Publications by authors named "Laure Mazzola"

13 Publications

  • Page 1 of 1

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

Epilepsy Behav 2021 Jun 15;122:108125. Epub 2021 Jun 15.

Lyon Neuroscience Research Center (CRNL), INSERM U1028, CNRS UMR5292, Lyon, France; Department of Neurology Neurological Hospital, Hospices Civils de Lyon and University of Lyon, France. Electronic address:

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.
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http://dx.doi.org/10.1016/j.yebeh.2021.108125DOI Listing
June 2021

Cardiac Autonomic Dysfunction and Risk of Sudden Unexpected Death in Epilepsy.

Neurology 2021 05 9;96(21):e2619-e2626. Epub 2021 Apr 9.

From the Department of Clinical Neurophysiology (W.S., A.L., B.P.), Amiens University Medical Center; Equipe Chimere UR7516-Université Picardie Jules Verne (W.Z.), Amiens; Neurology Department (A.N.), Rennes University Hospital, CIC 1414, LTSI, INSERM U1099; Department of Clinical Neurophysiology (P.D.)and INSERM CIC-IT 1403 (J.D.j.), Lille University Medical Center; Neurology Department (P.C., L.M.), University Hospital, St Etienne; INSERM U 1028 (L.M.), CNRS UMR, ''Central Integration of Pain'' Group, Lyon Neuroscience Research Center; Department of Clinical Neurophysiology (B.G.), Limoges University Medical Center; and Unité de Recherche Clinique et Epidémiologie (Département Information Médicale) (M.F., M.-C.P.), CHU Montpellier, and INSERM (M.-C.P.), Centre d'Investigation Clinique 1411, Université Montpellier, France.

Objective: We aimed to test whether patients who died of sudden unexpected death in epilepsy (SUDEP) had an abnormal cardiac autonomic response to sympathetic stimulation by hyperventilation.

Methods: We conducted a retrospective, observational, case-control study of a group of patients who died of SUDEP and controls who were matched to the patients for epilepsy type, drug resistance, sex, age at EEG recording, age at onset of epilepsy, and duration of epilepsy. We analyzed the heart rate (HR) and HR variability (HRV) at rest and during and after hyperventilation performed during the patient's last EEG recording before SUDEP. In each group, changes over time in HRV indexes were analyzed with linear mixed models.

Results: Twenty patients were included in each group. In the control group, the HR increased and the root mean square of successive RR-interval differences (RMSSD) decreased during the hyperventilation and then returned to the baseline values. In the SUDEP group, however, the HR and RMSSD did not change significantly during or after hyperventilation. A difference in HR between the end of the hyperventilation and 4 minutes after its end discriminated well between patients with SUDEP and control patients (area under the receiver operating characteristic curve 0.870, sensitivity 85%, specificity 75%).

Conclusion: Most of patients with subsequent SUDEP have an abnormal cardiac autonomic response to sympathetic stimulation through hyperventilation. An index reflecting the change in HR on hyperventilation might be predictive of the risk of SUDEP and could be used to select patients at risk of SUDEP for inclusion in trials assessing protective measures.
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http://dx.doi.org/10.1212/WNL.0000000000011998DOI Listing
May 2021

Ictal and Interictal Cardiac Manifestations in Epilepsy. A Review of Their Relation With an Altered Central Control of Autonomic Functions and With the Risk of SUDEP.

Front Neurol 2021 12;12:642645. Epub 2021 Mar 12.

Lyon Neuroscience Research Center, INSERM U 1028, CNRS UMR, Lyon, France.

There is a complex interrelation between epilepsy and cardiac pathology, with both acute and long-term effects of seizures on the regulation of the cardiac rhythm and on the heart functioning. A specific issue is the potential relation between these cardiac manifestations and the risk of Sudden and Unexpected Death in Epilepsy (SUDEP), with unclear respective role of centrally-control ictal changes, long-term epilepsy-related dysregulation of the neurovegetative control and direct effects on the heart function. In the present review, we detailed available data about ictal cardiac changes, along with interictal cardiac manifestations associated with long-term functional and structural alterations of the heart. Pathophysiological mechanisms of these cardiac changes are discussed, with a specific focus on central mechanisms and the investigation of a possible deregulation of the central control of autonomic functions in addition to the role of catecholamine and hypoxemia on heart.
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http://dx.doi.org/10.3389/fneur.2021.642645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994524PMC
March 2021

Progressive Myoclonus Epilepsy Caused by a Homozygous Splicing Variant of SLC7A6OS.

Ann Neurol 2021 02 5;89(2):402-407. Epub 2020 Nov 5.

Genetics Department, Lyon Civil Hospices, Lyon, France.

Exome sequencing was performed in 2 unrelated families with progressive myoclonus epilepsy. Affected individuals from both families shared a rare, homozygous c.191A > G variant affecting a splice site in SLC7A6OS. Analysis of cDNA from lymphoblastoid cells demonstrated partial splice site abolition and the creation of an abnormal isoform. Quantitative reverse transcriptase polymerase chain reaction and Western blot showed a marked reduction of protein expression. Haplotype analysis identified a ~0.85cM shared genomic region on chromosome 16q encompassing the c.191A > G variant, consistent with a distant ancestor common to both families. Our results suggest that biallelic loss-of-function variants in SLC7A6OS are a novel genetic cause of progressive myoclonus epilepsy. ANN NEUROL 2021;89:402-407.
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http://dx.doi.org/10.1002/ana.25941DOI Listing
February 2021

Transient hypoxemia induced by cortical electrical stimulation: A mapping study in 75 patients.

Neurology 2020 06 5;94(22):e2323-e2336. Epub 2020 May 5.

From the Departments of Functional Neurology and Epileptology (M.L., J.J., S.R.) and Functional Neurosurgery (M.G.), Hospices Civils de Lyon and University of Lyon, France; Department of Clinical Neurosciences (P.R.), Centre Hospitalo-Universitaire Vaudois, Lausanne, Switzerland; INSERM U1028/CNRS UMR 5292 (B.C., J.J., R.B., M.G., L.M., L.B., S.R.), Lyon's Neuroscience Research Center; Neurology Department (L.M.), University Hospital, Saint-Etienne; and Epilepsy Institute (L.B., S.R.), Lyon, France.

Objective: To identify which cortical regions are associated with direct electrical stimulation (DES)-induced alteration of breathing significant enough to impair pulse oximetry (SpO).

Methods: Evolution of SpO after 1,352 DES was analyzed in 75 patients with refractory focal epilepsy who underwent stereo-EEG recordings. For each DES, we assessed the change in SpO from 30 seconds prior to DES onset to 120 seconds following the end of the DES. The primary outcome was occurrence of stimulation-induced transient hypoxemia as defined by decrease of SpO ≥5% within 60 seconds after stimulation onset as compared to pre-DES SpO or SpO nadir <90% during at least 5 seconds. Localization of the stimulated contacts was defined according to MarsAtlas brain parcellation and Freesurfer segmentation.

Results: A stimulation-induced transient hypoxemia was observed after 16 DES (1.2%) in 10 patients (13%), including 6 in whom SpO nadir was <90%. Among these 16 DES, 7 (44%) were localized within the perisylvian cortex. After correction for individual effects and the varying number of DES contributed by each person, significant decrease of SpO was significantly associated with the localization of DES ( = 0.019).

Conclusion: Though rare, a significant decrease of SpO could be elicited by cortical direct electrical stimulation outside the temporo-limbic structures, most commonly after stimulation of the perisylvian cortex.
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http://dx.doi.org/10.1212/WNL.0000000000009497DOI Listing
June 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

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

Electrical Stimulations of the Human Insula: Their Contribution to the Ictal Semiology of Insular Seizures.

J Clin Neurophysiol 2017 Jul;34(4):307-314

*Department of Neurology, University Hospital of St-Etienne, France; †Team "Central Integration of Pain", Lyon Neuroscience Research Center, INSERM U 1028, CNRS UMR 5292, Lyon, France; ‡Jean Monnet University, St-Etienne, France; §Department of Functional Neurology and Epilepsy, Neurological Hospital, Hospices Civils de Lyon, Lyon, France; and ‖Claude Bernard University Lyon 1, Lyon, France.

Introduction: Stereotactic stimulations of the insular cortex through intracranial electrodes aim at characterizing the semiology of insular seizures. These stimulations, carried out in the context of Stereo-Electro-Encephalography (SEEG) during presurgical monitoring of epilepsy, reproduce the ictal symptoms observed during the development of insular seizures.

Methods: The authors reviewed the results of insular stimulations performed in 222 patients admitted between 1997 and 2015 for presurgical SEEG exploration of atypical temporal or perisylvian epilepsy. Stimulations (50 Hz, trains of 5 seconds, pulses of 0.5 ms, intensity 0.2-3.5 mA) were carried out using transopercular electrodes implanted orthogonal to midsagittal plane.

Results: Out of a total of 669 stimulations, 550 were clinically eloquent in the absence of any postdischarge (237 and 313, respectively, in the right and left insulae). Somatosensory responses (61% of evoked sensations) including pain and visceral sensations (14.9%) were the most frequent, followed by auditory sensations (8%), vestibular illusions (7.5%), speech impairment (5%), gustatory, (2.7%), and olfactory (1%) sensations. Although these responses showed some functional segregation (in particular a privileged pain representation in the postero-superior quadrant), there was a clear spatial overlap between representations of the different modalities.

Conclusions: Symptoms evoked by insular stimulations are multiple. None of them can be considered as absolutely specific to the insular cortex, but the occurrence in given seizure of a somatosensory symptom such as pain or of a laryngeal spasm associated with vestibular, auditory, aphasic, or olfacto-gustatory symptoms points to a discharge development in the insular cortex, which is the only cortical region where stimulations demonstrate such a multimodal representation.
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http://dx.doi.org/10.1097/WNP.0000000000000382DOI Listing
July 2017

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

Vestibular responses to direct stimulation of the human insular cortex.

Ann Neurol 2014 Oct 30;76(4):609-19. Epub 2014 Aug 30.

Neurology Department, University Hospital, St-Etienne; Team "Central Integration of Pain", Lyon Neuroscience Research Center, National Institute of Health and Medical Research Unit 1028, National Center for Scientific Research Mixed Unit of Research 5292, Lyon; Jean Monnet University, St-Etienne.

Objective: The present study provides a functional mapping of vestibular responses in the human insular cortex.

Methods: A total of 642 electrical stimulations of the insula were performed in 219 patients, using stereotactically implanted depth electrodes, during the presurgical evaluation of drug-refractory partial epilepsy. We retrospectively identified 41 contacts where stimulation elicited vestibular sensations (VSs) and analyzed their location with respect to (1) their stereotactic coordinates (for all contacts), (2) the anatomy of insula gyri (for 20 vestibular sites), and (3) the probabilistic cytoarchitectonic maps of the insula (for 9 vestibular sites).

Results: VSs occurred in 7.6% of the 541 evoked sensations after electrical stimulations of the insula. VSs were mostly obtained after stimulation of the posterior insula, that is, in the granular insular cortex and the postcentral insular gyrus. The data also suggest a spatial segregation of the responses in the insula, with the rotatory and translational VSs being evoked at more posterior stimulation sites than other less definable VSs. No left-right differences were observed.

Interpretation: These results demonstrate vestibular sensory processing in the insula that is centered on its posterior part. The present data add to the understanding of the multiple sensory functions of the insular cortex and of the cortical processing of vestibular signals. The data also indicate that lesion or dysfunction in the posterior insula should be considered during the evaluation of vestibular epileptic seizures.
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http://dx.doi.org/10.1002/ana.24252DOI Listing
October 2014

Spatial segregation of somato-sensory and pain activations in the human operculo-insular cortex.

Neuroimage 2012 Mar 5;60(1):409-18. Epub 2012 Jan 5.

Neurology Department, University Hospital, St-Etienne, France.

The role of operculo-insular region in the processing of somato-sensory inputs, painful or not, is now well established. However, available maps from previous literature show a substantial overlap of cortical areas activated by these stimuli, and the region referred to as the "secondary somatosensory area (SII)" is widely distributed in the parietal operculum. Differentiating SII from posterior insula cortex, which is anatomically contiguous, is not easy, explaining why the "operculo-insular" label has been introduced to describe activations by somatosensory stimuli in this cortical region. Based on the recent cyto-architectural parcellation of the human insular/SII cortices (Eickhoff et al., 2006, Kurth et al., 2010), the present study investigates with functional MRI (fMRI), whether these structural subdivisions could subserve distinct aspects of discriminative somato-sensory functions, including pain. Responses to five types of stimuli applied on the left hand of 25 healthy volunteers were considered: i) tactile stimuli; ii) passive movements; iii) innocuous cold stimuli; iv) non-noxious warm and v) heat pain. Our results show different patterns of activation depending on the type of somato-sensory stimulation. The posterior part of SII (OP1 area), contralateral to stimuli, was the only sub-region activated by all type of stimuli and might therefore be considered as a common cortical target for different types of somato-sensory inputs. Proprioceptive stimulation by passive finger movements activated the posterior part of SII (OP1 sub-region) bilaterally and the contralateral median part of insula (PreCG and MSG). Innocuous cooling activated the contralateral posterior part of SII (OP1) and the dorsal posterior and median part of insula (OP2, PostCG). Pain stimuli induced the most widespread and intense activation that was bilateral in SII (OP1, OP4) and distributed to all sub-regions of contralateral insula (except OP2) and to the anterior part of the ipsilateral insula (PreCG, MSG, ASG). However, the posterior granular part of insula contralateral to stimulus (Ig area) and the anterior part of SII bilaterally (OP4) were specifically activated during pain stimulation. This raises the question whether these latter areas could be the anatomical substrate of the sensory-discriminative processing of thermal pain.
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http://dx.doi.org/10.1016/j.neuroimage.2011.12.072DOI Listing
March 2012

Stimulation of the human cortex and the experience of pain: Wilder Penfield's observations revisited.

Brain 2012 Feb 27;135(Pt 2):631-40. Epub 2011 Oct 27.

Department of Neurology, University Hospital, St-Etienne, 42055 cedex 2, France.

Thanks to the seminal work of Wilder Graves Penfield (1891-1976) at the Montreal Neurological Institute, electrical stimulation is used worldwide to localize the epileptogenic cortex and to map the functionally eloquent areas in the context of epilepsy surgery or lesion resections. In the functional map of elementary and experiential responses he described through >20 years of careful exploration of the human cortex via stimulation of the cortical surface, Penfield did not identify any 'pain cortical area'. We reinvestigated this issue by analysing subjective and videotaped behavioural responses to 4160 cortical stimulations using intracerebral electrodes implanted in all cortical lobes that were carried out over 12 years during the presurgical evaluation of epilepsy in 164 consecutive patients. Pain responses were scarce (1.4%) and concentrated in the medial part of the parietal operculum and neighbouring posterior insula where pain thresholds showed a rostrocaudal decrement. This deep cortical region remained largely inaccessible to the intraoperative stimulation of the cortical surface carried out by Penfield after resection of the parietal operculum. It differs also from primary sensory areas described by Penfield et al. in the sense that, with our stimulation paradigm, pain represented only 10% of responses. Like Penfield et al., we obtained no pain response anywhere else in the cortex, including in regions consistently activated by pain in most functional imaging studies, i.e. the first somatosensory area, the lateral part of the secondary somatosensory area, anterior and mid-cingulate gyri (mid-cingulate cortex), anterior frontal, posterior parietal and supplementary motor areas. The medial parietal operculum and posterior insula are thus the only areas where electrical stimulation is able to trigger activation of the pain cortical network and thus the experience of somatic pain.
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http://dx.doi.org/10.1093/brain/awr265DOI Listing
February 2012

Angelman syndrome and pseudo-hypsarrhythmia: a diagnostic pitfall.

Epileptic Disord 2011 Sep;13(3):331-5

Department of Neonatology, CHU de Saint-Etienne, Saint Etienne, France.

Angelman syndrome is a rare genetic disorder scarcely diagnosed before the age of two years. We report the case of an eight-month-old female presenting with severe hypotonia, myoclonus, suspected spasms and an electroencephalogram with hypsarrhythmic-like features. She was initially treated with vigabatrin which resulted in worsening of myoclonic jerks. Fluorometric in situ hybridization revealed a chromosomal deletion at region 15q11-13. We discuss the case and differential diagnosis with other conditions including West syndrome. [Published with video sequences].
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http://dx.doi.org/10.1684/epd.2011.0446DOI Listing
September 2011
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