Rationale:
Premature birth is a risk factor for both autism spectrum disorder (ASD) and epilepsy (EPI) (Crump et al., 2021; Hirvonen et al., 2017). Additionally, ASD and EPI commonly co-occur (Brondino et al., 2019). While preterm birth-related disruptions to brain development may increase risk for both conditions (Robinson et al., 2010), it is not known whether premature birth, compared to full term birth, has a differential effect on epilepsy phenotype in patients subsequently diagnosed with ASD+EPI. The purpose of this study was to examine the relationship between gestational age (GA) and electroencephalographic (EEG) ictal and interictal epileptiform discharges (IED) in a cohort of patients with ASD+EPI.
Methods:
Retrospective review of electronic health records identified 244 patients with known GA and dual diagnosis of ASD+EPI who had at least one EEG conducted between January 1995 and December 2021. All EEG data were collected and interpreted by board-certified reviewers at a Level 4 Epilepsy Center. The presence and distribution (exclusively generalized, exclusively focal, or mixed/multifocal) of IED elements were extracted from clinical reports using a validated coding system with high interrater reliability. Data were averaged across all available EEG encounters (m=4.43, sd=4.64). Patients were subsequently categorized into Preterm (PT, GA < 37 weeks) and full-term (FT, GA 39-41 weeks).
Results:
The final sample consisted of 58 PT and 140 FT patients with ASD+EPI. Of the PT patients who had at least one seizure captured, 46.1% had exclusively generalized, 30.8% had exclusively focal, and 23.1% had mixed. In FT patients with at least one seizure captured, 35.3% had generalized, 44.1% had focal, and 17.6% had mixed. Of those with interictal activity, PT patients were less likely to exhibit exclusively generalized interictal activity (17.2% compared to 26.25% in FT) or mixed activity (37.1% compared to 46.25% in FT), but more likely to display exclusively focal interictal activity (45.7% compared to 27.5% in FT). PT patients were also more likely to display focal background slowing (34.5% compared to 23.6% of FT subjects). Predominance of focal activity was highest in subjects born very and extremely preterm (< 32weeks GA, n=17). Of those with interictal activity (n=12), 66.7% had exclusively focal activity and 33.3% had mixed. No participants born very or extremely preterm had exclusively generalized interictal activity.
Conclusions:
To our knowledge, this is the first study to explore GA in relation to epileptic activity in individuals with ASD+EPI. Patients with ASD+EPI born premature are more likely than those born full-term to demonstrate focal epileptic activity, providing potential clues to differing underlying disease etiology dependent on gestational age.
Funding:
This work was supported by the National Institutes of Health (NIH) - National Institute of Neurological Disorders and Stroke (NeuroNEXT, #U24NS107182), the NIH National Center for Advancing Translational Sciences (#UL1TR003015, #KL2TR003016), NIH grants 1R01NS120945 and R37 NS119012, and a Supporting Autism Research (STAR) Pilot Award.