Discussion
Smiles and laughter are universal human social gestures that involve a complex sequence of facial, pharyngeal and diaphragmatic muscle contractions and help to establish a friendly interaction with other people. Several regions of the brain are associated with laughing. Laughter consists of an affective and a motor component. The emotional aspects are processed in the temporal lobe, whereas motor features are processed in frontal cortex. The present data suggest that pericingulate premotor areas are involved in the triggering of the motor component of the laughter. Reported cases reveal a high likelihood of cingulate and basal temporal cortex contribution to laughter and mirth in humans, and suggest the possibility that the anterior cingulate region is involved in the motor act of laughter, while the basal temporal cortex is involved in the processing of laughter's emotional content in man. Studies have shown that a small area on the left superior frontal gyrus, when stimulated consistently, produces laughter.
Normal laughter is a human behavioral response to pleasant feeling whereas pathological laughter is disproportionate to the emotional context. Pathological laughter has been described in many clinical conditions including gelastic seizures and pseudobulbar palsy. In many of the cases described so far, laughter was not associated with feelings of mirth. However, there are a few case reports of the two occurring together. The epileptogenic zone was circumscribed in the anterior and ventral part of the supplementary motor area and the underlying dorsal cingulate cortex. The symptomatogenic area for ictal laughter in the frontal lobe may reside in the superior frontal gyrus; however, substantial data are missing about the anatomic locations of frontal regions supporting gelastic seizures. Ictal laughter is the cardinal clinical sign of gelastic seizures in hypothalamic hamartomas and may also occur in extrahypothalamic epilepsy. Focal brain lesions linked with gelastic seizure are generally located in the frontal or temporal region.
Gelastic seizures are most commonly described in patients with hypothalamic hamartoma causing precocious puberty. An MRI scan dedicated to the hypothalamus, infundibulum, and mammillary bodies may yield a hamartoma as a cause of gelastic seizure. Gelastic seizure associated with other types of lesions like focal cortical dysplasia is very uncommon and can usually be detected by high-resolution MRI but is difficult to localize with EEG. Ictal EEG shows flattening of cerebral activity, especially if associated with hypothalamic hamartoma.
Our case was distinct from gelastic seizure as laughter actually induced seizure activities that were recorded and confirmed by two-day video EEG. Theoretically, if laughter were to trigger a seizure, the focus would be in the motor component (the pericingulate premotor area or anterior cingulate region), but this could not be confirmed on the basis of the video EEG of our patient. Due to the need to establish laughter as the causative agent in the seizures, video EEG is necessary to prove the temporal association and thus to confirm the diagnosis.
Gelastic seizure without anatomical lesion usually responds well to polytherapy with topiramate and carbamazepine, though most evidence is from case reports and small case series. If it is caused by hypothalamic hamartoma, stereotactic radiofrequency ablation provides a minimally invasive and low-risk approach compared with a direct surgical approach. In our case, as no data were available in the literature, we started the patient on carbamazepine on top of the topiramate he was already on and laugh-provocation avoidance. He responded very well to the therapy. Further study is required to establish the standard treatment guidelines for this condition.