Tuesday, September 27, 2016

Levetiracetam in childhood absence epilepsy

Matricardi S, Verrotti A, Chiarelli F, Cerminara C, Curatolo P. Current
advances in childhood absence epilepsy. Pediatr Neurol. 2014 Mar;50(3):205-12.

From the article:

LEV mechanisms of action may be related to modulation of a synaptic vesicle protein. A recent study assessed the efficacy, safety, and tolerability of LEV monotherapy in absence seizures and demonstrated more than a 50% reduction in seizures in newly diagnosed patients with CAE. No adverse events occurred in any patient during the treatment.  Another recent randomized controlled trial showed that, although better than placebo, LEV had moderate efficacy for absence seizure control.  Auvin et al., however, reported six children with CAE who showed an aggravation of absence seizures after starting LEV.

Verrotti A, Cerminara C, Domizio S, Mohn A, Franzoni E, Coppola G, Zamponi N,
Parisi P, Iannetti P, Curatolo P. Levetiracetam in absence epilepsy. Dev Med
Child Neurol. 2008 Nov;50(11):850-3.

The aim of the study was to assess the efficacy, tolerability, and safety of levetiracetam therapy in children and adolescents with absence epilepsy. Twenty-one participants (11 male, 10 female) with typical absence seizures were enrolled in this prospective study from seven centres in Italy. The mean age and age range at time of enrollment into the study were 8 years 9 months (SD 0.9) and 5 years 1 month to 13 years respectively. All patients were carefully evaluated at 6 months from baseline, and 12 patients were also re-evaluated at 12 months after the beginning of therapy with levetiracetam. At the 6-month evaluation, out of 21 patients studied, 11 were seizure free and one showed 'decreased' seizures (more than 50% reduction in seizures). A less than 50% reduction in seizures was observed in nine patients. At the 12-month evaluation, 10 patients were completely seizure free and two were seizure free with some anomalies in electroencephalograms. Two patients who had shown no improvement at 6 months had decreased seizures at the second follow-up. Our results suggest that monotherapy with levetiracetam could be effective and well tolerated in patients with childhood absence epilepsy and juvenile absence epilepsy. Prospective, large, long-term double-blind studies are needed to confirm these findings.

Fattore C, Boniver C, Capovilla G, Cerminara C, Citterio A, Coppola G, Costa
P, Darra F, Vecchi M, Perucca E. A multicenter, randomized, placebo-controlled
trial of levetiracetam in children and adolescents with newly diagnosed absence
epilepsy. Epilepsia. 2011 Apr;52(4):802-9.


To evaluate the potential efficacy of levetiracetam as an antiabsence agent in children and adolescents with newly diagnosed childhood or juvenile absence epilepsy.


Patients were randomized in a 2:1 ratio to receive de novo monotherapy with levetiracetam (up to 30 mg/kg/day) or placebo for 2 weeks under double-blind conditions. Responder status (primary end point) was defined as freedom from clinical seizures on days 13 and 14 and from electroencephalographic (EEG) seizures during a standard EEG recording with hyperventilation and intermittent photic stimulation on day 14. The double-blind phase was followed by an open-label follow-up.


Nine of 38 patients (23.7%) were responders in the levetiracetam group, compared with one of 21 (4.8%) in the placebo group (p = 0.08). Seven of 38 patients (18.4%) were free from clinical and EEG seizures during the last 4 days of the trial (including 24-h EEG monitoring on day 14) compared with none of the patients treated with placebo (p = 0.04). Seventeen patients remained seizure-free on levetiracetam after 1 year follow-up. Of the 41 patients who discontinued levetiracetam due to lack of efficacy (n = 39) or adverse events (n = 2), 34 became seizure-free on other treatments.


Although superiority to placebo just failed to reach statistical significance for the primary end point, the overall findings are consistent with levetiracetam having modest efficacy against absence seizures. Further controlled trials exploring larger doses and an active comparator are required to determine the role of levetiracetam in the treatment of absence epilepsy.

Auvin S, Chhun S, Berquin P, Ponchel E, Delanoë C, Chiron C. Aggravation of
absence seizure related to levetiracetam. Eur J Paediatr Neurol. 2011


Recent data have reported the effectiveness of levetiracetam (LVT) on generalized seizures. Among them, it seems that LVT can be successfully used to treat absence seizures. Many antiepileptic drugs (AEDs) have been occasionally reported to paradoxically aggravate some seizures. We retrospectively identified patients with aggravation of absence seizures using LVT from the databases of 2 pediatric neurology departments (Robert-Debré, Paris and Amiens; France). We also used the prospective data from an open-label clinical trial performed in a third pediatric neurology department (Necker, Paris; France). We included 6 patients: n = 2 childhood absence epilepsy, n = 3 juvenile absence epilepsy and n = 1 epilepsy with myoclonic absences. All of them have had an aggravation of the absences with a causal and temporal relationship between introduction of the drug and the detrimental effect. The aggravation disappeared when LVT was decreased or was withdrawn. This report highlights that LVT may aggravate epilepsy with absence seizures.

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