Publications by authors named "Hélène Catenoix"

36 Publications

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

Epileptic Disord 2021 Apr;23(2):347-356

Department of Functional Neurosurgery, Hospices Civils de Lyon and University of Lyon, Lyon, France, University of Lyon, Lyon, France, Lyon's Neuroscience Research Centre, (INSERM U1028, CNRS UMR5292), University of Lyon, Lyon, France.

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.
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http://dx.doi.org/10.1684/epd.2021.1275DOI Listing
April 2021

Relation between coffee consumption and risk of seizure-related respiratory dysfunction in patients with drug-resistant focal epilepsy.

Epilepsia 2021 Mar 14;62(3):765-777. Epub 2021 Feb 14.

Department of Functional Neurology and Epileptology, Hospices Civils de Lyon and University of Lyon, Lyon, France.

Objective: Caffeine is an antagonist of the adenosine pathway, which is involved in regulation of breathing. Extracellular concentrations of adenosine are increased in the immediate aftermath of a seizure. Seizure-related overstimulation of adenosine receptors might promote peri-ictal apnea. However, the relation between caffeine consumption and risk of seizure-related respiratory dysfunction in patients with drug-resistant focal epilepsy remains unknown.

Methods: We performed a cross-sectional analysis of data collected in patients included in the SAVE study in Lyon's epilepsy monitoring unit at the Adult Epilepsy Department of the Lyon University Hospital between February 2016 and October 2018. The video-electroencephalographic recordings of 156 patients with drug-resistant focal epilepsy included in the study were reviewed to identify those with ≥1 focal seizure (FS), valid pulse oximetry (SpO ) measurement, and information about usual coffee consumption. This latter was collected at inclusion using a standardized self-questionnaire and further classified into four groups: none, rare (≤3 cups/week), moderate (4 cups/week to 3 cups/day), and high (≥4 cups/day). Peri-ictal hypoxemia (PIH) was defined as SpO < 90% for at least 5 s occurring during the ictal period, the post-ictal period, or both.

Results: Ninety patients fulfilled inclusion criteria, and 323 seizures were analyzed. Both the level of usual coffee consumption (p = .033) and the level of antiepileptic drug withdrawal (p = .004) were independent risk factors for occurrence of PIH. In comparison with FS in patients with no coffee consumption, risk of PIH was four times lower in FS in patients with moderate consumption (odds ratio [OR] = .25, 95% confidence interval [CI] = .07-.91, p = .036) and six times lower in FS in patients with high coffee consumption (OR = .16, 95% CI = .04-.66, p = .011). However, when PIH occurred, its duration was longer in patients with moderate or high consumption than in those with no coffee consumption (p = .042).

Significance: Coffee consumption may be a protective factor for seizure-related respiratory dysfunction, with a dose-dependent effect.
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http://dx.doi.org/10.1111/epi.16837DOI Listing
March 2021

Stereoelectroencephalography (SEEG) and epilepsy surgery in posttraumatic epilepsy: A multicenter retrospective study.

Epilepsy Behav 2020 11 21;112:107378. Epub 2020 Aug 21.

APHM, Timone Hospital, Epileptology Department, Marseille, France; Aix Marseille Univ, APHM, INSERM, INS, Inst Neurosci Syst, Timone Hospital, Epileptology Department, Marseille, France. Electronic address:

Purpose: Posttraumatic epilepsy (PTE) is a common cause of drug-resistant epilepsy, especially in young adults. Nevertheless, such patients are not common candidates for intracranial presurgical evaluation. We investigated the role of stereoelectroencephalography (SEEG) in defining epileptogenicity and surgical strategy in patients with PTE.

Methods: We analyzed ictal SEEG recordings from 18 patients. We determined the seizure onset zone (SOZ) by quantifying the epileptogenicity of the sampled structures, using the "epileptogenicity index" (EI). We also identified seizure onset patterns (SOPs) through visual and frequency analysis. Postsurgical outcome was assessed by Engel's classification.

Results: The SOZ in PTE was most often located in temporal lobes, followed by frontal lobes. The SOZ was network-organized in the majority of the cases. Half of the SOP did not contain fast discharges. Half of the recordings showed SOZ that were less extensive than the posttraumatic lesions seen on brain magnetic resonance imaging (MRI). All but one operated patient benefited from tailored cortectomy. Only 3 patients were contraindicated for surgical resection due to bilateral epileptogenicity. The overall surgical outcome was good in majority of patients (67% Engel I).

Conclusion: Despite the potential risk of bilateral or multifocal epilepsy, patients with PTE may benefit from presurgical assessment in well-selected cases. In this context, SEEG allows guidance of tailored resections adapted to the SOZ.
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http://dx.doi.org/10.1016/j.yebeh.2020.107378DOI Listing
November 2020

Epileptogenicity in tuberous sclerosis complex: A stereoelectroencephalographic study.

Epilepsia 2020 01 20;61(1):81-95. Epub 2019 Dec 20.

National Institute of Health and Medical Research U1028/National Center for Scientific Research, Mixed Unit of Research 5292, Lyon Neuroscience Research Center, Lyon, France.

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.
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http://dx.doi.org/10.1111/epi.16410DOI Listing
January 2020

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

Pain 2020 03;161(3):502-508

Central Integration of Pain (NeuroPain) Lab-Lyon Neuroscience Research Center, INSERM U1028, CNRS, UMR5292, Université Claude Bernard, Bron, France.

"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.
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http://dx.doi.org/10.1097/j.pain.0000000000001741DOI Listing
March 2020

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

Hum Brain Mapp 2019 06 28;40(9):2611-2622. Epub 2019 Feb 28.

NeuroPain Lab, Lyon Neuroscience Research Centre, CRNL - INSERM U 1028/CNRS UMR 5292, University of Lyon, Lyon, France.

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.
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http://dx.doi.org/10.1002/hbm.24548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865697PMC
June 2019

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

Seizure 2020 Apr 25;77:64-68. Epub 2019 Jan 25.

Department of Neurosurgery, Neurology & Neurosurgery Hospital Pierre Wertheimer, Hospices Civils de Lyon, France; University of Lyon, Faculty of medicine Claude Bernard, Lyon, France; NEUROPAIN team, Lyon Neuroscience Research Center, INSERM U1028, CNRS, 5292, Lyon, France.

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.
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http://dx.doi.org/10.1016/j.seizure.2019.01.021DOI Listing
April 2020

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

J Neurosurg 2018 Dec;131(6):1938-1946

1Department of Neurosurgery, Neurology & Neurosurgery Hospital Pierre Wertheimer, Hospices Civils de Lyon, Lyon, France.

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.
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http://dx.doi.org/10.3171/2018.7.JNS181164DOI Listing
December 2018

Stereo-electroencephalography-guided radiofrequency thermocoagulation in patients with focal epilepsy: A systematic review and meta-analysis.

Epilepsia 2018 12 21;59(12):2296-2304. Epub 2018 Oct 21.

Faculty of Medicine Claude Bernard, University of Lyon, Lyon, France.

Objective: Despite the increasing number of studies reporting results of stereo-electroencephalography (SEEG)-guided radiofrequency-thermocoagulation (SEEG-guided RF-TC) in the treatment of patients with drug-resistant focal epilepsy, the exact efficacy of this approach remains unclear. The seizure-freedom rate varies greatly across studies and the factors associated with efficacy have not been formally investigated.

Methods: All prospective or retrospective studies reporting efficacy and/or safety of SEEG-guided RF-TC in patients with drug-resistant focal epilepsy were included. The primary outcome was the seizure-free rate 1 year after the procedure. Secondary outcomes were (1) the responder rate 1 year after the procedure and (2) the proportion of patients with permanent neurologic deficit 1 year after the procedure. Each outcome was assessed in all patients and in 4 groups of patients defined by the etiology of epilepsy. Each outcome was pooled using inverse variance weighting, logit transformation of proportion, and a random-effects model.

Results: No prospective study was identified and a total of 6 retrospective studies, reporting efficacy and safety data of 296 patients, were included. The pooled rate of permanent neurologic deficit was 2.5% (95% confidence interval [CI] 1.2%-5.3%), without heterogeneity across studies. In contrast, both the seizure-free and responder rates varied greatly across studies, and statistical heterogeneity was high. The pooled seizure-free and responder rates were 23% (95% CI 8%-50%) and 58% (95% CI 36%-77%), respectively. Both for the seizure-free and responder rates, the greatest efficacy was observed in patients with periventricular nodular heterotopia and the lowest in patients with normal magnetic resonance imaging (MRI) findings.

Significance: SEEG-guided RF-TC is a safe procedure with low risk of complications. In contrast, the level of evidence regarding its efficacy remains low. Better identification of factors associated with seizure outcome are needed.
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http://dx.doi.org/10.1111/epi.14584DOI Listing
December 2018

Parasomnia versus epilepsy: An affair of the heart?

Neurophysiol Clin 2018 Oct 15;48(5):277-286. Epub 2018 Sep 15.

NeuroPain Team, Inserm U 1028/CNRS, UMR 5292, University of Lyon, Lyon Neuroscience Research Centre (CRNL), 69677 Bron, France.

Objective: Differential diagnosis between sleep-related epileptic seizures and NREM parasomnia remains challenging. Pathophysiological markers to differentiate both conditions are needed. Activation of autonomic system is present in arousal reactions and epileptic seizures. Our study investigated whether cardiac reactivity differed between arousal disorders and sleep-related seizures.

Methods: Nocturnal recordings of 50 patients (10 in each group: frontal lobe epilepsy [FLE], temporal lobe epilepsy [TLE], nocturnal terror [NT], confusional arousal [CA], normal arousals [NA]) were retrospectively selected. Timing of the first motor sign and description of behaviours were assessed. Beat-to-beat RR intervals (RRI) as well as heart rate variability were analysed over a period of 60 heartbeats before and after first motor manifestation. The slope and area under the curve (AUC) of RRI were calculated.

Results: A significant decrease in RRI was observed at the onset of all events. Statistical analysis revealed: lower RRI in TLE than in other groups; higher slope of RRI in FLE than in NA and TLE, and higher AUC in NT and FLE than in TLE, and in NT than in NA. Sleep stage, episode duration, vocalization characteristics, lateralized or abnormal posture, exploratory behaviour differed between epileptic and parasomnia groups.

Discussion: Analysis of cardiac reactivity seems to be a useful objective tool, together with clinical features, for diagnosing abnormal behaviour during sleep. Cardiac reactivity in TLE could reflect epileptic discharge propagation to brain areas involved in autonomic control, while FLE and NT might involve a strong non-specific activation of the sympathetic system.
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http://dx.doi.org/10.1016/j.neucli.2018.08.002DOI Listing
October 2018

The landscape of epilepsy-related GATOR1 variants.

Genet Med 2019 02 10;21(2):398-408. Epub 2018 Aug 10.

Stichting Epilepsie Instellingen Nederland, Zwolle/Heemstede, The Netherlands.

Purpose: To define the phenotypic and mutational spectrum of epilepsies related to DEPDC5, NPRL2 and NPRL3 genes encoding the GATOR1 complex, a negative regulator of the mTORC1 pathway METHODS: We analyzed clinical and genetic data of 73 novel probands (familial and sporadic) with epilepsy-related variants in GATOR1-encoding genes and proposed new guidelines for clinical interpretation of GATOR1 variants.

Results: The GATOR1 seizure phenotype consisted mostly in focal seizures (e.g., hypermotor or frontal lobe seizures in 50%), with a mean age at onset of 4.4 years, often sleep-related and drug-resistant (54%), and associated with focal cortical dysplasia (20%). Infantile spasms were reported in 10% of the probands. Sudden unexpected death in epilepsy (SUDEP) occurred in 10% of the families. Novel classification framework of all 140 epilepsy-related GATOR1 variants (including the variants of this study) revealed that 68% are loss-of-function pathogenic, 14% are likely pathogenic, 15% are variants of uncertain significance and 3% are likely benign.

Conclusion: Our data emphasize the increasingly important role of GATOR1 genes in the pathogenesis of focal epilepsies (>180 probands to date). The GATOR1 phenotypic spectrum ranges from sporadic early-onset epilepsies with cognitive impairment comorbidities to familial focal epilepsies, and SUDEP.
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http://dx.doi.org/10.1038/s41436-018-0060-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292495PMC
February 2019

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

J Neurol 2018 Sep 26;265(9):1998-2004. Epub 2018 Jun 26.

Department of Neurosurgery, Hospices Civils de Lyon, Neurology and Neurosurgery Hospital Pierre Wertheimer, 59, Bd Pinel, 69677, Bron, France.

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.
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http://dx.doi.org/10.1007/s00415-018-8958-9DOI Listing
September 2018

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

Epilepsy Behav 2018 08 14;85:76-84. Epub 2018 Jun 14.

Department of Functional Neurology and Epileptology, Hospices civils de Lyon, Lyon, France; Lyon 1 University, Lyon, France; Lyon's Neuroscience Research Center, INSERM U1028, CNRS UMR 5292, Lyon, France. Electronic address:

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.
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http://dx.doi.org/10.1016/j.yebeh.2018.05.017DOI Listing
August 2018

The combination of stereo-EEG and radiofrequency ablation.

Epilepsy Res 2018 05 9;142:117-120. Epub 2018 Jan 9.

Hospices Civils de Lyon, Hospital for Neurology and Neurosurgery Pierre Wertheimer, Department of Functional Neurology and Epileptology, Lyon, France; Neuroscience Research Center of Lyon, INSERM U1028, CNRS 5292, Lyon, France.

SEEG-guided radiofrequency thermocoagulation (SEEG-guided RFTC), a combination of Stereo-electroencephalography (SEEG) and radiofrequency thermocoagulation (RFTC), has been performed since 2001 in drug resistant epilepsy. The interest of this procedure is to aim at total or partial destruction of the epileptogenic zone, as tailored in each individual patient by the SEEG exploration. These multiple SEEG-guided RFTC lesions of epileptic foci are produced by using a radiofrequency generator connected to the electrode contacts. This review summarizes the results of SEEG-guided RFTC reported in 251 patients. This procedure appears to be safe since complications are rare, minor and usually reversible, which is explained by the use of functional electrical stimulations before RFTC. It makes it also possible to produce RF lesions located very close to cortical areas having a high functional value or being poorly accessible to a conventional surgical procedure. Even if seizure outcome is not as good as results of surgery, 41% of the patients are responders at 12 months with several seizure free patients. The benefit-risk ratio of the SEEG-guided RFTC procedure proved to be particularly favorable for the patients presenting with epileptogenic cortical malformation of development (nodular heterotopy as well as focal cortical dysplasia) and for those in whom surgery is not feasible or risky. For the patients in whom surgery is feasible, SEEG-guided RFTC could be used as a first step, as a predictive therapeutic test before resective surgery.
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http://dx.doi.org/10.1016/j.eplepsyres.2018.01.012DOI Listing
May 2018

French guidelines on stereoelectroencephalography (SEEG).

Neurophysiol Clin 2018 Feb 23;48(1):5-13. Epub 2017 Dec 23.

Neurology Department, CHU de Nancy, 54000 Nancy, France; CRAN UMR 7039, CNRS Lorraine-Université, 54506 Vandoeuvre cedex, France.

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.
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http://dx.doi.org/10.1016/j.neucli.2017.11.005DOI Listing
February 2018

Planning and management of SEEG.

Neurophysiol Clin 2018 Feb 15;48(1):25-37. Epub 2017 Dec 15.

Neurology Department, CHU de Nancy, Nancy, France; CRAN UMR 7039, CNRS Lorraine-Université, France.

Stereoelectroencephalography (SEEG) aims to define the epileptogenic zone (EZ), to study its relationship with functional areas and the causal lesion and to evaluate the possibility of surgical therapy. Planning of exploration is based on the validity of the hypotheses developed from electroclinical and imaging correlations. Further investigations can refine the implantation plan (e.g. fluorodeoxyglucose positron emission tomography [FDG-PET], single photon emission computerized tomography [SPECT], magnetoencephalography [MEG] and high resolution electroencephalography [EEG-HR]). The scheme is individualized according to the features of each clinical case, but a general approach can be systematized according to the regions involved (temporal versus extra-temporal), the existence of a lesion, its type and extent. It takes account of the hemispheric dominance for language if this can be determined. In "temporal plus" epilepsies, perisylvian and insular regions are among the key structures to investigate in addition to mesial and neocortical temporal areas. In frontal lobe epilepsies, determining the functional and anatomical organization of seizures (anterior versus posterior, mesial versus dorsolateral) allows better targeting of the implantation. Posterior epilepsies tend to have a complex organization leading to multilobar and often bilateral explorations. In lesional cases, it may be useful to implant one or several intralesional electrode(s), except in cases of vascular lesions or cyst. The strategy of implantation can be modified if thermocoagulations are considered. The management of SEEG implies continuous monitoring in a dedicated environment to determine the EZ with optimal safety conditions. This methodology includes spontaneous seizure recordings, low and high frequency stimulations and, if possible, sleep recording. SEEG is applicable in children, even the very young. Specific training of medical and paramedical teams is required.
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http://dx.doi.org/10.1016/j.neucli.2017.11.007DOI Listing
February 2018

Stereoelectroencephalography and surgical outcome in polymicrogyria-related epilepsy: A multicentric study.

Ann Neurol 2017 Nov 11;82(5):781-794. Epub 2017 Nov 11.

Research Center for Automatic Control of Nancy (CRAN), University of Lorraine, CNRS, UMR 7039, Vandoeuvre, France.

Objective: We aimed to (1) assess the concordance between various polymicrogyria (PMG) types and the associated epileptogenic zone (EZ), as defined by stereoelectroencephalography (SEEG), and (2) determine the postsurgical seizure outcome in PMG-related drug-resistant epilepsy.

Methods: We retrospectively analyzed 58 cases: 49 had SEEG and 39 corticectomy or hemispherotomy.

Results: Mean age at SEEG or surgery was 28.3 years (range, 2-50). PMG was bilateral in 9 (16%) patients and unilateral in 49, including 17 (29%) unilobar, 12 (21%) multilobar, 15 (26%) perisylvian, and only 5 (9%) hemispheric. Twenty-eight (48%) patients additionally had schizencephaly, heterotopia, or focal cortical dysplasia. The SEEG-determined EZ was fully concordant with the PMG in only 8 (16%) cases, partially concordant in 74%, and discordant in 10%. The EZ included remote cortical areas in 21 (43%) cases and was primarily localized in those in 5 (10%), all related to the mesial temporal structures. All but 1 PMG patient with corticectomy or hemispherotomy had a unilateral PMG. At last follow-up (mean, 4.6 years; range, 1-16), 28 (72%) patients remained seizure free. Shorter epilepsy duration to surgery was an independent predictor of seizure freedom.

Interpretation: PMG-related drug-resistant epilepsy warrants a comprehensive presurgical evaluation, including SEEG investigations in most cases, given that the EZ may only partially overlap with the PMG or include solely remote cortical areas. Seizure freedom is feasible in a large proportion of patients. PMG extent should not deter from exploring the possibility of epilepsy surgery. Our data support the early consideration of epilepsy surgery in this patient group. Ann Neurol 2017;82:781-794.
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http://dx.doi.org/10.1002/ana.25081DOI Listing
November 2017

Epileptogenic networks in nodular heterotopia: A stereoelectroencephalography study.

Epilepsia 2017 12 6;58(12):2112-2123. Epub 2017 Oct 6.

Inserm, Institut de Neurosciences des Systèmes (INS), Aix Marseille Univ, Marseille, France.

Objective: Defining the roles of heterotopic and normotopic cortex in the epileptogenic networks in patients with nodular heterotopia is challenging. To elucidate this issue, we compared heterotopic and normotopic cortex using quantitative signal analysis on stereoelectroencephalography (SEEG) recordings.

Methods: Clinically relevant biomarkers of epileptogenicity during ictal (epileptogenicity index; EI) and interictal recordings (high-frequency oscillation and spike) were evaluated in 19 patients undergoing SEEG. These biomarkers were then compared between heterotopic cortex and neocortical regions. Seizures were classified as normotopic, heterotopic, or normoheterotopic according to respective values of quantitative analysis (EI ≥0.3).

Results: A total of 1,246 contacts were analyzed: 259 in heterotopic tissue (heterotopic cortex), 873 in neocortex in the same lobe of the lesion (local neocortex), and 114 in neocortex distant from the lesion (distant neocortex). No significant difference in EI values, high-frequency oscillations, and spike rate was found comparing local neocortex and heterotopic cortex at a patient level, but local neocortex appears more epileptogenic (p < 0.001) than heterotopic cortex analyzing EI values at a seizure level. According to EI values, seizures were mostly normotopic (48.5%) or normoheterotopic (45.5%); only 6% were purely heterotopic. A good long-term treatment response was obtained in only two patients after thermocoagulation and surgical disconnection.

Significance: This is the first quantitative SEEG study providing insight into the mechanisms generating seizures in nodular heterotopia. We demonstrate that both the heterotopic lesion and particularly the normotopic cortex are involved in the epileptogenic network. This could open new perspectives on multitarget treatments, other than resective surgery, aimed at modifying the epileptic network.
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http://dx.doi.org/10.1111/epi.13919DOI Listing
December 2017

Gustatory and olfactory responses to stimulation of the human insula.

Ann Neurol 2017 Sep 30;82(3):360-370. Epub 2017 Aug 30.

Central Integration of Pain Team, Lyon Neuroscience Research Center, National Institute of Health and Medical Research Unit 1028, National Center for Scientific Research Mixed Unit of Research 5292, Lyon.

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.
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http://dx.doi.org/10.1002/ana.25010DOI Listing
September 2017

The neural bases of ictal tachycardia in temporal lobe seizures.

Clin Neurophysiol 2017 09 27;128(9):1810-1819. Epub 2017 Jun 27.

Dycog Lab, Lyon Neuroscience Research Center - Inserm U 1028/CNRS UMR 5292, University of Lyon, France; Epilepsy and Functional Neurology Department, Neurological Hospital Pierre Wertheimer, Hospices Civils de Lyon, Bron, France.

Objective: Due to limited information from scalp electroencephalographic (EEG) recordings, brain areas driving changes in cardiac rhythm during Temporal lobe (TL) seizures are not clearly identified. Using stereotactic EEG (SEEG) recordings, we aimed at identifying which of the brain regions involved in autonomic control trigger ictal tachycardia.

Methods: The neural activity of several mesial temporal lobe structures including amygdala, hippocampus, insula, and lateral temporal lobe recorded with SEEG were collected during 37 TL seizures in 9 patients, using indices based on High Frequency Activity (HFA). R-R intervals (RR) monitoring and time-frequency spectral analysis were performed to assess parasympathetic (High frequency power (HF)) and sympathetic (Low frequency/High frequency (LF/HF) ratio) reactivities.

Results: Tachycardia was associated with a significant increase in LF/HF ratio and decrease in HF. Autonomic cardiac changes were accompanied by simultaneous SEEG signal changes with an increase in seizure-related HFA in anterior hippocampal formation and amygdala, but not in insula.

Conclusion: In our sample, TL seizures are thus accompanied by an early decrease in parasympathetic control of cardiac rhythm and by an increase of sympathetic tone, concomitant to seizure activity in anterior hippocampus and amygdala.

Significance: These results support a pivotal role of hippocampus and amygdala in tachycardia occurring during TL seizures.
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http://dx.doi.org/10.1016/j.clinph.2017.06.033DOI Listing
September 2017

Stereotactic Electroencephalography Is a Safe Procedure, Including for Insular Implantations.

World Neurosurg 2017 Mar 19;99:353-361. Epub 2016 Dec 19.

Department of Neurosurgery, Hospital for Neurology and Neurosurgery Pierre Wertheimer, Hospices Civils de Lyon, Lyon, France; Université Claude Bernard, University of Lyon, Lyon, France; Neuroscience Research Center of Lyon, INSERM U1028, CNRS 5292, Lyon, France.

Background: In some cases of drug-resistant focal epilepsy, noninvasive presurgical investigation may be insufficient to identify the ictal onset zone and the eloquent cortical areas. In such situations, invasive investigations are proposed using either stereotactic electroencephalography (SEEG) or subdural grid electrodes. Meta-analysis suggests that SEEG is safer than subdural grid electrodes, but insular implantation of SEEG electrodes has been thought to carry an additional risk of intraparenchymal hemorrhagic complications. Our objectives were to determine whether an insular SEEG trajectory is a risk factor for intracranial hematoma and to report the global safety of the procedure and provide some guidelines to prevent and detect complications.

Methods: In a retrospective analysis of a surgical series of 525 consecutive procedures between 1995 and 2015, all electrodes were classified according to their insular or extrainsular trajectory. All complications were classified as major or minor according to their potential consequences regarding patient neurologic status.

Results: Four intraparenchymal hematomas, all related to extrainsular electrodes (4/4974; 0.08%) were reported; no hematoma was found along insular electrodes (0/1042; 0%). There were 8 major complications (1.52%): 7 intracranial hematomas (1.33%) and 1 case of meningitis. Two patients had long-term neurologic impairment (0.38%), and 1 death (not directly related to the procedure) occurred (0.19%). Eleven minor complications (2.09%) were encountered, including broken electrode (1.52%), acute pneumocephalus (0.38%), and local cutaneous infection (0.19%).

Conclusions: SEEG is a safe procedure. Insular trajectories cannot be considered an additional risk of intracranial bleeding.
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http://dx.doi.org/10.1016/j.wneu.2016.12.025DOI Listing
March 2017

Stereo electroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) in drug-resistant focal epilepsy: Results from a 10-year experience.

Epilepsia 2017 01 16;58(1):85-93. Epub 2016 Nov 16.

Department of Neurosurgery, Hospices Civils de Lyon (Lyon University Hospital), Hospital for Neurology and Neurosurgery Pierre Wertheimer, Lyon, France.

Objective: Stereo electroencephalography (SEEG)-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) has been proposed since 2004 as a possible treatment of some focal drug-resistant epilepsy. The aim of this study is to provide extensive data about efficacy and safety of SEEG-guided RF-TC.

Methods: Over a 10-year period, 162 patients with drug-resistant focal epilepsy were eligible for SEEG-guided RF-TG during phase II invasive investigation by SEEG. All follow-up and safety data were collected prospectively. The primary outcome was seizure freedom at 2 months and at 1 year after SEEG-guided RF-TC. Secondary outcomes were the responders' rate (patient with at least 50% decrease in seizure frequency) and their long-term follow-up.

Results: Twenty-five percent of patients were seizure-free at 2 months and 7% at 1 year. We reported 67% of responders at 2 months and 48% at 1 year; 58% of responders maintained their status during the long-term follow-up. The seizure outcome was significantly better when the SEEG-guided RF-TC involved the occipital region (p = 0.007). When surgery followed an SEEG-guided RF-TC, the positive predictive value of being a responder 2 months after an SEEG-guided RF-TC and to be Engel's class I or II after surgery was 93%. We reported 1.1% of permanent deficit and 2.4% of transient side effects.

Significance: Our results, gathered in a large population over a 10-year period, confirm that SEEG-guided RF-TC is a safe technique, being efficient in many cases. More than two thirds of patients showed a short-term improvement, and almost half of them were responders at 1-year follow-up. The technique appears to be especially interesting for limited epileptic zone inaccessible to surgery and when epilepsy is related to a large unilateral network (network disruption by multiple RF-TC). Furthermore, SEEG-guided RF-TC effect is a predictor of outcome after conventional cortectomy in patients eligible for surgery.
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http://dx.doi.org/10.1111/epi.13616DOI Listing
January 2017

Stereo-electro-encephalography-Guided Radiofrequency Thermocoagulation: From In Vitro and In Vivo Data to Technical Guidelines.

World Neurosurg 2016 Oct 29;94:73-79. Epub 2016 Jun 29.

Department of Neurosurgery, Hospital for Neurology and Neurosurgery Pierre Wertheimer, Hospices Civils de Lyon, Lyon, France; Université de Lyon, Université Claude Bernard, Lyon, France; Neuroscience Research Center of Lyon, Lyon, France.

Background: Deep brain electrodes have been used for the past 10 years to produce bipolar stereo-electro-encephalography-guided radiofrequency thermocoagulation (SEEG RF-TC). However, this technique is based on empiric knowledge. The aim of this study is 3-fold: 1) provide in vivo animal data concerning the effect of bipolar RF-TC on brain and its safety; 2) assess the parameters of this procedure (current delivery and dipole selection) that produce the most efficient lesion; and 3) provide technical guidelines.

Methods: First we achieved in vivo RF-TC on rabbit brains with several conditions (power delivered and lesioning duration) and analyzed their influence on the lesion produced. Only a difference in terms of volume was found, and type of histologic lesions was similar whatever the settings were. We then performed multiple RF-TC in vitro on egg albumen, first with several parameters of radiofrequency and then with different dipole spatial selections. The end point was the size of the radiofrequency thermolesion produced.

Results: Using unfixed parameters of radiofrequency current delivery and increasing it until the power delivered by the generator collapsed produced significantly larger lesions (P = 0.008) than other conditions. Concerning the dipole selection, the use of contiguous contacts on electrodes led to lesions with a higher volume (P = 7.7 × 10) than those produced with noncontiguous ones.

Conclusion: Besides the target selection in SEEG RF-TC, which is summarized on the basis of a literature review, we report the optimal parameters: Radiofrequency current must be increased until the power delivered collapses, and dipoles should be constituted by contiguous electrode contacts.
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http://dx.doi.org/10.1016/j.wneu.2016.06.095DOI Listing
October 2016

Long-lasting seizure-related anxiety in patients with temporal lobe epilepsy and comorbid psychiatric disorders.

Epileptic Disord 2015 Sep;17(3):340-4

Department of Functional Neurology and Epileptology and Institute of Epilepsies (IDEE), Hospices Civils de Lyon, Lyon, France.

Ictal anxiety is a frequent epileptic symptom; it is usually brief, associated with objective clinical signs, and is not positively influenced by external factors, in contrast to psychiatric disorders. These criteria can, however, be misleading, especially in patients with psychiatric comorbidities. We report two patients with a history of drug-resistant right temporal lobe epilepsy, who developed long-lasting psychiatric symptoms, suggestive of exacerbation of their comorbid anxiety disorder. However, intracranial EEG data and [(18)F] FDG-PET suggested that these symptoms were related to seizure activity, highlighting the difficulties in differentiating ictal symptoms from psychiatric episodes in some patients with epilepsy and comorbid psychiatric disorders. [Published with video sequence].
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http://dx.doi.org/10.1684/epd.2015.0757DOI Listing
September 2015

Seizures Outcome After Stereoelectroencephalography-Guided Thermocoagulations in Malformations of Cortical Development Poorly Accessible to Surgical Resection.

Neurosurgery 2015 Jul;77(1):9-14; discussion 14-5

*Service de Neurologie Fonctionnelle et d'Epileptologie, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron, France; ‡Centre de Recherche en Neurosciences, INSERM U1028, CNRS 5292, UCBL-1, Lyon, France; §Service de Neurochirurgie Fonctionnelle, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron, France.

Background: Radiofrequency thermocoagulation (RFTC) guided by stereoelectroencephalography (SEEG) has proved to be a safe palliative method to reduce seizure frequency in patients with drug-resistant partial epilepsy. In malformation of cortical development (MCD), increasing the number of implanted electrodes over that needed for mapping of the epileptogenic zone could help to maximize RFTC efficiency.

Objective: To evaluate the benefit of SEEG-guided RFTC in 14 patients suffering from drug-resistant epilepsy related to MCD located in functional cortical areas or in regions poorly accessible to surgery.

Methods: Ten men and 4 women were treated by RFTC. Thermolesions were produced by applying a 50-V, 120-mA current for 10 to 30 seconds within the epileptogenic zone as identified by the SEEG investigation.

Results: An average of 25.8 ± 17.5 thermolesions were made per procedure. The median follow-up after the procedure was 41.7 months. Sixty-four percent of the patients experienced a long-term decrease in seizure frequency of >50%, of whom 6 (43%) presented long-lasting freedom from seizure. When a focal low-voltage fast activity was present at seizure onset on SEEG recordings, 87.5% of patients were responders or seizure free. All of the patients in whom electric stimulation reproduced spontaneous seizures were responders.

Conclusion: Our results show the good benefit-risk ratio of the SEEG-guided procedure for patients suffering from MCD in whom surgery is risky. This study identifies 2 factors, focal low-voltage, high-frequency activity at seizure onset and lowered epileptogenic threshold in the coagulated area, that could be predictive of a favorable seizure outcome after RFTC.
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http://dx.doi.org/10.1227/NEU.0000000000000723DOI Listing
July 2015

On the origin of painful somatosensory seizures.

Neurology 2015 Feb;84(6):594-601

Objective: To explore whether painful somatosensory seizures (PSS) are generated in the primary somatosensory cortex (SI area) or in the operculo-insular cortex.

Methods: We analyzed ictal recordings and data from stimulation using intracerebral electrodes exploring the operculo-insular cortex (including secondary somatosensory [SII] region), SI area,and other areas of the pain matrix (cingulate gyrus and supplementary motor area) in a case series study of 5 patients with PSS.

Results: Clinical features of PSS were different from those of seizures arising from the SI area: (1)pain intensity was higher; (2) pain spreading was not from one somatotopic territory to adjacentones; and (3) the spatial extent of pain was large, fitting better with the size of somatosensory receptive fields of the insula and SII region than of the SI area. The insula and SII region were systematically involved at the onset of seizures, rapidly followed by the opercular portion of SI area.The upper part of SI cortex was involved at a lesser degree, with some delay, and pain duration did not correlate in time with that of the discharge in SI. Ictal pain was consistently reproduced by stimulation of the insula or SII region but never by stimulating the SI area.

Conclusions: These data strongly suggest that PSS originate in the operculo-insular cortex and not in the SI area and corroborate the concept that this region is involved in the sensory discriminative processing of pain inputs. Pain at the onset of PSS has a high value for localizing the epileptogenic area.
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http://dx.doi.org/10.1212/WNL.0000000000001235DOI Listing
February 2015

Positron emission tomography with α-[11C]methyl-L-tryptophan in tuberous sclerosis complex-related epilepsy.

Epilepsia 2013 Dec 28;54(12):2143-50. Epub 2013 Oct 28.

Nuclear Medicine Department, Hospital Clinic, Barcelona, Spain.

Objective: Tuberous sclerosis complex (TSC) is often associated with cerebral tubers and medically intractable epilepsy. We reevaluated whether increased uptake of α-[(11) C]methyl-l-tryptophan (AMT) in cerebral tubers is associated with tuber epileptogenicity.

Methods: We included 12 patients (six male, 4-53 years old) with TSC and refractory seizures who were evaluated for epilepsy surgery in our center, including video-electroencephalographic (EEG) monitoring, fluid-attenuated inversion recovery magnetic resonance imaging (FLAIR MRI), and positron emission tomography (PET) with α-[(11) C]methyl-l-tryptophan (AMT-PET). Nine of these 12 patients also underwent intracerebral EEG recording. AMT uptake in each tuber was visually evaluated on PET coregistered with MRI. An AMT uptake index based on lesional/healthy cortex ratio was also calculated. Sensitivity and specificity values of AMT-PET in the detection of epileptogenic lesions were obtained, using the available electroclinical and neuroimaging evidence as the gold standard for epileptogenicity.

Results: A total of 126 tubers were identified. Two of 12 patients demonstrated a tuber with clearly increased AMT uptake, one of whom also showed a subtle increased AMT uptake in another contralateral tuber. Four other patients showed only subtle increased AMT uptake. The only two tubers with clearly increased AMT uptake proved to be epileptogenic based on intracerebral EEG data, whereas none of the tubers associated with subtle increased AMT uptake were involved at ictal onset. In a per-patient approach, this yielded a sensitivity of clearly increased AMT uptake in detecting tuber epileptogenicity of 17% (2/12 patients), whereas the per-lesion sensitivity and specificity were 12% (95% confidence interval [CI]: 3-34%) and 100% (95% CI: 97-100%), respectively.

Significance: AMT-PET is a specific neuroimaging technique in the identification of epileptogenic tubers in TSC. Despite its low sensitivity, the clinical usefulness of AMT-PET still deserves to be considered according to the challenging complexity of epilepsy surgery in tuberous sclerosis.
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http://dx.doi.org/10.1111/epi.12412DOI Listing
December 2013

Periventricular [(11)C]flumazenil binding for predicting postoperative outcome in individual patients with temporal lobe epilepsy and hippocampal sclerosis.

Neuroimage Clin 2013 3;3:242-8. Epub 2013 Sep 3.

Neurodis Foundation, Lyon, France.

A third of patients with intractable temporal lobe epilepsy and hippocampal sclerosis (HS) are not seizure free (NSF) after surgery. Increased periventricular [(11)C]flumazenil (FMZ) binding, reflecting heterotopic neuron concentration, has been described as one predictor of NSF outcome at the group level. We aimed to replicate this finding in an independent larger cohort and investigated whether NSF outcome can be predicted in individuals. Preoperative [(11)C]FMZ summed radioactivity images were available for 16 patients with HS and 41 controls. Images were analyzed using SPM8, explicitly including the white matter, and correction for global radioactivity via group-specific ANCOVA. Periventricular increases were assessed with a mask and different cutoffs for distinguishing NSF and seizure free (SF) patients. NSF patients had increased [(11)C]FMZ binding around the posterior horn of the ventricles ipsilaterally (z = 2.53) and contralaterally (z = 4.44) to the seizure focus compared with SF patients. Compared with controls, SF patients had fewer periventricular increases (two clusters, total volume 0.87 cm(3), zmax = 3.8) than NSF patients (two ipsilateral and three contralateral clusters, 6.15 cm(3), zmax = 4.8). In individuals and at optimized cutoffs, five (63%) of eight NSF patients and one (13%) of eight SF patients showed periventricular increases compared with controls (accuracy 75%). Only one (2%) of the 41 controls had increases at the same cutoff. The association between periventricular [(11)C]FMZ increases and NSF outcome after temporal lobe resection for HS has been confirmed in an independent cohort on simple summed activity images. [(11)C]FMZ-PET may be useful for individual preoperative counseling with clinically relevant accuracy.
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http://dx.doi.org/10.1016/j.nicl.2013.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3814949PMC
November 2013