Epileptic disease of hypothalamic hamartomas manifesting with gelastic seizures. This often evolves to a generalized epileptic encephalopathy with severe seizures and cognitive and behavioral decline.

Prevalence
Extremely rare, probably 0.1% among patients with seizures.

Age at onset
Neonatal period or early childhood; peak at 2 to 3 years.

Sex
Twice as many males as females.

Etiology
Hypothalamic hamartomas that are directly involved in the pathogenesis of gelastic and dacrystic seizures; they have intrinsic epileptogenicity.

Clinical manifestations
Laughter is the defining and starting manifestation. The laughter is mirthless, silent or loud, and usually unmotivated. Dacrystic (crying) attacks may occur in 13% of the patients.

The attacks are usually brief (10 to 30 sec) and on a daily basis. Ictal impairment of consciousness occurs in half of patients. Ictal autonomic symptoms occur in 1/3 of patients.

More than half of patients (66%) also suffer from generalized seizures such as tonic, atonic, generalized tonic clonic, and absences.

Most patients develop cognitive and behavioral symptoms. Children with hypothalamic hamartomas and precocious puberty but without seizures do not develop cognitive and behavioral problems.

Diagnostic procedures
MRI for the detection of hypothalamic hamartoma.

Inter-ictal EEG
Normal or more usually shows non-specific and non-lateralizing episodic abnormalities.

Ictal EEG
Low-voltage episodic fast rhythms with simultaneous suppression of background activity.

Prognosis
Often progressive disorder with worsening of seizures and progressive cognitive and behavioral impairment for most patients. More than half (59%) suffer from precocious puberty.

Differential diagnosis
Non-epileptic conditions and gelastic seizures arising from other brain locations (temporal and frontal lobes).

Management options
Medical treatment is often ineffective and polytherapy may cause more harm than good. Two patients treated with gonadotropin-releasing hormone (GnRH) analogue for precocious puberty became free of gelastic seizures.

Surgical removal of the hamartoma is technically difficult, but it is highly effective if successful. Complete lesionectomy results in freedom from seizures and prevents neurobehavioral deterioration.

This section was adapted from:

The educational kit on epilepsies: The epileptic syndromes By C. P. Panayiotopoulos Originally published by MEDICINAE, 21 Cave Street, Oxford OX4 1BA

First published 2006 and reprinted in 2007. The Educational Kit on Epilepsies was produced through an unrestricted educational grant from UCB Pharma SA.

UCB Pharma SA assumes no responsibility of the views expressed and recommended treatments in these volumes.

Authored by: C. P. Panayiotopoulos MD PhD FRCP on 1/2005
Reviewed by: Steven C. Schachter MD on 6/2008
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