par Hrabovecky, Jeromy 
Président du jury Mary, Alison
Promoteur De Tiege, Xavier
Co-Promoteur Strauss, Mélanie
Publication Non publié, 2025-10-20
Président du jury Mary, Alison
Promoteur De Tiege, Xavier
Co-Promoteur Strauss, Mélanie
Publication Non publié, 2025-10-20
Thèse de doctorat
| Résumé : | Background: Multiple Sclerosis (MS) is a chronic, auto-immune, neuroinflammatory, neurodegenerative disease of the CNS that manifests in younger adults between the ages of 20-40 years old. Physical disability, cognitive impairment and neuropsychiatric disorders are among the main symptoms. Fatigue is commonly cited in up 90% of the MS population and is found even in early stages of the disease course; although, more recent research has called for a transition to fatigability for conceptualizing fatigue. Additionally, sleep disorders have been reported in up to 50 to 60% of persons with Multiple Sclerosis (PwMS). Despite the many contributions and advances that have been made, there are still only a limited number of studies that have investigated sleep disturbances with polysomnography (PSG). Taken together, this study aims to explore whether there are any possible links underlying disturbed sleep, problematic fatigue/fatigability and cognitive functioning, underpinned by neurophysiological correlates and controlled for with psychoaffective factors.Methods: A single-center, observational study was carried out between October of 2020 and December of 2024 of adult PwMS with the relapsing-remitting phenotype and a demographically-matched group of healthy controls (HC). Participants underwent a full neuropsychological battery, an individually adapted cognitive fatigue (CF)-induction task, overnight polysomnography and MRI recordings.Results: A total of 40 PwMS and 41 HC were enrolled, of which we were able to retain 34 PwMS and 32 HC. PwMS reported higher depression and anxiety scores, slower processing, and higher levels of long-term fatigue and state fatigue. Fatigability was normalized between the two groups when processing times were adapted. Cognitive abilities in the PwMS groups were significantly lower for verbal episodic memory, auditory short-term memory, processing speed, flexibility, reasoning and verbal fluency, however, performance was not more than 1 standard deviation below the norm (with the exception of episodic memory encoding). Sleep revealed lower sleep efficiency scores, lower total sleep time and more time awake after sleep onset, though these normalized after controlling for depression and anxiety. We found alterations in white matter and deep gray matter volumes (Thalamus, Basal Ganglia, Nucleus Accumbens, Cingulate Cortex). White matter and gray matter atrophy as well as lesion count correlated in varying ways with alterations in fatigue, processing speed, cognition and sleep, and though some mediation was found, we did not find conclusive evidence of mediating links between brain atrophy with sleep, fatigue or cognition. We did however find that processing speed mediated the impact of putamen and corpus callosum atrophy on long-term fatigue.Conclusion: Fatigue is a debilitating symptom of MS. Adapting tasks to match the individual’s capacities had a mediating effect on the perception of fatigue and reduced fatigability. This should be considered when developing strategies for symptom management. We found disruptions to sleep that normalized after controlling for psychoaffective factors, suggesting that the pathophysiology of MS may not be the underlying cause to disturbed sleep. Additionally, cognition, though slightly less performant than HC, was globally preserved. Moreover, we found atrophy in the thalamus, basal ganglia and white matter to be associated with decreased processing speed, but not necessarily fatigue, sleep or cognition. Instead, the lesion count seemed to be the most strongly associated with increased fatigue, impoverished sleep and cognitive difficulty. Lesser total sleep time correlated with cognitive performance. Taken together, we present results that favor an interest in fatigability over fatigue with consideration for processing capacity, in conjunction with anxiety and depression contributing considerably to sleep and cognition. This may provide new insights for treating MS early on in its evolution. |
