Faculty Bibliography

OBJECTIVE:To compare clinical and imaging features of multiple sclerosis (MS) severity between Black Americans (BA) and White Americans (WA) and evaluate the role of socioeconomic status. METHODS:We compared BA and WA participants in the Multiple Sclerosis Partners Advancing Technology Health Solutions (MS PATHS) cohort with respect to MS characteristics including self-reported disability, objective neurologic function assessments, and quantitative brain MRI measurements, after covariate adjustment (including education level, employment, or insurance as socioeconomic indicators). In a subgroup, we evaluated within-race, neighborhood-level indicators of socioeconomic status (SES) using 9-digit ZIP codes. RESULTS:Of 1,214 BAs and 7,530 WAs with MS, BAs were younger, had lower education level, and were more likely to have Medicaid insurance or be disabled or unemployed than WAs. BAs had worse self-reported disability (1.47-fold greater odds of severe vs. mild disability, 95% CI 1.18, 1.86) and worse performances on tests of cognitive processing speed (-5.06 fewer correct, CI -5.72, -4.41), walking (0.66 seconds slower, 95% CI 0.36, 0.96) and manual dexterity (2.11 seconds slower, 95% CI 1.69, 2.54). BAs had more brain MRI lesions and lower overall and gray matter brain volumes, including reduced thalamic (-0.77 mL, 95% CI -0.91, -0.64), cortical (-30.63 mL, 95% CI -35.93, -25.33), and deep (-1.58 mL, 95% CI -1.92, -1.23) gray matter volumes. While lower SES correlated with worse neuroperformance scores in WAs, this association was less clear in BA. CONCLUSION/CONCLUSIONS:We observed a greater burden of disease in BAs with MS relative to WAs with MS, despite adjustment for SES indicators. Beyond SES, future longitudinal studies should also consider roles of other societal constructs (e.g., systemic racism). Such studies will be important for identifying prognostic factors and optimal treatment strategies among BAs with MS is warranted.

Pediatric-onset multiple sclerosis (POMS), representing approximately 5% of all MS cases, affects the central nervous system during its ongoing development. POMS is most commonly diagnosed during adolescence but can occur in younger children as well. For pediatric patients with MS, it is critical to manage the full impact of the disease and monitor for any effects on school and social functioning. Disease management includes not only disease-modifying therapies but also strategies to optimize wellbeing. We review the interventions with the highest evidence of ability to improve the disease course and quality of life in POMS. High levels of vitamin D and a diet low in saturated fat are associated with lower relapse rates. Exercise ameliorates fatigue and sleep. Behavioral strategies for sleep hygiene and mood regulation can also improve fatigue and perceived health. POMS management should be addressed holistically, including assessing overall symptom burden as well as the psychological and functional impact of the disease.

Slowed information processing speed is among the earliest markers of cognitive impairment in multiple sclerosis (MS) and has been associated with white matter (WM) structural integrity. Localization of WM tracts associated with slowing, but not significant impairment, on specific cognitive tasks in pediatric and young age onset MS can facilitate early and effective therapeutic intervention. Diffusion tensor imaging data were collected on 25 MS patients and 24 controls who also underwent the Symbol Digit Modalities Test (SDMT) and the computer-based Cogstate simple and choice reaction time tests. Fractional anisotropy (FA), mean (MD), radial (RD) and axial (AD) diffusivities were correlated voxel-wise with processing speed measures. All DTI metrics of several white matter tracts were significantly different between groups (p < 0.05). Notably, higher MD, RD, and AD, but not FA, in the corpus callosum correlated with lower scores on both SDMT and simple reaction time. Additionally, all diffusivity metrics in the left corticospinal tract correlated negatively with SDMT scores, whereas only MD in the right superior fronto-occipital fasciculus correlated with simple reaction time. In conclusion, subtle slowing of processing speed is correlated with WM damage in the visual-motor processing pathways in patients with young age of MS onset.

Objective/UNASSIGNED:At the time of multiple sclerosis (MS) diagnosis, identifying those at risk for poorer health-related quality of life and emotional well-being can be a critical consideration for treatment planning. This study aimed to test whether adverse childhood experiences predict MS patients' health-related quality of life and emotional functioning at time of diagnosis and initial course of disease. Methods/UNASSIGNED:We recruited patients at the time of new MS diagnosis to complete self-report surveys at baseline and a one-year follow-up. Questionnaires included the Adverse Childhood Experiences (ACEs), as well as the MS Knowledge Questionnaire (MSKQ), the 36-Item Short Form Health Survey (SF-36), and Self-Management Screening (SeMaS). Results/UNASSIGNED: Conclusions/UNASSIGNED:Childhood adversity predicts health-related quality of life and emotional well-being at time of MS diagnosis and over the initial course of the disease. Measured using a brief screening inventory (ACEs), routine administration may be useful for identifying patients in need of increased supportive services.

Background and aims: Natalizumab extended interval dosing (EID) is associated with lower progressive multifocal leukoencephalopathy risk than standard interval dosing (SID) in anti-JC virus antibody positive multiple sclerosis patients. However, EID efficacy has yet to be demonstrated in a randomised controlled trial, and real-world efficacy data would be valuable. Method(s): This study compared Multiple Sclerosis Performance Test (MSPT) functional changes occurring during treatment with natalizumab EID versus SID in MS PATHS, a network of healthcare institutions providing access to real-world clinical data. An MSPT segment was defined as the time between two MSPT assessments six months apart. MSPT segments with average infusion cycles >35 days and 35 days were defined as EID and SID, respectively. Patients could contribute multiple segments to both groups. Missing covariate data were multiply imputed. Covariates at segment start (Table) were balanced between groups by inverse probability weighting (IPW) based on a logistic propensity score model. Differences in annualized change in MSPT scores were compared between EID/SID arms with weighted linear regression. Result(s): Data from 152 EID and 1,079 SID segments were analysed. After IPW, all baseline factors exhibited a standard mean difference 0.05. Annualised change in MSPT scores of processing speed, manual dexterity, and ambulation did not differ significantly between EID and SID. On average, MSPT scores were maintained or improved while on natalizumab (Figure). Conclusion(s): Functional outcomes between patients treated with natalizumab EID versus SID were comparable. Cognitive processing speed, manual dexterity, and walking speed were maintained or improved over time for both treatment groups

OBJECTIVE:Cognitive deficits following a traumatic brain injury (TBI) are a leading cause of disability in young adults and there is a critical need for novel approaches to improve cognitive outcomes in TBI survivors. Transcranial direct current stimulation (tDCS) paired with cognitive remediation has emerged as a viable, cost-effective, noninvasive approach for treating cognitive impairments in a wide variety of neurological conditions. Here, we report the first case study utilizing remotely supervised tDCS (RS-tDCS) protocol paired with cognitive remediation in a 29-year-old man with persisting cognitive and emotional sequelae following TBI. METHOD/METHODS:Neuropsychological measures were administered before and after the patient completed 20 daily sessions of RS-tDCS (2.0 mA × 20 minutes, left anodal dorsolateral prefrontal cortex montage). During the daily stimulation period, he completed adaptive cognitive training. All treatment procedures were delivered at home and monitored in real time via videoconference with a study technician. RESULTS:Following 20 RS-tDCS and cognitive training sessions, he had significant improvements (>1 SD) on tests of attention and working memory, semantic fluency, and information processing speed. Mood was also improved. CONCLUSIONS:This is the first demonstration of at-home telerehabilitation with RS-tDCS and cognitive training to improve cognitive outcomes following TBI.

Background/UNASSIGNED:People living with multiple sclerosis (MS) experience a high symptom burden that interferes with daily functioning. Virtual reality (VR) is an emerging technology with a range of potential therapeutic applications that may include ameliorating the experience of some common MS symptoms. Objective/UNASSIGNED:We tested the feasibility and tolerability of a VR intervention and its preliminary effects on affect. Methods/UNASSIGNED:Participants with MS were recruited to complete a pilot study of eight sessions of VR over four weeks. Results/UNASSIGNED: = 0.040). Conclusion/UNASSIGNED:VR interventions are feasible, safe, and tolerable for individuals living with MS and may improve affect.

AIM/UNASSIGNED:To adopt a computer-based protocol to assess grip fatigability in patients with pediatric-onset multiple sclerosis to provide detection of subtle motor involvement identifying those patients most at risk for future decline. METHOD/UNASSIGNED:Pediatric-onset multiple sclerosis patients were recruited during routine outpatient visits to complete a grip assessment and compared to a group of healthy age- and sex-matched controls. All participants completed a computer-based measurement of standard maximal grip strength and repetitive and sustained grip performance measured by dynamic and static fatigue indices. RESULTS/UNASSIGNED:< .001). CONCLUSION/UNASSIGNED:Brief repeatable grip assessment including measures of dynamic and sustained static output can be a sensitive indicator of upper extremity motor involvement in pediatric-onset multiple sclerosis, potentially identifying those in need of intervention to prevent future disability.

BACKGROUND:Cognitive impairment due to multiple sclerosis (MS) is common and often limits occupational functioning, contributes to disability, and reduces quality of life. Early detection of cognitive involvement in MS is critical for treatment planning and intervention, and frequent, regular cognitive monitoring may provide insight into subtle changes in disease progression. OBJECTIVE:To compare the sensitivity and specificity of clinical, computer-based and experimental measures to early cognitive involvement in MS. METHODS:Cognitive functioning was compared in MS participants early in the disease course to matched healthy controls using conventional, computer-based and functional assessments: the Brief International Cognitive Assessment in MS (BICAMS); the computer-based Cogstate Brief Battery (CBB); the Attention Network Test-Interaction (ANT-I), including intra-individual variability; and the Test of Everyday Cognitive Ability (TECA), a functional measure of instrumental activities of daily living. RESULTS:MS participants (n = 25, mean disease duration= 5.82 ± 3.65 years) and demographically matched healthy controls (n = 29) completed the cognitive assessments. The Cogstate measure of choice reaction time (AUC = 0.73, p = .004), intra-individual variability on the ANT-I (AUC = 0.79, p = .001), and TECA (AUC = 0.78, p = .001) scores were the most sensitive and specific markers of cognitive involvement in MS. CONCLUSIONS:Brief, repeatable, computer-based measures of reaction time and variability detect early MS associated cognitive involvement.