Abstracts

Rationale: Infantile spasms (ISS) is characterized in part by hypsarrhythmia on EEG and controversies continue regarding the elements of this pattern and their significance. Variations on the classic hysparrhythmia pattern have been described including modified and atypical forms. Few previous studies have examined quantitative EEG findings in subjects with ISS and correlated the pretreatment EEG with developmental outcome. We selected a cohort of infants with ISS of unknown cause to test the hypothesis that meaningful correlation may be made between pretreatment EEG findings using spectral analysis, phenotypes, and outcomes.Methods: Subjects with genotype-unknown ISS (n=15) were recruited through the Child Neurology division and the Strong Epilepsy Center at the University of Rochester Medical Center, and also through the Infantile Spasms Registry. Phenotype data, including EEG, brain imaging, and clinical and developmental history were obtained. Persyst 12 software was used to perform the spectral analyses on pre-treatment EEGs in both the awake and sleep states. The following spectral trends within the Persyst software system including EEG Asymmetry Index (amplitude symmetry), Relative EEG Asymmetry Index (amplitude symmetry), Peak Envelope (amplitude), Spike Density, and FFT spectrogram. R version 2.15 (http://cran.us.r-project.org/) was used for data analysis. Detailed medication histories were obtained for subjects, including ACTH use and duration of treatment. A cohort of neurologically normal infants and infants with epilepsy other than ISS were also analyzed using the same metrics with Persyst. Results: Pre-treatment EEGs from 6 subjects with ISS have been analyzed, and preliminarily found that subjects with ISS have statistically greater amplitude (p-value 0.009), spike density (p-value 0.04507), and mean absolute asymmetry (p-value 0.01702) compared to 3 age matched controls without ISS (Fig.1). Figure 2 demonstrates an example of spectral analysis of an infant without ISS (Fig.2A) and an infant with ISS (Fig.2B). The spectral analysis of the subject with ISS shows greater absolute asymmetry, a higher peak envelope (amplitude), and greater spike density. Follow up of clinical outcome data is ongoing.Conclusions: Spectral analysis allows statistical methods to be applied to EEG recordings, permitting quantitative relationships to be made between pre-treatment EEG features, response to treatment, and long-term outcome. Our preliminary data shows that we have mapped key spectral analyses to elements of hypsarrhythmia, and that EEGs of infants with ISS, other epilepsies, and normal controls may be differentiated. It is hypothesized that spectral analysis will allow the controversies regarding definitions and clinical significance of modified EEG patterns to be resolved through identification of specific spectral patterns that correlate statistically with response to treatment and developmental outcome.