Authors :
Presenting Author: Amandine Grenier, PhD – University of Texas San Antonio
Arianna Hurtado, BS – University of TexasSan Antonio
Dionne Onyemaizu, BS – University of Texas San Antonio
Mark Kos, PhD – University of Texas Rio Grande Valley
Melanie Carless, PhD – University of Texas San Antonio
Charles Szabo, MD – UT Health San Antonio
Rationale:
The diagnosis of epilepsy in baboons is challenging, in part due to clinically subtle seizures (myoclonic/absence seizures) and generalized tonic-clonic seizures, which occur mainly nocturnally. In the absence of witnessed seizures and scalp EEG confirmation of epilepsy, we propose clinical criteria for the diagnosis of epilepsy, mainly based upon evidence of seizure-induced injuries.
Methods:
We performed a retrospective review of clinical records of 735 genotyped baboons in a pedigreed colony housed at the Southwest National Primate Research Center in San Antonio, Texas. We identified witnessed seizures, some ketamine-induced, as well as craniofacial injuries, in particular periorbital and cephalic injuries, that are closely associated with seizure activity. Other injuries related to seizures included dental, jaw, or long bone fractures. We devised a point system to establish the risk for epilepsy with minimal reliance on witnessed seizures activity or scalp EEG recordings (see Table 1). A polygenic analysis was performed of the different clinical groups (see below) to validate our diagnostic criteria. Results:
We identified 157 (19%) epilepsy (EPI) baboons with greater than 4 points, and 256 (31%) asymptomatic control (CTL) animals with 0 points. The remaining baboons were characterized as having low (1-2 points) or moderate (3-4 points) risk for epilepsy. Witnessed seizures and scalp EEG abnormalities were noted 24 EPI baboons, respectively. A polygenic analysis comparing EPI and CTL groups yielded a heritability estimate of h2r=0.279 (P=0.0023).
Conclusions:
Heritability estimates distinguished the EPI group from all three groups (control, low risk, moderate risk), validating the use of the proposed point system relying on seizure-related injuries to establish the diagnosis of epilepsy. While these heritability estimates are lower than in a previous cohort relying more heavily on scalp EEG, this may be due to evidence of interictal epileptic discharges even in healthy controls, some of whom may have had epilepsy, most being only genetically predisposed to epilepsy. Nonetheless, development of a classification system relying solely on clinical findings will lower screening costs and increase access to baboons for future translational research in epilepsy.
Funding: NIH/NINDS
1R56NS135399-01