Faculty Bibliography

BACKGROUND: Cognitive impairment is a common and troubling feature of pediatric-onset multiple sclerosis (POMS). Brief cognitive assessment in the outpatient setting can identify and longitudinally monitor cognitive involvement so that early intervention is possible. OBJECTIVES: The goal of this study was to measure the sensitivity of two cognitive assessment approaches that are brief, repeatable, and suitable for clinical practice and for multicenter investigation. METHODS: Participants with POMS ( n = 69) were consecutively evaluated as part of outpatient neurologic visits and compared to healthy control participants (HC, n = 66) using the Brief International Cognitive Assessment for MS (BICAMS) approach and timed information processing measures from Cogstate, a computer-based assessment. RESULTS: There was strong agreement in the detection rate of impairment between both assessments, with 26% for the BICAMS and 27% for Cogstate. Two of the Cogstate tasks were the most sensitive individual measures. CONCLUSION: Both the BICAMS and Cogstate timed processing measures offer practical, sensitive, and standardized approaches for cognitive screening assessment in POMS.

[This corrects the article DOI: 10.1371/journal.pone.0177177.].

The remotely supervised tDCS (RS-tDCS) protocol enables participation from home through guided and monitored self-administration of tDCS treatment while maintaining clinical standards. The current consensus regarding the efficacy of tDCS is that multiple treatment sessions are needed to observe targeted behavioral reductions in symptom burden. However, the requirement for patients to travel to clinic daily for stimulation sessions presents a major obstacle for potential participants, due to work or family obligations or limited ability to travel. This study presents a protocol that directly overcomes these obstacles by eliminating the need to travel to clinic for daily sessions. This is an updated protocol for remotely supervised self-administration of tDCS for daily treatment sessions paired with a program of computer-based cognitive training for use in clinical trials. Participants only need to attend clinic twice, for a baseline and study-end visit. At baseline, participants are trained and provided with a study stimulation device, and a small laptop computer. Participants then complete the remainder of their stimulation sessions at home while they are monitored via videoconferencing software. Participants complete computerized cognitive remediation during stimulation sessions, which may serve a therapeutic role or as a "placeholder" for other computer-based activity. Computers are enabled for real-time monitoring and remote control by study staff. Outcome measures that assess feasibility and tolerance are administered remotely with the aid of visual analogue scales that are presented onscreen. Following completion of all RS-tDCS sessions, participants return to clinic for a study end visit in which all study equipment is returned. Results support the safety, feasibility, and scalability of the RS-tDCS protocol for use in clinical trials. Across 46 patients, 748 RS-tDCS sessions have been completed. This protocol serves as a model for use in future clinical trials involving tDCS.

Background: Fatigue is known for being one of the most debilitating and common symptoms of multiple sclerosis (MS). Despite its prevalence, though, reliable treatment options are lacking. Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation treatment that uses low amperage (2.0 mA) electric current to stimulate cortical regions. tDCS has been shown to improve fatigue in MS following consecutive daily treatment sessions. We have recently developed and shown the feasibility of a remotely supervised tDCS (RS-tDCS) protocol to ease the burden of daily sessions and allow patients to complete the treatment at home. We aim to evaluate the efficacy of RS-tDCS in fatigue management for patients with MS. Methods: We enrolled n = 31 patients with MS (all subtypes) into a randomly controlled, double-blind trial; n = 27 patients provided data for analysis with n = 15 randomized to the active group and n = 12 in the placebo or "sham" group. Participants came to the clinic for baseline and follow-up measures including self-report forms on fatigue. At baseline they were also trained in operating the tDCS headset. Participants then took the device home where they complete 20 sessions of tDCS (20 minutes, 2.0 mA, dorsolateral prefrontal cortex montage, left anodal) paired with cognitive training. Results: Our primary outcome measure was the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue scale. When comparing change in PROMIS Fatigue between the active and sham tDCS groups we found that active tDCS participants had significantly greater reductions in fatigue (mean change in Active =-5.6 +/- 8.9 vs. Sham = 0.9 +/- 1.9, p = 0.02 conditions). We analyzed the within-subject effect tDCS had and found a significant, beneficial effect in the active group (pre-treatment mean = 26.6 +/- 9.2, post-treatment mean = 21.0 +/- 6.4, p = 0.04) and no such effect in the sham group (pre-treatment mean = 22.9 +/- 7.9, post-treatment mean = 23.8 +/- 8.4, p = 0.15). Finally, we calculated Cohen's d effect size (Active d =-0.71, Sham d = 0.11). Conclusions: These data suggest that RS-tDCS provides significant reduction in MS-related fatigue