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Published on: December 22, 2016
Rapid eye movement sleep reduction in pediatric epilepsy: A propensity score-matched study
Alen Juginović1, Laura Rodman2
1Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA.
Insights
Pediatric epilepsy is linked to disrupted sleep architecture, particularly reduced rapid eye movement (REM) sleep, especially in children under six. Antiseizure medications (ASMs) can worsen these sleep disturbances.
Area of Science:
- Pediatric Neurology
- Sleep Medicine
- Clinical Neurophysiology
Background:
- Sleep disturbances are common in children with epilepsy.
- Differentiating between epilepsy-related sleep changes and medication side effects is crucial.
Purpose of the Study:
- To characterize sleep architecture in children with epilepsy compared to controls.
- To assess the impact of antiseizure medications (ASMs) on sleep in pediatric epilepsy.
Main Methods:
- Cross-sectional analysis of 560 pediatric epilepsy patients and 560 matched controls using polysomnography (PSG) data.
- Propensity score matching for age, sex, and BMI.
- Comparison of 15 PSG outcomes and secondary analysis of on- vs. off-ASM patients.
Main Results:
- Children with epilepsy showed reduced REM sleep, lower sleep efficiency, shorter total sleep time, prolonged REM latency, and lower arousal index.
- ASM use exacerbated the REM sleep deficit, particularly in younger children (<6 years).
- The impact of ASMs on REM sleep was more pronounced when excluding benzodiazepines and less so when excluding melatonin.
Conclusions:
- Epilepsy is associated with REM-predominant sleep disruption in children, most notably under age six.
- ASMs amplify these sleep disturbances, with a developmental gradient observed.
- Further prospective studies are needed to clarify the independent contribution of epilepsy to sleep disruption.
Objective:
This study was undertaken to characterize sleep architecture assessed by polysomnography (PSG) in children with epilepsy versus matched nonepilepsy clinical comparators and disentangle disease from antiseizure medication (ASM) effects.
Methods:
In this cross-sectional analysis of the Nationwide Children's Hospital Sleep DataBank (3647 PSG studies from 3392 patients aged ≤18 years), a clinical cohort referred for PSG, we compared 560 PSG studies in children with epilepsy to 3087 studies in nonepilepsy clinical comparators. Propensity score matching (1:1) on age, sex, and body mass index percentile yielded 560 pairs. Fifteen PSG outcomes were compared using Wilcoxon signed-rank tests with Hedges g and false discovery rate (FDR) correction. A secondary analysis compared 208 matched pairs of on- versus off-ASM epilepsy patients. Seven sensitivity analyses addressed age subgroups, medication exclusions, and comorbidity matching.
Results:
Children with epilepsy had reduced rapid eye movement (REM) sleep (median 18.2% vs. 20.9%, g = -.32 [95% confidence interval = -.41 to -.24], FDR p < .001), lower sleep efficiency (g = -.14, p = .007), shorter total sleep time (g = -.12, p = .015), prolonged REM latency (g = .14, p = .029), and lower arousal index (g = -.12, p = .013). ASM use amplified the REM deficit (15.8% vs. 19.8%, g = -.48, p < .001). The effect followed a developmental gradient: strongest at age < 6 years (g = -.38, p < .001), intermediate at 6-12 years (g = -.31, p = .002), and not detected at >12 years (g = -.07, p = .953). Excluding benzodiazepine users attenuated the signal (g = -.24), whereas excluding melatonin users preserved it (g = -.29).
Significance:
In the largest pediatric epilepsy PSG study to date, epilepsy is associated with an REM-predominant sleep disruption concentrated in children younger than 6 years and amplified by ASMs, although the independent contribution of epilepsy itself remains uncertain. These cross-sectional findings identify early childhood as a period of heightened vulnerability that warrants prospective study.
