'Striking' Link Between Sleep Disturbances and Stroke

Deborah Brauser

August 04, 2016

Sleep-disordered breathing (SDB) and sleep-wake disturbances (SWD) may increase the risk for a first or secondary stroke and decrease stroke recovery, a large literature review shows.

A meta-analysis of 29 studies and 2343 patients with an ischemic or hemorrhagic stroke or transient ischemic attack showed that more than 72% had an SDB condition, as defined by an apnea-hypopnea index of more than 5 episodes per hour. These conditions include obstructive sleep apnea, central sleep apnea, or Cheyne-Stokes breathing.

SDB was also found to be an independent risk factor for stroke in another large meta-analysis.

As for SWDs, several studies showed a significant association between increased stroke risk and insomnia, hypersomnia, and restless legs syndrome (RLS).

These disorders were also found to "impair neuroplasticity processes and functional stroke recovery," but the investigators note that this was based on "mainly experimental studies."

"This analysis showed in a very striking and convincing way that this stroke information is quite uniform for different types of sleep disturbances," lead author Dirk M. Hermann, MD, professor and chair of vascular neurology and dementia at the University Hospital Essen in Germany, told Medscape Medical News.

"The findings weren't surprising, but they were impressive" and should signal to clinicians "to pay attention and properly diagnose patients after a stroke," added Dr Hermann.

The review was published online August 3 in Neurology.

Sleep/Stroke Link

In 2015, the investigators searched PubMed for a variety of terms, including "stroke," "sleep," "insomnia," and "periodic limb movements." From the 2691 hits received, they selected articles to evaluate "based on their contribution to our current understanding of sleep/stroke links."

The evaluation of SDB as a possible risk factor for stroke included four population-based studies that included 1475 participants in Wisconsin and 4.5 million participants surveyed in Denmark.

The first showed a significant association between the condition and a history of stroke (adjusted odds ratio [OR], 4.33). There were also 22 incidents of first strokes over 4 years among a cohort of 1189 participants with SDB.

In the Danish study, sleep apnea was a significant predictor for ischemic stroke (adjusted hazard ratio [HR], 1.23), especially in those younger than 50 years (HR, 1.80).

A meta-analysis from 2012 of nine population-based and prospective trials showed an OR of 2.24 for SDB as a predictor of stroke.

And a recent evaluation from Taiwan of 29,961 patients with SDB and 119,844 age- and sex-matched healthy peers showed that women with SDB had an adjusted HR of 1.44 for stroke after 14 years of follow-up, while men had an HR of 1.21.

The HR increased to 4.90 for women younger than age 36 years.

Need for Sleep

Studies of hypersomnia/excessive sleep/excessive daytime sleepiness show that this condition is most likely to occur after a subcortical and pontomesencephalic stroke.

"Although hypersomnia improves during the first months poststroke, fatigue can persist for years," the researchers report, adding that paramedian thalamic stroke is "[t]he most dramatic form of poststroke hypersomnia."

In addition, a need for increased sleep is often reported "for years" by patients who have had a bilateral stroke.

As for insomnia, the investigators note that its prevalence can be as high as 50% in patients after a stroke, although a study showed that two thirds of these patients had insomnia before stroke.

Insomnia after a stroke is often caused by such environmental factors as lighting or noise from a stroke unit or comorbidities, such as depression or pain, note the investigators. "Less commonly, insomnia may be directly related to brain damage."

There were also reports that after pontomesencephalic strokes, patients experienced "near-complete loss of sleep."

Two additional studies showed that within 1 month after stroke, 12% to 13% of patients had RLS, which was frequently accompanied by periodic limb movements during sleep.

"Patients exhibiting RLS exhibited a higher neck circumference and higher diabetes prevalence than patients without RLS," the study authors report.

Rapid eye movement (REM) sleep behavior disorder was also shown in approximately 11% of 119 patients with ischemic stroke. Six of these patients with REM disorder had brainstem infarctions.

In addition, the review showed that excessive sleep, significant or frequent excessive daytime sleepiness, sleeping less than 5 hours per night, and RLS/periodic limb movements were all independent risk factors for stroke.

Recovery Outcomes, Treatment Suggestions

When examining whether SDB affects recovery and outcomes in 10 studies with a total of 1203 patients with stroke or transient ischemic stroke, the investigators found all showed that those with SDB had increased risks for death or vascular events within approximately 2 years.

However, "only two studies…were truly powered for multivariable regression analyses."

For SWDs, various studies showed that hypersomnia impaired stroke recovery; insomnia was linked to poor life satisfaction, depression, and severe stroke; and patients with RLS had worse stroke recovery scores on the Rankin Scale and Barthel Index vs patients without RLS.

But again the investigators note limitations: Most of these studies had few patients and/or used experimental models.

Still, the overall results show that "SDB and SWD increase the risk of stroke in the general population and affect short- and long-term stroke recovery and outcome," write the researchers.

They note that, on the basis of the evidence, continuous positive airway pressure should be used to treat obstructive SDB. And for those with central SDB, "oxygen, biphasic positive airway pressure, and adaptive servoventilation may be considered."

As for SWDs, they urge caution when it comes to treating with medications. This includes using sedative antidepressants and hypnotics for insomnia, antidepressants or stimulants for hypersomnia, clonazepam for parasomnias, and dopaminergic medications for RLS.

More Testing Needed

"Current knowledge supports the systematic implementation of clinical procedures for the diagnosis and treatment of poststroke SDB and SWD on stroke units," the researchers add.

For SDB, oximetry or nasal flow measurement can diagnose, while respirography can confirm the diagnosis. For SWD detection, the investigators suggest asking about a patient's history and using questionnaires and actigraphies.

Dr Hermann noted in a release that few stroke patients are actually tested for sleep disorders, but these findings show that "that should change, as people with sleep disorders may be more likely to have another stroke or other negative outcomes, such as having to go to a nursing home after leaving the hospital."

"There are so many acute medical conditions related to a stroke. But we simply want to communicate these important observations," he concluded.

The study authors have disclosed no relevant financial relationships.

Neurology. Published online August 3, 2016. Abstract

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