Effects of high-dose gamma-vinyl GABA (vigabatrin) administration on visual and somatosensory evoked potentials in dogs.
gamma-Vinyl GABA (GVG, vigabatrin) is a GABA transaminase-inhibiting antiepileptic agent. In dogs, chronic GVG administration produces reversible microvacuolation (intramyelinic edema) in discrete brain regions and slowing in central afferent transmission as measured by somatosensory evoked potentials (SEPs). Because this microvacuolation is especially prominent in the optic tract, this study tested the sensitivity of visual evoked potentials (VEPs) to GVG-induced changes in conduction. We also replicated the earlier SEP findings. Eight beagles received daily oral vigabatrin at the maximum tolerated dose (300 mg/kg/day); four were placebo controls. Cortical VEPs and SEPs were recorded using scalp needle electrodes at baseline and every 2 weeks throughout treatment. One treatment dog died at 2 weeks. The remainder showed an increase in central latencies beginning at 6 weeks, attaining significance (p < 0.05) at 8 and 10 weeks for SEPs and VEPs, respectively. No changes occurred in peripheral or spinal conduction in treated dogs, or in any measure in control dogs. Three GVG and two control dogs were followed after drug was withdrawn; both VEP and SEP measures returned to baseline values within 5 weeks. These findings support the use of VEPs and SEPs to monitor patients receiving vigabatrin therapy.
Schroeder
C E
CE
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461.
Gibson
J P
JP
Yarrington
J
J
Heydorn
W E
WE
Sussman
N M
NM
Arezzo
J C
JC
D000614:Aminocaproates / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001929:Brain Edema / Q000139:chemically induced / Q000175:diagnosis; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D004827:Epilepsy / Q000188:drug therapy; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects*; D005074:Evoked Potentials, Visual / Q000187:drug effects*; D008297:Male; D008954:Models, Biological; D020888:Vigabatrin
D000614:Aminocaproates; D000927:Anticonvulsants; D020888:Vigabatrin