Fatigue and Mobility Post-Stroke

Fatigue post-stroke is a disabling and persistent symptom affecting many stroke survivors. Despite its high prevalence, the pathophysiology underlying this phenomenon remains obscure. Thus, the aim of this thesis was to study the neuromuscular basis underlying fatigue post-stroke and its association with self-reported fatigue and with the performance of tasks incorporating balance and mobility components. Community-dwelling stroke survivors who had mild to moderate deficits in functional balance and mobility participated in a series of investigations. Chapter 2 describes the initial validation of the Community Balance and Mobility (CB&M) scale for use in persons with chronic stroke. Chapter 3 reported the presence of self-reported fatigue, assessed with the Fatigue Assessment Scale and restricted functional balance and mobility, measured with the 6-minute walk test and with the CB&M. Based on the findings obtained from the twitch interpolation and transcranial magnetic stimulation techniques, stroke resulted in a shift of the origin of neuromuscular fatigue such that the participants with stroke were more susceptible to the development of central fatigue following a standardized fatigue task, whereas healthy subjects had more evidence of peripheral fatigue. Also, the results from Chapter 3 demonstrated that the susceptibility to central failure was positively associated with the increased self-reported fatigability and negatively with the 6-MWT and CB&M scores. In Chapter 4 changes in the intrinsic properties of the spinal motoneurons, manifested as prolongation of the afterhyperpolarization time-course estimated with the interval death rate transform method were demonstrated. Prolonged afterhyperpolarization may have contributed to the increased central fatigue observed on the paretic side of the participants with stroke. In summary, the stroke-induced disturbances along the neuromuscular system together with the post-stroke deficits in functional balance and mobility may compromise the ability of the central nervous system to cope with the increased physiological demands during physical activities. This may lead to the increased perception of effort, which could influence the performance of activities of daily living and may partially underlie the general complaint of fatigue experienced by people with stroke. The findings reported in this thesis have advanced the understanding of a pathophysiological basis of fatigue post-stroke, which is essential for developing and guiding effective rehabilitation treatments

Modeling Human Atrial Patho-Electrophysiology from Ion Channels to ECG - Substrates, Pharmacology, Vulnerability, and P-Waves

Half of the patients suffering from atrial fibrillation (AF) cannot be treated adequately, today. This thesis presents multi-scale computational methods to advance our understanding of patho-mechanisms, to improve the diagnosis of patients harboring an arrhythmogenic substrate, and to tailor therapy. The modeling pipeline ranges from ion channels on the subcellular level up to the ECG on the body surface. The tailored therapeutic approaches carry the potential to reduce the burden of AF