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Comorbid Sleep Disturbances in Neurologic Disorders

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Comorbid Sleep Disturbances in Neurologic Disorders Review Article Address correspondence to Dr Yo-El S. Ju, Washington Comorbid Sleep University in St. Louis, 600 South Euclid Ave, Box 8111, St. Louis, MO 63110, Disturbances in [email protected]. Relationship Disclosure: Dr Ju has received personal Neurologic Disorders compensation for serving as a speaker and moderator for the American Academy of Yo-El S. Ju, MD, MSCI; Aleksandar Videnovic, MD, MSc, FAAN, FAASM; Neurology, as a speaker for Bradley V. Vaughn, MD, FAAN, FAASM the American Academy of Sleep Medicine and the World Association of Sleep Medicine, and as a consultant of C2N ABSTRACT Diagnostics. Dr Ju has Purpose of Review: This article provides a review of disturbances of sleep comorbid received research/grant support from the National with common neurologic disorders. Institutes of Health and as Recent Findings: A wide variety of neurologic disorders are frequently complicated principal investigator of a by comorbid sleep disturbances. In many cases, a bidirectional relationship appears to study for Philips Respironics. Dr Videnovic serves on occur between sleep function and the neurologic disease, such that treatment of the editorial board of comorbid sleep disturbances may improve the symptoms of the neurologic disease. Parkinsonism & Related Summary: Neurologic disorders are often associated with abnormalities of sleep. Disorders and has received personal compensation for Sleep influences the severity of both epilepsy and headache, and treatment of serving as chair of the data comorbid sleep disorders may improve seizure and headache frequency. Alzheimer and safety monitoring board disease is characterized by circadian phase delay and poor nighttime sleep and is of Acorda Therapeutics and for serving on the data and strongly associated with obstructive sleep apnea. Parkinson disease is associated with safety monitoring board of several sleep disorders, including insomnia, restless legs syndrome, rapid eye Wilson Therapeutics. movement (REM) sleep behavior disorder, daytime hypersomnia, and sleep- Dr Videnovic has received research grants from the disordered breathing. Hypoventilation in amyotrophic lateral sclerosis and other National Institute of neuromuscular disorders often presents initially with sleep problems, and treatment Neurological Disorders and with noninvasive ventilation improves survival and quality of life. Stroke and receives royalties from Springer International Publishing AG. Dr Vaughn Continuum (Minneap Minn) 2017;23(4):1117–1131. has received personal compensation as a speaker for the American Academy of Neurology, American Academy of Sleep Medicine, INTRODUCTION SLEEP AND EPILEPSY and Medical Education Sleep is a complex brain-generated Sleep provides an opportunity to Resources and receives royalties from Medlink behavior. Therefore, unsurprisingly, examine and potentially improve epi- Neurobase and UpToDate, neurologic diseases frequently are lepsy. A variety of physiologic re- Inc. Dr Vaughn has received personal compensation for associated with sleep disturbances. percussions of sleep influence the serving as chair of the sleep This article discusses the most com- electric and pathophysiologic mani- medicine examination committee of the American monly encountered comorbid sleep festations of epilepsy. These range Board of Internal Medicine. disorders in neurologic practice, with from promotion or inhibition of epi- Unlabeled Use of particular attention to the interaction leptic events to the theoretic effects Products/Investigational Use Disclosure: between sleep function and neurologic of kindling in epileptic pathophysiol- Dr Ju discusses the unlabeled/ disease. The article details sleep disor- ogy. In addition, epilepsy can cause investigational use of trazodone to treat comorbid ders in epilepsy, headache, Alzheimer further sleep disruption and changes sleep disturbances in disease (AD), Parkinson disease (PD), in sleep architecture. Likewise, the dementia. Drs Videnovic and and amyotrophic lateral sclerosis treatment of epilepsy can impact sleep. Vaughn report no disclosures. * 2017 American Academy (ALS). Key sleep-related features in These dynamic relationships lead to of Neurology. neurologic disorders are summarized patients with epilepsy frequently hav- in Table 10-1. ing sleep problems. Continuum (Minneap Minn) 2017;23(4):1117–1131 ContinuumJournal.com 1117 Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited. Comorbid Sleep Disturbances TABLE 10-1 Common Comorbid Sleep Comorbidities in Neurologic Diseases Common Neurologic Common Sleep Presenting Targeted Treatments Disease Comorbidities Symptoms Investigations and Notes Epilepsy Insomnia, Sleep fragmentation Polysomnography Treat underlying obstructive with full EEG seizure disorder sleep apnea and video Headache Insomnia, Sleep fragmentation Polysomnography Treat sleep apnea, obstructive improve sleep hygiene sleep apnea (see Table 10-2 for specific syndromes) Alzheimer Obstructive Snoring, apneas, Polysomnography, Positive airway disease sleep apnea, sundowning, actigraphy pressure if obstructive delayed nighttime wandering, sleep apnea circadian phase daytime sleepiness Parkinson Insomnia, rapid Early morning Polysomnography Adjust Parkinson disease eye movement awakenings, dream with video EEG disease medications, sleep behavior enactment, restless melatonin/clonazepam disorder, restless legs, daytime legs syndrome, sleepiness hypersomnia, sleep-disordered breathing Neuromuscular Hypoventilation, Orthopnea, morning Oximetry, Volume-targeted disorders obstructive headache, hypersomnia, polysomnography, noninvasive sleep apnea sleep fragmentation pulmonary function ventilation or tests, arterial bilevel positive blood gas airway pressure (see Table 10-3 for specific disorders) Stroke Obstructive Snoring, witnessed Polysomnography Central sleep apnea sleep apnea apneas, hypertension may resolve in and central the immediate apneas poststroke period Multiple Obstructive Multiple sclerosisYrelated Polysomnography Sleep disorders are sclerosis sleep apnea, fatigue associated with restless legs cognitive dysfunction syndrome EEG = electroencephalogram. KEY POINT The influence of sleep can be exam- selective sleep stage deprivation stud- h Seizures are more ined by the effect of total sleep and the ies have been performed in humans, likely to start during effect of each stage. Since Hippocrates, studies in animals suggest the selective nonYrapid eye patients with epilepsy have been loss of rapid eye movement (REM) movement sleep, whereas rapid eye warned to avoid sleep deprivation, and sleep may enhance the kindling pro- movement sleep several studies show the provocative cess and cause progression in intracta- 3 appears to be protective nature of sleep deprivation on epileptic bility of focal-onset seizures. Likewise, 1 against seizures. events. In addition, oversleeping ap- the sleep stage may influence seizure pears to increase the occurrence of onset. Seizures are more likely to start epileptic seizures.2 Although no good during non-REM sleep, whereas REM 1118 ContinuumJournal.com August 2017 Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited. KEY POINT sleep appears to be protective against or discharges. Some primary generalized h 4 Diagnosis and treatment seizures. Similarly, interictal discharges epilepsies, especially those including my- of comorbid sleep are more likely in non-REM sleep, with oclonus, are associated with seizures apnea may offer an the greatest increase in frequency, soon after awakening, indicating that opportunity to improve topography, and localization noted seizure generation is somehow more seizure frequency and with the approach of deeper stages of prominent during the sleep-to-wake tran- quality of life in patients non-REM sleep.5 REM sleep is the state sition period. with epilepsy. least likely to have interictal discharges, Epilepsy also produces changes in and these discharges are most re- sleep. Seizures are noted to cause stricted to near the epileptic focus; postictal somnolence, but also evoke thus, REM sleep offers an opportunity more wake after sleep onset, sleep for better localization of epileptic foci.6 fragmentation, and REM sleep suppres- Although these observations are clear, sion during the sleep period follow- the underlying reason for the differ- ing the seizure. This effect appears to ence of topography of the interictal extend beyond frank seizures. Interictal discharges is still somewhat unclear. discharges also cause sleep fragmenta- Most theories rest on the hypothesis tion, potentially by disrupting signals that more neurons are in the resting involved in sleep circuitry, thus disrupt- state in non-REM sleep and thus are ing the physiologic coordination of available for recruitment into the dis- sleep. This disruption may have some charge; however, during REM sleep, downstream effect as it has been overall greater neuronal firing occurs, hypothesized that nighttime discharges and neurons are less available to be may influence daytime learning.7 Re- recruited into the interictal firing. cent studies have shown correlations Some epilepsies are specifically between nighttime seizure activity and related to sleep.6 Benign epilepsy of complaints of nighttime disruption and childhood with central temporal spikes daytime symptoms.8 Similarly in adults, is typically associated with seizures patients with frequent interictal dis- manifesting as focal spasms of the face charges
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