A 2nd-generation Anti-epileptic Agent for Childhood Occipital Epilepsy
A 2nd-generation Anti-epileptic Agent for Childhood Occipital Epilepsy
Abstract & Commentary
By Padmaja Kandula, MD, Assistant Professor of Neurology and Neuroscience, Comprehensive Epilepsy Center, Weill Cornell Medical College. Dr. Kandula reports no financial relationships relevant to this field of study.
Synopsis: This open label trial reports on the long-term efficacy and tolerability of levetiracetam in children with late onset childhood occipital epilepsy.
Sources: Verrotti A, et al. Levetiracetam monotherapy for childhood occipital epilepsy of Gastaut. Acta Neurol Scand DOI: 10.1111/j.1600-0404.2009.01264.x.
Childhood occipital epilepsy-Gastaut type (COE-G) represents one of a few idiopathic focal types of epilepsy. The prevalence of this syndrome among all epilepsies is less than 1%. This unique syndrome presents with primarily visual symptoms with or without ictal and or post-ictal headache. Attenuation of occipital spike and wave discharges with eye opening is a characteristic electrographic hallmark of this disorder. Historically COE-G responds well to first generation anti-epileptic agents such as carbamazepine and valproic acid. However, long-term data regarding treatment of this rare syndrome with second-generation anti-epileptic agents such as levetiracetam is limited. Since the advent of several new anti-epileptic agents in the mid 1990s, renewed interest in finding optimal anti-epileptic medication regimens with potentially fewer side effects has emerged. The authors of this study present both clinical and electrographic outcomes of new-onset COE-G treated with levetiracetam monotherapy.
Patients were included in this prospective, multicenter, open-label trial if they met criteria for COE-G as defined by the International League Against Epilepsy.
Inclusion criteria were as follows: visual seizures (elementary or complex visual hallucinations, illusions, partial or complete transient visual loss, or ictal eye or head deviation), occipital spike and wave discharges on electroencephalography (EEG), and normal neurologic examination and brain imaging. Patients were excluded in the setting of intellectual impairment/abnormal neurologic examination, recurrent psychosis or major affective disorder, use of central nervous system-influencing medication less than one month prior to commencing study, metabolic derangements, acute infection or neoplasms, progressive medical illness, and previous treatment with any other anti-epileptic agents.
Twelve patients met final criteria for study inclusion. EEG was performed for 60 minutes during the awake and sleep states. Patients were initiated with levetiracetam 250 mg orally each evening, with target maintenance therapy after four weeks ranging from 20 mg/kg/day to 45 mg/kg/day based on clinical reporting of seizures. Seizures were recorded by patients or parents (legal guardians) along with any observed adverse events on a daily charting system. Patients were examined by physician investigators and underwent routine EEG testing at 6, 12, and 18 months. In addition, laboratory assessment for complete blood counts, basic metabolic profile, hepatic profile, urinalysis, and EKG were performed.
At the six-month mark, 11 out of 12 patients were seizure-free, and EEG normalized in six patients. At the 12-month mark, all patients were seizure-free. Four patients had persistent interictal abnormalities. Further, at the 18-month evaluation, all 12 patients remained seizure-free, and only two patients had less prominent occipital interictal abnormalities. Two patients reported transient dizziness and somnolence with introduction of levetiracetam.
Commentary
The treatment goal for any seizure disorder is striking a fine balance between control of seizures with the lowest effective dose and the least amount of drug-related side effects. The second-generation anti-epileptic agents were created in an attempt to achieve this fine balance. Of the new agents, levetiracetam has been efficacious in both partial and generalized seizures and has demonstrated tolerability in both adults and children. Interestingly enough, in this study one patient achieved seizure cessation with only 20 mg/kg/day of levetiracetam. A link between reduction of epileptiform activity and longer duration of levetiracetam therapy was also seen in the study. Previous studies1 have shown that levetiracetam produces a consistent long-term reduction of interictal epileptic activity in patients with refractory idiopathic generalized activity as well. Although the lack of randomization in this open-label study precludes making a firm conclusion regarding tolerability and efficacy in COE-G, there is a suggestion that levetiracetam may have clinical utility in this sub-population. A larger, blinded, randomized trial with separate treatment arms of varying dosages of levetiracetam would be useful in defining a minimal effective dose in COE-G. In addition, the correlation between reduction of interictal discharges as a predictor of possible long-term successful seizure control needs to be confirmed in a larger study.
References
1. Rocamora R, et al. Levetiracetam reduces frequency and duration of epileptic activity in patients with refractory primary generalized epilepsy. Seizure 2006;15:428-433.
This open label trial reports on the long-term efficacy and tolerability of levetiracetam in children with late onset childhood occipital epilepsy.Subscribe Now for Access
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