Electroclinical phenotypes in a pedigreed baboon colony

Abstract

Summary This is the first large-scale epidemiological study evaluating the prevalence of interictal epileptic discharges (IEDs) and photosensitivity (PS) recorded by scalp EEG in a natural nonhuman-primate model of photosensitive, generalized epilepsy. Scalp EEG was used to characterize electroclinical phenotypes in a large baboon pedigree housed at the Southwest National Primate Research Center at the Texas Biomedical Research Institute (Texas Biomed) based upon IEDs and photosensitivity. Scalp EEG studies including intermittent light stimulation (ILS) were performed in 671 baboons. Clinical histories were available for 531 (79%) of the animals. The EEG studies lasted 53 (±11) min, during which the baboons were lightly sedated with intramuscular ketamine doses of 5.6 (±0.8) mg. The animals were further classified according to electroclinical phenotypes recorded by scalp EEG: presence or absence of IEDs, seizures and photoparoxysmal or photoconvulsive responses. Effects of age, gender, and species on EEG phenotypes were compared using (Chi-square, two-sided, α < 0.05). Sensitivity and specificity of IEDs and photosensitivity to detect a history of seizures was calculated. Generalized IEDs and photosensitivity were identified in 324 (49%) and 156 (23%) pedigreed baboons, respectively. Only photosensitivity was associated with gender, significantly increased in males. Otherwise, while IEDs were marginally more prevalent among males, there were no other significant associations of IEDs or photosensitivity with age or subspecies. Photosensitivity was significantly associated with IEDs, with demonstrating a possible association with gender and subspecies. Of 531 baboons with histories of clinical events, 91 (17%) had witnessed seizures and 269 (51%) were asymptomatic. IEDs demonstrated sensitivity and specificity of 62% and 57%, and photosensitivity of 40% and 83%, for prediction of seizures, respectively. While these EEG findings mirror the high prevalence of seizures in the colony, the sensitivity and specificity of scalp EEG may have been affected by ketamine’s ability to lower the threshold for IEDs and seizures, particularly in animals predisposed to epilepsy. Photosensitivity provides a specific biological marker for epilepsy in future epidemiological, genetic, behavioral and histopathological studies.

Epileptic baboons have lower numbers of neurons in specific areas of cortex

“…9 and 10). Cortical cell and neuron numbers were determined using the flow fractionator method (37,38) in epileptic baboon tissue obtained from the Texas Biomedical Research Institute, where a number of individuals develop generalized epilepsy within a pedigreed baboon colony (31)(32)(33)(34)(35)(36). Our results reveal a regionally specific neuron reduction in the cortex of baboons with naturally occurring, generalized seizures.…”

“…Selected strains of baboons have been studied as a natural primate model of generalized epilepsy (30)(31)(32)(33)(34)(35)(36) that is analogous to juvenile myoclonic epilepsy in humans. The baboons demonstrate generalized myoclonic and tonic-clonic seizures, and they have generalized interictal and ictal epileptic discharges on scalp EEG.…”

Generalized myoclonic epilepsy with photosensitivity in juvenile dogs caused by a defective DIRAS family GTPase 1

“…There is also strong evidence for a genetic component of photoparoxysmal response (PPR) in humans and many loci have been identified (27)(28)(29)(30). Thus, affected RRs provide another spontaneous large animal model to investigate the neural mechanisms of photosensitivity (31,32).…”

Cerebrospinal Fluid Levels of Monoamine Metabolites in the Epileptic Baboon

“…More than 20% of the pedigreed baboon colony housed at the Southwest National Primate Research Center (SNPRC, Texas Biomedical Research Institute, San Antonio, Texas), have been witnessed to have generalized myoclonic, absence and/or tonic-clonic seizures [13]. In addition to witnessed seizures, craniofacial trauma (CFT), such as orbital bruising or muzzle lacerations, may be due to seizure activity [14,15]. The baboons demonstrate generalized ictal and interictal epileptic discharges on scalp EEG and about 40% of the epileptic baboons are also photosensitive.…”

“…Therefore, we were interested in the evaluating the relationship of seizures and EEG markers for epilepsy, such as generalized interictal epileptic discharges (IEDs) or photosensitivity (PS), with cerebrospinal fluid (CSF) concentrations of monoamine metabolites, including 3-hydroxy-4-methoxyphenylglycol (MHPG), 5-HIAA, and homovanillic acid (HVA). We aimed to do this retrospectively, combining two separately acquired datasets of electroclinical phenotypes [14] and CSF studies [18]. In order to test the hypothesis that epileptic baboons will have altered levels of the monoamine metabolites, we compared their CSF concentrations based upon clinical, EEG and electroclinical classification.…”