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Neuropathologic Findings in Patients Receiving Long-Term Vigabatrin Therapy for Chronic Intractable Epilepsy
D.J. Cannon, BSc, PhD
Marion Merrell Dow Research Centre, UK
W.H. Butler, MB, BS, FRCPath, ATS
BIBRA, Carshalton, UK
J.P. Mumford, MB, ChB, FFPM
Marion Merrell Dow Research Centre, UK
P.J. Lewis, MD, PhD, FRCP
Marion Merrell Dow Research Centre, UK
Vigabatrin is a new antiepileptic drug that acts by the irreversible inhibition of -aminobutyric acid (GABA) aminotransferase. During animal safety testing, vigabatrin was found to cause reversible intramyelinic edema in the brains of rodents and dogs but not in primates. In humans, the drug is well tolerated, and extensive clinical, neurophysiologic, neurochemical, and psychometric testing has failed to demonstrate any evidence of neurotoxicity. Neuropathologic examination has now been carried out on 62 patients with refractory epilepsy, who were on vigabatrin therapy either prior to undergoing neurosurgery for their epilepsy or before death. A further ten similar cases have been included in the study from age-matched patients with refractory epilepsy who had not been treated with vigabatrin prior to surgery or death. None of the neuropathologic changes seen in the preclinical animal studies have been observed in the human cases. In no case was there considered to be any evidence of myelin microvacuolation or myelin sheath splitting that could be attributed to vigabatrin treatment. Demyelination has never been observed in either the animal or human material. These findings support the clinical tolerability seen in long-term treatment. (J Child Neurol 1991;6(Suppl):2517-2524).
Journal of Child Neurology, Vol. 6, No. 2 Suppl,
2S17-2S24 (1991)
DOI: 10.1177/0883073891006002051

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J. Mumford and O. Dulac
Vigabatrin: A New Antiepileptic Medication
J Child Neurol,
October 1, 1991;
6(2_suppl):
2S3 - 2S6.
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