Vigabatrin in the treatment of epilepsy in children.

Livingston, J. H.; Beaumont, Daniel; Arzimanoglou, Alexis; Aicardi, Jean

doi:10.1111/j.1365-2125.1989.tb03470.x

Cited by 100 publications

(41 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Concerns that long-term VGB administration might have potentially irreversible adverse effects in the developing brain (9) led to this study. We have shown that immature rats at comparable stages of brain development to that of human infants (1 0,11), when given doses of VGB comparable to the low average doses used clinically for the treatment of infantile spasms (2)(3)(4), have a range of cytologic and metabolic disturbances. The unique findings include observations of behavioral abnormalities, delayed myelination, axonal degeneration, glial cell death, white matter edema, and microvacuolation.…”

Section: Discussionmentioning

confidence: 99%

“…VGB was administered at these ages because brain development at this stage in rats corresponds roughly to that in children with infantile spasms (1 0,ll). The dose chosen is comparable to that used clinically for the treatment of infantile spasms (2)(3)(4)12). Half of the animals were killed at P26 and the rest at P40, 2 weeks after cessation of VGB administration.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Effect of Long‐Term Vigabatrin Administration on the Immature Rat Brain

et al. 2000

View full text Add to dashboard Cite

Summary:Purpose: To determine whether the neuropathologic changes produced by vigabatrin (VGB; y-vinyl GABA) administration in the developing rat brain are reversible.Methods: We injected rats daily with VGB (2540 mglkgl day, s.c.) from age 12 days for 2 weeks followed by 2 weeks of a drug-free period. Behavioral testing, magnetic resonance (MR) imaging, biochemical assays, and histologic technique were used to assess the adverse effect of VGB in developing brain and its reversibility.Results: At the end of 2 weeks' VGB administration: (a) there was a hyperactivity and a shortened latency to escape out of cool water; (b) white matter appeared hyperintense in T, and diffusion-weighted MR images with 4-15% increases in T,; (c) microvacuolation, TUNEL-positive nuclei, and swollen axons were observed in the corpus callosum; (d) myelin staining indicated a reduction in myelination, as did the reduction in activities of myelin and oligodendrocyte-associated enzymes and the decrease in myelin basic protein on Western blots. Two weeks after stopping VGB administration: (a) MR images were normal, and microvacuolation was no longer in the white matter; (b) reduction in myelination reversed partially; (c) the T, relaxation time remained elevated in the hypothalamus; and (d) the behavioral response remained abnormal.Conclusions: Long-term VGB administration to young rats causes brain injury, which recovers partially on its cessation. The observed cell death, disrupted myelination, and alterations in behavior indicate a need for further safety assessment in infants and children. Key Words: Development-Magnetic resonance imaging-Vigabatrin-White matter.Vigabatrin (VGB; y-vinyl-aminobutyric acid) elevates tissue levels of GABA by irreversibly binding to GABA transaminase, thereby inhibiting GABA degradation. VGB is considered an effective and safe antiepileptic drug (AED) in both adults and children and now is the preferred treatment for infantile spasms (1 4). However, Holmes ( 5 ) has emphasized that the detrimental effects of AEDs may be greater in the developing brain than in the mature brain. In addition, Marson et al. (6) have drawn attention to the paucity of information on the "new" AEDs in childhood epilepsy and advocated the need for randomized clinical trials at an earlier stage of drug development than is currently the case. Although prolonged administration of VGB to adult animals causes potentially reversible intramyelinic edema or microvacuolation (7,8), we demonstrated recently (9) that the adverse effects of VGB may be greater in immature than mature brains. Treatment of rats at age 12-16 days Accepted February 8, 2000. Address correspondence and reprint requests to Dr. U. Tuor at Institute for Biodiagnostics, National Research Council of Canada, 435 Ellice Ave., Winnipeg, Manitoba R3B 1Y6, Canada. E-mail: Ursula. Tuor@ nrc.ca with 15-50 mglkg of VGB daily for 5 days caused decreased myelin staining, axonal degeneration, glial cell death in the white matter, and reactive astrogliosis in the frontal cortex. Whe...

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Effect of Long‐Term Vigabatrin Administration on the Immature Rat Brain

et al. 2000

View full text Add to dashboard Cite

show abstract

“…Independent observations derived from open studies of efficacy and safety of VGB in children provide strong evidence that this drug can cause behavioral disturbances in children (83)(84)(85)(86)(87)(88). Agitation, aggressivity, irritability, or hyperactivity was reported in 9-30% of children after the addition of VGB.…”

Section: Case Reportsmentioning

confidence: 99%

Antiepileptic Drugs, Learning, and Behavior in Childhood Epilepsy

Bourgeois

1998

Epilepsia

133

View full text Add to dashboard Cite

Summary:Cognitive and behavioral impairments are found more often among epileptic children than among their peers. The cause of these impairments is multifactorial. Identifying the relative contribution of antiepileptic drugs (AEDs) to these problems has been the object of a large number of clinical investigations. This area of research has been characterized by an unusually high number of methodological challenges and pitfalls. Accordingly, results have often been inconsistent and contradictory, except for the more obvious observations that can be derived from clinical experience. Overall, the effects of AEDs on cognition and behavior in children have been overrated in the past. More recent research has benefited from the methodological lessons of previous studies and it suggests that the majority of children taking AEDs do not experience clinically relevant cognitive of behavioral adverse effects from these medications. In addition, some of the newer AEDs may indeed have a better cognitive profile. Nevertheless, clinical experience must be used to identify the subgroup of children who remain at risk for significant and clinically relevant cognitive and behavioral adverse effects of AEDs. Key Words: Epilepsy-Childhood-Antiepileptic drugs-IntelligenceBehavior.Among children and adolescents with epilepsy, the prevalence of cognitive and behavioral disorders is higher than among their nonepileptic peers. There are multiple underlying causes of these cognitive and behavioral abnormalities and they include factors related to the etiology of the epilepsy, ongoing seizure activity, genetics, and treatment, as well as psychosocial issues. It is often difficult to determine the relative contribution of any given factor. This complex interrelation has been the object of several reviews (1-10). Trying to assess the effects of antiepileptic drugs (AEDs) on learning and behavior in patients with epilepsy has revealed itself as being a considerable methodological challenge. The intent of the present review of these effects of AEDs in children with epilepsy is to go beyond an analysis of published neuropsychological investigations and to view the problem from the perspective of its practical relevance and of conventional wisdom in the clinical practice of pediatric epileptology. this area? (a) Undoubtedly, within a clinical practice, one will notice that a disproportionate percentage of children with epilepsy have learning and behavioral problems. Sometimes, based on their time course, these problems can be attributed to antiepileptic medication, but more often the relationship is blurred or nonexistent and problems precede the introduction of the very first AED. (b) Parents of children whose AEDs are temporarily discontinued for the purpose of presurgical monitoring are at times amazed at how much more alert and more responsive their child has suddenly become. (c) However, the same observation is reported by parents of children who have become seizure-free following epilepsy surgery, but whose AED regimen is exactly the same...

show abstract

“…However, with the exception of FBM, pediatric experience with most of these AEDs is still limited. Vigabatrin (VGB) has appeared to be most effective in partial seizures in children ( 17), reflecting the adult experience, but may worsen seizures in some pediatric populations (1 8). LTG has been studied primarily in open trials in children (8), with some positive findings reported in LennoxGastaut syndrome ( 19,20) and in atypical absence seizures (8,2 1).…”

Section: Discussionmentioning

confidence: 99%

Preliminary Observations on Topiramate in Pediatric Epilepsies

Glauser

1997

Epilepsia

View full text Add to dashboard Cite

Summary:Preliminary results of studies of topiramate (TPM) in children are now available. In a pharmacokinetic study among 18 male and female children, target daily dosages of up to 9 mg/kg/day were evaluated. TPM pharmacokinetics in children were linear. Mean TPM oral clearance (CL/F) was 44-54% higher in children [depending on concomitant antiepileptic drugs (AEDs)] compared with historical data from adults, and steady-state plasma TPM concentrations for the same mg/kg dose were 33% lower in children compared with historical adult data. In a long-term, open-label pilot study of adjunctive TPM therapy in 18 patients with Lennox-Gastaut syndrome, six of the eight patients (75%) still receiving TPM report a greater than 50% reduction in total seizures, with the best results observed in tonic-atonic, atypical absence, and generalized tonic-clonic seizures. Subsequent large double-blind, placebo-controlled trials of adjunctive TPM therapy in Lennox-Gastaut syndrome and refractory partial-onset pediatric epilepsy are ongoing, with high percentages of enrolled patients in both studies completing double-blind treatment and entering long-term TPM open extension trials. A small TPM monotherapy substitution trial in children with well controlled partial onset seizures showed that TPM monotherapeutic substitution can be achieved successfully with an acceptable amount of adverse experiences with a weekly increase of 1 mg/kg/day to a maximal dose of 3 mg/kg/day. These preliminary results suggest that TPM may be a useful new AED in pediatric patients with a variety of seizure disorders.

show abstract

Vigabatrin in the treatment of epilepsy in children.

Cited by 100 publications

References 7 publications

Effect of Long‐Term Vigabatrin Administration on the Immature Rat Brain

Effect of Long‐Term Vigabatrin Administration on the Immature Rat Brain

Antiepileptic Drugs, Learning, and Behavior in Childhood Epilepsy

Preliminary Observations on Topiramate in Pediatric Epilepsies

Contact Info

Product

Resources

About