Hypothalamic hamartoma: Is the epileptogenic zone always hypothalamic? Arguments for independent (third stage) secondary epileptogenesis

Abstract

SUMMARYGelastic seizures associated with hypothalamic hamartomas (HHs) are a clinicoradiologic syndrome presenting with a variety of symptoms, including pharmacoresistant epilepsy with multiple seizure types, electroencephalography (EEG) abnormalities, precocious puberty, behavioral disturbances, and progressive cognitive deterioration. Surgery in adults provides seizure freedom in only one third of patients. The poor results of epilepsy surgery could be explained by an extrahypothalamic epileptogenic zone. The existence of an independent, secondary epileptogenic area with persistent seizures after resection of the presumably primary lesion supports the concept of a "hypothalamic plus" epilepsy. "Hypothalamic plus" epilepsy could be related to either an extrahypothalamic structural lesion (visible on magnetic resonance imaging [MRI] or on neuropathology) or if the former is absent, to a functional alteration with enhanced epileptogenic properties due to a process termed secondary epileptogenesis. We report two patients with gelastic seizures with HH (gelastic seizures isolated or associated with dyscognitive seizures of temporal origin). Both patients underwent twostep surgery: first an endoscopic resection of the HH, followed at a later time by temporal lobectomy. Both patients became seizure-free only after the temporal lobectomy. In both cases, neuropathology failed to demonstrate a significant structural lesion in the temporal lobe. To our knowledge, for the first time, these two cases suggest the existence of independent secondary epileptogenesis in humans.

Clinical features and evolution of the gelastic seizures–hypothalamic hamartoma syndrome

“…The latter hypothesis, consisting of a kindling model of epileptogenesis, introduces the variable “time” in the prognosis of the syndrome after surgery. Scholly et al . recently highlighted that successful surgery is often achievable for children with HH and should be performed as early as possible.…”

The long-term course of temporal lobe epilepsy: From unilateral to bilateral interictal epileptiform discharges in repeated video-EEG monitorings

“…[28] It is assumed that seizure-induced neuronal death and associated fibre degeneration leads to mossy fibre sprouting and synaptic reorganization thus forming recurrent excitatory circuits. This is regarded as the underlying pathological mechanism.…”

Hypothalamic hamartoma: Epileptogenesis beyond the lesion?

“…However, it has been observed that additional seizure types often appeared with a clear delay following the start of gelastic seizures during the clinical course . We also observed this phenomenon in the Strasbourg‐Kork series of 15 patients explored for an HH . All patients experienced gelastic seizures, and they also presented one or several other seizure types.…”

“…These cases illustrate the existence of an independent, extrahypothalamic secondary epileptogenic zone, without running down after the removal of the presumably primary epileptogenic lesion. Thus they argue for existence of a third, independent stage of secondary epileptogenesis in humans …”