Long-term outcomes of CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) in a consecutive series of 12 patients.

BACKGROUND: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a central nervous system inflammatory disease. OBJECTIVE: To describe the disease course of CLIPPERS. DESIGN: A nationwide study was implemented to collect clinical, magnetic resonance imaging, cerebrospinal fluid, and brain biopsy specimen characteristics of patients with CLIPPERS. SETTING: Academic research. PATIENTS: Twelve patients with CLIPPERS. MAIN OUTCOME MEASURES: The therapeutic management of CLIPPERS was evaluated. RESULTS: Among 12 patients, 42 relapses were analyzed. Relapses lasted a mean duration of 2.5 months, manifested frequent cerebellar ataxia and diplopia, and were associated with a mean Expanded Disability Status Scale (EDSS) score of 4. Besides typical findings of CLIPPERS, magnetic resonance imaging showed brainstem mass effect in 5 patients, extensive myelitis in 3 patients, and closed ring enhancement in 1 patient. Inconstant oligoclonal bands were found on cerebrospinal fluid investigation in 4 patients, with an increased T-cell ratio of CD4 to CD8. Among 7 available brain biopsy specimens, staining was positive for perivascular CD4 T lymphocytes in 5 samples. Thirty-eight of 42 relapses were treated with pulse corticosteroid therapy, which led to improvement, with a mean residual EDSS score of 1.9 (range, 0-7). In 1 patient with untreated relapses, scores on the EDSS progressively increased to a score of 10 at death. Among 5 patients without long-term corticosteroid therapy, the mean annualized relapse rate was 0.5 (range, 0.25-2.8). Among 7 patients taking oral corticosteroids, no relapses occurred in those whose daily dose was 20 mg or higher. No progressive course of CLIPPERS was observed. Four patients with a final EDSS score of 4 or higher had experienced previous severe relapses (EDSS score, ≥5) and brainstem and spinal cord atrophy. CONCLUSIONS: CLIPPERS is a relapsing-remitting disorder without progressive forms. Long-term disability is correlated with the severity of previous relapses. Further studies are needed to confirm that prolonged corticosteroid therapy prevents further relapses.journal article2012 Julimporte

Mécanismes d’amplification des messages nociceptifs dans le complexe sensitif du trijumeau chez le rat : approche électrophysiologique

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Lack of effect of diffuse noxious inhibitory controls triggered by cold on trigeminal convergent neurons in the anaesthetized rat

National audienceNoxious stimuli activate suprasegmental descending inhibitory controls, providing a negative feedback mechanism to dampen the nociceptive transmission at the level of the spinal cord and the trigeminal system. Orofacial nociception thus, can be regulated by heterotopic application of noxious stimuli, a phenomenon also called diffuse noxious inhibitory controls (DNIC). The present study investigated the effect of DNIC triggered by noxious cold or heat stimulation on trigeminal convergent nociceptive neurons and blood pressure. Extracellular unitary recordings were made from spinal trigeminal nucleus convergent neurons in halothane-anaesthetized rats and the mean arterial blood pressure (MAP) was simultaneously monitored. One hundred and five repetitive (0.66 Hz) electrical shocks were applied to the excitatory receptive field of trigeminal convergent neurons at intensity equal to twice the threshold for nociceptive C-fiber activation. Between the 35th and the 60th stimuli (i. e. for 37.5 s) one animal paw was immersed into hot (48°C) or cold (3 to -12°C) water.All tested units responded to C-fiber stimulation. All were under the influence of DNIC triggered by noxious heat stimulation, which depressed C-fiber-evoked responses by 98 ± 1 %. Such inhibition was accompanied by a significant increase in MAP (23.1 ± 4.5 %). Both the neuronal inhibition and the increase in MAP evoked by noxious heat stimulation were significantly reduced following systemic naloxone (0.4 mg/kg). In contrast, heterotopic noxious cold stimulation had no effect on either neuronal responses or MAP changes.The present results suggest that, contrary to human, in the anaesthetized rat, DNIC can not be triggered by noxious cold stimulation

Étude de la production verbale orale chez les patients parkinsoniens : corrélations entre activité neuronale de structures sous-thalamiques et dénomination d'images

National audienceIntroduction.– La production verbale orale (PVO) implique notamment les ganglions de la base. Deux boucles d’encodage sont proposées : phonologique via le noyau caudé, le pallidum interne et le thalamus ventro-antérieur, et phonétique articulatoire via le putamen, le pallidum interne et le thalamus ventro-latéral. Nous avons émis l’hypothèse que l’activité neuronale de structures ventro-thalamiques et sous-thalamiques était modifiée lors de la PVO, en intra opératoire chez des patients parkinsoniens.Patients et méthode.– Huit patients droitiers (quatre hommes, 60 ± 8 ans) souffrant d’une maladie de Parkinson sévère depuis 9 ± 3 ans ont été implantés bilatéralement dans la région du noyau sous-thalamique (NST) sous anesthésie locale. Les trajectoires étaient déterminées après segmentation manuelle de structures sous-thalamiques sur une séquence IRM d’inversion-récupération : NST, zona incerta, substance noire, noyau rouge, noyau de l’anse lenticulaire et champs de Forel. La PVO a été étudiée pendant les enregistrements électrophysiologiques réalisés chaque millimètre sur une distance de 10 mm, simultanément sur deux trajectoires. Trente trois images correspondant à des mots monosyllabiques et monomorphémiques étaient présentées dans trois conditions :– repos, sans stimulation (contrôle) ;– le patient pensait au nom de l’image sans le prononcer (nP) ;– le patient devait prononcer le nom, et dans ce cas la période de préparation (préP) et celle d’exécution (execP) ont été distinguées.Nous avons calculé la fréquence moyenne des neurones (FMN, Hz). Les données ont été étudiées avec un modèle mixte de régression linéaire (variables : patients, régions anatomiques et activité électrophysiologique).Résultats ou cas rapporté.– 1248 sur 1760 enregistrements étaient exploitables. La FMN était supérieure en condition execP que dans les autres conditions (Contrôle-execP, p = 0,05 ; nP-execP, p = 0,02 ; préP-execP, p = 0,004), cela exclusivement dans le NST (Contrôle-execP, p = 0,02 ; nP-execP, p = 0,002 ; préP-execP, p = 0,005).Conclusion.– Le NST semble avoir une activité augmentée pendant la PVO. Ces résultats doivent être interprétés prudemment pour cet échantillon de huit patients parkinsoniens droitiers

Electrophysiological correlates from the subthalamic region for the performance of simple speech sequences

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A Role For Wind-Up in Trigeminal Sensory Processing: Intensity Coding of Nociceptive Stimuli in the Rat

International audienceWind-up is a progressive, frequency-dependent increase in the excitability of trigeminal and spinal dorsal horn wide dynamic range (WDR) nociceptive neurons evoked by repetitive stimulation of primary afferent nociceptive C-fibres. The correlate of wind-up in humans is temporal summation, which is an increase in pain perception to repetitive constant nociceptive stimulation. Although wind-up is widely used as a tool for studying the processing of nociceptive information, including central sensitization, its actual role is still unknown. Here, we recorded from trigeminal WDR neurons using in vivo electrophysiological techniques in rats and assessed the wind-up phenomenon in response to stimuli of different intensities and frequencies. First, we found that the amplitude of C-evoked responses of WDR neurons to repetitive stimulation increased progressively to reach a peak, then consistently showed a stable or slightly decreasing plateau phase. Only the first phase of this time course fitted in with the wind-up description. Therefore, to assess wind-up, we measured a limited number of initial responses. Second, we showed that wind-up, i.e. the slope of the frequency-dependent increase in the response to C-fibre stimulation, was linearly correlated to the stimulus intensity. Intensities of brief C-fibre inputs were thus coded into frequencies of action potentials by second-order neurons through frequency-dependent potentiation of the evoked responses. Third, wind-up also occurred at stimulation intensities below the threshold for C-evoked responses in WDR neurons, suggesting that wind-up can amplify subthreshold C-fibre inputs to WDR neurons. This might account for the observation that sparse, subliminal, neuronal activity in nociceptors can become painful via central integration of neural responses. Altogether, the present results show that wind-up can provide trigeminal WDR neurons with the capability to encode the intensity of short-duration orofacial nociceptive stimuli and to detect subthreshold nociceptive input. Thus, not only may wind-up play a physiological role in trigeminal sensory processing, but its enhancement may also underlie the pathophysiology of chronic orofacial pain conditions

Une nouvelle approche pour corriger le pied équin de l'hémiplégique par électro-stimulation fonctionnelle

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Development and implementation of a concept for automatic patient-specific DBS parameter identification

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Diffuse noxious inhibitory controls depend on arterial blood pressure in the anaesthetized rat

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How Many is Enough? The Influence of patient count on structural normative template quality.

International audienceStructural brain templates are the foundational element for group analysis in neuroscience, providing an anatomical reference when analyzing data from different patients. When creating such templates, the topic of the appropriate number of brains to obtain a stable anatomy must be addressed. The goal of this study was to estimate the number of patients required to reach convergence in the creation of a cohort-specific anatomical template through exemplary calculations for data (Ptolemee Electrophysiologie project: IRB 5921, CE-CIC-GREN-18-03) from Clermont-Ferrand university hospital (France). Preoperative imaging data from a group of 47 patients (Parkinson’s: 30, essential tremor: 17) who received deep brain stimulation was used in an iterative, non-linear, mixed-modality, unbiased anatomical normalization pipeline published previously. It consists of iterative non-linear normalization of all original images to an anatomical template updated after each iteration and implemented to use both T1 and WAIR (white matter attenuated inversion recovery, a modality specially designed to enhance grey matter contrast). During the pre-operative planning, up to 35 deep brain structures were manually labeled by a single expert. The normalization process was repeated, increasing the number of included patients, resulting in 5 different templates. The performance of the normalization was quantified using the pairwise overlap between anatomical structures across patients. A logistic function was then fitted on the median values of that score for each template to estimate the number of patients necessary to obtain a variation lower than 5%. In this study we estimated the number of patient images required to obtain a stable group-specific anatomical template. Manual segmentation of deep brain structures was used to benchmark templates with increasing number of patients included. Results might differ depending on the specific MR sequences used