Childhood Absence Epilepsy

• Childhood absence epilepsy (CAE) is an age-dependent, idiopathic form of generalised epilepsy (IGE) characterised by multiple absence seizures per day, as well as bilateral, symmetrical, and synchronous discharges of 3-Hz generalised spike and waves (GSW) in the electroencephalogram.
• The 2017 International League Against Epilepsy (ILAE)classification suggested that the term IGE could be reserved for the four syndromes including childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), Juvenile Myoclonic Epilepsy (JME), and epilepsy with generalized tonic–clonic seizures alone (GTCA)^[1].
• CAE makes for 2% to 10% of all paediatric epilepsies and 8-15% of school-aged childhood epilepsies. Seizures occur many times daily and consist of brief staring spells, sometimes with rhythmic eye blinking or motor automatisms, lasting seconds, with immediate return to the baseline level of awareness and activity. Children with CAE develop normally, although attentional deficiencies or other subtle behavioural or cognitive abnormalities may be present at onset.

Fig. 1: A typical absence seizure on electroencephalogram, characterized by 3 Hz generalized spike wave discharges, with abrupt onset and offset, lasting several second

• On electroencephalography (EEG), seizures are characterized by a highly recognizable pattern of generalized (bilateral, symmetric and synchronous) 3 Hz spike and wave discharges. See figure 1
• Consider the possibility of Glucose transporter 1 deficiency syndrome in a child who has absence seizures that started before the age of 4 years or who has absence seizures along with an abnormal neurologic exam or significant developmental delays.

Three antiepileptic medications, namely ethosuximide (ETX), valproic acid (VPA), and Lamotrigine (LTG), have traditionally been the primary choices for treating childhood absence epilepsy (CAE). The 2010 Childhood Absence Epilepsy research presented conclusive evidence, classified as class I, supporting the use of ETX as the most effective initial treatment for CAE^[2]. See algorithm figure 2.

Fig. 2: Treatment Algorithm for Childhood Absence Epilepsy

• Because VPA slows down the metabolism of LTG by blocking liver enzymes, titration of LTG starts at an even lower dose, moves more slowly, and hits a lower target in a person who is also taking VPA than in a person who is not taking any other medication.
• There are important cognitive, behavioural, and psychological problems associated with CAE that need to be identified early and dealt with. Anxiety and attention deficit hyperactivity disorder (ADHD) are significantly associated with CAE^[3].

• Age at onset of CAE is considered to be 2 to 13 years of age and for Juvenile Absence Epilepsy (JAE) to be 8 to 20 years of age; there is five years of overlap^[4].
• Patients with JAE more often have GTCS and more frequently experience seizure-related injuries compared with patients with CAE
• Valproate can be considered as the drug of choice in men and lamotrigine as the first drug of choice in women with JAE. See table 1
• CAE has a good prognosis (most patients will become seizure-free off ASMs^[5], whereas in JAE many patients have poor seizure control and the syndrome may last a long time^[6].

While reporting an EEG the following terms are suggested, whenever appropriate: spike-and-slow-wave complex, 3 c/s spike-and-slow-wave complex, sharp-and-slow wave complex. Use of the term “absences” is discouraged when describing EEG patterns.

• Absence seizures result from disruptions in thalamocortical rhythms via T-type calcium channel dysfunction.

see also Absence Seizures

• There are few genes that confer monogenic risk for CAE, found through family studies or large cohort studies (e.g., GABRG2, GABRA1, SLC2A1^[7]).
• The CACNA1H missense variant (rs61734410/P640L), though not a CAE disease-causing variant, has been reported to be more often associated with ETX non-response in the CAE trial, supported by in vitro neurophysiologic studies^[8].
• Several recurring Copy Number Variations (CNVs), such as 15q11.2, 15q13.3, and 16p13.11 microdeletion^[9], contribute to a complicated inheritance pattern seen in CAE.A chromosomal microarray should be requested for children with substantial learning difficulties due to the higher probability of pathogenic CNVs

• If first- and second-line drugs don't work, clobazam might be worth a try. However, there isn't much literature on its use in treatment-resistant CAE
• The ketogenic diet has also been used successfully in children with treatment-resistant CAE^[10]
• There is mixed evidence about how well levetiracetam works for children absence epilepsy. Some reports say it works pretty well^[11][12], while another report says it makes absence seizures worse^[13].