Journal of Child Neurology

Topiramate has been shown to be safe and effective in refractory partial epilepsy in children. Pharmacokinetic studies show that the clearance of topiramate is greater in children than in adults; therefore, higher doses may be needed in children than adults. It is generally well tolerated, except for cognitive dysfunction. Weight loss and the risk of renal stones can be significant in some cases. However, when compared with other anticonvulsant medications, topiramate has few serious idiosyncratic reactions such as rash, hematologic reactions, and hepatotoxicity. (J Child Neurol 2000;15:S3-S6).

Topiramate is a sulfamate derivative of the naturally occurring monosaccharide D-fructose. It was initially approved in the United States as adjunctive therapy for partial seizures in 1997. However, there is increasing evidence that it is effective in the treatment of generalized seizures and epilepsy syndromes. Initially, open-label studies using topiramate as add-on therapy in children with refractory generalized seizure types were performed. These showed improvement in patients with the following generalized seizure types: typical and atypical absence, atonic, myoclonic, generalized tonic-clonic, and juvenile myoclonic epilepsy. Double-blind, placebo-controlled multicentered studies in patients with refractory primary generalized tonic-clonic seizures and epilepsy syndromes were performed. The median reduction in seizure frequency for primary generalized tonic-clonic seizures was 56.7% for topiramate and 9% for placebo. Additionally, 13.6% of topiramate-treated patients were primary generalized tonic-clonic seizure free for the study period. In the topiramate-treated juvenile myoclonic epilepsy patients, primary generalized tonic-clonic seizures were reduced >50% in 73% of patients. Open-label extension showed that primary generalized tonic-clonic seizures were reduced >50% in 63% of topiramate-treated patients for ≥ 6 months, and 16% were primary generalized tonic-clonic seizure free ≥ 6 months. Accumulating evidence suggests that topiramate has a broad spectrum of antiepileptic effect. Moreover, life-threatening organ toxicity has not been attributed to topiramate. Topiramate is an effective treatment for refractory generalized seizure types and epilepsy syndromes encountered in children. (J Child Neurol 2000;15:S7-S13).

Several epileptic syndromes that occur during childhood are characterized by severe treatment-resistant seizures, progressive loss of higher intellectual functions, and characteristic electroencephalographic abnormalities. These catastrophic epileptic syndromes include epileptic encephalopathy with diffuse slow spike waves (Lennox-Gastaut syndrome), West syndrome, progressive myoclonic epilepsies, and electrical status epilepticus during sleep. This article summarizes each syndrome and reviews the most recent information concerning the effectiveness of topiramate with respect to each condition. Suggestions are offered to help clinicians maximize topiramate's efficacy and tolerability in patients suffering with these syndromes. Overall, topiramate is a valuable antiepileptic medication in the treatment of catastrophic pediatric epileptic syndromes. (J Child Neurol 2000;15:S14-S21).

Three double-blind, randomized, placebo-controlled studies of topiramate that include children have been published and prospective but unblinded and retrospective reviews have been reported providing information regarding topiramate's safety and tolerability. These studies indicate that side effects tend to occur early in treatment with topiramate, especially in children receiving polypharmacy. Two classes of adverse events are commonly reported: central nervous system and anorexia/weight loss. Central nervous system effects include somnolence, difficulties with concentration, and behavior changes. Tolerance to these effects seems to develop in most children. When it occurs, weight loss has been noted in the first 12 to 18 months, after which normal weight gain resumes, without long-term impact on growth. As opposed to the experience in adults, aphasia and word-finding difficulties are not commonly seen, and parasthesiae are not reported by children. Renal calculi are rare. Life-threatening idiosyncratic reactions have not been attributed to topiramate. While metabolic acidosis has been reported, no other clinically significant laboratory abnormalities have been associated with the use of topiramate in children. (J Child Neurol 2000;15:S22-S26).

In the treatment of children with epilepsy, the role of topiramate has been expanding gradually. The main factor that has contributed to this trend is the relatively large body of information that has accumulated on the clinical pharmacology of topiramate in children, including its broad-spectrum efficacy, pediatric pharmacokinetics, side-effect profile, and safety. It has also become increasingly apparent with time that topiramate, in contrast to other broad-spectrum antiepileptic drugs used in children, does not seem to be associated with a significant risk of any serious or life-threatening adverse effects. The present review summarizes the available evidence related to the clinical pharmacology of topiramate in children and provides an update on its known mechanisms of action. Finally, available experimental data on the neuroprotective effect of topiramate are reviewed because of their considerable clinical potential in the treatment of children and newborns. (J Child Neurol 2000;15:S27-S30).