Sleep Burden Index Predicts Recurrent Stroke

Pauline Anderson

May 26, 2020

A sleep burden index that considers multiple sleep-wake disturbances (SWDs) predicts subsequent cardio-cerebrovascular events during the 2 years after a stroke, preliminary results on an ongoing study suggest.

The index, which combines sleep duration, sleep disordered breathing, restless leg syndrome (RLS), insomnia, and sleep duration, is a better predictor of new events than a single sleep disorder alone.

Dr Simone B. Duss

With further evidence of its usefulness, "the sleep burden index could be integrated into clinical routine," Simone B. Duss, PhD, Department of Neurology, Bern University Hospital, Switzerland, told a press briefing.

The findings were presented online at the Congress of the European Academy of Neurology (EAN) 2020, which transitioned to a virtual meeting because of the COVID-19 pandemic.

Sleep-wake disorders are very common in stroke patients and may pre-exist or appear de novo as a consequence of brain damage, said Duss.

"They may also be a result of medical, psychological or environmental challenges these patients face after a stroke," she added.

Clear Evidence

There's "clear evidence" that sleep disordered breathing is a risk factor for stroke, and negatively affects stroke outcome if left untreated, said Duss.

But for other SWDs such as insomnia, RLS, and long and short sleep duration, "the evidence is less compelling," she said. "However, some studies still suggest they influence stroke risk and outcome."

Experts believe that sleep disturbances after a stroke lead to sleep fragmentation, as well as decreased slow wave sleep and REM sleep.

"This negatively affects inflammatory neuroprotective and synaptic plasticity processes during the recovery process of a stroke," said Duss. "In the end, this results in worse outcomes with regard to recurrent events but also in activities of daily living and mood."

The new analysis aimed to assess the impact of sleep-wake disturbances on recurrent events and outcomes following a stroke or transient ischemic attack (TIA).

It included 438 patients with acute stroke (85%) or TIA (15%). The mean age of the study population was 65 years, and 64% were male.

Researchers used the National Institutes of Health Stroke Scale (NIHSS) to assess stroke severity. At admission, the mean NIHSS score was 4. Most strokes (77.2%) were supratentorial.

About one fifth of stroke patients and one third of TIA patients had had a previous event.

Researchers used functional outcome scores to assess the clinical course of the stroke or TIA. In addition, they regularly asked patients about recurrence of cardio-cerebrovascular events.

Investigators assessed sleep disordered breathing during the acute phase of stroke, so within the first few days, using respirography.

They collected information on the presence of other sleep-wake disturbances from questionnaires and clinical interviews at 1 month, 3 months, 1 year, and 2 years after the event.

About 26% of subjects showed severe sleep disordered breathing, "meaning that they had more than 20 apnea-hypopnea events per hour," said Duss.

More than a quarter of patients reported subclinical symptoms of insomnia (measured using the Insomnia Severity Index), and up to 10% reported severe insomnia symptoms corresponding to the clinical diagnosis of insomnia, she said.

About 9% of patients in the acute phase of stroke, and 6% in the more chronic phase, fulfilled the diagnostic criteria of RLS.

More "Skewed"

The results for sleep duration were relatively "skewed," said Duss. More patients reported longer sleep duration (more than 9 hours) at 1 month than at month 3, and more reported shorter sleep duration (4.0 hours or less) at month 3 than at month 1.

The researchers built a sleep burden index for the combined impact of the various sleep-wake disturbances.

They used this index as a predictor of subsequent cardio-cerebrovascular events within 3 months after an event. They used a composite outcome that included recurrent stroke or TIA, myocardial infarction, heart failure, and urgent revascularization, as well as new cardio-cerebrovascular events, from 3 to 24 months.

The analysis showed that the mean sleep burden index was higher for stroke patients with a recurrent event compared with stroke or TIA patients without a recurrent event (Wilcoxon rank-sum test; P = .0002).

A multiple logistical regression model with the presence or absence of a recurrent event as an outcome showed that the sleep burden index is a significant predictor of recurrent events (odds ratio, 2.10; P = .001).

This was true even after controlling for age, gender, and baseline stroke severity.

The baseline apnea/hypopnea index and sleep duration were also significant predictors of new events. Importantly, though, the sleep burden index remained a significant predictor of recurrent events even after excluding the apnea/hypopnea index component, said Duss.

"So the predictive power of the sleep burden index is not only driven by the apnea/hypopnea index at the beginning of a stroke."

Sleep-wake disturbances "should be more carefully assessed and considered in comprehensive treatment approaches," not only in stroke patients, but in neurological patients in general, said Duss

She noted that these are preliminary observations from an ongoing study. The results need to be confirmed and should be when the study is finalized, she said.

Researchers are also analyzing MRI data to assess whether certain brain lesions are associated with sleep disturbances.

Commenting for Medscape Medical News, Jesse Dawson, MD, professor of stroke medicine, University of Glasgow, Scotland, said the clinical scoring system the study included "will be a big help in design and conduct of clinical trials."

Although he and other stroke experts are aware of the high prevalence of sleep disorders after stroke, "we don't routinely look for them as we're uncertain whether intervention is of benefit," said Dawson.

This new study "suggests there is an association with adverse outcome," he said.

The research was supported by grants from the Swiss National Science Foundation and the Swiss Heart Foundation. Duss and Dawson have disclosed no relevant financial relationships.

Congress of the European Academy of Neurology (EAN) 2020: Abstract #2078. Presented online May 24, 2020.

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