From hypothalamic hamartoma to cortex: what can be learnt from depth recordings and stimulation?

Patients having a hypothalamic hamartoma (HH) frequently present gelastic or dacrystic seizures, and they often later experience multiple additional seizure types which lead to a severe epileptic encephalopathy. There is now increasing evidence that the HH itself plays a crucial role in this syndrome, but the relationships between the lesion and the different types of seizures remain a questionable issue. Stereotactic intracerebral EEG recordings were performed in 5 patients suffering from a medically intractable epilepsy associated with a HH. The hamartoma was investigated in all cases, and various cortical areas were also evaluated in 4 of the 5 patients. The epileptic discharges arose and remained confined within the hamartoma in 3 of the 4 patients in whom laughing and crying episodes were recorded. In addition, interictal spikes were recorded from the hamartoma in 4 of the 5 patients, whereas the stimulation of the HH could reproduce gelastic or dacrystic episodes in 3. The three patients in whom other types of seizure were recorded showed that the latter were associated with cortical ictal discharges not affecting the HH. Ictal onset appeared either bifrontal, right fronto-central and lateral temporal, or bifrontal with a right side predominance. The cingulate gyrus was involved in all these 3 cases, and the lateralization of the ictal discharges was always ipsilateral to the predominating side of the hamartoma. Interestingly, these seizure types were sometimes immediately preceded by the laughing or crying attacks, as if ictal discharges within the hamartoma triggered those which seemed to originate in the cortex. Therefore, if these findings confirm the intrinsic epileptogenicity of HH, they also demonstrate that epileptic seizures associated with HH can exhibit different types of electroclinical patterns. We propose a speculative pathophysiology in which the mamillo-thalamo-cingulate tract would serve as a relay of HH discharges towards the cortex, the excitability of which would then progressively increase, first leading to cortical interictal epileptiform abnormalities and then to seizures of cortical origin. Whether this proposal of secondary epileptogenesis is valid or not remains a major issue, since it could provide arguments on the moment to discuss surgery.