Epilepsy in nonhuman primates

Abstract

Objectives Nonhuman primates (NHPs) are model organisms for understanding the pathophysiology and treatment of epilepsy in humans, while data from human patients informs the diagnosis and treatment of NHP with seizures and epilepsy. We reviewed the literature and surveyed veterinarians at zoos and NHP research centers to (a) better define the range of seizures and epilepsy in NHP, (b) understand how NHPs can inform our knowledge of the pathophysiology and treatment of epilepsy in humans, and (c) identify gaps of knowledge and develop more effective guidelines to treat seizures and epilepsy in NHP. Methods We searched PrimateLit, PubMed, and Google Scholar for studies on experimental models of epilepsy in NHPs and on naturally occurring seizures and epilepsy in NHPs in captivity. In addition, we created a survey to assess methods to diagnose and treat epilepsy in NHPs. This survey was sent to 41 veterinarians at major international zoos and research facilities with NHP populations to study seizure phenomenology, diagnostic criteria for seizures and epilepsy, etiology, and antiseizure therapies in NHPs. Results We summarize the data from experimental and natural models of epilepsy in NHPs and case reports of epilepsy of unknown origin in captive primates. In addition, we present survey data collected from veterinarians at eight zoos and one research facility. Experimental data from NHP epilepsy models is abundant, whereas data from primates who develop epilepsy in the wild or in zoos is very limited, constraining our ability to advance evidence‐based medicine. Significance Characterization of seizure or epilepsy models in NHPs will provide insights into mechanisms and new therapies that cannot be addressed by other animal models. NHP research will better inform species‐specific diagnoses and outcomes.

A natural marmoset model of genetic generalized epilepsy

“…Unlike photosensitive baboons, epileptic marmosets are not sensitive to different frequencies of light. Since the epileptic marmosets reported in other studies have similar behavioral phenotypes, researchers attribute it to a viral infection [5] . Based on our observations, a genetic etiology may be the causes of the epileptic seizure in this marmosets family.…”

“…Due to the differences in genetic constitution and brain structure, rodent models can not fully mimic the human epilepsy. To address this issue, non-human primate models are considered as suitable models of nervous system disease because the non-human primate brain have very similar genetic, neurochemical, neurophysiologic, and structure features with human brains [5] . Killam et al firstly described an non-human primate baboon model of photosensitive epilepsy in 1966, which was characterized by intermittent light stimulation (ILS) induced seizures [6] .…”

Whole Genome Sequence Data From Captive Baboons Implicate RBFOX1 in Epileptic Seizure Risk

“…Baboons have been used as animal models in a broad range of human diseases, including diabetes, heart disease, osteoporosis, and chronic infectious diseases ( Rogers and Hixson, 1997 ). Baboons also represent a natural model for GGE ( Szabó et al, 2012 , 2013 ; Croll et al, 2019 ). For the pedigreed baboon colony housed at the Southwest National Primate Research Center (SNPRC; San Antonio, TX, United States), absence, myoclonic, and generalized tonic–clonic seizures have been reported to occur spontaneously or triggered by intermittent light stimulation, with electroclinical findings suggesting strong similarities with human epilepsy, in particular juvenile myoclonic epilepsy ( Szabó et al, 2013 ).…”

“…For the pedigreed baboon colony housed at the Southwest National Primate Research Center (SNPRC; San Antonio, TX, United States), absence, myoclonic, and generalized tonic–clonic seizures have been reported to occur spontaneously or triggered by intermittent light stimulation, with electroclinical findings suggesting strong similarities with human epilepsy, in particular juvenile myoclonic epilepsy ( Szabó et al, 2013 ). In a preliminary analysis of 1,400 animals, ( Croll et al, 2019 ) we previously estimated moderate heritabilities for seizures ( h 2 = 0.33, p < 1 × 10 –7 ) and interictal epileptic discharges ( h 2 = 0.19, p < 0.002), although the underlying genetic variants are unknown. With high-throughput whole-genome sequencing (WGS) now performed on a subset of these animals and the potential enrichment of rare pathogenic variants within large multigenerational pedigrees that improve statistical power for detecting their risk effects, the SNPRC baboon colony represents a largely untapped genetic resource for epilepsy research ( Jun et al, 2018 ).…”

A natural marmoset model of genetic generalized epilepsy

“…Due to the differences in genetic constitution and brain structure, rodent models cannot fully mimic human epilepsy. To address this issue, non-human primate models are considered suitable models of nervous system diseases because the non-human primate brain has very similar genetic, neurochemical, neurophysiologic, and structural features to human brains [ 5 ]. Killam et al first described a non-human primate baboon model of photosensitive epilepsy in 1966, which was characterized by intermittent light stimulation (ILS)-induced seizures [ 6 , 7 ].…”