Multiple Sclerosis related Fatigue and the Hypothalamic-Pituitary-Adrenal Axis

Abstract

Introduction: Multiple sclerosis (MS) is a complex immune-mediated inflammatory and neurodegenerative disease of the central nervous system (CNS). Recent studies were repeatedly able to demonstrate hypothalamic-pituitary-adrenal axis (HPA axis) hyperactivity in MS patients. MS related fatigue (MSF) is one of its most disabling symptoms. Postulated mechanisms for MSF development include neuroendocrine, neuroimmune and structural abnormalities of the central nervous system. Other diseases with fatigue (e.g. chronic fatigue syndrome, major depression) have been found to be associated with HPA axis deregulation. Objective: This study investigated, whether MSF severity correlates with the extent of HPA axis hyperactivity. Patients and methods: In a prospective, cross-sectional study, 31 clinically stable MS patients definitely fulfilling MS-diagnostic criteria were recruited from the database of the MS outpatient clinic of the Department of Neurology, University Hospital Eppendorf. Exclusion criteria were applied (incomplete address in the database, a missing fatigue screening score (see next paragraph), an incomplete medical record, current pregnancy, current MS relapse, relapse during the last three months, steroid treatment within the last three months, known endocrine abnormality or clinical evident psychiatric disease). 16 Patients with MSF and 15 patients without MSF were enrolled into the study, using empirical cut-offs for the scores determined by the fatigue severity scale (FSS). Fatigue severity was correlated with endocrine parameters (ACTH, Cortisol) won by the combined dexamethasone/corticotropin-releasing hormone test (Dex/CRH test). Clinical characteristics (sleep quality, daytime sleepiness, disability, cognitive impairment, depression, quality of life) of the participants were examined. Results: MSF severity and endocrine parameters were not significantly associated. MSF severity significantly correlated with disease disability, diminished sleep quality, excessive daytime sleepiness and reduced quality of life. No correlation was found between MSF severity and cognitive impairment. The degree of cognitive impairment significantly correlated with the extent of HPA axis hyperactivity. Discussion: MSF severity did not significantly correlate with HPA axis hyperactivity. MSF and HPA axis activity may be secondary phenomena to the body‘s reaction to MS, possibly having a prognostic value in early stages of MS. HPA axis hyperactivity in cognitively impaired MS patients might be the result of neural loss of inhibiting cortico-subcortical pathways. Future studies should involve larger and more homogeneous patient samples.