Long-term characterization of cognitive phenotypes in children with seizures over 36 months.

RATIONALE: Children with new-onset epilepsies often exhibit co-morbidities including cognitive dysfunction, which adversely affects academic performance. Application of unsupervised machine learning techniques has demonstrated the presence of discrete cognitive phenotypes at or near the time of diagnosis, but there is limited knowledge of their longitudinal trajectories. Here we investigate longitudinally the presence and progression of cognitive phenotypes and academic status in youth with new-onset seizures as sibling controls. METHODS: 282 subjects (6-16 years) were recruited within 6 weeks of their first recognized seizure along with 167 unaffected siblings. Each child underwent a comprehensive neuropsychological assessment at baseline, 18 and 36 months later. Factor analysis of the neuropsychological tests revealed four underlying domains - language, processing speed, executive function, and verbal memory. Latent trajectory analysis of the mean factor scores over 36 months identified clusters with prototypical cognitive trajectories. RESULTS: Three unique phenotypic groups with distinct cognitive trajectories over the 36-month period were identified: Resilient, Average, and Impaired phenotypes. The Resilient phenotype exhibited the highest neuropsychological factor scores and academic performance that were all similar to controls; while the Impaired phenotype showed the polar opposite with the worst performances across all test metrics. These findings remained significant and stable over 36 months. Multivariate logistic regression indicated that age of onset, EEG, neurological examination, and sociodemographic disadvantage were associated with phenotype classification. CONCLUSIONS: This study demonstrates the presence of diverse latent cognitive trajectory phenotypes over 36 months in youth with new-onset seizures that are associated with a stable neuropsychological and academic performance longitudinally.

Impact of sociodemographic disadvantage on neurobehavioral outcomes in children with newly diagnosed seizures and their unaffected siblings over 36 months.

OBJECTIVE: This study was undertaken to determine the short-term and longer term impact of sociodemographic disadvantage on the emotional-behavioral status of youths with new onset epilepsy and their unaffected siblings at the time of diagnosis and the subsequent 3 years. METHODS: Three hundred twelve youths with newly diagnosed epilepsies and 223 unaffected siblings, aged 6-16 years, were independently assessed regarding their emotional and behavioral status by their parents and teachers at baseline, and at 18 at 36 months later; youths with seizures also completed self-report measures of depression, anxiety, and hostility at those three time points. A sociodemographic disadvantage score was computed for each family (children with newly diagnosed seizures and their siblings), and families were separated into four categories from most disadvantaged to least disadvantaged. RESULTS: In both children and siblings, the least disadvantaged group exhibited the lowest level of neurobehavioral problems, whereas the most disadvantaged group showed a higher level of neurobehavioral problems across all the same behavior metrics. Findings remained stable and significant across all informants (parent, teacher, child) and across all time periods (throughout the 3-year period). Furthermore, both corrected and uncorrected linear regression analyses indicated that disadvantage was a more constant and stable predictor of behavioral and emotional problems over time compared to clinical seizure characteristics and abnormalities in magnetic resonance imaging and electroencephalographic testing. SIGNIFICANCE: Sociodemographic disadvantage bears a strong relationship to youths with emotional and behavioral problems both at the time of diagnosis as well as prospectively. The relationship is robust and reflected in reports from multiple informants (parent, teacher, child self-report), evident in siblings as well, and possibly more explanatory than traditional clinical seizure variables. Future studies will be needed to determine whether this disadvantage factor is modifiable with early intervention.

Transcranial Alternating Current Stimulation (tACS) as a Treatment for Insomnia.

We investigated the effects of transcranial alternating stimulation (tACS) in patients with insomnia. Nine patients with chronic insomnia underwent two in-laboratory polysomnography, 2 weeks apart, and were randomized to receive tACS either during the first or second study. The stimulation was applied simultaneously and bilaterally at F3/M1 and F4/M2 electrodes (0.75 mA, 0.75 Hz, 5-minute). Sleep onset latency and wake after sleep onset dropped on the stimulation night but they did not reach statistical significance; however, there were significant improvements in spontaneous and total arousals, sleep quality, quality of life, recall memory, sleep duration, sleep efficiency, and daytime sleepiness.

The Impact of Sociodemographic Disadvantage on Cognitive Outcomes in Children With Newly Diagnosed Seizures and Their Unaffected Siblings Over 36 Months.

BACKGROUND: Accumulating evidence indicates that children with newly diagnosed epilepsy have comorbidities including cognitive challenges. Research investigating comorbidities has focused on clinical epilepsy characteristics and neurobiological/genetic correlates. The role that sociodemographic disadvantage (SD) may play has received less attention. We investigated the role of SD in cognitive status in youth with newly diagnosed epilepsy over a follow-up of 36 months to determine the degree, extent, and duration of the role of disadvantage. METHODS: A total of 289 children (six to 16 years) within six weeks of their first seizure along with 167 siblings underwent comprehensive neuropsychological assessments (intelligence, language, memory, executive function, processing speed, and academic achievement) at baseline, 18 months later, and at 36 months from baseline. Baseline demographic information (race, caregivers education, household income, and parental marital status), clinical epilepsy characteristics (e.g., age of onset), and magnetic resonance imaging (MRI) and electroencephalographic (EEG) information was collected. RESULTS: An SD index was computed for each family and categorized into four groups by level of disadvantage. In children and siblings, the least disadvantaged group exhibited the highest Full-Scale IQ, neuropsychological factor scores, and academic performances, whereas the most disadvantaged showed the polar opposite with the worst performances across all tests. Findings remained stable and significant over 36 months. Linear regression analyses indicated that disadvantage was a more constant and stable predictor of cognitive and academic performance over time compared with clinical epilepsy characteristics and MRI/EEG abnormalities. CONCLUSIONS: This study indicates the strong association between SD and cognitive/academic performance in children with newly diagnosed epilepsy and their siblings is significant and predictive of three-year cognitive outcomes.

Continuous Positive Airway Pressure Use for Obstructive Sleep Apnea in Pediatric Patients.

Pediatric obstructive sleep apnea is becoming more common and better diagnosed and treated. It is seen in children with obesity, genetic disorders, neuromuscular disorders, and congenital malformations. After adenotonsillectomy, continuous positive airway pressure (CPAP) is a major mode of treatment. CPAP is traditionally initiated by titrating in the laboratory. However, auto-CPAP titration in the home environment is becoming more accepted as an option. When children are adherent to CPAP, there are significant benefits to treatment, both short-term and long-term. The short-term benefits include improved behavior, focus, attention, and improved sleep. The long-term benefits include improved cardiovascular and metabolic comorbidities.

Characterizing Sleep Phenotypes in Children With Newly Diagnosed Epilepsy.

BACKGROUND: Children with epilepsy frequently have sleep, behavior, and cognitive problems at the time of or before the epilepsy diagnosis. The primary goal of this study was to determine if specific sleep disturbance phenotypes exist in a large cohort of children with new-onset epilepsy and if these phenotypes are associated with specific cognitive and behavioral signatures. METHODS: A total of354 children with new-onset epilepsy, aged six to 16 years, were recruited within six weeks of initial seizure onset. Each child underwent evaluation of their sleep along with self, parent, and teacher ratings of emotional-behavioral status. Two-step clustering using sleep disturbance (Sleep Behavior Questionnaire), naps, and sleep latency was employed to determine phenotype clusters. RESULTS: Analysis showed three distinct sleep disturbance phenotypes-minimal sleep disturbance, moderate sleep disturbance, and severe sleep disturbance phenotypes. Children who fell into the minimal sleep disturbance phenotype had an older age of onset with the best cognitive performance compared with the other phenotypes and the lowest levels of emotional-behavioral problems. In contrast, children who fell into the severe sleep disturbance phenotype had the youngest age of onset of epilepsy with poor cognitive performance and highest levels of emotional-behavioral problems. CONCLUSIONS: This study indicates that there are indeed specific sleep disturbance phenotypes that are apparent in children with newly diagnosed epilepsy and are associated with specific comorbidities. Future research should determine if these phenotypic groups persist over time and are predictive of long-term difficulties, as these subgroups may benefit from targeted therapy and intervention.

The Relationship Between Sleep, Cognition and Behavior in Children With Newly-Diagnosed Epilepsy Over 36 Months.

Introduction: There is substantial evidence that children with epilepsy experience more sleep, behavior and cognitive challenges than children without epilepsy. However, the literature is limited in describing the relationship between sleep, epilepsy, cognition and behavioral challenges and the interactions amongst these factors over time. This study aims to understand the nature and strength of the relationship between sleep, cognition, mood and behavior in children with new-onset epilepsy as assessed by multiple informants at multiple time periods using multiple different dependent measures. Methods: 332 participants (6-16years) were recruited within 6 weeks of their first recognized seizure. The comparison group was comprised of 266 healthy siblings. Participants underwent sleep evaluation by a parent using the Sleep Behavioral Questionnaire (SBQ), cognitive evaluation using a comprehensive neuropsychological test battery, a behavioral evaluation using the Child Behavior Checklist (CBCL from parents and TRF from teachers) and the Children's Depression Inventory (CDI). These evaluations were completed at baseline (B), at 18 months, and at 36 months. Results: Compared to siblings, children with new-onset epilepsy had more sleep disturbance (SBQ), higher rates of behavioral problems (CBCL and TRF), lower cognitive testing scores, and higher rates of depression; which persisted over the 36-month study. Sleep significantly correlated with behavioral problems, cognitive scores and depression. When divided into categories based of sleep disturbance scores, 39.7% of children with epilepsy experienced "Persistently Abnormal Sleep", while 14.8% experienced "Persistently Normal Sleep". Children with persistently abnormal sleep experienced the highest rates of behavioral problems, depression and cognitive impairment compared to those with persistently normal sleep, regardless of epilepsy syndrome. Younger age of seizure onset, younger age at testing, and lower grade level at baseline were associated with persistently abnormal sleep. Conclusions: To our knowledge, this is the first demonstration of the nature, strength, reliability, stability and persistence of the relationship between sleep, cognition, and behavioral problems over time in a large cohort of children with newly diagnosed epilepsy, as assessed by multiple informants at different timepoints. The results of this study indicate that children with epilepsy are at a high risk of significant persisting neurobehavioral multimorbidity. Therefore, early screening for these challenges may be essential for optimizing quality of life long-term.