Sustained seizure remission on perampanel in progressive myoclonic epilepsy (Lafora disease)

Abstract

AimThe aim of this report is to provide initial evidence that add-on treatment with perampanel might be highly effective in progressive myoclonic epilepsy such as Lafora disease.Case reportWe report on a 21-year-old woman suffering from persistent myoclonus and generalized tonic–clonic seizures for more than seven years. Additionally, ataxia, a disturbance in speech and gait, as well as a cognitive decline were rapidly progressing. Subsequently, the diagnosis of Lafora disease was confirmed by the identification of a novel homozygous missense mutation in exon 3 of the EPM2A gene (c.538C>G; p.L180V).Adjunctive therapy with perampanel was started in this patient with advanced Lafora disease and was titrated up to 8 mg/day. A sustained and reproducible remission of myoclonus and GTCS could be achieved for a follow-up of three months. After dosage reduction to 6 mg/day, seizures recurred; however, on increasing the daily dose to 10 mg, seizures stopped for another three months. The patient also regained her ability to walk with help and the aid of a walker.ConclusionsPerampanel is a selective, noncompetitive antagonist of AMPA-type glutamate receptors and recently licensed as adjunctive therapy for the treatment of refractory focal onset seizures. There is evidence for its effectiveness in generalized epilepsies, and phase III studies for this indication are on the way. Our case illustrates the possibility that perampanel might be a valuable option for treatment in PME. Considering its impressive efficacy in this case, we suggest a prospective, multicenter study evaluating perampanel in PME.

Efficacy and tolerability of perampanel in ten patients with Lafora disease

“…When the dose was reduced seizures recurred, only to re-disappear for three months of follow-up when the dose was again increased. The patient's walking ability also improved 5 . In the second case, an 18 year-old Bahraini girl with an EPM2B mutation, perampanel monotherapy was titrated to 10 mg/day.…”

“…Two recent single case studies reported the effects of the relatively new AED and selective AMPA receptor antagonist perampanel in LD. The drug appeared to lead to sustained remission in myoclonus and generalized tonic-clonic seizures 5-6 . In the first case, a 21 year-old Turkish girl with an EPM2A mutation, adjunctive therapy with 8 mg/day of perampanel led to dramatic reduction in seizure and myoclonus frequency over three months.…”

Update on Pharmacological Treatment of Progressive Myoclonus Epilepsies

“…It has been approved by FDA and EMA as an add-on treatment of partial seizures and of primary GTCS (in the setting of idiopathic generalized epilepsies) in patients older than 12 years. Two single case reports [49,50] and 2 open-label studies [51, 52] suggest its potential use in PMEs. Schorlemmer et al [49] described a 21-year- old bedridden patient with LD on VPA LEV, ZNS, CNZ, PIR, and ketogenic diet, who experienced a drastic improvement of myoclonus and seizures with PER at 3-month-follow-up.…”

“…Two single case reports [49,50] and 2 open-label studies [51, 52] suggest its potential use in PMEs. Schorlemmer et al [49] described a 21-year- old bedridden patient with LD on VPA LEV, ZNS, CNZ, PIR, and ketogenic diet, who experienced a drastic improvement of myoclonus and seizures with PER at 3-month-follow-up. Dirani et al [50] prescribed PER to a 15-year-old LD girl in whom previous treatment with VPA, LTG, TPM, LEV and CNZ were abruptly stopped a few days before.…”

Lafora Disease: A Case Report

“…Selektif, non-kompetetif AMPA tipi glutamat reseptör antagonisti olan perampanelin kullanıldığı sınırlı sayıdaki olguda, ilacın etkinliği sadece nöbet sıklığında azalma ile değil, nörokognitif ve serebellar disfonksiyondaki iyileşme şeklinde tanımlanmıştır. [20,21] Ancak bu verilerin doğrulana-bilmesi için daha fazla sayıda çalışma yapılması gereklidir.…”