Dominique Guehl

French National Centre for Scientific Research, Lutetia Parisorum, Île-de-France, France

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Publications (118)503.06 Total impact

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    ABSTRACT: Objective: To confirm the efficacy and safety of deep brain stimulation (DBS) of the internal part of the globus pallidus in improving severe tardive dyskinesia (TD). Methods: Nineteen patients with severe pharmacoresistant TD were included. All were assessed at baseline and at 3, 6 (main outcome measure), and 12 months, and in the long term (6-11 years) for 14 patients, after bilateral pallidal DBS, using motor scales (Extrapyramidal Symptoms Rating Scale [ESRS], Abnormal Involuntary Movement Scale [AIMS]), cognitive scales, and a psychiatric assessment. At 6 months, a double-blind ESRS evaluation was performed in the stimulation "on" and stimulation "off" conditions. Results: At 6 months, all patients had a decrease of more than 40% on the ESRS. The efficacy of the procedure was confirmed by a double-blind evaluation. This improvement was maintained at 12 months (ESRS: decrease of 58% [21%-81%]; AIMS: decrease of 50% [7%-77%]) and in the long term (ESRS: decrease of 60% [22%-90%]; AIMS: decrease of 63% [14%-94%], n = 14). All the subscores of the ESRS (parkinsonism, dystonia, and chorea) and of the AIMS (facial, oral, extremities, and trunk movements) improved. Despite psychiatric comorbidities at baseline, cognitive and psychiatric tolerability of the procedure was excellent. No cognitive decline was observed and mood was improved in most of the patients. Conclusions: Pallidal DBS procedure should be considered as a therapeutic option in disabling TD refractory to medical treatment. Classification of evidence: This study provides Class II evidence that in patients with severe pharmacoresistant TD with implanted pallidal leads, the stimulation "on" condition significantly improved ESRS scores compared to the stimulation "off" condition.
    No preview · Article · Jan 2016 · Neurology
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    ABSTRACT: Objectives: To highlight the risk of clinical worsening after deep brain stimulation in histologically proven multiple system atrophy (MSA) patients presenting slow and relatively benign disease progression mimicking Parkinson's disease (PD). In such cases but also in more typical MSA patients, the results of deep brain stimulation have been mostly reported as case reports and small patient series. Methods: The present study describes the outcome of the largest series of histologically proven MSA patients who underwent deep brain stimulation (DBS) of the subthalamic nucleus because they were considered as having PD at the time of surgery. Results: Three patients showed significant improvement of motor signs after surgery while two did not. Clinical improvement was short-lasting and rapidly followed by the occurrence of disabling manifestations of MSA that counteracted DBS benefits. Conclusions: Together with previous reports, our study demonstrates that DBS should not be recommended for MSA patients. It also underlines that detecting subtle red flags is crucial to avoid DBS surgery in this population.
    Full-text · Article · Jan 2016 · Parkinsonism & Related Disorders
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    ABSTRACT: Purpose: A previous study reported an increased prevalence of bruxism (25%) in patients with cranio-cervical dystonia (CCD) compared to normal controls (13%). CCD can affect the muscles of the head and neck. Besides the CCD affecting these muscles, hemifacial spasm (HFS) is a form of peripheral myoclonus due to a neurovascular conflict affecting the muscles of the face. The fact that they affect the same muscle regions could lead to other links in clinical manifestations such as bruxism, which is more common in patients with CCD than in the normal population. The aim was to study the prevalence of bruxism in patients with HFS. Materials and methods: Patients with HFS were enrolled in the department of clinical neurophysiology (Bordeaux University Hospital) over a 6-month period. They were paired regarding age, the absence of neurological pathology or neuroleptics intake. To be included in the study, patients needed to have had unilateral involuntary facial muscle contractions affecting one hemiface. A hetero-questionnaire and a clinicial study were performed. The diagnostic criteria of bruxism included parafunction items such as grinding and clenching and at least one of the following clinical signs: abnormal tooth wear, temporomandibular joint (TMJ) pain, TMJ clicking, muscle hypertonia (masseter or temporal muscles). Additional epidemiological data were collected including age, sex, disease duration, stress, and sleep disorders. Stress symptoms inventory included symptoms like depression, strong heartbeat, dry mouth, anger, inability to concentrate, weakness, fatigability, insomnia, headache, and excessive sweating. The sleep disorder diagnosis included at least two of the symptoms described in the ICSD-3. All these criteria were recorded as either present (scored "1") or absent (scored "0"). Results: The prevalence of bruxism in the two groups (normal and HFS) was not significantly different (p = 0.37). The rate was not significantly different between sleep and awake bruxism (p = 0.15) in both groups. Stress influenced the occurrence of bruxism in these two groups (p < 0.001). Conclusion: The results of this study indicated that clenching behaviors were higher in the HFS group, and that factors such as stress affected this group. The prevalence of bruxism was not higher in this population than in the normal control.
    No preview · Article · Nov 2015 · Journal of Prosthodontics
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    Full-text · Dataset · Aug 2015
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    ABSTRACT: Involuntary movements, or dyskinesia, represent a debilitating complication of levodopa (L-dopa) therapy for Parkinson's disease (PD). L-dopa-induced dyskinesia (LID) are ultimately experienced by the vast majority of patients. In addition, psychiatric conditions often manifested as compulsive behaviours, are emerging as a serious problem in the management of L-DOPA therapy. The present review attempts to provide an overview of our current understanding of dyskinesia and other L-DOPA-induced dysfunctions, a field that dramatically evolved in the past twenty years. In view of the extensive literature on LID, there appeared a critical need to re-frame the concepts, to highlight the most suitable models, to review the central nervous system (CNS) circuitry that may be involved, and to propose a pathophysiological framework was timely and necessary. An updated review to clarify our understanding of LID and other L-dopa-related side effects was therefore timely and necessary. This review should help in the development of novel therapeutic strategies aimed at preventing the generation of dyskinetic symptoms. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Jul 2015 · Progress in Neurobiology
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    Full-text · Dataset · Jun 2015
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    Full-text · Dataset · Jun 2015
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    DESCRIPTION: accepté pour publication (NCCN) Summary Somatosensory evoked potentials (SSEPs) are increasingly performed for the assessment of peripheral neuropathies, but no practical guidelines have been established in this specific application. For this purpose, a survey was conducted among the French-speaking practitioners having an experience of SSEP recording in the context of peripheral neuropathies. The objectives were to determine the relevant indication criteria and technical settings for SSEP recording in this condition. From this survey, SSEPs appeared to be a second-line test when electroneuromyographic investigation was not enough conclusive, providing complementary and valuable information on peripheral proximal conduction and central conduction in the somatosensory pathways. Guidelines for a standardized recording protocol, including the various variables to measure, are proposed. This consensus statement is an important step in the process to recognize the value of this technique in assessing peripheral neuropathies in clinical practice. Keywords: diagnosis; evoked potentials; indication; parameters; peripheral neuropathies; technique.
    Full-text · Research · Apr 2015
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    ABSTRACT: After more than 50 years of treating Parkinson's disease with l-DOPA, there are still no guidelines on setting the optimal dose for a given patient. The dopamine transporter type 1, now known as solute carrier family 6 (neurotransmitter transporter), member 3 (SLC6A3) is the most powerful determinant of dopamine neurotransmission and might therefore influence the treatment response. We recently demonstrated that methylphenidate (a dopamine transporter inhibitor) is effective in patients with Parkinson's disease with motor and gait disorders. The objective of the present study was to determine whether genetic variants of the dopamine transporter type 1-encoding gene (SLC6A3) are associated with differences in the response to treatment of motor symptoms and gait disorders with l-DOPA and methylphenidate (with respect to the demographic, the disease and the treatment parameters and the other genes involved in the dopaminergic neurotransmission). This analysis was part of a multicentre, parallel-group, double-blind, placebo-controlled, randomized clinical trial of methylphenidate in Parkinson's disease (Protocol ID:2008-005801-20; ClinicalTrials.gov:NCT00914095). We scored the motor Unified Parkinson's Disease Rating Scale and the Stand-Walk-Sit Test before and after a standardized acute l-DOPA challenge before randomization and then after 3 months of methylphenidate treatment. Patients were screened for variants of genes involved in dopamine metabolism: rs28363170 and rs3836790 polymorphisms in the SLC6A3 gene, rs921451 and rs3837091 in the DDC gene (encoding the aromatic L-amino acid decarboxylase involved in the synthesis of dopamine from l-DOPA), rs1799836 in the MAOB gene (coding for monoamine oxidase B) and rs4680 in the COMT gene (coding for catechol-O-methyltransferase). Investigators and patients were blinded to the genotyping data throughout the study. Eighty-one subjects were genotyped and 61 were analysed for their acute motor response to l-DOPA. The SLC6A3 variants were significantly associated with greater efficacy of l-DOPA for motor symptoms. The SLC6A3 variants were also associated with greater efficacy of methylphenidate for motor symptoms and gait disorders in the ON l-DOPA condition. The difference between motor Unified Parkinson's Disease Rating Scale scores for patients with different SLC6A3 genotypes was statistically significant in a multivariate analysis that took account of other disease-related, treatment-related and pharmacogenetic parameters. Our preliminary results suggest that variants of SLC6A3 are genetic modifiers of the treatment response to l-DOPA and methylphenidate in Parkinson's disease. Further studies are required to assess the possible value of these genotypes for (i) guiding l-DOPA dose adaptations over the long term; and (ii) establishing the risk/benefit balance associated with methylphenidate treatment for gait disorders. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    Full-text · Article · Mar 2015 · Brain
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    ABSTRACT: When a subject faces conflicting situations, decision-making becomes uncertain. The human dorsal anterior cingulate cortex (dACC) has been repeatedly implicated in the monitoring of such situations, and its neural activity is thought to be involved in behavioral adjustment. However, this hypothesis is mainly based on neuroimaging results and is challenged by animal studies that failed to report any neuronal correlates of conflict monitoring. This discrepancy is thought be due either to methodological or more fundamental cross-species differences. In this study, we eliminated methodological biases and recorded single-neuron activity in monkeys performing a Stroop-like task. We found specific changes in dACC activity during incongruent trials but only in a small subpopulation of cells. Critically, these changes were not related to reaction time and were absent before any incorrect action was taken. A larger fraction of neurons exhibited sustained activity during the whole decision period, whereas another subpopulation of neurons was modulated by reaction time, with a gradual increase in their firing rate that peaked at movement onset. Most of the neurons found in these subpopulations exhibited activity after the delivery of an external negative feedback stimulus that indicated an error had been made. These findings, which are consistent with an executive control role, reconcile various theories of prefrontal cortex function and support the homology between human and monkey cognitive architectures. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
    No preview · Article · Jan 2015 · Cerebral Cortex
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    ABSTRACT: Background: Attentional resources appear to be involved in the occurrence of FoG. The Parkgait study recently reported that methylphenidate reduces gait hypokinesia and freezing of gait (FoG) in advanced PD patients receiving STN-DBS in the off-dopaminergic drug condition. Methylphenidate is considered to improve attention. The primary objective of the present ancillary study was to determine whether methylphenidate reduced the interference between a cognitive task and gait in patients with FoG. The study's secondary objective was to compare attentional performance in methylphenidate-treated and placebo-treated patients. Methods: A total of 24 patients (from two centers) were included in the study. Patients were randomly assigned 1:1 to a three-month course of methylphenidate (1mg/kg/day) or placebo. Patients were assessed after an acute L-dopa challenge. The primary outcome criterion was the stride length ratio ((dual-task stride length minus free gait stride length)/free gait stride length). Trials with FoG episodes were excluded from the analysis. Secondary outcomes included changes in reaction times for computerized attention tasks and FoG severity. Results: When comparing patients receiving methylphenidate with those receiving placebo, we did not observe any significant differences in the interaction between the dual task and gait or in attentional performance. Conclusion: As in the main Parkgait study, methylphenidate did not reduce gait hypokinesia in patients receiving dopaminergic treatment. Our present results suggest that the reduction in the number of FoG episodes previously observed in patients on methylphenidate was neither due to interaction between a dual-task and gait nor an increase in attentional performance.
    No preview · Article · Oct 2014 · Gait & Posture
  • F. Caire · D. Guehl · P. Burbaud · A. Benazzouz · E. Cuny
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    ABSTRACT: Objective: O-arm(®) now gives us the opportunity not only to perform 2D but also 3D scans during deep brain stimulation (DBS) procedures. We present our experience with the intraoperative use of this device. Our objective was to measure the geometrical accuracy of electrode placement during surgical procedures driven under O-arm(®) control. Methods: Fifteen patients underwent STN-DBS. For the first 4 patients, 3D scans were performed at the end of the procedure. We calculated the accuracy of electrode positioning, i.e. the distance between final electrode positioning and the planned trajectory. For the next 11 patients, who underwent both intraoperative and final 3D scan, we also calculated the accuracy of the microelectrode positioning. Results: Average stimulation-induced improvement of UPDRS-III score was 52.5±15%. For the first 4 patients, the mean electrode positioning accuracy was 1.46±0.56mm. For the 11 patients who underwent intraoperative 3D scan, the mean microelectrodes positioning accuracy was 1.59±1.1mm. Aberrant positioning was detected in two cases, and was analyzed by fusing 3D scan with preoperative MR images. The definite electrodes positioning accuracy was 1.05±0.54mm. Conclusion: Intraoperative 3D scan is feasible, and can help us detect and correct early aberrant trajectories.
    No preview · Article · Sep 2014 · Neurochirurgie
  • D. Guehl · E. Cuny · F. Lafourcade · P. Burbaud

    No preview · Article · May 2014 · Fundamental and Clinical Pharmacology

  • No preview · Article · Apr 2014 · Revue Neurologique

  • No preview · Article · Apr 2014 · Revue Neurologique
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    ABSTRACT: Chorea-acanthocytosis (ChAc) is a neuroacanthocytosis syndrome presenting with severe movement disorders poorly responsive to drug therapy. Case reports suggest that bilateral deep brain stimulation (DBS) of the ventro-postero-lateral internal globus pallidus (GPi) may benefit these patients. To explore this issue, the present multicentre (n=12) retrospective study collected the short and long term outcome of 15 patients who underwent DBS. Data were collected in a standardized way 2-6 months preoperatively, 1-5 months (early) and 6 months or more (late) after surgery at the last follow-up visit (mean follow-up: 29.5 months). Motor severity, assessed by the Unified Huntington's Disease Rating Scale-Motor Score, UHDRS-MS), was significantly reduced at both early and late post-surgery time points (mean improvement 54.3% and 44.1%, respectively). Functional capacity (UHDRS-Functional Capacity Score) was also significantly improved at both post-surgery time points (mean 75.5% and 73.3%, respectively), whereas incapacity (UHDRS-Independence Score) improvement reached significance at early post-surgery only (mean 37.3%). Long term significant improvement of motor symptom severity (≥20 % from baseline) was observed in 61.5 % of the patients. Chorea and dystonia improved, whereas effects on dysarthria and swallowing were variable. Parkinsonism did not improve. Linear regression analysis showed that preoperative motor severity predicted motor improvement at both post-surgery time points. The most serious adverse event was device infection and cerebral abscess, and one patient died suddenly of unclear cause, 4 years after surgery. This study shows that bilateral DBS of the GPi effectively reduces the severity of drug-resistant hyperkinetic movement disorders such as present in ChAc.
    Full-text · Article · Nov 2013 · PLoS ONE
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    ABSTRACT: Obsessive-compulsive disorder (OCD) is associated with visuospatial working memory deficits. Intolerance of uncertainty is thought to be a core component of OCD symptoms. Recent findings argue for a possible relationship between abilities in visuospatial memory and uncertainty. However, this relationship remains unclear in both OCD patients and healthy subjects. To address this issue, we measured performance in visuospatial working memory and the propensity to express uncertainty during decision making. We assessed their relationship and the temporal direction of this relationship in both OCD patients and healthy subjects. Baseline abilities in visuospatial working memory were measured with the Corsi block-tapping test. A delayed matching-to-sample task was used to identify explicit situations of certainty, uncertainty and ignorance and to assess continuous performance in visuospatial working memory. Behavioural variables were recorded over 360 consecutive trials in both groups. Baseline scores of visuospatial working memory did not predict the number of uncertain situations in OCD patients whereas they did in healthy subjects. Uncertain trials led to reduced abilities in visuospatial working memory to 65% of usual performance in OCD patients whereas they remained stable in healthy subjects. The present findings show an opposite temporal direction in the relationship between abilities in working memory and uncertainty in OCD patients and healthy subjects. Poor working memory performance contributes to the propensity to feel uncertainty in healthy subjects whereas uncertainty contributes to decreased continuous performance in working memory in OCD patients.
    Full-text · Article · Oct 2013 · Psychological Medicine
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    Full-text · Article · Oct 2013 · Annals of Physical and Rehabilitation Medicine
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    Full-text · Article · Oct 2013 · Annals of Physical and Rehabilitation Medicine
  • B Julliac · P Cotillon · D Guehl · B Richez · F Sztark
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    ABSTRACT: Epileptiform discharges (ED) can occur during sevoflurane induction, especially in young female patients and when high alveolar concentrations are used. The aim of this study was to evaluate whether low sevoflurane concentration reduces the occurrence of ED in female patients. Thirty-four female patients scheduled for minor gynecological surgery were prospectively included and randomized in two groups. In group A, anesthesia was induced with sevoflurane inspired 8% manually set via the circuit of the Zeus(®) (Dräger Medical, Lübeck, Germany) anesthesia workstation (fresh gas flow 8L.min(-1)) for 2min and then 2.5%. In group B, induction was performed by target-controlled inhalation with a target end-tidal concentration of sevoflurane set at 2.5% (fresh gas flow in auto-control mode). Electroencephalogram (EEG) was recorded in the operating room throughout induction till two min after intubation and analyzed off-line by a neurophysiologist blinded to the randomization. ED occurred in five patients (15%): one in group A and four in group B (P>0.05). ED occurred with a median delay of 303 s [25-75 interquartiles: 135-418] and the median duration of ED episode was 13 s [3-78]. Fifteen patients had abnormal movements without simultaneous EEG abnormality. Induction of anesthesia with low target concentration of sevoflurane (2.5%) fails to totally prevent the occurrence of ED in young female patients and should be used carefully in this population.
    No preview · Article · Sep 2013 · Annales francaises d'anesthesie et de reanimation

Publication Stats

3k Citations
503.06 Total Impact Points

Institutions

  • 1998-2015
    • French National Centre for Scientific Research
      • Institut des maladies neurodégénératives (MN)
      Lutetia Parisorum, Île-de-France, France
    • University of Bordeaux
      Burdeos, Aquitaine, France
  • 2002-2013
    • Centre Hospitalier Universitaire de Bordeaux
      Burdeos, Aquitaine, France
  • 1997-2012
    • Université Victor Segalen Bordeaux 2
      • • Institut des Maladies Neurodégénératives IMN
      • • Centre de Résonance Magnétique des Systèmes Biologiques
      Burdeos, Aquitaine, France
  • 2011
    • Université de Poitiers
      Poitiers, Poitou-Charentes, France