Therapeutic Options for Childhood Absence Epilepsy

Abstract

Childhood absence epilepsy (CAE) is a common pediatric generalized epileptic syndrome. Although it is traditionally considered as a benign self-limited condition, the apparent benign nature of this syndrome has been revaluated in recent years. This is mainly due to the increasing evidence that children with CAE can present invalidating neuropsychological comorbidities that will affect them up to adulthood. Moreover, a percentage of affected children can develop drug-resistant forms of CAE. The purpose of this review is to summarize the most recent studies and new concepts concerning CAE treatment, in particular concerning drug-resistant forms of CAE. A Pubmed search was undertaken to identify all articles concerning management and treatment of CAE, including articles written between 1979 and 2021. Traditional anticonvulsant therapy of CAE that is still in use is based on three antiepileptic drugs: ethosuximide which is the drug of choice, followed by valproic acid and lamotrigine. In the case of first line treatment failure, after two monotherapies it is usual to start a bi-therapy. In the case of absence seizures that are refractory to traditional treatment, other antiepileptic drugs may be introduced such as levetiracetam, topiramate and zonisamide.

Prospective Evaluation of Ghrelin and Des-Acyl Ghrelin Plasma Levels in Children with Newly Diagnosed Epilepsy: Evidence for Reduced Ghrelin-to-Des-Acyl Ghrelin Ratio in Generalized Epilepsies

“…Interestingly, it was suggested that network changes might be syndrome-specific, and thus patterns of altered default mode network connectivity in genetic generalized epilepsy syndromes should differ from those in focal epilepsies [37,38]. Among the genetic generalized epilepsy syndromes, childhood absence epilepsy could occasionally become refractory [39,40] to standard treatments and might be related to a reduced functional connectivity between frontomesial regions and the anterior insula and/or frontal operculum [41]. At variance, another genetic generalized epilepsy syndrome, known as juvenile myoclonic epilepsy, could be associated with a reduced connectivity within the prefrontal cognitive networks that were supposed to be responsible of working memory difficulties during working memory tasks [42,43].…”

Genetic Mutations That Lead to Ohtahara Syndrome and Childhood Absence Epilepsy

“…LEV was designed to be used as monotherapy or as adjunctive therapy to treat various generalized epilepsies and also used to treat Therapy-Resistant CAE. LEV can not only affect the a-amino-3hydroxy-5-methyl-4-isoxazole propionic acid receptor channels, but also won't affect glutamate or GABA-mediated synaptic transmission and modulation of voltage-dependent sodium or T-type calcium currents by blinding to SV2A synaptic vesicle glycoprotein [33]. As for now, it has been shown that LEV has a great curative effect on those patients who suffer from the Therapy-Resistant CAE.…”

“…Cross et al (2002) [35] tested the therapeutic utility of TPM in five children with TAs on 24-hour ambulatory EEG in an open-label, single-site pilot experiment. The youngsters had previously been untreated or had failed to respond to other ASMs [33]. After six weeks, ambulatory EEG monitoring was used to assess response.…”

“…By inhibiting carbonic anhydrase and blocking T-type calcium channels as well as voltagesensitive sodium channels, zonisamide (ZSN) is thought to impede sustained, repetitive neuronal activity [33]. Wilfong et al [36] studied the safety and efficacy of ZNS in 45 patients aged 18 years with absence seizures, despite the fact that there are minimal of data on its use.…”

Replacement of Valproic Acid with New Anti-Seizure Medications in Idiopathic Generalized Epilepsy

“…Even though physicians are generally aware of the advantages of the new ASMs, some old ASMs are still recognized as efficacious. Among the old ASMs, valproic acid (VPA) is one of the representative mainstay ASMs in the real world [ 10 , 11 , 12 , 13 ]. However, considering the advantageous and disadvantageous characteristics of each ASM, since ideal ASMs should offer sufficient efficacy with minimal AEs, physicians naturally wonder whether they should continue to prescribe VPA or instead replace VPA with new ASMs.…”