Scalp EEG for the diagnosis of epilepsy and photosensitivity in the baboon

Abstract

Spontaneous seizures have been observed in several baboon species housed at the Southwest National Primate Research Center (SNPRC), including Papio hamadryas anubis and cynocephalus/anubis, hamadryas/anubis, and papio/anubis hybrids. The goal of this study was to establish a noninvasive, reliable electroencephalographic technique to characterize epilepsy phenotypes and assess photosensitivity in these subspecies. Thirty baboons with witnessed seizures, and 15 asymptomatic baboons underwent scalp electroencephalograms (EEGs) with photic stimulation (PS). The sensitivity and specificity of surface EEG for identifying interictal epileptic discharges (IEDs) in baboons with witnessed seizures were examined. The morphology of IEDs, electroclinical features of seizures and responses to PS, reproducibility of EEG findings, and intrarater reliability were also evaluated. Twenty-three seizure baboons (77%) demonstrated IEDs, predominantly with frequencies of 4-6 Hz in 18 baboons and 2-3 Hz in six baboons. Two seizure animals had a mixture of 2-3-Hz and 4-6-Hz IEDs. All animals with 2-3-Hz IEDs were 3 years old or younger. Myoclonic seizures (MS) and generalized tonic-clonic seizures (GTCS) were recorded in 13 baboons (43%). PS activated IEDs in 15 baboons (50%) and seizures in nine baboons. The presence of IEDs or seizures was not associated with a particular gender or species (Fisher exact test, alpha=0.05). Seizures were more common in animals >3 years old, while PS-induced IEDs and seizures were more prevalent in P.h. anubis/cynocephalus crosses compared to P.h. anubis. In the asymptomatic controls, IEDs were recorded in five baboons (33%), and photoparoxysmal responses were observed in two (13%). Surface EEG is a sensitive and reliable instrument for characterizing the epilepsy encountered in Papio species. Electroclinically, the seizure animals had generalized epilepsy with photosensitivity. The variation in IED morphology may be age-related or it may reflect different epileptic phenotypes. Ketamine provoked IEDs and seizures in most seizure animals and only in a few asymptomatic baboons; therefore, it may enhance the sensitivity of surface EEG for detecting a predisposition to epilepsy.

Electroclinical phenotypes in a pedigreed baboon colony

“…A previous scalp EEG studies in a smaller group of animals selected from this pedigree, demonstrated that the natural epilepsy of the baboon model closely resembles one of the most common epilepsy syndromes in humans, juvenile myoclonic epilepsy (JME; Szabó et al, 2004, 2005). The seizures are generalized myoclonic or tonic–clonic in character, present chiefly in adolescence, occur predominantly in the morning and can be provoked by stress, handling and ketamine administration.…”

“…The methods for the scalp EEG studies were described by our group previously (Szabó et al, 2004, 2005). The surface electrodes are placed according to the standard international 10–20 electrode placement system at FP1, FP2, T8, C4, Cz, C3, T7, O1, O2, A1 and A2 positions.…”

“…Ketamine was injected intramuscularly using a mean dose of 5.6 (±0.8) mg/kg, transiently sedating the animal without suppression their respiratory drive. At these doses, ketamine can activate interictal and ictal epileptic discharges, with minimal effect on photosensitivity (Szabó et al, 2004). ILS was performed at least 15 min apart, the first time while the baboons were still sedated, and the second time after they were able to track movement in their environment.…”

“…The baboons were recorded for 10 min after the second injection for ictal or interictal epileptic discharges acutely provoked by the ketamine (peak dose effect). Ketamine’s maximal effect on the EEG is visible between 2 and 15 min from the time of the intramuscular injection, and is characterized by a burst suppression pattern, with myoclonus associated with the bursts of high amplitude slow waves (Szabó et al, 2004). The EEG studies lasted a mean of 53 (±11) min.…”

Functional PET Evaluation of the Photosensitive Baboon

“…All of the EEG studies lasted for about one hour, and included repeated trials of ILS. The baboons were sedated with ketamine, which at low doses, similar to humans with a predisposition to epilepsy, can activate IEDs [10, 11] without suppressing the photoparoxysmal response [12]. …”