Expanding the Mutational Landscape and Clinical Phenotype of CHD2-Related Encephalopathy.

Objectives: To present a case series of novel CHD2 variants in patients presenting with genetic epileptic and developmental encephalopathy. Background: CHD2 gene encodes an ATP-dependent enzyme, chromodomain helicase DNA-binding protein 2, involved in chromatin remodeling. Pathogenic variants in CHD2 are linked to early-onset conditions such as developmental and epileptic encephalopathy, drug-resistant epilepsies, and neurodevelopmental disorders. Approximately 225 diagnosed patients from 28 countries exhibit various allelic variants in CHD2, including small intragenic deletions/insertions and missense, nonsense, and splice site variants. Results: We present the molecular and clinical characteristics of 17 unreported individuals from 17 families with novel pathogenic or likely pathogenic variants in CHD2. All individuals presented with severe global developmental delay, childhood-onset myoclonic epilepsy, and additional neuropsychiatric features, such as behavioral including autism, ADHD, and hyperactivity. Additional findings include abnormal reflexes, hypotonia and hypertonia, motor impairment, gastrointestinal problems, and kyphoscoliosis. Neuroimaging features included hippocampal signal alterations (4/10), with additional volume loss in 2 cases, inferior vermis hypoplasia (7/10), mild cerebellar atrophy (4/10), and cerebral atrophy (1/10). Discussion: Our study broadens the geographic scope of CHD2-related phenotypes, providing valuable insights into the prevalence and clinical characteristics of this genetic disorder in previously underrepresented populations.

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.

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.

Neural correlates of verbal working memory in children with epilepsy with centro-temporal spikes.

BACKGROUND: Previous functional magnetic resonance imaging (fMRI) studies have identified brain systems underlying different components of working memory (WM) in healthy subjects. The aim of this study was to compare the functional integrity of these neural networks in children with self-limited childhood epilepsy with centro-temporal spikes (ECTS) as compared to healthy controls, using a verbal working memory task (WMT). METHODS: Functional MRI of WM in seventeen 6-to-13 year-old children, diagnosed with ECTS, and 17 sex- and age-matched healthy controls were conducted at 3 T. To estimate BOLD responses during the maintenance of low, medium, and high WMT loads, we used a Sternberg verbal WMT. Neuropsychological testing prior to scanning and behavioral data during scanning were also acquired. RESULTS: Behavioral performances during WMT, in particular accuracy and response time, were poorer in children with ECTS than in controls. Increased WM load was associated with increased BOLD signal in all subjects, with significant clusters detected in frontal and parietal regions, predominantly in the left hemisphere. However, under the high load condition, patients showed reduced activation in the frontal, temporal and parietal regions as compared to controls. In brain regions where WM-triggered BOLD activation differed between groups, this activation correlated with neuropsychological performances in healthy controls but not in patients with ECTS, further suggesting WM network dysfunction in the latter. CONCLUSION: Children with ECTS differ from healthy controls in how they control WM processes during tasks with increasing difficulty level, notably for high WM load where patients demonstrate both reduced BOLD activation and behavioral performances.

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.

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.

Predictive factors and prognostic value for status epilepticus in newborns.

OBJECTIVES: To evaluate the predictive factors for status epilepticus (SE) in neonates and prognostic factors for patient outcomes in newborns suffering either isolated seizures or SE. METHODS: A retrospective single-center study from January 2010 to December 2014, included 91 newborns who had neonatal seizures. Among them, 50 newborns experienced SE and 41 newborns presented isolated seizures only. SE was defined as a single seizure lasting more than 15 min or repeated seizures without return to preictal neurological baseline for more than 15 min. Isolated seizures were defined as one single seizure lasting less than 15 min or more seizures with complete recovery of consciousness between seizures. Perinatal and electroclinical data were recorded. Outcomes were evaluated at one year follow up. RESULTS: In multivariate analysis, the factors identified as being predictive of SE were a severely abnormal initial neurological examination (OR 15.7, 95% CI (3.8-109) p = 0.00075) and hypoglycaemia (OR 6.8, 95% CI (1.5-49.2) p = 0.024), found mostly in newborns with hypoxic-ischemic encephalopathy. When studying our global cohort, SE was found to be a negative prognostic factor for outcome only in univariate analysis. In newborns with isolated seizures only, the postictal clinical examination results were the only independent prognostic factor found, normal results being associated with a more favorable evolution (OR 48.9, 95% CI (7.16-571) p = 0.0003). CONCLUSION: Two independent risk factors for SE in newborns have been identified: a severely abnormal initial neurological examination and hypoglycaemia. In newborns with isolated seizures, the only positive prognostic factor was found to be a normal postictal clinical examination.

Effective accuracy of stereoelectroencephalography: robotic 3D versus Talairach orthogonal approaches.

OBJECTIVE: Stereoelectroencephalography (SEEG) was first developed in the 1950s by Jean Talairach using 2D angiography and a frame-based, orthogonal approach through a metallic grid. Since then, various other frame-based and frameless techniques have been described. In this study the authors sought to compare the traditional orthogonal Talairach 2D angiographic approach with a frame-based 3D robotic procedure that included 3D angiographic interoperative imaging guidance. MRI was used for both procedures during surgery, but MRI preplanning was done only in the robotic 3D technique. METHODS: All study patients suffered from drug-resistant focal epilepsy and were treated at the same center by the same neurosurgical team. Fifty patients who underwent the 3D robotic procedure were compared to the same number of historical controls who had previously been successfully treated with the Talairach orthogonal procedure. The effectiveness and absolute accuracy, as well as safety, of the two procedures were compared. Moreover, in the 3D robotic group, the reliability of the preoperative MRI to avoid vascular structures was evaluated by studying the rate of trajectory modification following the coregistration of the intraoperative 3D angiographic data onto the preoperative MRI-based trajectory plans. RESULTS: Effective accuracy (96.5% vs 13.7%) and absolute accuracy (1.15 mm vs 4.00 mm) were significantly higher in the 3D robotic group than in the Talairach orthogonal group. Both procedures showed excellent safety results (no major complications). The rate of electrode modification after 3D angiography was 43.8%, and it was highest for frontal and insular locations. CONCLUSIONS: The frame-based, 3D angiographic, robotic procedure described here provided better accuracy for SEEG implantations than the traditional Talairach approach. This study also highlights the potential safety advantage of trajectory planning using intraoperative frame-based 3D angiography over preoperative MRI alone.

Task-induced gamma band effect in type II focal cortical dysplasia: An exploratory study.

OBJECTIVE: Few data are available about the functionality of type II focal cortical dysplasia (FCD). Identification of high-frequency activities (HFAs) induced by cognitive tasks has been proposed as an additional way to map cognitive functions in patients undergoing presurgical evaluation using stereoelectroencephalography (SEEG). However, the repetitive subcontinuous spiking pattern which characterizes type II FCD might limit the reliability of this approach, and its feasibility in these patients remains to be evaluated. METHODS: Seven patients whose magnetic resonance imaging (MRI) data, SEEG data, and/or pathological data were consistent with the diagnosis of type II FCD were included. All patients performed standardized cognitive tasks specifically designed to map task-induced increase of HFA (50 Hz to 150 Hz) at the recorded sites. Electrode contacts which showed an interictal SEEG pattern typical of type II FCD were considered to be localized within the FCD. A site was considered responsive if it was significantly different from baseline in at least one cognitive task. RESULTS: Three of the seven patients (43%) had significant task-induced increase of HFA in the FCD for a total of 15 sites with an interictal SEEG pattern typical of type II FCD. These sites were always localized at the external border of the FCD whereas no HFA response was in the core of FCD. In three of the four other patients, a significant task-induced increase of HFA was observed in a cortical site immediately adjacent to the dysplastic cortex. SIGNIFICANCE: Detection of task-induced HFA remains feasible despite the repetitive subcontinuous spiking pattern which characterizes type II FCD. Depending on the localization of the FCD, some sites of the dysplastic cortex were included in large-scale functional networks. However, these sites were always those closest to the nondysplastic cortex suggesting that persistence of cortical functions might be restricted to a limited part of the FCD.

SEEG-guided radiofrequency coagulation (SEEG-guided RF-TC) versus anterior temporal lobectomy (ATL) in temporal lobe epilepsy.

BACKGROUND: Stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) is a super-selective procedure. Hippocampus has a limited volume and is widely accessible to SEEG so that SEEG-guided RF-TC could be an alternative to the anterior temporal lobectomy (ATL) in case of temporal lobe epilepsy (TLE) syndrome. OBJECTIVE: To compare seizure-free rate at 1-year follow-up between patients undergoing SEEG-guided RF-TC and patients undergoing ATL in TLE over a 15-year period. METHODS: All patients had a drug-resistant epilepsy and underwent SEEG after non-conclusive phase I investigations suspecting a TLE. Two groups were selected according to the procedure which the patients underwent (ATL or SEEG-guided RF-TC); TLE had to be confirmed by SEEG in the two groups. The primary outcome was seizure freedom at 1 year. The secondary outcome was response (at least 50% reduction of seizure frequency) at 1 year. In case of persistent seizures after SEEG-guided RF-TC, ATL was performed. RESULTS: A total of 21 patients underwent SEEG-guided RF-TC and 49 ATL. At 12 months, none of the patients of the SEEG-guide RF-TC group was seizure free, while 37 (75.5%) in the ATL group were so (p < 0.001). Ten patients (47.6%) were responders after 12 months of follow-up after SEEG-guided RF-TC; all patients in the ATL group who were seizure free were responders. CONCLUSION: SEEG-guided RF-TC is not as effective as ATL in TLE. As no memory impairment following SEEG-guided RF-TC was found, patients with dominant mesial involvement for whom hippocampectomy is not an option could benefit from the technique.

Indications and limits of stereoelectroencephalography (SEEG).

Epilepsy surgery is now an accepted treatment to achieve seizure control in carefully selected patients, both children and adults, suffering from drug-resistant focal epilepsy. Although surgical strategies can often be defined on the basis of non-invasive diagnostic procedures, and despite the recent advances in this field, an increasing number of more complex cases requires invasive EEG (iEEG) to provide precise information on the localization of the epileptogenic zone (EZ), its relationships with eloquent cortex (EC), and the feasibility of a tailored surgical resection. Stereoelectroencephalography (SEEG) is one of the iEEG techniques currently used in the presurgical work-up, and it is well-distinguished from other invasive techniques, such as subdural grids and strips. SEEG depth electrodes enable exploration of deeply located structures and lesions, and of buried cortex, which are not easily assessable by subdural or other iEEG methods. Simultaneous recording of SEEG signals from deep and superficial brain structures allows, when the position of each electrode is precisely determined, delineation of a three-dimensional, spatial and temporal organization of epileptic activities. In the following chapter we discuss some specific indications (temporal or extra-temporal, lesional or non-lesional epilepsies) as well as the limits of the SEEG technique, with respect to some epileptological issues during presurgical evaluation.

French guidelines on stereoelectroencephalography (SEEG).

Stereoelectroencephalography (SEEG) was designed and developed in the 1960s in France by J. Talairach and J. Bancaud. It is an invasive method of exploration for drug-resistant focal epilepsies, offering the advantage of a tridimensional and temporally precise study of the epileptic discharge. It allows anatomo-electrical correlations and tailored surgeries. Whereas this method has been used for decades by experts in a limited number of European centers, the last ten years have seen increasing worldwide spread of its use. Moreover in current practice, SEEG is not only a diagnostic tool but also offers a therapeutic option, i.e., thermocoagulation. In order to propose formal guidelines for best clinical practice in SEEG, a working party was formed, composed of experts from every French centre with a large SEEG experience (those performing more than 10 SEEG per year over at least a 5 year period). This group formulated recommendations, which were graded by all participants according to established methodology. The first part of this article summarizes these within the following topics: indications and limits of SEEG; planning and management of SEEG; surgical technique; electrophysiological technical procedures; interpretation of SEEG recordings; and SEEG-guided radio frequency thermocoagulation. In the second part, those different aspects are discussed in more detail by subgroups of experts, based on existing literature and their own experience. The aim of this work is to present a consensual French approach to SEEG, which could be used as a basic document for centers using this method, particularly those who are beginning SEEG practice. These guidelines are supported by the French Clinical Neurophysiology Society and the French chapter of the International League Against Epilepsy.

Migraine with brainstem aura: Why not a cortical origin?

Background Migraine with brainstem aura is defined as a migraine with aura including at least two of the following symptoms: dysarthria, vertigo, tinnitus, hypacusis, diplopia, ataxia and/or decreased level of consciousness. Aim The aim of this study is to review data coming from clinical observations and functional mapping that support the role of the cerebral cortex in the initiation of brainstem aura symptoms. Results Vertigo can result from a vestibular cortex dysfunction, while tinnitus and hypacusis can originate within the auditory cortex. Diplopia can reflect a parieto-occipital involvement. Dysarthria can be caused by dysfunctions located in precentral gyri. Ataxia can reflect abnormal processing of vestibular, sensory, or visual inputs by the parietal lobe. Alteration of consciousness can be caused by abnormal neural activation within specific consciousness networks that include prefrontal and posterior parietal cortices. Conclusion Any symptom of so-called brainstem aura can originate within the cortex. Based on these data, we suggest that brainstem aura could have a cortical origin. This hypothesis would explain the co-occurrence of typical and brainstem aura during attacks and would fit with the theory of cortical spreading depression. We propose that migraine with brainstem aura should be classified as a typical migraine aura.

Gustatory and olfactory responses to stimulation of the human insula.

OBJECTIVE: Despite numerous studies suggesting the role of insular cortex in the processing of gustatory and olfactory inputs, the exact location of olfactogustatory 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 presurgical 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. Ann Neurol 2017;82:360-370.