PS13.01 - Rehabilitative and Pharmacological Therapies for MS Fatigue: Current Trends and Gaps in Knowledge
Fatigue one of the most common and consequential symptoms of MS, yet it remains one of the most challenging symptoms to treat.
This presentation aims to summarize the most frequently studied and promising rehabilitative and pharmacological treatments for MS-related fatigue. Pertinent study findings, knowledge gaps, and opportunities for future research directions will be discussed. The epidemiology and impact of MS-related fatigue will also be briefly reviewed.
Invited presentation for ACTRIMS-ECTRIMS MSVirtual2020 Session PS13: Innovations in Symptomatic and Rehabilitative Therapy.
Review of the most commonly used and promising non-pharmacological (cognitive behavioral therapy, exercise-based strategies) and pharmacological (amantadine, modafinil, and methylphenidate) treatments for MS fatigue, including supporting literature.
Multiple rehabilitative (non-pharmacological) and pharmacological treatments have been studied for MS-fatigue. Non-pharmacological treatments including cognitive behavioral therapy and exercise-based strategies have shown promise, with some demonstrating moderate efficacy in clinical trials. Additional research that incorporates individual patient traits, multimodal fatigue measures, and important effect modifiers is necessary to better understand the most appropriate role for pharmacological treatments, treatment sequencing, and combination therapies to optimize fatigue management for persons with MS.
PS13.02 - Randomized Trial of Amantadine, Modafinil and, Methylphenidate for Multiple Sclerosis Fatigue
Methylphenidate, modafinil, and amantadine are commonly prescribed medications for alleviating fatigue in multiple sclerosis (MS); however, the evidence supporting their efficacy is sparse and conflicting.
Our goal was to compare the efficacy of these three medications against each other and placebo in patients with MS-related fatigue.
In this randomized, double-blind, placebo-controlled, four-sequence, four-period crossover trial, patients with MS fatigue received twice-daily oral amantadine, modafinil, methylphenidate, or placebo, each given for up to six weeks. The primary outcome measure was the Modified Fatigue Impact Scale (MFIS) measured while taking the highest tolerated dose. Secondary outcomes included measures of sleepiness, adverse events, and the maximal tolerated dose of each medication.
A total of 141 patients were enrolled and randomly assigned to one of four medication administration sequences. Data from 136 participants were available for the intent-to-treat analysis of the primary outcome. The estimated mean values of MFIS total scores at baseline and the maximal tolerated dose were as follows: 51.3 at baseline, 40.7 with placebo, 41.2 with amantadine, 39.0 with modafinil, and 38.7 with methylphenidate (P=0.20 for the overall medication effect). As compared to placebo (30.6%), higher proportions of participants reported adverse events while taking amantadine (38.6%), modafinil (40.0%), and methylphenidate (39.5%).
Amantadine, modafinil, and methylphenidate were not superior to placebo in improving MS-related fatigue and caused more frequent adverse events. The results of this study do not support an indiscriminate use of amantadine, modafinil, and methylphenidate for the treatment of fatigue in MS. (ClinicalTrials.gov number, NCT03185065.)
PS13.03 - MRI correlates of Cognitive Improvement after Home-Based EEG Neurofeedback Training in MS: A Pilot Study
Neurofeedback training shows promise to improve cognitive function in neurological patients. However, to date the underlying brain mechanisms of such improvements are poorly understood.
To investigate MRI correlates of cognitive improvement after EEG-based neurofeedback training in patients with MS (pwMS).
Fourteen pwMS (7 female; mean age = 38.9, SD=2.2; disease duration = 9 years, SD= 1.9; median EDSS= 2.5 (3.5)) performed ten neurofeedback training sessions within 3-4 weeks at home using a tele-rehabilitation system. Half of the pwMS (N = 7 Responder) successfully learned to self-regulate sensorimotor rhythm (SMR, 12-15 Hz) in the EEG by receiving visual feedback and showed cognitive improvements (assessed by the overall T-score change of the BRB-N) after neurofeedback training. Non-responders (N=7) did neither improve in cognitive function nor were able to modulate their brain activity. Diffusion-tensor imaging and resting-state fMRI was performed before and after neurofeedback training. Whole brain fractional anisotropy (FA) and functional connectivity (FC) of the default-mode, sensorimotor and salience network were explored.
At baseline, responders and non-responders were comparable regarding sex, age, education, disease duration, physical and cognitive function and T2-lesion-load. Responders showed increased FA and FC within the salience network (FCSal) and sensorimotor network after neurofeedback training compared to non-responders. Training-related increases in FCSal correlated with cognitive improvement (r=0.886, p<0.0001).
This exploratory study suggests that neurofeedback training could successfully lead to cognitive improvement and associated changes in brain microstructure and FC.