Abstracts

Rationale:
Sleep comorbidities are thought to be common - and in some cases severe - for children with early-life epilepsies (ELE). Yet, there is a paucity of data regarding the profile of these sleep disturbances and their complications.
Method:
Between 2014 and 2018, caregivers of people with rare epilepsy syndromes (mostly ELEs) registered with the Rare Epilepsy Network (REN). Responses from participants with ELE who were asked about sleep concerns were included in the analysis. Binomial distributions, Fisher’s exact tests and logistic regression were performed.
Results:
Among the 1,458 REN participants, 530 were asked about sleep concerns. Median age of the children was 93 months (IQR 42-168) and 55% were female. The ELE diagnoses were: Tuberous Sclerosis (n=117), Dravet Syndrome (n=99), Aicardi Syndrome (n=61), hypothalamic hamartoma (n=43), Doose Syndrome (n=41), West Syndrome (n=39), Dup15q variant (n=38), PCDH19 variant (n=27), CDKL5 variant (n=18), SCN8A variant (n=17), and SYNGAP1 variant (n=9). The remaining 21 had other ELEs. A sleep concern was endorsed by 58% (297/515) of respondents. The most common sleep concerns were: (1) frequent nighttime awakenings (243/504;49%), (2) difficulty falling asleep (213/504;43%), and (3) very restless sleep (183/493;38%). Nocturnal seizures were reported in 80% (410/515) of children and were associated with a reported sleep concern (Fisher’s exact test p=0.0077). Sleep concerns were most often reported in children with Dup15 variants (29/38;76%). Multivariable logistic regression was performed with nocturnal seizures as the dependent variable and sleep concern (β =0.43, OR 1.54, 95% CI 0.98, 2.42, p= 0.06,), female sex (β = 0.47, OR 1.59, 95% CI 1.02, 2.50, p=0.04,), age in months (β= 0.01, OR 1.01, 95%CI 1.01, 1.02 p< 0.0001), and ELE diagnosis (β = 0.03, OR 1.03, 95%CI 0.98, 1.09, p= 0.24) as the independent variables. There was an interaction between ELE diagnosis and age in months (β= - 0.00066, OR 0.9, 95% CI 0.99, 1.00, p= 0.003). Age was further categorized (0 to ≤ 6 months, 6 to ≤ 12 months, 12 to ≤ 24 months, 24 to ≤ 36 months, 36 to ≤ 48 months and >48 months). Increasing age was associated with presence of sleep concerns, nocturnal seizures, and specific ELE diagnoses (most children were in the >48 month category, except for West and Ohtahara syndromes) (all Fisher’s exact tests p< 0.05).
Conclusion:
Most children with ELE have a reported sleep concern and these sleep concerns may be important predictors of nocturnal seizures regardless of ELE syndrome. The interaction between age and ELE diagnosis may reflect the natural history of the ELE syndromes. The effect of female sex on nocturnal seizures may reflect the sample characteristics, or a biological predisposition of girls toward nocturnal seizures. The prevalence of sleep concerns in children with ELE increased with age, in contrast to the natural progression of sleep consolidation expected in healthy children. This could reflect altered neurodevelopment or untreated sleep pathology in children with ELE. Taken together, these results suggest potential unmet clinical needs related to sleep disturbances for children with ELE.
Funding:
:NIH T32 Multi-Institutional Training in Genetic/Genomic Approaches to Sleep Disorders (2T32HL110952-06) Patient-Centered Outcomes Research Institute (PCORI) (PPRN-1306-04577)