Gelastic Epilepsy

Gelastic epilepsy is a focal epilepsy with seizures of ictal laughter (gelastic seizures) without a sense of mirth, most often from a hypothalamic hamartoma, and sometimes from temporal or frontal lesions. Onset is usually in infancy or early childhood.

Gelastic seizures with hypothalamic hamartoma may progress to a severe epileptic encephalopathy with other seizure types, cognitive decline, behavioural disturbance and, in some, central precocious puberty.

Pathophysiology. Intrinsic epileptogenic activity within the hamartoma spreads through the mammillothalamic and other connections to cortex, producing generalisation and secondary epileptogenesis.

Stereotyped, brief (10 to 30 seconds), often daily, unprovoked laughing or giggling that appears mirthless, sometimes with a smirk, autonomic signs, and no clear impairment of awareness early on. Other seizure types (focal impaired awareness, tonic, atonic, generalised tonic clonic) appear later. Rage attacks, hyperactivity, learning difficulty and precocious puberty occur with hypothalamic hamartoma.

Red flags.

• Escalating seizure types with regression.
• Early puberty in a child with gelastic seizures.

MRI of the brain with thin coronal sections through the hypothalamus shows a hamartoma (isointense on T1, iso- to hyperintense on T2, non-enhancing). Video EEG may be normal interictally early, with later generalised and multifocal discharges. Endocrine assessment for precocious puberty (luteinising hormone, follicle stimulating hormone, sex steroids, bone age). Neuropsychological and behavioural assessment.

Differential diagnosis.

• Pathological laughter and crying (pseudobulbar affect), dacrystic seizures.
• Non-epileptic events, tic disorders and behavioural laughter.
• Other focal lesions (temporal, frontal) and cataplexy.

Antiseizure drugs. Seizures are usually drug resistant. Carbamazepine, oxcarbazepine or lamotrigine can be tried, with levetiracetam, valproate, clobazam or topiramate as add on, using the usual doses.

Surgery and ablation (preferred early for hypothalamic hamartoma). Stereotactic radiofrequency thermocoagulation, laser interstitial thermal therapy, endoscopic disconnection, stereotactic radiosurgery or open microsurgical resection or disconnection. Seizure freedom in about 50 to 70% of gelastic seizures, with improved cognition and behaviour if done early. Risks include memory loss, hypothalamic dysfunction (weight gain, hypopituitarism) and third nerve injury.

Precocious puberty. Gonadotrophin releasing hormone analogue (leuprorelin 3.75 mg IM every 4 weeks, or the dose by weight in children) under endocrinology.

Behaviour and learning. Psychology, behavioural therapy and educational support.

Monitoring. Seizure diary, EEG, development, endocrine function and MRI.

Referral and escalation. Refer early to a paediatric epilepsy surgery centre.