Fatigue and associated factors in myasthenia gravis: a nationwide registry study

Abstract

Fatigue is commonly associated with myasthenia gravis (MG), but factors contributing to fatigue development in MG are incompletely understood. This nationwide cross-sectional registry study included 1464 patients diagnosed with autoimmune MG, recruited between February 2019 and April 2023. Frequency and severity of fatigue was assessed at study inclusion using the patient-reported Chalder Fatigue Questionnaire (CFQ). Frequency of fatigue was 59%. Fatigue severity strongly correlated with both patient-reported and physician-assessed MG outcome measures (MG-ADL, MG-QoL15, QMG and MGFA classes) and was associated with a history of myasthenic exacerbation and/or myasthenic crises and a delay in diagnosis of more than 1 year after symptom onset. Fatigue was more prevalent in women and coincided with symptoms of depression, anxiety, and sleep dissatisfaction. Differences in fatigue severity were observed between antibody (ab) subgroups, with highest fatigue severity in LRP4-ab-positive patients and lowest fatigue severity in AChR-ab-positive patients. Fatigue is a frequent and clinically highly relevant symptom of MG. Early diagnosis and prevention of MG crises may limit the long-term burden of fatigue in patients with MG.

Fig. 1

Association of MG-related outcome measures, demographical and clinical features with fatigue severity. A Spearman’s Rank Correlation analysis of MG-ADL, MG-QoL15 and QMG with fatigue score, displayed as scatterplots with trendlines, and Kruskal–Wallis test comparing MGFA classes with respect to their median (mdn) fatigue scores. B Results of multiple linear regression analysis (n = 1464) with fatigue severity (CFQ) as dependent variable and demographical and disease-related features as independent variables; F-Ratio = 20.5, p < .001, R² = 0.43. The unstandardized regression coefficient (β) with 95% confidence interval indicates how much the dependent variable changes when the predictor variable changes by one unit. C Spearman’s Rank Correlation analysis of HADS-Depression (HADS-D), sleep disorders (ISI) and HADS-Anxiety (HADS-A) with fatigue severity, presented as scatterplots with trendlines, and univariate analyses comparing median fatigue scores in relation to sex, history of crises/exacerbations and time to diagnosis < / > 1 year. MGFA, current Myasthenia Gravis Foundation of America classification at examination date; CFQ, Chalder Fatigue Questionnaire; HADS, Hospital Anxiety and Depression Scale; ISI, Insomnia Severity Index; MG-ADL, Myasthenia Gravis Activities of Daily Living scale; MG-QoL15, Myasthenia Gravis Quality-of-Life15 score; QMG, Quantitative Myasthenia Gravis score