Vigabatrin Caused Rapidly Progressive Deterioration in Two Cases With Early Myoclonic Encephalopathy Associated With Nonketotic Hyperglycinemia

Abstract

Vigabatrin, a structural analogue of γ-aminobutyric acid (GABA), is used for the treatment of generalized and partial seizures in infants. The drug inhibits the GABA transaminase and elevates the GABA concentration in the brain. Here we present the vigabatrin experience in two patients with early myoclonic encephalopathy owing to nonketotic hyperglycinemia (glycine encephalopathy). Both patients had early infantile seizures characterized by fragmentary myoclonic jerks associated with burst-suppression pattern on electroencephalography. Nonketotic hyperglycinemia was diagnosed with elevated cerebrospinal fluid and plasma glycine levels. The seizures were initially thought to be infantile spasms, and vigabatrin (50 mg /kg/day) was started for the treatment of seizures. Rapidly progressive deterioration was noticed after a few days. Acute encephalopathy associated with sleepiness and respiratory failure developed. Vigabatrin produced acute encephalopathy, which regressed in a few days after vigabatrin was stopped in the first patient. However, in the second case, despite the discontinuation of vigabatrin, there was no recovery of general conditions. Our observations in two cases indicate the risk of using vigabatrin in patients with nonketotic hyperglycinemia. The elevated GABA concentration in the brain can enhance the encephalopathy, together with the elevated levels of glycine. (J Child Neurol 2006;21:82—84).

Get full access to this article

View all access options for this article.

References

Ohtahara S. : Clinico-electrical delineation of epileptic encephalopathies in childhood . Asian Med J 1978;21:7—17.

Murakami N. , Ohtsuku Y. , Ohtahara S. : Early infantile epileptic syndromes with suppression bursts: Early myoclonic encephalopathy vs. Ohtahara's syndrome. Jpn J Psychiatry Neurol 1993;47:197—200.

Tada K. , Kure S. : Non-ketotic hyperglycinaemia: Molecular lesion, diagnosis and pathophysiology . J Inherit Metab Dis 1993; 16:691-703.

Boney A. , Degani Y. , Harari M. : Prognostic clues and outcome of early treatment of nonketotic hyperglycinemia . Pediatr Neurol 1996; 15: 137—141.

Lombroso CT : Early myoclonic encephalopathy, early infantile epileptic encephalopathy, and benign and severe infantile myoclonic epilepsies: A critical review and personal contributions. J Clin Neurophysiol 1990;7:380—408.

Baxter PS , Gardner-Medwin D. , Barwick DD , et al: Vigabatrin monotherapy in resistant neonatal seizures. Seizure 1995;4:57—59.

Meldrum BS : GABAergic mechanisms in the pathogenesis and treatment of epilepsy. Br J Clin Pharmacol 1989;27(Suppl 1):3—11.

Mumford J. , Dulac O. : Vigabatrin: A new antiepileptic medication. J Child Neurol 1991;6(Suppl 2):3—5.

Wong IC , Lhatoo SD : Adverse reactions to new anticonvulsant drugs. Drug Saf 2000;23:35—56.

10.

Haas-Lude K. , Wolff M. , Riethmuller J. , et al: Acute encephalopathy associated with vigabatrin in a six-month old girl. Epilepsia 2000;41:628—630.

11.

Sharief MK , Sander JW , Shorvon SD : Acute encephalopathy with vigabatrin. Lancet 1993;342:619.

12.

Salke-Kellermann A. , Baier H. , Rambeck B. , et al: Acute encephalopathy with vigabatrin. Lancet 1993;342:185.

13.

Garcia PA , Garcia-Zarza E. , Peraita AR : Acute encephalopathy and myoclonic status induced by vigabatrin monotherapy . Neurologia 2000;15:370—374.

14.

Lortie A. , Chiron C. , Dumas C. , et al: Optimizing the indication of vigab a t r i n i n c h i l d r e n w i t h r e f r a c t o r y e p i l e p s y. J C h i l d Neuro l 1997;12:253—259.

15.

Huisman TA , Thiel T. , Steinmann B. , et al: Proton magnetic resonance spectroscopy of the brain of a neonate with nonketotic hyperglycinemia: In vivo-in vitro (ex vivo) correlation. Eur Radiol 2002; 12: 858—861.