A sleeping beast: Obstructive sleep apnea and stroke

CLINICAL MANIFESTATIONS OF OSA NOT OBVIOUS AFTER STROKE

OSA typically causes both daytime symptoms (excessive sleepiness, poor concentration, morning headache, depressive symptoms) and nighttime signs and symptoms (snoring, choking, gasping, night sweats, insomnia, nocturia, witnessed episodes of apnea).^3,4,26 Unfortunately, because these are nonspecific, OSA is often underdiagnosed.^4,26

Identifying OSA after a stroke may be a particular challenge, as patients often do not report classic symptoms, and the typical picture of OSA may have less predictive validity in these patients.^1,27,28 Within the first 24 hours after a stroke, hypersomnia, snoring history, and age are not predictive of OSA.¹ Patients found to have OSA after a stroke frequently do not have the traditional symptoms (sleepiness, snoring) seen in usual OSA patients. And they have higher rates of OSA at a younger age than the usual OSA patients, so age is not a predictive risk factor. In addition, daytime sleepiness and obesity are often absent or less prominent.^1,9,27,28  Finally, typical OSA signs and symptoms may be attributed to the stroke itself or to comorbidities affecting the patient, lowering suspicion for OSA.

OSA MAY HINDER STROKE RECOVERY, WORSEN OUTCOMES

OSA, particularly when moderate to severe, is linked to pathophysiologic changes that can hinder recovery from a stroke.

Intermittent hypoxemia during sleep can worsen vascular damage of at-risk tissue: nocturnal hypoxemia correlates with white matter hyperintensities on magnetic resonance imaging, a marker of ischemic demyelination.²⁹ Oxidative stress and release of inflammatory mediators associated with intermittent hypoxemia may impair vascular blood flow to brain tissue attempting to repair itself.³⁰ In addition, sympathetic overactivity and Pco₂ fluctuations associated with OSA may impede cerebral circulation.

Taken together, such ongoing nocturnal insults can lead to clinical consequences during this vulnerable period.

A 1996 study³¹ of patients recovering from a stroke found that an oxygen desaturation index (number of times that the blood oxygen level drops below a certain threshold, as measured by overnight oximetry) of more than 10 per hour was associated with worse functional recovery at discharge and at 3 and 12 months after discharge. This study also noted an association between time spent with oxygen saturations below 90% and the rate of death at 1 year.

A 2003 study³² reported that patients with an AHI greater than 10 by polysomnography spent an average of 13 days longer on the rehabilitation service and had worse functional and cognitive status on discharge, even after controlling for multiple confounders. Several subsequent studies have confirmed these and similar findings.^8,33,34

OSA has also been linked to depression,³⁵ which is common after stroke and may worsen outcomes.³⁶ The interaction between OSA, depression, and poststroke outcomes warrants further study.

In the general population, OSA has been independently associated with increased risk of stroke or death from any cause.^21,22,37 These associations have also been reported in the poststroke population: a 2014 meta-analysis found that OSA increased the risk of a repeat stroke (relative risk [RR] 1.8, 95% confidence interval [CI] 1.2–2.6) and all-cause mortality (RR 1.69, 95% CI 1.4–2.1).³⁸

TESTING FOR OSA AFTER STROKE

Because of the high prevalence of OSA in patients who have had a stroke and the potential for worse outcomes associated with untreated OSA, there should be a low threshold for evaluating for OSA soon after stroke. Objective testing is required to qualify for therapy,  and the gold standard for diagnosis of OSA is formal polysomnography conducted in a sleep laboratory.^2–4 Unfortunately, polysomnography may be unacceptable to some patients, is costly, and is resource-intensive, particularly in an inpatient or rehabilitation setting.²⁸ Ideally, to optimize testing efficiency, patients should be screened for the likelihood of OSA before polysomnography is ordered.

Questionnaires can help determine the need for further testing

Questionnaires developed to assess OSA risk³⁹ include the following:

The Berlin questionnaire, developed in 1999, has 10 questions assessing daytime and nighttime signs and symptoms and presence of hypertension.

The STOP questionnaire, developed in 2008, assesses snoring, tiredness, observed apneic episodes, and elevated blood pressure.

The STOP-BANG questionnaire, published in 2010, includes the STOP questions plus BMI over 35 kg/m², age over 50, neck circumference over 41 cm, and male gender.

A 2017 meta-analysis³⁹ of 108 studies with nearly 50,000 people found that the STOP-BANG questionnaire performed best with regard to sensitivity and diagnostic odds ratio, but with poor specificity.

These screening tools and modified versions of them have also been evaluated in patients who have had a stroke.

In 2015, Boulos et al²⁸ found that the STOP-BAG (a version of STOP-BANG that excludes neck circumference) and the 4-variable (4V) questionnaire (sex, BMI, blood pressure, snoring) had moderate predictive value for OSA within 6 months after sroke.

In 2016, Katzan et al⁴⁰ found that the STOP-BAG2 (STOP-BAG criteria plus continuous variables for BMI and age) had a high sensitivity for polysomnographically diagnosed OSA within the first year after a stroke. The specificity was significantly better than the STOP-BANG or the STOP-BAG questionnaire, although it remained suboptimal at 60.5%.

In 2017, Sico et al⁴¹ developed and assessed the SLEEP Inventory (sex, left heart failure, Epworth Sleepiness Scale, enlarged neck, weight in pounds, insulin resistance or diabetes, and National Institutes of Health Stroke Scale) and found that it outperformed the Berlin and STOP-BANG questionnaires in the poststroke setting. The SLEEP Inventory had the best specificity and negative predictive value, and a slightly better ability to correctly classify patients as having OSA or not, classifying 80% of patients correctly.

These newer screening tools (eg, STOP-BAG, STOP-BAG2, SLEEP) can be used to identify with reasonable accuracy which patients need definitive testing after stroke.

Pulse oximetry is another possible screening tool          

Overnight pulse oximetry may also help screen for sleep apnea and stratify risk after a stroke. A 2012 study⁴² of overnight oximetry to screen patients before surgery found that the oxygen desaturation index was significantly associated with the AHI measured by polysomnography. However, oximetry testing cannot distinguish between OSA and central sleep apnea, so it is insufficient to diagnose OSA or qualify patients for therapy. Further study is needed to examine the ability of overnight pulse oximetry to screen or to stratify risk for OSA after stroke.

Polysomnography vs home testing

Polysomnography is the gold standard for diagnosing OSA. Benefits include technical support and trouble-shooting, determining relationships between OSA, body position, and sleep stage, and the ability to intervene with treatment.² However, polysomnography can be cumbersome, costly, and resource-intensive.

A home sleep apnea test, ie, an unattended, limited-channel sleep study, may be an acceptable alternative.^2–4,43,44 Home testing does not require a sleep technologist to be present during testing, uses fewer sensors, and is less expensive than overnight polysomnography, but its utility can be limited: it fails to accurately discriminate between episodes of OSA and central sleep apnea, there is potential for false-negative results, and it can underestimate sleep apnea burden because it does not measure sleep.²

Institutional resources and logistics may influence the choice of diagnostic modality. No data exist on outcomes from different diagnostic testing methods in poststroke patients. Further research is needed.