Abstracts

Epilepsy treatments are generally a long-term, daily therapy in otherwise healthy people. The risk of teratogenicity from antiseizure treatments, therefore, is a major concern regarding their use. All available antiseizure medications are teratogenic in animal studies, most consistently at high dose exposures. The effect of vagus nerve stimulation (VNS) on fertility and teratogenicity needs to be assessed because it is used as a chronic epilepsy treatment. However, any teratogenicity associated with VNS would likely not be mechanistically similar to that of antiseizure medications.
The VNS device was implanted in ten female adult rabbits and stimulation parameters were set at a typical human dose of 1 mAmp stimulus intensity, 30 seconds on alternating with 5 seconds off. Based on body weight, this setting is approximately 14 times the human dose. As control groups, ten additional female rabbits were implanted with VNS leads but nonfunctional generators and four female rabbits were not implanted. All animals were mated, and at mid-gestation, half the animals were euthanized. The dam and uterine contents were then examined grossly and by histologic methods, including serial sections of all available fetal brains. The remaining animals were euthanized and identically studied 1 week after birthing the litter. Toxikon Corporation of Bedford, Massachusetts performed this reproductive/developmental toxicity screening test. The testing conformed to all applicable laws and regulations including FDA 21 CFR, Part 58, Good Laboratory Practice for Nonclinical Laboratory Studies (AAALAC, International), [quot]Guide for the Care and Use of Laboratory Animals,[quot] National Research Council, 1996. (NIH) (OLAW), [quot]Public Health Service Policy on Humane Care and Use of Laboratory Animals,[quot] Health Research Extension Act of 1985 (Public Law 99-158 November 20, 1985).
There was no difference between the VNS active group and the surgical control or non-implanted groups on any reproductive parameter, including mating behavior, number of matings required, viable and dead fetuses, litter size, individual kit weights, organ weights, and relative organ weights. Histological assessment in the VNS active group did not reveal any changes or abnormalities in selected tissues including neural tissue.
VNS does not affect fertility or cause teratogenicity in this standard animal model.
[Supported by: an unrestricted grant from Cyberonics, Inc.]