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International audience; ObjectiveThe acoustic characteristics of stimuli influence the characteristics of the corresponding evoked potentials in healthy subjects. Own-name stimuli are used in clinical practice to assess the level of consciousness in intensive care units. The influence of the acoustic variability of these stimuli has never been evaluated. Here, we explored the influence of this variability on the characteristics of the subject’s own name (SON) P300.MethodsWe retrospectively analyzed 251 disorders of consciousness patients from Lyon and Paris Hospitals who underwent an “own-name protocol”. A reverse correlation analysis was performed to test for an association between acoustic properties of own-names stimuli used and the characteristics of the P300 wave observed.ResultsOwn-names pronounced with increasing pitch prosody showed P300 responses 66 ms earlier than own-names that had a decreasing prosody [IC95% = 6.36; 125.9 ms].ConclusionsSpeech prosody of the stimuli in the “own name protocol” is associated with latencies differences of the P300 response among patients for whom these responses were observed. Further investigations are needed to confirm these results.SignificanceSpeech prosody of the stimuli in the “own name protocol” is a non-negligible parameter, associated with P300 latency differences. Speech prosody should be standardized in SON P300 studies.

Summary: The definition of consciousness has been the subject of great interest for many scientists and philosophers. To better understand how evoked potentials may be identified as biomarkers of consciousness and recovery, the different theoretical models sustaining neural correlates of consciousness are reviewed. A multimodal approach can help to better predict clinical outcome in patients presenting with disorders of consciousness. Evoked potentials are inexpensive and easy-to-implement bedside examination techniques. Evoked potentials are an integral part of prognostic evaluation, particularly in cases of cognitive motor dissociation. Prognostic criteria are well established in postanoxic disorders of consciousness, especially postcardiac arrest but are less well determined in other etiologies. In the early examination, bilateral absence of N20 in disorder of consciousness patients is strongly associated with unfavorable outcome (i.e., death or unresponsive wakefulness syndrome) especially in postanoxic etiologies. This predictive value is lower in other etiologies and probably also in children. Both N20 and mismatch negativity are proven outcome predictors for acute coma. Many studies have shown that mismatch negativity and P3a are characterized by a high prognostic value for awakening, but some patients presenting unresponsive wakefulness syndrome also process a P3a. The presence of long-latency event-related potential components in response to stimuli is indicative of a better recovery. All neurophysiological data must be integrated within a multimodal approach combining repeated clinical evaluation, neuroimaging, functional imaging, biology, and neurophysiology combining passive and active paradigms.

Decisions of withdrawal of life-sustaining therapy for patients with severe brain injury are often based on prognostic evaluations such as analysis of electroencephalography (EEG) reactivity (EEG-R). However, EEG-R usually relies on visual assessment, which requires neurophysiological expertise and is prone to inter-rater variability. We hypothesised that quantitative analysis of EEG-R obtained 3 days after patient admission can identify new markers of subsequent awakening and consciousness recovery.In this prospective observational study of patients with severe brain injury requiring mechanical ventilation, quantitative EEG-R was assessed using standard 11-lead EEG with frequency-based (power spectral density) and functional connectivity-based (phase-lag index) analyses. Associations between awakening in the intensive care unit (ICU) and reactivity to auditory and nociceptive stimulations were assessed with logistic regression. Secondary outcomes included in-ICU mortality and 3-month Coma Recovery Scale-Revised (CRS-R) score.Of 116 patients, 86 (74%) awoke in the ICU. Among quantitative EEG-R markers, variation in phase-lag index connectivity in the delta frequency band after noise stimulation was associated with awakening (adjusted odds ratio=0.89, 95% confidence interval: 0.81-0.97, P=0.02 corrected for multiple tests), independently of age, baseline severity, and sedation. This new marker was independently associated with improved 3-month CRS-R (adjusted β=-0.16, standard error 0.075, P=0.048), but not with mortality (adjusted odds ratio=1.08, 95% CI: 0.99-1.18, P=0.10).An early-stage quantitative EEG-R marker was independently associated with awakening and 3-month level of consciousness in patients with severe brain injury. This promising marker based on functional connectivity will need external validation before potential integration into a multimodal prognostic model.

Objective: To measure the impact of skull-to-brain conductivity ratios on interictal spikes source localizations, using high resolution EEG (HR EEG). In previous studies, two ratios were mainly employed: 1/80 and 1/40. Consequences of the employed ratios on source localization results are poorly studied. Methods: Twenty patients with drug-resistant epilepsy were studied using HR EEG (sixty-four scalp electrodes). For each patient, three-layers realistic head models based on individual MRI were elaborated using boundary element model. For each interictal spike, source localization was performed six times, using six skull-to-brain conductivity ratios (1/80, 1/50, 1/40, 1/30, 1/20 and 1/10), exploring all the spectrum of values reported in the literature. We then measured distances between the different sources obtained and between the sources and the anterior commissure (in order to estimate sources depth) Results: We measured a mean distance of 5.3 mm (sd: 3 mm) between the sources obtained with 1/40 vs 1/80 ratio. This distance increased when the discrepancy between the two evaluated ratio increased. We measured a mean distance of 14.2 mm (sd: 4.9 mm) between sources obtained with 1/10 ratio vs 1/80 ratio. Sources localized using 1/40 ratio were 4.3 mm closer to the anterior commissure than sources localized using 1/80 ratio. Significance: Skull-to-brain conductivity ratio is an often-neglected parameter in source localization studies. The different ratios mainly used in the litterature (1/80 and 1/40) lead to significant differences in source localizations. These variations mainly occur in source depth. A more accurate estimation of skull-to-brain conductivity is needed to increase source localization accuracy.

Background and Purpose: In acute stroke, preventing infarct growth until complete recanalization occurs is a promising approach as an adjunct to reperfusion therapies to reduce infarct size and improve outcome. In rodent models, cathodal transcranial direct current stimulation (C-tDCS) decreases peri-infarct depolarizations and reduces infarct volume. We hypothesized that C-tDCS would nonpharmacologically reduce infarct growth in hyperacute middle cerebral artery territory stroke patients receiving reperfusion therapy. Methods: STICA (Cathodal Transcranial Direct Stimulation in Acute Middle Cerebral Artery Stroke) was a pilot single-center, double-blind, 2-arms 1:1 randomized trial evaluating the safety, feasibility, and efficacy of C-tDCS versus sham stimulation in patients eligible for recanalization therapies. Magnetic resonance imaging was obtained both on admission and 24 hours later. The primary end point was 24-hour infarct growth. Secondary outcomes were (1) National Institutes of Health Stroke Scale score difference between day 7 and admission and (2) 3-month modified Rankin Scale score. Results: Forty-five patients were randomized. Median magnetic resonance imaging-to-C-tDCS start time was 45 minutes; C-tDCS was started before completion of recanalization procedure in all patients. The intervention proved feasible in all patients. No major adverse effects occurred in either group. There was no significant difference between active and sham groups for any end point. However, an apparent trend towards smaller infarct growth in the C-tDCS arm was observed in the whole group (unadjusted median difference [IC 95% ]: −2.2 mL [−12.2 to 1.5]) and in the prespecified subsamples with moderate-to-severe stroke and large vessel occlusion (−5.7 mL [−21.6 to 2.6] and −7.7 mL [−24.2 to 2.6], respectively). Conclusions: C-tDCS was feasible and well tolerated. No significant difference was found between the active and sham groups. However, the data suggest potential benefits of C-tDCS in patients with National Institutes of Health Stroke Scale score of >10 or large vessel occlusion. Using the observed effect size and standard α=5% and β=20%, samples of 102 and 86, respectively, can be estimated for future trials in patients with these characteristics. Randomized trials particularly targeting these populations may be warranted.

Summary Introduction In France, a systematic EEG is performed during initial examination in military aircrew applicants, which may provide an estimation of the prevalence of benign epileptiform variants in healthy adults. Methods We analyzed standard EEG (21 scalp electrodes, 20 minutes, 400 Hz sampling rate) of military aircrew applicants examined in the French Main Aeromedical Center in 2016. EEGs were analyzed using both bipolar and referential montages. The collected data were EEG abnormalities and benign epileptiform variants. The kappa inter-observer index for the detection of benign epileptiform variants was calculated. Results Our population was composed of 495 subjects (86.7% males, mean age 22.5 ± 4.8 years), wishing to become a pilot in 69.7% of cases. None of the applicants reported any neurological disease and none was taking regular medication. EEG was considered as normal for 96.4% of them. Encountered EEG abnormalities were mainly asymmetric and sharp slow wave bursts. Drowsiness was recorded during 13.9% of these EEG. Benign epileptiform variants were present in 7.7% of our population: anterior theta activities (4%), posterior slow waves (2.8%), alpha variants (0.6%) and wicket spikes (0.2%). Hyperventilation induced EEG slowing in 14.1% of cases. During intermittent photic stimulation, physiological photic driving was observed in 15.2% of subjects. Discussion Many previous studies have been dedicated to the prevalence of benign epileptiform variants but results are often heterogeneous and based on patients in whom there was an indication for EEG. Our results thus bring data on benign epileptiform variants prevalence in a young adult population characterized by the absence of neurologic disorders. Our study demonstrates that anterior theta activities, posterior slow waves, alpha variants and wicket spikes are the most frequent benign EEG variants in such a young adult population.

Contexte L’evaluation multimodale du pronostic neurologique des patients cerebro-leses graves en reanimation inclut la realisation d’un EEG et conditionne la prise en charge ainsi que le devenir de ces patients. Si certains patterns EEG sont de pronostic defavorable, l’interpretation de cet examen reste delicate. Objectifs L’objectif de cette etude est d’evaluer la variabilite inter-observateurs dans l’interpretation des EEG de patients en reanimation. Methodes Tous les patients cerebroleses graves ayant beneficie d’un bilan neurophysiologique en reanimation au centre hospitalier Sainte-Anne du 01/09/2017 au 28/02/2019 ont ete inclus prospectivement dans l’etude. Cinq neurophysiologistes independants dont trois experimentes et deux en formation ont relu retrospectivement l’ensemble des EEG sans video. La concordance inter-observateurs pour la classification de l’activite de fond (7 sous-types : isoelectrique, hypovolte, suppression burst, discontinu, epileptiforme, ralenti ou normal) et la reactivite ont ete evaluees a l’aide de la statistique alpha de Krippendorff. Resultats Un total de 79 patients pour lesquels ont ete realises 87 EEG ont ete inclus. La concordance inter-observateurs etait forte concernant l’analyse de l’activite de fond (α = 0,64, IC95 % : 0,60–0,69) et semblait encore plus importante pour le sous-groupe des neurophysiologistes experimentes (α = 0,73, IC95 % : 0,59–0,85). Par contre, la concordance inter-observateurs concernant l’analyse de la reactivite etait faible (α = 0,37, IC95 % : 0,31–0,44). Conclusion Une variabilite inter-observateurs importante est mise en evidence, en particulier pour l’analyse de la reactivite, confirmant d’autres etudes. Le developpement d’analyses quantitatives de l’EEG devrait permettre d’eviter cet ecueil. Les evaluations a visee pronostique doivent etre multimodales (clinique, biologique, imagerie, EEG, PE).

Contexte Des depolarisations incontrolees (Cortical Spreading Depolarizations ou CSD et Peri-Infarct Depolarization ou PID) se propagent du cœur vers la penombre ischemique des infarctus cerebraux aigus et precipitent la mort neuronale. La stimulation transcrânienne cathodique a courant continu (tDCS) diminuerait l’excitabilite corticale par hyperpolarisation de la region ciblee. Sur modele murin, la tDCS cathodique bloque l’initiation de CSD induites par piqure du cortex. A l’inverse, la tDCS anodique augmente la vitesse de propagation des CSD. Trois etudes sur modeles murins d’infarctus cerebraux aigus ont demontre un effet neuroprotecteur de la tDCS cathodique (diminution des PID et du volume ischemique). A l’inverse, apres tDCS anodique le volume lesionnel augmentait. Objectifs Evaluer la faisabilite, la tolerance et l’efficacite de la tDCS cathodique associee a la recanalisation arterielle d’urgence dans les infarctus cerebraux aigus chez l’homme. Le critere de jugement principal est la croissance ischemique. Methodes « STICA » est une etude de preuve de concept, prospective, randomisee (1/1), en double aveugle (CPP : 3373), portant sur 50 patients ayant un infarctus sylvien aigu eligibles a une strategie de recanalisation. La stimulation comporte 20 min/h de stimulation cathodique ou placebo durant 6 h, le plus tot possible apres l’instauration des symptomes parallelement a la recanalisation arterielle. Resultats Le recrutement est en cours (42 inclusions). En moyenne, la tDCS a ete initiee dans les 25 minutes suivant la thrombolyse. Il n’y a pas eu d’effet indesirable severe. Conclusion La tDCS est realisable en contexte d’urgence. Les donnees d’efficacite sont en attente.

Le bortezomib (Velcade®) est un inhibiteur du proteasome indique dans le traitement de premiere ou deuxieme ligne des myelomes multiples. Il peut etre administre en monotherapie ou associe au melphalan, a la prednisone ou a la thalidomide. Plus rarement, il est utilise pour d’autres indications (protocoles de desimmunisation sur rejets de greffes notamment). Le risque de survenue d’une neuropathie induite par bortezomib est compris entre 31 et 45 % selon la litterature [1] , [2] , [3] . Les deux principaux facteurs de risque de neuropathies induites par bortezomib sont la dose cumulee totale recue et l’existence d’une neuropathie sous-jacente. Ces neuropathies necessitent parfois l’arret du bortezomib pourtant essentiel chez ces patients. Les neuropathies sous bortezomib sont classiquement decrites comme des polyneuropathies distales douloureuses symetriques cliniques associees a un electroneuromyogramme compatible avec une polyneuropathie axonale distale et symetrique a predominance sensitive. Une implication motrice est decrite dans 10 % des cas et quelques cas de neuropathies demyelinisantes ont egalement ete evoques. Dans ce travail, nous rapportons les presentations clinico-electriques des neuropathies survenues sous bortezomib dans le service de neurophysiologie clinique du CHU Bicetre. Ces 10 patients illustrent le veritable polymorphisme de ces neuropathies : douloureuses, ataxiantes, mononeuropathies multiples, polyradiculoneuropathies aigues possiblement asymetriques et polyneuropathies axonales longueur dependantes. Les facteurs favorisants retrouves dans notre revue de cas sont concordants avec ceux de la litterature. Deux mecanismes physiopathologiques semblent se degager : un mecanisme causal dose-dependant et lie a une sensibilite individuelle et un mecanisme favorisant dependant de l’existence d’une neuropathie sous-jacente. Il semble donc important de depister precocement et surveiller les signes neurologiques et neurophysiologiques chez tous les patients devant recevoir du bortezomib quel qu’en soit la dose pour limiter le developpement de ces neuropathies.

Introduction Il est classiquement admis que les potentiels evoques somesthesiques (PES) sont abolis dans les neuronopathies sensitives par atteinte du ganglion rachidien posterieur. Pourtant, malgre la reduction marquee des potentiels sensitifs observee en electroneuromyographie (ENMG) au cours de ces neuronopathies, la severite de l’ataxie proprioceptive est variable et depend des etiologies. Des formes familiales de neuronopathie sensitive associees a une toux chronique et des reflexes osteotendineux preserves sont souvent paucisymptomatiques contrairement aux formes subaigues. L’objectif de notre travail est de decrire les PES chez ces patients. Methodes Cinq patients suivis pour une neuronopathie sensitive chronique parasympatholytique ont ete inclus. Des PES par stimulation des nerfs medians et tibiaux posterieurs ont ete realises (intensite de stimulation au moins egale au seuil moteur, au moins 250 stimulations par acquisition, au moins deux acquisitions reproductibles). Les reponses peripheriques, medullaires, cervico-bulbaires et corticales ont ete enregistrees. Resultats Ces 5 patients presentent une forme parasympatholytique. Tous sont ambulatoires et n’ont qu’une hypopallesthesie moderee des membres inferieurs. Les reflexes osteotendineux sont preserves. Une toux chronique est constamment presente. Le diagnostic de neuronopathie sensitive est confirme en ENMG. Les examens paracliniques larges ont exclu une cause acquise (dysimmune, carentielle ou paraneoplasique). Les PES confirment des reponses evoquees peripheriques tres diminuees en amplitude. Des reponses corticales de morphologie desynchronisee et latences allongees ont pu etre enregistrees chez tous ces patients avec un temps de conduction central dans les limites de la normale. Conclusion Les reponses corticales en PES peuvent etre enregistrees chez des patients paucisymptomatiques avec neuronopathie sensitive chronique de type heredodegenerative, meme severe a l’ENMG, associee a une toux chronique. La preservation des reponses corticales possiblement liee a une plasticite des aires somesthesiques, pourrait expliquer la discordance entre un faible retentissement fonctionnel et l’atteinte severe des fibres sensitives peripheriques chez ces patients.

A 60-year-old man presented with an ataxic and spastic gait with paraparesis, having reported a tick bite. Brain MRI depicted bilateral corticospinal tract hyperintensities (figure). He had a mild lymphocytic meningitis (12 leukocytes/mm3, proteinorachia 1.48 g/L). ELISA was positive for Lyme disease in serum (immunoglobulin G [IgG] 176 UI and immunoglobulin M