Original ArticleAmantadine for the Treatment of Refractory Absence Seizures in Children
Introduction
Absence seizures are frequently encountered in a number of pediatric epilepsy syndromes, including childhood absence epilepsy, juvenile absence epilepsy, and juvenile myoclonic epilepsy. Seventy-eight percent of children with childhood absence epilepsy will ultimately achieve freedom from seizures, although a subset of patients fails standard treatments [1]. A smaller proportion of patients (35%) achieve freedom from seizures when other seizure types are associated, because the epilepsy phenotype contributes to the ultimate outcome [1]. Ethosuximide, lamotrigine, and valproic acid are considered primary medications for the treatment of absence seizures. Valproic acid and ethosuximide are more effective than lamotrigine, whereas ethosuximide demonstrates fewer adverse effects on attention [2]. Despite these therapies, a considerable proportion of patients may fail to achieve freedom from seizures, and may become refractory to multiple antiepileptic drugs (AEDs).
Amantadine hydrochloride is approved for the treatment of Parkinson disease, as influenza A prophylaxis, and for drug-induced extrapyramidal disorders. Rare reports demonstrated the use of amantadine as an anticonvulsant drug, initially as a serendipitous finding during the treatment of a viral syndrome in children with epilepsy [3], [4]. Shahar and Brand used amantadine in four children with refractory absence epilepsy, and demonstrated rapid achievement of freedom from seizures, which was sustained for 24-36 months [3]. Shields et al. used amantadine as add-on therapy in 10 children with refractory epilepsy, primarily generalized type, and reported that absence and myoclonic seizures responded favorably, whereas tonic, tonic-clonic, and atonic seizures were exacerbated [4]. In the present study, we sought to review our experience using amantadine hydrochloride as add-on therapy for refractory absence seizures in children.
Section snippets
Study Design and Methods
After approval of our protocol by the Institutional Review Board of Cook Children’s Medical Center, we retrospectively reviewed the medical charts of all patients less than 18 years of age who had manifested absence seizures treated with amantadine since January 2007, and who had been followed in the Comprehensive Epilepsy Program of Cook Children’s Medical Center. Patients with less than 3 months of follow-up after the initiation of amantadine were excluded. Baseline demographic data were
Results
Fourteen patients (five male and nine female) were treated with amantadine during the inclusion period. One patient from out of state has not returned for a follow-up visit and was excluded, leaving 13 patients with more than 3 months of follow-up data available for analysis. The mean age of seizure onset was 5.38 years (range, ages 2-8 years). Eight (62%) patients experienced only absence seizures, whereas two manifested coexisting myoclonic seizures, two manifested generalized tonic-clonic
Discussion
Regarded as a more benign seizure type, absence seizures may be refractory in a subset of patients, especially in the setting of epilepsy syndromes other than childhood absence epilepsy. Although conventional therapies are effective, alternative treatments are needed for those who fail to respond to first-line agents. Amantadine may be an effective treatment for patients with refractory absence seizures, because >50% of our patients reported >50% seizure reduction. A majority of patients who
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