(Stroke. 1995;26:2361-2365.)
© 1995 American Heart Association, Inc.
Articles |
Transient Ischemic Attacks and Minor Stroke During Sleep
Relationship to Obstructive Sleep Apnea Syndrome
From the Sleep Disorders Center, Section of Sleep Medicine, Division of Pulmonary and Critical Care Medicine (M.R.P., W.G.F., D.D.P.), and Divisions of General Internal Medicine (W.R.S.) and Neurology (H.J.C.), Department of Medicine, The Lankenau Hospital and Medical Research Center, Wynnewood; Department of Medicine, Jefferson Medical College, Philadelphia; and Department of Medicine (B. Van U.), Presbyterian Medical Center of Philadelphia (Pa).
Correspondence to Mark R. Pressman, PhD, Sleep Disorders Center, The Lankenau Hospital and Medical Research Center, 100 Lancaster Ave, Wynnewood, PA 19096-3498.
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Abstract |
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Background It is reported that 13% to 44% of all cerebrovascular accidents (CVAs) occur during sleep. In addition to other well-known risk factors, snoring, sleep apnea, obesity, and daytime sleepiness have been shown to significantly increase the risk of stroke. We describe two cases that support the statistical relationship between snoring, sleep apnea, and CVA during sleep.
Case Descriptions In the first case, motor aphasia was noted in a 64-year-old, 5-ft, 1-in, 218-lb woman when she awakened from sleep at approximately 4 AM. This completely resolved within 3 hours. During her subsequent hospitalization she was found to have severe obstructive sleep apnea that responded well to treatment with nasal continuous positive airway pressure. There has been no recurrence of symptoms in this patient. The second patient was a 59-year-old, 5-ft, 6-in, 260-lb woman who presented to the Sleep Disorders Center with signs and symptoms of severe sleep apnea. In addition, she had awakened from sleep approximately 6 months earlier with numbness and weakness on her right side. Although these symptoms had greatly improved, she continued to complain about residual weakness that was worse on awakening from sleep. Sleep studies confirmed severe obstructive sleep apnea that responded very well to treatment with nasal continuous positive airway pressure.
Conclusions Snoring and obstructive sleep apnea not only increase the statistical risk of CVA but could be the proximal trigger that precipitates these events during sleep. These two cases provide clinical support for this relationship. Successful diagnosis and treatment of obstructive sleep apnea in the patient with transient ischemic attacks and minor stroke may be an important tool for preventing recurrence.
Key Words: cerebral ischemia, transient • risk factors • sleep apnea syndromes
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Introduction |
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The circadian pattern in CVAs is similar to that in cardiovascular events, with a peak in the early morning after the patient awakens.1 2 3 4 5 6 7 8 The circadian pattern of TIAs has not been reported, but transient myocardial ischemic events have a circadian pattern similar to that of other cardiovascular events.9 10 TIAs are likely to have a circadian pattern similar to that of other CVAs. Other risk factors have not been shown to be statistically different for TIAs and minor stroke.11 12 13 Although the peak in CVA occurrence is most often reported to be in the morning after the patient awakens, 13% to 44% of all CVAs are reported to occur during sleep, with symptoms becoming evident once the patient awakens.2 3 4 5 6 14
Recently, snoring has been shown to be an independent risk factor for the occurrence of stroke during wakefulness and sleep.15 16 17 18 19 A history of snoring increases the odds ratio for admission to the hospital for stroke 3.2-fold.19 Additionally, the severity of snoring has been found to be significantly related to increased mortality for the next 6 months after hospitalization.19 When a history of sleep apnea, excessive daytime sleepiness, and obesity are all present in addition to snoring, the odds ratio for stroke has been shown to increase to 8.0.17
This report presents two cases of patients presenting with either TIA or minor stroke immediately on awakening from sleep; in both patients severe OSA was found, and treatment of the OSA by NCPAP eliminated any further episodes.
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Case Reports |
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Case 1
The patient is a 64-year-old, 5-ft, 1-in, 218-lb white woman admitted to the medical inpatient unit of the hospital. On the night before her admission the patient awoke suddenly from sleep at approximately 4 AM. According to family members and to the patient herself, she was unable to produce any speech, although she could communicate by other means. Based on this description, her symptoms were thought to be consistent with a motor aphasia. On arrival at the emergency department an hour later, the patient's speech had improved and was described as "thick," characterized by significant hesitancy with difficulty in making transitions from sound to sound and very simplified vocabulary. Within 1 hour speech fluency had completely returned to normal with no apparent residual difficulties. She was additionally noted by emergency department physicians to be mildly dizzy and lethargic at admission, although she was responsive and cooperative. These symptoms persisted for an additional hour after normal speech returned. Neurological examination was unremarkable except for the dysphasia. Blood pressure was 154/82 mm Hg. A CT of the head, carotid and transcranial Doppler sonograms, and an MRI angiogram of the carotid arteries were unremarkable. An echocardiogram showed left ventricular hypertrophy. The patient does not smoke or use alcohol. She reported her usual sleep period as 12:30 AM to 8 AM. The patient's medical history was unremarkable, and she was taking no medications. Her laboratory studies were unremarkable except for borderline glucose intolerance, with blood glucose levels of 119 to 132 mg/dL. Arterial blood gases were measured several times during her hospitalization and were found to be within normal limits. Pulmonary function tests were also within normal limits.
During her hospitalization the patient was noted to be somnolent,
especially in the morning, and was noted by staff and
doctors to snore loudly. All-night pulse oximetry was ordered and
showed continuous, repetitive, and brief periods of O2
desaturation of 5% to 50% throughout the night, with four periods
approximately 90 to 120 minutes apart in which O2
saturation fell well below 50% (Fig 1
).
These periods of O2 desaturation were associated with a
clear bradycardia-tachycardia pattern in the
electrocardiographic rate, with changes of 30 to 50 beats per minute
occurring frequently. This pattern was read as consistent with
severe OSA. Because of family problems the patient was discharged from
the hospital against medical advice with an NCPAP machine empirically
set at a pressure of 10 cm H2O. She later returned as an
outpatient to the Sleep Disorders Center laboratory for full
polysomnography. This confirmed the presence of severe OSAS, and the
periods of O2 desaturation below 50% were shown to have
occurred during definite REM sleep (summary data are presented
in the Table). The patient returned the next night for
an NCPAP titration trial. Administration of NCPAP at a pressure of 7.5
cm H2O reduced the RDI to 3.7/h of sleep, which was within
normal limits. SaO2 did not decline below 87%
even during REM sleep. The overall quality of sleep also showed
substantial improvement, with deep sleep and REM sleep rebound
present. During the subsequent 12 months since the start of
treatment there has been no recurrence of TIAs and the patient
has reported sleeping well, with increased daytime alertness.
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Case 2
The patient is a 59-year-old, 5-ft, 6-in, 260-lb black woman
who presented to the Sleep Disorders Center as an outpatient
with complaints of severe morning headaches and excessive daytime
sleepiness. Additionally, she noted that approximately 6 months ago she
had awakened from sleep with mild but noticeable numbness of the right
side of her face and weakness in her right arm and hand and to a lesser
degree in her right leg. She was able to move her limbs but had minor
impairment in motor ability and dexterity on the right compared with
the left side. These symptoms have improved in the last 4 months,
although she still complains of mild numbness and weakness during her
waking hours. However, no objective neurological deficits were found on
examination at this time. Once or twice weekly she reports that the
numbness and weakness are more severe on awakening from sleep in the
morning but return to milder levels within 1 to 6 hours. She also
complained of loud snoring and had awakened herself briefly with snores
at least twice nightly. Additionally, she awakened two to three times
for up to 30 minutes each time with sensations of gasping for breath
associated with palpitations and occasionally with night sweats. During
the last year the patient has become increasingly sleepy during the
day, falling asleep unintentionally whenever inactive. Twice she fell
asleep briefly while driving.
The patient reported that these symptoms occurred as a result of a
30-lb weight gain during the last year. The patient related that the
weight gain had occurred as a result of anxiety and depression after
the sudden and unexplained death of her son. Her son (age, 39 years;
height, 6 ft, 6 in; weight, 
350 lb) had been found dead on his bed in
the morning, fully clothed, with the television on. Two postmortem
examinations had failed to determine the cause of the death. On further
questioning, the patient stated that her son had almost all of the
symptoms she herself had reported to us. He was known as a loud snorer,
noted by family members to awaken gasping for breath from sleep, and
was extremely sleepy, prone to fall asleep suddenly whenever inactive.
Based on his body habitus and history provided by his family, it seemed
highly likely that her son had suffered from untreated OSAS. Untreated
moderate-to-severe OSAS is known to result in a statistically
higher rate of mortality than in treated patients.20
The patient's neurological examination, CT of the head, electrocardiogram, and carotid Doppler sonogram were unremarkable except for weakness noted above. She was hypertensive and had been treated for the last 5 years (currently with enalaprilat 20 mg, diltiazem 60 mg bid, and furosemide 40 mg). She took no other medications. Her medical history was remarkable for complaints of chest pain and palpitations for the last 2 years and edema of the right ankle and leg. Arterial blood gases had not been examined recently. However, waking SaO2 was 95% to 97% with the patient in the supine position.
Because of her own symptoms and her family history, the patient
returned to the sleep laboratory for a diagnostic
polysomnogram (Table
and Fig 2). It was
consistent with severe OSA, with falls in
SaO2 well below 50% during REM sleep only. The
overall pattern was unusual in that although sleep-disordered
breathing was present in non-REM sleep, it was of mild to moderate
severity with minimal O2 desaturation, while in REM sleep
it was extremely severe. Additionally, the patient reported that she
had slept better in the sleep laboratory than she typically does at
home. She awakened without the symptoms of weakness/numbness or
headache. This was reflected in the better-than-expected
quality of sleep. Many of the apneas and hypopneas produced only minor
arousals, allowing the patient to accumulate good quantities of deep
sleep. Because sleep stages 3 and 4 (deep sleep) are reported to
suppress the appearance of sleep apnea, this strongly suggested to us
that during a "normal" night of sleep, apneas and hypopneas would
occur more frequently.21 The patient later returned for a
treatment trial of NCPAP during which administration of a pressure of
10.0 cm H2O resulted in reduction in the RDI to 4.5/h of
sleep, which was within normal limits. SaO2 did
not decline below 86% during REM sleep. A home NCPAP unit was
prescribed, and in 6 months of home use the patient has reported only
low levels of numbness and weakness on awakening. Headaches and other
symptoms have been eliminated.
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Discussion |
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Both patients awoke from sleep with signs and symptoms of TIA or minor stroke. Both patients were shown to have severe OSAS with highly significant periods of O2 desaturation, particularly in REM sleep. With successful treatment of OSA with NCPAP, there has been no recurrence of TIAs in the first patient or exacerbation of symptoms in the second patient.
A direct causal relationship between sleep apnea and cerebrovascular symptoms cannot unequivocally be established because we did not directly observe the onset of cerebrovascular symptoms during sleep. Rather, they were reported to be present immediately on awakening. However, a review of the literature found a single, brief case report in abstract form of symptoms of TIA that appeared immediately after witnessed OSA and were confirmed by polysomnography.22 This report suggests that snoring and sleep apnea may not only be risk factors for TIAs but may sometimes be the immediate trigger. This relationship is further supported by the fact that administration of NCPAP in these two cases apparently prevented the recurrence of further symptoms.
OSAS is associated with many of the risk factors hypothesized to be related to TIA and stroke. Reviews have reported that 48% to 96% of patients with diagnosed OSAS are hypertensive, and the severity of sleep apnea has been noted to be highly positively correlated with waking blood pressure, increases in intracranial pressure, decreases in cerebral perfusion pressure with resultant changes in cerebral blood flow, and cardiac arrhythmias.23 24 25 26 27 28 29 30 Balfors and Franklin29 recently reported that changes in cerebral blood flow and perfusion are so significant and rapid in patients with sleep apnea that cerebral autoregulation is insufficient to protect the brain from changes in arterial blood pressure. They suggest that along with apnea/hypopnea–induced hypoxemia, these changes in cerebral blood flow parameters predispose patients with sleep apnea to nocturnal cerebral ischemia.
Significant hypoxemia was associated with apneas and hypopneas that occurred primarily during REM sleep in both patients. The severity of these periods of O2 desaturation may have been exacerbated by the patients' obesity. Obesity has been shown to result in low lung volumes, particularly in the supine position, and has been reported to be significantly correlated with the degree of hypoxemia.31 32 REM sleep may have further exacerbated the hypoxemia as a result of longer durations of apnea/hypopnea noted during REM sleep in these patients and changes in lung mechanics caused by loss of intercostal muscle activity and reduction in diaphragmatic tonic activity.31 32 33 Others have suggested that REM sleep–related hypoxemia is due to relative hypoventilation compared with non-REM sleep.31 32 33 Upper airway closing pressures are also reported to be lower in REM sleep compared with non-REM sleep, which suggests that airway collapse may occur more easily in REM sleep.34 Obesity, alcohol, and age are also known risk factors of CVAs.17 35 36 OSAS is highly correlated with obesity, and alcohol is known to significantly exacerbate the severity of sleep apnea by increasing apnea duration and consequently O2 desaturation.37 38 39 40
OSAS is an easily diagnosed condition that should always be part of the differential diagnosis when TIAs or strokes occur during sleep. Not only is OSAS a risk factor for the occurrence of CVAs, but because of its episodic and repetitive nature it could be the proximal trigger of TIAs and other CVAs. Successful treatment of patients with OSAS has been shown to reduce morbidity and mortality due to cardiovascular causes.41 42 Although long-term clinical and epidemiological data are lacking, our diagnosis and successful treatment of two patients with TIA and minor stroke during sleep by NCPAP suggests that patients with sleep-related CVAs should be evaluated for the presence of OSAS and treated if appropriate. Since the occurrence of TIAs greatly increases the risk for future stroke, eliminating a risk factor such as sleep apnea might be considered primary prevention of stroke.11 12 Only long-term follow-up will show how effective the diagnosis and treatment of OSAS is as a preventive measure for TIAs and other CVAs.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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This study was supported in part by the Lankenau Medical Research Center.
Received May 9, 1995; revision received September 20, 1995; accepted September 20, 1995.
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