Abstracts

Rationale: Adrenocorticotropic hormone (ACTH) is the standard of care for treatment of Infantile Spasms (IS), with its efficacy assessed by both the resolution of epileptic spasms (ES) and of hypsarrhythmia (HYP) on electroencephalogram (EEG). Epileptic disorders have been postulated to promote the development of abnormal connectivity and neuronal networks. However, little is known about how the treatment responses of IS to ACTH may improve the neurophysiological profile of IS compared to nonresponders. Our goal is to evaluate resting background brain activity using MEG both before and after treatment with ACTH in order to use MEG as a marker for ACTH response and as a predictor for the development of other seizure types after IS. Methods: Data was obtained for three subjects at the time of diagnosis of IS and after 2 weeks of ACTH (150 units/m2) (Subject 2 had only 10 days of ACTH.). All subjects displayed HYP and electroclinical ES on initial EEG. For each patient, 5 minutes of resting MEG data was recorded using a 248-channel whole-head neuromagnetometer. A minimum of 5 segments of resting MEG data (5 s duration) not affected by the presence of biogenic or environmental artifacts were selected after visual inspection for digital fast Fourier transformation (FFT) power spectrum analysis, and spectral power was summarized using the standard frequency bands of delta (0–4 Hz), theta (4–7 Hz), alpha (8–12 Hz) and beta (12–20 Hz). Results: Subjects presented at 5-8 months of age, two with unknown etiologies and one with lissencephaly. Subject 1 had initial resolution of HYP and ES. However, ES resumed during ACTH wean. Subject 2 had resolution of HYP but continued to have ES which later resolved with VGB. Subject 3 had resolution of ES but HYP persisted so ACTH was continued for one week with subsequent resolution of HYP. While visual inspection of the MEG spectral profiles in each individual patient revealed some variability in patterns of background activity, consistent differences across patients were present most notably in the delta and theta bands, pre- and post- treatment. Specifically, Subject 1 demonstrated reductions in delta and theta power, with a visible decrease in delta power in right anterior regions. In Subject 2 reductions in delta and theta power were most prominent bilaterally in central and temporal regions, whereas in Subject 3 alterations in background cortical activity were better defined by a preponderance of reduced delta power in the left temporal, posterior and bi-anterior regions. Conclusions: While preliminary, the present findings provide some insights into short-term effects of ACTH on resting cortical rhythms in children with IS. Applying this approach to a larger sample of patients may further highlight the utility of MEG as a marker for ACTH response, with implications for neurodevelopment, in particular as it relates to integration of sensorimotor processes and higher cognitive functions, which may be adversely effected in IS. Funding: Funding support provided by Mallinckrodt Pharmaceuticals.