Infantile spasms vigabatrin

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... 

Elterman RD et al Randomized trial of vigabatrin in patients with infantile spasms. Neurology 2001 57 1416. 

Drowsiness, hypotonia, and irritability were observed in 37% of infants given corticotropin in a randomized comparison of corticotropin with vigabatrin in the treatment of infantile spasms (SEDA-22, 442 11). 

Vigevano F, Cilio MR. Vigabatrin versus ACTH as first-line treatment for infantile spasms a randomized, prospective study. Epilepsia 1997 38(12) 1270-4. 

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],... 

The recommended initial dose of vigabatrin as adjunctive therapy in adults is 1.0 g daily by mouth, increased if necessary in increments of 0.5 g at weekly intervals to a maximum of 3.0 g daily. A recommended initial dose in children is 40 mg/kg body-weight daily. For infantile spasms the dose is from 50 mg to 150 mg/kg daily [2]. 

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. 

The efficacy and adverse effects of steroids and vigabatrin in children with infantile spasms have been reviewed (38). The authors found a high rate of visual field defects and concluded that although vigabatrin is efficacious it does not seem to be more effective than steroids or corticotrophin, and that the benefits of vigabatrin do not justify the associated risks of possible irreversible visual changes. 

The long-term retinal effects of vigabatrin in children are unknown, and visual field testing is usually impossible. Recent evidence has suggested that a short course of vigabatrin (6 months) in children with infantile spasms may be sufficient (54) and minimizes the potential for visual adverse effects. 

Of 30 children with epilepsy (14 boys and 16 girls, aged 4-20 years) taking vigabatrin for infantile spasms and simple and complex partial epilepsy, who had never complained of ophthalmologic disturbances, 4 had visual field... 

Elterman RD, Shields WD, Mansfield KA, Nakagawa J. US Infantile Spasms Vigabatrin Study Group. Randomized trial of vigabatrin in patients with infantile spasms. Neurology 2001 57(8) 1416-21. 

Nabbout R, Melki 1, Gerbaka B, Dulac O, Akatcherian C. Infantile spasms in Down syndrome good response to a short course of vigabatrin. Epilepsia 2001 42(12) 1580-3. 

Vigabatrin is useful as adjunct therapy in the therapy of refractive partial seizures. It also may be effective in the therapy of infantile spasm syndrome and GABA-mediated muscle spasticity. 

Vigabatrin causes a trivial decrease in phenobarbital and primidone levels. There is some evidence that phenobarbital may reduce the efficacy of vigabatrin in infantile spasms. 

There appears to be no change in phenobarbital levels with vigabatrin, but some suggestion that vigabatrin may be less effective for infantile spasms in the presence of phenobarbital. Bear this possibility in mind. 

A case is described of a child with infantile spasm who had MRI abnormahties in globi pallidi and brainstem induced by vigabatrin [358]. 

A 6-month-old boy with infantile spasms and tuberous sclerosis complex was treated with vigabatrin for 1 month. A routine follow-up MRI demonstrated asymptomatic diffusion abnormalities in bilateral thalami. Similar abnormalities were also identified in globi pallidi and brainstem. 

In a letter it has been discussed whether, in view of recent findings which demonstrate vigabatrin toxicity in the retina and also in the brain, it is still justified to continue to treat patients with infantile spasm with this drug [359 ]. 

Dracopoulos A, Widjaja E, Raybaud C, Westall CA, Snead OC. Vigabatrin-associated reversible MRI signal changes in patients with infantile spasms. Epilepsia 2010 51(7) 1297-304. 

Jaseja H. Vigabatrin administration in patients with infantile spasms the risks. Clin Neurol Neurosurg 2010 112(9) 835. 

There are other seizure conditions in which pyridoxine therapy finds a place. Infantile spasm (spastic convulsions), in combination with diffuse electroenceph-alographic abnormalities (hypsarrhythmia), is referred to as West syndrome. Mental retardation is associated with this condition (32). ACTH is effective for the short-term treatment of infantile spasms. In view of the elevated therapy-associated morbidity, valproic acid and vigabatrin have been used (33). Following reports of beneficial effects of high doses of pyridoxine, initial treatment for one to two weeks with high doses of pyridoxine is the established therapy in some European countries and in Japan (34). Combined therapy with high-dose pyridoxine in association with low-dose corticotrophin has also been reported as a promising therapy for seizure control, normalized EEG, and intellectual outcome. 

Schmitt B, Landau K. Vigabatrin therapy in infantile spasms solving one problem and inducing another Epilepsia 2009 50 (8) 2006-8. 

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