Diurnal and sleep/wake patterns of epileptic spasms in different age groups

Summary Purpose: Epileptic spasms are seizures that occur predominantly in children and are characterized by clusters of brief axial movements. Epileptic spasms may occur in the context of a variety of syndromes. Previous research has found that epileptic spasms occur in a sleep/wake and diurnal rhythm. The purpose of this study was to identify these patterns in different age groups. Methods: Charts of 2,021 patients with epilepsy undergoing video–electroencephalography (EEG) monitoring over a 10-year period were reviewed for presence of epileptic spasms and analyzed for their occurrence during the day (6 a.m. to 6 p.m.) or night, out of wake or sleep, and in 3-h time-blocks throughout the day. Exact epileptic spasm time, EEG localization, and the presence or absence of magnetic resonance imaging lesion were also recorded. Patients were separated into two age groups: A ages 3 and under, and over age 3. Statistical analysis of seizure occurrence in time bins was carried out using binomial calculations. p-Values <0.05 were taken as significant. Using exact seizure times, a generalized linear mixed model of the Poisson-family with a square root link function was used to calculate mean seizure times. Age, as a binary variable, and time, as a categorical variable, was treated as fixed effect predictors, and individual effects were modeled as random effects. For comparison between the two age groups, over age 3 and under age 3, seizure times were transformed into circular variables. A circular analysis of variance test was used to assess for the difference in mean seizure time, assuming a von Mises distribution of the circle. Key Findings: We analyzed 219 clusters of epileptic spasms in 51 patients (15 girls; mean age 2.15 ± 2.22 years). Forty-two patients younger than 3 years of age had 163 seizures and nine patients older than 3 years had 56 seizures. Epileptic spasms occurred predominantly during wakefulness (p < 0.001) and during daytime (p < 0.001). Epileptic spasms occurred most frequently between 9 a.m. and noon (p < 0.05) and between 3 p.m. and 6 p.m. (p < 0.001). Patients without magnetic resonance imaging lesions had most seizures between 9 a.m. and noon (p < 0.01) and 3 p.m. and 6 p.m. (p < 0.001). Thirty-seven patients had 157 epileptic spasms (71.2%) with generalized EEG patterns and 14 patients had 62 epileptic spasms (28.8%) with focal EEG patterns. Generalized EEG seizures occurred more frequently than focal EEG seizures (p < 0.001). Following age stratification, patients younger than 3 years had most epileptic spasms between 9 a.m. and noon (p < 0.05) and 3 p.m. and –6 p.m. (p < 0.01) and patients older than 3 years had most epileptic spasms between 6 a.m. and –9 a.m. (p < 0.05) and a second peak between 3 p.m. and 6 p.m., although the difference was not statistically significant due to insufficient numbers. Using continuous time analysis, the mean seizure time in the under age 3 and the over age 3 groups was 2:24 p.m. and 11:40 a.m. Using a circular analysis of variance test, the difference between mean seizure times in these groups was found to be statistically significant (p = 0.038). Significance: Epileptic spasms occur more frequently in the waking state and daytime. Younger patients have epileptic spasms mostly between 9 a.m. and noon and 3 p.m. and –6 p.m., and older patients have epileptic spasms mostly between 6 a.m. and 9 a.m. These findings emphasize age-related changes in epileptic spasm pathophysiology or potentially evolution of disease with age.