Depressive symptoms, but not OSA severity, are associated with general fatigue in myasthenia gravis

General fatigue is a common and disabling symptom in myasthenia gravis (MG), distinct from muscle fatigability, and often associated with impaired quality of life. Sleep-disordered breathing, particularly obstructive sleep apnea (OSA), has been proposed as a potential contributor, but evidence in MG remains limited and inconsistent.

We conducted a prospective observational study of clinically stable MG patients recruited from two neuromuscular clinics in Toronto, Canada (April 2022-February 2023). Participants completed validated questionnaires assessing fatigue (Neuro-QoL, MFIS), sleep quality (PSQI), daytime sleepiness (ESS), depression (BDI), and MG symptom severity (MGII), and performed a 10-min psychomotor vigilance task (PVT). Home sleep apnea testing (HSAT) was performed over two nights using the MediByte device, with indices including apnea-hypopnea index (AHI), oxygen desaturation index (ODI), mean SpO₂, and percent time below 90% oxygen saturation (T90%). Separate linear regression models examined associations between each predictor and fatigue, separately adjusting for age, sex, or BMI. Partial rank-order Spearman correlations adjusting for age, sex, and BMI were performed. Additional analyses further adjusted for AHI (alongside age, sex, and BMI) when examining the relationship between depression and fatigue and similarly, when examining the relationship between AHI and fatigue, we adjusted for depression, age, sex, and BMI.

Of 66 approached patients, 25 were enrolled with complete HSAT data. The mean age was 62.2 ± 14.5 years, 40% were female, and median BMI was 26.5 [23.3, 31.4] kg/m². OSA severity indices (AHI, ODI, mean SpO₂, T90%) were not significantly associated with Neuro-QoL or MFIS fatigue scores. Depression (BDI) was consistently associated with greater fatigue across all models (p < 0.001). MG symptom severity (MGII) and PVT performance showed selective associations with fatigue depending on the scale used.

In this cohort, general fatigue in MG was not statistically associated with OSA-related variables, nor with other sleep parameters. However, these findings should be interpreted as an absence of detected association rather than evidence of no relationship. Conversely, depressive symptoms demonstrated consistent associations with fatigue scales, perhaps highlighting an importance for screening in MG patients. However, given the cross-sectional nature of this study, longitudinal studies are needed to clarify causal relationships amongst these variables. Given the modest sample size, risk of Type II error, and use of HSAT (which may not capture the full spectrum of sleep-disordered breathing) these results should be interpreted as hypothesis-generating.