Seizures vigabatrin

Vigabatrin can exacerbate myoclonic and absence seizures and occasionally other seizure types, especially in children with generalized epilepsies. After the administration of vigabatrin, seizures worsened in all of four children with Angelman syndrome (10), and generalized seizures occurred for the first time in a boy with succinic semialdehyde dehydrogenase deficiency (SEDA-21, 77). De novo myoclonic jerks and precipitation of status epi-lepticus have also been reported (SEDA-20, 70). 

Krakow K, Polizzi G, Riordan-Eva P, Holder G, MacLeod WN, Fish DR. Recovery of visual field constriction following discontinuation of vigabatrin. Seizure 2000 9(4) 287-90. 

A 30-year-old female with partial seizures is treated with vigabatrin. What is the principal mechanism of action of vigabatrin ... 

Petroff, O. A., Mattson, R. H., Behar, K. L., Hyder, F., and Rothman, D. L. (1998). Vigabatrin increases human brain homocarnosine and improves seizure control. Ann. Neurol. 44, 948-952. 

Vigabatrin is a new antiepileptic for use in epilepsy unresponsive to other therapy. It is an irreversible inhibitor of GABA-transaminase, the enzyme responsible for inactivation of the neurotransmitter GABA and it has shown efficacy against partial and secondarily generalized seizures. The principal unwanted effects are psychiatric disorders, including depression and psychosis, in a small number of patients. 

At present, the primary indication for vigabatrin is in the treatment of patients with partial seizures, but it appears to be an effective and generally well tolerated antiepileptic medication for other seizure types as well. It should not be used in patients with absence epilepsy or with myoclonic seizures. Vigabatrin is not approved as an AED in the United States, although it is approved in many other countries. 

The answer is c. (Hardman, p 481. Katzung, pp 404-405.) Vigabatrin is useful in partial seizures. It is an irreversible inhibitor of GABA aminotransferase, an enzyme responsible for the termination of GABA action. This results in accumulation of GABA at synaptic sites, thereby enhancing its effect. 

Vigabatrin Irreversibly inhibits GABA-transaminase 70% bioavailable not bound to plasma proteins not metabolized, ti/2 5-7 h (not relevant because of mechanism of action) Partial seizures, infantile spasms Toxicity Drowsiness, dizziness, psychosis, visual field loss Interactions Minimal... 

Vigabatrin is used as an adjunctive antiepileptic in patients with resistant partial epilepsy with or without secondary generalization, unresponsive to other therapy [2]. Nowadays, vigabatrin is rarely used in the treatment of partial seizures due to several irreversible visual field constrictions associated with its chronic use [57-62], It is regarded by many authorities as a drug of choice in infants with west syndrome (infantile spasms), particularly in cases associated with tuberous sclerosis [62],... 

Psychiatric complications occur in both children and adults. While there is some evidence that a positive psychiatric history may increase the risk (and may represent a relative contraindication), behavioral and mood disturbances can occur in patients who had no similar episodes in the past. A retrospective survey of 50 patients with vigabatrin-associated psychosis (n = 28) or depression (n = 22) suggested that psychosis tends to occur in patients with more severe epilepsy and may be related to asided EEG focus or suppression of seizures (64% of patients were free of seizures). On the other hand,... 

Beran RG, Berkovic SF, Buchanan N, Danta G, Mackenzie R, Schapel G, Sheean G, Vajda F. A doubleblind, placebo-controlled crossover study of vigabatrin 2 g/ day and 3 g/day in uncontrolled partial seizures Seizure 1996 5(4) 259-65. 

Vigabatrin is effective in partial, secondary generalised seizures which are not satisfactorily controlled by other anticonvulsants, and in infantile spasms, as monotherapy. It worsens absence and myoclonic seizures... 

Vigabatrin is used mainly in the treatment of refractory partial seizures and infantile spasms. Weight gain and mostly transient sedation are its most common adverse effects, but visual field defects are the main cause for concern and severely restrict its use. 

Like other GABAergic drugs, vigabatrin can aggravate absence seizures and may precipitate absence status in patients with generalized epilepsies. Occasionally, absence seizures are also precipitated in patients with partial epilepsy, as in a 28-year old man who developed de novo absence status 4 days after the dosage of vigabatrin was increased to 2 g/day (7). 

Gingival overgrowth occurred in a 29-year-old man who had taken vigabatrin for 5 years for partial epileptic seizures (71). 

Although vigabatrin is not metabolized by liver enzymes it increased serum carbamazepine concentrations by at least 10% in 66 epileptic patients aged 10-66 years with focal seizure onset with or without secondary generalization (74). 

Dean C, Mosier M, Penry K. Dose-Response Study of Vigabatrin as add-on therapy in patients with uncontrolled complex partial seizures. Epilepsia 1999 40(l) 74-82. 

Guberman A, Bruni J. Long-term open multicentre, add-on trial of vigabatrin in adult resistant partial epilepsy. The Canadian Vigabatrin Study Group. Seizure 2000 9(2) 112-18. 

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