Publications by authors named "Laurent Vercueil"

65 Publications

FASICS: fasciculation anxiety syndrome in clinicians.

Authors:
Laurent Vercueil

Pract Neurol 2020 Dec;20(6):514-515

Clinical Neurophysiology Unit, Univ. Grenoble Alpes, INSERM U1216, CHU Grenoble Alpes, Grenoble Institut Neurosciences, Grenoble, France

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http://dx.doi.org/10.1136/practneurol-2020-002770DOI Listing
December 2020

A 12-month pilot study outcomes of vagus nerve stimulation in Crohn's disease.

Neurogastroenterol Motil 2020 10 8;32(10):e13911. Epub 2020 Jun 8.

Inserm, U1216, Grenoble Institute Neurosciences, University of Grenoble Alpes, Grenoble, France.

Background: The vagus nerve has anti-inflammatory properties. We aimed to investigate vagus nerve stimulation (VNS) as a new therapeutic strategy targeting an intrinsic anti-inflammatory pathway in a pilot study in Crohn's disease patients. The main objectives addressed the questions of long-term safety, tolerability, and anti-inflammatory effects of this therapy. This study is the continuation of previous reported findings at 6 months.

Methods: Nine patients with moderate active disease underwent VNS. An electrode wrapped around the left cervical vagus nerve was continuously stimulated over 1 year. Clinical, biological, endoscopic parameters, cytokines (plasma, gut), and mucosal metabolites were followed-up.

Key Results: After 1 year of VNS, five patients were in clinical remission and six in endoscopic remission. C-reactive protein (CRP) and fecal calprotectin decreased in six and five patients, respectively. Seven patients restored their vagal tone and decreased their digestive pain score. The patients' cytokinergic profile evolved toward a more "healthy profile": Interleukins 6, 23, 12, tumor necrosis factor α, and transforming growth factorβ1 were the most impacted cytokines. Correlations were observed between CRP and tumor necrosis factor α, and some gut mucosa metabolites as taurine, lactate, alanine, and beta-hydroxybutyrate. VNS was well tolerated.

Conclusion & Inferences: Vagus nerve stimulation appears as an innovative and well-tolerated treatment in moderate Crohn's disease. After 12 months, VNS has restored a homeostatic vagal tone and reduced the inflammatory state of the patients. VNS has probably a global modulatory effect on the immune system along with gut metabolic regulations. This pilot study needs replication in a larger randomized double-blinded control study.
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http://dx.doi.org/10.1111/nmo.13911DOI Listing
October 2020

Modulation of visual hallucinations originating from deafferented occipital cortex by robotized transcranial magnetic stimulation.

Clin Neurophysiol 2020 Aug 28;131(8):1728-1730. Epub 2020 Apr 28.

Univ. Grenoble-Alpes, Univ. Savoie Mont Blanc, CNRS, LPNC, F-38000 Grenoble, France.

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http://dx.doi.org/10.1016/j.clinph.2020.04.009DOI Listing
August 2020

Emergency room diagnoses of psychogenic nonepileptic seizures with psychogenic status and functional (psychogenic) symptoms: Whopping.

Epilepsy Behav 2020 03 24;104(Pt A):106882. Epub 2020 Jan 24.

Univ. Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, Grenoble Institut Neurosciences, GIN, 38000 Grenoble, France. Electronic address:

Collecting 130 electronic medical records and diagnoses from emergency room stays of eleven patients with confirmed psychogenic nonepileptic seizure (PNES) over a 17-year period (2001-2018), 48 different diagnostic terms were retrieved. This emphasized the need for a consensual terminology encompassing not only PNES but also all functional transient (paroxysmal) events, including episodes of motor or sensory deficits, and cognitive symptoms. Rather than defining what it is not (PNES, stroke mimicks…), it would be more accurate to define what it is: a paroxysmal functional event.
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http://dx.doi.org/10.1016/j.yebeh.2019.106882DOI Listing
March 2020

PNESSE 1: Psychogenic status and status epilepticus: Could they be distinguished retrospectively? A survey among neurologists.

Epilepsy Behav 2020 01 21;102:106665. Epub 2019 Nov 21.

EFSN, CHU Grenoble Alpes, 38043 Grenoble, France. Electronic address:

Objective: The aim of this study was to evaluate neurologists' reliability in recognizing retrospectively a diagnosis of psychogenic status and status epilepticus (SE) based solely on clinical semiology, as reported in medical charts.

Methods: This is a retrospective analysis of medical records of patients with suspected SE, diagnosed with psychogenic status and SE, proven by video-electroencephalography (EEG) monitoring, over a two-year period, from January 1st 2012 to December 31st 2013. Eight additional patients outside this time frame were included in this series because they had video-EEG proven psychogenic status, and they met all the inclusion criteria. The group with SE was divided into symptomatic SE (SSE) if a precipitating factor was identified, and undetermined SE (USE) if none were identified. Twenty-two neurologists from the CHU de Grenoble-Alpes were asked to fill out a survey where they were asked to score, for each patient, their agreement, using Likert scales, for the respective diagnoses of psychogenic status and SE. Their opinions were based on a provided written sheet summarizing the clinical description of the event and patients' clinical context. Neurologists were blinded to video-EEG monitoring results and final diagnosis. The level of agreement, disagreement, and the homogeneity of neurologist's responses according to the final diagnosis were then calculated. Finally, clinical data, as provided in the event's clinical description and context, considered as highly relevant by neurologists to establish an accurate diagnosis were gathered.

Results: Eighteen neurologists completed the survey for 48 patients, including 11 diagnosed with psychogenic status and 37 with SE (30 with SSE and 7 with USE). For patients diagnosed with SE, the presence of a precipitating factor increased the likelihood and the homogeneity among neurologists of a diagnosis of SE (77%), with a specificity (Sp) of 96% and a positive predictive value of 95%. The lack of a precipitating factor significantly decreased the diagnosis likelihood of SE (55%) with a predictive value of 82%. For patients diagnosed with psychogenic status, most of neurologists agreed with the diagnosis of psychogenic status (69%) with a predictive value of 82%, although heterogeneity in the diagnosis was found. According to neurologists participating in this study, most significant terms, found in the medical charts, helping to distinguish SE from psychogenic status were "stereotypical movements", "limb myoclonus", "epilepsy", and "vigilance alteration". To differentiate psychogenic status from SE, most relevant terms used by neurologists were "resistance to eyes opening", "anarchic movements", "prolonged motor manifestations", "limb tremor" and "opisthotonus". However, analysis of the distribution of the terms among the different groups (SSE, USE, and psychogenic status) showed no significant difference.

Significance: This study is in line with previous literature highlighting the difficulty in retrospectively differentiating SE from psychogenic status based on clinical events description recorded in the medical chart.
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http://dx.doi.org/10.1016/j.yebeh.2019.106665DOI Listing
January 2020

A Case of Peripherally Induced Task-Specific "Lipstick Dystonic Tremor".

Tremor Other Hyperkinet Mov (N Y) 2019 1;9. Epub 2019 Oct 1.

Movement Disorders Unit, Neurology Department, Grenoble Alpes University Hospital, Grenoble, FR.

Background: Peripherally induced movement disorders (PIMDs) represent a rare and debated complication of peripheral trauma.

Phenomenology Shown: We report a case of task-specific "lipstick" jerky dystonic tremor as a consequence of traumatic shoulder injury, successfully treated with EMG-guided botulinum toxin injections.

Educational Value: This case expands the phenotypic spectrum of PIMDs, with a visual example of a task-specific dystonic tremor after peripheral trauma, and the efficacy of EMG-guided botulinum toxin treatment in the setting of posttraumatic dystonic tremor.
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http://dx.doi.org/10.7916/tohm.v0.689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778424PMC
September 2020

Temporal Dynamics of Natural Static Emotional Facial Expressions Decoding: A Study Using Event- and Eye Fixation-Related Potentials.

Front Psychol 2018 12;9:1190. Epub 2018 Jul 12.

Laboratoire InterUniversitaire de Psychologie - Personnalité, Cognition, Changement Social, Université Grenoble Alpes, Université Savoie Mont Blanc, Grenoble, France.

This study aims at examining the precise temporal dynamics of the emotional facial decoding as it unfolds in the brain, according to the emotions displayed. To characterize this processing as it occurs in ecological settings, we focused on unconstrained visual explorations of natural emotional faces (i.e., free eye movements). The General Linear Model (GLM; Smith and Kutas, 2015a,b; Kristensen et al., 2017a) enables such a depiction. It allows deconvolving adjacent overlapping responses of the eye fixation-related potentials (EFRPs) elicited by the subsequent fixations and the event-related potentials (ERPs) elicited at the stimuli onset. Nineteen participants were displayed with spontaneous static facial expressions of emotions (Neutral, Disgust, Surprise, and Happiness) from the DynEmo database (Tcherkassof et al., 2013). Behavioral results on participants' eye movements show that the usual diagnostic features in emotional decoding (eyes for negative facial displays and mouth for positive ones) are consistent with the literature. The impact of emotional category on both the ERPs and the EFRPs elicited by the free exploration of the emotional faces is observed upon the temporal dynamics of the emotional facial expression processing. Regarding the ERP at stimulus onset, there is a significant emotion-dependent modulation of the P2-P3 complex and LPP components' amplitude at the left frontal site for the ERPs computed by averaging. Yet, the GLM reveals the impact of subsequent fixations on the ERPs time-locked on stimulus onset. Results are also in line with the valence hypothesis. The observed differences between the two estimation methods (Average vs. GLM) suggest the predominance of the right hemisphere at the stimulus onset and the implication of the left hemisphere in the processing of the information encoded by subsequent fixations. Concerning the first EFRP, the Lambda response and the P2 component are modulated by the emotion of surprise compared to the neutral emotion, suggesting an impact of high-level factors, in parieto-occipital sites. Moreover, no difference is observed on the second and subsequent EFRP. Taken together, the results stress the significant gain obtained in analyzing the EFRPs using the GLM method and pave the way toward efficient ecological emotional dynamic stimuli analyses.
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http://dx.doi.org/10.3389/fpsyg.2018.01190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052106PMC
July 2018

Long-term negative impact of an inappropriate first antiepileptic medication on the efficacy of a second antiepileptic medication in mice.

Epilepsia 2018 07 14;59(7):e109-e113. Epub 2018 Jun 14.

Univ Rennes, CHU Rennes, INSERM, LTSI - UMR 1099, Rennes, France.

Childhood absence epilepsy (CAE) is one of the most frequent epilepsies in infancy. The first-line recommended therapy for CAE is based on the prescription of the narrow-spectrum ethosuximide and the broad-spectrum valproic acid, which have similar efficacy in the first 12 months. Nevertheless, some antiepileptic drugs (AEDs) may worsen seizure duration and type in this syndrome. In line with this, we have encountered a case of identical twins with CAE and early exposure to different antiseizure drugs leading to divergent outcomes. From this, we hypothesized that the first AED to treat CAE may determine the long-term prognosis, especially in the developing brain, and that some situations leading to drug resistance may be explained by use of an inappropriate first AED. Therefore, we investigated this hypothesis by using a genetic mouse model of absence epilepsy (BS/Orl). Mice received a first appropriate or inappropriate AED followed by the same appropriate AED. Our data demonstrate that an inappropriate first AED has a negative impact on the long-term efficacy of a second appropriate AED. This work supports the necessity to effectively diagnose epileptic syndromes prior to medication use, particularly in children, in order to prevent the deleterious effects of an inappropriate initial AED.
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http://dx.doi.org/10.1111/epi.14454DOI Listing
July 2018

Recommendations for the use of electroencephalography and evoked potentials in comatose patients.

Neurophysiol Clin 2018 Jun 18;48(3):143-169. Epub 2018 May 18.

Service de neurophysiologie clinique, CHRU de Lille, 59037 Lille cedex, France; Université de Lille, Inserm U 1171, Troubles cognitifs dégénératifs et vasculaires, centre d'excellence des maladies neurodégénératives de Lille (LiCEND), 59000 Lille cedex, France. Electronic address:

Predicting the outcome of a comatose or poorly responsive patient is a major issue for intensive care unit teams, in order to give the most accurate information to the family and to choose the best therapeutic option. However, determining the level of cortical activity in patients with disorders of consciousness is a real challenge. Reliable criteria are required to help clinicians in the decision-making process, especially in the acute phase of coma. In this paper, we propose recommendations for recording and interpreting electroencephalography and evoked potentials in comatose patients based on the literature and the clinical experience of a group of neurophysiologists trained in the management of comatose patients. We propose methodological guidelines and discuss prognostic value of each test as well as the limitations concerning recording and interpretation. Recommendations for the strategy and timing of neurophysiological assessments are also proposed according to various clinical situations.
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http://dx.doi.org/10.1016/j.neucli.2018.05.038DOI Listing
June 2018

Electroencephalographic correlates of low-frequency vagus nerve stimulation therapy for Crohn's disease.

Clin Neurophysiol 2018 05 10;129(5):1041-1046. Epub 2018 Mar 10.

Univ. Grenoble Alpes, F-38000 Grenoble, France; Inserm, U1216, Grenoble Institut des Neurosciences, F-38000 Grenoble, France. Electronic address:

Objectives: In the context of the first clinical trial of vagus nerve stimulation (VNS) in Crohn's disease (CD), our main objective was to quantify the acute and chronic effects of VNS on brain activity in CD patients.

Methods: We measured the electroencephalogram (EEG) in 9CD patients under VNS at 10 Hz just before VNS initiation, after 6 weeks and after 12 months of chronic VNS.

Results: Acute VNS induced increased spectral power in delta and theta bands on frontal, temporal and occipital electrodes. The main significant modulation was the 12 months' chronic effect of VNS which consisted mainly in a decreased power in the alpha frequency band which was correlated with the normalization of bowel mucosal inflammation, anxiety state and vagal tone.

Conclusions: In addition to the activation of vagal efferent fibers that regulate the autonomic nervous system, our data suggest that chronic VNS has a regulatory action via afferent vagal fibers on anxio-depressive symptomatology associated to CD, which could be directly highlighted by the modulation of EEG alpha power known to be associated to depressed states.

Significance: This is the first report of the central effects of VNS in CD patients.
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http://dx.doi.org/10.1016/j.clinph.2018.02.127DOI Listing
May 2018

An Eye Fixation-Related Potential Study in Two Reading Tasks: Reading to Memorize and Reading to Make a Decision.

Brain Topogr 2018 07 15;31(4):640-660. Epub 2018 Feb 15.

Univ. Grenoble Alpes, CNRS, Grenoble INP, GIPSA-lab, 38000, Grenoble, France.

We investigated how two different reading tasks, namely reading to memorize [Read & Memorize (RM)] and reading to decide whether a text was relevant to a given topic [Read & Decide (RD)], modulated both eye movements (EM) and brain activity. To this end, we set up an ecological paradigm using the eye fixation-related potentials (EFRP) technique, in which participants freely moved their eyes to process short paragraphs, while their electroencephalography (EEG) activity was recorded in synchronization with their EM. A general linear model was used to estimate at best EFRP, taking account of the overlap between adjacent potentials, and more precisely with the potential elicited at text onset, as well as saccadic potentials. Our results showed that EM patterns were top-down modulated by different task demands. More interestingly, in both tasks, we observed slow-wave potentials that gradually increased across the first eye fixations. These slow waves were larger in the RD task than in the RM task, specifically over the left hemisphere. These results suggest that the decision-making process during reading in the RD task engendered a greater memory load in working memory than that generated in a classic reading task. The significance of these findings is discussed in the light of recent theories and models of working memory processing.
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http://dx.doi.org/10.1007/s10548-018-0629-8DOI Listing
July 2018

Clinical, Biomarker, and Molecular Delineations and Genotype-Phenotype Correlations of Ataxia With Oculomotor Apraxia Type 1.

JAMA Neurol 2018 04;75(4):495-502

Service de Neurologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Importance: Ataxia with oculomotor apraxia type 1 (AOA1) is an autosomal recessive cerebellar ataxia due to mutations in the aprataxin gene (APTX) that is characterized by early-onset cerebellar ataxia, oculomotor apraxia, axonal motor neuropathy, and eventual decrease of albumin serum levels.

Objectives: To improve the clinical, biomarker, and molecular delineation of AOA1 and provide genotype-phenotype correlations.

Design, Setting, And Participants: This retrospective analysis included the clinical, biological (especially regarding biomarkers of the disease), electrophysiologic, imaging, and molecular data of all patients consecutively diagnosed with AOA1 in a single genetics laboratory from January 1, 2002, through December 31, 2014. Data were analyzed from January 1, 2015, through January 31, 2016.

Main Outcomes And Measures: The clinical, biological, and molecular spectrum of AOA1 and genotype-phenotype correlations.

Results: The diagnosis of AOA1 was confirmed in 80 patients (46 men [58%] and 34 women [42%]; mean [SD] age at onset, 7.7 [7.4] years) from 51 families, including 57 new (with 8 new mutations) and 23 previously described patients. Elevated levels of α-fetoprotein (AFP) were found in 33 patients (41%); hypoalbuminemia, in 50 (63%). Median AFP level was higher in patients with AOA1 (6.0 ng/mL; range, 1.1-17.0 ng/mL) than in patients without ataxia (3.4 ng/mL; range, 0.8-17.2 ng/mL; P < .01). Decreased albumin levels (ρ = -0.532) and elevated AFP levels (ρ = 0.637) were correlated with disease duration. The p.Trp279* mutation, initially reported as restricted to the Portuguese founder haplotype, was discovered in 53 patients with AOA1 (66%) with broad white racial origins. Oculomotor apraxia was found in 49 patients (61%); polyneuropathy, in 74 (93%); and cerebellar atrophy, in 78 (98%). Oculomotor apraxia correlated with the severity of ataxia and mutation type, being more frequent with deletion or truncating mutations (83%) than with presence of at least 1 missense variant (17%; P < .01). Mean (SD) age at onset was higher for patients with at least 1 missense mutation (17.7 [11.4] vs 5.2 [2.6] years; P < .001).

Conclusions And Relevance: The AFP level, slightly elevated in a substantial fraction of patients, may constitute a new biomarker for AOA1. Oculomotor apraxia may be an optional finding in AOA1 and correlates with more severe disease. The p.Trp279* mutation is the most frequent APTX mutation in the white population. APTX missense mutations may be associated with a milder phenotype.
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http://dx.doi.org/10.1001/jamaneurol.2017.4373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933354PMC
April 2018

How Long Should Routine EEG Be Recorded to Get Relevant Information?

Clin EEG Neurosci 2018 Sep 21;49(5):335-341. Epub 2017 Mar 21.

1 Clinical Neurophysiology Unit, Neurology Department, University Grenoble Alpes Hospital, Grenoble, France.

Objective: The optimal duration of routine EEG (rEEG) has not been determined on a clinical basis. This study aims to determine the time required to obtain relevant information during rEEG with respect to the clinical request.

Method: All rEEGs performed over 3 months in unselected patients older than 14 years in an academic hospital were analyzed retrospectively. The latency required to obtain relevant information was determined for each rEEG by 2 independent readers blinded to the clinical data. EEG final diagnoses and latencies were analyzed with respect to the main clinical requests: subacute cognitive impairment, spells, transient focal neurologic manifestation or patients referred by epileptologists.

Results: From 430 rEEGs performed in the targeted period, 364 were analyzed: 92% of the pathological rEEGs were provided within the first 10 minutes of recording. Slowing background activity was diagnosed from the beginning, whereas interictal epileptiform discharges were recorded over time. Moreover, the time elapsed to demonstrate a pattern differed significantly in the clinical groups: in patients with subacute cognitive impairment, EEG abnormalities appeared within the first 10 minutes, whereas in the other groups, data could be provided over time.

Conclusion: Patients with subacute cognitive impairment differed from those in the other groups significantly in the elapsed time required to obtain relevant information during rEEG, suggesting that 10-minute EEG recordings could be sufficient, arguing in favor of individualized rEEG. However, this conclusion does not apply to intensive care unit patients.
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http://dx.doi.org/10.1177/1550059417698549DOI Listing
September 2018

Pallidal deep brain stimulation for dystonia: a long term study.

J Neurol Neurosurg Psychiatry 2017 11 28;88(11):960-967. Epub 2017 Sep 28.

Division of Neurology, CHU of Grenoble, Grenoble Alpes University, Grenoble, France.

Background: Pallidal deep brain stimulation (globus pallidus internus (GPi) DBS) is the best therapeutic option for disabling isolated idiopathic (IID) and inherited (INH) dystonia. Acquired dystonia (AD) may also benefit from GPi DBS. Efficacy and safety in the long-term remained to be established.

Objective: To retrospectively assess long-term clinical outcomes and safety in dystonic patients who underwent GPi DBS.

Methods: Patients were videotaped and assessed preoperatively and postoperatively (1-year and at last available follow-up) using the Burke-Fahn-Marsden Dystonia Rating Scale (motor score (BFMDRS-M); disability score (BFMDRS-D)).

Results: Sixty-one patients were included (follow-up 7.9±5.9 years; range 1-20.7). In IID and INH (n=37), the BFMDRS-M improved at first (20.4±24.5; p<0.00001) and last (22.2±18.2; p<0.001) follow-ups compared with preoperatively (50.5±28.0). In AD (n=19), the BFMDRS-M ameliorated at 1-year (40.8±26.5; p<0.02) and late follow-ups (44.3±24.3; p<0.04) compared with preoperatively (52.8±24.2). In INH dystonia with other neurological features (n=4) there was no motor benefit. In IID and INH, the BFMDRS-D improved at 1-year (9.5±7.5; p<0.0002) and late follow-ups (10.4±7.8; p<0.016) compared with preoperatively (13.3±6.9). In AD, the BFMDRS-D reduced at 1-year (12.0±8.1; p<0.01) and late follow-ups (12.7 ±6.1; p=0.2) compared with preoperatively (14.35±5.7). Most adverse events were hardware related.

Conclusions: GPi DBS is an effective and safe treatment in most patients with dystonia.
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http://dx.doi.org/10.1136/jnnp-2016-315504DOI Listing
November 2017

"Bright flashes in the dark": a close time-locked relationship between posterior lateralized periodic discharges and visual flashes.

Epileptic Disord 2017 Sep;19(3):383-384

Department of Neurology, Grenoble University Hospital, Grenoble, France.

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http://dx.doi.org/10.1684/epd.2017.0928DOI Listing
September 2017

[Psychogenic NonEpileptic Seizures: Current Knowledge and Contributions of the Study of Emotions].

Sante Ment Que Spring 2016;41(1):123-39

Professeur des universités, chercheur, CNRS, Laboratoire de psychologie et neurocognition, Département de psychologie, Université Savoie Mont Blanc, Chambéry, France.

Psychogenic nonepileptic seizures (PNES) are paroxysmal attacks that can imitate epileptic seizures but do not have a neurological origin. There has been mounting interest these last few years to unravel psychological and neuronal factors that contribute to the development of PNES. The objective of this review is twofold. First, we examine recent contributions of clinical and researches studies to define the main features of PNES. Then, we focus on the possible link between changes in processing of emotional information and the onset of PNES. In this article, we identify promising directions for future research and argue that affective neuroscience may provide original findings to better understand this disease.
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January 2017

Exploratory Phase II Trial to Evaluate the Safety and the Antiepileptic Effect of Pitolisant (BF2.649) in Refractory Partial Seizures, Given as Adjunctive Treatment During 3 Months.

Clin Neuropharmacol 2016 Jul-Aug;39(4):188-93

*Clinical Center of investigation, INSERM U1434, University Hospital of Strasbourg, Strasbourg; †Neurology and Epileptology Department, Pierre Wertheimer University Hospital, Lyon; ‡Neurology Department, Albert Michallon University Hospital, Grenoble; §Neurology Department, University Hospital, Lille; ∥Neurology Department, Pontchaillou University Hospital, Rennes; ¶Bioprojet, Paris, France; and #Neurology Department, University Hospital of Strasbourg, Strasbourg, France.

Background: Pitolisant (BF2.649) is a nonimidazole histamine 3 receptor antagonist. In previous animal studies, it has been shown that pitolisant might be helpful in chronic seizure treatment of both partial and generalized epilepsies. The present study is a multicenter, national, pragmatic, noncomparative, open-label, exploratory phase II trial. It is the first reported study of the clinical effects of pitolisant in human epilepsy.

Objective: The goal of this trial was to explore the antiepileptic effect of 3 different doses of pitolisant (20, 30, and 40 mg once daily) in patients presenting partial seizure onset despite therapy with adequate dose of 1 to 3 appropriate antiepileptic drugs.

Methods: The study has been conducted in 6 study sites in France between 2005 and 2006. The primary end point was the proportion of responders having a seizure rate decrease by at least 50%. A larger clinical trial could be started according to the results. An interim analysis was planned in the protocol to decide if the study should be continued or not according to the efficacy and safety results. Descriptive statistics were used for the analysis.

Results: An initial goal of 40 patients included had been planned; 23 were finally included. Pitolisant was well tolerated and achieved a clinical response in one third of patients after 3 months of treatment.

Conclusions: Despite encouraging data, there is no evidence for the efficacy of the drug for the regimen that was used, but no firm conclusions can be drawn because the number of included subject was small and the study was not placebo controlled.
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http://dx.doi.org/10.1097/WNF.0000000000000159DOI Listing
January 2017

Epilepsy diagnostic and treatment needs identified with a collaborative database involving tertiary centers in France.

Epilepsia 2016 May 1;57(5):757-69. Epub 2016 Apr 1.

Epilepsy Observatory, Paris, France.

Objective: To obtain perspective on epilepsy in patients referred to tertiary centers in France, and describe etiology, epilepsy syndromes, and identify factors of drug resistance and comorbidities.

Methods: We performed a cross-sectional analysis of the characteristics of 5,794 pediatric and adult patients with epilepsy included in a collaborative database in France between 2007 and 2013. Comparisons between groups used Student's t-test or Fisher's exact test for binary or categorical variables. Factors associated with drug resistance and intellectual disability were evaluated in multi-adjusted logistic regression models.

Results: Mean age at inclusion was 17.9 years; children accounted for 67%. Epilepsy was unclassified in 20% of patients, and etiology was unknown in 65%, including those with idiopathic epilepsies. Etiologies differed significantly in adult- when compared to pediatric-onset epilepsy; however, among focal structural epilepsies, mesial temporal lobe epilepsy with hippocampal sclerosis began as often in the pediatric as in adult age range. Drug resistance concerned 53% of 4,210 patients evaluable for seizure control and was highest in progressive myoclonic epilepsy (89%), metabolic diseases (84%), focal cortical dysplasia (70%), other cortical malformations (69%), and mesial temporal lobe epilepsy with hippocampal sclerosis (67%). Fifty-nine percent of patients with focal structural epilepsy and 69% with epileptic encephalopathies were drug resistant; however, 40-50% of patients with West syndrome and epileptic encephalopathy with continuous spike-and-waves during sleep were seizure-free. Ages at onset in infancy and in young adults shared the highest risk of drug resistance. Epilepsy onset in infancy comprised the highest risk of intellectual disability, whereas specific cognitive impairment affected 36% of children with idiopathic focal epilepsy.

Significance: Our study provides a snapshot on epilepsy in patients referred to tertiary centers and discloses needs for diagnosis and treatment. Large databases help identify patients with rare conditions that could benefit from specific prospective studies.
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http://dx.doi.org/10.1111/epi.13368DOI Listing
May 2016

Long term effects of low frequency (10 hz) vagus nerve stimulation on EEG and heart rate variability in Crohn's disease: a case report.

Brain Stimul 2014 Nov-Dec;7(6):914-6. Epub 2014 Aug 7.

Grenoble Institut des Neurosciences (GIN), Centre de Recherche INSERM 836 UJF-CEA-CHU, F-38043, France; Clinique Universitaire d'Hépato-Gastroentérologie, CHU de Grenoble, F-38043, France. Electronic address:

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http://dx.doi.org/10.1016/j.brs.2014.08.001DOI Listing
September 2015

Voltage-gated potassium channels autoantibodies in a child with rasmussen encephalitis.

Neuropediatrics 2014 Oct 25;45(5):336-40. Epub 2014 Jul 25.

Service de Neurochirurgie Pédiatrique, Fondation Ophtalmologique A.de Rothschild, Paris, France.

Rasmussen encephalitis (RE) is a severe epileptic and inflammatory encephalopathy of unknown etiology, responsible for focal neurological signs and cognitive decline. The current leading hypothesis suggests a sequence of immune reactions induced by an indeterminate factor. This sequence is thought to be responsible for the production of autoantibody-mediated central nervous system degeneration. However, these autoantibodies are not specific to the disease and not all patients present with them. We report the case of a 4-year-old girl suffering from RE displaying some atypical features such as fast evolution and seizures of left parietal onset refractory to several antiepileptics, intravenous immunoglobulins, and corticosteroids. Serum autoantibodies directed against voltage-gated potassium channels (VGKC) were evidenced at 739 pM, a finding never previously reported in children. This screening was performed because of an increased signal in the temporolimbic areas on brain magnetic resonance imaging, which was similar to what is observed during limbic encephalitis. The patient experienced epilepsia partialis continua with progressive right hemiplegia and aphasia. She underwent left hemispherotomy at the age of 5.5 years after which she became seizure free with great cognitive improvement. First described in adults, VGKC autoantibodies have been recently described in children with various neurological manifestations. The implication of VGKC autoantibodies in RE is a new observation and opens up new physiopathological and therapeutic avenues of investigation.
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http://dx.doi.org/10.1055/s-0034-1383822DOI Listing
October 2014

Brain processing of emotional scenes in aging: effect of arousal and affective context.

PLoS One 2014 16;9(6):e99523. Epub 2014 Jun 16.

Laboratoire de Psychologie et Neurocognition (LPNC), Univ. Grenoble Alpes, Grenoble, France; LPNC, Centre National de la Recherche Scientifique, Grenoble, France.

Research on emotion showed an increase, with age, in prevalence of positive information relative to negative ones. This effect is called positivity effect. From the cerebral analysis of the Late Positive Potential (LPP), sensitive to attention, our study investigated to which extent the arousal level of negative scenes is differently processed between young and older adults and, to which extent the arousal level of negative scenes, depending on its value, may contextually modulate the cerebral processing of positive (and neutral) scenes and favor the observation of a positivity effect with age. With this aim, two negative scene groups characterized by two distinct arousal levels (high and low) were displayed into two separate experimental blocks in which were included positive and neutral pictures. The two blocks only differed by their negative pictures across participants, as to create two negative global contexts for the processing of the positive and neutral pictures. The results show that the relative processing of different arousal levels of negative stimuli, reflected by LPP, appears similar between the two age groups. However, a lower activity for negative stimuli is observed with the older group for both tested arousal levels. The processing of positive information seems to be preserved with age and is also not contextually impacted by negative stimuli in both younger and older adults. For neutral stimuli, a significantly reduced activity is observed for older adults in the contextual block of low-arousal negative stimuli. Globally, our study reveals that the positivity effect is mainly due to a modulation, with age, in processing of negative stimuli, regardless of their arousal level. It also suggests that processing of neutral stimuli may be modulated with age, depending on negative context in which they are presented to. These age-related effects could contribute to justify the differences in emotional preference with age.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0099523PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059675PMC
October 2015

A simple febrile seizure with focal onset.

Epileptic Disord 2014 Mar;16(1):112-5

Grenoble Institut des Neurosciences, Inserm U836, Université Joseph Fourier, Centre Hospitalier Universitaire, Grenoble, France.

Simple febrile seizures last for less than 10 minutes and resolve spontaneously, in the context of a febrile illness, without focal features or recurrence during the subsequent 24 hours. We report the case of fortuitous video-EEG recording of a FS, clinically classified as "simple", which demonstrated a focal, temporal onset. This clinical finding is in agreement with animal model studies demonstrating focal onset.
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http://dx.doi.org/10.1684/epd.2014.0639DOI Listing
March 2014

Similar early characteristics but variable neurological outcome of patients with a de novo mutation of KCNQ2.

Orphanet J Rare Dis 2013 May 22;8:80. Epub 2013 May 22.

INSERM, UMR_S 910 Faculté de médecine, Marseille, France.

Background: Early onset epileptic encephalopathies (EOEEs) are dramatic heterogeneous conditions in which aetiology, seizures and/or interictal EEG have a negative impact on neurological development. Several genes have been associated with EOEE and a molecular diagnosis workup is challenging since similar phenotypes are associated with mutations in different genes and since mutations in one given gene can be associated with very different phenotypes. Recently, de novo mutations in KCNQ2, have been found in about 10% of EOEE patients. Our objective was to confirm that KCNQ2 was an important gene to include in the diagnosis workup of EOEEs and to fully describe the clinical and EEG features of mutated patients.

Methods: We have screened KCNQ2 in a cohort of 71 patients with an EOEE, without any brain structural abnormality. To be included in the cohort, patient's epilepsy should begin before three months of age and be associated with abnormal interictal EEG and neurological impairment. Brain MRI should not show any structural abnormality that could account for the epilepsy.

Results: Out of those 71 patients, 16 had a de novo mutation in KCNQ2 (23%). Interestingly, in the majority of the cases, the initial epileptic features of these patients were comparable to those previously described in the case of benign familial neonatal epilepsy (BFNE) also caused by KCNQ2 mutations. However, in contrast to BFNE, the interictal background EEG was altered and displayed multifocal spikes or a suppression-burst pattern. The ongoing epilepsy and development were highly variable but overall severe: 15/16 had obvious cognitive impairment, half of the patients became seizure-free, 5/16 could walk before the age of 3 and only 2/16 patient acquired the ability to speak.

Conclusion: This study confirms that KCNQ2 is frequently mutated de novo in neonatal onset epileptic encephalopathy. We show here that despite a relatively stereotyped beginning of the condition, the neurological and epileptic evolution is variable.
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http://dx.doi.org/10.1186/1750-1172-8-80DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3670812PMC
May 2013

Ictal inner speech jargon.

Epilepsy Behav 2013 May 21;27(2):307-9. Epub 2013 Mar 21.

CHU Grenoble, 38043 Grenoble, France.

We report on the case of a woman with jargon aphasic seizures who provided a careful written report of inner speech jargon occurring during her seizures. This inner speech jargon description is an unusual finding since in most aphasic disorders, patients also suffer from anosognosia. This case report may suggest that jargon could also involve inner speech and could be innerly detected as such. It provides an argument supporting the idea that common mechanisms may underlie both "overt" and "covert" production of jargon during aphasia.
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http://dx.doi.org/10.1016/j.yebeh.2013.02.007DOI Listing
May 2013

Persistence of cortical sensory processing during absence seizures in human and an animal model: evidence from EEG and intracellular recordings.

PLoS One 2013 4;8(3):e58180. Epub 2013 Mar 4.

Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, UPMC/INSERM UMR-S 975; CNRS UMR 7225, Hôpital Pitié-Salpêtrière, Paris, France.

Absence seizures are caused by brief periods of abnormal synchronized oscillations in the thalamocortical loops, resulting in widespread spike-and-wave discharges (SWDs) in the electroencephalogram (EEG). SWDs are concomitant with a complete or partial impairment of consciousness, notably expressed by an interruption of ongoing behaviour together with a lack of conscious perception of external stimuli. It is largely considered that the paroxysmal synchronizations during the epileptic episode transiently render the thalamocortical system incapable of transmitting primary sensory information to the cortex. Here, we examined in young patients and in the Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a well-established genetic model of absence epilepsy, how sensory inputs are processed in the related cortical areas during SWDs. In epileptic patients, visual event-related potentials (ERPs) were still present in the occipital EEG when the stimuli were delivered during seizures, with a significant increase in amplitude compared to interictal periods and a decrease in latency compared to that measured from non-epileptic subjects. Using simultaneous in vivo EEG and intracellular recordings from the primary somatosensory cortex of GAERS and non-epileptic rats, we found that ERPs and firing responses of related pyramidal neurons to whisker deflection were not significantly modified during SWDs. However, the intracellular subthreshold synaptic responses in somatosensory cortical neurons during seizures had larger amplitude compared to quiescent situations. These convergent findings from human patients and a rodent genetic model show the persistence of cortical responses to sensory stimulations during SWDs, indicating that the brain can still process external stimuli during absence seizures. They also demonstrate that the disruption of conscious perception during absences is not due to an obliteration of information transfer in the thalamocortical system. The possible mechanisms rendering the cortical operation ineffective for conscious perception are discussed, but their definite elucidation will require further investigations.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0058180PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587418PMC
September 2013

Mosaic DCX deletion causes subcortical band heterotopia in males.

Neurogenetics 2012 Nov 26;13(4):367-73. Epub 2012 Jul 26.

Génétique Clinique Centre de référence "Maladies Rares" CLAD-Ouest CHU Rennes, Rennes, France.

Subcortical band heterotopia (SBH) is a neuronal migration disorder usually described in females carrying heterozygous mutations in the X-linked doublecortin (DCX) gene. Hemizygous DCX mutations in males result in lissencephaly. Recently, exonic deletions of DCX resulting in a severer form of agyria have been reported. Nevertheless, rare male patients with SBH have been described with somatic mosaicism of point mutations. Here, we identified a somatic mosaicism for a deletion of exon 4 in the DCX gene in a male patient with SBH detected prenatally. This finding points to the possible implication of mosaic deletions in the DCX gene in unexplained forms of SBH and may allow for detection of SBH prenatally.
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http://dx.doi.org/10.1007/s10048-012-0339-4DOI Listing
November 2012

Low-frequency photoparoxysmal response in adults: an early clue to diagnosis.

J Clin Neurophysiol 2012 Apr;29(2):160-4

EFSN, Grenoble University Hospital, Grenoble, France.

Intermittent photic stimulation is performed during an EEG to evoke photoparoxysmal response. When they appear triggered by low-frequency stimulation in children, they are suggestive of rare diagnosis, that is, neuronal ceroid lipofuscinosis. Among adults, their significance is less well understood. Low-frequency (<5 Hz) intermittent photic stimulation was performed over a period of 5 years during adult standard EEG. This retrospective study included all patients exhibiting low-frequency photoparoxysmal response. Five cases were identified. Three of them presented with active epilepsy (two progressive myoclonus epilepsy, one unclassifiable), two had visual deficiency, and three had dementia. The etiologies were MELAS (two), Creutzfeldt-Jakob disease (one), Kufs disease (one), and remained undetermined for one patient. In all patients, low-frequency photoparoxysmal response was observed years or months before the final diagnoses have been reached. Low-frequency photoparoxysmal response, classically associated with childhood progressive myoclonus epilepsy, seems to have a wider etiological spectrum in adult population. Moreover, this neurophysiological feature could be present before the final diagnosis in most cases. Systematically testing low frequencies during intermittent photic stimulation even during adult EEG seems warranted, particularly in a context of severe progressive neurologic deterioration.
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http://dx.doi.org/10.1097/WNP.0b013e31824d949fDOI Listing
April 2012

Is ictal dystonia associated with an inhibitory effect on seizure propagation in focal epilepsies?

Epilepsy Res 2012 May 23;99(3):274-80. Epub 2012 Jan 23.

Epilepsy Center, Department of Neurology, University of Munich, Marchioninistrasse 15, Munich, Germany.

Purpose: In focal epilepsy, ictal version and ictal dystonia are thought to reflect seizure spread into the frontal eye field and the basal ganglia, respectively. Here we investigated whether the occurrence of dystonia during seizure evolution reflects mechanisms preventing secondary generalization. To this aim, the evolution of seizures in patients with focal epilepsies was compared as to whether concomitant (1) dystonia, (2) dystonia and version, or (3) version occurred.

Methods: Seizure evolutions of 79 patients characterized by either dystonia (n=29; 232 seizures), dystonia and head version in the same seizure evolution (n=9; 83 seizures) or head version (n=41; 330 seizures), were included in the study.

Results: The rate of secondary generalization was significant lower in seizures with ictal dystonia (8%, 6 of 72 seizures) compared to seizures with ictal dystonia and version (62%, 13 of 21 seizures, p<0.0001) or compared to seizures with version (95%, 82 of 86 seizures, p<0.0001).

Conclusion: This study shows that seizures with unilateral ictal dystonia are less likely to generalize as compared to seizures associated with version. This effect is likely to reflect the involvement of inhibitory mechanisms related to the basal ganglia, which exert an inhibiting effect on secondary seizure generalization.
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http://dx.doi.org/10.1016/j.eplepsyres.2011.12.007DOI Listing
May 2012

[Transient Epileptic Amnesia: a case report and a reappraisal].

Geriatr Psychol Neuropsychiatr Vieil 2011 Mar;9(1):83-9

Unité Epilepsie et malaises, CHU de GrenobleUnité Epilepsie et malaises, CHU de Grenoble.

Transient Epileptic Amnesia is a late-onset form of temporal lobe epilepsy characterized by recurrent attacks of transient retrograde and anterograde amnesia usually lasting less than one hour and beginning in late-middle to old age. Attacks commonly occur on waking, a potentially helpful diagnostic clue. The amnesic attacks may be associated with persistent memory complaints. The diagnosis is made on the basis of the clinical history, wake or sleep - deprived EEG (often repeated) and/or a clear - cut response to anticonvulsivant therapy. The pathophysiology remains poorly understood. It is uncertain whether recurrent episodes of amnesia represent ictal or post-ictal phenomena.
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http://dx.doi.org/10.1684/pnv.2011.0254DOI Listing
March 2011

Multimodal imaging reveals the role of γ activity in eating-reflex seizures.

J Neurol Neurosurg Psychiatry 2011 Oct 19;82(10):1171-3. Epub 2010 Nov 19.

INSERM, U836, Grenoble Institute of Neuroscience, Grenoble, France.

In reflex epilepsies, alteration of γ oscillations may mediate transition between interictal and ictal states. Here, we explored a patient having seizures triggered by syrup intake. From intracranial electroencephalography combined with functional MRI, the overlap of the gustatory cortex and of the preictal and ictal onset zones, as defined by early gamma changes, motivated the successful resective surgery of the middle short gyrus of the right insula. This case provides a rare demonstration from human gamma activity that the route to seizure may be supported by the interplay between physiological and epileptogenic networks.
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http://dx.doi.org/10.1136/jnnp.2010.212696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338065PMC
October 2011