[show abstract][hide abstract] 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.
Psychological Medicine 10/2013; · 5.59 Impact Factor
[show abstract][hide abstract] 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.
Annales francaises d'anesthesie et de reanimation 09/2013; · 0.77 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: The dorso-lateral part of the subthalamic nucleus (STN) is considered as the usual target of deep brain stimulation for Parkinson's disease. Nevertheless, the exact anatomical location of the electrode contacts used for chronic stimulation is still a matter of debate. The aim of this study was to perform a systematic review of the existing literature on this issue. METHOD: We searched for studies on the anatomical location of active contacts published until December 2012. RESULTS: We identified 13 studies, published between 2002 and 2010, including 260 patients and 466 electrodes. One hundred and sixty-four active contacts (35 %) were identified within the STN, 117 (25 %) at the interface between STN and the surrounding structures, 184 (40 %) above the STN and one within the substantia nigra. We observed great discrepancies between the different series. The contra-lateral improvement was between 37 and 78.5 % for contacts located within the STN, between 48.6 and 73 % outside the STN, between 65.3 and 66 % at the interface. The authors report no clear correlation between anatomical location and stimulation parameters. CONCLUSIONS: Post-operative analysis of the anatomical location of active contacts is difficult, and all the methods used are debatable. The relationship between the anatomical location of active contacts and the clinical effectiveness of stimulation is unclear. It would be necessary to take into account the volume of the electrode contacts and the diffusion of the stimulation. We can nevertheless assume that the interface between dorso-lateral STN, zona incerta and Forel's fields could be directly involved in the effects of stimulation.
[show abstract][hide abstract] ABSTRACT: Adult-onset epilepsy is commonly thought to be secondary to a brain lesion. However, the etiology of adult-onset epilepsy remains unknown in approximately 25% of patients, despite progress in medical and diagnostic tools. In the present study, we investigated whether late-onset partial cryptogenic epilepsies could be subgrouped based on seizure semiology and clinical characteristics. A total of 41 patients with late-onset cryptogenic epilepsy were included, and the corresponding clinical and electrophysiological data were analyzed. The following three clinical subgroups were identified: 1) a group that fulfilled the diagnostic criteria of transient epileptic amnesia (TEA); 2) a group with late-onset cryptogenic epilepsies with a temporal seizure semiology; and 3) a cryptogenic extratemporal group, which was consistent with the categorization of cryptogenic epilepsies, i.e., epilepsies involving unknown lesions. The temporal group showed homogeneous clinical characteristics, especially a rapid evolution and a greater tendency toward generalization and pharmacoresistance compared with the other two groups. Transient epileptic amnesia was associated with a higher frequency of sleep disorders than either of the other groups. Our findings argue for the clinical identification of a subgroup of late-onset temporal epilepsy that might constitute an idiopathic form. The association between TEA and sleep disorders would suggest a possible pathophysiological role of sleep apnea syndromes in TEA.
[show abstract][hide abstract] ABSTRACT: Background: 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. Methods: 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). Results: 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. Conclusion: This study shows that bilateral DBS of the GPi effectively reduces the severity of drug-resistant hyperkinetic movement disorders such as present in ChAc. Funding: This study was supported by the ERA-net E-Rare consortium European Multidisciplinary Initiative on Neuroacanthocytosis (EMINA); www.e-rare.eu/node/474. Western blot analysis for chorein was performed with the financial support of the Neuroacanthocytosis Advocacy and the EMINA consortium (BMBF 01GM1003). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist.
[show abstract][hide abstract] 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.
PLoS ONE 01/2013; 8(11):e79241. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: INTRODUCTION: Behavioral adaptation generally follows the contextual changes arising from the consequences (rewards and punishments) of an action. According to the reciprocal determinism model, there is a mutual influence between external context, cognitive processes and behavior. The maladaptive behaviors observed in obsessive-compulsive disorder (OCD) have been hypothesized to result from the disruption of the interactions between these three entities. For this, we assessed the influence of error signals and checking behavior on prefrontal cortical functions during decision-making in 14 OCD patients and 14 matched healthy participants. METHODS: We used a behavioral task designed to elicit intolerance of uncertainty (IU) followed by the free expression of checking behaviors, which was coupled with functional magnetic resonance imaging. RESULTS: At the behavioral level, IU intensity was correlated to the number of checking behaviors in both checking OCD patients and healthy controls during decision-making. However, external error signals did not influence checking behaviors in OCD patients, whereas they appeared to trigger checking behaviors in healthy subjects. At the neural level, IU intensity was positively correlated with activation in the orbitofrontal cortex (OFC) in both the OCD and control groups. At the region of interest (ROI) level, error signals increased IU-related OFC activations; in contrast, checking behaviors contributed to decreasing these neural activations in the healthy subjects, but no such modulation was observed in the OCD patients. CONCLUSIONS: Our results show that IU-related OFC dysfunctions are not under the influence of the context and the behavioral response in OCD, suggesting that alterations of the dynamic features for this neural network may contribute to the expression of OCD symptoms.
[show abstract][hide abstract] ABSTRACT: OBJECTIVE: Bispectral index (BIS) may be used in traumatic brain-injured patients (TBI) with intractable intracranial hypertension to adjust barbiturate infusion but it is obtained through a unilateral frontal electrode. The objective of this study was to evaluate differences in BIS between hemispheres in two groups: unilateral frontal (UFI) and diffuse (DI) injured. PATIENTS AND METHODS: Prospective monocenter observational study in 24 TBI treated with barbiturates: 13 UFI and 11 DI. Simultaneous BIS and EEG was recorded for 1h. Goal of monitoring was a left BIS between 5 and 15. Biases in BIS were considered as clinically relevant if greater than 5. Differences in biases were interpreted from both statistical (Mann-Whitney test) and clinical points of view. RESULTS: Mean BIS in the two hemispheres remained in the same monitoring range. There were statistic and clinical differences in some values in the two groups of patients (15% of bias greater than I5I in UFI group and 10% in DI group). BIS monitoring allowed the adequate number of bursts/minutes to be predicted in 18 patients and did not detect an overdosage in 2. CONCLUSIONS: While asymmetric BIS values in TBI patients occur whatever the kind of injury, they were not found to be clinically relevant in most of these heavily sedated patients. Asymmetrical BIS monitoring might be sufficient to monitor barbiturate infusion in TBI provided that the concordance between BIS and EEG is regularly checked.
Annales francaises d'anesthesie et de reanimation 11/2012; · 0.77 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Huntington's disease is characterized by neuronal loss throughout the disease course. Voxel-based morphometry studies have reported reductions in gray matter concentration (GMC) in many brain regions in patients with Huntington. The description of the time course of gray matter loss may help to identify some evolution markers. Here, we conducted a meta-analysis of voxel-based morphometry studies of Huntington's disease to describe the evolution of brain gray matter loss. METHODS: A systematic search led to the inclusion of 11 articles on Huntington's disease (297 patients and 205 controls). We extracted data from patients with preclinical Huntington, patients with clinical Huntington, and controls. Finally, anatomical likelihood estimation analyses were conducted to identify GMC changes between preclinical patients and controls, between clinical patients and controls, and between preclinical and clinical patients. RESULTS: Preclinical patients exhibited gray matter loss in the left basal ganglia and the prefrontal cortex. Clinical patients had bilateral gray matter loss in the basal ganglia, the prefrontal cortex, and the insula. The left striatum was smaller in clinical patients than preclinical patients. CONCLUSIONS: Neurodegenerative processes associated with Huntington's disease, as assessed by GMC reduction, begin in the left hemisphere and extend to the contralateral hemisphere throughout the inexorable course of the disease. Changes in gray matter, especially the volumetric side ratio of the striatum, could represent a relevant biomarker for characterizing the different progression stages of the disease.
European Journal of Neurology 08/2012; · 4.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: Refractory status epilepticus (SE) is a current daily therapeutic challenge. Electroconvulsive therapy (ECT), which is frequently used to treat psychiatric disorders, is known to raise the seizure threshold. As such, ECT could be of major interest in refractory SE. In this paper, we provide a brief overview of ECT in refractory SE. Although no placebo-controlled or open-label study has been published on the efficacy or safety of ECT in refractory SE, eight case reports have been identified. SE cessation was obtained in 80% of cases, and complete recovery was achieved in 27% of patients. Despite the heterogeneity of the ECT parameters used in these articles, we identified some common features that may be recommended for the use of ECT in refractory SE. ECT might be a viable therapeutic strategy for the most resistant and severe cases of SE, particularly after the failure of two inductions of anesthetic coma. This potential indication highlights the urgent need for clinical trials that assess the usefulness of ECT in refractory SE.
[show abstract][hide abstract] ABSTRACT: Despite optimum medical management, many patients with Parkinson's disease are incapacitated by gait disorders including freezing of gait. We aimed to assess whether methylphenidate--through its combined action on dopamine and noradrenaline reuptake--would improve gait disorders and freezing of gate in patients with advanced Parkinson's disease without dementia who also received subthalamic nucleus stimulation.
This multicentre, parallel, double-blind, placebo-controlled, randomised trial was done in 13 movement disorders departments in France between October, 2009, and December, 2011. Eligible patients were younger than 80 years and had Parkinson's disease, severe gait disorders, and freezing of gate despite optimised treatment of motor fluctuations with dopaminergic drugs and subthalamic stimulation. We randomly assigned patients (1:1 with a computer random-number generator in blocks of four) to receive methylphenidate (1 mg/kg per day) or placebo capsules for 90 days. Patients, their carers, study staff, investigators, and data analysts were masked to treatment allocation. To control for confounding effects of levodopa we assessed patients under standardised conditions with an acute levodopa challenge. Our primary outcome was a change in the number of steps during the stand-walk-sit (SWS) test without levodopa. We compared the respective mean numbers of steps at day 90 in the methylphenidate and placebo groups in a covariance analysis and adjusted for baseline differences. This trial is registered with ClinicalTrials.gov, number NCT00914095.
We screened 81 patients and randomly assigned 35 to receive methylphenidate and 34 to receive placebo. 33 patients in the methylphenidate group and 32 patients in the placebo group completed the study. Efficacy outcomes were assessed in the patients who completed the study. Compared with patients in the placebo group (median 33 steps [IQR 26-45]), the patients in the methylphenidate group made fewer steps at 90 days (31 [26-42], F((1, 62))=6·1, p=0·017, adjusted size effect 0·61). Adverse events were analysed in all randomly assigned patients. There were significantly more adverse events in the methylphenidate group compared with placebo. Patients on methylphenidate had a significant increase in heart rate (mean 3·6 [SD 7·2] beats per min) and decrease in weight (mean 2·2 [SD 1·8] kg) compared with the placebo group.
Methylphenidate improved gait hypokinesia and freezing in patients with advanced Parkinson's disease receiving subthalamic nucleus stimulation. Methylphenidate represents a therapeutic option in the treatment of gait disorders at the advanced stage of Parkinson's disease. The long term risk-benefit balance should be further studied.
French Ministry of Health and Novartis Pharma.
The Lancet Neurology 05/2012; 11(7):589-96. · 23.92 Impact Factor
[show abstract][hide abstract] ABSTRACT: Obsessive-compulsive disorder (OCD) is a frequent psychiatric disorder characterized by repetitive intrusive thoughts and severe anxiety, leading to compulsive behaviors. Although medical treatment is effective in most cases, resistance is observed in about 30% of patients. In this context, deep brain stimulation (DBS) of the caudate or subthalamic nuclei has been recently proposed with encouraging results. However, some patients were unimproved or exhibited awkward side effects. Therefore, exploration of new targets for DBS remains critical in OCD. In the latter, functional imaging studies revealed overactivity in the limbic and associative cortico-subcortical loops encompassing the thalamus. However, the role of the thalamus in the genesis of repetitive behaviors and related anxiety is unknown. Here, we tested the hypothesis that pharmacological-induced overactivity of the medial thalamus could give rise to abnormal behaviors close to that observed in OCD. We modulated the ventral anterior (VA) and medial dorsal (MD) nuclei activity by in situ bicuculline (GABA(A) antagonist) microinjections in subhuman primates and assessed their pharmacological-induced behavior. Bicuculline injections within the VA caused significant repetitive and time-consuming motor acts whereas those performed within the MD induced symptoms of dysautonomic dysregulation along with abnormal vocalizations and marked motor hypoactivity. These findings suggest that overactivation of the VA and MD nuclei of the thalamus provokes compulsive-like behaviors and neurovegetative manifestations usually associated with the feeling of anxiety in OCD patients. In further research, this translational approach should allow us to test the effectiveness and side effects of these thalamic nuclei DBS in monkey and perhaps, in a second step, to propose a transfer of this technique to severely disabled OCD patients.
[show abstract][hide abstract] ABSTRACT: To determine the safety and the self-reported efficacy of botulinum toxin injections for adult spasticity in current clinical practice.
A prospective observational study.
A total of 406 adult patients with focal spasticity received of 1136 series botulinum toxin injections at Bordeaux University Hospital from January 2007 to December 2009.
Adverse events following botulinum toxin injections were reported. Their severity and the therapeutic efficacy of botulinum toxin injections were estimated with a four-point self-reporting scale (0 to 3). Latency and duration of adverse events and subjective improvement were also noted.
The data of 640 series of injections were analyzed. Forty-six (7.2%) adverse events were reported, of which 36 (78%) were local. There were 18 (39%) cases of local muscular weakness with an average duration of 30.0 (SD 38.2) days, and an average severity score of 1.0 (SD 0.97). Among systemic adverse events, there were 8 (17%) cases of excessive fatigue without global muscular weakness and 2 (4%) cases of transitory generalized muscular weakness. The average subjective improvement score was 1.89 (SD 0.97) and was higher for upper, than for lower, limbs (P=0.007).
Self-reported adverse events following botulinum toxin injections in spasticity are rare, often benign and of short duration in current clinical practice. Botulinum toxin is considered effective by patients in treating spasticity of the upper and lower limbs.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Compulsive checking behaviors are common in obsessive-compulsive disorder (OCD). Several authors have suggested that these checking rituals could be related to memory deficits. Our aim was to test whether patients with OCD show working memory impairment in relation to their checking behavior. METHODS: We evaluated the verbal and visuospatial components of patients' and controls' working memory using the reading span and backward location span tests. Checking behaviors were measured by recording participants' eye movements during an image comparison task using a non-invasive, infra-red TOBII 1750 eyetracker. Participants were seated, head-free, in a natural position in front of the eyetracker screen where the images were displayed. RESULTS: Patients with OCD made more gaze moves to compare images than controls. Both patients' working memory spans were reduced, and the patients' deficit in the comparison task was negatively related to their working memory spans. CONCLUSIONS: This work demonstrates that checking behavior in OCD is linked to a general reduction of the patients' verbal and visuospatial working memory span.
[show abstract][hide abstract] ABSTRACT: Botulinum toxin (BTA) is a safe and effective therapeutic tool for many neurological conditions but few studies have investigated its real cost in neurological practice. We evaluated the daily cost of botulinum toxin type A (BTA) treatment through a cost effectiveness analysis alongside a prospective study of BTA injections at a French University Hospital over a 2-year follow-up period. The data of 3,108 BTA injections performed in 870 adult patients presenting with dystonia, facial hemispasm, or spasticity were entered in the database. Patients were questioned at each visit about the subjective effectiveness of the previous injection. The daily cost of BTA treatment was calculated as the ratio of each session's cost (including all additional costs) to the duration of subjective efficacy. The subjective rating of efficacy duration was 17.3 ± 7.7 weeks for facial hemispasm, 15.4 ± 7.7 for blepharospasm, 14.3 ± 6.7 for cervical dystonia, 14.5 ± 7.8 and 14.1 ± 7.4 weeks for upper and lower limb spasticity, respectively. The daily cost of BTA injections was 0.57 ± 0.20 for facial hemispasm, 0.95 ± 0.30 for blepharospasm, 2.85 ± 0.86 for cervical dystonia, 3.38 ± 1.49 and 3.62 ± 1.81 for upper and lower limb spasticity, respectively. When associated costs were considered, the daily cost of BTA injections was clearly increased (45-93%) in limb spasticity or rigidity but remained only modestly increased (15-37%) in other indications. These results obtained in a large cohort of patients show that BTA treatment has a low daily cost for a long-lasting effect, with a daily cost/benefit ratio that greatly depends on the indications.
Journal of Neurology 03/2011; 258(9):1670-5. · 3.58 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of this study was to investigate the relationship between the levels of insight and checking-related uncertainty in patients with obsessive-compulsive disorder (OCD).
Twenty OCD patients with checking compulsions and without current comorbidity were recruited. We used an experimental paradigm that gave subjects the opportunity to check during a decision-making task, thereby allowing for the calculation of a response time index (RTI) as the 'uncertainty cost' during decision-making. The level of insight was assessed with the Brown Assessment of Beliefs Scale (BABS).
Regression analyses indicated a significant positive correlation between RTI and BABS scores (r = 0.49).
The level of insight is related to cognitive characteristics underlying OCD symptoms, in particular, checking-related uncertainty in checking OCD patients.
The absence of a comparison group and the low number of included patients are the main limitations of the present study.