title: Integrity of hypothalamic fibers and cognitive fatigue in multiple sclerosis.
abstract: Cognitive fatigue is a common and disabling symptom of multiple sclerosis (MS), but little is known about its pathophysiology. The present study investigated whether the posterior hypothalamus, which is considered as the waking center, is associated with MS-related cognitive fatigue. We analyzed the integrity of posterior hypothalamic fibers in 49 patients with relapsing-remitting MS and 14 healthy controls. Diffusion tensor imaging (DTI) parameters were calculated for fibers between the posterior hypothalamus and, respectively, the mesencephalon, pons and prefrontal cortex. In addition, DTI parameters were computed for fibers between the anterior hypothalamus and these regions and for the corpus callosum. Cognitive fatigue was assessed using the Fatigue Scale for Motor and Cognitive Functions. Analyses of variance with repeated measures were performed to investigate the impact of cognitive fatigue on diffusion parameters. Cognitively fatigued patients (75.5%) showed a significantly lower mean axial and radial diffusivity for fibers between the posterior hypothalamus and the mesencephalon than cognitively non-fatigued patients (Group(⁎)Target area(⁎)Diffusion orientation: F=4.047; p=0.023). For fibers of the corpus callosum, MS patients presented significantly higher axial and radial diffusivity than healthy controls (Group(⁎)Diffusion orientation: F=9.904; p<0.001). Depressive mood, used as covariate, revealed significant interaction effects for anterior hypothalamic fibers (Target area(⁎)Diffusion orientation(⁎)Depression: F=5.882; p=0.021; Hemisphere(⁎)Diffusion orientation(⁎) Depression: F=8.744; p=0.008). Changes in integrity of fibers between the posterior hypothalamus and the mesencephalon appear to be associated with MS-related cognitive fatigue. These changes might cause an altered modulation of hypothalamic centers responsible for wakefulness. Furthermore, integrity of anterior hypothalamic fibers might be related to depression in MS.
authors: Klinikum Bremen-Ost, Department of Neurology, Züricher Str. 40, 28325 Bremen, Germany.
authors: Katrin
authors: K
authors: Hanken
authors: Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands.
authors: Paul
authors: P
authors: Eling
authors: Klinikum Bremen-Ost, Department of Neurology, Züricher Str. 40, 28325 Bremen, Germany.
authors: Andreas
authors: A
authors: Kastrup
authors: Fraunhofer-MeVis Institute, University of Bremen, Germany.
authors: Jan
authors: J
authors: Klein
authors: Klinikum Bremen-Ost, Department of Neurology, Züricher Str. 40, 28325 Bremen, Germany; University of Oldenburg, Institute of Psychology, 26111 Oldenburg, Germany. Electronic address: helmut.hildebrandt@uni-oldenburg.de.
authors: Helmut
authors: H
authors: Hildebrandt
mesh_terms: D000328:Adult; D001284:Atrophy / Q000473:pathology; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000209:etiology*; D003337:Corpus Callosum / Q000473:pathology; D038524:Diffusion Magnetic Resonance Imaging; D004185:Disability Evaluation; D005221:Fatigue / Q000209:etiology*; D005260:Female; D006801:Humans; D007034:Hypothalamus, Posterior / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications* / Q000473:pathology*; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D009483:Neuropsychological Tests; D016011:Normal Distribution
keywords: Brainstem; Diffusion tensor imaging; Fatigue; Histamine; Multiple sclerosis; Posterior hypothalamus