Therapeutic Options for Childhood Absence Epilepsy

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.

P.102 Childhood Absence Epilepsy: Prevalence of treatment resistance and neuropsychiatric comorbidity.

Background: Seizures in childhood absence epilepsy (CAE) are usually easily controlled with anti-seizure medications (ASMs). Factors predictive of treatment resistance remain unclear. Our objectives were to assess prevalence of neuropsychiatric problems and factors influencing refractoriness in a cohort of CAE at a single centre. Methods: We retrospectively reviewed patients with CAE (ILAE 2017 classification) diagnosed between January 1999 and December 2016 with at least 1-year follow-up. Treatment resistance was defined as failure to respond to two or more appropriate ASMs. Exclusion criteria included eyelid myoclonia with absence, myoclonic absence, and generalized tonic-clonic (GTC) seizure before developing absences. Results: The study population comprised 164 patients (65 males) 6.25-year-old on average at absence onset. 22% had treatment-resistant seizures. The first ASM was Ethosuximide in 63.4%, Valproic acid in 23.2%, and Lamotrigine in 6.7%. Statistical differences between response groups included developing a second seizure type specifically GTC, the second and third ASM, and absence of EEG normalization. At last follow-up, 43.3% of children were seizure-free off ASMs. 32.9% of children had learning disabilities, 28% ADHD, and 12.8 % anxiety. Conclusions: 22% of children with CAE had treatment-resistant seizures. Photoparoxysmal response was not predictive of treatment resistance. Neuropsychiatric problems were common with learning disabilities increased with refractory absences.

Pretreatment Source Location and Functional Connectivity Network Correlated With Therapy Response in Childhood Absence Epilepsy: A Magnetoencephalography Study

Objective: This study aims to investigate the differences between antiepileptic drug (AED) responders and nonresponders among patients with childhood absence epilepsy (CAE) using magnetoencephalography (MEG) and to additionally evaluate whether the neuromagnetic signals of the brain neurons were correlated with the response to therapy.Methods: Twenty-four drug-naïve patients were subjected to MEG under six frequency bandwidths during ictal periods. The source location and functional connectivity were analyzed using accumulated source imaging and correlation analysis, respectively. All patients were treated with appropriate AED, at least 1 year after their MEG recordings, their outcome was assessed, and they were consequently divided into responders and nonresponders.Results: The source location of the nonresponders was mainly in the frontal cortex at a frequency range of 8–12 and 30–80 Hz, especially 8–12 Hz, while the source location of the nonresponders was mostly in the medial frontal cortex, which was chosen as the region of interest. The nonresponders showed strong positive local frontal connections and deficient anterior and posterior connections at 80–250 Hz.Conclusion: The frontal cortex and especially the medial frontal cortex at α band might be relevant to AED-nonresponsive CAE patients. The local frontal positive epileptic network at 80–250 Hz in our study might further reveal underlying cerebral abnormalities even before treatment in CAE patients, which could cause them to be nonresponsive to AED. One single mechanism cannot explain AED resistance; the nonresponders may represent a subgroup of CAE who is refractory to several antiepileptic drugs.