EEG endophenotypes in autism spectrum disorder.

OBJECTIVES: The association between autism spectrum disorder (ASD) and epilepsy is well-known. Abnormalities on electroencephalography (EEG) results have been reported in patients with ASD without a history of seizures. However, little is known about the relationship between abnormalities on EEG results and the core features of ASD. The purpose of the study was to determine the relationship between the presence of epilepsy and/or abnormalities on EEG results and disease-associated impairments in young children with ASD. METHODS: Data were collected from medical records at Cincinnati Children's Hospital Medical Center (CCHMC) of patients with well-characterized ASD. Patients were subdivided into three groups: ASD without epilepsy but with abnormal EEG results, ASD without epilepsy and normal EEG results, and ASD with epilepsy. Developmental (Mullen Scales of Early Learning (MSEL)), adaptive (Vineland Adaptive Behavior Scales (VABS)), behavioral (Child Behavior Checklist), and language (Preschool Language Scales (PLS)) assessments, along with birth and developmental histories, medications, and medical comorbidities were collected. Electroencephalography data were abstracted from reports and included presence, characterization, and location of abnormalities. RESULTS: Analysis was performed on 443 patients with ASD. Seventy patients (15.8%) had epilepsy at the time of ASD diagnosis. Out of 372 patients with ASD and no epilepsy, 95 (25.5%) had an abnormal EEG result (67.4% epileptiform, 36.8% other abnormalities). Majority of epileptiform discharges were focal (83%) and most commonly seen in the left temporal region. The group with abnormal EEG results exhibited more impaired adaptive functioning when compared with the group with normal EEG results (p < 0.05). The group with abnormal EEG results was more similar to the group with epilepsy, differing only in expressive language (p < 0.01) and fine motor (p < 0.05) skills on the Mullen Scales. The group with epilepsy exhibited lower scores in all areas of developmental and adaptive functioning compared with the group with normal EEG results (p < 0.05). At the time of analysis, 13 patients (8 in the group with abnormal EEG results, 5 in the group with normal EEG results) developed epilepsy at a mean age of 10.5 years ±â€¯3.3 years. CONCLUSIONS: The presence of an abnormal EEG result or epilepsy in the setting of ASD suggests worse developmental and adaptive functioning. Further analysis will help to clarify associations and offer insight into treatment for this subpopulation without epilepsy but with abnormal EEG results.

Sleep apnea, hypoxia, and late-onset epilepsy: the Atherosclerosis Risk in Communities study.

STUDY OBJECTIVE: Sleep apnea is associated with unexplained epilepsy in older adults in small studies. We sought to determine the relationship between sleep apnea and additional sleep characteristics and late-onset epilepsy, adjusting for comorbidities, using data from the large, prospective Atherosclerosis Risk in Communities (ARIC) Study cohort. METHODS: We used Medicare claims to identify cases of late-onset epilepsy (LOE) in ARIC participants. We used polysomnography data from 1309 ARIC participants who also participated in the Sleep Heart Health Study in 1995-1998, and demographic and comorbidity data from ARIC. Later risk of LOE was evaluated using survival analysis with a competing risk of death. We also used survival analysis in 2672 ARIC participants to identify the association between self-reported obstructive sleep apnea (2011-2013), and the risk of subsequent LOE. RESULTS: Late-midlife oxygen desaturation to less than 80% during sleep was associated with subsequent development of LOE, adjusted subhazard ratio 3.28 (1.18-9.08), but the apnea-hypopnea index was not related. Participant report of diagnosis of sleep apnea in 2011-2013 was also associated with subsequent LOE, adjusted subhazard ratio 2.59 (1.24-5.39). CONCLUSIONS: Sleep apnea and oxygen saturation nadir during sleep are associated with LOE, independently of hypertension and other comorbidities. These potentially modifiable risk factors could have large clinical implications for LOE.

Night of Kentucky blues: the case of the hypoxic child in the sleep laboratory.

CITATION: Sleep-disordered breathing is an increasingly identified condition in the pediatric population, resulting in an increasing number of direct-to-lab referrals for polysomnography (PSG). We present a unique case of a pediatric patient who demonstrated continuous hypoxemia during PSG. A 6-year-old Black female presented for PSG via direct referral with obstructive sleep apnea as a concern. At the onset of the PSG, oxygen saturation of 85% while awake and at rest was noted. The oxygen saturation did not improve despite troubleshooting, probe and patient repositioning, or probe replacement. The PSG demonstrated an average sleep oxygen saturation of 81%, with oxygen saturation nadir of 73% and apnea-hypopnea index = 6.1 events/h, consistent with mild obstructive sleep apnea with persistent desaturation. Hemoglobin electrophoresis was consistent with hemoglobin Louisville. This case illustrates that communication between the sleep medicine physician and the community physician after a direct to lab referral is crucial to avoid concern and confusion. CITATION: Sendon C, Carosella C, Melendres C. Night of Kentucky blues: the case of the hypoxic child in the sleep laboratory. J Clin Sleep Med. 2021;17(10):2125-2128.

Sleep disordered breathing in children receiving vagus nerve stimulation therapy.

OBJECTIVE: The effects of vagus nerve stimulation (VNS) on sleep disordered breathing (SDB) have been reported in limited case series. Detailed studies, particularly in the pediatric population, have not been performed. The primary purpose of this study is to describe clinical characteristics, polysomnographic findings, and management of children treated with VNS. METHODS: A retrospective review of medical records and polysomnography data was performed in patients ages 0-20 years old receiving VNS therapy for refractory epilepsy at Cincinnati Children's Hospital Medical Center. RESULTS: 22 subjects met the inclusion criteria. 50% were male. The mean age at the time of VNS insertion was 8.4 ± 4.0 years. The mean age at the first PSG was 10.6 ± 4.3 years. Common presentations to sleep clinics included snoring (77.3%), frequent nighttime awakening (68.1%), and parasomnias (63.6%). The median apnea-hypopnea index (AHI) was 4.5/hr (IQR 3.0-13.1) and the median obstructive index (OI) was 4.1/hr (1.5-12.8). Obstructive sleep apnea (OSA) was diagnosed after VNS insertion in 19 patients (86.4%), 8 of which (36.3%) had severe OSA. Six patients (27.3%) had significant hypoventilation. For management, 6 patients (27.2%) were treated with bilevel PAP, 3 patients (13.6%) with CPAP, 2 patients (9.1%) with ventilator, 4 patients (18.2%) with upper airway surgeries, and 9 patients (40.9%) received medications only. CONCLUSIONS: SDB is common in pediatric patients with medically refractory epilepsy managed with VNS who were referred to sleep medicine clinics. Both OSA and nocturnal alveolar hypoventilation are relatively common in this population. Management of SDB often involves the use of positive airway pressure therapy or upper airway surgeries. Further studies are needed to assess the prevalence, risk factors, and the effect of treatments on epilepsy control. This study highlights the need for screening of SDB prior to and following VNS implantation.

Vagus Nerve Stimulation for Electrographic Status Epilepticus in Slow-Wave Sleep.

BACKGROUND: Electrographic status epilepticus in slow sleep or continuous spike and waves during slow-wave sleep is an epileptic encephalopathy characterized by seizures, neurocognitive regression, and significant activation of epileptiform discharges during nonrapid eye movement sleep. There is no consensus on the diagnostic criteria and evidence-based optimal treatment algorithm for children with electrographic status epilepticus in slow sleep. PATIENT DESCRIPTION: We describe a 12-year-old girl with drug-resistant electrographic status epilepticus in slow wave sleep that was successfully treated with vagus nerve stimulation. Her clinical presentation, presurgical evaluation, decision-making, and course after vagus nerve stimulator implantation are described in detail. FINDINGS: After vagus nerve stimulator implantation, the girl remained seizure free for more than a year, resolved the electrographic status epilepticus in slow sleep pattern on electroencephalography, and exhibited significant cognitive improvement. CONCLUSION: Vagus nerve stimulation may be considered for electrographic status epilepticus in slow sleep.