Deep retroinsular and parieto-opercular origin of vestibular symptoms: A stereoelectrocenphalography (SEEG) study.

Several studies have shown that the retroinsular and posterior parietal operculum regions play a central role in vestibular processing. Electrical stimulations performed during stereoelectroencephalography (SEEG) in patients with focal drug-resistant epilepsy could contribute to the analysis of this area. Among the 264 SEEGs performed in both an adult and a paediatric epilepsy surgery centre, we retrospectively identified 24 patients (9%) reporting vertigo during electrical stimulations (ES). In seven of them (29% of patients experiencing vertigo during ES), it was evoked by stimulating the retroinsular region. The reported responses were mostly not rotatory sensations but actually illusions of body, limb or limb segment movement. The involved area is limited. Moreover, two patients reported having the same symptoms at the beginning of their seizures starting in the same region. Our case study confirms the pivotal role of the retroinsular and posterior parietal operculum areas in vestibular responses, and we therefore advise the exploration of this region when patients report an illusion of body movement at the beginning of their seizures.

Predictors of outcomes after surgery for medically intractable insular epilepsy: A systematic review and individual participant data meta-analysis.

Insular epilepsy (IE) is an increasingly recognized cause of drug-resistant epilepsy amenable to surgery. However, concerns of suboptimal seizure control and permanent neurological morbidity hamper widespread adoption of surgery for IE. We performed a systematic review and individual participant data meta-analysis to determine the efficacy and safety profile of surgery for IE and identify predictors of outcomes. Of 2483 unique citations, 24 retrospective studies reporting on 312 participants were eligible for inclusion. The median follow-up duration was 2.58 years (range, 0-17 years), and 206 (66.7%) patients were seizure-free at last follow-up. Younger age at surgery (≤18 years; HR = 1.70, 95% CI = 1.09-2.66, P = .022) and invasive EEG monitoring (HR = 1.97, 95% CI = 1.04-3.74, P = .039) were significantly associated with shorter time to seizure recurrence. Performing MR-guided laser ablation or radiofrequency ablation instead of open resection (OR = 2.05, 95% CI = 1.08-3.89, P = .028) was independently associated with suboptimal or poor seizure outcome (Engel II-IV) at last follow-up. Postoperative neurological complications occurred in 42.5% of patients, most commonly motor deficits (29.9%). Permanent neurological complications occurred in 7.8% of surgeries, including 5% and 1.4% rate of permanent motor deficits and dysphasia, respectively. Resection of the frontal operculum was independently associated with greater odds of motor deficits (OR = 2.75, 95% CI = 1.46-5.15, P = .002). Dominant-hemisphere resections were independently associated with dysphasia (OR = 13.09, 95% CI = 2.22-77.14, P = .005) albeit none of the observed language deficits were permanent. Surgery for IE is associated with a good efficacy/safety profile. Most patients experience seizure freedom, and neurological deficits are predominantly transient. Pediatric patients and those requiring invasive monitoring or undergoing stereotactic ablation procedures experience lower rates of seizure freedom. Transgression of the frontal operculum should be avoided if it is not deemed part of the epileptogenic zone. Well-selected candidates undergoing dominant-hemisphere resection are more likely to exhibit transient language deficits; however, the risk of permanent deficit is very low.

Visceral and emotional responses to direct electrical stimulations of the cortex.

OBJECTIVE: Visceral sensations are bodily symptoms which are component manifestations of emotions frequently reported during epileptic seizures. Nowadays, the underlying mechanism and location of brain areas involved in the processing of these sensations remain unclear. Our objectives were to characterize the type and frequency of visceral and emotional responses evoked by electrical stimulations, to produce a mapping of brain structures involved in their processing, and to assess the link between visceral sensations and emotional feelings. METHODS: We reviewed 12,088 bipolar stimulations performed in 203 patients during the presurgical evaluation of drug refractory epilepsy. Responses to stimulation were divided into viscero-sensitive, viscero-vegetative, and emotional sensations. Univariate analysis and conditional logistic regression were used to assess the association between visceral and emotional sensations and localization of the stimulated contacts. RESULTS: In total, 543 stimulations evoked visceral and emotional sensations. Stimulations of operculo-insulolimbic structures (amygdala, anterior and posterior insula, anterior and mid-cingulate cortex, hippocampus, parahippocampus, temporal pole, frontal and parietal operculum) were significantly more associated with visceral and emotional sensations than all other cortical regions. Preferential implication of certain brain structures, depending on the type of visceral responses was evidenced: temporo-mesial structures, insula, and frontoparietal operculum for viscero-sensitive sensations; amygdala, insula, anterior and mid-cingulate cortex, and temporal pole for viscero-vegetative sensations; temporo-mesial structures, anterior cingulate cortex, and frontal operculum for emotional sensations. INTERPRETATION: Our data can help to guide SEEG explorations when visceral or emotional symptoms are part of the ictal semiology. They also bring some insights into the mechanisms of visceroception and the functional significance of the co-localization of visceral and emotional representations in the human brain.

Epileptic spasms are associated with increased stereo-electroencephalography derived functional connectivity in tuberous sclerosis complex.

OBJECTIVE: 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. METHODS: 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, h2 . We calculated (1) intrazone FC within all sampled tubers and normal-appearing cortical zones, respectively; and (2) interzone FC involving connections between DT, other tubers, and normal cortex. The relationship between FC and (1) presence of ES as a current seizure type at the time of SEEG, (2) EZ organization, and (3) epileptogenicity was analyzed using a mixed generalized linear model. Spike rate and distance between zones were considered in the model as covariates. RESULTS: Six 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. SIGNIFICANCE: 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.

Peri-ictal hypoxemia during temporal lobe seizures: A SEEG study.

Focal seizures originating from the temporal lobe are commonly associated with peri-ictal hypoxemia (PIH). During the course of temporal lobe seizures, epileptic discharges often not only spread within various parts of the temporal lobe but also possibly insula and frontal lobe. The link between spatial propagation of the seizure discharges and PIH is still unclear. The present study investigates the involvement of several brain structures including medial temporal structures, temporal pole, anterior insula, and frontal cortex in the occurrence of PIH. Using quantitative indices obtained during SEEG (stereoencephalography) recordings in 38 patients, we evaluated the epileptogenicity, the spatial propagation, and functional connectivity between those structures during seizures leading to PIH. Multivariate statistical analyses of SEEG quantitative indices showed that temporal lobe seizures leading to PIH are characterized by a strong involvement of amygdala and anterior insula during seizure propagation and a more widespread involvement of medial temporal lobe structures, lateral temporal lobe, temporal pole, and anterior cingulate at the end of the seizures. On the contrary, seizure-onset zone was not associated with PIH occurrence. During seizure propagation, anterior insula, temporal pole, and temporal lateral neocortex activities were correlated with intensity of PIH. Lastly, PIH occurrence was also related to a widespread increase of synchrony between those structures. Those results suggest that PIH occurrence during temporal lobe seizures may be related to the activation of a widespread network of cortical structures, among which amygdala and anterior insula are key nodes.

Surgical outcome of temporal plus epilepsy is improved by multilobar resection.

OBJECTIVE: 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. METHODS: 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 χ2 test or Fisher exact test of independence on tables of frequency for each categorical variable of interest and Student t-test for each continuous variable of interest, when appropriate. RESULTS: Twenty-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. SIGNIFICANCE: 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.

The role of hybrid FDG-PET/MRI on decision-making in presurgical evaluation of drug-resistant epilepsy.

BACKGROUND: When MRI fails to detect a potentially epileptogenic lesion, the chance of a favorable outcome after epilepsy surgery becomes significantly lower (from 60 to 90% to 20-65%). Hybrid FDG-PET/MRI may provide additional information for identifying the epileptogenic zone. We aimed to investigate the possible effect of the introduction of hybrid FDG-PET/MRI into the algorithm of the decision-making in both lesional and non-lesional drug-resistant epileptic patients. METHODS: In a prospective study of patients suffering from drug-resistant focal epilepsy, 30 nonlesional and 30 lesional cases with discordant presurgical results were evaluated using hybrid FDG-PET/MRI. RESULTS: The hybrid imaging revealed morphological lesion in 18 patients and glucose hypometabolism in 29 patients within the nonlesional group. In the MRI positive group, 4 patients were found to be nonlesional, and in 9 patients at least one more epileptogenic lesion was discovered, while in another 17 cases the original lesion was confirmed by means of hybrid FDG-PET/MRI. As to the therapeutic decision-making, these results helped to indicate resective surgery instead of intracranial EEG (iEEG) monitoring in 2 cases, to avoid any further invasive diagnostic procedures in 7 patients, and to refer 21 patients for iEEG in the nonlesional group. Hybrid FDG-PET/MRI has also significantly changed the original therapeutic plans in the lesional group. Prior to the hybrid imaging, a resective surgery was considered in 3 patients, and iEEG was planned in 27 patients. However, 3 patients became eligible for resective surgery, 6 patients proved to be inoperable instead of iEEG, and 18 cases remained candidates for iEEG due to the hybrid FDG-PET/MRI. Two patients remained candidates for resective surgery and one patient became not eligible for any further invasive intervention. CONCLUSIONS: The results of hybrid FDG-PET/MRI significantly altered the original plans in 19 of 60 cases. The introduction of hybrid FDG-PET/MRI into the presurgical evaluation process had a potential modifying effect on clinical decision-making. TRIAL REGISTRATION: Trial registry: Scientific Research Ethics Committee of the Medical Research Council of Hungary. TRIAL REGISTRATION NUMBER: 008899/2016/OTIG . Date of registration: 08 February 2016.

Headaches provoked by cortical stimulation: Their localizing value in focal epileptic seizures.

OBJECTIVE: Electrical stimulations performed in awake patients identified dura mater, venous sinuses, and arteries as pain-sensitive intracranial structures. However, cephalic pain has been only occasionally reported in patients with epilepsy undergoing stereo-electroencephalography (SEEG) stimulations. METHODS: The aim of our study was to investigate whether headache can be triggered by SEEG stimulations and might be related to specific cortical areas. Data were gathered from 16 050 stimulations collected in 266 patients who underwent a SEEG as part of a presurgical assessment of their drug-resistant epilepsy. RESULTS: Two-hundred and eight stimulations (1.3%) evoked headaches. Pain was more frequently described as bilateral (42.31%) than ipsilateral (16.83%) or contralateral (14.42%) to the stimulated hemisphere. Headache was more frequently elicited during stimulation of the insulo-limbic regions such as the anterior and medial cingulate gyrus, the mesial part of temporal lobe, and the insula. CONCLUSION: This study shows that cortical stimulation can evoke headache, mostly during stimulation of the temporo-frontal limbic regions. It suggests that brief epileptic headache can be an epileptic symptom caused by a cortical discharge involving somatic or visceral network and does not reflect only trigemino-vascular activation. Although not specific, the occurrence of a brief epileptic headache may point to a seizure origin in the temporo-frontal limbic regions.

Awake craniotomy for epilepsy surgery on eloquent speech areas: a single-centre experience.

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.

Brain-scale cortico-cortical functional connectivity in the delta-theta band is a robust signature of conscious states: an intracranial and scalp EEG study.

Long-range cortico-cortical functional connectivity has long been theorized to be necessary for conscious states. In the present work, we estimate long-range cortical connectivity in a series of intracranial and scalp EEG recordings experiments. In the two first experiments intracranial-EEG (iEEG) was recorded during four distinct states within the same individuals: conscious wakefulness (CW), rapid-eye-movement sleep (REM), stable periods of slow-wave sleep (SWS) and deep propofol anaesthesia (PA). We estimated functional connectivity using the following two methods: weighted Symbolic-Mutual-Information (wSMI) and phase-locked value (PLV). Our results showed that long-range functional connectivity in the delta-theta frequency band specifically discriminated CW and REM from SWS and PA. In the third experiment, we generalized this original finding on a large cohort of brain-injured patients. FC in the delta-theta band was significantly higher in patients being in a minimally conscious state (MCS) than in those being in a vegetative state (or unresponsive wakefulness syndrome). Taken together the present results suggest that FC of cortical activity in this slow frequency band is a new and robust signature of conscious states.

Surgical techniques: Stereoelectroencephalography-guided radiofrequency-thermocoagulation (SEEG-guided RF-TC).

Stereoelectroencephalography-guided radiofrequency-thermocoagulation (SEEG-guided RF-TC) consists of coupling SEEG investigation with RF-TC stereotactic lesioning directly through the recording electrodes. In this systematic review the surgical technique, indications, and outcomes are described. Maximum accuracy is reached when a frame-based procedure with a robotic assistance and a per-operative vascular X-ray imaging are performed. Monitoring of the lesioning procedure based on the impedance, a sharp modification of which indicates that the thermocoagulation has reached its maximum volume, allows the optimization of the lesion size. The first indication concerns patients in whom a SEEG is required to determine whether surgery is feasible and in whom resection is indeed possible. Even if surgery is performed owing to insufficient efficacy of SEEG-guided RF-TC, the procedure remains interesting owing to its high positive predictive value for good outcome after surgery. The second indication concerns patients in whom phase I non-invasive investigations have concluded to surgical contraindication and who may still undergo SEEG in a purely therapeutic perspective (small deep zones inaccessible to surgery and network nodes of large epileptic networks). Lastly, SEEG-guided RF-TC can be considered as a first-line treatment for periventricular nodular heterotopia (PNH). Independently of indication, the overall seizure-free rate is 23% and the responder rate is 58%. The best results are obtained for PNH (38% seizure-free and 81% responders), while the worst results have been reported for temporal lobe-epilepsy in a dedicated study. The overall complication rate is 2.5%. More evidence is needed to help determine the exact place of SEEG-guided RF-TC in the surgical management algorithm.

Epileptogenicity in tuberous sclerosis complex: A stereoelectroencephalographic study.

OBJECTIVE: In tuberous sclerosis complex (TSC)-associated drug-resistant epilepsy, the optimal invasive electroencephalographic (EEG) and operative approach remains unclear. We examined the role of stereo-EEG in TSC and used stereo-EEG data to investigate tuber and surrounding cortex epileptogenicity. METHODS: We analyzed 18 patients with TSC who underwent stereo-EEG (seven adults). One hundred ten seizures were analyzed with the epileptogenicity index (EI). In 13 patients with adequate tuber sampling, five anatomical regions of interest (ROIs) were defined: dominant tuber (tuber with highest median EI), perituber cortex, secondary tuber (tuber with second highest median EI), nearby cortex (normal-appearing cortex in the same lobe as dominant tuber), and distant cortex (in other lobes). At the seizure level, epileptogenicity of ROIs was examined by comparing the highest EI recorded within each anatomical region. At the patient level, epileptogenic zone (EZ) organization was separated into focal tuber (EZ confined to dominant tuber) and complex (all other patterns). RESULTS: The most epileptogenic ROI was the dominant tuber, with higher EI than perituber cortex, secondary tuber, nearby cortex, and distant cortex (P < .001). A focal tuber EZ organization was identified in seven patients. This group had 80% Engel IA postsurgical outcome and distinct dominant tuber characteristics: continuous interictal discharges (IEDs; 100%), fluid-attenuated inversion recovery (FLAIR) hypointense center (86%), center-to-rim EI gradient, and stimulation-induced seizures (71%). In contrast, six patients had a complex EZ organization, characterized by nearby cortex as the most epileptogenic region and 40% Engel IA outcome. At the intratuber level, the combination of FLAIR hypointense center, continuous IEDs, and stimulation-induced seizures offered 98% specificity for a focal tuber EZ organization. SIGNIFICANCE: Tubers with focal EZ organization have a striking similarity to type II focal cortical dysplasia. The presence of distinct EZ organizations has significant implications for EZ hypothesis generation, invasive EEG approach, and resection strategy.

Pain behavior without pain sensation: an epileptic syndrome of "symbolism for pain"?

"Asymbolia for pain" has shown the potentiality of diseased insular networks to dissociate sensory from affective-behavioral dimensions of pain, resulting in the lack of appropriate motor and affective responses despite preserved sensory aspect of pain. Here, we describe 4 patients with an inverse phenomenon of asymbolia for pain, namely an isolated "symbolism for pain" triggered by epileptic seizures, characterized by pain behavior without declarative pain sensation despite fully preserved contact and vigilance. Stereoelectroencephalography demonstrated in each case focal seizure discharges within the posterior insulo-opercular cortex, with little or no propagation to other cortical structures, especially those considered to drive subjective pain experiences. The pain behavior might reflect seizure propagation from the insula to brain networks serving for behavioral responses associated with pain, including the cingulate motor region and possibly also the basal ganglia. We propose that the isolated symbolism for pain is a novel epileptic syndrome of dissociation between pain perception and behaviors associated with the insular nociceptive-related networks.

BLAST: A short computerized test to measure the ability to stay on task. Normative behavioral data and detailed cortical dynamics.

This article provides an exhaustive description of a new short computerized test to assess on a second-to-second basis the ability of individuals to «â€¯stay on task ¼, that is, to apply selectively and repeatedly task-relevant cognitive processes. The task (Bron/Lyon Attention Stability Test, or BLAST) lasts around 1 min, and measures repeatedly the time to find a target letter in a two-by-two letter array, with an update of all letters every new trial across thirty trials. Several innovative psychometric measures of attention stability are proposed based on the instantaneous fluctuations of reaction times throughout the task, and normative data stratified over a wide range of age are provided by a large (>6000) dataset of participants aged 8 to 70. We also detail the large-scale brain dynamics supporting the task from an in-depth study of 32 participants with direct electrophysiological cortical recordings (intracranial EEG) to prove that BLAST involves critically large-scale executive attention networks, with a marked activation of the dorsal attention network and a deactivation of the default-mode network. Accordingly, we show that BLAST performance correlates with scores established by ADHD-questionnaires.

Surgical outcomes related to invasive EEG monitoring with subdural grids or depth electrodes in adults: A systematic review and meta-analysis.

PURPOSE: Resective epilepsy surgery based on an invasive EEG-monitors performed with subdural grids (SDG) or depth electrodes (stereo-electroencephalography, SEEG) is considered to be the best option towards achieving seizure-free state in drug-resistant epilepsy. The authors present a meta-analysis, due to the lack of such a study focusing on surgical outcomes originating from SDG- or SEEG-monitors. METHOD: English-language studies published until May 2018, highlighting surgical outcomes were reviewed. Outcome measures including total number of SDG- or SEEG-monitors and resective surgeries; consecutively followed surgical cases; surgical outcomes classified by Engel in overall, temporal/extratemporal and lesional/nonlesional subgroups were analyzed. RESULTS: 19 articles containing 1025 SDG-interventions and 16 publications comprising 974 SEEG-monitors were researched. The rate of resective surgery deriving from SDG-monitoring hovered at 88.8% (95%CI:83.3-92.6%) (I2 = 77.0%;p < 0.001); in SEEG-group, 79.0% (95%CI:70.4-85.7%) (I2 = 72.5%;p < 0.001) was measured. After SDG-interventions, percentage of post-resective follow-up escalated to 96.0% (95%CI:92.0-98.1%) (I2 = 49.1%;p = 0.010), and in SEEG-group, it reached 94.9% (95%CI:89.3-97.6%) (I2 = 80.2%;p < 0.001). In SDG-group, ratio of seizure-free outcomes reached 55.9% (95%CI:50.9-60.8%) (I2 = 54.47%;p = 0.002). Using SEEG-monitor, seizure-freedom occurred in 64.7% (95%CI:59.2-69.8%) (I2 = 11.9%;p = 0.32). Assessing lesional cases, likelihood of Engel I outcome was found in 57.3% (95%CI:48.7%-65.6%) (I2 = 69.9%;p < 0.001), using SDG; while in SEEG-group, it was 71.6% (95%CI:61.6%-79.9%) (I2 = 24.5%;p = 0.225). In temporal subgroup, ratio of seizure-freedom was found to be 56.7% (95%CI:51.5%-61.9%) (I2 = 3.2%;p = 0.412) in SDG-group; whereas, SEEG-group reached 73.9% (95%CI:64.4%-81.6%); (I2 = 0.00%;p = 0.45). Significant differences between seizure-free outcomes were found in overall (p = 0.02), lesional (p = 0.031), and also, temporal (p = 0.002) comparisons. CONCLUSIONS: SEEG-interventions were associated, at least, non-inferiorly, with seizure-freedom compared with SDG-monitors in temporal, lesional and overall subgroups.

How the insula speaks to the heart: Cardiac responses to insular stimulation in humans.

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.

The Insula and Its Epilepsies.

Insular seizures are great mimickers of seizures originating elsewhere in the brain. The insula is a highly connected brain structure. Seizures may only become clinically evident after ictal activity propagates out of the insula with semiology that reflects the propagation pattern. Insular seizures with perisylvian spread, for example, manifest first as throat constriction, followed next by perioral and hemisensory symptoms, and then by unilateral motor symptoms. On the other hand, insular seizures may spread instead to the temporal and frontal lobes and present like seizures originating from these regions. Due to the location of the insula deep in the brain, interictal and ictal scalp electroencephalogram (EEG) changes can be variable and misleading. Magnetic resonance imaging, magnetic resonance spectroscopy, magnetoencephalography, positron emission tomography, and single-photon computed tomography imaging may assist in establishing a diagnosis of insular epilepsy. Intracranial EEG recordings from within the insula, using stereo-EEG or depth electrode techniques, can prove insular seizure origin. Seizure onset, most commonly seen as low-voltage, fast gamma activity, however, can be highly localized and easily missed if the insula is only sparsely sampled. Moreover, seizure spread to the contralateral insula and other brain regions may occur rapidly. Extensive sampling of the insula with multiple electrode trajectories is necessary to avoid these pitfalls. Understanding the functional organization of the insula is helpful when interpreting the semiology produced by insular seizures. Electrical stimulation mapping around the central sulcus of the insula results in paresthesias, while stimulation of the posterior insula typically produces painful sensations. Visceral sensations are the next most common result of insular stimulation. Treatment of insular epilepsy is evolving, but poses challenges. Surgical resections of the insula are effective but risk significant morbidity if not carefully planned. Neurostimulation is an emerging option for treatment, especially for seizures with onset in the posterior insula. The close association of the insula with marked autonomic changes has led to interest in the role of the insula in sudden unexpected death in epilepsy and warrants additional study with larger patient cohorts.