Feasibility of Actigraphy for Evaluating Sleep and Daytime Physical Activity in Children with Autism Spectrum Disorder.

This research evaluated the feasibility of actigraphy to measure sleep and physical activity in children (ages 2-8 years) with autism spectrum disorder (ASD). We also explored associations between sleep and physical activity. Validated screening measures established eligibility. Questionnaires, diaries, and 5 days and 5 nights of actigraphy monitoring were used to collect data. Of the 32 children enrolled, 27 (84.4%) completed actigraphy monitoring. Based on the median steps per day, children with high physical activity had lower total sleep time and more disruptive behaviors than children with low physical activity. Findings support the feasibility of using actigraphy to measure sleep and physical activity in children with ASD. Larger studies are needed to evaluate interactions of physical activity on sleep in this population.

Characterizing sleep disorders in an autism-specific collection of electronic health records.

OBJECTIVE/BACKGROUND: Sleep problems are common in people on the autism spectrum. This study reviews one detailed approach to querying the electronic health record (EHR) in a large tertiary care center. PATIENTS/METHODS: We developed methods for identifying people on the autism spectrum and defined their sleep problems using the key words, "sleep" or "melatonin", or International Classification of Diseases (ICD) codes. We examined treatment responses of these individuals to melatonin supplementation. RESULTS: Sleep problems were documented in 86% of patients with ages ranging from 6 to 30 years old. Our specific keyword search yielded more patients with sleep diagnoses than ICD codes alone. About two-thirds of patients who received melatonin supplementation reported benefit from its use. CONCLUSIONS: Our study provides a framework for using deidentified medical records to characterize sleep, a common co-occurring condition, in people on the autism spectrum. Using specific keywords could be helpful in future work that queries the EHR.

Characterizing Sleep in Adolescents and Adults with Autism Spectrum Disorders.

We studied 28 adolescents/young adults with autism spectrum disorders (ASD) and 13 age/sex matched individuals of typical development (TD). Structured sleep histories, validated questionnaires, actigraphy (4 weeks), and salivary cortisol and melatonin (4 days each) were collected. Compared to those with TD, adolescents/young adults with ASD had longer sleep latencies and more difficulty going to bed and falling asleep. Morning cortisol, evening cortisol, and the morning-evening difference in cortisol did not differ by diagnosis (ASD vs. TD). Dim light melatonin onsets (DLMOs) averaged across participants were not different for the ASD and TD participants. Average participant scores indicated aspects of poor sleep hygiene in both groups. Insomnia in ASD is multifactorial and not solely related to physiological factors.

Sleep in children and adolescents with Angelman syndrome: association with parent sleep and stress.

BACKGROUND: Sleep concerns are common in children with Angelman syndrome, with 20-80% of individuals having a decreased sleep need and/or abnormal sleep-wake cycles. The impact of these sleep behaviours on parental sleep and stress is not known. METHOD: Through the use of standardised questionnaires, wrist actigraphy and polysomnography, we defined the sleep behaviours of 15 children/adolescents with Angelman syndrome and the association of the child/adolescents sleep behaviours on parental sleep behaviours and parental stress. RESULTS: Both children/adolescents and their parents exhibited over 1 h of wake time after sleep onset and fragmented sleep. Prolonged sleep latency in the child was associated with parent insomnia and daytime sleepiness. Additionally, variability in child total sleep time was associated with parental stress. CONCLUSIONS: Poor sleep in children/adolescents with Angelman syndrome was associated with poor parental sleep and higher parental stress. Further work is warranted to identify the underlying causes of the poor sleep, and to relate these findings to daytime functioning, behaviour and the family unit.

Sleep patterns and daytime sleepiness in adolescents and young adults with Williams syndrome.

BACKGROUND: Sleep disorders are common in individuals with neurodevelopmental disorders and may adversely affect daytime functioning. Children with Williams syndrome have been reported to have disturbed sleep; however, no studies have been performed to determine if these problems continue into adolescence and adulthood. METHODS: This study examined overnight sleep patterns and daytime sleepiness in 23 adolescents and adults with Williams syndrome age 25.5 (8.0) years [mean (SD)]. Interviewer-administered sleep questionnaires were used to evaluate nighttime sleep behaviours and daytime sleepiness. Wrist actigraphy was used to evaluate sleep patterns. RESULTS: Although individuals in our sample averaged 9 h in bed at night, daytime sleepiness and measures of sleep disruption were common and comparable to those of other populations with neurodevelopmental disorders. These measures included reduced sleep efficiency [74.4 (7.0)%] with prolonged sleep latency [37.7 (37.3) min], increased wake time after sleep onset [56.1 (17.6) min], and an elevated movement and fragmentation index [14.3 (4.6)]. CONCLUSION: Adolescents and young adults with Williams syndrome were found to be sleepy despite averaging 9 h in bed at night. Implications are discussed for associated causes of sleep disruption and future polysomnographic evaluation.

Treating obstructive sleep apnea in adults with epilepsy: a randomized pilot trial.

OBJECTIVE: Small uncontrolled series suggest that treatment of obstructive sleep apnea (OSA) in patients with epilepsy may improve seizure control. Prior to conducting a definitive randomized controlled trial, we addressed critical design issues in a pilot study. METHODS: We identified a cohort of adult patients with medically refractory epilepsy and coexisting OSA, documented by polysomnography (PSG). After an 8-week baseline period, subjects with OSA were randomized to therapeutic or sham continuous positive airway pressure (CPAP) for 10 weeks. Subjects maintained seizure calendars and antiepileptic drug dosages were held constant. RESULTS: Sixty-eight subjects with suspected OSA were enrolled and 35 subjects randomized to therapeutic CPAP (22 subjects) or sham (13 subjects) CPAP. Male gender and an elevated sleep apnea questionnaire score were predictive of OSA on PSG. Nineteen subjects in the therapeutic group and all 13 subjects in the sham group completed the trial. Baseline apnea-hypopnea index (AHI) and CPAP adherence were comparable between groups. A significant reduction in AHI was observed in the therapeutic CPAP group as compared to the sham group. Subjects, study coordinators, and principal investigators were unable to predict treatment allocation. CONCLUSIONS: This pilot study provided critical information related to study design and feasibility for planning a comprehensive trial to test the hypothesis that treating obstructive sleep apnea in patients with epilepsy improves seizure control.

Rasmussen's syndrome and new-onset narcolepsy, cataplexy, and epilepsy in an adult.

We report a case of new-onset seizures and narcolepsy in a previously healthy 40-year-old man. He developed severe daytime somnolence and cataplexy over the course of a few months. Brain MRI was normal, and polysomnography with multiple sleep latency testing confirmed a diagnosis of narcolepsy. His HLA haplotype is DQB1*0602 and cerebrospinal fluid analysis showed no detectable hypocretin. Approximately 18 months later, he developed complex partial seizures. Further MRI showed a progressively enlarging lesion involving the left frontotemporal and insular areas. Pathology from a partial resection was consistent with Rasmussen's syndrome. Evaluation for tumor, infectious, and paraneoplastic etiologies was negative. There was no further progression of the residual lesion on serial MRI. Although the pathophysiologic bases of narcolepsy and Rasmussen's syndrome are unknown, they may have an autoimmune basis. This unique case of both disorders in a single patient suggests the possibility of a common underlying disease process.

Sleep deprivation does not affect seizure frequency during inpatient video-EEG monitoring.

OBJECTIVE: To determine whether acute sleep deprivation facilitates seizures during inpatient monitoring in a controlled protocol. METHODS: Eighty-four patients with medically refractory partial epilepsy undergoing inpatient monitoring were assigned in consecutive blocks to either sleep deprivation every other night or to normal sleep. In both groups, subjects were requested to stay awake during the day, from 6 AM to 10 PM. In the sleep deprivation group, patients also stayed awake between 10 PM and 6 AM every other night beginning with Day 2. Patients were removed from sleep deprivation if they had two or more secondarily generalized seizures within 24 hours. Patients were removed from the normal sleep group and were sleep deprived if they did not have a complex partial or secondarily generalized seizure by Day 6 of monitoring. In these patients removed from sleep deprivation or from normal sleep, data were analyzed up to and including the day of removal from the protocol. RESULTS: The sleep deprivation and normal sleep subjects did not differ in age, sex, seizure localization, or percent dosage reduction in antiepileptic drugs from baseline at days 1 to 3 of monitoring. Protocol duration was 6.5 +/- 2.4 days (mean +/- SD) for the sleep deprivation group and 5.8 +/- 2.0 days for the normal sleep group. Seizures per day for complex partial, secondarily generalized, and combined complex partial and secondarily generalized, calculated from admission until end of protocol, did not differ significantly between the two groups. CONCLUSION: Acute sleep deprivation did not affect seizure frequency during inpatient monitoring in our patients with intractable complex partial seizures with secondary generalization.

Vagus nerve stimulation reduces daytime sleepiness in epilepsy patients.

BACKGROUND: Given that vagal afferents project to brainstem regions that promote alertness, the authors tested the hypothesis that vagus nerve stimulation (VNS) would improve daytime sleepiness in patients with epilepsy. METHODS: Sixteen subjects with medically refractory seizures underwent polysomnography and multiple sleep latency tests (MSLT) and completed the Epworth Sleepiness Scale (ESS), a measure of subjective daytime sleepiness, before and after 3 months of VNS. Most subjects (>80%) were maintained on constant doses of antiepileptic medications. RESULTS: In the 15 subjects who completed baseline and treatment MSLT, the mean sleep latency (MSL) improved from 6.4 +/- 4.1 minutes to 9.8 +/- 5.8 minutes (+/- SD; p = 0.033), indicating reduced daytime sleepiness. All subjects with stimulus intensities of < or =1.5 mA showed improved MSL. In the 16 subjects who completed baseline and treatment ESS, the mean ESS score decreased from 7.2 +/- 4.4 to 5.6 +/- 4.5 points (p = 0.049). Improvements in MSLT and ESS were not correlated with reduction in seizure frequency. Sleep-onset REM periods occurred more frequently in treatment naps as compared to baseline naps (p < 0.008; Cochran-Mantel-Haenszel test). The amount of REM sleep or other sleep stages recorded on overnight polysomnography did not change with VNS treatment. CONCLUSIONS: Treatment with VNS at low stimulus intensities improves daytime sleepiness, even in subjects without reductions in seizure frequency. Daytime REM sleep is enhanced with VNS. These findings support the role of VNS in activating cholinergic and other brain regions that promote alertness.

Effects of vagus nerve stimulation on respiration during sleep: a pilot study.

BACKGROUND: Vagus nerve stimulation (VNS) is associated with respiratory effects such as hoarseness, dyspnea, and laryngeal irritation. The effects of VNS on sleep-related breathing in humans have not been reported previously. METHODS: Four epilepsy patients underwent polysomnography (PSG) before and after 3 months of treatment with VNS. Two of the four patients also underwent follow-up PSG to assess the effects of changing stimulus parameters on sleep-related breathing. RESULTS: All patients showed consistent sleep-related decreases in airflow and effort coinciding with VNS activation, although most events did not meet laboratory criteria for apneas or hypopneas. Apneas and hypopneas were more frequent during VNS activation than during nonactivation. Apnea-hypopnea index (AHI) for three subjects during VNS treatment PSG was <5 apneas and hypopneas/hour. In one patient with obstructive sleep apnea (OSA) before VNS treatment, AHI rose from 4 (pretreatment) to 11.3 (treatment). In this patient and in another patient without clinically significant OSA, lowering stimulus frequency, but not stimulus intensity, pulse width, or on-time, ameliorated VNS-related apneas and hypopneas. CONCLUSIONS: VNS is associated with adverse changes in respiration during sleep. In patients without preexisting OSA, this VNS effect is probably not clinically significant. In patients with preexisting OSA, VNS should be administered with care. Lowering VNS stimulus frequency or prolonging off-time may prevent exacerbation of OSA.

Obstructive sleep apnea is common in medically refractory epilepsy patients.

BACKGROUND: Previous reports have documented the coexistence of obstructive sleep apnea (OSA) and epilepsy and the therapeutic effects of treatment on seizure frequency and daytime sleepiness. The authors' objective was to determine the prevalence of OSA and its association with survey items in a group of patients with medically refractory epilepsy undergoing polysomnography (PSG). METHODS: Thirty-nine candidates for epilepsy surgery without a history of OSA underwent PSG as part of a research protocol examining the relationship of interictal epileptiform discharges to sleep state. Subjects also completed questionnaires about their sleep, including validated measures of sleep-related breathing disorders (Sleep Apnea Scale of the Sleep Disorders Questionnaire [SA/SDQ]) and subjective daytime sleepiness (Epworth Sleepiness Scale [ESS]). RESULTS: One-third of subjects had OSA, defined by a respiratory disturbance index (RDI) > or = 5. Five subjects (13%) had moderate to severe OSA (RDI > 20). Subjects with OSA were more likely to be older, male, have a higher SA/SDQ score, and more likely to have seizures during sleep than those without OSA (p < 0.05). Seizure frequency per month, the number or type of antiepileptic drugs (AED) prescribed, the localization of seizures (temporal versus extratemporal), and the ESS were not statistically different between the two groups. CONCLUSIONS: In our sample, previously undiagnosed obstructive sleep apnea was common, especially among men, older subjects, and those with seizures during sleep. The impact of treating OSA on seizure frequency and daytime sleepiness in medically refractory epilepsy patients warrants further controlled study.

Lateralizing value of interictal spikes on overnight sleep-EEG studies in temporal lobe epilepsy.

PURPOSE: To determine the lateralizing value of interictal epileptiform discharges (IEDs) recorded during overnight sleep-EEG studies in temporal lobe epilepsy. Because IEDs are more prevalent in non-rapid eye movement (NREM) sleep than in wakefulness, overnight sleep-EEG recordings may contribute additional lateralizing information to the epilepsy surgery evaluation beyond daytime EEGs. METHODS: Twenty-four subjects with medically refractory temporal lobe epilepsy underwent continuous overnight sleep-EEG recordings. Subjects were seizure free > or =24 h before study and receiving stable doses of medication. The IED foci recorded on overnight studies were compared with daytime EEGs, interictal samples, and ictal recordings during long-term monitoring, brain magnetic resonance images (MRIs), and surgical outcome. RESULTS: (a) In all 24 subjects, including 13 without IEDs on daytime EEGs, temporal IEDs were present during NREM sleep and were exclusively or predominantly (>95%) unilateral in 15 and bitemporal in nine. (b) Unilateral NREM IEDs were concordant with surface or depth ictal-onset regions in 14 subjects, even if MRIs were normal (three subjects) or surface ictal-onset regions were bilateral (five subjects). Eleven of 12 subjects with unilateral concordant NREM IEDs who have undergone surgery are seizure free. (c) Bitemporal IEDs were associated with postoperative seizures in all subjects with normal MRIs or widespread MRI abnormalities. However, all subjects with bitemporal IEDs and MRI hippocampal abnormalities concordant with ictal-onset regions had good to excellent surgical outcomes. CONCLUSIONS: When combined with other investigations, IEDs recorded on overnight studies add prognostic data to the epilepsy surgery evaluation not provided by daytime EEGs.

Hippocampal sleep spindles revisited: physiologic or epileptic activity?

OBJECTIVE: Few reports have described sleep spindles in intracranial electrode recordings from human hippocampus. Controversy exists regarding whether hippocampal spindles represent a physiologic or epileptic phenomenon. METHODS: We reviewed hippocampal recordings in 8 subjects to characterize events resembling sleep spindles. RESULTS: In 6 subjects, events occurred exclusively during non-rapid eye movement (NREM) sleep, were similar in morphology to surface spindles, occurred simultaneously or independently of surface spindles, and did not show a consistent relationship to the epileptic region. In an additional subject, a proportion of the hippocampal activity recorded differed slightly in morphology from surface spindles, was present during both NREM and rapid eye movement (REM) sleep, occurred in the same channels as isolated interictal epileptiform discharges, attenuated just prior to seizures, and occurred postictally as repetitive discharges. This activity occurred simultaneously or independently of surface spindles, but differed from surface spindles by both visual and signal analysis measures. CONCLUSIONS: Most examples of hippocampal activity resembling spindles are probably physiologic, originating within the hippocampus or propagated from neighboring regions. However, in one subject, spindle activity and epileptiform discharges may have coincided, supporting experimental evidence that neurophysiological processes associated with spindle generation and NREM sleep contribute to the activation of epileptiform discharges.

Cost-utility of three approaches to the diagnosis of sleep apnea: polysomnography, home testing, and empirical therapy.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is usually diagnosed with overnight polysomnography in a sleep laboratory. Home sleep studies can be performed at lower cost, but results are somewhat less reliable. Bedside diagnosis of OSAS without any testing has also been discussed. OBJECTIVE: To model the costs and utility of laboratory polysomnography, home study, and no testing during the 5 years after initial evaluation for OSAS. DESIGN: Cost-utility analysis. DATA SOURCES: Published data. TARGET POPULATION: Hypothetical cohort of persons suspected of having OSAS. TIME HORIZON: The 5 years after initial evaluation for OSAS. PERSPECTIVE: Societal. INTERVENTION: Nasal continuous positive airway pressure when OSAS was diagnosed. MEASUREMENTS: Quality of life, survival and charges (as proxies for costs) for each diagnostic method. RESULTS OF BASE-CASE ANALYSIS: Under almost all modeled conditions, polysomnography provided maximal quality-adjusted life-years in the 5 years after the initial diagnostic evaluation. The incremental charges for polysomnography over home study or no testing were about $13,400 and $9200, respectively, per quality-adjusted life-year gained during this period. RESULTS OF SENSITIVITY ANALYSIS: Results were sensitive to the utility of treatment in the absence of OSAS. CONCLUSIONS: The cost-utility of polysomnography instead of home study or no testing in the diagnosis of OSAS compares favorably with that of other procedures for which society judges the added utility per dollar spent to be worthwhile. More precise determination of certain key variables in this model should be a goal of future research.

Interictal spiking increases with sleep depth in temporal lobe epilepsy.

PURPOSE: To test the hypothesis that deepening sleep activates focal interictal epileptiform discharges (IEDs), we performed EEG-polysomnography in 21 subjects with medically refractory temporal lobe epilepsy. METHODS: At the time of study, subjects were seizure-free for > or =24 h and were taking stable doses of antiepileptic medications (AEDs). Sleep depth was measured by log delta power (LDP). Visual sleep scoring and visual detection of IEDs also were performed. Logistic-regression analyses of IED occurrence in relation to LDP were carried out for two groups of subjects, nine with frequent IEDs (group 1) and 12 with rare IEDs (group 2). RESULTS: The LDP differentiated visually scored non-rapid eye movement (NREM) sleep stages (p = 0.0001). The IEDs were most frequent in NREM stages 3/4 and least frequent in REM sleep. Within NREM sleep, in both groups, IEDs were more frequent at higher levels of LDP (p < 0.05). In group 1, after accounting for the level of LDP, IEDs were more frequent (a) on the ascending limb of LDP and with more rapid increases in LDP (p = 0.007), (b) in NREM than in REM sleep (p = 0.002), and (c) closer to sleep onset (p < 0.0001). Fewer than 1% of IEDs occurred within 10 s of an EEG arousal. CONCLUSIONS: Processes underlying the deepening of NREM sleep, including progressive hyperpolarization in thalamocortical projection neurons, may contribute to IED activation in partial epilepsy. Time from sleep onset and NREM versus REM sleep also influence IED occurrence.

Value of the multiple sleep latency test (MSLT) for the diagnosis of narcolepsy.

Since its introduction, the multiple sleep latency test (MSLT) has played a major role in the diagnosis of narcolepsy. We assessed its diagnostic value in a series of 2,083 subjects of whom 170 (8.2%) were diagnosed with narcolepsy. The sensitivity of the combination of two or more sleep onset rapid eye movement (REM) periods (SOREMPs) with a mean sleep latency of < 5 minutes on an initial MSLT was 70% with a specificity of 97%, but 30% of all subjects with this combination of findings did not have narcolepsy. In some narcoleptics who had more than one MSLT, the proportion of naps with SOREMPs varied substantially from the initial MSLT to the follow-up test. The highest specificity (99.2%) and positive predictive value (PPV) (87%) for MSLT findings was obtained with the criteria of three or more SOREMPs combined with a mean sleep latency of < 5 minutes, but the sensitivity of this combination was only 46%. The combination of a SOREMP with a sleep latency < 10 minutes on polysomnography yielded a specificity (98.9%) and PPV (73%) almost equal to those obtained from combinations of MSLT findings, but the sensitivity was much lower. Our results suggest that the MSLT cannot be used in isolation to confirm or exclude narcolepsy, is indicated only in selected patients with excessive daytime sleepiness, and is most valuable when interpreted in conjunction with clinical findings.

Usefulness of polysomnography in epilepsy patients.

We reviewed the records of 63 adult epilepsy patients who underwent polysomnograms in our laboratory since 1985 to determine the indications for polysomnography and the results of testing. Reasons for referral included excessive daytime sleepiness, suspected obstructive sleep apnea (OSA), and characterization of nocturnal spells. The most common polysomnographic diagnosis was OSA, although we also found narcolepsy, insufficient sleep syndrome with possible idiopathic hypersomnolence, and previously unrecognized nocturnal seizures. We treated OSA with continuous positive airway pressure in 28 patients, 15 of whom were using the device at follow-up appointments. The majority of patients treated for OSA or other disorders reported an improvement in sleepiness or seizure control. Polysomnography, when indicated, is beneficial in epilepsy patients.

A direct comparison of PET activation and electrocortical stimulation mapping for language localization.

Mapping eloquent language cortex in presurgical patients typically is accomplished using highly invasive direct cortical stimulation techniques. Functional imaging during language activation using positron emission tomography (PET) is a promising, noninvasive alternative that requires validation. In seven patients undergoing surgical evaluation for intractable epilepsy, we performed both direct cortical stimulation and PET activation mapping of language cortex using identical tasks. MRI, PET, and CT scans were coregistered to directly compare the location of language centers determined by cortical stimulation versus activation PET. We found that cortical regions that showed increased cerebral blood flow during both visual and auditory naming tasks were located in the same regions as subdural electrodes which disrupted language during electrical stimulation. Cortical regions underlying electrodes that did not disrupt language also showed no consistent changes in regional cerebral blood flow during PET activation. Used cautiously, PET activation produces language maps similar to those obtained with direct cortical stimulation, with more complete brain coverage and considerably less invasion.