Is central fatigue in multiple sclerosis a disorder of movement preparation?

Abstract

We tested the hypothesis that fatigue in MS is related to a dysfunction in cortical areas involved in movement preparation. Thirty-three patients with clinically definite MS (16 with fatigue MS-F, 17 without fatigue MS-NF) and a relapsing-remitting course, matched for disease severity and duration, disability scores and level of depression were enrolled. They underwent a combined assessment with magnetic resonance imaging (MRI) and transcranial magnetic stimulation (TMS) and, for the electrophysiological study, were compared with 12 healthy controls. MRI was used to assess regional and total lesion-load volume (LL) on T1- and T2-weighted sequences and total brain volume on T1-weighted sequences. With TMS we tested central motor conduction time, short intracortical inhibition (SICI) and facilitation (ICF), pre-movement facilitation related to a simple reaction time paradigm and the effect of short trains of 5-Hz repetitive TMS (rTMS). No significant differences were found in total and regional LL between MS-F and MS-NF, except for a significant increase in frontal lobe LL in MS-F. Neurophysiological assessment did not disclose any difference of SICI and ICF among the three groups. The significant increase of MEP size produced by 5 Hz rTMS in controls was absent in both MS-NF and MS-F. MS-F lacked pre-movement facilitation compared with MS-NF and controls. The lack of pre-movement facilitation and the increased frontal lobe lesion load were significantly correlated to the FSS score, suggesting that central fatigue in MS is probably due to a dysfunction of cortical motor areas involved in movement preparation.

Fatigue in multiple sclerosis – Insights into evaluation and management

“…Additionally, the short-interval intracortical inhibition (SICI), which reflects the GABAergic intracortical inhibitory mechanisms, was examined in two trials that yielded inconsistent outcomes. In other words, while Liepert et al found reduced SICI in highly fatigued MS patients compared to those with low fatigue [116], Morgante et al failed to obtain similar results [135]. The observed discrepancy might be due to differences in inclusion criteria with relatively more disabled patients in the first work.…”

“…TMS permits study of various interhemispheric and intrahemispheric processes. Three studies examined corticospinal excitability in fatigued and non-fatigued MS patients, but could not detect any relationship between fatigue and any of the following: motor threshold, motor evoked potentials (MEP) amplitude or central motor conduction time (CMCT) [116,135]. To note, motor threshold depends on the biophysical properties of motor neuron membranes; MEP amplitude and CMTC mainly assess the excitability and integrity of the corticospinal pathways [28].…”

Fatigue induced changes to kinematic and kinetic gait parameters following six minutes of walking in people with multiple sclerosis

“…The observed increases in positive work may also contribute to the 13 reported increase in effort and fatigue in people with MS, compared to healthy controls. People with MS are likely to increase the underlying central corticomotor activity needed to increase or maintain muscle power during walking, which could contribute further to walking-induced fatigue [38,[53][54][55].…”

Progress in multiple sclerosis research in the last year

“…To investigate this hypothesis, they recruited 33 patients with RRMS, who underwent MRI and transcranial magnetic stimulation (TMS). Results showed a significant increase in the burden of lesion load in frontal areas correlating with the degree of fatigue, expressed by the fatigue severity scale (FSS) score, thus demonstrating that frontal lobe impairment is associated with fatigue in MS [3].…”

“…Patients with fatigue (representing 40 % of the cohort) had higher expanded disability status scale (EDSS) scores, as well as a more pronounced CC atrophy [2]. Morgante et al [3] tested the hypothesis that central fatigue in MS might be correlated with a dysfunction in the cortical areas upstream of the pyramidal tract involved in motor planning and preparation. To investigate this hypothesis, they recruited 33 patients with RRMS, who underwent MRI and transcranial magnetic stimulation (TMS).…”