Actual and Imagined Music-Cued Gait Training in People with Multiple Sclerosis: A Double-Blind Randomized Parallel Multicenter Trial.

BACKGROUND: Actual and imagined cued gait trainings have not been compared in people with multiple sclerosis (MS). OBJECTIVE: To analyze the effects of cued motor imagery (CMI), cued gait training (CGT), and combined CMI and cued gait training (CMI-CGT) on motor, cognitive, and emotional functioning, and health-related quality of life in people with MS. METHODS: In this double-blind randomized parallel-group multicenter trial, people with MS were randomized (1:1:1) to CMI, CMI-CGT, or CGT for 30 minutes, 4×/week for 4 weeks. Patients practiced at home, using recorded instructions, and supported by ≥6 phone calls. Data were collected at weeks 0, 4, and 13. Co-primary outcomes were walking speed and distance, analyzed by intention-to-treat. Secondary outcomes were global cognitive impairment, anxiety, depression, suicidality, fatigue, HRQoL, motor imagery ability, music-induced motivation, pleasure and arousal, self-efficacy, and cognitive function. Adverse events and falls were continuously monitored. RESULTS: Of 1559 screened patients, 132 were randomized: 44 to CMI, 44 to CMI-CGT, and 44 to CGT. None of the interventions demonstrated superiority in influencing walking speed or distance, with negligible effects on walking speed (η2 = 0.019) and distance (η2 = 0.005) observed in the between-group comparison. Improvements in walking speed and walking distance over time corresponded to large effects for CMI, CMI-CGT, and CGT (η2 = 0.348 and η2 = 0.454 respectively). No severe study-related adverse events were reported. CONCLUSIONS: CMI-GT did not lead to improved walking speed and distance compared with CMI and CGT alone in people with MS. Lack of a true control group represents a study limitation. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00023978.

Evaluation of the T25FW in minimally disabled people with multiple sclerosis.

BACKGROUND: Walking impairment is one of the most prevalent symptoms in people with multiple sclerosis (pwMS). In this study, we aimed to explore the usefulness of a simple walking test, the Timed 25 Foot Walk (T25FW), in detecting subtle differences in "fully ambulatory" pwMS compared to HC. METHODS: We therefore investigated retrospective data from a clinical real-life cohort of 650 pwMS. We first analyzed the amount of patients showing clinically relevant impairment in the T25FW (T25FW > 6 s) within different levels of disability according to the Expanded Disability Status Scale (EDSS). For detailed analysis in "fully ambulatory" pwMS, we formed four groups according to the respective levels of disability (EDSS 0, EDSS 1, EDSS 1.5-2, EDSS 2.5-3), and compared their walking speed to age- and sex-matched healthy controls (HC). RESULTS: In our cohort, the number of patients showing clinically relevant slowing in the T25FW ranged from 15% in "fully ambulatory" patients (EDSS 0-3) to 69% in patients with moderate (EDSS 3.5-5.5) and 100% in patients with severe impairment (EDSS ≥6). Further analyses in "fully ambulatory" patients revealed that all EDSS-subgroups showed significant slowing compared to HC. The mean difference to walking speed of HC became gradually more pronounced from 0.15 m/s in asymptomatic patients (EDSS 0) to 0.5 m/s in patients with EDSS 2.5-3. CONCLUSION: These findings underline the ability of the T25FW to detect slowing even in patients with minimal disability. While the difference to HC was slightly below clinical relevance in asymptomatic patients (EDSS 0), slowing gradually worsened from EDSS 1 onwards and exceeded published thresholds for clinical meaningfulness.

Evaluation of a self-administered iPad®-based processing speed assessment for people with multiple sclerosis in a clinical routine setting.

BACKGROUND: Limited resources often hinder regular cognitive assessment of people with multiple sclerosis (pwMS) in standard clinical care. A self-administered iPad®-based cognitive screening-tool (Processing Speed Test; PST) might mitigate this problem. OBJECTIVE: To evaluate the PST in clinical routine. METHODS: We investigated the feasibility of the PST in both a quiet and a waiting room setting. We assessed the validity of the PST in comparison with the established Symbol Digit Modalities Test (SDMT). We explored associations between processing speed assessments and the Brief International Cognitive Assessment for MS (BICAMS), magnetic resonance imaging (MRI) parameters, and psychological factors. Additionally, we explored the ability of the PST to detect impairment in processing speed compared to the SDMT. RESULTS: The PST was feasible in the waiting room setting. PST and SDMT correlated comparably with the BICAMS, MRI parameters, and psychological variables. Of 172 pwMS, 50 (30.8%) showed cognitive impairment according to the BICAMS; respective values were 47 (27.3%) for the SDMT and 9 (5.2%) for the PST. CONCLUSIONS: The PST performed in a waiting room setting correlates strongly with established cognitive tests. It thus may be used to assess processing speed in a resource-efficient manner and complement cognitive assessment in clinical routine. Despite comparable validity of the PST and SDMT, we identified more pwMS with impaired processing speed using normative data of the SDMT compared to the PST and advise caution, that the common cut-off score of - 1.5 SD from the current PST is not appropriate in Europe.

Psychological factors and brain magnetic resonance imaging metrics associated with fatigue in persons with multiple sclerosis.

BACKGROUND: Besides demographics and clinical factors, psychological variables and brain-tissue changes have been associated with fatigue in persons with multiple sclerosis (pwMS). Identifying predictors of fatigue could help to improve therapeutic approaches for pwMS. Therefore, we investigated predictors of fatigue using a multifactorial approach. METHODS: 136 pwMS and 49 normal controls (NC) underwent clinical, neuropsychological, and magnetic resonance imaging examinations. We assessed fatigue using the "Fatigue Scale for Motor and Cognitive Functions", yielding a total, motor, and cognitive fatigue score. We further analyzed global and subcortical brain volumes, white matter lesions and microstructural changes (examining fractional anisotropy; FA) along the cortico striatal thalamo cortical (CSTC) loop. Potential demographic, clinical, psychological, and magnetic resonance imaging predictors of total, motor, and cognitive fatigue were explored using multifactorial linear regression models. RESULTS: 53% of pwMS and 20% of NC demonstrated fatigue. Besides demographics and clinical data, total fatigue in pwMS was predicted by higher levels of depression and reduced microstructural tissue integrity in the CSTC loop (adjusted R2 = 0.52, p < 0.001). More specifically, motor fatigue was predicted by lower education, female sex, higher physical disability, higher levels of depression, and self-efficacy (adjusted R2 = 0.54, p < 0.001). Cognitive fatigue was also predicted by higher levels of depression and lower self-efficacy, but in addition by FA reductions in the CSTC loop (adjusted R2 = 0.45, p < 0.001). CONCLUSIONS: Our results indicate that depression and self-efficacy strongly predict fatigue in MS. Incremental variance in total and cognitive fatigue was explained by microstructural changes along the CSTC loop, beyond demographics, clinical, and psychological variables.

Information processing speed as a prognostic marker of physical impairment and progression in patients with multiple sclerosis.

BACKGROUND: Prediction of disability progression in patients with MS (pwMS) is challenging. So far, scarce evidence exists suggesting knowledge about how cognitive performance may potentially improve prediction of physical impairment and disability progression in MS. Therefore, we wanted to assess the prognostic value of cognitive performance regarding physical impairment and disability progression in pwMS. METHODS: 85 patients (64% female; 60% relapse-remitting MS; mean age=36.78 ± 9.63 years) underwent clinical, neuropsychological (Brief Repeatable Battery for Neuropsychological Test (BRB-N)) and brain MRI (T1-weighted and T2-weighted FLAIR images) assessment at baseline and after an average of 7 years (SD=3.75) at follow-up. We assessed physical impairment and annualized disability progression (disability progression divided by follow-up duration) using the Expanded Disability Status Scale (EDSS). To compare patients with no or mild physical impairment (EDSS≤2.5) and patients with moderate to severe physical impairment (EDSS≥3.0), we used an EDSS score ≥3.0 as cut-off. Silent progression was defined by an EDSS worsening of at least 0.5 in the absence of relapses and inflammation in relapsing-remitting MS. RESULTS: In hierarchical regression models (method "STEPWISE", forward) performance in information processing speed was a significant and independent predictor of physical impairment (EDSS≥3.0) at follow-up (model R²=0.671, b=-1.46, OR=0.23, p=0.001) and annualized disability progression (adjusted model R²=0.257, ß=-0.26, 95% CI: -0.066, -0.008, p=0.012), in addition to demographics (age, education, individual follow-up time), clinical (EDSS, disease duration, clinical phenotype, annualized-relapse-rate) and MRI measures (brain volumes and T2-lesion load). In a MANCOVA controlled for age, disease duration and individual follow-up time, worse baseline performance in information processing speed was found in patients with higher EDSS at follow-up (m=-1.91, SD=1.18, p<0.001) and silent progression (m=-2.19, SD=1.01, p=0.038). CONCLUSION: Performance in information processing speed might help to identify patients at risk for physical impairment. Therefore, neuropsychological assessment should be integrated in clinical standard care to support disease management in pwMS.