Germline, germline mosaic, and brain somatic DEPDC5 mutations may cause epilepsy associated with FCD, reinforcing the link between mTORC1 pathway and FCDs. Similarly to other mTORopathies, a "2-hit" mutational model could be responsible for cortical lesions. Our study also indicates that epilepsy surgery is a valuable alternative in the treatment of drug-resistant DEPDC5-positive focal epilepsies, even if the MRI is unremarkable.

mcgill.ca).

Summary Purpose:  Recent evidence suggesting that some epilepsy surgery failures could be related to unrecognized insular epilepsy have led us to lower our threshold to sample the insula with intracerebral electrodes. In this study, we report our experience resulting from this change in strategy. Methods:  During the period extending from October 2004 to June 2007, 18 patients had an intracranial study including 10 with insular coverage. The decision to sample the insula with intracerebral electrodes was made in the context of (1) nonlesional parietal lobe‐like epilepsy; (2) nonlesional frontal lobe‐like epilepsy; (3) nonlesional temporal lobe‐like epilepsy; and (4) atypical temporal lobe‐like epilepsy. Results:  Intracerebral recordings confirmed the presence of insular lobe seizures in four patients. Cortical stimulation performed in 9 of 10 patients with insular electrodes elicited, in decreasing order of frequency, somatosensory, viscerosensory, motor, auditory, vestibular, and speech symptoms. Discussion:  Our results suggest that insular cortex epilepsy may mimic temporal, frontal, and parietal lobe epilepsies and that a nonnegligeable proportion of surgical candidates with drug‐resistant epilepsy have an epileptogenic zone that involves the insula.