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BACKGROUND: Chronic fatigue is a prominent symptom in many sarcoidosis patients, affecting quality of life and interfering with treatment. This study investigated neuropsychobiological mechanisms and markers of chronic fatigue in sarcoidosis. METHODS: Thirty patients with a histological diagnosis of sarcoidosis were included. The Multidimensional Fatigue Inventory was used to define patients with and without chronic fatigue. All patients were then characterised using several depression, quality of life questionnaires, and executive functioning. Cognitive functioning and underlying neural correlates were assessed using an n-back task measuring working memory and (sustained) attention during functional magnetic resonance imaging. Sarcoidosis disease activity was determined using lung function, laboratory parameters, and exercise capacity. RESULTS: Nineteen patients had chronic fatigue and 11 did not; both groups had similar demographic and disease activity characteristics. Chronic fatigue patients showed more symptoms of depression and anxiety, and lower quality of life. During the n-back task, chronic fatigue was associated with a smaller increase in brain activation with increasing task difficulty versus the group without fatigue, especially in the angular gyrus. CONCLUSION: Inadequate adjustment of brain activation with increasing demands appears to be a potential neurobiological marker of chronic fatigue in sarcoidosis patients. The angular gyrus, which plays an important role in the working memory system, was the major area in which fatigue patients showed smaller increase of brain activation compared to those without fatigue. These findings might be relevant for a deeper understanding of chronic fatigue mechanisms in sarcoidosis and future clinical treatment of this disabling syndrome. TRIAL REGISTRATION: ClinicalTrials.gov, Trial registration number: NCT04178239Date of registration: November 26, 2019, retrospectively registeredURL: https://clinicaltrials.gov/ct2/show/NCT04178239.
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INTRODUCTION: Sarcoidosis is a chronic inflammatory disease often associated with chronic fatigue. Prevalence of fatigue can be measured via neuropsychological testing. Its pathophysiology is insufficiently understood. Structural analysis might help with the development of novel treatment methods. METHODS: We recruited 30 sarcoidosis patients whose fatigue severity and depressive symptom presence was measured through validated neuropsychological self-assessment. T1-weighted structural images were acquired and VBM preprocessing was conducted. Total scores of these tests and subscales were correlated through multiple regression analysis to the brain morphometry. RESULTS: Fatigue severity positively correlated with gray matter volumes in the striatum, the cingulate cortex and the cerebellum and negatively in the parietal and temporal lobe and posterior insula. Subscale analysis indicated a correlation between cognitive fatigue and striatum involvement as well as between physical and psychosocial fatigue and cerebellar alterations. DISCUSSION: Structural analysis delineated two structural patterns associated with the presence of fatigue. One such pattern mainly seemed to involve structures with a focus on decision-making processes while the other indicated alterations in regions vital for perception. Fatigue seems to be a heterogeneous disease, where varying dimensions of reported symptoms correlate with different patterns of structural changes.