Association of daily physical activity with brain volumes and cervical spinal cord areas in multiple sclerosis.

BACKGROUND: Remote activity monitoring has the potential to evaluate real-world, motor function, and disability at home. The relationships of daily physical activity with spinal cord white matter and gray matter (GM) areas, multiple sclerosis (MS) disability and leg function, are unknown. OBJECTIVE: Evaluate the association of structural central nervous system pathology with ambulatory disability. METHODS: Fifty adults with progressive or relapsing MS with motor disability who could walk >2 minutes were assessed using clinician-evaluated, patient-reported outcomes, and quantitative brain and spinal cord magnetic resonance imaging (MRI) measures. Fitbit Flex2, worn on the non-dominant wrist, remotely assessed activity over 30 days. Univariate and multivariate analyses were performed to assess correlations between physical activity and other disability metrics. RESULTS: Mean age was 53.3 years and median Expanded Disability Status Scale (EDSS) was 4.0. Average daily step counts (STEPS) were highly correlated with EDSS and walking measures. Greater STEPS were significantly correlated with greater C2-C3 spinal cord GM areas (ρ = 0.39, p = 0.04), total cord area (TCA; ρ = 0.35, p = 0.04), and cortical GM volume (ρ = 0.32, p = 0.04). CONCLUSION: These results provide preliminary evidence that spinal cord GM area is a neuroanatomical substrate associated with STEPS. STEPS could serve as a proxy to alert clinicians and researchers to possible changes in structural nervous system pathology.

Correction: Application of an Adaptive, Digital, Game-Based Approach for Cognitive Assessment in Multiple Sclerosis: Observational Study.

[This corrects the article DOI: 10.2196/24356.].

Application of an Adaptive, Digital, Game-Based Approach for Cognitive Assessment in Multiple Sclerosis: Observational Study.

BACKGROUND: Cognitive impairment is one of the most debilitating manifestations of multiple sclerosis. Currently, the assessment of cognition relies on a time-consuming and extensive neuropsychological examination, which is only available in some centers. OBJECTIVE: To enable simpler, more accessible cognitive screening, we sought to determine the feasibility and potential assessment sensitivity of an unsupervised, adaptive, video game-based digital therapeutic to assess cognition in multiple sclerosis. METHODS: A total of 100 people with multiple sclerosis (33 with cognitive impairment and 67 without cognitive impairment) and 24 adults without multiple sclerosis were tested with the tablet game (EVO Monitor) and standard measures, including the Brief International Cognitive Assessment for Multiple Sclerosis (which included the Symbol Digit Modalities Test [SDMT]) and Multiple Sclerosis Functional Composite 4 (which included the Timed 25-Foot Walk test). Patients with multiple sclerosis also underwent neurological evaluations and contributed recent structural magnetic resonance imaging scans. Group differences in EVO Monitor performance and the association between EVO Monitor performance and standard measures were investigated. RESULTS: Participants with multiple sclerosis and cognitive impairment showed worse performance in EVO Monitor compared with participants without multiple sclerosis (P=.01) and participants with multiple sclerosis without cognitive impairment (all P<.002). Regression analyses indicated that participants with a lower SDMT score showed lower performance in EVO Monitor (r=0.52, P<.001). Further exploratory analyses revealed associations between performance in EVO Monitor and walking speed (r=-0.45, P<.001) as well as brain volumetric data (left thalamic volume: r=0.47, P<.001; right thalamic volume: r=0.39, P=.002; left rostral middle frontal volume: r=0.28, P=.03; right rostral middle frontal volume: r=0.27, P=.03). CONCLUSIONS: These findings suggest that EVO Monitor, an unsupervised, video game-based digital program integrated with adaptive mechanics, is a clinically valuable approach to measuring cognitive performance in patients with multiple sclerosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT03569618; https://clinicaltrials.gov/ct2/show/NCT03569618.

A novel in-home digital treatment to improve processing speed in people with multiple sclerosis: A pilot study.

OBJECTIVE: To assess whether a videogame-like digital treatment is superior to a control in improving processing speed in adults with multiple sclerosis (MS). METHODS: Adults with MS and baseline Symbol Digit Modalities Test (SDMT) z-scores between -2 and 0 were enrolled in a double-blind randomized controlled clinical trial. After completing a baseline in-clinic evaluation (Visit 1), they were randomized to complete an in-home, tablet-based videogame-like digital treatment (AKL-T03) or control word game (AKL-T09) for up to 25 minutes/day, 5 days/week, for 6 weeks. A repeat in-clinic evaluation occurred at 6 weeks (Visit 2), and again 8 weeks later to determine persistence of effects (Visit 3). The pre-specified primary outcome was change in SDMT score between Visits 1 and 2. RESULTS: SDMT increased at Visit 2 for participants randomized to both AKL-T03 (p < 0.001) and AKL-T09 (p = 0.024). These respective mean improvements were +6.10 and +3.55 (comparison p = 0.21). At Visit 3, 70% of participants randomized to AKL-T03 maintained a clinically meaningful 4+-point increase in SDMT above their baseline, compared with 37% for AKL-T09 (p = 0.038). CONCLUSION: This in-home digital intervention resulted in substantial and durable improvements in processing speed. A larger randomized controlled clinical trial is planned. TRIAL REGISTRATION: This trial is registered on ClinicalTrials.gov under "NCT03569618," https://clinicaltrials.gov/ct2/show/NCT03569618.

Brain MRI Predicts Worsening Multiple Sclerosis Disability over 5 Years in the SUMMIT Study.

BACKGROUND AND PURPOSE: Brain MRI-derived lesions and atrophy are related to multiple sclerosis (MS) disability. In the Serially Unified Multicenter MS Investigation (SUMMIT), from Brigham and Women's Hospital (BWH) and University of California, San Francisco (UCSF), we assessed whether MRI methodologic heterogeneity may limit the ability to pool multisite data sets to assess 5-year clinical-MRI associations. METHODS: Patients with relapsing-remitting (RR) MS (n = 100 from each site) underwent baseline brain MRI and baseline and 5-year clinical evaluations. Patients were matched on sex (74 women each), age, disease duration, and Expanded Disability Status Scale (EDSS) score. MRI was performed with differences between sites in both acquisition (field strength, voxel size, pulse sequences), and postprocessing pipeline to assess brain parenchymal fraction (BPF) and T2 lesion volume (T2LV). RESULTS: The UCSF cohort showed higher correlation than the BWH cohort between T2LV and disease duration. UCSF showed a higher inverse correlation between BPF and age than BWH. UCSF showed a higher inverse correlation than BWH between BPF and 5-year EDSS score. Both cohorts showed inverse correlations between BPF and T2LV, with no between-site difference. The pooled but not individual cohort data showed a link between a lower baseline BPF and the subsequent 5-year worsening in disability in addition to other stronger relationships in the data. CONCLUSIONS: MRI acquisition and processing differences may result in some degree of heterogeneity in assessing brain lesion and atrophy measures in patients with MS. Pooling of data across sites is beneficial to correct for potential biases in individual data sets.

APB differentially affects the cone contributions to the zebrafish ERG.

APB (DL-2-amino-4-phosphonobutyric acid) has been found to affect the retinal processing of many vertebrate species as evidenced by the suppression of the b-wave component of the electroretinogram (ERG). The present study examined the effects of APB on the cone contributions to the ERG response of adult zebrafish (Danio rerio). ERG responses were obtained from light-adapted adult zebrafish following intravitreal injection of either saline alone or saline with various concentrations of APB ranging from 10 microm to 500 microM. Visual stimuli were 200-ms flashes of various wavelengths and irradiances. Spectral sensitivity functions were calculated from the irradiance versus response amplitude functions of the a-, b-, and d-wave components of the ERG response. Saline had no effects on the ERG response. However, APB had differential effects on the sensitivity of the b- and d-wave components. The effects of APB on the b-wave component were most apparent in the ultraviolet and short-wavelength portions (320-440 nm) of the spectral sensitivity function, although the b-wave was not completely eliminated at these wavelengths. APB-treated subjects were found to possess the same cone mechanisms (L-M and M-S) in the middle- and long-wavelength areas of the spectrum as saline injected subjects, although absolute sensitivity was lower for the APB-injected subjects. Spectral sensitivity based on the d-wave response was affected by APB but only in the short-wavelength region. All results appear to be independent of the APB dose. These results support the notion that glutamate receptors play a specific role in zebrafish visual processing. In addition, the effects of APB support recent anatomical evidence that the zebrafish retina may possess different types of glutamate receptors.