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Epileptic spasms (ES) are common in tuberous sclerosis complex (TSC). However, the underlying network alterations and relationship with epileptogenic tubers are poorly understood. We examined interictal functional connectivity (FC) using stereo-electroencephalography (SEEG) in patients with TSC to investigate the relationship between tubers, epileptogenicity, and ES.We analyzed 18 patients with TSC who underwent SEEG (mean age = 11.5 years). The dominant tuber (DT) was defined as the most epileptogenic tuber using the epileptogenicity index. Epileptogenic zone (EZ) organization was quantitatively separated into focal (isolated DT) and complex (all other patterns). Using a 20-min interictal recording, FC was estimated with nonlinear regression, hSix patients had ES as a current seizure type at time of SEEG. ES patients had a greater number of tubers with a fluid-attenuated inversion recovery hypointense center (p .001), and none had TSC1 mutations. The presence of ES was independently associated with increased FC within both intrazone (p = .033) and interzone (p = .011) networks. Post hoc analyses identified that increased FC was associated with ES across tuber and nontuber networks. EZ organization and epileptogenicity biomarkers were not associated with FC.Increased cortical synchrony among both tuber and nontuber networks is characteristic of patients with ES and independent of both EZ organization and tuber epileptogenicity. This further supports the prospect of FC biomarkers aiding treatment paradigms in TSC.

Temporal plus epilepsy (TPE) represents a rare type of epilepsy characterized by a complex epileptogenic zone including the temporal lobe and the close neighboring structures. We investigated whether the complete resection of temporal plus epileptogenic zone as defined through stereoelectroencephalography (SEEG) might improve seizure outcome in 38 patients with TPE.Inclusion criteria were as follows: epilepsy surgery performed between January 1990 and December 2001, SEEG defining a temporal plus epileptogenic zone, unilobar temporal operations ("temporal lobe epilepsy [TLE] surgery") or multilobar interventions including the temporal lobe ("TPE surgery"), magnetic resonance imaging either normal or showing signs of hippocampal sclerosis, and postoperative follow-up of at least 12 months. For each assessment of postoperative seizure outcome, at 1, 2, 5, and 10 years, we carried out descriptive analysis and classical tests of hypothesis, namely, Pearson χTwenty-one patients underwent TPE surgery and 17 underwent TLE surgery with a follow-up of 12.4 ± 8.16 years. In the multivariate models, there was a significant effect of the time from surgery on Engel Class IA versus IB-IV outcome, with a steadily worsening trend from 5-year follow-up onward. TPE surgery was associated with better results than TLE surgery.This study suggests that surgical outcome in patients with TPE can be improved by a tailored, multilobar resection and confirms that SEEG is mandatory when a TPE is suspected.

In patients with intractable partial epilepsy who are eligible for epilepsy surgery, the best seizure control requires complete resection of the epileptogenic zone. When the epileptogenic zone is located very near to, or even with the eloquent cortex, this can be a challenge. In this study, we investigated the efficacy of awake craniotomy techniques to completely resect these epileptic zones while preserving the neural functions. We conducted a retrospective cohort study of 17 consecutive patients with intractable partial seizures of different aetiologies (non-lesional epilepsy [n=3], tuberous sclerosis [n=1], hypoxic ischaemic insult [n=1], dysembryoplastic neuroepithelial tumours [DNET] [n=2], focal cortical dysplasia type 2 [FCD] [n=4], and other malformations of cortical development [n=6]), located in eloquent language cortex (frontal [n=7], insular [n=5], and latero-temporal [n=5] regions). All patients were operated on between 2010 and 2019 for resective epilepsy surgery under awake conditions, with the aid of direct cortical stimulation. This report aimed to study the feasibility, efficacy and limitations of using the awake craniotomy technique for surgical resections of epileptogenic zones involving eloquent language cortex. Postoperative epilepsy control and neurological function were assessed and followed. The mean follow-up period was 5.7 years. In one patient, the surgery was aborted before resection. In the other patients, Engel Class I was achieved in seven patients (43.75%) and Engel Class II in four patients (25%), and worthwhile improvement (Engel Class I and II) was achieved in 11 patients (68.75%). Postoperative neurological deficits were encountered in four patients (23.5%). However, all these deficits were regressive and were absent at the last follow-up visit. Using the awake craniotomy technique, seizure freedom can be achieved in a high proportion of patients with epileptogenic zones located in language areas, who were previously considered only candidates for palliative measures.

Despite numerous studies suggesting the role of insular cortex in the control of autonomic activity, the exact location of cardiac motor regions remains controversial. We provide here a functional mapping of autonomic cardiac responses to intracortical stimulations of the human insula. The cardiac effects of 100 insular electrical stimulations into 47 epileptic patients were divided into tachycardia, bradycardia, and no cardiac response according to the magnitude of RR interval (RRI) reactivity. Sympathetic (low frequency, LF, and low to high frequency powers ratio, LF/HF ratio) and parasympathetic (high frequency power, HF) reactivity were studied using RRI analysis. Bradycardia was induced by 26 stimulations (26%) and tachycardia by 21 stimulations (21%). Right and left insular stimulations induced as often a bradycardia as a tachycardia. Tachycardia was accompanied by an increase in LF/HF ratio, suggesting an increase in sympathetic tone; while bradycardia seemed accompanied by an increase of parasympathetic tone reflected by an increase in HF. There was some left/right asymmetry in insular subregions where increased or decreased heart rates were produced after stimulation. However, spatial distribution of tachycardia responses predominated in the posterior insula, whereas bradycardia sites were more anterior in the median part of the insula. These findings seemed to indicate a posterior predominance of sympathetic control in the insula, whichever the side; whereas the parasympathetic control seemed more anterior. Dysfunction of these regions should be considered when modifications of cardiac activity occur during epileptic seizures and in cardiovascular diseases.

Objective: Despite numerous studies suggesting the role of insular cortex in the processing of gustatory and olfactory inputs, the exact location of olfacto-gustatory representation in the insula remains controversial. Here we provide a functional mapping of olfactory-gustatory responses to stimulation of the human insular cortex. Methods: We reviewed 651 electrical stimulations of the insula that were performed in 221 patients, using stereotactically implanted depth electrodes, during the pre-surgical evaluation of drug refractory epilepsy. Results: Gustatory sensations were evoked in 15 (2.7%) of the 550 stimulations that elicited a clinical response. They were exclusively obtained after stimulation of a relatively delimited zone of insula, located in its mid-dorsal part (posterior short gyrus). Six olfactory sensations (1.1%) could be obtained during stimulations of an insular region that partially overlapped with the gustatory representation. Interpretation: Our study provides a functional mapping of gustatory representation in the insular posterior short gyrus and the first detailed description of olfactory sensations obtained by direct stimulation of mid-dorsal insula. Our data also show a spatial overlap between gustatory, olfactory and oral somatosensory representation in the mid-dorsal insula, and suggest that this part of the insula may be an integrated oral sensory region that plays a key role in flavor perception. It also indicates that dysfunction in this region should be considered during the evaluation of gustatory and olfactory epileptic seizures. This article is protected by copyright. All rights reserved.

Objective: The present study provides a functional mapping of vestibular responses in the human insular cortex. Methods: A total of 642 electrical stimulations of the insula were performed in 219 patients, using stereotactically implanted depth electrodes, during the presurgical evaluation of drug-refractory partial epilepsy. We retrospectively identified 41 contacts where stimulation elicited vestibular sensations (VSs) and analyzed their location with respect to (1) their stereotactic coordinates (for all contacts), (2) the anatomy of insula gyri (for 20 vestibular sites), and (3) the probabilistic cytoarchitectonic maps of the insula (for 9 vestibular sites). Results: VSs occurred in 7.6% of the 541 evoked sensations after electrical stimulations of the insula. VSs were mostly obtained after stimulation of the posterior insula, that is, in the granular insular cortex and the postcentral insular gyrus. The data also suggest a spatial segregation of the responses in the insula, with the rotatory and translational VSs being evoked at more posterior stimulation sites than other less definable VSs. No left-right differences were observed. Interpretation: These results demonstrate vestibular sensory processing in the insula that is centered on its posterior part. The present data add to the understanding of the multiple sensory functions of the insular cortex and of the cortical processing of vestibular signals. The data also indicate that lesion or dysfunction in the posterior insula should be considered during the evaluation of vestibular epileptic seizures.

Summary: Purpose: Several animal studies suggest that the thalamus might be involved in the maintenance and propagation of epileptic seizures. However, electrophysiologic evidence for this implication in human partial epileptic seizures is still lacking. Considering the rich and reciprocal connectivity of the medial pulvinar (PuM) with the temporal lobe, we evaluated a potential participation of this thalamic nucleus in temporal lobe epilepsy (TLE). Methods: The electrophysiologic activity of PuM was recorded during stereoelectroencephalographic exploration of spontaneous temporal lobe seizures in 14 patients referred for presurgical assessment of refractory TLE. Results: We recorded PuM ictal activity in 80% of the 74 seizures that we analyzed. This activity was characterized by rhythmic slow-waves or rhythmic spikes (RSW-RS) or both or by low-voltage fast activity (LVFA) in 64% and 36% of seizures, respectively. RSW-RS occurred mostly in seizures arising from mesiotemporal structures, whereas LVFA was more frequently observed in seizures of neocortical origin. In the 15 seizures without PuM ictal activity, spreading of the seizure outside the onset zone never occurred, whereas it did in 78% of seizures with PuM ictal involvement. Discharge propagation was systematic when PuM involvement corresponded to LVFA, whatever the seizure onset zone was, whereas it represented only 66% of the seizures when PuM exhibited RSW-RS. Conclusions: This study shows that ictal changes in PuM activity are frequently observed during temporal lobe seizures and suggests that this thalamic nucleus might participate in their propagation.

Summary: Purpose: The lateralizing value of ictal head deviation (HD) in frontal lobe epilepsy (FLE) is a matter of debate. Although FLE is typically associated with tonic or clonic HD contralateral to seizure onset, ipsilateral HD has been noted in numerous reports. Whether both types of HD can be distinguished according to their clinical patterns has not yet been specifically investigated. Methods: We studied the clinical pattern and time of occurrence of HD of 129 seizures in 13 consecutive patients, who underwent successful surgery for FLE, including 12 investigated with an intracerebral stereotactic EEG procedure. Results: Ictal HD was ipsilateral to the epileptogenic zone (EZ) in four (30%) patients and 27 (20.9%) seizures and contralateral in five (38%) patients and 15 (11.6%) seizures. Ipsilateral HD was rarely tonic and never associated with clonic manifestation. Contralateral HD was always tonic, unnatural, and associated with hemifacial clonic movements in 86% of seizures. Ipsilateral HD occurred earlier than contralateral HD (p < 0.03), with a mean delay of 1 ± 2s after the first detectable ictal sign, as compared with a delay of 17 ± 11 s for contralateral HD. Moreover, ipsilateral HD always occurred before contralateral HD when both signs coexisted in the same seizure. Our patients with ipsilateral HD demonstrated either an anterior or dorsolateral frontal EZ. Conclusions: Ipsilateral HD is a common ictal sign during FLE and can be distinguished from contralateral HD by its time of occurrence at or immediately after seizure onset and its lacking association with clonic movements. Ke yW ords: Version— Head deviation—Frontal lobe epilepsy.

Summary: Purpose: Depth electrodes recordings may be required in some cases of epilepsy surgery to delineate the best region for cortical resection. We usually implant depth electrodes according to Talairach’s stereoelectroencephalography (SEEG) method. By using these permanently implanted depth electrodes, we are able to perform radiofrequency (RF)-thermolesions of the epileptic foci. We report the technical data required to perform such multiple cortical thermolesions, as well as preliminary results in terms of seizure outcome in a group of 20 patients. Methods: Lesions were performed by using 100- to 110-mA bipolar current (50 V), applied for 10 to 50 s. Each thermocoagulation produced a 5- to 7-mm diameter cortical lesion. In total, two to 16 lesions were performed in each of the 20 patients. Lesions were placed without anesthesia. No general or neurologic complication occurred during the procedures. Two transient postprocedure side effects, consisting of paresthetic sensations in the mouth and mild apraxia of the hand, were observed. Results: At a follow-up time of 8 to 31 months (mean, 19 months), 15% of the patients became seizure free, 40% experienced a ≥80% reduction of their seizure frequency, and 45% were not significantly improved. Conclusions: SEEG-guided RF thermolesions is a safe technique. Our preliminary results indicate that such lesions can lead to a significant reduction of seizure frequency and could be proposed as a palliative procedure if no resective surgery is possible. A randomized controlled trial is needed to determine which patients are likely to respond to SEEG-guided RF ther

Summary: Purpose: In this study, we report the clinical features of insular lobe seizures based on data from video and stereo-electroencephalographic (SEEG) ictal recordings and direct electric insular stimulation of the insular cortex performed in patients referred for presurgical evaluation of temporal lobe epilepsy (TLE). Methods: Since our first recordings of insular seizures, the insular cortex has been included as one of the targets of stereoelectroencephalographic (SEEG) electrode implantation in 50 consecutive patients with TLE whose seizures were suspected to originate from, or rapidly to propagate to, the perisylvian cortex. In six, a stereotyped sequence of ictal symptoms associated with intrainsular discharges could be identified. Results: This ictal sequence occurred in full consciousness, beginning with a sensation of laryngeal constriction and paresthesiae, often unpleasant, affecting large cutaneous territories, most often at the onset of a complex partial seizure (five of the six patients). It was eventually followed by dysarthric speech and focal motor convulsive symptoms. The insular origin of these symptoms was supported by the data from functional cortical mapping of the insula by using direct cortical stimulations. Conclusions: This sequence of ictal symptoms looks reliable enough to characterize insular lobe epileptic seizures (ILESs). Observation of this clinical sequence at the onset of seizures on video-EEG recordings in TLE patients strongly suggests that the seizure-onset zone is located not in the temporal but in the insular lobe; recording directly from the insular cortex should occur before making any decision regarding epilepsy surgery. Key Words: Insula—Temporal lobe epilepsy—Partial seizures—SEEG—Epilepsy surgery.

The human brain is expert in analyzing rapidly and precisely facial features, especially emotional expressions representing a powerful communication vector. The involvement of insula in disgust recognition has been reported in behavioral and functional imaging studies. However, we do not know whether specific insular fields are involved in disgust processing nor what the processing time course is. Using depth electrodes implanted during presurgical evaluation of patients with drug-refractory temporal lobe epilepsy, we recorded intracerebral event-related potentials to human facial emotional expressions, that is, fear, disgust, happiness, surprise, and neutral expression. We studied evoked responses in 13 patients with insular contacts to specify the insular fields involved in disgust processing and assess the timing of their activation. We showed that specific potentials to disgust beginning 300 milliseconds after stimulus onset and lasting 200 milliseconds were evoked in the ventral anterior insula in four patients. The occurrence and latency of event-related potentials to disgust in the ventral anterior insula were affected by selective attention. The analysis of spatial and temporal characteristics of insular responses to disgust facial expression lead us to underline the crucial role of ventral anterior insula in the categorization of facial emotional expressions, particularly the disgust.

The role of the insular cortex in the genesis of temporal lobe epileptic (TLE) seizures has been investigated in 21 patients with drug-refractory TLE using chronic depth stereotactic recordings of the insular cortex activity and video recordings of ictal symptoms during 81 spontaneous electroclinical seizures. All of the recorded seizures were found to invade the insula, most often after a relay in the ipsilateral hippocampus (19/21 patients). However, 2 patients had seizures that originated in the insular cortex itself. Ictal symptoms associated with the insular discharges were similar to those usually attributed to mesial temporal lobe seizures, so that scalp video-electroencephalographic monitoring does not permit making any difference between ictal symptoms of temporo-mesial and insular discharges. A favorable outcome was obtained after a temporal cortectomy sparing the insular cortex in 15 of 17 operated patients. Seizures propagating to the insular cortex were found to be fully controlled by surgery, whereas those originating in the insular cortex persisted after temporal cortectomy. The fact that seizures originating in the insular cortex are not influenced by temporal lobectomy is likely to explain some of the failures of this surgical procedure in TLE.

Summary: Purpose: We report the results of 75 intracortical electrical stimulations of the insular cortex performed in 14 patients during stereo-electroencephalography (SEEG) investigation of drug-resistant partial epilepsy. The insular cortex was investigated on electroclinical arguments suggesting the possibility of a perisylvian spread or a rapid multilobar diffusion of the discharges during video EEG. Methods: In these 14 patients, 27 stereotactically implanted transopercular electrodes reached the insular cortex (11 the right insula, 16 the left insula). Square pulses of current were applied between the two deepest adjacent contacts of each transopercular electrode using low (1 Hz) or high-frequency (50 Hz) stimulation. Only symptoms evoked in the absence of afterdischarges were analyzed. Results: Clinical responses were evoked in 10 of the 14 patients (in 20 of the 27 insular sites) and showed a clear topographic specificity inside the insular cortex. Viscerosensitive and visceromotor responses, similar to those evoked by temporomesial stimulation, were evoked by anterior insular stimulation and somesthetic sensation, similar to those evoked by opercular cortex stimulation, by posterior insular stimulation. Conclusions: The topographic organization of the induced responses within the insular cortex suggest that two different cortical networks, a visceral network extending to the temporomesial structures and a somesthetic network reaching the opercular cortex, are disturbed with stimulation of the anterior or the posterior insula, respectively. Thus ictal symptoms associated with the spread of the epileptic discharges to the insular cortex might be difficult to distinguish from those usually reported during temporomesial or opercular discharges.