Neurological

The Bidirectional Relationship Between Sleep Disorders and Stroke

Stroke is one of the major causes of disability and mortality worldwide, and the prevalence of stroke is expected to increase due to an aging population. People who suffer from a stroke can experience a wide range of symptoms, including sleep disorders, which can increase the risk for subsequent stroke. Additionally, patients with preexisting sleep disorders are at a greater risk for stroke.1

“Sleep disorders are associated with worsened stroke outcome, including both recurrent stroke and worsened functional recovery,” said Sandeep Prakash Khot, MD, MPH, associate professor of neurology at the University of Washington, and director of the Harborview Medical Center Consult Service in Seattle .

As the incidence of stroke increases in the US, organizations such as the American Heart Association and American Stroke Association recommend that more sleep studies be conducted to help prevent stroke recurrence or transient ischemic attack (TIA).2

While sleep is one of the most important physiological processes for healing, the relationship between sleep disorders and stroke is under continued investigation.

Sleep disorders are associated with worsened stroke outcome, including both recurrent stroke and worsened functional recovery.

Bidirectionality of Sleep Disorders and Stroke

Different types of sleep disorders are shown to be associated with stroke, including sleep-related breathing disorders, rapid eye movement (REM) sleep behavior disorders, and sleep-wake cycle disorders.3

Sleep-disordered breathing (SDB) is the most common sleep disorder experienced poststroke, with the most prevalent type being obstructive sleep apnea (OSA).4 “Obstructive sleep apnea is found in over 60% of stroke survivors in the acute setting, whereas insomnia , a sleep-wake cycle disorder, is prevalent in about 30% to 40% of stroke survivors,” Dr. Khot noted.

OSA is an established modifiable risk factor for stroke and is estimated to double the risk for stroke.3 This direct relationship was established in the Sleep Heart Health study, which reported an association between OSA severity and stroke risk.5 More recently, evidence shows that some comorbidities, such as stroke and heart failure, may predispose an individual to develop OSA.6

The bidirectional nature of sleep disorders and stroke could potentially lie in mechanisms for individual comorbidities. A 2022 study published in the European Respiratory Review demonstrates that poststroke sleep architecture can impair breathing control mechanisms centrally and can impact upper airway muscle function. Additionally, patients with OSA who present with stroke have higher National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale scores upon discharge

A 2019 study published in Sleep Medicine Reviews reported that prolonged sleep duration, defined as at least 8 hours of sleep or more, was associated with a 3.90-fold increased risk for stroke. Researchers also found that the endogenous sleep rhythm is disrupted after stroke and can be associated with increased stroke severity and worsened outcome. This study also identified that shift work, a circadian rhythm disorder, which was another risk factor for all-cause stroke (risk ratio [RR], 1.05; 95% CI, 1.01-1.09).7

Nonapnea sleep disorders, such as restless leg syndrome (RLS), REM sleep behavior disorder, and insomnia also increase the risk for an acute ischemic stroke. Sleep-related movement disorders were associated with an increased risk for all-cause stroke, with a hazard ratio of 2.29 (95% CI, 1.42-3.80).8

The Role of CPAP in Poststroke Treatment

Continuous positive airway pressure (CPAP) is the mainstay of treatment for OSA, but its role in poststroke treatment has conflicting recommendations.

Many studies show that CPAP use in treating OSA for patients with stroke provides more benefits compared with those who do not receive or are noncompliant with treatment.9 Some studies suggest beneficial effects in sleepiness, depression, and functional recovery.10-12 Other studies reported no apparent advantages in vascular event recurrence and no significant improvement in neurologic cognition, despite improvements in motor function.13,10

“CPAP use after stroke is currently limited. Screening for OSA is rarely initiated after stroke, estimated to occur in only about 6% of patients within 3 months of stroke,” Dr. Khot explained. “Stroke patients with OSA are not like OSA patients in the general population in that they are not typically overweight, sleepy, or even likely to snore, which makes our clinical suspicion of the disease difficult and makes the screening questionnaire insensitive.”

While an early diagnosis and treatment of OSA prior to stroke is strongly recommended, the role of screening and prevention for OSA is unclear poststroke. “Based on limited data, the American Stroke Association does not recommend routine screening in acute stroke but does suggest a role for stroke prevention,” Dr. Khot stated. “There may be more of an understanding that OSA is common and portends worse outcomes, but actual testing is rarely offered to many patients who might benefit, including those with refractory hypertension.”

Future Studies and Recommendations

One of the primary initial recommendations for people with sleep disorders and stroke is improving sleep hygiene by limiting noise and light in the bedroom. Another recommended therapy is cognitive-behavioral therapy (CBT) for patients with chronic sleep disorders. This therapy has been shown to reduce insomnia after stroke, although the long-term effects are not clear.1

In addition to patient education and therapy recommendations, further research is necessary to answer unresolved questions in this area.

“It’s important to understand that along with the effect on stroke recovery, OSA is an independent risk factor for stroke and is known to worsen other common stroke risk factors, such as hypertension, diabetes, and atrial fibrillation. It may be that the changes are too well-established for studies to show a significant effect of CPAP or that CPAP is just not the best therapy for this population as it is in the general population. Thus, there is an important knowledge gap and a need for rigorous trials in the field,” said Dr. Khot, on the need for further CPAP research.

A 2021 study published in Stroke assessed the body of data surrounding CPAP and poststroke OSA and proposed some considerations for future studies. Some suggestions were to ensure that patients are using CPAP for at least 4 hours, to initiate therapy within 48 hours of stroke, and to include patients with varying OSA severity and compliance.14

The American Heart Association and American Stroke Association also recommend future studies to consider the following:

  • Selection of patients who would likely benefit from CPAP;
  • Timing of CPAP treatment and testing relative to stroke onset;
  • home testing vs facility testing; other
  • Dosage and type of CPAP.15

dr Khot highlights a particular ongoing study with the potential to have a profound clinical impact in treatment of sleep disorders and stroke, stating “There is a large multicenter trial called Sleep for Stroke Management and Recovery Trial or Sleep SMART (ClinicalTrials.gov Identifier: NCT03812653) , which will evaluate in over 3000 participants the treatment of OSA with CPAP on both secondary prevention and acute stroke recovery. The study is part of a network of hospitals across the country called NIH StrokeNET.”

Other ongoing studies highlighted by the American Heart Association and American Stroke Association include the Recovery in Stroke Using PAP (RISE-UP) trial (ClinicalTrials.gov Identifier: NCT04130503) and the Addressing Sleep Apnea Post Stroke/TIA (ASAP) trial (ClinicalTrials. gov identifier: NCT04322162). The RISE-UP trial is determining the optimal timing of CPAP initiation poststroke and the ASAP trial is focused on assessing a quality improvement initiative in the Veterans Affairs Medical Administration.15

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