Integrity of hypothalamic fibers and cognitive fatigue in multiple sclerosis

• The posterior hypothalamus plays a key role in the regulation of wakefulness.
• We analyzed the relation between integrity of posterior hypothalamic fibers (DTI) and cognitive fatigue in 49 MS patients.
• Patients with and without cognitive fatigue differed in fiber integrity between mesencephalon and posterior hypothalamus.
• These differences might alter the modulation of neurotransmitter systems contributing to cognitive fatigue in MS patients.

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.