Jean-Marc Saint-Hilaire

Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy.

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 α1 subunit of the γ-aminobutyric acid receptor subtype A (GABAA), is found in affected individuals of a large French Canadian family with juvenile myoclonic epilepsy. Compared with wildtype receptors, GABAA 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.

Revisiting the role of the insula in refractory partial epilepsy

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 for separating temporally overlapping sources of neuroelectric data

SummaryThe localization of intracranial sources of EEG or MEG signals can be misled by the combined effect of several sources, as illustrated by simulated MEG data in which two of the three dipolar sources have slightly out of phase activity and partly complementary scalp topographies. These data were analysed by three different source localization methods. Fitting a single source to each sequential topography worked perfectly when only one source was active; this could also account for as much as 95% of the spatial variance of topographies resulting from two overlapping sources, although the solution was then far from any source. A principal component analysis approach followed by an oblique rotation (fitting one source to the spatial aspect of each component) correctly localized two of the sources but severely mislocated the source that was never active alone. Spatiotemporal source modeling (simultaneously fitting a set of sources to all consecutive topographies) correctly localized all three sources, provided that the parameter optimization method could escape sub-optimal local minima of the error function. Temporally overlapping sources can thus be separated and correctly identified if the mathematical model is adequate and the optimization procedure is well adapted.

Target Detection Deficits in Frontal Lobectomy

We examined the hypothesis of dorsomedial frontal lobe involvement in target detection through the effects of distractor interference and multiple target interference on unilateral lobectomy patients. Seven patients who underwent a unilateral frontal lobectomy for epilepsy involving dorsomedial cortex and variable amounts of lateral cortex were compared to 10 patients with a unilateral temporal lobectomy and to 10 normal adults on a visual character cancellation task. The task involved detecting occurrences of target characters embedded in rows of characters under three conditions: detection of one target character in the absence of distractors, detection of one target character among distractors, and detection of three targets among distractors. Visual detection performance was compared to that in the Stroop reading interference task. Frontals were predictably slower than the other groups in the baseline conditions of the character cancellation task and the Stroop task. After partialing out baseline detection performance in the character cancellation task, frontals showed an almost normal detection in the presence of distractors but were distinctly slower and made more errors than the other groups in multiple target detection. Frontals were also slower on the Stroop even after partialing out baseline naming performance. Temporals were normal on all tasks. Results suggest that frontal damage can affect selectivity in target detection as well as the Stroop and that this deficit is independent of the general psychomotor slowing observed in these patients.

Temporal and Spatial Characteristics of Intracerebral Seizure Propagation: Predictive Value in Surgery for Temporal Lobe Epilepsy

Summary: We examined the prognostic value of spatial and temporal characteristics of intracerebral propagation of seizures during temporal lobe epilepsy (TLE) surgery. Seven TLE patients resistant to standard anterotemporal lobectomy who had no known causes of resistance [e.g., extratemporal (ET), lesions, multifocal epilepsy] were matched with 7 seizure‐free patients and 7 others who were almost seizure‐free after operation. Intracerebral ictal propagation pathways were not different in the three groups. Propagation was multidirectional, most frequently to the frontal lobes and sometimes to the contra‐lateral temporal lobe (CTL). ET propagation delays were significantly shorter in resistant patients than in markedly improved patients. The resistant group also had more frequent propagation delays <1·0 s, but propagation times >1·0 s were equally likely in all groups. The extent of ET propagation and frequency of focal onsets were not different among the groups. Results suggest that very short propagation times predict reduced efficacy of operation, and that long propagation times are not related to surgical success.

Nocturnal sleep recording in partial epilepsy: a study with depth electrodes.

It has been known for centuries that sleep and epilepsy have strong reciprocal influences. This is true for all kinds of epilepsies, although the nature of this influence varies quite markedly for each type. This extensive literature cannot be reviewed here, but some recent applications of these early studies will be given.

Correlations Between Magnetic Resonance Imaging‐Based Hippocampal Sclerosis and Depth Electrode Investigation in Epilepsy of the Mesiotemporal Lobe

Summary: Quantitative analysis of hippocampal formations (HF) by magnetic resonance imaging (MRI) was correlated with depth electrode recordings in 18 patients with partial epilepsy. All had seizures of mesiotemporal origin. Electrodes explored three HF segments: amygdala and HF head and anterior and posterior HF body. Corresponding. HF measurements were made on coronal MRI sequences, and atrophy was quantified by one global and three segmental indexes of asymmetry per patient. HF from which seizure originated showed global atrophy in 15 patients. Segmental analysis demonstrated discrete tissue damage in 1 patient; thus, 16 patients (88%) had significant hippocampal atrophy ipsilateral to the mesial focus. The existence of more pronounced atrophy in segments giving rise to ictal onset than in segments without ictal onset was not statistically significant. Nevertheless, in posterior HF, all segments (four) with seizure onset were atrophied and none of the nonatrophied posterior segments (four) were at seizure origin. These findings confirm that MRI‐detected hippocampal atrophy is a powerful indicator of a mesiotemporal focus and strongly contributes to consideration of resective surgery without intracerebral EEG monitoring. Study of the distribution of maximal tissue damage may add some information, and help surgeons decide on the posterior extent of hippocampus removal. As illustrated by 3 patients who had multiple sites of seizure onset, however, the presence of this marker should not be interpreted systematically as evidence of pure mesiotemporal epilepsy.

Stimulation of human somatosensory cortex : tactile and body displacement perceptions in medial regions

We examined the somatosensory perceptions evoked by stimulation of rolandic and parietal brain regions in 40 epileptic patients undergoing a presurgical investigation with intracerebral electrodes. Bipolar stimulation trains were delivered in an incremental sequence at medial and/or lateral contact pairs of stereotaxically implanted, multi-contact electrodes, while monitoring stimulus afterdischarge propagation with electrodes in frontal and temporal lobes. Rolandic stimulation evoked contralateral sensations, whereas sensations from either side were evoked in the opercular region. Stimulation of lateral posterior parietal cortex evoked only few sensations and these were restricted to the supramarginal gyrus. Contralateral sensations were evoked in the posterior cingulate gyrus, whereas ipsilateral sensations were evoked in the vicinity of the cingulate sulcus. Complex proprioceptive sensations in the form of bilateral feelings of levitation were elicited in a medial parietal region around the subparietal sulcus and not at any other site. These perceptions were not accompanied by any movement, tactile, or vestibular sensations, suggesting that the human sub-parietal sulcus region is linked to the proprioceptive processing system.

Electrical stimulation of the human brain in epilepsy.

Summary: The concordance between the epileptogenic area as determined by intracranially recorded spontaneous seizure onset and that determined by electrically induced auras or seizures in 126 patients with medically intractable epilepsy was studied. Four to 11 multicontact depth electrodes were chronically implanted in patients as part of a preoperative investigation procedure. Local‐ ization of the epileptic area was obtained from the record‐ ing of three spontaneous seizures and from stimulation data including self‐reported auras, seizures, and intracra‐ nial EEG afterdischarges recorded during an incremental stimulation sequence at all cortical pairs of contacts. Positive responses to stimulation were obtained in 63% of patients. Concordance between spontaneous and induced auras or seizures was >90% with single unilateral foci and less with multiple foci. Stimulation data reliably predicted the resection area in unilateral and bilateral temporal foci but not in other locations. Afterdischarge thresholds were not reliable predictors of the spontaneous seizure focus. The intracranial stimulation procedure used appears to provide useful confirmatory and complementary localiz‐ ing information in relation to that obtained from sponta‐ neous seizures.

Jumping Frenchmen of Maine.

The “Jumping Frenchmen of Maine” were described by George Beard in 1878. They had an excessive startle response, sometimes with echolalia, echopraxia, or forced obedience. In 1885, Gilles de la Tourette concluded that “jumping” was similar to the syndrome that now bears his name. Direct observations of jumpers have been scarce. We studied eight jumpers from the Beauce region of Quebec. In our opinion, this phenomenon is not a neurologic disease, but can be explained in psychological terms as operant conditioned behavior. Our cases were related to specific conditions in lumber camps in the 19th and the beginning of the 20th century.