Faculty Bibliography

BACKGROUND:Childhood environmental factors back to the prenatal environment can contribute to MS risk. Childhood adversity, which causes biological, behavioral, and epigenetic changes that can be passed down through families, has been understudied in MS. Here, we emphasize the need to understand the role that intergenerational adversity may play among families affected by MS. OBJECTIVE:To evaluate the frequency and types of adverse childhood experiences among parents of children with MS. METHODS:Individuals with pediatric MS (n = 68) were enrolled in a longitudinal study of cognition. At enrollment, the patient and one caregiver or parent completed questionnaires. As the pediatric participants were under age 18 at time of enrollment, one parent completed the Adverse Childhood Experiences (ACEs, a 10-item self-report measure) about the parents' own childhood. Results from the ACE questionnaire among parents of pediatric healthy controls (n = 96) and adults in a national cohort are also reported for comparison. RESULTS:Over half of pediatric MS parents reported at least one ACE exposure. Of parents that did have ACE exposures, the exposures were broad in terms of abuse, neglect, and household dysfunction. Over 10 % of parents reported total ACE scores of 7 or above. CONCLUSION/CONCLUSIONS:Over half of pediatric MS parents experienced some degree of childhood adversity. The impact of intergenerational adversity on the development of pediatric onset MS warrants further study.

Fatigue is a common and often debilitating feature of multiple sclerosis (MS) that lacks reliably effective treatment options for most patients. Transcranial direct current stimulation (tDCS), a safe and well-tolerated type of noninvasive brain stimulation, is a low-cost and home-based approach with the potential to reduce fatigue in MS. We conducted a double-blind, sham-controlled, randomized clinical trial to compare active vs. low-dose (sham) tDCS paired with computer-based cognitive training, delivered as a home-based intervention, to reduce MS-related fatigue. Participants with MS-related fatigue, but without depression, were stratified by neurologic disability using the Extended Disability Status Scale (EDSS) and randomized to complete 30 daily sessions over six weeks of either active or sham tDCS paired with online cognitive training (BrainHQ). The primary outcome was the change in PROMIS Fatigue score from baseline to the end of the intervention. A total of 117 participants were randomized, with 92% completing all treatment sessions. Both groups showed significant reductions in fatigue, with no significant difference between them. This suggests that tDCS does not provide any additional benefit over cognitive training alone in reducing fatigue, but confirms the feasibility and tolerance of this home-based intervention.

INTRODUCTION/UNASSIGNED:Gait is a critical indicator of neurological health, with changes often signaling underlying decline. We developed a remote gait monitoring protocol using off-the-shelf shoe-based sensors (RunScribe) to assess gait parameters in real-world home settings. This protocol, known as Gait Assessment with Innovative Technologies - Home-based Use and Benefit (GAIT-HUB), was tested in individuals with multiple sclerosis (MS), a population at high risk for gait impairment due to the disease's variable progression. METHODS/UNASSIGNED:Participants with MS completed an in-clinic baseline gait assessment using a validated sensor (G-Sensor®) and three weekly, remotely supervised gait assessments at home using the RunScribe sensors. Gait parameters were compared across devices using intra-class correlation coefficients (ICCs) and Bland-Altman analyses. Longitudinal reliability of remote assessments and system usability score (SUS) were evaluated. RESULTS/UNASSIGNED:Twenty-nine participants (76% women, ages 19-67, PDDS range 0-5) successfully completed the home-based assessments. High agreement between devices was observed for gait speed, stride length, and cadence (ICCs >0.90), though phases like stance and swing showed more variability. Bland-Altman analyses indicated minimal bias in most parameters. Longitudinal assessments demonstrated strong reliability (ICCs >0.87) for key metrics, and SUS indicated good-to-excellent usability of the remote protocol. CONCLUSION/UNASSIGNED:The GAIT-HUB protocol enables reliable and feasible home-based gait monitoring using wearable sensors that patients can easily self-apply. This approach provides valuable insights into daily mobility patterns beyond clinical visits, supporting more precise and timely assessments of functional status between appointments and offering the potential for seamless integration into telemedicine routine care.

BACKGROUND/OBJECTIVES/UNASSIGNED:Primary progressive aphasia (PPA) is managed with speech-language therapy (SLT) to slow language decline. Pairing transcranial direct current stimulation (tDCS) with SLT can enhance its effects. However, further research is needed to confirm these findings and guide its clinical use. We evaluated the feasibility of providing an intervention combining tDCS with SLT as a home-based and remotely supervised intervention. METHODS/UNASSIGNED:Participants with confirmed PPA who had word-finding difficulties were recruited for an open-label observational study. The intervention consisted of 20 daily sessions over 1 month, each with 45-min of personalized word retrieval training. During the first 30-min, participants received tDCS over the left inferior frontal gyrus (anode F7, cathode O1) at 2.0 mA. Language measures were remotely administered at baseline and intervention end. RESULTS/UNASSIGNED:= 0.016) from baseline to intervention end. CONCLUSIONS/UNASSIGNED:Our case series demonstrates that home-based tDCS added to SLT is feasible for patients with PPA. However, larger controlled studies are required to confirm its effectiveness in slowing language decline and to fully determine the benefits of this approach. This approach not only facilitates broader access to participation but also enables the extended treatment necessary to evaluate its clinical benefits, moving this treatment closer to clinical availability as a telehealth treatment.

Depression is a common and debilitating disorder affecting millions. First-line treatments fail to achieve remission in about one-third of patients, highlighting a critical treatment need. Transcranial direct current stimulation (tDCS) has emerged as a novel treatment for depression. Therefore, the aim of this review was to provide a comprehensive overview of the last decade of tDCS trials for depression and propose future research directions. To compile studies of the past decade, we conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) of tDCS for depression. A total of 21 RCTs were included, presenting a moderate effect for active tDCS compared to placebo. We also provided a description of study designs, stimulation parameters, and patients' characteristics. Following, we proposed possible strategies to enhance clinical effectiveness and reduce variability in results, including 1) optimization/personalization of tDCS via spatial and temporal target localization; 2) optimized methodological strategies, including home-based, accelerated tDCS protocols and novel trial designs; and 3) investigate patient profile to identify features that can predict treatment response. In conclusion, tDCS holds promise as a treatment for depression, but variability in trial parameters and outcomes underscores the need for its further optimization. Refining and standardizing protocols may enhance its effectiveness.

OBJECTIVE/UNASSIGNED:Chronic non-specific lower back pain (cNSLBP) is a prevalent and disabling condition, imposing a substantial socioeconomic burden due to high healthcare costs and productivity losses, with limited accessible and effective long-term treatment options. Automated Thermo-mechanical Therapy (ATT) is a promising, non-drug intervention that leverages innovative technical advances to provide multimodal pain relief, offering accessibility and low-cost delivery. This study tested ATT for immediate pain relief in individuals with cNSLBP in a single-session, double-blind, randomized controlled trial. METHODS/UNASSIGNED:= 20) in a 40-min session with urn randomization. The active device applied heated cylindrical rollers along the spine, using far-infrared heat and mechanical tissue stimulation tailored to spinal alignment. In the control condition, the device used minimal mechanical therapy intensity without heat, targeting only the cervical area to avoid lower back therapeutic effects. Pre- and post-intervention assessments measured changes in pain intensity (primary outcome) via a 100-mm Visual Analog Scale for Pain (VAS-P100), alongside secondary outcomes assessing pain characteristics, anxiety, and functional mobility. RESULTS/UNASSIGNED:= 0.0031). No adverse events were reported, and all participants tolerated the intervention well. CONCLUSIONS/UNASSIGNED:A single session of ATT provides immediate, significant pain relief in individuals with cNSLBP, supporting its potential as a safe, non-invasive option for managing chronic back pain. Future studies should examine the long-term benefits of repeated ATT sessions and explore mechanistic insights into thermo-mechanical stimulation's effects on pain and function. CLINICAL TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov, identifier: NCT06769321.

BACKGROUND/UNASSIGNED:Cognitive impairment is common in multiple sclerosis (MS). Transcranial direct current stimulation (tDCS) combined with adaptive cognitive training (aCT) may improve clinical outcomes. OBJECTIVE/UNASSIGNED:To evaluate the effect of active vs. sham home-based tDCS + aCT on cognitive function. METHODS/UNASSIGNED:-scores. RESULTS/UNASSIGNED: = .411). CONCLUSIONS/UNASSIGNED:Active vs. sham tDCS + aCT resulted in significantly better cognitive outcomes, with the greatest benefit in those with high neurologic disability.CLINICALTRIALS.GOV; https://clinicaltrials.gov/study/NCT03838770; IDENTIFIER: NCT03838770.

BACKGROUND/UNASSIGNED:Many individuals with progressive multiple sclerosis (PMS) are challenged by reduced manual dexterity and limited rehabilitation options. Transcranial direct current stimulation (tDCS) during motor training can improve rehabilitation outcomes. We developed a protocol for remotely supervising tDCS to deliver sessions of stimulation paired with training at home. OBJECTIVE/UNASSIGNED:This study evaluated the effectiveness of at-home tDCS paired with manual dexterity training for individuals with PMS. METHODS/UNASSIGNED:Sixty-five right-hand dominant participants with PMS and hand impairment were randomized to receive either active or sham M1-SO tDCS paired with manual dexterity training over 4 weeks. Clinical outcomes were measured by the changes in Nine-Hole Peg Test (9-HPT) and Dellon-Modified-Moberg-Pick-Up Test (DMMPUT). RESULTS/UNASSIGNED:= 0.04). CONCLUSION/UNASSIGNED:At-home tDCS paired with manual dexterity training is effective for individuals with PMS, with M1-SO tDCS enhancing training outcomes and offering a promising intervention for improving and preserving hand dexterity.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Psychosocial adversity and stress, known to predispose adults to neurodegenerative and inflammatory immune disorders, are widespread among children who experience socioeconomic disadvantage, and the associated neurotoxicity and proinflammatory profile may predispose these children to multiple sclerosis (MS). We sought to determine associations of socioeconomic disadvantage and psychosocial adversity with odds of pediatric-onset MS (POMS), age at POMS onset, and POMS disease activity. METHODS:This case-control study used data collected across 17 sites in the United States by the Environmental and Genetic Risk Factors for Pediatric Multiple Sclerosis Study. Cases (n = 381) were youth aged 3-21 years diagnosed with POMS or a clinically isolated demyelinating syndrome indicating high risk of MS. Frequency-matched controls (n = 611) aged 3-21 years were recruited from the same institutions. Prenatal and postnatal adversity and postnatal socioeconomic factors were assessed using retrospective questionnaires and zip code data. The primary outcome was MS diagnosis. Secondary outcomes were age at onset, relapse rate, and Expanded Disability Status Scale (EDSS). Predictors were maternal education, maternal prenatal stress events, child separation from caregivers during infancy and childhood, parental death during childhood, and childhood neighborhood disadvantage. RESULTS:= 0.025). There were no associations of the socioeconomic variables with age at onset, relapse rate, or EDSS, or of prenatal or postnatal adverse events with risk of POMS, age at onset, relapse rate, or EDSS. DISCUSSION/CONCLUSIONS:Low socioeconomic status at the neighborhood level may increase the risk of POMS while high parental education may be protective against POMS. Although we did not find associations of other evaluated prenatal or postnatal adversities with POMS, future research should explore such associations further by assessing a broader range of stressful childhood experiences.