Case Report: Right frontal periventricular heterotopia underlying secondary network epilepsy with a Lennox-Gastaut phenotype: multimodal SEEG, CCEP, and rs-fMRI evidence.

OBJECTIVE

Lennox-Gastaut syndrome (LGS) is generally regarded as a developmental and epileptic encephalopathy involving distributed brain networks, although a focal structural abnormality may occasionally recruit bilateral cortical and thalamic circuits and produce an LGS phenotype. We characterized the spatiotemporal organization of such a network and its changes after focal SEEG-guided radiofrequency thermocoagulation (RF-TC).

METHODS

A 50-year-old woman with drug-resistant epilepsy, multiple seizure types, diffuse slow spike-and-wave discharges, generalized paroxysmal fast activity, intellectual impairment, and right frontal periventricular heterotopia (PVH) underwent stereo-electroencephalography (SEEG). Cortico-cortical evoked potentials (CCEPs) were acquired before and after SEEG-guided radiofrequency thermocoagulation (RF-TC). Resting-state functional MRI (rs-fMRI), obtained before and 3 months after RF-TC, was analyzed using three seeds: the entire right frontal PVH and the right and left centromedian thalamic nuclei (CM).

RESULTS

SEEG identified the earliest sustained ictal activity within the sampled right frontal PVH-related medial contacts, accompanied by high-frequency activity. This was followed by ipsilateral lateral frontal recruitment, contralateral frontal synchronization, and subsequent bilateral CM involvement. Two-stage RF-TC of the onset and early-recruited networks was followed by seizure freedom through 9 months. After RF-TC, right-sided stimulation produced markedly attenuated lesion-related CCEP responses, whereas left-sided responses and responses between thalamic contacts showed little appreciable change. Descriptive rs-fMRI difference maps demonstrated decreased local frontal connectivity around the treated territory and increased long-range connectivity for the PVH seed; both CM seeds showed predominantly increased connectivity with distributed cortical and cerebellar regions.

CONCLUSION

In this patient, a focal PVH-related epileptogenic network was associated with secondary bilateral cortical and thalamic recruitment underlying an LGS phenotype. CCEP and rs-fMRI captured complementary aspects of postoperative network change: attenuation of stimulation-evoked propagation and postoperative changes in intrinsic functional connectivity, respectively.