Childhood Absence Epilepsy

Childhood absence epilepsy (CAE) is an age-dependent, idiopathic form of generalised epilepsy 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. CAE makes for 2% to 10% of all paediatric epilepsies and 8-15% of school-aged childhood epilepsies¹⁾. 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^[1]. 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^[2].

• 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^[3]
• There is mixed evidence about how well levetiracetam works for children absence epilepsy. Some reports say it works pretty well^[4][5], while another report says it makes absence seizures worse^[6].

• 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^[7].
• 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^[8], whereas in JAE many patients have poor seizure control and the syndrome may last a long time^[9].

• Absence seizures result from disruptions in thalamocortical rhythms via T-type calcium channel dysfunction.
• 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^[10].