Neuropathology of a human hippocampus following long-term treatment with vigabatrin: lack of microvacuoles

Agosti, R.; Yasargil, Gazi; Egli, M; Wieser, Heinz Gregor; Wiestler, Otmar D.

doi:10.1016/0920-1211(90)90092-a

Cited by 33 publications

(10 citation statements)

References 14 publications

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“…This has been shown to result in delayed VERs in dogs [2]. A case report of an autopsy on a patient treated with vigabatrin for 11 months showed no microvacuoles or intramyelin oedema in an amygdalohippocampectomy specimen [1]. However, we propose that in our case vigabatrin caused reversible intramyelin oedema in both opitc nerves.…”

mentioning

confidence: 46%

Vigabatrin-induced optic neuropathy

Crofts

Brennan

Kearney

et al. 1997

Journal of Neurology

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mentioning

confidence: 46%

Vigabatrin-induced optic neuropathy

Crofts

Brennan

Kearney

et al. 1997

Journal of Neurology

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“…VGB is a novel antiepileptic drug marketed successfully in Europe. The result of extensive toxicity studies and clinical trials suggest that VGB-induced intramyelinic edema is species specific (rodent and dogs), since similar changes have not been observed in monkeys (4), or in humans during treatment periods ranging from several months to years evaluated by either surgical and postmortem histopathology specimens (11)(12)(13)(14)(15)(16), MRI (17,18), or evoked potential studies (1,2,19). The findings in this dog study suggest that MRI is a useful noninvasive method for detection of vigabatrin VGBinduced intramyelinic edema.…”

Section: Discussionmentioning

confidence: 99%

Use of Ex Vivo Magnetic Resonance Imaging to Detect Onset of Vigabatrin‐Induced Intramyelinic Edema in Canine Brain

Peyster

Sussman²,

Hershey

et al. 1995

Epilepsia

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Vigabatrin (VGB) causes intramyelinic edema (microvacuolation) in brain of dogs and rodent, which has encouraged development of noninvasive methods to monitor for this effect during clinical trials. We report the qualitative ex vivo magnetic resonance imaging (MRI) changes observed in a neuropathology study in dogs to detect time of onset and regression of VGB-induced intramyelinic edema. Beagles were randomly assigned to 18 groups of 6 dogs per group and administered vigabatrin orally (p.o.) at a dose of 300 mg/kg/day (2 males, 2 females) or placebo (1 male, 1 female). Animals were killed and examined at weekly intervals during the 12 weeks of treatment and at 1, 2, 4, 8, 12, and 16 weeks after discontinuation of drug treatment. Myelin microvacuolation in thalamus, hypothalamus, and fornix were noted histologically after 4-5 weeks of treatment. Increases in MRI T2 intensity were observed in hypothalamus after 4 weeks and in thalamus and columns of the fornix after 7 weeks. Both MRI T2 intensity and microvacuolation continued to increase during 12-week VGB treatment. When VGB treatment was discontinued after 12 weeks, both MRI T2 intensity and microvacuolation began to decrease. Sixteen weeks after VGB discontinuation, histopathology had returned to normal and MRI examination demonstrated a marked trend toward reversal of the increased T2 signal intensity. MRI thus has potential as a noninvasive surveillance technique in certain experimental and clinical conditions associated with intramyelinic edema.

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“…No microvacuolation has as yet been observed in humans (Pedersen et al 1987;Butler 1989;Graham 1989;Agosti et al 1990). Furthermore, studies of evoked potentials have not disclosed any evidence or vigabatrin-induced neurotoxicity in humans (Liegeois-C hauvel et Mervaala et al 1989;Tartara et al 1989).…”

Section: Clinical and Laboratory Safety Testsmentioning

confidence: 95%

Pharmacology of Vigabatrin

Sabers

Gram

1992

Pharmacology & Toxicology

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Vigabatrin (gamma-vinyl GABA) is a relatively new antiepileptic drug. Vigabatrin increases the concentration of gamma-aminobutyric acid (GABA) in the brain by inhibiting the major GABA metabolizing enzyme, GABA transaminase. Controlled clinical trials have demonstrated an excellent antiepileptic effect of vigabatrin, especially in the treatment of partial epilepsies. Long-term evaluations have shown no signs of tolerance development. Vigabatrin decreases the plasma concentration of phenytoin during concomitant therapy, the only drug with which an interaction seems to occur. In general, vigabatrin is well tolerated. Psychotic reactions occur in 3-6% of patients. Other frequent side effects are sedation and weight increase. Chronic vigabatrin intoxication in animals caused development of intramyelinic oedema, appearing as microvacuoles in brain white matter. No microvacuolation has been observed in humans, even after long-term treatment. Vigabatrin seems a very valuable new antiepileptic drug.

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Neuropathology of a human hippocampus following long-term treatment with vigabatrin: lack of microvacuoles

Cited by 33 publications

References 14 publications

Vigabatrin-induced optic neuropathy

Vigabatrin-induced optic neuropathy

Use of Ex Vivo Magnetic Resonance Imaging to Detect Onset of Vigabatrin‐Induced Intramyelinic Edema in Canine Brain

Pharmacology of Vigabatrin

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