Fatigue in MS is a strange duck, on many levels obvious and frequently described by PwMS (80-90%), but one that lacks sound medical explanation and science doesn’t even know how to test it yet. I was sure that the fatigue in MS, particularly exercise induced fatigue, was somehow related to the conduction block caused by the demyelination in the long tracts (corticospinal tract). It would seem that I was wrong.
In a study testing this specifically, Mordillo-Mateos et al. (see abstract at the bottom) used a hand grip task to squeeze a hand dynamometer for two mins to induce fatigue, and measured post-exercise motor evoked potentials, MEP (a measure of the descending corticospinal tract drive) and conduction times (CMCT) in the long tracts to the arms, to see if there was any depression in the readings. Additionally, they also evaluated the electrical pulse arising from the activated muscle fibres in the target muscle supplied by the nerve (compound muscle action potential, CMAP). The findings were compared with controls who didn’t have MS.
As expected, both MEP and CMCTs were smaller in the MS group than controls. The latter correlated with diminished maximal hand strength, i.e. the more prolonged the CMCT (corticopinal tract dysfunction) the less the maximal hand grip strength.
Following exercise, however, the MEP in the control group decreased immediately afterwards and then recovered slightly, while no changes were observed in the MS group (see figure below). The motor system fatigability (measured as a decrement in MEP as a percentage of the baseline value) was therefore larger in controls than the MS group. Similarly, the CMAP was decreased after exercise in the controls but not the MS group.
Both the MS group and the control group perceived a similar fatigue state of the executed task (i.e. the muscle effort produced during the handgrip task was somewhat hard irrespective of whether the person had MS). However, unlike in the control group where the fatigue was related to the task at hand, in the MS group the fatigue state was independent of the fatigue trait (i.e. MS group had higher perceived fatigue generally).
But, it would seem that the fatigue trait is independent of the corticospinal tract dysfunction, at least. One explanation for these findings is that in MS there is compensatory increase in central motor drive – previously reported by other researchers.
The problem of fatigue in MS may therefore be higher up, a result of the changes in brain connectivity, including reward and motivation brain circuits, as well as the re-organization that have taken place. So, exercise isn’t a bad thing, and possibly mindfulness programs can be tailored to tackle the brain fatigue.
Front Neurol. 2019 Apr 9;10:339. doi: 10.3389/fneur.2019.00339. eCollection 2019.
Fatigue in Multiple Sclerosis: General and Perceived Fatigue Does Not Depend on Corticospinal Tract Dysfunction.
Mordillo-Mateos L, Soto-Leon V, Torres-Pareja M, Peinado-Palomino D1, Mendoza-Laiz N3, Alonso-Bonilla C1, Dileone M4, Rotondi M5, Aguilar J6, Oliviero A1.
Background: Multiple sclerosis (MS) is an autoimmune disorder of the CNS in which inflammation, demyelination, and axonal damage of the central nervous system coexist. Fatigue is one of the most disabling symptoms in MS and little is known about the neurophysiological mechanisms involved. Methods: To give more mechanistic insight of fatigue in MS, we studied a cohort of 17 MS patients and a group of 16 age-matched healthy controls. Baseline Fatigue Severity Scales and Fatigue Rating were obtained from both groups to check the level of fatigue and to perform statistical correlations with fatigue-induced neurophysiologic changes. To induce fatigue we used a handgrip task. During the fatiguing task, we evaluated fatigue state (using a dynamometer) and after the task we evaluated the Borg Rating of Perceived Exertion Scale. Transcranial magnetic stimulation and peripheral electric stimulation were used to assess corticospinal tract and peripheral system functions before and after the task. Results: Clinically significant fatigue and central motor conduction time were greater in patients than in controls, while motor cortex excitability was decreased and maximal handgrip strength reduced in patients. Interestingly, fatigue state was positively correlated to perceived fatigue in controls but not in patients. Furthermore, in the presence of similar fatigue state over time, controls showed a significant fatigue-related reduction in motor evoked potential (a putative marker of central fatigue) whereas this effect was not seen in patients. Conclusions: in MS patients the pathogenesis of fatigue seems not driven by the mechanisms directly related to corticospinal function (that characterize fatigue in controls) but seems probably due to other “central abnormalities” upstream to primary motor cortex.