Juvenile Myoclonic Epilepsy

Juvenile myoclonic epilepsy is a genetic generalised epilepsy with myoclonic jerks on awakening, generalised tonic clonic seizures and, in about one third, absences. It usually begins at 12 to 18 years and is lifelong in most patients.

It accounts for about 5 to 10% of all epilepsy and is slightly more common in girls. Photosensitivity occurs in about 30%.

Triggers. Sleep deprivation, alcohol, stress, flashing lights and abrupt awakening.

Course. Seizures are well controlled by drugs in about 80 to 90%, but relapse is very common (over 80%) when treatment is stopped, so long term therapy is usual.

Pathophysiology.

Cortical and thalamic hyperexcitability with abnormal frontal lobe networks produces polyspike-and-wave discharges. Complex polygenic inheritance is typical, with rare variants in genes such as GABRA1 and EFHC1.

Impaired inhibitory control in prefrontal regions may explain executive and personality traits.

• Bilateral myoclonic jerks of the arms, mainly shortly after waking, causing dropped objects.
• Generalised tonic clonic seizures, often after jerks cluster, especially after sleep loss.
• Absences in 15 to 40%.
• Normal intelligence, with executive dysfunction and impulsivity in some.

Red flags.

• Prolonged myoclonic or tonic clonic seizures.
• Drug induced worsening of seizures (carbamazepine, phenytoin).
• Progressive deterioration or ataxia suggesting a progressive myoclonic epilepsy.

• EEG: generalised 4 to 6 Hz polyspike-and-wave and spike-and-wave bursts, with photoparoxysmal response in some; sleep deprived and morning recordings increase yield.
• Video EEG for characterisation; MRI is normal and needed only when atypical.
• Careful history of jerks on awakening, which patients often do not report.

Differential diagnosis. Juvenile absence epilepsy, focal frontal lobe epilepsy, progressive myoclonic epilepsies (Unverricht-Lundborg disease, Lafora disease), benign myoclonus, tics and non-epileptic events.

• Counsel on regular sleep, alcohol avoidance and trigger control; contraception and pregnancy planning in women.
• 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 and weight. 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.
• Levetiracetam first line in girls and women of childbearing potential: 500 mg orally twice daily, increased by 500 mg twice daily every 2 weeks as needed to a maximum of 1500 mg twice daily. Monitor mood, irritability 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.
• Lamotrigine is an alternative, but may worsen myoclonus: 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. Maximum 400 mg daily. Monitor rash and Stevens-Johnson syndrome; reduce dose in hepatic impairment; levels fall with oestrogen containing contraception and in pregnancy.
• Topiramate as an add on: 25 mg orally at night for 1 week, increased by 25 to 50 mg every 1 to 2 weeks to a usual 100 to 200 mg daily in 2 divided doses. Maximum 400 mg daily. Monitor bicarbonate, renal stones, mood, weight and visual symptoms. Halve the dose when creatinine clearance is under 70 mL/min; use caution in hepatic impairment; avoid in pregnancy because of oral clefts and growth restriction.
• Avoid carbamazepine, oxcarbazepine, phenytoin, gabapentin, pregabalin, vigabatrin and tiagabine, which can worsen myoclonus and absences.
• Women planning pregnancy: 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).

Monitoring. Review every 6 months; check adherence, sleep and mood; monitor drug levels in pregnancy.

Referral and escalation. Epilepsy specialist for diagnosis and for women of childbearing potential; urgent review for drug resistant disease or status.

Special groups. Women: valproate pregnancy prevention, contraception interactions (enzyme inducing drugs reduce hormonal efficacy). Driving rules vary by jurisdiction.