Muriel Stoppe1, Klara Meyer2, Maike Schlingmann2, Sebastian Olbrich3, Florian Then Bergh4. 1. Department of Neurology, University of Leipzig, Germany; Translational Centre for Regenerative Medicine, University of Leipzig, Germany. 2. Department of Neurology, University of Leipzig, Germany. 3. Department of Psychiatry, University Zurich, Germany. 4. Department of Neurology, University of Leipzig, Germany; Translational Centre for Regenerative Medicine, University of Leipzig, Germany. Electronic address: ThenBerF@medizin.uni-leipzig.de.
Abstract
BACKGROUND: Fatigue is common in multiple sclerosis (MS) patients. Exhaustion of physiological reserves and mental stress are postulated causes, the latter supported by more pronounced hypothalamic-pituitary-adrenal (HPA) axis activation in fatigued patients. Divergent dysregulation of arousal appears to play important roles in depression- (hyperstable arousal) and in cancer-related (unstable arousal) fatigue, where HPA axis is hyperactive or hypoactive, respectively. OBJECTIVE: This study assessed arousal regulation in multiple sclerosis patients, explored if fatigue can be physiologically described by altered arousal regulation, and if HPA axis activity corresponds to the type(s) of arousal regulation. METHODS: 51 mildly-affected patients with relapsing-remitting MS (86% on disease-modifying treatment) and 20 healthy controls were analysed via Vigilance Algorithm Leipzig and combined dexamethasone/corticotropin releasing hormone test. RESULTS: Hyperstable arousal pattern was significantly more frequent in patients than in controls (62.7% vs. 45.0%, p = 0.011). Patients scored higher on all fatigue, but not on sleepiness scales. All patients combined showed mild activation of the hypothalamic-pituitary-adrenal axis (p < 0.05 for post-CRH ACTH and AUC ACTH; cortisol n.s.). While fatigue was numerically more pronounced in both hyperstable and unstable arousal, HPA axis activity was highest in hyperstable and lowest in unstable arousal (p = 0.013 for post-CRH ACTH; p = 0.087 for AUC ACTH; cortisol n.s.). CONCLUSION: Frequency of arousal patterns are altered in MS. An association with HPA axis activity was weak, possibly because the present sample was stable on immunotherapy.
BACKGROUND:Fatigue is common in multiple sclerosis (MS) patients. Exhaustion of physiological reserves and mental stress are postulated causes, the latter supported by more pronounced hypothalamic-pituitary-adrenal (HPA) axis activation in fatiguedpatients. Divergent dysregulation of arousal appears to play important roles in depression- (hyperstable arousal) and in cancer-related (unstable arousal) fatigue, where HPA axis is hyperactive or hypoactive, respectively. OBJECTIVE: This study assessed arousal regulation in multiple sclerosispatients, explored if fatigue can be physiologically described by altered arousal regulation, and if HPA axis activity corresponds to the type(s) of arousal regulation. METHODS: 51 mildly-affected patients with relapsing-remitting MS (86% on disease-modifying treatment) and 20 healthy controls were analysed via Vigilance Algorithm Leipzig and combined dexamethasone/corticotropin releasing hormone test. RESULTS: Hyperstable arousal pattern was significantly more frequent in patients than in controls (62.7% vs. 45.0%, p = 0.011). Patients scored higher on all fatigue, but not on sleepiness scales. All patients combined showed mild activation of the hypothalamic-pituitary-adrenal axis (p < 0.05 for post-CRHACTH and AUC ACTH; cortisol n.s.). While fatigue was numerically more pronounced in both hyperstable and unstable arousal, HPA axis activity was highest in hyperstable and lowest in unstable arousal (p = 0.013 for post-CRHACTH; p = 0.087 for AUC ACTH; cortisol n.s.). CONCLUSION: Frequency of arousal patterns are altered in MS. An association with HPA axis activity was weak, possibly because the present sample was stable on immunotherapy.
Authors: Oliver Neuhaus; Wolfgang Köhler; Florian Then Bergh; Wolfgang Kristoferitsch; Jürgen Faiss; Thorsten Rosenkranz; Dirk Reske; Robert Patejdl; Hans-Peter Hartung; Uwe K Zettl Journal: Biomolecules Date: 2021-03-07