Interictal spike EEG source analysis in hypothalamic hamartoma epilepsy

Abstract

Objective: The epilepsy associated with the hypothalamic hamartomas constitutes a syndrome with peculiar seizures, usually refractory to medical therapy, mild cognitive delay, behavioural problems and multifocal spike activity in the scalp electroencephalogram (EEG). The cortical origin of spikes has been widely assumed but not specifically demonstrated.Methods: We present results of a source analysis of interictal spikes from 4 patients (age 2-25 years) with epilepsy and hypothalamic hamartoma, using EEG scalp recordings (32 electrodes) and realistic boundary element models constructed from volumetric magnetic resonance imaging (MRIs). Multifocal spike activity was the most common finding, distributed mainly over the frontal and temporal lobes. A spike classification based on scalp topography was done and averaging within each class performed to improve the signal to noise ratio. Single moving dipole models were used, as well as the Rap-MUSIC algorithm.Results: All spikes with good signal to noise ratio were best explained by initial deep sources in the neighbourhood of the hamartoma, with late sources located in the cortex. Not a single patient could have his spike activity explained by a combination of cortical sources.Conclusions: Overall, the results demonstrate a consistent origin of spike activity in the subcortical region in the neighbourhood of the hamartoma, with late spread to cortical areas. q

Analysis of the EEG dynamics of epileptic activity in gelastic seizures using decomposition in independent components

“…1(c)-3(c). This is also compatible with deep sources strongly attenuated and low pass filtered before their detection in scalp electrodes and agrees well with a similar trend demonstrated for interictal spikes in a previous study in patients with hypothalamic hamartoma (Leal et al, 2002). The more superficial ictal generators are located in the lobes with more consistent interictal spike activity (Table 1), which suggests a selective propagation of deep epileptic activity to particular cortical areas, frontal in patient 1 and temporal in patient 3.…”

“…Clinical data is presented in Table 1, and has been detailed previously for patients 2 (Leal et al, 2003) and 3 (Leal et al, 2002).…”

“…In previous studies, we used source analysis techniques of the interictal spike activity of patients with hypothalamic hamartomas to demonstrate the existence of deep generators in the neighborhood of the lesion (Leal et al, 2002) and also that the EEG scalp topography can show frontal or temporal dominance depending on the particular anatomy of the connection of the hamartoma to the hypothalamus (Leal et al, 2003).…”

Hypothalamic Hamartoma

“…27,37) The results of ictal single photon emission computed tomography studies and interictal EEG source analysis gave further support to the hypothesis of intrinsic epileptogenicity. 38,39) MR spectroscopy 26,38,56) or stereotactic radiation 5,62) supports this suggestion. A neuroendocrine mechanism was suggested to explain the intrinsic epileptogenesis.…”

Radiosurgery for hypothalamic hamartomas

“…The hypothesis of an intrinsic epileptogenesis of HH gained impetus after the stereo-EEG demonstration of ictal onsets originating from the hypothalamic lesion, 32 and was further corroborated by subsequent reports showing production of typical gelastic seizures by depth electrode stimulation, ictal SPECT studies demonstrating HH hyperperfusion, and interictal spike source analysis. 4,9,11,12,16,21,22,26,35,45 The epileptogenic activity of HHs has been recently demonstrated at the cellular level: detailed electrophysiological analysis of slices taken from surgical specimens showed the predominance of small GABAergic inhibitory neurons exhibiting an intrinsic "pacemaker-like" behavior. 54 The concept that surgical intervention should mainly target the HH was not easy to accept.…”