Clinical dissection of early onset absence epilepsy in children and prognostic implications

Abstract

SUMMARYPurpose: To investigate whether patients with typical absence seizures (TAS) starting in the first 3 years of life, conformed to Panayiotopoulos's definition of childhood absence epilepsy (CAE), show different electroclinical course than those not fulfilling CAE criteria. Methods: In this multicenter retrospective study, we choose a fixed duration follow-up of 36 months to examine the electroclinical course of epilepsy in all children with TAS starting before 3 years of age. The probands who fulfilled Panayiotopoulos's criteria for CAE were classified as having pure early onset absence epilepsy (P-EOAE), whereas those who did not as nonpure EOAE (NP-EOAE). In addition, these two groups of patients were further stratified according to the number of antiepileptic drugs taken to obtain initial seizure control (mono-, bi-, and tritherapy). Key Findings: Patients with P-EOAE (n = 111) showed earlier initial seizure control (p = 0.030) and better seizure-free survival curve (p = 0.004) than those with NP-EOAE (n = 77). No mutation in SLC2A1 gene or abnormal neuroimaging was observed in P-EOAE. Among patients with NP-EOAE, those receiving tritherapy showed increased risk of structural brain abnormalities (p = 0.001) or SLC2A1 mutations (p = 0.001) but fewer myoclonic features (p = 0.031) and worse seizure-free survival curve (p = 0.047) than those treated with mono-and bitherapy. Children with NP-EOAE had 2.134 the odds of having relapse during the follow-up compare to those with P-EOAE. Significance: Children with early onset TAS who did meet Panayiotopoulos's criteria showed a favorable course of epilepsy, whereas patients not fulfilling Panayiotopoulos's criteria showed increased risk of relapse at long-term follow-up.

Rare coding variants in genes encoding GABAA receptors in genetic generalised epilepsies: an exome-based case-control study

“…The GGE diagnoses included mainly the classical four phenotypes of childhood or juvenile absence epilepsy (CAE, JAE), juvenile myoclonic epilepsy (JME), or GGE with generalized tonic-clonic seizures alone (EGTC); we included few cases with early-onset absence epilepsy (EOAE, defined as beginning below three years of age), epilepsy with myoclonic absences (EMA) and up to 30% unclassified GGE, since these entities in our view are close to classical GGE. For EOAE it has been recently suggested by a large study that it is likely genetically similar to classical CAE 11 , EMA may also have genetic overlaps with GGE 12 and we often find in family studies both well classified and unclassified GGE cases in the same pedigrees (see appendix for detailed phenotypes in all cohorts). The first, discovery WES case cohort included 152 subjects (after quality control (QC)) with GGE from multiplex families, collected by the Epicure and the EuroEPINOMICS-CoGIE consortia.…”

Genetic generalized epilepsies

“…GLUT1 deficiency is seen in 10% of those with typical absence seizures starting before 4 years of age and around 1% of people with typical GGE overall . With a narrow definition of EOAE that excludes not only those with intellectual impairment but also those who have ever had GTCS, myoclonic seizures, or photosensitivity on EEG, the rate of GLUT1 deficiency in EOAE is probably closer to the 1% seen in GGE overall …”

“…Although these subsyndromes are broadly accepted, the diagnostic classification for epilepsy does not draw clear lines between them, and the limits, particularly of CAE, are a matter of active debate. There are also cases that fit the broad definition of GGE but not the classical age at onset, for instance adult‐onset GGE and some early onset absence epilepsies (EOAEs), where seizures start before 4 years of age . There are also situations where the epilepsy is consistent with GGE but intellectual impairment or autism is also present, which fall outside the strict definition of GGE but are important as the genetic causes appear to overlap …”

“…[17][18][19] With a narrow definition of EOAE that excludes not only those with intellectual impairment but also those who have ever had GTCS, myoclonic seizures, or photosensitivity on EEG, the rate of GLUT1 deficiency in EOAE is probably closer to the 1% seen in GGE overall. 4 GLUT1 deficiency is also remarkable for having a specific remedy in the ketogenic diet. Ketones utilize a different transporter so that the ketogenic diet bypasses the metabolic defect, leading to excellent seizure control in even the most severe cases, and likely improvement in intellectual function, making a diagnosis of mild GLUT1 deficiency clinically important.…”

Epilepsy and glucose transporter 1 deficiency syndrome

“…Two patients inherited the missense mutations from a parent with idiopathic epilepsy including juvenile absence epilepsy and adult-onset absence epilepsy. In a recent study describing the clinical features of children with early-onset absence epilepsy, authors found that SLC2A1 gene mutation is present only in children with atypical clinical features including history of developmental delay, myoclonic or other seizure types and electroencephalography (EEG) findings of 3-4 Hz polyspike discharges [15]. Studies describing familial GLUT-1 DS expanded the spectrum of absence epilepsy [6,8,16].…”