NonREM Disorders of Arousal and Related Parasomnias: an Updated Review.

Parasomnias are abnormal behaviors and/or experiences emanating from or associated with sleep typically manifesting as motor movements of varying semiology. We discuss mainly nonrapid eye movement sleep and related parasomnias in this article. Sleepwalking (SW), sleep terrors (ST), confusional arousals, and related disorders result from an incomplete dissociation of wakefulness from nonrapid eye movement (NREM) sleep. Conditions that provoke repeated cortical arousals, and/or promote sleep inertia, lead to NREM parasomnias by impairing normal arousal mechanisms. Changes in the cyclic alternating pattern, a biomarker of arousal instability in NREM sleep, are noted in sleepwalking disorders. Sleep-related eating disorder (SRED) is characterized by a disruption of the nocturnal fast with episodes of feeding after arousal from sleep. SRED is often associated with the use of sedative-hypnotic medications, in particular the widely prescribed benzodiazepine receptor agonists. Compelling evidence suggests that nocturnal eating may in some cases be another nonmotor manifestation of Restless Legs Syndrome (RLS). Initial management should focus upon decreasing the potential for sleep-related injury followed by treating comorbid sleep disorders and eliminating incriminating drugs. Sexsomnia is a subtype of disorders of arousal, where sexual behavior emerges from partial arousal from nonREM sleep. Overlap parasomnia disorders consist of abnormal sleep-related behavior both in nonREM and REM sleep. Status dissociatus is referred to as a breakdown of the sleep architecture where an admixture of various sleep state markers is seen without any specific demarcation. Benzodiazepine therapy can be effective in controlling SW, ST, and sexsomnia, but not SRED. Paroxetine has been reported to provide benefit in some cases of ST. Topiramate, pramipexole, and sertraline can be effective in SRED. Pharmacotherapy for other parasomnias continues to be less certain, necessitating further investigation. NREM parasomnias may resolve spontaneously but require a review of priming and predisposing factors.

Sleep disorders in anti-NMDAR encephalitis.

OBJECTIVE: To describe the sleep disorders in anti-NMDA receptor encephalitis (anti-NMDARe). METHODS: Patients recovering from anti-NMDARe were invited to participate in a prospective observational single-center study including comprehensive clinical, video-polysomnography (V-PSG) sleep assessment, and neuropsychological evaluation. Age- and sex-matched healthy participants served as controls. RESULTS: Eighteen patients (89% female, median age 26 years, interquartile range [IQR] 21-29 years) and 21 controls (81% female, median age 23 years, IQR 18-26 years) were included. In the acute stage, 16 (89%) patients reported insomnia and 2 hypersomnia; nightmares occurred in 7. After the acute stage, 14 (78%) had hypersomnia. At study admission (median 183 days after disease onset, IQR 110-242 days), 8 patients still had hypersomnia, 1 had insomnia, and 9 had normal sleep duration. Patients had more daytime sleepiness than controls (higher Barcelona Sleepiness Index, p = 0.02, and Epworth Sleepiness Score, p = 0.04). On V-PSG, sleep efficiency was similar in both groups, but patients more frequently had multiple and longer confusional arousals in non-REM (NREM) sleep (videos provided). In addition, 13 (72%) patients had cognitive deficits; 12 (67%) had psychological, social, or occupational disability; and 33% had depression or mania. Compared with controls, patients had a higher body mass index (median 23.5 [IQR 22.3-30.2] vs 20.5 [19.1-21.1] kg/m2; p = 0.007). Between disease onset and last follow-up, 14 (78%) patients developed hyperphagia, and 6 (33%) developed hypersexuality (2 requiring hospitalization), all associated with sleep dysfunction. CONCLUSIONS: Sleep disturbances are frequent in anti-NMDARe. They show a temporal pattern (predominantly insomnia at onset; hypersomnia during recovery), are associated with behavioral and cognitive changes, and can occur with confusional arousals during NREM sleep.

Two mutations in the nicotinic acetylcholine receptor subunit A4 (CHRNA4) in a family with autosomal dominant sleep-related hypermotor epilepsy.

Sleep-related hypermotor epilepsy, or nocturnal frontal lobe epilepsy, as it was formerly called, is a focal epilepsy with mostly sleep-related seizures of hypermotor, tonic or dystonic semiology. Sleep-related hypermotor epilepsy may be attributed to a monogenetic cause with autosomal dominant inheritance. Mutations are described in different genes, including the genes for three subunits of the nicotinic acetylcholine receptor. We present a family with members over four generations exhibiting sleep-related hypermotor epilepsy. Genetic testing was available for three members from three generations, and revealed two variants in the alpha-4 subunit of the nicotinic acetylcholine receptor (one of them being novel) which are likely to be disease-causing. As these mutations were identified in cis configuration (on the same allele), we do not know whether one of the variants alone or a combination of the two is responsible for the pathogenicity.

Clinical neurophysiology of NREM parasomnias.

The nonrapid eye movement (NREM) parasomnias range from age-related developmental phenomena in children to aggressive and injurious motor behaviors in all age groups. These parasomnias are commonly referred to as disorders of arousal and are an important cause of sleep-related injury. Genetic predisposition plays a role in the disorders of arousal, most evident in sleepwalking. Important concepts guiding our current understanding of the pathophysiology of the NREM parasomnias include sleep state instability (a propensity for arousal during NREM sleep), sleep inertia (incomplete awakening from NREM sleep), state dissociation (an ability to simultaneously straddle both NREM sleep and wakefulness), and activation of central pattern generators (permitting expression of subcortically determined motor behaviors without conscious higher cortical input). Management is multifaceted with an emphasis on education and nonpharmacologic measures. The purpose of this chapter is to review wake and NREM neurobiology and update our current understanding of NREM parasomnia pathophysiology, epidemiology, genetics, clinical features, precipitating factors, neurophysiologic evaluation, diagnosis, and clinical management.

Pathogenesis of Obstructive Sleep Apnea.

The pathogenesis of obstructive sleep apnea (OSA) has undergone major revisions since it was first described in 1978. This article focuses on new advances. Although it is still necessary to have a collapsible airway to develop OSA, it is primarily the response to obstruction that determines OSA severity and clinical presentation. Identifying factors that determine whether the response is stable or unstable through phenotyping is a promising approach that may lead to pharmacologic therapy in selected patients.

Effects of long-term non-invasive ventilation on sleep structure in children with Spinal Muscular Atrophy type 2.

OBJECTIVE: Changes of sleep architecture have been reported in children with Spinal Muscular Atrophy type 2 (SMA2), mainly represented by a decrease of arousability. No studies have evaluated the effect of long-term ventilation on sleep parameters in these children. The aim of this study was to evaluate the effects of long-term non-invasive positive pressure ventilation (LTNPPV) on sleep architecture and to assess the residual differences from normal controls. METHODS: Nine consecutive children with SMA2 underwent two distinct polysomnographic (PSG) studies, one in spontaneous breathing, and subsequently after LTNPPV. The results were then compared to 15 age-matched controls. RESULTS: SMA2 patients showed only slightly modified sleep architecture on LTNPPV: increased stage N2% and decreased number of awakenings, while several significant differences persisted between SMA2 patients on LTNPPV and controls (decreased total sleep time, number of awakenings, sleep efficiency, and percentage of REM sleep). Sleep microstructure, evaluated by means of the Cyclic alternating pattern (CAP) showed only marginal changes on LTNPPV (small shortening of CAP A1 subtype duration and small increase in CAP A3 index). Conversely, CAP parameters on LTNPPV showed significant differences between SMA2 patients vs. controls, with increased A1 subtype percentage and decreased percentage of A2 and A3 subtypes. CONCLUSIONS: This is the first study in children affected by SMA2 reporting data on sleep microstructure and their changes after LTNPPV. We found persisting, small but important changes in sleep microstructure during LTNPPV in these children, suggesting that this treatment only partially improves their arousability.

Obstructive sleep apnea, nighttime arousals, and leukocyte telomere length: the Multi-Ethnic Study of Atherosclerosis.

STUDY OBJECTIVES: Sleep disturbances and sleep apnea are associated with increased vulnerability to age-related disease, altering molecular pathways affecting biological aging. Telomere length captures one component of biological aging. We evaluated whether objectively assessed sleep and sleep apnea relate to leukocyte telomere length (LTL) in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS: Men and women aged 44-84 years (n = 672) from the MESA Stress and MESA Sleep studies underwent polysomnography and 7 day actigraphy (at Exam 5) and assessment of LTL (at baseline [Exam 1] and about 10 years later [Exam 5]). RESULTS: General linear models adjusting for age, sex, race/ethnicity, BMI, physical activity, and smoking found that severe obstructive sleep apnea (OSA; apnea-hypopnea index > 30) was cross-sectionally associated with shorter LTL (p = 0.007). Modest associations of shorter LTL with less rapid eye movement sleep, more stage 1 sleep, wake after sleep onset >30 min, and long sleep duration were found, but these effects were diminished after adjusting for lifestyle and OSA. Exploratory analyses found that higher arousal index at Exam 5 was associated with greater LTL decline over the prior 10 years (p = 0.004). CONCLUSIONS: OSA was associated with shorter LTL. Individuals with high-arousal frequency had greater leukocyte telomere attrition over the prior decade. These findings suggest that sleep apnea and sleep fragmentation are associated with accelerated biological aging.

Sexsomnia in an Adolescent.

ABSTRACT: Sexsomnia has been reported and is well described in 115 prior cases in the literature. There have been associations with other sleep disorders serving as triggers for confusional arousals, thereby worsening sexsomnia episodes. We present a case of an adolescent boy with a history of resected and treated pineoblastoma who later developed sexsomnia marked by multiple episodes of masturbatory events per night. He had additional suspicions of obstructive sleep apnea. Polysomnography confirmed severe obstructive sleep apnea and captured multiple episodes of sexsomnia from both REM and NREM sleep. The patient also had daytime symptoms of severe anxiety and hypersomnia that required pharmacological intervention, cognitive behavioral techniques, and hypnosis. The patient showed improvement with hypnosis along with a multimodal approach to the treatment of sexsomnia.

Cardiovascular reactivity and psychological hyperarousal in hot flash-associated insomnia disorder.

OBJECTIVES: Given the neurocognitive hyperarousal observed in patients with insomnia disorder and associations of nocturnal hot flashes with cardiovascular disease risk, we examined whether women with hot flash-associated insomnia disorder demonstrate exaggerated cardiovascular responsivity to acute stressors, and also a profile of psychological hyperarousal. METHODS: Peri and postmenopausal women with and without hot flash-associated insomnia disorder underwent assessments of cardiovascular autonomic responsivity to acute stress paradigms and psychological hyperarousal. Hemodynamic responses (heart rate, blood pressure) to nociceptive, social-evaluative, and cognitive stress paradigms were measured in the morning. Psychological hyperarousal was evaluated using questionnaires assessing daytime and presleep hyperarousal, anxiety, and sleep-related cognitions. RESULTS: Women (25 with and 15 without hot flash-associated insomnia) aged 53.4 ±â€Š4.8 years reported a range of insomnia symptoms. Resting-state hemodynamics were similar between groups. Heart rate and blood pressure responses to stress paradigms did not differ by group nor did they correlate with insomnia severity. Women with insomnia disorder had higher generalized anxiety disorder scores (mean 2.7 ±â€Š3.0 vs 1.0 ±â€Š1.4; P = 0.05) and sleep-related cognitions than those without insomnia (P ≤ 0.05). Insomnia symptom severity was moderately correlated with presleep and daytime hyperarousal, anxiety, and sleep-related cognition (all r ≥ 0.43). CONCLUSIONS: Though hot flash-associated insomnia is characterized by psychological hyperarousal before sleep and during the daytime, it does not relate to cardiovascular responsiveness to acute stressors. Our findings do not support the hypothesis that altered cardiovascular control is a potential mechanism by which hot flash-associated insomnia confers higher cardiovascular disease risk.

Confusional arousals during non-rapid eye movement sleep: evidence from intracerebral recordings.

Study Objectives: Confusional arousals (CA) are characterized by the association of behavioral awakening with persistent slow-wave electroencephalographic (EEG) activity during non-rapid eye movement (NREM) sleep-suggesting that sensorimotor areas are "awake" while non-sensorimotor areas are still "asleep." In the present work, we aimed to study the precise temporo-spatial dynamics of EEG changes in cortical areas during CA using intracerebral recordings. Methods: Nineteen episodes of CA were selected in five drug-resistant epileptic patients suffering incidentally from arousal disorders. Spectral power of EEG signal recorded in 30 non-lesioned, non-epileptogenic cortical areas and thalamus was compared between CA and baseline slow-wave sleep. Results: Clear sequential modifications in EEG activity were observed in almost all studied areas. In the last few seconds before behavior onset, an increase in delta activity occurred predominantly in frontal regions. Behavioral arousal was associated with an increase of signal power in the whole studied frequency band in the frontal lobes, cingulate cortex, insular cortex, and precuneus. Afterwards, a diffuse cessation of very low frequencies (<1 Hz) occurred. Simultaneously, a hypersynchronous delta activity (HSDA) (1-1.5 Hz) arose in a broad network involving medial and lateral frontoparietal cortices, whereas higher frequency activities increased in sensorimotor, orbitofrontal, and temporal lateral cortices. This HSDA was predominantly observed in the inferior frontal gyrus. Conclusions: During CA, the level of activity changed in almost all the studied areas. The embedding of a broad frontoparietal network, especially the inferior frontal gyrus, in an HSDA might explain the participants' altered state of consciousness.

Non-Rapid Eye Movement Sleep and Overlap Parasomnias.

PURPOSE OF REVIEW: This article reviews the spectrum of non-rapid eye movement (non-REM) sleep parasomnias, including sleepwalking, confusional arousals, and sleep terrors, which represent the range of phenotypic disorders of arousal from non-REM sleep that occurs in children and adults. RECENT FINDINGS: The International Classification of Sleep Disorders, Third Edition (ICSD-3) classifies parasomnias according to the sleep stage they emerge from: REM, non-REM, or other. Demographics, clinical features, and diagnosis of non-REM parasomnias are reviewed in this article, and an up-to-date synopsis of guidelines for management strategies to assist in the treatment of these sleep disorders is provided. SUMMARY: The non-REM parasomnias are most common in children and adolescents but may persist into adulthood. They can be distinguishable from REM parasomnias and nocturnal epilepsies, and, importantly, may lead to injury. Additionally, other parasomnias in this spectrum include sleep-related eating disorder and sexsomnia. Overlap parasomnia disorder includes one or more manifestations of a non-REM parasomnia seen in combination with REM sleep behavior disorder, representing an apparent erosion of the normally distinct stages of non-REM and REM sleep. A similar yet much more extreme dissociation of states underlies agrypnia excitata and status dissociatus, which represent rare, severe dissociations between non-REM, REM, and wake states resulting clinically in oneiric behaviors and severe derangement of normal polysomnographic wake and sleep stage characteristics. Management of non-REM and overlap parasomnias and state dissociation disorders include ensuring bedroom safety and prescription of clonazepam or hypnosis, in select cases, although in children and adolescents with noninjurious behaviors, non-REM parasomnias are often age-limited developmental disorders, which may ultimately remit by adulthood, and, in these cases, counseling and education alone may suffice. Timely and accurate recognition of the non-REM and overlap parasomnias is crucial to limiting potential patient injury.

Obstructive sleep apnea exaggerates cognitive dysfunction in stroke patients.

BACKGROUND: Obstructive sleep apnea (OSA) is very common in stroke survivors. It potentially worsens the cognitive dysfunction and inhibits their functional recovery. However, whether OSA independently damages the cognitive function in stroke patients is unclear. A simple method for evaluating OSA-induced cognitive impairment is also missing. METHODS: Forty-four stroke patients six weeks after onset and 24 non-stroke patients with snoring were recruited for the polysomnographic study of OSA and sleep architecture. Their cognitive status was evaluated with a validated Chinese version of Cambridge Prospective Memory Test. The relationship between memory deficits and respiratory, sleeping, and dementia-related clinical variables were analyzed with correlation and multiple linear regression tests. RESULTS: OSA significantly and independently damaged time- and event-based prospective memory in stroke patients, although it had less power than the stroke itself. The impairment of prospective memory was correlated with increased apnea-hypopnea index, decreased minimal and mean levels of peripheral oxygen saturation, and disrupted sleeping continuity (reduced sleep efficiency and increased microarousal index). The further regression analysis identified minimal levels of peripheral oxygen saturation and sleep efficiency to be the two most important predictors for the decreased time-based prospective memory in stroke patients. CONCLUSIONS: OSA independently contributes to the cognitive dysfunction in stroke patients, potentially through OSA-caused hypoxemia and sleeping discontinuity. The prospective memory test is a simple but sensitive method to detect OSA-induced cognitive impairment in stroke patients. Proper therapies of OSA might improve the cognitive function and increase the life quality of stroke patients.

Sleep biosignature of Type 2 diabetes: a case-control study.

AIM: To determine whether or not the sleep disturbances associated with Type 2 diabetes affect the structure of sleep. METHODS: We designed a case-control study in 76 patients with Type 2 diabetes and 76 control subjects without Type 2 diabetes, matched by age, gender, BMI and waist and neck circumferences. A subgroup of 32 patients with Type 2 diabetes was also matched with 64 control subjects without Type 2 diabetes according to apnoea-hypopnoea index score. Examination included an overnight full polysomnography. RESULTS: No differences in the percentage of time spent in either rapid eye movement or non-rapid eye movement sleep were observed between groups; however, patients with Type 2 diabetes had more microarousal events during sleep than control subjects [41.4 (total range 4.0-104.4) vs 20.7 (total range 1.3-94.5) events/h; P < 0.001]. These differences were mainly observed during the non-rapid eye movement sleep [7.4 (total range 0-107.2) vs 0.2 (total range 0-65.2) events/h; P < 0.001]. In addition, sleep variables related to oxygen saturation measures, such as the percentage of time spent with oxygen saturation ≤90%, were significantly greater during the rapid eye movement sleep in patients with Type 2 diabetes [20.3 (total range 0-99.2) vs. 10.5 (total range 0-94.0)%; P = 0.047]. This pattern was maintained in the subgroup of patients matched by apnoea-hypopnaea index. Finally, stepwise regression analyses showed that apnoea-hypopnoea index, the presence of Type 2 diabetes and fasting plasma glucose value were independently associated with the number of microarousals (R2 =0.667). CONCLUSIONS: Type 2 diabetes is associated with an altered sleep structure, with different effects according to rapid eye movement (increase in nocturnal hypoxia) or non-rapid eye movement (increase in sleep fragmentation) sleep.

Hyperarousal in insomnia and hypnotic dose escalation.

BACKGROUND: Given concerns about the abuse liability of hypnotics, this study assessed hyperarousal in people with insomnia and its relation to hypnotic self-administration over 12 months of nightly hypnotic use. METHODS: Ninety-five subjects with insomnia (age 32-64 years) underwent screening nocturnal polysomnogram (NPSG) and Multiple Sleep Latency Test (MSLT) the following day and, then, were randomized to receive zolpidem 10 mg or placebo nightly for 12 months. NPSGs and MSLTs were conducted and urine was collected (0700-1500 h) and analyzed for norepinephrine (NE) levels during months one and eight on study medication. A subset (n = 54) underwent hypnotic self-administration assessments in months one, four, and 12. RESULTS: Mean daily sleep latency on screening MSLT was distributed across the full range of MSLT latencies (2-20 min). The highest screening MSLT latencies were detected in subjects with higher NE levels, compared to those with the lowest MSLT latencies. In the subset undergoing self-administration assessment, those with the highest MSLT latencies chose more capsules (placebo and zolpidem) and increased the number of capsules chosen in months four relative to month one, compared to those with the lowest MSLT latencies. CONCLUSIONS: These data show that some insomniacs are hyperaroused with high MSLT/NE levels and, compared to low MSLT/NE insomniacs, they increase the number of capsules (zolpidem and placebo) self-administered on months four and 12 relative to Month one.

Sleep architecture in children with spinal muscular atrophy type 2.

OBJECTIVE: There have been few published reports on the sleep patterns of patients with spinal muscular atrophy (SMA) type 2, and none on sleep microstructure. The aim of this study was to analyze sleep architecture and microstructure in a group of children with SMA type 2, compared with age-matched and sex-matched controls. METHODS: Seventeen SMA type 2 children (seven males, mean age 4.2 years) and 12 controls (five males, mean age 5.0 years) underwent full polysomnography to evaluate sleep architecture and microstructure by means of the Cyclic Alternating Pattern (CAP). RESULTS: Compared with the control children, the SMA type 2 patients showed a mild increase in the apnea/hypopnea index. Sleep was characterized by a decrease in the number of sleep stage shifts per hour, of percentage of stage N3, of stage R, and of sleep efficiency. On the contrary, significant increases of awakenings per hour, wake after sleep onset, and percentage of stage N1 were found. The CAP analysis revealed a significant increase in the percentage of A1 CAP subtypes, a reduction of that of A3 subtypes, and of A2 and A3 indexes. CONCLUSIONS: The results indicated an abnormality of sleep macrostructure and microstructure in SMA type 2 patients, which was characterized by a reduction of A2 and A3 subtypes (low and high power arousals), supporting the concept of a decreased arousability in SMA type 2 patients. Similar to a previous report on SMA type 1, the findings might be additional proof of central nervous system involvement, although these alterations are less severe than those observed in infants with SMA type 1.

Insomnia with physiological hyperarousal is associated with hypertension.

Previous studies have suggested that insomnia with objective short sleep duration is associated with a higher risk of hypertension, and it has been speculated that the underlying mechanism is physiological hyperarousal. In this study, we tested whether insomnia with physiological hyperarousal measured by Multiple Sleep Latency Test (MSLT), a standard test of sleepiness/alertness, is associated with increased risk of hypertension. Two hundred nineteen chronic insomniacs and 96 normal sleepers were included in this study. Chronic insomnia was defined based on standard diagnostic criteria with symptoms lasting ≥6 months. All subjects underwent 1 night in laboratory polysomnography followed by a standard MSLT. We used the median mean MSLT value (ie, >14 minutes) and the 75th percentile of mean MSLT value (ie, >17 minutes) to define hyperarousal. Hypertension was defined based either on blood pressure measures or on diagnosis treatment by a physician. After controlling for age, sex, body mass index, apnea-hypopnea index, diabetes mellitus, smoking, alcohol, and caffeine use, insomnia combined with MSLT >14 minutes increased the odds of hypertension by 300% (odds ratio=3.27; 95% confidence interval=1.20-8.96), whereas insomnia combined with MSLT >17 minutes increased even further the odds of hypertension by 400% (odds ratio=4.33; 95% confidence interval=1.48-12.68) compared with normal sleepers with MSLT ≤14 minutes. Insomnia associated with physiological hyperarousal is associated with a significant risk of hypertension. Long MSLT values may be a reliable index of the physiological hyperarousal and biological severity of chronic insomnia.

Sleep-related cortical arousals in adult subjects with negative polysomnography.

PURPOSE: The arousal index (AI) quantifies cortical arousal relative to total sleep time and is widely used to determine the severity of sleep fragmentation. It usually includes arousals secondary to respiratory events, limb movements, and spontaneous arousals. No systematic studies have been undertaken to determine AI cutoff in subjects with negative polysomnography. METHODS: Three hundred fifty polysomnograms of subjects ≥18 years of age with no sleep disorders (apnea-hypopnea index (AHI) <5, periodic limb movement index (PLMI) <10, no upper airway resistance syndrome) or minimum oxygen saturation > 90 % and no comorbid health problems were reviewed. RESULTS: Basic sleep architecture appears within normal range, except for increased stage N2 and decreased stage N3. AI significantly correlated with age (r = 0.7), sleep efficiency (r =-0.16), sleep latency (r = 0.14), rapid eye movement (REM) latency (r = 0.12), stage N1 (r = 0.15), stage N2 (r = 0.12), stage N3 (r = -0.27), AHI (r = 0.24), PLMI (r = 0.18), and nadir oxygen saturation (r = -0.17) [p < 0.05 for all]. A significant correlation was noted between age and sleep efficiency (r = -0.19), REM latency (r = 0.13), stage N1 (r = 0.16), stage N2 (r = 0.21), stage N3 (r = -0.39), and nadir oxygen saturation (r = -0.16) [p < 0.05 for all]. Multiple linear regression analysis showed that age is only the independent predictor of AI (R (2) = 0.70, p < 0.01). The prediction equation for the arousal index in subject with negative polysomnography is AI = 0.276 × age (year) + 8.018. CONCLUSIONS: Age is the most important independent factor in predicting increasing AI in subjects with negative polysomnography.

Sleep architecture in infants with spinal muscular atrophy type 1.

OBJECTIVE: Few reports on sleep patterns of patients with spinal muscular atrophy type 1 (SMA1) have been published and none on sleep microstructure. The aim of this study was to analyze sleep architecture and microstructure in a group of infants with SMA1, compared with age- and sex-matched controls. METHODS: Twelve SMA1 patients (six males, mean age 5.9 months) and 10 controls (five males, mean age 4.8 months) underwent full polysomnography to evaluate their sleep architecture and microstructure by means of the cyclic alternating pattern (CAP). RESULTS: Compared with control children, SMA1 patients showed increased sleep latency and apnea/hypopnea index. CAP analysis revealed a significant increase in the percentage of A1 CAP subtypes, a reduction of that of A3 subtypes and of A2 and A3 indexes (number/h), indicating a dysfunction of the arousal system in these patients. CONCLUSION: The results indicate the presence of an abnormality of sleep microstructure in SMA1 patients, characterized by a reduction of A2 and A3 CAP subtypes. We hypothesize that SMA1 patients have reduced arousability during non-rapid eye movement sleep, which could be interpreted as additional evidence of central nervous system involvement in this disease.

Do respiratory cycle-related EEG changes or arousals from sleep predict neurobehavioral deficits and response to adenotonsillectomy in children?

STUDY OBJECTIVES: Pediatric obstructive sleep apnea (OSA) is associated with hyperactive behavior, cognitive deficits, psychiatric morbidity, and sleepiness, but objective polysomnographic measures of OSA presence or severity among children scheduled for adenotonsillectomy have not explained why. To assess whether sleep fragmentation might explain neurobehavioral outcomes, we prospectively assessed the predictive value of standard arousals and also respiratory cycle-related EEG changes (RCREC), thought to reflect inspiratory microarousals. METHODS: Washtenaw County Adenotonsillectomy Cohort II participants included children (ages 3-12 years) scheduled for adenotonsillectomy, for any clinical indication. At enrollment and again 7.2 ± 0.9 (SD) months later, children had polysomnography, a multiple sleep latency test, parent-completed behavioral rating scales, cognitive testing, and psychiatric evaluation. The RCREC were computed as previously described for delta, theta, alpha, sigma, and beta EEG frequency bands. RESULTS: Participants included 133 children, 109 with OSA (apnea-hypopnea index [AHI] ≥ 1.5, mean 8.3 ± 10.6) and 24 without OSA (AHI 0.9 ± 0.3). At baseline, the arousal index and RCREC showed no consistent, significant associations with neurobehavioral morbidities, among all subjects or the 109 with OSA. At follow-up, the arousal index, RCREC, and neurobehavioral measures all tended to improve, but neither baseline measure of sleep fragmentation effectively predicted outcomes (all p > 0.05, with only scattered exceptions, among all subjects or those with OSA). CONCLUSION: Sleep fragmentation, as reflected by standard arousals or by RCREC, appears unlikely to explain neurobehavioral morbidity among children who undergo adenotonsillectomy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT00233194.