Post-stroke fatigue: a deficit in corticomotor excitability?

Abstract

The pathophysiology of post-stroke fatigue is poorly understood although it is thought to be a consequence of central nervous system pathophysiology. In this study we investigate the relationship between corticomotor excitability and self-reported non-exercise related fatigue in chronic stroke population. Seventy first-time non-depressed stroke survivors (60.36 ± 12.4 years, 20 females, 56.81 ± 63 months post-stroke) with minimal motor and cognitive impairment were included in the cross-sectional observational study. Fatigue was measured using two validated questionnaires: Fatigue Severity Scale 7 and Neurological Fatigue Index - Stroke. Perception of effort was measured using a 0-10 numerical rating scale in an isometric biceps hold-task and was used as a secondary measure of fatigue. Neurophysiological measures of corticomotor excitability were performed using transcranial magnetic stimulation. Corticospinal excitability was quantified using resting and active motor thresholds and stimulus-response curves of the first dorsal interosseous muscle. Intracortical M1 excitability was measured using paired pulse paradigms: short and long interval intracortical inhibition in the same hand muscle as above. Excitability of cortical and subcortical inputs that drive M1 output was measured in the biceps muscle using a modified twitch interpolation technique to provide an index of central activation failure. Stepwise regression was performed to determine the explanatory variables that significantly accounted for variance in the fatigue and perception scores. Resting motor threshold (R = 0.384; 95% confidence interval = 0.071; P = 0.036) accounted for 14.7% (R(2)) of the variation in Fatigue Severity Scale 7. Central activation failure (R = 0.416; 95% confidence interval = -1.618; P = 0.003) accounted for 17.3% (R(2)) of the variation in perceived effort score. Thus chronic stroke survivors with high fatigue exhibit high motor thresholds and those who perceive high effort have low excitability of inputs that drive motor cortex output. We suggest that low excitability of both corticospinal output and its facilitatory synaptic inputs from cortical and sub-cortical sites contribute to high levels of fatigue after stroke.

Mechanisms of poststroke fatigue

“…Those with slower movement speeds also reported heaviness of the affected limb,109 possibly a central sensory processing problem, which in turn may have led to choosing slower movement speeds. Those with slower movement speeds also exhibited low motor cortex excitability 106. It is unclear if these two findings have a direct relationship as it has previously been shown that motor cortex excitability does not encode movement speeds,110however, motor cortex excitability seems to be crucial in motor learning involving movement speeds 111.…”

“…However, a closer look at these investigations show that tests used to identify motor deficits are normally questionnaire-based scores of activities of daily living such as Barthel index, Rankin scale and National Institutes of Health Stroke Scale 25 28 34 46 56 86 104 105. Some studies use laboratory-based tasks to measure motor function such as action research arm test, nine-hole peg test (NHPT), grip strength106 and scales such as Fugl-Meyer 107. These measures, although useful to identify gross motor limitations relevant to daily life, are not accurate measures of motor impairment.…”

“…Low motor cortex excitability was also significantly correlated with high levels of PSF, but interestingly, voluntary activation, a measure of excitability of structures upstream of motor cortex such as secondary motor areas, was not significantly related to fatigue. Thus, PSF appears to be associated with behavioural108 and perceptual109 sensorimotor deficits with some underlying neurophysiological106 perturbations in the sensorimotor pathway.…”

Poststroke Fatigue: Emerging Evidence and Approaches to Management: A Scientific Statement for Healthcare Professionals From the American Heart Association

“…30,77 Physiologically, PSF appears be related to low excitability of corticospinal output and facilitatory synaptic inputs from cortical and subcortical sites. 85 Impaired motor control, as assessed by the Fugl-Meyer test, seems to be predictive of PSF. 41 …”

“…Some researchers theorize that PSF may be associated with disturbances in cortical excitability. One study examining patients after stroke with minimal neurological deficits 85 found that PSF was explained, in part, by higher motor thresholds measured with transcranial magnetic stimulation. It was suggested that low excitability of both corticospinal output and its facilitatory synaptic inputs from cortical and subcortical sites may contribute to PSF.…”