ACKNOWLEDGEMENTS AND DISCLOSURES

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Current thumbnail : The efforts to understand the pathophysiology of gelastic seizures has led to significant improvement in management of the most frequent cause of these seizures, namely hypothalamic hamartomas. It is reasonable to expect that the insights learnt from studying the association between gelastic seizures and hypothalamic hamartomas will have wider implications for understanding the generalized epileptic encephalopathies of childhood.

HISTORICAL NOTE AND NOMENCLATURE
Daly and Mulder coined the term "gelastic epilepsy" from the Greek word gelos, laughter, to emphasize the main character of these seizures (Daly and Mulder 1957). The possibility of sudden emotions as a manifestation of an epileptic seizure had been recognized since the end of the 19th century (Sher and Brown 1976). These emotions were usually characterized as unpleasant. Emotions of fear were most often described. Laughing seizures were first described by Trousseau (Trousseau 1877). Gowers observed emotions "with a cheerful character" as part of a seizure (Gowers 1881). Since then, ictal laughing or gelastic seizures have been described in different epileptic conditions associated with the temporal or frontal lobes. Gelastic seizures have been described most often in association with hypothalamic hamartomas. Gascon and Lombroso suggested the following criteria for the diagnosis of gelastic epilepsy: stereotyped recurrence; absence of external precipitants; concomitance of other manifestations generally accepted as epileptic; presence of interictal or ictal EEG epileptiform discharges; and absence of conditions in which pathological laughter might occur (Gascon and Lombroso 1971). Some patients have experienced both gelastic and crying seizures, termed "dacrystic” or "quiritarian” seizures (Sethi and Rao 1976).

CLINICAL MANIFESTATIONS

The clinical manifestations of gelastic seizures depend on the associated pathology. Laughter is usually a short manifestation (about 30s), particularly when it occurs as an isolated event. Although inappropriate, it can be so similar to the patients natural laughter that it can go without diagnosis for a long period of time. It has been recognized as part of a manifestation of several kinds of seizures such as partial seizures with motor symptoms, myoclonic seizures, axial tonic seizures, flexor spasms, generalized convulsive seizures, and petit mal absences (Loiseau et al 1971). The laughter is often prolonged if it is part of a more complex seizure disorder; occasional cases of gelastic status epilepticus have also been reported (Glassman et al 1986). The laughing component of the seizure can be differentiated regarding possible manifestations of mirth during the seizure (or sorrow during a crying seizure) as well as the affected level of consciousness. Such manifestations seem to be more commonly associated with other focalities than hypothalamic hamartomas (mirth generated from a temporal focus). Uncomplicated gelastic seizures generated from hypothalamic hamartoma usually neither show components of mirth nor altered level of consciousness (Arroyo et al 1993).

Age of onset of gelastic seizures also varies depending on the associated pathology. If related to hypothalamic hamartoma, the main distribution of onset seems to be from neonate to 5 years, with the gelastic manifestations starting before other, eventually later appearing seizure types. But if associated to other focalities, as frontal lobe or temporal lobe pathology, onset is usually above the age of 5 years, gelastic seizures usually presenting in close relation to, or later than other seizure types. Gelastic seizures associated with hypothalamic hamartoma often appear several times daily or even hourly. This differs from the less frequently appearing gelastic seizures associated with other localizations. Although occurring frequently, gelastic seizures with hypothalamic hamartoma appear benign in infancy . Subsequently, during school-age years, the seizures usually become more complicated, other seizure types develop, and cognitive deterioration occurs. Severe behavior problems are common, and the seizures are usually intractable (Berkovic et al 1988; Valdueza et al 1994; Sturm et al 2000).

LOCALIZATION

It has been suggested that normal laughter is the result of an interaction of several different brain structures: the frontal and temporal neocortex; the temporo-basal cortex; the visual, olfactorial, and auditorial associative areas; the limbic system with the cingulate gyrus; and the brainstem. The motor manifestations of laughter and the feeling of amusement or mirth have been claimed to be separable functions and, consequently, neurologically dissociated (Lopes da Silva et al 1990; Arroyo et al 1993).

Gelastic seizures have been observed to be associated with many different conditions: mainly hypothalamic hamartomas, but also as a seizure manifestation of temporal and frontal lobe lesions as well as other focalities.

Hypothalamic hamartoma. Nonneoplastic malformations resembling gray matter.

Temporal lobe lesions. Tumors (Clements et al 1957; Daly and Mulder 1957; Loiseau et al 1971; Chen and Forster 1973; Sethi and Rao 1976), dilated temporal horns (Gascon and Lombroso 1971; Jandolo et al 1977), atrophy (Gascon and Lombroso 1971; Chen and Forster 1973), tuberous sclerosis foci (Yamamoto et al 1988), and post infectious foci (Chen and Forster 1973). Many of these patients could report "a funny feeling" as part of the seizure (Lehtinen and Kivalo 1965; Arroyo et al 1993), but in most patients the seizures occurred without any affective component (Loiseau et al 1971; Ames and Enderstein 1975). Several authors have described neurovegetative manifestations following the laughter (ie, flushing and dilation of the pupils) (Clements et al 1957; Daly and Mulder 1957; Jacome et al 1980). Other phenomena described are automatisms (Gascon and Lombroso 1971), crying, running, and drops (Jacome and Risko 1984).

Frontal lobe lesions. Tumors and hemangiomas (Mills 1912; Striano et al 1990; Arroyo et al 1993). None of the patients involved experienced any sense of mirth, and the laughter was described as "unnatural" in all cases. Crying was described instead of or following laughing (Loiseau et al 1971; Striano et al 1990; Arroyo et al 1993; Kurle and Sheth 2000).

PATHOPHYSIOLOGY

The pathogenetic mechanisms of gelastic seizures are not fully understood. The interictal and ictal EEGs are unspecific in gelastic seizures. Both focal spikes and generalized spike-and-wave discharges can be seen, indicating the involvement of both frontal and temporal lobes as well as subcortical structures (Arroyo et al 1993). Dipole source localization has been tried to investigate the relationship between hypothalamic hamartoma and gelastic seizure but demonstrated limited value, even though the findings suggested that gelastic seizures were likely to originate in the hypothalamic hamartoma (Hiraiwa et al 2000). Postictal SPECT has shown a suggested frontal focus to create hypoperfusion in both frontoparietal regions as well as in both cerebellar hemispheres (Iannetti et al 1997). Cascino and colleagues retrospectively studied 12 patients with gelastic seizures and hypothalamic hamartomas where intracranial EEG recordings, performed in 8 patients, indicated focal onset of seizures in the anterior temporal lobe in 7 and frontal lobe in 1 (Cascino et al 1993). None of the 7 patients who underwent a focal cortical resection experienced any significant reduction in seizure activity. Ictal SPECT performed during typical gelastic seizures in three patients with hypothalamic hamartomas demonstrated hyperperfusion in the hamartoma, hypothalamic region and thalamus, without cortical or cerebellar hyperperfusion (Kuzniecky et al 1997). Stereo-EEG recordings from hypothalamic hamartoma, neighboring hypothalamic structures and other bilateral cortical areas have shown that gelastic seizures are linked to ictal discharges localized in the hamartoma, whereas surface recordings have failed to define an epileptogenic cortical area (Munari et al 1995). Even though much effort has been put into understanding how gelastic seizures are being generated, the relationship between a presumed epileptogenic focus and gelastic fits still remains mysterious.

DIFFERENTIAL DIAGNOSIS

See the clinical manifestations section.


DIAGNOSTIC WORKUP

Video-EEG, preferably with sphenoidal electrodes, and MRI with high resolution technique in order to reveal the origin of gelastic seizures is of utmost importance. In specific cases, dipole recordings can be performed. Sometimes, where a hypothalamic hamartoma has been revealed, other malformations of cortical development can be found (Minns et al 1994; Sisodiya et al 1997; Brandberg et al 2004). These may influence the clinical picture with seizures and focal seizure activity, which is why depth electrode recording from the hypothalamic hamartoma is of importance. In such cases, the performance of interictal and ictal SPECT may be of interest as well (DiFazio and Davis 2000).

SYNDROMES AND DISEASES IN WHICH THE SEIZURE TYPE OCCURS

Gelastic seizures are known to occur in the following syndromes and diseases: hypothalamic hamartoma, frontal lobe epilepsy, temporal lobe epilepsy, epileptic encephalopathy, precocious puberty (Gulati et al 2002), and autistic spectrum disorders.

PROGNOSIS AND COMPLICATIONS

The prognosis of gelastic seizures originating from frontal lobes, temporal lobes, or other regions of the brain is dependent of the underlying pathology. They usually have a better outcome than those associated with a hypothalamic origin. Although improvement in management, that is different neurosurgical options, has introduced hope of better longtime outcome in the syndrome of hypothalamic hamartomas and gelastic seizures. Otherwise, if neurosurgery cannot be offered a secondary epileptic encephalopathy commonly develops with additional generalized seizures, cognitive deterioration and severe behavior problems (Berkovic et al 1988; Frattali et al 2001; Brandberg et al 2004).

MANAGEMENT

Because of the therapy resistance of gelastic seizures a spectrum of antiepileptic drugs have been tried. Although the gelastic seizures usually are intractable, secondary seizure manifestations may improve with medication. If hypothalamic hamartoma is diagnosed, there are several surgical options, complete removal, destruction, disconnection of the hamartoma, and in these cases, there are now mounting evidence that the condition through individually tailored surgical approach is a treatable epileptic encephalopathy (Parrent 1999; Likavec et al 2000; Palmini et al 2002; Berkovic et al 2003; Delalande and Fohlen 2003).


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ABBREVIATIONS
EEG:electroencephalography
MRI:magnetic resonance imaging
SPECT:single photon emission computed tomography

MAJOR KEYWORD DESCRIPTORS
crying seizures
dacrystic seizures
frontal lobe epilepsy
hypothalamic hamartoma
laughing seizures
queritarian seizures
temporal lobe epilepsy

MINOR KEYWORD DESCRIPTORS
altered consciousness
epilepsy
laughing
myoclonic
partial
seizures

AGE OF PRESENTATION
0-01 months
01-23 months
02-05 years
06-12 years
13-18 years

AGE OF TYPICAL PRESENTATION
01-23 months
02-05 years

PERMUTED TOPIC, SYNONYMS, VARIANTS
Gelastic seizures
seizures, Gelastic

RELATED TOPICS
Epilepsy
GM2 gangliosidoses
Hypothalamic hamartoma with gelastic seizures

DIFFERENTIAL DIAGNOSIS
partial seizures with motor symptoms
myoclonic seizures
axial atonic seizures
flexor spasms
generalized convulsive seizures
petit mal absences
frontal lobe seizures
temporal lobe seizures