Prevalence and correlates of periodic limb movements in OSA and the effect of CPAP therapy

Abstract

ObjectiveWe sought to assess the prevalence, correlates, and consequences of periodic limb movements of sleep (PLMS) in persons with obstructive sleep apnea (OSA) and the effect (worsening or improvement) of continuous positive airway pressure (CPAP) therapy on PLMS in a large prospective multicenter randomized controlled trial.MethodsWe performed retrospective analyses of data from the Apnea Positive Pressure Long-term Efficacy Study, a prospective multicenter randomized controlled trial. A total of 1,105 persons with OSA enrolled in this study underwent a polysomnographic investigation at baseline, another one for CPAP titration, and another study 6 months after randomization to either active CPAP or sham CPAP.ResultsOf all participants, 19.7% had PLM index (PLMI) ≥10/hour, 14.8% had PLMI ≥15/hour, 12.1% had PLMI ≥20/hour, 9.3% had PLMI ≥25/hour, and 7.5% had PLMI ≥30/hour. The odds of having a PLMI ≥10 were higher in older participants (odds ratio [OR] 1.03, p < 0.001), men (OR 1.63. p = 0.007), those using antidepressants (OR 1.48. p = 0.048), and those with higher caffeine use (OR 1.01, p = 0.04). After controlling for OSA and depression, PLMS were associated with increased sleep latency, reduced sleep efficiency, and reduced total sleep time. No significant relationships were noted between PLMS frequency and subjective sleepiness (Epworth Sleepiness Scale score) or objective sleepiness (Maintenance of Wakefulness Test). There was no differential effect of CPAP in comparison to sham CPAP on PLMS after 6 months of therapy.ConclusionsPLMS are common in patients with OSA and are associated with a significant reduction in sleep quality over and above that conferred by OSA. Treatment with CPAP does not affect the severity of PLMS.

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

“…1 The incidence of PLMS increases with age and is associated with several predisposing medical conditions, including narcolepsy, Parkinson’s disease, idiopathic REM sleep behavior disorder, and diabetes mellitus. 3 Though there appears to be no clear link between PLMS and excessive daytime sleepiness, 4 , 5 PLMS has been reported to be associated with poorer sleep quality, 6 arousals 7 , 8 and possibly sleep fragmentation 4 and increased risks of cardiovascular diseases. 9 PLM is also observed in 80% of patients with restless legs syndrome (RLS) 10 and 24–48% of patients with Obstructive Sleep Apnea (OSA).…”

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

“…Transient hyperventilation response after awakening causes blood CO levels to continue to decline after the end of apnea events, aggravating ventilatory instability and perpetuates the cycle of repetitive arousals, leading to sleep disruption 17,32 . Indeed, this mechanism of low arousal threshold could offer an explanation for the increased arousals and reduced sleep e ciency in OSA-PLMS patients seen in some studies 6,7 , bridging the gap between the ostensibly unrelated symptoms of PLMS and OSA. Crucially, this negative effect is further compounded by the more recent nding that put into doubt the traditional belief that arousals are necessary for re-opening of the obstructed airway 18,33 , that is, arousals are not a "protective" mechanism as traditionally suggested and low ArTH contributes to the pathogenesis of severe OSA 34 .…”

“…Evidently, the underlying link between PLMS and a whole host of comorbidities warrant further investigation into this clinical disorder, despite its lack of frank clinical symptoms. In PLMS patients who are often treated by CPAP for their concomitant OSA, studies have shown that CPAP treatment has no clear impact on the severity of PLMS 6,13 . The current treatment approaches of PLMS mainly "borrow" from the pharmacological treatments of RLS, where the current guideline presents a "standard" level of recommendation for pramipexole and ropinirole and a "guideline" level of recommendation for levodopa with dopa decarboxylase inhibitor, opioids, gabapentin enacarbil in the treatment of RLS 45 .…”

“…The incidence of PLMS increases with age and is associated with several predisposing medical conditions, including narcolepsy, Parkinson's disease, idiopathic REM sleep behavior disorder, and diabetes mellitus 3 . Though there appears to be no clear link between PLMS and excessive daytime sleepiness 4,5 , PLMS has been reported to be associated with poorer sleep quality 6 , arousals 7,8 and possibly sleep fragmentation 4 and increased risks of cardiovascular diseases 9 . PLM is also observed in 80% of patients with restless legs syndrome (RLS) 10 and 24-48% of patients with Obstructive Sleep Apnea (OSA) 11 .…”

“…A large body of literature has demonstrated the close clinical association between Obstructive Sleep Apnea (OSA) and Periodic Limb Movements (PLM) [4][5][6]12 .…”