Fatigue is one of the most disabling side effects in people with multiple sclerosis. While this fact is well known, there has been a remarkable lack of progress in determining the pathophysiological mechanisms behind fatigue and the establishment of effective treatments. The main barrier has been the lack of a unified definition of fatigue that can be objectively tested with validated experimental models. In this “perspective article” we propose the use of the following model and definition of fatigue: the decrease in physical and/or mental performance that results from changes in central, psychological, and/or peripheral factors. These changes depend on the task being performed, the environmental conditions it is performed in, and the physical and mental capacity of the individual. Our definition and model of fatigue outlines specific causes of fatigue and how it affects task performance. We also outline the strengths and weaknesses of commonly used measures of fatigue and suggest, based on our model and definition, new research strategies, which should include multiple measures. These studies should be mechanistic with validated experimental models to determine changes in central, psychological, and/or peripheral factors that explain fatigue. The proposed new research strategies may lead to the identification of the origins of MS related fatigue and the development of new, more effective treatments.
Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique used to modulate cortical activity. However, measured effects on clinically relevant assessments have been inconsistent, possibly due to the non-focal dispersion of current from traditional two electrode configurations. High-definition (HD)-tDCS uses a small array of electrodes ( N = 5) to improve targeted current delivery. The purpose of this study was to determine the effects of a single session of anodal and cathodal HD-tDCS on gait kinematics and kinetics and the corticomotor response to transcranial magnetic stimulation (TMS) in individuals post-stroke. We hypothesized that ipsilesional anodal stimulation would increase the corticomotor response to TMS leading to beneficial changes in gait. Eighteen participants post-stroke (average age: 64.8 years, SD : 12.5; average months post-stroke: 54, SD : 42; average lower extremity Fugl-Meyer score: 26, SD : 6) underwent biomechanical and corticomotor response testing on three separate occasions prior to and after HD-tDCS stimulation. In a randomized order, anodal, cathodal, and sham HD-tDCS were applied to the ipsilesional motor cortex for 20 min while participants pedaled on a recumbent cycle ergometer. Gait kinetic and kinematic data were collected while walking on an instrumented split-belt treadmill with motion capture. The corticomotor response of the paretic and non-paretic tibialis anterior (TA) muscles were measured using neuronavigated TMS. Repeated measures ANOVAs using within-subject factors of time point (pre, post) and stimulation type (sham, anodal, cathodal) were used to compare effects of HD-tDCS stimulation on measured variables. HD-tDCS had no effect on over ground walking speed ( P > 0.41), or kinematic variables ( P > 0.54). The corticomotor responses of the TA muscles were also unaffected by HD-tDCS (resting motor threshold, P = 0.15; motor evoked potential (MEP) amplitude, P = 0.25; MEP normalized latency, P = 0.66). A single session of anodal or cathodal HD-tDCS delivered to a standardized ipsilesional area of the motor cortex does not appear to alter gait kinematics or corticomotor response post-stroke. Repeated sessions and individualized delivery of HD-tDCS may be required to induce beneficial plastic effects. Contralesional stimulation should also be investigated due to the altered interactions between the cerebral hemispheres post-stroke.
BACKGROUND: In patients with Multiple Sclerosis (MS), comparative leg muscle strength asymmetries are common and typically accompanied by walking difficulties. Underlying mechanisms for these asymmetries are not completely known, but altered muscle energetics may play a role. OBJECTIVE: To investigate glucose uptake asymmetries in leg muscles of patients with mild MS during walking. METHODS: Eight MS and 8 healthy control (CON) participants performed a 15-min treadmill walking test at self-selected speed. They were injected with a glucose tracer ( 18 F-FDG) two minutes into the test and immediately upon completion, underwent Positron Emission Tomography/Computed Tomography (PET/CT) imaging. RESULTS: MS group walked at a lower speed than the healthy control group (P < 0.01), however it was found that: 1) ([ 18 F]-FDG) uptake in knee and hip flexors was higher compared to the CON group (P = 0.02); 2) the MS group exhibited asymmetrical strength of the knee flexors (P = 0.03); 3) [ 18 F]-FDG uptake was significantly lower in the weaker knee flexors of patients with MS (P < 0.01). CONCLUSIONS: [ 18 F]-FDG uptake and strength asymmetries in the legs of patients with MS indicate greater metabolic costs during activity, which may play a major role in premature muscle fatigability and subsequent impaired walking capacity.
Background: In this pilot study, we examined the effects of ipsilesional high-frequency rTMS (iHF-rTMS) and contralesional low-frequency rTMS (cLF-rTMS) applied via a double-cone coil on neurophysiological and gait variables in patients with chronic stroke. Objective/Hypothesis: To determine the group and individual level effects of two types of stimulation to better individualize neuromodulation for rehabilitation. Methods: Using a randomized, within-subject, double-blind, sham-controlled trial with 14 chronic stroke participants iHF-rTMS and cLF-rTMS were applied via a double-cone coil to the tibialis anterior cortical representation. Neurophysiological and gait variables were compared pre-post rTMS. Results: A small effect of cLF-rTMS indicated increased MEP amplitudes (Cohen's D; cLF-rTMS, d = −0.30). Group-level analysis via RMANOVA showed no significant group effects of stimulation (P > 0.099). However, secondary analyses of individual data
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