Current and emerging treatments for absence seizures in young patients

Abstract

In this report, we review the pharmacological and non-pharmacological treatments of the different absence seizure types as recently recognized by the International League Against Epilepsy: typical absences, atypical absences, myoclonic absences, and eyelid myoclonia with absences. Overall, valproate and ethosuximide remain the principal anti-absence drugs. Typical absence seizures exhibit a specific electroclinical semiology, pathophysiology, and pharmacological response profile. A large-scale comparative study has recently confirmed the key role of ethosuximide in the treatment of childhood absence epilepsy, more than 50 years after its introduction. No new antiepileptic drug has proven major efficacy against typical absences. Of the medications under development, brivaracetam might be an efficacious anti-absence drug. Some experimental drugs also show efficacy in animal models of typical absence seizures. The treatment of other absence seizure types is not supported with a high level of evidence. Rufinamide appears to be the most promising new antiepileptic drug for atypical absences and possibly for myoclonic absences. The efficacy of vagal nerve stimulation should be further evaluated for atypical absences. Levetiracetam appears to display a particular efficacy in eyelid myoclonia with absences. Finally, it is important to remember that the majority of antiepileptic drugs, whether they be old or new, may aggravate typical and atypical absence seizures.

G protein-coupled potassium channels implicated in mouse and cellular models of GNB1 Encephalopathy

“…Owing to the short half-life of both drugs, SWDs progressively recovered an hour after treatment. On the other hand, phenytoin (PHT), an AED with a probable worsening effect on absence seizures in humans and rodents (Kim et al, 2015;Manning et al, 2003;Marescaux et al, 1992;Vrielynck, 2013), did not affect SWD occurrence ( Figure 4A).…”

“…Ethosuximide (ETX) and valproic acid (VPA) are two antiepileptic drugs (AED) commonly used to treat absence seizures in humans, which also interrupt SWDs rodent models (Kim et al, 2015;Manning et al, 2003;Marescaux et al, 1992;Vrielynck, 2013). Acute treatment of Gnb1 K78R/+ mice with either ETX or VPA nearly abolished SWDs ( Figure 4A).…”

Pronounced antiepileptic activity of the subtype‐selective GABAA‐positive allosteric modulator PF‐06372865 in the GAERS absence epilepsy model

“…4 Given these rats present with behavioral, electrophysiological, and pharmacological features of absence seizures, 5 it is a favorable model to enable translation of novel AEDs with varied mechanisms of action to the clinic. Accordingly, both clinically and in the GAERS model, SWDs are suppressed by some AEDs (eg, valproate, 6,7 ethosuximide, 7,8 levetiracetam, 9,10 and diazepam 11 ), whereas other AEDs can exacerbate SWDs, particularly carbamazepine, 12,13 and phenytoin. 13,14 Various classes of GABAergic drugs have also been shown to both suppress and aggravate absence epilepsy.…”

Safety and efficacy of newer anticonvulsant medications in pediatric epilepsy

“…The overall response rate to the drug was 44%, which did not isolate out the patients with absence seizures. Based on these results Vrielynck [13] postulates that brivaracetam may be a reasonable option for patients with absence epilepsy. There are ongoing studies of the safety and efficacy of brivaracetam in children; however, the data is not yet available [10].…”