Frontal Lobe Epilepsy

Frontal lobe epilepsy is a focal epilepsy arising from the frontal lobes, characterised by brief, frequent, stereotyped seizures, often from sleep, with complex motor behaviour and rapid recovery. It is frequently misdiagnosed as a psychiatric or sleep disorder.

It accounts for about 20 to 30% of focal epilepsies, second to temporal lobe epilepsy. Onset occurs at any age, often in childhood.

Causes. Focal cortical dysplasia (the commonest in surgical series), tumours, trauma, infection, vascular lesions and genetic forms. Autosomal dominant nocturnal frontal lobe epilepsy is linked to CHRNA4, CHRNB2, CHRNA2, DEPDC5 and KCNT1.

Course. Seizures cluster, often many each night, and about one third to one half are drug resistant.

Pathophysiology.

Hyperexcitable frontal cortex, often dysplastic, spreads rapidly through the dense frontal connections, producing prominent motor and behavioural manifestations with little postictal disturbance.

Nicotinic receptor channel variants lower the threshold for sleep related seizures.

• Brief (under 30 seconds) clusters of stereotyped seizures, often from sleep, with abrupt onset and offset.
• Hypermotor features: pedalling, thrashing, rocking, bizarre posturing, vocalisation and screaming.
• Tonic posturing (fencing posture), versive head and eye deviation, and focal clonic activity.
• Little or no postictal confusion; consciousness may be retained despite bilateral movements.

Red flags.

• Seizures clustered in sleep, resembling parasomnia, with injury risk.
• Failure of 2 appropriate drugs.
• Progressive deficit or new focal signs suggesting a tumour.

• Scalp EEG is often normal or non-localising between and during attacks because of the deep origin of seizures; video EEG with sleep recording is the key test.
• High resolution MRI with epilepsy specific sequences for focal cortical dysplasia; FDG-PET, ictal SPECT and magnetoencephalography in surgical assessment; intracranial EEG when needed.
• Genetic testing in familial or early onset sleep related hypermotor epilepsy.
• Polysomnography when the distinction from parasomnias is unclear.

Differential diagnosis. NREM and REM parasomnias, psychogenic non-epileptic seizures, sleep terrors, movement disorders, panic attacks and temporal lobe epilepsy.

• Carbamazepine modified release is often the most effective drug, particularly in sleep related hypermotor epilepsy: 100 to 200 mg orally once or twice daily, increased by 100 to 200 mg every 1 to 2 weeks to a usual 800 to 1200 mg daily. Maximum 1600 mg daily. Monitor sodium, full blood count, liver function and levels. Check HLA-B*1502 in people of Han Chinese, Thai or other at risk Asian ancestry before starting; avoid in atrioventricular block; reduce dose in hepatic impairment; many drug interactions (including reduced hormonal contraceptive efficacy); use only when needed in pregnancy.
• Lamotrigine 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. Maximum 400 mg daily (200 mg daily with valproate, 600 mg daily with enzyme inducers). Monitor rash and Stevens-Johnson syndrome. Reduce dose in moderate to severe hepatic impairment; acceptable in pregnancy with monitoring of levels.
• Levetiracetam 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 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.
• After 2 adequate drug regimens fail, refer for surgery: resection of a lesion gives seizure freedom in about 50 to 60%, and better results with focal dysplasia that is fully removed. Neuromodulation for non-resectable cases.
• Safety: nighttime supervision and bed safety; trigger and sleep management.

Monitoring. Review every 6 months; sodium and full blood count on carbamazepine; repeat MRI when features change.

Referral and escalation. Early referral to an epilepsy centre for drug resistance or an MRI lesion.

Special groups. Women: pregnancy planning with folic acid 5 mg orally once daily from before conception to the end of the first trimester (maximum 5 mg daily; no monitoring beyond B12 status; no renal adjustment). Children: surgical results are better with early referral.