Low Arousal Threshold: A potential bridge between OSA and Periodic Limb Movements of Sleep

Objective: Periodic Limb Movements of Sleep (PLMS) is a poorly understood comorbidity with close association to Obstructive Sleep Apnea (OSA). The mechanistic link between the two is unclear. Recent studies on the latter have uncovered low respiratory arousal threshold as an important non-anatomical cause of the disorder. This study sought to investigate whether periodic limb movements are associated with the low respiratory arousal threshold (ArTH) in OSA. Methods: : Retrospective data on 720 OSA patients (mean age = 47.0) who underwent Polysomnography (PSG) were collected. Patients were divided into the OSA-PLMS group (n=116) and the OSA-only group (n=604). Multiple logistic regression analysis was used to examine the correlation between PLMS and its potential risk factors including clinical variables, polysomnographic parameters as well as low ArTH. The resulting model was validated in the external MrOS database. Results: The patients in the OSA-PLMS group tend to be older, with a higher prevalence of hypertension, diabetes, and stroke. Significant predictors of PLMS included age, diabetes, proportion of Stage N1 Sleep, average SaO₂, and low respiratory arousal threshold (OR=5.51 (3.35-9.05), p< 0.001). When validated against the MrOS database, low ArTH remained a significant predictor of PLMS with an odds ratio of 1.46 (1.18-1.81, p < 0.001). Interpretation: This is the first study that demonstrated a strong correlation between PLMS and low respiratory arousal threshold. This suggests a possible mechanistic link between the physical manifestations of PLMS and the non-anatomical low arousal threshold phenotype in OSA.