Obstructive sleep apnea is associated with risk for sudden unexpected death in epilepsy (SUDEP) using rSUDEP-7.

BACKGROUND AND OBJECTIVE: Evaluate relationships between PSG-confirmed OSA and SUDEP risk using the revised SUDEP Risk Inventory (rSUDEP-7). METHODS: Identified adults with epilepsy (AWE) who underwent PSG 2004-2016 at Cleveland Clinic. OSA was defined as apnea-hypopnea index (AHI)- ≥-5/h sleep; moderate/severe OSA as AHI≥15. SUDEP risk was assessed using rSUDEP-7: higher rSUDEP-7 score, greater SUDEP risk. Associations between rSUDEP-7 score and OSA groups (AHI≥15 vs. <15) were evaluated using Wilcoxon rank-sum tests and multivariable linear models adjusting for age, sex, BMI, and smoking status. Spearman correlations measured relationships between rSUDEP-7 score with AHI and oxygen desaturation indices (ODI). RESULTS: OSA was present in 134 (62.6 %) of 214 AWE; moderate/severe in 75 (35 %). AWE with AHI≥15 were more likely to be male and older, had higher BMI, greater frequency of tonic-clonic seizures (TCS), longer epilepsy duration, and more likely to have drug-resistant epilepsy (DRE) and sleep-related seizures (all p< 0.05). The median rSUDEP-7 score was 1 (0,3) but 37.4 % had a score ≥3 (high SUDEP risk), and 11.7 % ≥5 (highest SUDEP risk). rSUDEP-7 scores were higher in those with AHI≥15 (3 vs. 1, p = 0.001). Higher AHI and ODI 3% positively correlated with rSUDEP-7 (p=0.002 and p=0.016) while SpO2 nadir negatively correlated with rSUDEP-7 (p=0.007). After adjustments, AWE with AHI≥15 had mean rSUDEP-7 score 1.14 points (95% CI 0.55-1.72, p<0.001) higher than those with AHI<15. DISCUSSION: AWE with PSG-confirmed moderate/severe OSA especially those who are older and have GTC had higher rSUDEP-7 scores potentially increasing their risk for SUDEP. Our findings support routine screening for OSA in AWE. Further studies confirming the significance and impact of OSA on SUDEP risk are needed.

Real world challenges and barriers for positive airway therapy use in acute ischemic stroke patients.

PURPOSE: Untreated obstructive sleep apnea (OSA) in patients with acute ischemic stroke (AIS) is associated with increased morbidity and mortality. However, diagnosing and treating OSA in AIS is challenging. We aimed to determine the feasibility of portable monitoring (PM) for diagnosis and positive airway pressure therapy for treatment of OSA in an inpatient stroke population. METHODS: We recruited inpatients with AIS from Cleveland Clinic. Those who consented underwent PM; participants with a respiratory event index (REI) ≥ 10 were offered auto-titrating positive airway pressure therapy (APAP). Ease-of-use questionnaires were completed. We summarized categorical variables using n(%) and continuous variables using mean ± SD or median [IQR]. RESULTS: 27 participants (age 59.8 ± 11.8, 51.9% female, 51.9% Black, BMI 33.4 ± 8.5) enrolled. The study ended early due to Medicare contracting that forced most patients to complete stroke rehabilitation outside the Cleveland Clinic health system. 59.3% had large vessel occlusions and 53.8% had moderate/severe disability (Modified Rankin score ≥ 2). PM was attempted in 21 participants, successful in 18. Nurses and patients rated the PM device as highly easy to use. 13 of 18 (72%) patients who had an REI ≥ 10 consented to APAP titration, but only eight (61.5%) of those 13 used APAP for more than one night, and only five (27.8%) used APAP up to 90 days with data captured for only one participant. Five required troubleshooting at titration, and only one had adherent APAP usage by objective assessment after discharge. CONCLUSIONS: This study demonstrates the real-world challenges of assessing and treating OSA in an AIS population, highlighting the necessity for further research into timely and feasible screening and treatment.

The Epworth Sleepiness Scale in epilepsy: Internal consistency and disease-related associations.

BACKGROUND: The Epworth Sleepiness Scale (ESS) is the most common instrument for measuring subjective sleep propensity in people with epilepsy but has not yet been validated in this population. STUDY OBJECTIVES: We aimed to systematically assess the validity, performance, and internal consistency of the ESS, as well as correlations between the ESS and disease-specific variables and patient-reported outcome measures in a cohort of adults with epilepsy (AWE). METHODS: Ninety-five AWE completed sleep and seizure diaries, in-laboratory polysomnography (PSG) and patient-reported outcome measures, including the ESS, Insomnia Severity Index (ISI), and the Beck Depression Inventory (BDI). Demographic information and data from 95 matched controls referred for PSG for suspected obstructive sleep apnea (OSA) was taken from the electronic medical record. Frequencies of high ESS item ratings (item score ≥2) were calculated for each group. Cronbach's α and factor analysis were performed to assess the internal consistency and validity of the ESS within cases and controls. Multivariable linear models were used to assess the association between ESS and predictors of interest, adjusting for demographic and disease-specific variables, including seizure type, frequency, and anti-seizure medication (ASM) therapy. RESULTS: While suspected OSA controls had significantly greater mean ESS total scores (9.9 vs 7.9, p = 0.004) and proportion with ESS >10 (42% vs 25%, p = 0.014), there were no significant differences in the severity of item responses, with the exception of "lying down to rest in the afternoon when circumstances permit," for which more controls rated as likely/very likely (79% vs 64%), p = 0.024). AWE with ESS >10 had higher mean standardized ASM dose (2.5 vs 1.7, p = 0.026). All ESS items were significantly correlated with the total score within each group. Cronbach's α was 0.75 for cases and 0.85 for controls, indicating good internal consistency of the ESS for both groups. After adjusting for demographic and sleep characteristics, higher ESS scores were associated with greater insomnia scores on the ISI (p = 0.024) and depressive symptoms on the BDI (p = 0.018). CONCLUSIONS: This study provides validity for the use of the ESS in adult populations with epilepsy.

Sleep disorders in adults with epilepsy: past, present, and future directions.

PURPOSE OF REVIEW: To summarize recent studies on the complex relationships between sleep disorders, sleep, and epilepsy. RECENT FINDINGS: Insomnia in adults with epilepsy (AWE) warrants consideration of depression, anxiety, and suicidal ideation. Daytime sleepiness in AWE is more often due to undiagnosed sleep disorders. Sleep deprivation is an important provoker of seizures in juvenile myoclonic epilepsy. Abnormalities in frontal lobe executive function with difficulties making advantageous decisions may explain failure of juvenile myoclonic epilepsy patients to adhere to treatment recommendations and regulate their sleep habits. Sleep architecture in AWE is more likely to be abnormal if seizures are poorly controlled or occur during sleep. Obstructive sleep apnea is much more common in AWE who are man, older, heavier, or whose seizures are poorly controlled. Chronobiology and chronopharmacology of epilepsy is an emerging field worthy of future research and clinical applications. SUMMARY: Identifying and treating unrecognized sleep disorders and understanding the impact of circadian rhythms on epilepsy can improve quality of life and seizure control in AWE.

Sleep/Wake Disorders After Sports Concussion: Risks, Revelations, and Interventions.

SUMMARY: Sleep-wake disturbances (SWDs) are among the most prevalent, persistent, and often disregarded sequelae of traumatic brain injury. Identification and treatment of SWDs in patients with traumatic brain injury is important and can complement other efforts to promote maximum functional recovery. SWDs can accentuate other consequences of traumatic brain injury, negatively affect mood, exacerbate pain, heighten irritability, and diminish cognitive abilities and the potential for recovery. The risk for sports injuries increases when athletes are sleep deprived. Sleep deprivation increases risk-taking behaviors, predisposing to injuries. SWDs are an independent risk factor for prolonged recovery after sports-related concussion. SWDs following sports-related concussion have been shown to impede recovery, rehabilitation, and return to preinjury activities.

Sleep and Epilepsy: Practical Implications.

Sleep is a restorative balm for many, often less so for people with epilepsy. Complex bidirectional interactions between sleep and epilepsy can be detrimental to sleep, epilepsy and those affected. Sleep is a state of variable activation of the EEG and seizure occurrence in people with epilepsy. Sleep disorders are highly prevalent and portend worse seizure and epilepsy-related outcomes. Randomized clinical trials of sleep interventions in epilepsy populations are few, yet warranted, given the effects of sleep dysfunction on quality of life and the risk of SUDEP in people with epilepsy.

Recognizing New-Onset Sleep Disorders in Autoimmune Encephalitis Often Prompt Earlier Diagnosis.

SUMMARY: Sleep/wake disorders are common in patients with autoimmune encephalitis, sometimes the most prominent or sole initial symptom, then delaying diagnosis. Sleep/wake disorders in autoimmune encephalitis vary and include severe sleeplessness, hypersomnia, central and/or obstructive sleep apnea, rapid eye movement sleep behavior disorder, indeterminate sleep/wake states, and loss of circadian sleep/wake rhythms. N-methyl- d aspartate receptor encephalitis (NMDAR) is often associated with insomnia, then hypersomnia and sleep-related central hypoventilation. Profound sleeplessness and rapid eye movement sleep behavior disorder are seen in patients with voltage-gated potassium channel-complex antibodies. Fragmented sleep and hypersomnia are common in paraneoplastic syndromes associated with anti-MA protein encephalitis; rapid eye movement sleep behavior disorder in those with antibodies against leucine-rich glioma inactivated protein (LGI1) or contactin-associated protein 2 (CASPR2) antibodies. Antibodies against a cell adhesion protein IGLON5 may result in obstructive sleep apnea, inspiratory stridor, disorganized nonrapid eye movement sleep, and excessive movements and parasomnias fragmenting nonrapid and rapid eye movement sleep. Recognizing a particular sleep/wake disorder is often a presenting or prominent feature in certain autoimmune encephalitis permit for earlier diagnosis. This is important because reduced morbidity and better short- and long-term outcomes are associated with earlier diagnosis and immunotherapies.

Sleep Biomarkers Help Predict the Development of Alzheimer Disease.

SUMMARY: Middle-aged or older adults who self-report sleep-wake disorders are at an increased risk for incident dementia, mild cognitive impairment, and Alzheimer disease. Dementia in people with mild cognitive impairment and Alzheimer disease who complain of sleep-wake disorders progress faster than those without sleep-wake disorders. Removal of amyloid-beta and tau tangles occurs preferentially in non-rapid eye movement 3 sleep and fragmented or insufficient sleep may lead to accumulation of these neurotoxins even in preclinical stages. Selective atrophy in the medial temporal lobe on brain MRI has been shown to predict impaired coupling of slow oscillations and sleep spindles. Impaired slow wave-spindle coupling has been shown to correlate with impaired overnight memory consolidation. Whereas, a decrease in the amplitude of 0.6 to 1 Hz slow wave activity predicts higher cortical Aß burden on amyloid PET scans. Overexpression of the wake-promoting neurotransmitter orexin may predispose patients with mild cognitive impairment and Alzheimer disease to increased wakefulness, decreasing time they need to clear from the brain the neurotoxic accumulation of amyloid-beta and especially tau. More research exploring these relationships is needed and continuing.

What Is the Prognostic Significance of Rapid Eye Movement Sleep Without Atonia in a Polysomnogram?

SUMMARY: Freud said we are lucky to be paralyzed during sleep, so we cannot act out our dreams. Atonia of skeletal muscles normally present during rapid eye movement sleep prevents us from acting out our dreams. Observing rapid eye movement sleep without atonia in a polysomnogram in older adults first and foremost warrants consideration of rapid eye movement behavior disorder. Seventy-five to 90% of older adults with isolated rapid eye movement behavior disorder will develop a neurodegenerative disease within 15 years, most often a synucleinopathy. Rapid eye movement sleep without atonia in those younger than 50 years is commonly found in individuals with narcolepsy and those taking antidepressant medications.

Sleep Spindles and K-Complexes Are Favorable Prognostic Biomarkers in Critically Ill Patients.

SUMMARY: In this narrative review, we summarize recent research on the prognostic significance of biomarkers of sleep in continuous EEG and polysomnographic recordings in intensive care unit patients. Recent studies show the EEG biosignatures of non-rapid eye movement 2 sleep (sleep spindles and K-complexes) on continuous EEG in critically ill patients better predict functional outcomes and mortality than the ictal-interictal continuum patterns. Emergence of more complex and better organized sleep architecture has been shown to parallel neurocognitive recovery and correlate with functional outcomes in traumatic brain injury and strokes. Particularly interesting are studies which suggest intravenous dexmedetomidine may induce a more biomimetic non-rapid eye movement sleep state than intravenous propofol, potentially providing more restorative sleep and lessening delirium. Protocols to improve intensive care unit sleep and neurophysiological studies evaluating the effect of these on sleep and sleep architecture are here reviewed.

Stroke: What's Sleep Got to Do With It?

SUMMARY: Ischemic strokes most often occur between 6 am and 12 am after awakening from sleep but up to 30% occur during sleep. Wake-up strokes (WUS) are new focal neurological deficit(s) persisting for ≥ 24 hours attributable to an ischemic event present on patient awakening. Obstructive sleep apnea (OSA) is a major risk factor for WUS because it compounds the instability of the morning environment and increases the likelihood of cardiovascular events, including hypertension, atrial fibrillation, right-to-left shunts, and stroke. Circadian-driven alterations in structural, homeostatic, and serological factors also predispose to WUS. Also, WUS patients are often not considered candidates for time-dependent intravenous thrombolysis therapy because of an uncertain onset time. However, using the tissue clock (positive diffusion weighted imaging-negative fluid-attenuated inversion recovery mismatch) dates the WUS as 3 to 4.5 hours old and permits consideration for intravenous thrombolysis and if needed mechanical thrombectomy. Given the high prevalence of moderate/severe OSA in stroke patients and its impact on stroke outcomes, screening with overnight pulse oximetry and home sleep apnea test is needed. Treating OSA poststroke remains challenging. Polysomnographic changes in sleep architecture following acute/subacute stroke may also impact upon stroke outcome.

Minimum Technical Requirements for Performing Ambulatory EEG.

SUMMARY: Ambulatory EEG (AEEG) devices offer portable, multichannel, digital EEG recording with or without video in the patient's natural environment. The technology applied for AEEG recording is like the technology for routine EEG and inpatient long-term video-EEG monitoring but designed to be compact and wearable. Computer-based AEEG technology is well-suited to digital recording, signal processing, and visual display. However, acquiring interpretable EEG outside of the hospital setting presents its own technical challenges. Published guidelines have established technical standards for performing routine EEG and inpatient video-EEG monitoring, but technical standards for AEEG are lacking. Therefore, this guideline provides minimal technical standards for the performance of AEEG which are essential to ensure the quality of studies for clinical and research practice. We expect these minimum standards to evolve over time with improved performance and advances in the technology.

The AASM scoring manual: a critical appraisal.

PURPOSE OF REVIEW: Summarize recently published studies and critiques evaluating the effects of the American Academy of Sleep Medicine (AASM) Sleep Scoring Manual. RECENT FINDINGS: Only a few retrospective studies have been published evaluating the new AASM Scoring Manual. These have shown that when scoring polysomnograms (PSGs) using the AASM rules compared to previous standards and guidelines: increased amount and percentage of sleep time in Non-Rapid Eye Movement Sleep (NREM) 1 (N1) and N3 sleep, and decreased NREM 2 (N2) sleep; improved interscorer reliability when scoring sleep stages in adults; large differences in apnea-hypopnea indexes (AHIs) using different hypopnea scoring definitions; and PSGs scored using the 'recommended' hypopnea definition in the new manual identified no significant sleep disordered breathing in 40% of lean individuals with symptomatic OSA (AHI ≥5/h by 1999 'Chicago' criteria) and a favorable response to treatment. SUMMARY: Two years have passed since the AASM Scoring Manual was published, garnering less criticism than was feared by those who developed it. The improvement in interscorer reliability using the Manual is heartening since this goal shaped many of the choices made. The alternative hypopnea rule should be endorsed as a recommended option. The AASM Scoring Manual provides a foundation upon which we all can build rules and methods that quantify the complexity of sleep and its disorders. Multicenter validation and refinement of the Manual is encouraged.

Night Stepping: Fitbit Cracks the Case.

ABSTRACT: The most common sleep disorders that can result in injurious or violent behaviors include REM sleep behavioral disorder, sleepwalking, comorbid parasomnias, sleep-related dissociative disorder, and obstructive sleep apnea. Video polysomnography is usually indicated to evaluate recurring sleep-related injury in adults. Only one-third of patients with complex paroxysmal nocturnal events will have one of their habitual events on a single night of in-laboratory video polysomnography, most often those who have prominent, high-frequency motor features. We report evidence of sleep walking induced by sodium oxybate identified by steps recorded on a consumer wearable device coinciding with clinical history and evidence of injury.

Epilepsy and Sleep-Related Breathing Disturbances.

Epilepsy is the fourth most common neurologic disorde in the United States, affecting over 2.2 million people. Epilepsy is associated with a number of medical and psychiatric comorbidities, higher health-care use and cost, and substantial economic burden. OSA is twofold more common in adults with epilepsy than in age-matched control subjects, and the incidence increases with age. Self-reported daytime sleepiness is not helpful in predicting OSA, possibly related to the ceiling effect of general sleepiness among people with epilepsy from diverse causes. Mostly small retrospective series found a significant reduction in seizures in people with epilepsy and OSA adherent with positive airway pressure therapy compared with untreated individuals. This finding illustrates the potential beneficial effects of sleep therapies on epilepsy. Central apnea, oxygen desaturations, and hypercapnia can occur during the ictal and immediate postictal period, especially with generalized tonic-clonic seizures. Central apneas have been produced by electrical stimulation of mesial temporal structures. These respiratory disturbances suggest activation of the central autonomic network and may contribute to sudden unexpected death in epilepsy (SUDEP), the leading cause of epilepsy-related death in people with drug-resistant epilepsy. SUDEP typically occurs during sleep, and patients are more often found in a prone position and have a history of nocturnal seizures. Whether OSA contributes to SUDEP is unknown. Vagus nerve stimulation is a form of neuromodulation for drug-resistant focal epilepsy. When the device activates during sleep it causes reduction in airflow and respiratory effort, airflow obstruction, and oxygen desaturations, sometimes producing a clinical sleep apnea syndrome. The goal of this review is to discuss firmly established and recently recognized clinical, neurobiologic, electrophysiologic, and polysomnographic relationships between sleep-disordered breathing and epilepsy.

The Visual Scoring of Sleep in Infants 0 to 2 Months of Age.

UNLABELLED: In March 2014, the American Academy of Sleep Medicine (AASM) Board of Directors requested the Scoring Manual Editorial Board develop rules, terminology, and technical specifications for scoring sleep/wake states in full-term infants from birth to 2 mo of age, cognizant of the 1971 Anders, Emde, and Parmelee Manual for Scoring Sleep in Newborns. On July 1, 2015, the AASM published rules for scoring sleep in infants, ages 0-2 mo. This evidence-based review summarizes the background information provided to the Scoring Manual Editorial Board to write these rules. The Anders Manual only provided criteria for coding physiological and behavioral state characteristics in polysomnograms (PSG) of infants, leaving specific sleep scoring criteria to the individual investigator. Other infant scoring criteria have been published, none widely accepted or used. The AASM Scoring Manual infant scoring criteria incorporate modern concepts, digital PSG recording techniques, practicalities, and compromises. Important tenets are: (1) sleep/wake should be scored in 30-sec epochs as either wakefulness (W), rapid eye movement, REM (R), nonrapid eye movement, NREM (N) and transitional (T) sleep; (2) an electroencephalographic (EEG) montage that permits adequate display of young infant EEG is: F3-M2, F4-M1, C3-M2, C4-M1, O1-M2, O2-M1; additionally, recording C3-Cz, Cz-C4 help detect early and asynchronous sleep spindles; (3) sleep onsets are more often R sleep until 2-3 mo postterm; (4) drowsiness is best characterized by visual observation (supplemented by later video review); (5) wide open eyes is the most crucial determinant of W; (6) regularity (or irregularity) of respiration is the single most useful PSG characteristic for scoring sleep stages at this age; (7) trace alternant (TA) is the only relatively distinctive EEG pattern, characteristic of N sleep, and usually disappears by 1 mo postterm replaced by high voltage slow (HVS); (8) sleep spindles first appear 44-48 w conceptional age (CA) and when present prompt scoring N; (9) score EEG activity in an epoch as "continuous" or "discontinuous" for inter-scorer reliability; (10) score R if four or more of the following conditions are present, including irregular respiration and rapid eye movement(s): (a) low chin EMG (for the majority of the epoch); (b) eyes closed with at least one rapid eye movement (concurrent with low chin tone); (c) irregular respiration; (d) mouthing, sucking, twitches, or brief head movements; and (e) EEG exhibits a continuous pattern without sleep spindles; (11) because rapid eye movements may not be seen on every page, epochs following an epoch of definite R in the absence of rapid eye movements may be scored if the EEG is continuous without TA or sleep spindles, chin muscle tone low for the majority of the epoch; and there is no intervening arousal; (12) Score N if four or more of the following conditions are present, including regular respiration, for the majority of the epoch: (a) eyes are closed with no eye movements; (b) chin EMG tone present; (c) regular respiration; and (d) EEG patterns of either TA, HVS, or sleep spindles are present; and (13) score T sleep if an epoch contains two or more discordant PSG state characteristics (either three NREM and two REM characteristics or two NREM and three REM characteristics). These criteria for ages 0-2 mo represent far more than baby steps. Like all the other AASM Manual rules and specifications none are fixed in stone, all open for debate, discussion and revision with the fundamental goal to provide standards for comparison of methods and results. COMMENTARY: A commentary on this article appears in this issue on page 291.

Primary sleep disorders in people with epilepsy: clinical questions and answers.

The questions facing clinicians with patients with sleep disorder and epilepsy are addressed in this article. Both adult and child epilepsy are discussed in the context of the most typical questions a clinician would have, such as "Are parasomnias more common in people with epilepsy?", "Is sleep architecture abnormal in children with epilepsy", along with outcomes of numerous questionnaire-based, case-based, and double-blind placebo studies on such aspects as sleep duration, daytime sleepiness, anxiety and fears, limb movement, nocturnal seizures, agitation, behavioral disorders, and learning disorders.