Journal of child neurology
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Vigabatrin has been studied in adult drug-resistant epilepsy since 1982 in single-blind and double-blind studies followed by long-term, open evaluations. These studies have provided evidence that vigabatrin is a potent and well-tolerated antiepileptic drug and support its potential value in pediatric epilepsy. The lack of any evidence of human neurotoxicity in these patients is also reassuring regarding its use in children.
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In this report, we examine the interrelationships between attention deficit disorder (ADD), learning disabilities (LD), and conduct and oppositional disorders (COD). We indicate that it is reasonable to consider ADD as a distinct entity, frequently co-occurring with LD on the one hand, and COD on the other. ⋯ In the next section, we review the evidence linking ADD with COD, a distinction blurred in earlier investigations by problems with referral bias. More recent studies suggest that the antecedents, clinical characteristics, and prognosis may differ in children with ADD alone compared to those with ADD in association with COD.
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Vigabatrin is an enzyme-activated, irreversible inhibitor of gamma-aminobutyric acid (GABA) aminotransferase, which causes a marked increase in cerebral GABA concentration and a resulting anticonvulsant action. Recovery from its effects requires the synthesis of new enzyme, and this may take several days following a single dose. The pharmacokinetics of vigabatrin are not a good guide to its duration of action. ⋯ Also, vigabatrin does not induce liver enzymes, as do many of the standard antiepileptic drugs. In several trials, however, a small but significant reduction in phenytoin levels has been seen following the addition of vigabatrin to the antiepileptic medication. The mechanism for this reduction in phenytoin levels has not yet been elucidated, though it does not appear to be of clinical significance.
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Twenty children aged 2 months to 18 years were included in a dose-response study of vigabatrin as add-on therapy to preexisting antiepileptic drugs (up to two per patient). All children had severe refractory epilepsy: partial seizures with or without secondary generalization in 19, and myoclonic seizures in one. After a 2-month observation period and a 1-month add-on placebo period, a fixed dose of add-on vigabatrin was given for 2 months: 1, 1.5, or 2 g/day, according to body weight (mean dose, 60 mg/kg/day). ⋯ These effects were generally transient, being observed during the dose-modification phase and disappearing either spontaneously or on reduction of vigabatrin dose. Clinical and laboratory tolerability to vigabatrin appeared to be very good, with no patients having withdrawn from the study because of side effects. A slight reduction in red blood cell count and hemoglobin levels was noted but was of doubtful clinical significance.(ABSTRACT TRUNCATED AT 250 WORDS)
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Sixty-six children with various types of severe drug-resistant epilepsy were entered into a long-term, dose-rising study of vigabatrin after a 4-week run-in placebo period. All the children were receiving one to three other antiepileptic drugs, the doses of which were not changed during the 6-month dose titration phase. Following the introduction of vigabatrin, 11 patients became seizure free, and 28 responded with a greater than 50% reduction in seizure frequency. ⋯ All these patients had a history of hyperkinesia or mental retardation. In patients in whom vigabatrin dose was reduced because of hyperkinesia, a dose increase could later be instituted without recurrence of symptoms. There was no change in neurologic examination and no drug-related abnormalities in clinical laboratory data.(ABSTRACT TRUNCATED AT 250 WORDS)