Childhood Absence Epilepsy

Childhood absence epilepsy is a genetic generalised epilepsy of school age children with frequent brief absence seizures and a characteristic 3 Hz generalised spike-and-wave EEG pattern. It begins between 4 and 10 years, with a peak at 5 to 7 years.

It accounts for about 10 to 12% of childhood epilepsy, with an incidence of about 6 to 8 in every 100,000 children each year. Girls are affected more often. Most children have normal development.

Genetics. Polygenic inheritance with a family history in about 15 to 40%; a small number have variants in GABRG2, GABRA1 and CACNA1A.

Course. Remission occurs by adolescence in 60 to 70%. Generalised tonic clonic seizures develop in a minority, and some evolve to juvenile myoclonic epilepsy. Attention and learning difficulties are common.

Pathophysiology.

Abnormal oscillation in thalamocortical circuits, driven by T-type calcium channels in thalamic neurons, produces synchronised spike-and-wave discharges and loss of awareness.

Hyperventilation triggers discharges by lowering carbon dioxide and increasing cortical excitability.

• Sudden brief staring with unresponsiveness lasting 5 to 20 seconds, with no postictal confusion, and abrupt return to activity.
• Frequent episodes, often dozens or hundreds each day, with automatisms (lip smacking, blinking) in some.
• Eyelid flutter, mild clonic or atonic components, and urinary leaks may occur.
• Triggered by hyperventilation; poor school performance and daydreaming.

Red flags.

• Prolonged unresponsiveness lasting over 30 minutes with continuing confusion (absence status).
• Developmental regression or focal neurological signs.
• Myoclonic jerks, generalised tonic clonic seizures or onset before age 4.

• EEG: bilateral synchronous 3 Hz spike-and-wave bursts on a normal background, provoked by 3 minutes of hyperventilation; record an absence during the test.
• MRI is not needed when the clinical and EEG picture is typical; it is done for atypical features.
• Blood tests only when metabolic or genetic disease is suspected.
• Developmental, school and attention assessment.

Differential diagnosis. Daydreaming and inattention, focal impaired awareness seizures, juvenile absence epilepsy, epilepsy with myoclonic absences, syncope, tics, and Lennox-Gastaut syndrome.

• Ethosuximide is the first line drug for absence seizures alone. Age 3 to 6 years: 250 mg orally once daily; age 6 years and over: 500 mg once daily, increased by 250 mg every 4 to 7 days to a usual 20 mg/kg daily in 1 or 2 doses. Usual dose 500 to 1500 mg daily; maximum 1500 mg daily. Continue until seizure free for about 2 years, then withdraw slowly. Monitor full blood count, liver and renal function, mood, behaviour and drug levels (usual range 40 to 100 mg/L). Reduce dose in hepatic and renal impairment; do not stop abruptly; limited data in pregnancy; common effects include nausea and drowsiness.
• Sodium valproate if tonic clonic seizures coexist, or if ethosuximide fails: initial 10 to 15 mg/kg orally daily in 2 divided doses, increased by 5 to 10 mg/kg weekly to a usual 20 to 30 mg/kg daily. Maximum 60 mg/kg daily. Monitor liver function, full blood count, platelets and weight; monitor for pancreatitis. Avoid in liver disease, mitochondrial disease (including POLG variants), urea cycle disorders and porphyria. Contraindicated in girls and women of childbearing potential unless no alternative works and a pregnancy prevention programme is in place, because of major malformations (about 10%) and neurodevelopmental disorders (30 to 40%).
• Lamotrigine as an alternative: monotherapy for age 2 to 11 years, 0.3 mg/kg daily in 1 or 2 doses for 2 weeks, then 0.6 mg/kg daily for 2 weeks, then increases of 0.6 mg/kg every 1 to 2 weeks to a usual 1 to 10 mg/kg daily. Maximum 200 mg daily. With valproate: 0.15 mg/kg once daily for 2 weeks, then 0.3 mg/kg daily for 2 weeks, then increases of 0.3 mg/kg every 1 to 2 weeks to a usual 1 to 5 mg/kg daily. Monitor for rash, hypersensitivity and Stevens-Johnson syndrome (stop at the first rash). Reduce dose in moderate to severe hepatic impairment; use caution in renal impairment; acceptable in pregnancy with dose monitoring.
• Avoid carbamazepine, oxcarbazepine, phenytoin, gabapentin, tiagabine and vigabatrin, which can worsen absence seizures.
• Counsel on safety: supervision when swimming and bathing, and school support.

Monitoring. Review every 3 to 6 months; repeat EEG before withdrawal; monitor learning and mood.

Referral and escalation. Paediatric neurology for diagnosis and treatment; urgent review for absence status or drug resistance after 2 adequate drugs.

Special groups. Girls approaching childbearing age: choose treatment with future pregnancy in mind, and review before puberty.