Faculty Bibliography

OBJECTIVE: Recent data suggest that both disordered sleep and low serum iron occur more frequently in children with autism compared with children with typical development. Iron deficiency has been linked to specific sleep disorders. The goal of the current study was to evaluate periodic limb movements in sleep and iron status in a group of children with autism compared with typically developing children and children with nonautism developmental delay to determine if iron status correlated with polysomnographic measures of latency and continuity and periodic limb movements in sleep. METHODS: A total of 102 children (68 with autism, 18 typically developing, 16 with developmental delay) aged 2 to 7 years underwent a one-night modified polysomnography study and phlebotomy at the National Institutes of Health to measure serum markers of iron status (ferritin, iron, transferrin, percent transferrin saturation). RESULTS: No serum iron marker was associated with periodic limb movements of sleep or any other sleep parameter; this did not differ among the diagnostic groups. No significant differences among groups were observed on serum iron markers or most polysomnogram parameters: periodic limb movements in sleep, periodic limb movements index, wake after sleep onset, or sleep efficiency. Children in the autism group had significantly less total sleep time. Serum ferritin was uniformly low across groups. CONCLUSIONS: This study found no evidence that serum ferritin is associated with polysomnogram measures of latency or sleep continuity or that young children with autism are at increased risk for higher periodic limb movements index compared with typically developing and developmental delay peers.

Introduction: Obstructive sleep apnea (OSA) is prevalent in nearly a third of patients with epilepsy. Treatment with continuous positive airway pressure (CPAP) is associated with improvement in seizure control. However, CPAP is often dificult to tolerate for various reasons, and it has been suggested that noncompliant patients with epilepsy and OSA are at higher risk of recurrent seizures than are CPAP-compliant patients. Our objective is to determine short-term compliance, which predicts long-term adherence, to CPAP therapy in patients with OSA and epilepsy. Our preliminary data were presented earlier at the 2013 WASM Annual Meeting in Valencia, Spain. Methods: We retrospectively identiied patients with moderate to severe OSA (AHI > 15) started on nasal CPAP between 2012-2013 at the New York Sleep Institute. We divided them into OSA-only (control) and epilepsy- OSA groups. Patients with history of non-epileptic seizures, poor compliance with anti-epileptic drugs, greater than ten seizures a day, diagnosis of epilepsy within the past six months, a signiicant history of medical, psychiatric or substance abuse, or a two month compliance rate of less than ten percent were excluded. CPAP compliance (deined as percent of days with greater than 4 hours usage) was obtained via a monitoring card within the CPAP system. Results: Seventy-ive epilepsy patients were identiied, forty-nine (65%) of which were diagnosed with concomitant OSA. Thirty-three patients from the control group and fourteen epilepsy patients met inclusion criteria. Mean age was 50.7 and 60.5 (p = 0.016), BMI was 32.3 and 32.2 (p = 0.47), Epworth Sleepiness Scale was 8.4 and 9.6 (p = 0.27), spontaneous arousal index 10.0 and 7.5 (p = 0.16), sleep eficiency was 80.7% and 79.2% (p = 0.38), optimal CPAP pressure was 11.4 and 10.6 cm H20 (p = 0.21), and AHI 30.2 and 40.2 (p = 0.09), in the epilepsy- OSA and OSA-only groups, respectively. One month compliance rates were 65.7% in epilepsy patients and 78.9% in the control group (p = 0.029), !

Introduction: Obstructive sleep apnea (OSA) is prevalent in nearly a third of patients with epilepsy. Treatment with Continuous Positive Airway pressure (CPAP) is associated with improvement in seizure control. However, CPAP is often difficult to tolerate for various reasons, and it has been suggested that noncompliant patients with epilepsy and OSA are at higher risk of recurrent seizures than are CPAP-compliant patients. Our objective is to determine short-term compliance, which predicts long-term adherence, to CPAP therapy in patients with OSA and epilepsy. Materials and methods: We retrospectively identified patients with moderate to severe OSA (AHI P15) started on nasal CPAP between 2012-2013 at the New York Sleep Institute. We divided them into OSA-only (control) and epilepsy-OSA groups. Patients with history of non-epileptic seizures, poor compliance with anti-epileptic drugs, greater than ten seizures a day, diagnosis of epilepsy within the past six months, a significant history of medical, psychiatric or substance abuse, or a two month compliance rate of less than ten percent were excluded. CPAP compliance (defined as percent of days with greater than 4 h usage) was obtained via a monitoring card within the CPAP system. Results: Sixty-five epilepsy patients were identified, forty-one (65%) of which were diagnosed with concomitant OSA. Thirty-two patients from the control group and fourteen epilepsy patients met inclusion criteria. Mean age was 50.7 and 60.4 (p = 0.018), BMI was 32.3 and 32.4 (p = 0.48), Epworth Sleepiness Scale was 8.4 and 9.8 (p = 0.23), spontaneous arousal index 10.0 and 7.7 (p = 0.19), sleep efficiency was 80.7% and 78.7% (p = 0.35), optimal CPAP pressure was 11.4 and 10.6 cm H2O (p = 0.22), and AHI 30.2 and 41.0 (p = 0.075), in the epilepsy-OSA and OSA-only groups, respectively. One month compliance rates were 65.7% in epilepsy patients and 78.3% in the control group (p = 0.038), and 2 month compliance rates were 68.3% and 71.5%, respectively (p = 0.33). Conclusion!

Abstract Background: Rapid eye movement (REM) sleep is greatest in the developing brain, is driven by acetylcholine, and may represent a protected time for neuroplasticity. Recently published data from our lab observed that children with autism spent significantly less time in this state during a single night recording than did typically developing children and those with developmental delay without autism. The objective of this study was to determine whether or not donepezil can increase the REM % in children with diagnosed autism spectrum disorder (ASD) found to have REM % values of at least two standard deviations below expected for age. Methods: Five subjects found to have an ASD (ages 2.5-6.9 years) and demonstrated deficits in REM sleep compared with within-lab controls were enrolled in a dose finding study of donepezil. Each subject was examined by polysomnography for REM sleep augmentation after drug administration. Results: REM sleep as a percentage of Total Sleep Time was increased significantly and REM latency was decreased significantly after drug administration in all subjects. No other observed sleep parameter was changed significantly. Conclusions: Donepezil can increase the amount of time that children with an ASD spend in the REM sleep state. A double-blind, placebo-controlled trial is needed to assess the association between REM sleep augmentation and learning, cognition, and behavior in such children

OBJECTIVE: Panayiotopoulos syndrome is a benign idiopathic childhood epilepsy characterized by altered autonomic activity at seizure onset. METHODS: Three siblings with Panayiotopoulos syndrome underwent 24-hour EEG recording and head-up tilt testing with continuous blood pressure and RR interval monitoring. Plasma catecholamines and vasopressin were measured while supine, upright, and during a typical seizure. RESULTS: Patient 1, a 12-year-old girl, had a history of involuntary lacrimation, abdominal pain, and recurrent episodes of loss of muscle tone and unresponsiveness followed by somnolence. Her EEG revealed bilateral frontotemporal spikes. Patient 2, a 10-year-old boy, had episodic headaches with pinpoint pupils, skin flushing of the face, trunk, and extremities, purple discoloration of hands and feet, diaphoresis, nausea, and vomiting. Tilt testing triggered a typical seizure after 9minutes; there was a small increase in blood pressure (+5/4mm Hg, systolic/diastolic) and pronounced increases in heart rate (+59bpm) and norepinephrine (+242pg/mL), epinephrine (+175pg/mL), and vasopressin (+22.1pg/mL) plasma concentrations. Serum glucose was elevated (206mg/dL). His EEG revealed right temporal and parietal spikes. Patient 3, an 8-year-old boy, had a history of restless legs at night, enuresis, night terrors, visual hallucinations, cyclic abdominal pain, and nausea. His EEG showed bitemporal spikes. CONCLUSION: Hypertension, tachycardia, and the release of vasopressin suggest activation of the central autonomic network during seizures in familial Panayiotopoulos syndrome. These autonomic and neuroendocrine features may be useful in the diagnosis and may have therapeutic implications

Narcolepsy is a neurologic disorder characterized by excessive daytime sleepiness and manifestations of disrupted rapid eye movement sleep stage. The pathologic hallmark is loss of hypocretin neurons in the hypothalamus likely triggered by environmental factors in a susceptible individual. Patients with narcolepsy, in addition to excessive daytime sleepiness, can present with cataplexy, sleep paralysis, sleep fragmentation, and hypnagogic/hypnopompic hallucinations. Approximately 60% to 90% of patients with narcolepsy have cataplexy, characterized by sudden loss of muscle tone. Only 15% of patients manifest all of these symptoms together. Narcolepsy can be misdiagnosed as a psychiatric disorder or even epilepsy. An appropriate clinical history, polysomnogram, Multiple Sleep Latency Test, and, at times, cerebrospinal fluid hypocretin levels are necessary for diagnosis. The treatment of narcolepsy is aimed toward the different symptoms that the patient manifests. Excessive daytime sleepiness is treated with amphetamine-like or non-amphetamine-like stimulants. Cataplexy is treated with sodium oxybate, tricyclic antidepressants, or selective serotonin and norepinephrine reuptake inhibitors. Sleep paralysis, hallucinations, and fragmented sleep may be treated with benzodiazepine hypnotics or sodium oxybate. Patients with narcolepsy should avoid sleep deprivation, sleep at regular hours, and, if possible, schedule routine napping.

OBJECTIVE: To compare objective polysomnographic parameters between 3 cohorts: children with autism, typical development, and developmental delay without autism. DESIGN: Overnight polysomnographic recordings were scored for sleep architecture according to American Academy of Sleep Medicine criteria by a board-certified sleep medicine specialist blind to diagnosis for studies collected between July 2006 and September 2009. SETTING: Subjects were evaluated in the pediatric ward in the Clinical Research Center of the National Institutes of Health. PARTICIPANTS: First 60 consecutive children with autism, 15 with typical development, and 13 with developmental delay matched for nonverbal IQ to the autism group, ranging in age from 2 to 13 years, selected without regard to the presence or absence of sleep problem behavior. MAIN OUTCOME MEASURES: Total sleep time, latencies to non-rapid eye movement (REM) and REM sleep, and percentages of total sleep time for stages 1 and 2 sleep, slow-wave sleep, and REM sleep. RESULTS: There were no differences between the typical vs developmental delay groups. Comparison of children with autism vs typical children revealed shorter total sleep time (P = .004), greater slow-wave sleep percentage (P = .001), and much smaller REM sleep percentage (14.5% vs 22.6%; P < .001). Comparison of children with autism vs children with developmental delay revealed shorter total sleep time (P = .001), greater stage 1 sleep percentage (P < .001), greater slow-wave sleep percentage (P < .001), and much less REM sleep percentage (14.5% v 25%; P < .001). CONCLUSION: A relative deficiency of REM sleep may indicate an abnormality in neural organization in young children with autism that is not directly associated with or related to inherent intellectual disability but may serve as a window into understanding core neurotransmitter abnormalities unique to this disorder