Abstracts

Rationale: Epilepsy associated with nodular heterotopia, especially in those with multiple heterotopic nodules, is particularly difficult to treat. A large epileptic network that can involve heterotopic nodules and overlying cortices is believed to be responsible for the epileptogenicity. The connectivity between the nodules and the cortices has been studied but not the connectivity between the nodules themselves. We sought to determine if the connectivity between nodules is detectable using fMRI and if this connectivity measure actually reflects synchronized neuronal activity between the nodules. If it does, we want to know the role of this inter-nodular connectivity in the epileptogenicity associated with multiple heterotopic nodules. Methods: We studied 15 patients with epilepsy associated with multiple heterotopic nodules; eight underwent subsequent stereo-EEG and had at least two nodules implanted, each with at least one electrode. We first examined the connectivity between nodules using functional MRI. We then examined the correspondence between the connectivities measured using fMRI and using intracerebral EEG. To explore the role of connectivity between nodules in seizure generation, we examined the seizures recorded during the intracerebral EEG study and compared (1) the speed of seizure spread between connected and unconnected nodules; and (2) the connectivity among three possible combinations of nodule pairs: both nodules involved at seizure onset, only one nodule involved, and none of the nodules involved. Results: Sixty-three nodules from 15 patients were studied: each patient had two to nine separable non-contiguous nodules. Connectivity analysis using fMRI revealed significant connection to at least one other nodule in 81% of nodules. Significant connection was found in 66.7% (26.8-91.7%), median (interquartile range), of the possible nodule pairs of each patient. There was no difference in the likelihood of two nodules being connected for nodule pairs located within the same hemisphere and those located in different hemispheres (p=0.8569). Among the 49 heterotopic nodule pairs studied with iEEG, the likelihood of interictal activity, represented by the gamma envelope of the iEEG, being synchronized between two nodules was significantly higher in connected than in unconnected pairs (p<0.05). Seizure spread faster between connected than unconnected nodules (p<0.05). Connectivity was significantly higher when both nodules of a pair were involved at seizure onset than when only one or none was involved. Conclusions: This study revealed that the connectivity between heterotopic nodules can be reliably and non-invasively detected using fMRI and is more prevalent than has been reported. These functional connections are predictive of the synchrony of interictal epileptic activity between the nodules and to the ability of nodules to generate synchronous seizure onsets or rapid seizure spread. These findings may help understand the treatment-resistance of these patients and better target the likely epileptogenic nodules. Funding: This work was supported by the Canadian Institutes of Health Research (FDN 143208). Dr. H.M.K. was supported by Mark Rayport and Shirley Ferguson Rayport fellowship in epilepsy surgery and the Preston Robb fellowship of the Montreal Neurological Institute (Canada), a research fellowship of the Uehara Memorial Foundation (Japan), travel grants from Osaka Medical Research Foundation for Intractable Diseases (Japan) and Japan Epilepsy Research Foundation (Japan).