Investigation of Effects of Vigabatrin with Magnetic Resonance Imaging and Spectroscopy in Vivo

Abstract

Vigabatrin (gamma vinyl GABA, GVG) is an irreversible inhibitor of gamma-aminobutyric acid (GABA) transaminase, the enzyme that is responsible for degradation of GABA in the CNS. Vigabatrin is effective against partial seizures (Rimmer and Richens, 1984; Mumford and Dam, 1989; Reynolds, 1992). In toxicological studies involving rodents and dogs, high doses of GVG were associated with the development of a site-selective intramyelinic oedema that was accompanied by an astrocytic reaction (Butler et al., 1987; Gibson et al, 1990). A concern has been expressed about whether similar neuropathological changes may develop in human patients receiving long-term GVG therapy. No such changes have been identified in 51 surgical specimens and 13 autopsy cases (Cannon, 1991). Evoked response latencies have been shown to be prolonged in dogs with GVG-associated intramyelinic oedema, and these parameters have not been delayed in GVG-treated patients (Hammond and Wilder, 1985; Tartara et al., 1986). Evoked responses, however, only sample a small part of the neuraxis.