Although many genes that predispose for epilepsy in humans have been determined, those that underlie the classical syndromes of idiopathic generalized epilepsy (IGE) have yet to be identified. We report that an Ala322Asp mutation in GABRA1, encoding the alpha1 subunit of the gamma-aminobutyric acid receptor subtype A (GABA(A)), is found in affected individuals of a large French Canadian family with juvenile myoclonic epilepsy. Compared with wildtype receptors, GABA(A) receptors that contain the mutant subunit show a lesser amplitude of GABA-activated currents in vitro, indicating that seizures may result from loss of function of this inhibitory ligand-gated channel. Our results confirm that mutation of GABRA1 predisposes towards a common idiopathic generalized epilepsy syndrome in humans.

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.

Insular surgery is both safe and beneficial when it is well planned and performed with modern microsurgical techniques and good anatomical knowledge. Insulectomy is associated with little permanent morbidity and a high rate of seizure control. To the authors' knowledge, this is the first series of insulectomies predominantly performed for refractory epilepsy since those performed by Penfield.