Objective Rates of worsening and evolution to secondary progressive multiple sclerosis (MS) may be substantially lower in actively treated patients compared to natural history studies from the pretreatment era. Nonetheless, in our recently reported prospective cohort, more than half of patients with relapsing MS accumulated significant new disability by the 10th year of follow‐up. Notably, “no evidence of disease activity” at 2 years did not predict long‐term stability. Here, we determined to what extent clinical relapses and radiographic evidence of disease activity contribute to long‐term disability accumulation. Methods Disability progression was defined as an increase in Expanded Disability Status Scale (EDSS) of 1.5, 1.0, or 0.5 (or greater) from baseline EDSS = 0, 1.0–5.0, and 5.5 or higher, respectively, assessed from baseline to year 5 (±1 year) and sustained to year 10 (±1 year). Longitudinal analysis of relative brain volume loss used a linear mixed model with sex, age, disease duration, and HLA‐DRB1*15:01 as covariates. Results Relapses were associated with a transient increase in disability over 1‐year intervals ( p = 0.012) but not with confirmed disability progression ( p = 0.551). Relative brain volume declined at a greater rate among individuals with disability progression compared to those who remained stable ( p < 0.05). Interpretation Long‐term worsening is common in relapsing MS patients, is largely independent of relapse activity, and is associated with accelerated brain atrophy. We propose the term silent progression to describe the insidious disability that accrues in many patients who satisfy traditional criteria for relapsing–remitting MS. Ann Neurol 2019;85:653–666

Introduction Self-administered in-home digital therapeutics could expand access to cognitive rehabilitation for individuals with multiple sclerosis (MS), over half of whom experience cognitive impairment (CI). However, feasibility in an MS population must be clarified. This study was conducted to assess the feasibility of deploying a videogame-like digital treatment for CI in MS, including initial efficacy and barriers to adherence. Methods In this pilot study, 21 participants with MS completed an in-clinic baseline neurological evaluation. Cognitive tests included paper-and-pencil Brief International Cognitive Assessment for Multiple Sclerosis [BICAMS—which included the Symbol Digit Modalities Test (SDMT)] and other unsupervised tablet-based tests (including Match: an unsupervised test of executive functions and processing speed, developed at UCSF; and the Cogstate MS Battery). Participants then completed an in-home, tablet-based, videogame-like investigational digital treatment (Project: EVO™) for 25 min daily, 5 days weekly, for 4 weeks. This was followed by a repeat in-clinic evaluation. Results Of the 21 participants (mean [standard deviation, SD] age 53.8 [11.6] years, median Expanded Disability Status Scale (EDSS) 2.5 [SD 2.0, IQR [2–3.5]]) enrolled to use the digital therapeutic at home (mean [SD] SDMT z score: − 0.21 [1.16]), 18 completed the study, during which they completed an average of 19.7 days (median [SD]: 20.5 [8.4]). Overall, 78% of these 18 participants completed 75% of prescribed days (i.e., at least 15), and 50% completed all 20 days or more. Over the 4-week period, scores of processing speed improved significantly (based on one-sided t test), including SDMT ( p = 0.003) and Match ( p = 0.006). The Cogstate DET test (psychomotor function) also increased ( p = 0.006). Mean increase in SDMT was 3.6 points. Male sex, not being employed, and higher baseline anxiety all were significantly associated with greater improvement in SDMT over the 4-week period. Interestingly, lower baseline cognitive scores were associated with greater number of sessions completed (e.g., SDMT: p = 0.003, R 2 = 0.44). Adjusting for employment, a proxy for time available, did not significantly improve the model fit. Discussion Deploying an in-home digital tool to improve processing speed in MS is feasible, and shows preliminary efficacy. A larger, randomized controlled clinical trial is ongoing. Electronic supplementary material The online version of this article (10.1007/s40120-018-0121-0) contains supplementary material, which is available to authorized users.

Introduction: Chronic pain conditions are common among children and engender cascading effects across social, emotional, and behavioral domains for the child and family. Mobile health (mHealth) describes the practice of delivering healthcare via mobile devices and may be an ideal solution to increase access and reach of evidence-based behavioral health interventions. Areas Covered:The aim of this narrative review is to present a state-of-the-art overview of evidence-based mHealth efforts within the field of pediatric chronic pain and consider new and promising directions for study. Given the nascent nature of the field, published mHealth interventions in all stages of development are discussed. Literature was identified through a nonsystematic search in PubMed and Google Scholar, and a review of reference lists of papers that *

Diagnostic uncertainty, the perceived lack of an accurate explanation of the patient’s health problem, remains relatively unstudied in children. This study examined the prevalence, familial concordance, and correlates of diagnostic uncertainty in children and their parents presenting to a multidisciplinary pain clinic in the United States. One hundred and twenty-six parents and 91 of their children (Mage = 13.93 years, range = 8–18 years) completed a brief three-item measure of diagnostic uncertainty, as well as measures of pain-related distress and functioning. Forty-eight percent of children and 37% of parents believed something else was going on with the child’s pain that doctors had not found out about yet. Across the three items, 66%–77% of children and their parents agreed in their endorsement of diagnostic uncertainty. Parents who believed that something else was going on with their child’s pain had children with higher avoidance of pain-related activities (F = 5.601, p = 0.020) and lower pain willingness (F = 4.782, p = 0.032). Neither parent nor child diagnostic uncertainty was significantly related to the child’s pain-related functioning. Diagnostic uncertainty, particularly in parents, is relevant in the experience of pediatric chronic pain and warrants further investigation as both a risk factor and therapeutic target.

No abstract