDMT improvement correlated positively with treatment exposure (r = 0.38, p = 0.007). Increased post-rehabilitation improvement on SDMT was predicted by baseline relapsing-remitting course (ß=-0.34, p = 0.017), higher trait Conscientiousness-Orderliness (ß=0.29, p = 0.040), and higher baseline gray matter volume (GMV; ß=0.31, p = 0.030). CONCLUSION: The study was designed to explore the variables that predict favorable outcome in a home-based application of a validated restorative cognitive training program. We find good outcomes are most likely in patients with higher trait Conscientiousness-Orderliness, and relapsing-remitting course. The same was found for individuals with higher GMV. Future work in larger cohorts is needed to support these findings and to investigate the unique needs of individuals according to baseline factors.