Abstract

A male squirrel monkey (Saimiri boliviensis) which was suffering from regular fits, underwent extensive investigation including radiography, blood tests, EEG, and an MRI scan. True epilepsy with a photosensitive component was diagnosed. The animal was managed with anti-epileptics and the seizures were fully controlled, but 18 months later had to be euthanatized for other reasons. The postmortem examination failed to detect any cause for the epilepsy, thus confirming the clinical findings. As true epilepsy has a familial component, we would like to encourage other collections to investigate cases of fits/fainting which appear to be regularly reported in squirrel monkeys and take them into consideration when considering breeding decisions for the captive breeding programme.

Introduction

Squirrel monkeys (genus Saimiri) are commonly kept in captivity in zoological collections and are also frequently used in biomedical research. Fainting related to hypoglycemia has been reported⁵ and fits/seizures have also been observed relatively frequently in captive squirrel monkeys (Jan Vermeer, personal communication). Squirrel monkeys have been widely used as experimental lab models for human epilepsy studies, but as far as the authors are aware there are no reports of epilepsy in squirrel monkeys except one case of seizures due to Encephalitozoon cuniculi (Nosema cuniculi).¹ This case report describes a case of photosensitive epilepsy affecting a male black-capped Bolivian squirrel monkey (Saimiri boliviensis).

Case Report

A 5-year-old male Bolivian squirrel monkey “Casper” was imported to ZSL London zoo from a collection in France, along with another male of the same age and origin, as part of the EEP (European Endangered Species Programme) captive-breeding programme. During the 6-month rabies quarantine, when both males were housed in an indoor enclosure with no outdoor or natural light access, there were no major health concerns. Following this, both males were introduced to the female group housed in an outdoor, walk-through, naturalistic enclosure. Four weeks following the move it was reported that the group of females was repeatedly picking on Casper and that he had been observed “sleeping on the path.” Shortly after this he sustained very severe bite injuries that required surgical repair. Therefore, Casper was temporarily separated from the group for postop treatment and monitoring in an indoor enclosure with no outdoor access, but a large glass window. The following day the keepers reported him holding his head with both hands, falling off a branch, having a short fit, and then recovering very quickly. Ten days later he had another fit and lost consciousness completely. Both fits had similar characteristics: seeking out a particular area near a window, holding of the head, apparent altered awareness, neck ventroflexion, falling, and possible tonic-clonic activity. There was a suspicion that the episodes may have been exacerbated by bright light. As the frequency of these seizure was very close together, a full investigation was carried out under general anesthesia and on induction of anesthesia he had another fit. Radiographic examination did not reveal any trauma to the skull or any other part of the skeleton. Full hematology and biochemistry results were unremarkable, serologic screening for E. cuniculi and toxoplasmosis was negative. Fecal screening was also negative for any pathologic bacteria, protozoa, and parasites.

The fits were becoming very frequent, with at least one fit observed weekly. It was decided to investigate further, and the monkey was taken to the Royal Veterinary College (RVC University of London) epilepsy referral clinic for full assessment, brain MRI (magnetic resonance imaging), and an EEG (electroencephalogram).

The MRI revealed normal brain structure. There was normal grey-white matter architecture, no asymmetry or mass effect, and normal ventricular system. Digital electroencephalography exhibited some possible spike-wave activity; however, this was difficult to localise as only a limited number of leads could be placed on such a small skull. The EEG findings were consistent with epileptiform activity.

In light of the clinical signs, MRI, EEG, and blood test results, a diagnosis of idiopathic epilepsy with a photosensitive component was made.

As this type of epilepsy seems to be familial, Casper was subsequently castrated as it was decided that he should be taken out of the breeding programme but remain part of the group in the future if possible. Casper was kept separated from the main group and put on anti-epileptic treatment. During this time of separation, the other male was taken out of the group to be a companion to Casper.

Casper was treated with sodium valproate oral suspension (Epilim syrup®, Sanofi Aventis, Guildford, Surrey, UK) at an initial dose of 20 mg/kg PO once daily as recommended initially by the neurologist. This dosage did not control the fits and the treatment was increased to 30 mg/kg daily. At this rate, the seizures seem to be under control for a short while and a month later he was observed to have a pre-ictal stage that did not go into full seizure and recovered very quickly. A blood sample was taken then to assess possible side effects and measure plasma levels of sodium valproate which were <5 µmol/L (human values <34.6 µmol/L). The treatment was increased to 40 mg/kg and this dose seemed to control the seizures completely. However, a month later plasma levels of valproate were found to be 20 µmol/L 24-hours post-administration of the drug. This was perceived as slightly high and the dose was reduced to 35 mg/kg once daily. This dose rate seemed to control the seizures completely for a period of two months when he was observed to have another fit before the new dose was due. The frequency of the treatment was then increased to 35 mg/kg of sodium valproate every 12 hours and with this regime the seizures were fully controlled for the rest of Casper’s life.

During the time that Casper was on anti-epileptic treatment regular blood samples were taken not only to measure sodium valproate plasma levels, but also to assess possible side effects of therapy. The only change observed during treatment was a transient elevation of some liver enzymes, ALT, and AST.

Five months after the start of treatment Casper’s epilepsy was under control and it was decided to reintroduce both males to the group of females in the outdoor enclosure. In order to assess fully the effect of full, bright sunlight on Casper before the reintroduction to the females, both males were moved to a new enclosure with full outdoor access for a period of two months where they could be fully monitored. During this period both males had amoebic diarrhoea and were treated with paromomycin sulphate (Humatin®, Pfizer S.A., Alcobendas, Spain) at 100 mg/kg daily for 10 days and recovered clinically.

As Casper’s seizures did not recur during the two months of close observation with outdoor access, both males were reintroduced back to the group of females. However, during the following months Casper was repeatedly beaten and attacked by the females, sustaining numerous injuries and having to be separated for short periods on several occasions. As the reintroduction to the group of females was unsuccessful and keeping him isolated greatly compromised his welfare, Casper was euthanatized on humane grounds.

Postmortem examination revealed emaciation and the most relevant histopathologic findings were eosinophilic gastroenteritis due to protozoal infection, thought to be amoebic. No gross or histopathologic lesions were found which could account for the epilepsy, confirming the clinical diagnosis of idiopathic epilepsy.

Discussion

Fainting and fits have commonly been observed in squirrel monkeys. Fainting due to hypoglycemia following periods of starvation has been well-recorded (husbandry manual) in squirrel monkeys; however, normoglycameia was observed in all the multiple blood samples from Casper. Seizures due to head trauma and brain neoplasia usually show other clinical signs such as personality changes or neurologic deficits. There were no behavioural or personality changes observed in Casper and no overt neurologic deficits were observed, although a detailed neurologic examination could not be performed. All the blood tests revealed no significant metabolic abnormalities or infectious disease. The only published case of seizures in a squirrel monkey was due to E. cuniculi, but Casper tested negative to this, and to toxoplasmosis.

In light of the amoebic enteritis discovered on postmortem examination the possibility of cerebral amoebiasis as being the cause of the seizures was also investigated, but we were not able to demonstrate this in any of the multiple sections examined from the brain.

Given the clinical signs, investigations carried out at the RVC, and the lack of evidence suggesting otherwise, the diagnosis of idiopathic or true epilepsy was the most likely.

There was a strong suspicion that the episodes were exacerbated by bright light. The fact that the monkey only started showing clinical signs when it was put in an outdoor enclosure in the summer and that when separated from the group, he was observed to have fits when he was sitting by the window further reinforced the possibility of a photosensitive component. Casper seemed to be seeking the sunlight through the window even if this triggered a fit. In children with photosensitive epilepsy, a similar behaviour has been observed; children seem to compulsively seek bright light, flickering lights, or nod their heads in front of bright TV or computer screen before a fit is triggered.² Casper had previously been reported to be seen “sleeping in the path” of the outdoor enclosure, this was later suspected to maybe have been during a fit or when recovering from one.

This relationship to light made it very suspicious of photosensitive epilepsy, which is seen in both human and non-human primates. Photosensitive epilepsy characterized by an abnormal EEG response to light has been reported in several baboon species in captivity as well as in the wild.^3,4 Although squirrel monkeys have been used extensively as human models for epilepsy, as far as the authors are aware this is the first fully investigated and reported case of idiopathic or true epilepsy in a squirrel monkey. As idiopathic epilepsy has a genetic or familial component it was decided to castrate Casper and exclude him from the breeding programme. Before these two males arrived at ZSL we rejected another pair of males from a different European collection because one of them was epileptic and we did not feel the outdoor naturalistic exhibit was appropriate for him. No investigation or treatment was carried out in this monkey. Investigating Casper’s case, it came to light that all these males came from the same blood line, emphasising the importance of excluding these males from the breeding programme. At the time of writing, the one remaining male at London Zoo has been reported to have had a fit and we are in the process of investigating it. Therefore, we would like to encourage other collections to investigate these cases of fits/fainting and take them into consideration for inclusion or exclusion to the captive breeding programme.

Acknowledgments

The authors would like to thank Dr. Kate Chandler, neurologist specialist at the Royal Veterinary College, and the rest of our colleagues at the veterinary department at London Zoo for all their help and support with this case and to the keepers in the Mammals South section that did such an excellent job in looking after Casper.

Literature Cited

1.  Brown RJ, Hinkle DK, Trevethan WP, Kuppatr JL, McKee AE. Nosematosis in a squirrel monkey (Saimiri sciureus). Report of the Naval Aerospace Medical Research Laboratory. Naval Aerospace Medical Center, Florida. 1972.

2.  Meinhard E, Oozeer R, Cameron D. Photosensitive epilepsy in children who set fires. British Medical Journal. 1988;1296:1773.

3.  Nquet R. Photosensitive epilepsy of the baboons Papio papio. Seizures in mammals. 180 In: Proceedings of the Royal Society of Medicine. 1972;65:8.

4.  Szabó CA, Leland M, Sztonák L, Restrepo S, Haines R, Mahaney MA, Williams JT. Scalp EEG for the diagnosis of epilepsy and photosensitivity in the baboon. American Journal of Primatology. 2004;65:95–106

5.  Vermeer J. EEP husbandry guidelines for squirrel monkeys (genus Saimiri). 2006;38–39.