Assessment Committee:
- Professor Christina Kruuse (Chairperson)
- Professor Zsolt Illés
- Associate Professor Marco Bove
Supervisors:
- Professor Hartwig Roman Siebner
- Professor Finn Thorup Sellebjerg
- Associate Professor Tim Bjørn Dyrby
- PhD Kasper Winther Andersen
- PhD Kathrine Skak Madsen
Department:
Clinical Medicine
Graduate Programme:
Neuroscience
Summary:
Fatigue is one of the most common symptoms in multiple sclerosis (MS) patients. It is reported as one of the most invalidating symptoms in more than 50 per cent of the patients (Induruwa et al., 2012). Fatigue among MS patients has a tremendous impact on life quality and is thus one of the main reasons for unemployment (Krupp et al., 2010). The origin of fatigue still remains elusive despite of prior comprehensive studies. Fatigue has been related to disease-related alterations in the central nervous system (CNS), which is defined as primary causes. Other mechanisms, such as medication, poor sleep quality, pain, depression or physical or mental decline, have also been suggested, which is defined as secondary causes (Kos et al., 2008). Fatigue is considered a subjective feeling. Thus, there is an unmet need for objective measurements, which is beneficial in future MS fatigue studies, but also in other neurological diseases. MS diffusively attacks the whole CNS, and it is suggested that the grey and white matter is affected independently (Trapp et al., 2018). The aim of this project was to investigate whether fatigue was associated with the degree of grey- and white matter alterations. Since fatigue previously has shown to persist over time (Téllez et al., 2006), I hypothesize that the pathological structural alterations in MS might be an underlying mechanism. As the pivot in this study was motor fatigue, we investigated the corticospinal tracts (CST), which are responsible for the motor output, and the cortical and subcortical regions involved in motor performance.
Forty-six MS patients underwent diffusion weighted imaging (DWI) and clinical magnetic resonance imaging (MRI). Twenty-five healthy subjects were recruited as healthy controls (HC). Twenty-nine patients reported severe fatigue whereas 17 patients reported mild or no fatigue. The results revealed apparent increased anatomical connectivity in the left and dominant CST in fatigued MS patients compared to non-fatigued MS patients and HC. Contrarily, increased anatomical connectivity in the right CST was found in non-fatigued patients compared to HC. In general, increased connectivity was found in the bilateral CST among patients compared to HC. Moreover, fatigue was not associated with atrophy or lesion load. However, fatigued patients showed increased cortical thickness in some non-motor regions compared to non-fatigued patients.
The results suggest that motor fatigue is related to central motor fibres and crossing fibre systems. However, increased connectivity seems to reflect pathological alterations rather than an actual anatomical connectivity increase. Future studies are encouraged to focus on interactions between brain networks rather than focal regions in fatigued MS patients.