Fatigue in Cancer and Neuroinflammatory and Autoimmune Disease: CNS Arousal Matters.

Christine Ulke,Galina Surova,Christian Sander,Philippe Jawinski,Christoph Engel,Kerstin Wirkner,Ulrich Hegerl,Tilman Hensch

doi:10.3390/brainsci10090569

Abstract

The term fatigue is not only used to describe a sleepy state with a lack of drive, as observed in patients with chronic physical illnesses, but also a state with an inhibition of drive and central nervous system (CNS) hyperarousal, as frequently observed in patients with major depression. An electroencephalogram (EEG)-based algorithm has been developed to objectively assess CNS arousal and to disentangle these pathophysiologically heterogeneous forms of fatigue. The aim of this study was to test the hypothesis that fatigued patients with CNS hyperarousal score higher on depressive symptoms than those without this neurophysiological pattern. Methods: Subjects with fatigue (Multidimensional Fatigue Inventory sum-score > 40) in the context of cancer, neuroinflammatory, or autoimmune diseases were drawn from the 60+ cohort of the Leipzig Research Center for Civilization Diseases. CNS arousal was assessed by automatic EEG-vigilance stage classification using the Vigilance Algorithm Leipzig (VIGALL 2.1) based on 20 min EEG recordings at rest with eyes closed. Depression was assessed by the Inventory of Depressive Symptomatology (IDS-SR). Results: Sixty participants (33 female; median age: 67.5 years) were included in the analysis. As hypothesized, fatigued patients with CNS hyperarousal had higher IDS-SR scores than those without hyperarousal (F1,58 = 18.34; p < 0.0001, η2 = 0.240). Conclusion: hyperaroused fatigue in patients with chronic physical illness may be a sign of comorbid depression.

Highlights

Fatigue is a widespread symptom among patients with cancer, neuroinflammatory or autoimmune disease
Associations between TNF-α and sleepiness have been reported [25,37]. In view of these findings, we have proposed to define two subtypes of fatigue based on their assumed underlying neurobiological mechanisms concerning arousal regulation [11,12]—hyperaroused fatigue with reduced sleep propensity, inhibition of drive and exhaustion, and hypoaroused fatigue with increased sleepiness, a lack of drive, and sickness behaviour, typical in context of inflammatory and immunological processes [11]
Those 19 participants were assigned to the hyperaroused fatigue subgroup; all the others (n = 41) were assigned to the non-hyperaroused fatigue subgroup

Summary

Introduction

Fatigue is a widespread symptom among patients with cancer, neuroinflammatory or autoimmune disease. Severe chronic fatigue is reported in 41–57% of patients with rheumatoid arthritis [1], and in 67% of patients with Sjogren’s syndrome [2]. The prevalence rate ranges from 59% to 100%, depending on the clinical status of the cancer [3]. Parkinson’s disease, prevalence rates between 37% and 57% [4] have been reported. More than 80% of multiple sclerosis patients suffer from intractable chronic fatigue within the first year of disease onset [5]. Brain Sci. 2020, 10, 569; doi:10.3390/brainsci10090569 www.mdpi.com/journal/brainsci

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