Juvenile Absence Epilepsy

Juvenile absence epilepsy is a genetic generalised epilepsy beginning around puberty with absence seizures that are less frequent than in childhood absence epilepsy and with generalised tonic clonic seizures in most. Seizure freedom is often lifelong treatment dependent.

It accounts for about 2 to 3% of epilepsy. Onset is between 9 and 13 years, with equal frequency in both sexes.

Features of the syndrome. Absences are less frequent and less severe than in childhood absence epilepsy, with partial awareness in some. Generalised tonic clonic seizures occur in about 80%, often after waking, and myoclonic jerks in about 15 to 20%.

Course. Seizures often persist into adult life, and treatment is usually long term. Sleep deprivation and alcohol are common triggers.

Pathophysiology.

Generalised 3 to 4 Hz spike-and-wave discharges arise from thalamocortical networks with abnormal GABA and T-type calcium channel function.

Genetic susceptibility is polygenic, and some patients share variants with other genetic generalised epilepsies.

• Brief absences of staring lasting 10 to 30 seconds, with impaired awareness, usually occurring less often than daily.
• Generalised tonic clonic seizures, particularly on awakening or after sleep deprivation.
• Occasional myoclonic jerks.
• Normal cognition in most, with attention and mood problems in some.

Red flags.

• Prolonged confusion (absence status).
• Frequent falls, regression or focal deficits.
• Seizures triggered by drugs, alcohol or sleep loss.

• EEG: generalised 3 to 4 Hz spike-and-wave and polyspike-and-wave bursts, often faster than in childhood absence epilepsy; sleep deprived recordings improve the yield.
• Video EEG when the diagnosis is uncertain, and MRI when focal features are present.
• Review of triggers: sleep, alcohol, drugs, photic stimulation.

Differential diagnosis. Childhood absence epilepsy, juvenile myoclonic epilepsy, focal impaired awareness seizures, syncope, panic attacks and non-epileptic events.

• Counsel on sleep regularity, alcohol and trigger avoidance.
• Sodium valproate is the most effective first line drug in males: 600 mg orally daily in 2 divided doses, increased by 200 mg every 3 days to a usual 1000 to 2000 mg daily. Maximum 2500 mg daily. Monitor liver function, full blood count, platelets, weight and drug interactions. 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 and neurodevelopmental disorders.
• Girls and women of childbearing potential: lamotrigine first. Lamotrigine monotherapy (age 12 years and over): 25 mg orally once daily for 2 weeks, then 50 mg daily for 2 weeks, then increases of 50 to 100 mg every 1 to 2 weeks to a usual 100 to 200 mg daily in 1 or 2 doses. With valproate: 25 mg on alternate days for 2 weeks, then 25 mg daily for 2 weeks, then increases of 25 to 50 mg every 1 to 2 weeks to a usual 100 to 200 mg daily. Maximum 400 mg daily (200 mg daily with valproate). Monitor for rash, hypersensitivity and Stevens-Johnson syndrome (stop at the first rash). Reduce dose in moderate or severe hepatic impairment; halve the dose with oestrogen containing contraception and adjust, since levels fall; acceptable in pregnancy with level monitoring.
• Levetiracetam as an alternative or add on: 500 mg orally twice daily, increased by 500 mg twice daily every 2 weeks to a maximum of 1500 mg twice daily. Monitor mood and behaviour, and renal function. Reduce dose when creatinine clearance is 50 to 80 mL/min (500 to 1000 mg twice daily), 30 to 50 mL/min (250 to 750 mg twice daily) and under 30 mL/min (250 to 500 mg twice daily). Acceptable in pregnancy.
• Avoid carbamazepine, oxcarbazepine, phenytoin, gabapentin, pregabalin and vigabatrin.
• Withdrawal is considered after 2 to 3 years seizure free, with the patient's agreement, and relapse is common.

Monitoring. Review every 6 months; check adherence, mood and contraception.

Referral and escalation. Epilepsy specialist for all women of childbearing potential and for drug resistance; urgent review for status.

Special groups. Women: pre-conception counselling and folic acid 5 mg orally once daily from before conception until the end of the first trimester (maximum 5 mg daily; no monitoring beyond B12 status; no renal adjustment). Driving and employment advice varies by jurisdiction.