Antonio Culebras

Sleep Apnea and Cardiovascular Disease

Sleep-related breathing disorders are highly prevalent in patients with established cardiovascular disease. Obstructive sleep apnea (OSA) affects an estimated 15 million adult Americans and is present in a large proportion of patients with hypertension and in those with other cardiovascular disorders, including coronary artery disease, stroke, and atrial fibrillation.1–14 In contrast, central sleep apnea (CSA) occurs mainly in patients with heart failure.15–19 The purpose of this Scientific Statement is to describe the types and prevalence of sleep apnea and its relevance to individuals who either are at risk for or already have established cardiovascular disease. Special emphasis is given to recognizing the patient with cardiovascular disease who has coexisting sleep apnea, to understanding the mechanisms by which sleep apnea may contribute to the progression of the cardiovascular condition, and to identifying strategies for treatment. This document is not intended as a systematic review but rather seeks to highlight concepts and evidence important to understanding the interactions between sleep apnea and cardiovascular disease, with particular attention to more recent advances in patient-oriented research. Implicit in this first American Heart Association/American College of Cardiology Scientific Statement on Sleep Apnea and Cardiovascular Disease is the recognition that, although holding great promise, this general area is in need of a substantially expanded knowledge base. Specific questions include whether sleep apnea is important in initiating the development of cardiac and vascular disease, whether sleep apnea in patients with established cardiovascular disease accelerates disease progression, and whether treatment of sleep apnea results in clinical improvement, fewer cardiovascular events, and reduced mortality. Experimental approaches directed at addressing these issues are limited by several considerations. First, the close association between obesity and OSA often obscures differentiation between the effects of obesity, the effects of OSA, and the effects of synergies between these conditions. Second, multiple comorbidities, …

An Updated Definition of Stroke for the 21st Century A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

Despite the global impact and advances in understanding the pathophysiology of cerebrovascular diseases, the term “stroke” is not consistently defined in clinical practice, in clinical research, or in assessments of the public health. The classic definition is mainly clinical and does not account for advances in science and technology. The Stroke Council of the American Heart Association/American Stroke Association convened a writing group to develop an expert consensus document for an updated definition of stroke for the 21st century. Central nervous system infarction is defined as brain, spinal cord, or retinal cell death attributable to ischemia, based on neuropathological, neuroimaging, and/or clinical evidence of permanent injury. Central nervous system infarction occurs over a clinical spectrum: Ischemic stroke specifically refers to central nervous system infarction accompanied by overt symptoms, while silent infarction by definition causes no known symptoms. Stroke also broadly includes intracerebral hemorrhage and subarachnoid hemorrhage. The updated definition of stroke incorporates clinical and tissue criteria and can be incorporated into practice, research, and assessments of the public health.

Magnetic resonance findings in REM sleep behavior disorder.

Rapid eye movement (REM) sleep behavior disorder is characterized by bizarre acts during nocturnal sleep that may lead to physical injuries. Dream content suggests that motor overactivity is an attempted dream enactment and polygraphic studies reveal REM stage without atonia, an alteration of REM sleep generation that facilitates excessive motor activity. In 6 patients with REM sleep behavior disorder, MRI of the brain showed multifocal signal intensity lesions suggestive of lacunar infarcts in periventricular regions (5 patients) and in dorsal pontomesencephalic areas (3 patients). REM sleep behavior disorder may be the result of injury to the midrostral tegmentum nuclei, the tegmentoreticular tracts, or both. This condition is easily controlled with clonazepam.

Triflusal vs aspirin for prevention of cerebral infarction: A randomized stroke study

Background: Triflusal is an antiplatelet agent that has shown clinical advantages when compared with aspirin in the secondary prevention of vascular events. TAPIRSS (Triflusal versus Aspirin for Prevention of Infarction: a Randomized Stroke Study) explored the efficacy and safety of triflusal in the secondary prevention of stroke in a Latin American homogeneous population with the ultimate aim of preparing for a larger trial in the same setting. Methods: A double-blind, multicenter, randomized, pilot trial was conducted in Buenos Aires, Argentina, from October 1996 to November 1999. The study sample was 431 patients, randomized to receive aspirin 325 mg daily or triflusal 600 mg daily for a mean of 586 days. All patients had experienced either an ischemic stroke or TIA within 6 months from enrollment. Data from 429 patients were analyzed. Results: No differences were observed in the primary endpoint that combined the incidence of vascular death, cerebral ischemic infarction, nonfatal myocardial infarction, or major hemorrhage (aspirin 13.9%, triflusal 12.7%; odds ratio [OR] 1.11, 95% CI 0.64 to 1.94) or in the individual analysis of each component of the primary endpoint. In a post hoc analysis, the overall incidence of major and minor hemorrhagic events was significantly lower in triflusal-treated patients (aspirin 8.3%, triflusal 2.8%; OR 3.13, 95% CI 1.22 to 8.06). Conclusions: This pilot trial has not found differences between triflusal and aspirin in the prevention of vascular complications after TIA or ischemic stroke, although given the wide CI, potentially important group differences could not be ruled out. Triflusal may be associated with a lower risk of hemorrhagic complications. A larger, prospective clinical trial is necessary to verify these results.

Summary of evidence-based guideline update: Prevention of stroke in nonvalvular atrial fibrillation Report of the Guideline Development Subcommittee of the American Academy of Neurology

Objective: To update the 1998 American Academy of Neurology practice parameter on stroke prevention in nonvalvular atrial fibrillation (NVAF). How often do various technologies identify previously undetected NVAF? Which therapies reduce ischemic stroke risk with the least risk of hemorrhage, including intracranial hemorrhage? The complete guideline on which this summary is based is available as an online data supplement to this article. Methods: Systematic literature review; modified Delphi process recommendation formulation. Major conclusions: In patients with recent cryptogenic stroke, cardiac rhythm monitoring probably detects occult NVAF. In patients with NVAF, dabigatran, rivaroxaban, and apixaban are probably at least as effective as warfarin in preventing stroke and have a lower risk of intracranial hemorrhage. Triflusal plus acenocoumarol is likely more effective than acenocoumarol alone in reducing stroke risk. Clopidogrel plus aspirin is probably less effective than warfarin in preventing stroke and has a lower risk of intracranial bleeding. Clopidogrel plus aspirin as compared with aspirin alone probably reduces stroke risk but increases the risk of major hemorrhage. Apixaban is likely more effective than aspirin for decreasing stroke risk and has a bleeding risk similar to that of aspirin. Major recommendations: Clinicians might obtain outpatient cardiac rhythm studies in patients with cryptogenic stroke to identify patients with occult NVAF (Level C) and should routinely offer anticoagulation to patients with NVAF and a history of TIA/stroke (Level B). Specific patient considerations will inform anticoagulant selection in patients with NVAF judged to need anticoagulation.

Absence of sleep‐related growth hormone elevations in myotonic dystrophy

There is evidence that in myotonic dystrophy, the endocrine and central nervous systems are affected. To study a possible relationship between both defects, we investigated nocturnal sleep patterns and associated growth hormone secretion in two men and three women with myotonic dystrophy. In three patients who were clinically the most severely affected by myotonic dystrophy, plasma growth hormone elevations related to the slow-wave phase of sleep were absent. The two least severely affected patients had plasma growth hormone increases of low magnitude and brief duration (from 0.4 ng per milliliter to 13.0 ng per milliliter). These data suggest a failure of integration at a subcortical level of the slow-wave phase of sleep with the hypothalamic-pituitary mechanisms of growth hormone secretion. Thalamic neuronal lesions occurring in myotonic dystrophy could be responsible for such failure.

Sleep Disorders and Neurological Disease

Historical Perspective on Sleep and ManMichael J. ThorpyNeurobiology and Segmental Neurology of SleepAntonio CulebrasDisorders of Development and Maturation of Sleep, and Sleep Disorders in Infancy, Childhood, and Cerebral PalsyStephen H. SheldonSleep-Related Respiratory Physiology in Infancy, Sleep Apnea Syndromes in Infancy and Childhood, and PolysomnographyGabriele M. Barthlen and Stephen H. SheldonDissociated States of Brain and MindMark W. Mahowald and Carlos H. SchenckThe Role of Melatonin in Sleep and Sleep DisordersIrina V. ZhdanovaDelayed-Sleep-Phase Syndrome and Other Circadian-Rhythm Sleep DisordersCharles P. PollakInsomnia in NeurologyElio Lugaresi, Federica Provini, and Giuseppe PlazziMotor Disorders of Sleep: Periodic, Aperiodic, and Rhythmic Motor Disorders and ParasomniasPasquale MontagnaSleep in Neurodegenerative DisordersSudhansu ChokrovertyParkinsons Disease and Extrapyramidal DisordersRobert L. RodnitzkySleep and Nocturnal Delirium in the Dementias: Alzheimers Disease, Multi-Infarct Dementia, and Parkinsons DiseaseDonald L. BliwiseObstructive and Nonobstructive Sleep Apnea: The Neurological PerspectiveChristian Guilleminault and Ali G. BassiriSleep and StrokeHeikki Palom?ki and Markku PartinenSleep, Epilepsy, and Sudden DeathChristine Quinto and Sudhansu ChokrovertyNarcolepsy, Idiopathic Hypersomnia, and Periodic HypersomniasClaudio Bassetti and Michael S. AldrichHeadache Disorders and SleepAntonio CulebrasSleep in Traumatic Brain Injury and Other Acquired CNS ConditionsMark W. MahowaldSleep Disorders Associated with Multiple SclerosisAntonio CulebrasSleep Disorders and Neuromuscular DisordersAntonio Culebras

Sleep and Stroke

Sleep affects brain function and may contribute to vascular cerebral pathology through a diversity of direct and indirect mechanisms. Circadian rhythm investigation shows increased incidence of stroke between 6 AM and 12 noon. Risk factors for stroke such as high blood pressure, ischemic heart disease, and diabetes are modified by sleep and sleep apnea. Epidemiological studies have shown a dose-response relationship between the severity of sleep apnea and the odds ratio for development of systemic hypertension. There is now evidence of a causal relationship between sleep apnea and stroke. Following stroke, both in the acute and chronic stages, patients have a high prevalence of sleep apnea that reduces the potential for rehabilitation, further increases the risk of secondary stroke, and heightens mortality. Successful correction of sleep apnea with noninvasive positive airway pressure ventilation lowers mean blood pressure, and indirectly lowers the risk of stroke. Unfortunately, patients with stroke tolerate positive noninvasive ventilation poorly, and other means of correcting sleep apnea need to be investigated.

Sleep in Neuromuscular Diseases

Sleep disorders in neuromuscular disorders are generally caused by respiratory dysfunction associated with these diseases. Hypoventilation in neuromuscular diseases results from both respiratory muscle weakness and reduced chemoreceptor sensitivity, which is required for ventilatory drive. This condition results in repeated arousals, sleep fragmentation, and nocturnal hypoxemia, manifesting most commonly as excessive daytime somnolence. Polysomnography can identify sleep disordered breathing in patients with neuromuscular disorders and treatment with noninvasive ventilation may improve quality of life.

Sleep, Stroke and Poststroke

There is abundant and still evolving scientific clinical evidence linking sleep apnea with stroke risk factors, cardiovascular disease, and stroke. Sleep apnea is a modifiable risk factor and efforts to control this condition should be pursued vigorously, particularly in patients at risk of vascular disease. Emerging evidence has also linked other sleep disorders, such as periodic limb movements of sleep and restless legs syndrome, with vascular risk.