Abstracts

Rationale: Epilepsy (EPI) is one of the most common medical comorbidities in autism (ASD) (Brondino et al 2019). Estimates of EPI prevalence in ASD are ~⅓ compared to ~1% in the general population (Spence & Schneider 2009; Zack & Kobau, 2017). The pathophysiological link between these two conditions is not known. Three studies have rigorously assessed seizure focus in this population, with results showing predominantly frontal and temporal/centrotemporal onset (Alaimo et al., 2020; Sansa et al., 2011; Capal et al., 2018). The objective of our pilot study was to evaluate focality in epilepsy using a rigorous, expert-review process. We hypothesized that frontal and temporal epileptic focality would predominate in a sample of comorbid ASD+EPI.

Methods: Retrospective review of electronic health records at a single center identified 470 patients (ages 2-25) with ASD+EPI. For a pilot study, we included patients with a comprehensive neuropsychological assessment, allowing us to ascertain accuracy of ASD diagnosis (n=28/33). EPI in these patients was evaluated using an expert review process modeled after an epilepsy surgery conference. Two epileptologists reviewed EPI risk factors, seizure semiology, EEG, and structural brain MRI to verify the diagnosis, classify EPI type (generalized, focal, undetermined), and rate the likelihood of seizure lateralization (right, left) and localization (frontal, temporal, central, parietal, occipital) on a scale of 0-3 (0=unknown, 1=low, 2=medium, 3=high). Likelihood ratings, as opposed to forced categorization, more accurately reflect the complexity of seizure onset determination.

Results: EPI diagnosis was confirmed in 23/28 of participants. Focal (n=16) was significantly more common than generalized (n=6) epilepsy (Chi-Squared test, p=0.03; excluding 1 with undetermined type). The 16 with focal EPI featured a high level of interrater agreement (κ >.90 for right, left, central, temporal; κ >.70 for frontal, parietal, and occipital). For lateralization likelihood, we created difference scores by subtracting left from right (M=0.31, SD=2.24, range=-3-3). The proportion of left versus right-lateralized seizures was not significantly different (8 right, 6 left, and 2 with equal likelihood left/right). Overall, the highest location likelihood ratings were for temporal, frontal, and central regions. Data for localization likelihood are shown by group (right versus left) in Figure 1.

Conclusions: In a sample of ASD+EPI, a novel expert- review process determined that 1) epilepsy type was predominantly focal and 2) seizures were more often localized to frontotemporal regions of equal lateralization. This pilot study validated methods of expert classification that will guide design of larger, retrospective and prospective studies of the pathophysiology of ASD+EPI, with implications for treatment strategy.

Funding: Please list any funding that was received in support of this abstract.: This research was funded by NIH-NINDS U24NS107182 Clinical Research Site for the Network of Excellence in Neuroscience Clinical Trials (NEURONEXT) Fellowship Award and a Supporting Transformative Autism Research (STAR) Pilot Award.