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

Excitability properties of mouse motor axons in the mutant SOD1(G93A) model of amyotrophic lateral sclerosis

Non-invasive excitability studies of motor axons in patients with amyotrophic lateral sclerosis (ALS) have revealed a changing pattern of abnormal membrane properties with disease progression, but the heterogeneity of the changes has made it difficult to relate them to pathophysiology. The SOD1(G93A) mouse model of ALS displays more synchronous motoneuron pathology. Multiple excitability measures of caudal and sciatic nerves in mutant and wild-type mice were compared before onset of signs and during disease progression (4-19 weeks), and they were related to changes in muscle fiber histochemistry. Excitability differences indicated a modest membrane depolarization in SOD1(G93A) axons at about the time of symptom onset (8 weeks), possibly due to deficient energy supply. Previously described excitability changes in ALS patients, suggesting altered sodium and potassium conductances, were not seen in the mice. This suggests that those changes relate to features of the human disease that are not well represented in the animal model

Excitabilité neuromusculaire et fatigue à l'effort (exploration neurophysiologique et application à la pathologie)

Les travaux menés dans cette thèse ont porté sur l exploration électrophysiologique de l excitabilité neuromusculaire et de la fatigue à l effort chez l homme sain et malade. Des techniques d exploration non-invasives ont été développées dans ce but, pour appréhender les mécanismes physiopathologiques impliqués au niveau cortical, médullaire, nerveux et musculaire. Après validation chez le sujet sain, ces tests ont été appliqués à l étude de pathologies neurologiques affectant le système nerveux central (sclérose en plaques), nerveux périphérique (diverses neuropathies) ou musculaire (dystrophie myotonique). Les résultats obtenus dans ce travail ont été discutés avec l objectif de préciser les mécanismes physiopathologiques potentiellement incriminés. La rapidité, le caractère non douloureux et la bonne répétabilité de ces tests font envisager leur future application en pratique neurophysiologique pour assurer le suivi longitudinal ou l évaluation des effets d un traitement.The present work focused on electrophysiological assessment of neuromuscular excitability and effort-related fatigability in healthy humans and patients. Non-invasive techniques have been developed in this goal, to appraise the pathophysiological mechanisms involved at cortical, spinal, neural or muscular level. Following validation in healthy subjects, these tests have been applied to patients who suffered from disease affecting the central or the peripheral nervous system (multiple sclerosis, neuropathies) or the skeletal muscle (myotonic dystrophy). The results have been interpreted to enlighten the potential pathophysiological causes of such diseases. These studies are not painful and can be rapidly performed with a good repetability, authorizing their future application to ensure long-term follow-up and assessment of therapy in neurophysiological practice.PARIS12-CRETEIL BU Multidisc. (940282102) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Potassium and the excitability properties of normal human motor axons in vivo.

Hyperkalemia is an important cause of membrane depolarization in renal failure. A recent theoretical model of axonal excitability explains the effects of potassium on threshold electrotonus, but predicts changes in superexcitability in the opposite direction to those observed. To resolve this contradiction we assessed the relationship between serum potassium and motor axon excitability properties in 38 volunteers with normal potassium levels. Most threshold electrotonus measures were strongly correlated with potassium, and superexcitability decreased at higher potassium levels (P = 0.016), contrary to the existing model. Improved modelling of potassium effects was achieved by making the potassium currents obey the constant-field theory, and by making the potassium permeabilities proportional to external potassium, as has been observed in vitro. This new model also accounted well for the changes in superexcitability and other excitability measures previously reported in renal failure. These results demonstrate the importance of taking potassium levels into account when assessing axonal membrane dysfunction by excitability testing, and provide evidence that potassium currents are activated by external potassium in vivo

Validity of multi-fiber muscle velocity recovery cycles recorded at a single site using submaximal stimuli

To examine the validity of multi-fiber muscle velocity recovery cycles (VRCs) recorded by direct muscle stimulation with submaximal stimuli

Muscle velocity recovery cycles: Comparison between surface and needle recordings.

INTRODUCTION Recording of muscle velocity recovery cycles (MVRCs) has been developed as a technique to investigate the pathophysiology of muscle diseases. MVRCs have been measured by direct muscle stimulation and concentric electromyographic needle recording. This study was undertaken to determine whether recordings can be made with surface electrodes. METHODS MVRCs with 1 and 2 conditioning stimuli were recorded simultaneously with concentric needle and surface electrodes from the brachioradialis muscle in 12 healthy volunteers. Muscle relative refractory period, early and late supernormality, and extra-late supernormality were compared between the recording techniques. RESULTS Surface recordings were possible in all subjects. The multifiber action potentials recorded with surface electrodes were smaller than those recorded with needles, but there was no significant difference between any of their MVRC properties. CONCLUSIONS MVRCs can be recorded with surface electrodes in healthy subjects. The use of surface electrodes may facilitate the technique of recording MVRCs. Muscle Nerve 53: 205-208, 2016

Effects of ostreolysin, a protein from the oyster mushroom Pleurotus ostreatus, on the mouse neuromuscular system in vivo

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

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

Comparison between the three models in their ability to account for the effects of changes in serum potassium levels on multiple measures of nerve excitability.

<p>Data from Medium K data was fitted to nerve model, and then adjusted for different potassium levels according to Models 1, 2 and 3. Discrepancies score difference between model and recorded data and discrepancy reductions score improvement over no allowance for potassium. For each data set Model 3 provides lowest discrepancy (figures in bold).</p