Prefrontal tDCS Decreases Pain in Patients with Multiple Sclerosis

Background: In the last few years, transcranial direct current stimulation (tDCS) has emerged as an appealing therapeutic option to improve brain functions. Promising data support the role of prefrontal tDCS in augmenting cognitive performance and ameliorating several neuropsychiatric symptoms, namely pain, fatigue, mood disturbances, and attentional impairment. Such symptoms are commonly encountered in patients with multiple sclerosis (MS). Objective: The main objective of the current work was to evaluate the tDCS effects over the left dorsolateral prefrontal cortex (DLPFC) on pain in MS patients.Our secondary outcomes were to study its influence on attention, fatigue, and mood. Materials and Methods: Sixteen MS patients with chronic neuropathic pain were enrolled in a randomized, sham-controlled, and cross over study Patients randomly received two anodal tDCS blocks (active or sham), each consisting of three consecutive daily tDCS sessions, and held apart by 3 weeks. Evaluations took place before and after each block. To evaluate pain, we used the Brief Pain Inventory (BPI) and the Visual Analog Scale (VAS). Attention was assessed using neurophysiological parameters and the Attention Network Test (ANT). Changes in mood and fatigue were measured using various scales. Results: Compared to sham, active tDCS yielded significant analgesic effects according to VAS and BPI global scales.There were no effects of any block on mood, fatigue, or attention. Conclusion: Based on our results, anodal tDCS over the left DLPFC appears to act in a selective manner and would ameliorate specific symptoms, particularly neuropathic pain. Analgesia might have occurred through the modulation of the emotional pain network. Attention, mood, and fatigue were not improved in this work. This could be partly attributed to the short protocol duration, the small sample size, and the heterogeneity of our MS cohort. Future large-scale studies can benefit from comparing the tDCS effects over different cortical sites, changing the stimulation montage, prolonging the duration of protocol, and coupling tDCS with neuroimaging techniques for a better understanding of its possible mechanism of action

Neuropathies démyélinisantes inflammatoires. Classification, évolution et pronostic

Les neuropathies démyélinisantes inflammatoires peuvent être classées selon la topographie de l'atteinte nerveuse. Atteinte diffuse à prédominance proximale et multifocale pour les polyradiculonévrites aiguës et chroniques, atteinte multifocale à distribution tronculaire pour les neuropathies motrices et sensitivo-motrices à blocs de conduction, atteinte à prédominance distale pour les neuropathies à IgM monoclonale à activité anti-MAG (Myelin Associated Glycoprotein). Les caractéristiques cliniques des neuropathies démyélinisantes inflammatoires varient selon le type de neuropathie. Leur évolution peut être rémittente ou progressive mais est surtout marquée par le risque de lésions axonales définitives, source d'un déficit permanent et irréversible. Ces entités correspondent à des mécanismes que l'on peut en partie différencier selon la cible antigénique, le désordre immunitaire sous-jacent (à prédominance cellulaire ou humorale), et les modalités thérapeutiques envisagées. Les processus inflammatoires s'accompagnent d'une défaillance de production des ressources énergétiques (ATP) nécessaires à la mise en jeu des pompes Na+/K+ qui permettent d'extruder les ions Na+ entrant dans l'axone lors de la genèse de l'influx nerveux. Cette défaillance conduit à l'activation d'échangeurs Na+/ Ca2+, provoquant une cascade protéolytique secondaire à l'entrée de calcium dans le neurone, qui aboutit à la dégénérescence de l'axone

Blocs de conduction nerveuse et neuropathies

Un bloc de conduction motrice est défini par une réduction d'amplitude et/ou de surface d'une réponse motrice évoquée par une stimulation nerveuse proximale par rapport à celle évoquée par une stimulation distale appliquée sur le même tronc nerveux. Les mécanismes physiopathologiques pouvant mener à l'existence d'une figure de bloc de conduction comprennent des processus de démyélinisation segmentaire, d'interruption axonale récente, ou des anomalies d'excitabilité axonale par dysfonction canalaire ionique ou modification du potentiel membranaire. Ces phénomènes peuvent être d'origine mécanique compressive, ischémique ou inflammatoire dysimmunitaire. La confrontation des données cliniques, biologiques, et des éléments fournis par l'examen électroneuromyographique permet d'établir le diagnostic étiologique d'une atteinte nerveuse comprenant des blocs de conduction. Parmi les neuropathies caractérisées par l'existence de blocs de conduction, on distinguera un groupe de neuropathies très particulières, d'origine dysimmunitaire, qui sont les neuropathies multifocales avec blocs de conduction persistants, dont on distingue des formes purement motrices et des formes sensitivo-motrices. Les spécificités cliniques, électrophysiologiques, biologiques et thérapeutiques de ces deux entités seront discutées

A non-invasive method to appraise time-dependent effects of toxins on the mouse neuromuscular excitability in vivo, and its clinical applications

Epub on http://www.sfet.asso.f

High-dose pharmaceutical-grade biotin in patients with demyelinating neuropathies: a phase 2b open label, uncontrolled, pilot study

Abstract Background We proposed to investigate high-dose pharmaceutical-grade biotin in a population of demyelinating neuropathies of different aetiologies, as a proof-of-concept. Methods Phase IIb open label, uncontrolled, single center, pilot study in 15 patients (three groups of five patients) with chronic demyelinating peripheral neuropathy, i.e. chronic inflammatory demyelinating polyradiculoneuropathy, anti-myelin-associated glycoprotein neuropathy and Charcot-Marie-Tooth 1a or 1b. The investigational product was high-dose pharmaceutical-grade biotin (100 mg taken orally three times a day over a maximum of 52 weeks. The primary endpoint was a 10% relative improvement in 2 of the following 4 electrophysiological variables: motor nerve conduction velocity, distal motor latency, F wave latency, duration of the compound muscle action potential. The secondary endpoints included Overall Neuropathy Limitations Scale (ONLS) score, Medical Research Council (MRC) sum score, Inflammatory Neuropathy Cause and Treatment (INCAT) sensory sum score, 10-m walk test, 6-min walk test, posturography parameters, and nerve excitability variables. Results The primary endpoint was reached in one patient. In the full population analysis, some secondary endpoints parameters improved: MRC score, INCAT sensory sum score, 6-min walk distance, strength-duration time constant, and rheobase. There was a positive correlation between the improvement in the 6-min walk distance and the strength-duration time constant. Regarding the safety results, 42 adverse events occurred, of which three were of severe intensity but none was considered as related to the investigational product. Conclusions Even if the primary endpoint was not met, administration of high-dose pharmaceutical-grade biotin led to an improvement in various sensory and motor parameters, gait abilities, and nerve excitability parameters. The tolerance of the treatment was satisfactory. Trial registration ClinicalTrials.gov Identifier: NCT02967679; date 2016/12/05

TEC-ADHERE : étude non interventionnelle sur la persistance au diméthyl fumarate (DMF, Tecfidera®) chez des patients atteints de sclérose en plaques rémittente récurrente et bénéficiant d’un soutien dans le cadre du programme d’accompagnement OroSEP

International audienc

Human Endogenous Retroviruses in Neurological Diseases

International audienceThe causes of multiple sclerosis and amyotrophic lateral sclerosis have long remained elusive. A new category of pathogenic components, normally dormant within human genomes, has been identified: human endogenous retroviruses (HERVs). These represent ∼8% of the human genome, and environmental factors have reproducibly been shown to trigger their expression. The resulting production of envelope (Env) proteins from HERV-W and HERV-K appears to engage pathophysiological pathways leading to the pathognomonic features of MS and ALS, respectively. Pathogenic HERV elements may thus provide a missing link in understanding these complex diseases. Moreover, their neutralization may represent a promising strategy to establish novel and more powerful therapeutic approaches

High effector-memory CD8+ T-cell levels correlate with high PML risk in natalizumab-treated patients

International audienceBackground: Progressive multifocal leukoencephalopathy (PML) is a severe complication of natalizumab (NTZ) treatment in multiple sclerosis (MS) patients. Based on the analysis of cryopreserved cells, several reports have showed that CD62L+ CD4+ T-cells percentage drops before PML onset.Objective: To analyze CD62L and CD45RA expression on fresh-blood CD4+ and CD8+ T-cells from NTZ-treated patients, according to their estimated PML risk.Methods: We prospectively enrolled 74 MS patients, including 62 NTZ-treated, and stratified them into low, intermediate and high PML risk groups. Circulating naïve and memory T-cell subsets were analyzed by flow cytometry.Results: We found no correlation between the percentage of CD62L+ CD4+ T-cells and PML risk. In contrast, the repartition of CD8+ T-cells subpopulations was altered in the high risk group: both the percentage and absolute count of CD8+ CD62L- CD45RA- effector memory T- cells (TEM) was significantly higher compared to patients at lower risk despite similar CD3+ and CD8+ T-cell counts. One high-risk patient with elevated CD8+ TEM and CD62L+ CD4+ T-cell levels developed PML six months after sampling.Conclusion: Our results suggest that CD8+ TEM cells should be evaluated in larger studies as a potential surrogate marker of PML risk in NTZ-treated patients