Brief Report

Strokes More Severe When Occurring During Sleep

By Alan Z. Segal, MD, Associate Professor of Clinical Neurology, Weill Cornell Medical College, New York, NY. Dr. Segal reports no financial relationships relevant to this field of study.

This article originally appeared in the October issue of Neurology Alert. At that time it was peer reviewed by M. Flint Beal, MD, Anne Parrish Titzel Professor, Department of Neurology and Neuroscience, Weill Cornell Medical Center, New York, NY. Dr. Beal reports no financial relationships relevant to this field of study.

Source: Kim BJ, et al. Ischemic stroke during sleep: Its association with worse early functional outcome. Stroke 2011; 42:1901-1906.

It has been well recognized that a peak in stroke onset occurs during the early morning hours. This possible circadian periodicity is not well understood, and may in part represent stroke onset earlier during the night that goes unrecognized until the patient arouses. "Wake up stroke" (WUS) presents a challenge to treatment, since time of onset has been strictly defined as the last time the patient was seen normal, and therefore these patients fail to be candidates for thrombolytic treatment. Recently, some investigators have suggested that a subset of WUS patients could be thrombolysis candidates, especially if imaging could be suggestive of a shorter time of onset.

In the current study, Kim et al compare outcomes among 2289 patients retrospectively reviewed, with 637 (27.8%) of these being WUS. Three separate analytic techniques were used. In a dichotomized analysis, with patients split into a functionally independent group (modified Rankin score 0-1) or functionally dependent group (Rankin > 2); there was no difference between WUS and non-WUS. However, when stroke severity was taken into account, WUS patients fell into a more unfavorable category more frequently (odds ratio [OR] 1.33). Additionally, when the Rankin score was used as a continuous variable, patients with WUS consistently trended toward being more dependent at discharge (OR 1.22).

Patients with WUS had a higher proportion of strokes attributed to large vessel atherosclerotic disease, which is not unexpected given their increased severity. Also, not surprisingly, patients with WUS were less likely to be treated with intravenous thrombolysis, though a subset did receive endovascular interventions.


As the investigators note, adverse outcomes for WUS patients may be due to more than merely delay in presentation and lack of thrombolytic therapy. Hemodynamic changes during sleep, especially autonomic shifts during early morning rapid eye movement sleep, may act as stroke precipitants. An increase in platelet aggregation also has been shown to peak during this time period, which has been thought to contribute to a circadian variability in myocardial infarction, sudden cardiac death, and stroke. Sleep-disordered breathing also may be a factor due to associated hypoxia, hypertension, or cardiac arrhythmias. Of note, body mass index (a known risk factor for obstructive sleep apnea) was not different between WUS and non-WUS patients. Sleep apnea is nevertheless a well-recognized risk factor for stroke and needs to be investigated and treated among patients at risk.