- Summary:Purpose: Partial seizures in early postnatal life may be catastrophic and associated with poor long-term outcome. Epilepsy surgery can alleviate partial seizures in older children and adults, but there is little experience with surgical therapy in infancy apart from hemispheric epilepsy syndromes.Methods: We analyzed the results of cortical resection to treat medically refractory partial epilepsy in 31 children (16 boys, 15 girls) aged <3 years (mean, 18.3 months). Subjects were included only if seizure relief was the primary indication for surgery.Results: Follow-up of at least 1 year (mean, 4.6 years) in 26 patients revealed that 16 were seizure-free, 4 had >90% seizure reduction, and 6 had <90% reduction. There was no significant difference in seizure outcome between hemispherectomy/ multilobar resections and lobar resections or temporal versus extratemporal resection. Seizure outcome was independent of the amount of cortex removed in nonlesional patients. Only the presence of a discrete lesion on preoperative neuroimaging correlated with a favorable outcome. Family perceptions of accelerated development in seizure-free patients were not confirmed on developmental assessment.Conclusions: We conclude that cortical resection often benefits very young children with catastrophic partial seizures, but does not guarantee enhanced neurological development. The location and extent of the excised cortex may not be critical as long as the entire epileptogenic region and tesion are removed.

Summary:Purpose: Children with tuberous sclerosis complex (TSC) benefit from excisional surgery if seizures can be localized to a single tuber. We evaluated the role of noninvasive studies to localize the epileptogenic tuberhegion (ET/R) and the outcome of focal resection.Methods: We identified 21 children with TSC, ages 3 months to 15 years (mean 4.8 years). All had video-(electroencephalogram) EEG and magnetic resonance imaging (MRI) scans, and 18 also had ictal single photon emission-computed tomography (SPECT) studies. An ET/R was localized in 17 patients. Thirteen patients underwent resection guided by intraoperative electrocorticography (n = 7) or subdural monitoring (n = 6).Results: Interictal EEG revealed a principal spike focus (PSF) that corresponded to the ET/R in 14 children. In seven, PSFs occurred in rhythmic runs. PSFs were not observed remote from the ET/R. Focal polymorphic slowing and attenuation occurred in the region of the PSF in 1 I patients. Sixteen patients demonstrated an ictal focus corresponding to the ET/R. Ictal SPECT revealed focal hyperperfusion correlating with the ET/R in 10 patients. Although the MRIs in all children revealed multiple tubers, the E T R corresponded to a large discrete tuber in 8 patients and a calcified tuber in 13 patients. Patchy calcified tubers were also seen elsewhere in six patients. At a mean follow-up of 26 months, 9 of the 13 children who underwent surgery were seizure-free, one had greater than 75% reduction in seizures, two were unchanged, and one was lost to follow-up. New seizures developed in one child from a contralateral tuber.Conclusions: Surgical resection of an ET/R alleviates seizures in most children with TSC and intractable epilepsy. The scalp EEG and MRI help define the ET/R and improve case selection when ictal SPECT is nonlocalizing.

Lamotrigine was effective for the adjunctive treatment of partial seizures in children and demonstrated an acceptable safety profile.

Pharmacokinetic and pharmacodynamic data are crucial in determining dosage regimens for newly developed drugs. While sufficient information to ensure safe and effective therapy is usually available for the general population, these data may rarely be available for patient subpopulations. In reviewing the paediatric data, there is an obvious dearth of pharmacokinetic and pharmacodynamic information for most therapeutic agents in newborns, infants and children. The information that is often available for this population consists largely of anecdotal and case reports or studies with low patient enrolments. This type of data is frequently of poor scientific merit and inappropriate for the extrapolation of meaningful information for the basis of dosage determinations. Unfortunately, this situation often leads to rudimentary, experiential pharmacotherapy in neonates and children which may result in incomplete therapeutic responses or even devastating outcomes. Recognising this danger, drug selection in children is often based solely on the availability of data. One agent may be selected over an alternative simply as a result of more paediatric experience and available pharmacokinetic information. Alternative agents may actually be more effective and less toxic than the drug selected, but lack sufficient paediatric documentation. This article discusses issues related to the paucity ofpharmacokinetic and pharmacodynamic data in newborns and children and, along with the review of Kauffman & Kearns (1992), elsewhere in this issue, proposes means of overcoming the obstacles of performing research in children.

Generic substitution is practiced widely in both hospital and community settings. There have been several reports of reduced serum concentrations and seizure exacerbation following generic substitution of Tegretol. We describe the first 2 cases of carbamazepine toxicity resulting from the substitution of Tegretol with Epitol. Two 6-year-old children experienced increases in the maximum serum carbamazepine concentration, one of 22% and one of 41%. Both became asymptomatic when their serum concentrations were lowered and had no residual effects.

Six neonates with prolonged, intractable seizures were treated with valproic acid (VPA). Each patient had received maximum doses of phenobarbital (greater than 40 micrograms/ml), and five patients received at least two additional anticonvulsants, without success. Seizure activity was controlled in five of six (83%) cases. In four cases, all other anticonvulsants could be withdrawn, and seizures were controlled on VPA monotherapy. VPA was discontinued in three patients because of VPA-induced hyperammonemia. VPA pharmacokinetic measurements were as follows: for total VPA, volume of distribution (V) = 0.40 l/kg (range, 0.36 to 0.47 l/kg), serum clearance (Cl) = 14.4 ml/h/kg (5.5 to 18.2 ml/h/kg), half-life (T1/2) = 26.4 hours (8.6 to 48.5); for unbound VPA, V = 2.02 l/kg (1.14 to 2.44 l/kg), Cl = 108.9 ml/h/kg (42.0 to 252.0 ml/h/kg). T1/2 = 17.6 hours (6.7 to 34.2). VPA free fraction ranged from 11.3 to 31.6% (mean, 19.2%).

We evaluated the pharmacokinetics of lamotrigine in 12 children with epilepsy who were receiving no other antiepileptic drugs. Each patient received a single oral dose of lamotrigine 2 mg/kg. Plasma concentrations of the drug were measured up to 48 hours after dosing. Pharmacokinetic parameters were calculated using noncompartmental methods. After rapid absorption, the lamotrigine concentration declined monoexponentially. Oral clearance was 0.64 +/- 0.26 ml/min/kg. The apparent volume of distribution was 1.50 +/- 0.51 L/kg. Weight-normalized clearance and volume were higher in children than in adults. The mean half-life was 32 hours, similar to that in adults. Should similar plasma lamotrigine concentrations in adults and children be desirable, children will likely require higher weight-normalized doses at the same dosing frequency.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and adverse effects of vigabatrin and its role in the management of seizure disorders. METHODS: A MEDLINE search of English-language literature from January 1993 through January 1999 was conducted using vigabatrin as a search term to identify pertinent studies and review articles. Additional studies were identified from the bibliographies of reviewed literature. The manufacturer provided postmarketing surveillance data. Priority was given to randomized, double-blind, placebo-controlled studies. FINDINGS: Vigabatrin is a selective and irreversible inhibitor of γ-aminobutyric acid transaminase. In controlled clinical trials of vigabatrin add-on therapy in patients with uncontrolled partial seizures, 24–67% of patients achieved a ≤50% reduction in seizure frequency. Data from two comparative trials with carbamazepine monotherapy indicate that vigabatrin monotherapy reduces the frequency of partial seizures in patients with newly diagnosed epilepsy. Vigabatrin also controls infantile spasms, particularly those associated with tuberous sclerosis. Vigabatrin is more effective in patients with partial seizures than in those with generalized seizures. The drug is generally well tolerated. Headache and drowsiness were the most common adverse effects observed in controlled clinical trials; visual field defects, psychiatric reactions, and hyperactivity also have been reported. There are no known clinically significant drug interactions. CONCLUSIONS: Vigabatrin improves seizure control as add-on therapy for refractory partial seizures and may produce therapeutic benefits in the treatment of infantile spasms. Vigabatrin is generally well tolerated, with a convenient administration schedule, a lack of known significant drug interactions, and no need for routine monitoring of plasma concentrations.