Low Arousal Threshold: A Potential Bridge Between OSA and Periodic Limb Movements of Sleep

Abstract

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. Using PLMS diagnostic criteria of PLMS index ≥ 15, patients were divided into the OSA-PLMS group (n=95) and the OSA-only group (n=625). Binary logistic regression analysis was used to examine the correlation between PLMS and the presence of low ArTH, classified using a predicted tool (developed by Edward et al) requiring meeting at least two of the three criteria: apnea-hypopnea index (AHI) < 30/h, nadir oxygen saturation (SaO2) > 82.5%, and fraction of hypopneas > 58.3%. 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. PLMS was associated with age, diabetes, oxygen desaturation index, and low respiratory arousal threshold (OR=8.78 (4.73–16.30), p<0.001). When validated against the MrOS database, low ArTH remained a significant predictor of PLMS with an odds ratio of 1.33 (1.08–1.64, p = 0.009).

Conclusion

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 manifestation of PLMS and the non-anatomical low arousal threshold phenotype in OSA.

Keywords:

• obstructive sleep apnea
• periodic limb movements
• low respiratory arousal threshold

Ethics approval

Approved by the Research Ethics Committee of the Second Affiliated Hospital of Soochow University, Suzhou, China (JD-LK-2018-004-02). Our study was conducted in accordance with the Declaration of Helsinki.

Consent for participation and publication

Informed consent was sought from all patients involved, with the understanding that anonymized data could be used for research and publications.

Acknowledgment

The authors thank Fei Han and Hao Gui for conducting PSG scoring and Delu Wang for providing helpful suggestions for the study protocol.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work. The two first authors have contributed equally to the manuscript.

Disclosure

The authors report no conflicts of interest for this work.

Additional information

Funding

National Natural Science Foundation of China (NSFC 81770085, 82070095); Discipline Construction Program of the Second Affiliated Hospital of Soochow University (XKTJ-TD202003). MrOS Dataset: The National Heart, Lung, and Blood Institute provided funding for the ancillary MrOS Sleep Study and the National Sleep Research Resource.