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Background Approximately 50% of newly diagnosed glioblastomas (GBMs) harbor epidermal growth factor receptor gene amplification (EGFR-amp). Preclinical and early-phase clinical data suggested efficacy of depatuxizumab mafodotin (depatux-m), an antibody–drug conjugate comprised of a monoclonal antibody that binds activated EGFR (overexpressed wild-type and EGFRvIII-mutant) linked to a microtubule-inhibitor toxin in EGFR-amp GBMs. Methods In this phase III trial, adults with centrally confirmed, EGFR-amp newly diagnosed GBM were randomized 1:1 to radiotherapy, temozolomide, and depatux-m/placebo. Corneal epitheliopathy was treated with a combination of protocol-specified prophylactic and supportive measures. There was 85% power to detect a hazard ratio (HR) ≤0.75 for overall survival (OS) at a 2.5% 1-sided significance level (ie traditional two-sided p ≤ 0.05) by log-rank testing. Results There were 639 randomized patients (median age 60, range 22–84; 62% men). Prespecified interim analysis found no improvement in OS for depatux-m over placebo (median 18.9 vs. 18.7 months, HR 1.02, 95% CI 0.82–1.26, 1-sided p = 0.63). Progression-free survival was longer for depatux-m than placebo (median 8.0 vs. 6.3 months; HR 0.84, 95% confidence interval [CI] 0.70–1.01, p = 0.029), particularly among those with EGFRvIII-mutant (median 8.3 vs. 5.9 months, HR 0.72, 95% CI 0.56–0.93, 1-sided p = 0.002) or MGMT unmethylated (HR 0.77, 95% CI 0.61–0.97; 1-sided p = 0.012) tumors but without an OS improvement. Corneal epitheliopathy occurred in 94% of depatux-m-treated patients (61% grade 3–4), causing 12% to discontinue. Conclusions Interim analysis demonstrated no OS benefit for depatux-m in treating EGFR-amp newly diagnosed GBM. No new important safety risks were identified.

IntroductionArthrogryposis multiplex congenita (AMC) refers to a clinical presentation of congenital contractures involving two or more body areas. More than 400 distinct conditions may lead to AMC, making the aetiological diagnosis challenging. The objective of this work was to set up evidence-based recommendations for the diagnosis of AMC by taking advantage of both data from our nation-wide cohort of children with AMC and from the literature.Material and methodsWe conducted a retrospective single-centre observational study. Patients had been evaluated at least once at a paediatric age in the AMC clinic of Grenoble University Hospital between 2007 and 2019. After gathering data about their diagnostic procedure, a literature review was performed for each paraclinical investigation to discuss their relevance.ResultsOne hundred and twenty-five patients were included, 43% had Amyoplasia, 27% had distal arthrogryposis and 30% had other forms. A definitive aetiological diagnosis was available for 66% of cases. We recommend a two-time diagnostic process: first, non-invasive investigations that aim at classifying patients into one of the three groups, and second, selected investigations targeting a subset of patients.ConclusionThe aetiological management for patients with AMC remains arduous. This process will be facilitated by the increasing use of next-generation sequencing combined with detailed phenotyping. Invasive investigations should be avoided because of their limited yield.

Marburg variant is a severe and fulminant pseudotumor form of multiple sclerosis (MS) with high morbidity and mortality rates. Because of its scarcity, it remains incompletely characterized and physicians' experiences will influence the treatment. We report the inflammatory explosive case of a 31-year-old woman presenting with rapid neurological degradation of histology proven Marburg's disease, successfully treated with early administration of Mitoxantrone (MITX). To our knowledge, it is the first case describing complete remission after MITX in a biopsy-proven condition.

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is scarce and usually presents as meningoencephalomyelitis. Here, we offer the case of an atypical presentation of GFAP-astrocytopathy. We report the case of a 26-year-old woman admitted to our neurology department for a 3-week progressive and worsening neurologic picture, with secondary worsening. Initial imaging showed a Mild Encephalitis with Reversible Splenium of corpus callosum lesion (MERS). Full infectious and autoimmune workup then revealed positivity of GFAP antibodies, leading us to diagnose GFAP astrocytopathy. Our case is the first reported association between MERS and GFAP astrocytopathy in an adult patient. Clinical presentation of GFAP astrocytopathy usually includes various neurologic symptoms and can lead to misdiagnosis.

Background and ObjectivesTo report the clinical, biological, and imaging features and clinical course of a French cohort of patients with glial fibrillary acidic protein (GFAP) autoantibodies.MethodsWe retrospectively included all patients who tested positive for GFAP antibodies in the CSF by immunohistochemistry and confirmed by cell-based assay using cells expressing human GFAPα since 2017 from 2 French referral centers.ResultsWe identified 46 patients with GFAP antibodies. Median age at onset was 43 years, and 65% were men. Infectious prodromal symptoms were found in 82%. Other autoimmune diseases were found in 22% of patients, and coexisting neural autoantibodies in 11%. Tumors were present in 24%, and T-cell dysfunction in 23%. The most frequent presentation was subacute meningoencephalitis (85%), with cerebellar dysfunction in 57% of cases. Other clinical presentations included myelitis (30%) and visual (35%) and peripheral nervous system involvement (24%). MRI showed perivascular radial enhancement in 32%, periventricular T2 hyperintensity in 41%, brainstem involvement in 31%, leptomeningeal enhancement in 26%, and reversible splenial lesions in 4 cases. A total of 33 of 40 patients had a monophasic course, associated with a good outcome at last follow-up (Rankin Score ≤2: 89%), despite a severe clinical presentation. Adult and pediatric features are similar. Thirty-two patients were treated with immunotherapy. A total of 11/22 patients showed negative conversion of GFAP antibodies.DiscussionGFAP autoimmunity is mainly associated with acute/subacute meningoencephalomyelitis with prodromal symptoms, for which tumors and T-cell dysfunction are frequent triggers. The majority of patients followed a monophasic course with a good outcome.

work still needs to be done to measure the impact of sialorrhea on quality of life and define the efficacy of different therapies. The Drooling Impact Scale showed good validity and sensitivity to change, especially after botulinum toxin injection. The aim of this study is to present its French translation and to explore its validity, reliability and responsiveness to change in a group of children with Cerebral Palsy.multicentre study at six rehabilitation centres in France. Children with Cerebral Palsy aged 4-18 years with sialorrhea problems were included (The French Drooling Impact Scale total score at inclusion was meanly 53.9 (Standard Deviation 11.9) in the stable control group and 66.0 (16.1) in the intervention group (the French Drooling Impact Scale has shown sufficient clinometric properties to be used now by clinicians or researchers.IMPLICATIONS FOR REHABILITATIONThe Drooling Impact scale has now its French version.The French version of the Drooling Impact Scale has shown its validity and a good test-retest reliability.The responsiveness to change was explored in a group of children undergoing saliva-control interventions and the scale was able to show a big change.The authors recommend to use this questionnaire in a semi-directed interview conducted by a health professional.

Summary Introduction Based on the radiological responses obtained with a schedule of ten mg/kg every two weeks bevacizumab was approved by the FDA for recurrent glioblastomas. Due to the negative results concerning overall survival of patients receiving bevacizumab, the European application was rejected. Despite this, many centers apply an off-label prescription. Our aim was to evaluate the safety and efficacy of schedules of low doses of bevacizumab. Methods From September 2013 to August 2016, we recruited patients with progressive glioblastoma, whatever the previous treatments. We compared a routine control group (CG) of ten mg/kg, to a low dose group (LDG) composed of 5 subgroups: G5: five mg/kg, G4: four mg/kg, G3: three mg/kg, G2: two mg/kg, G1: one mg/kg; each patient was treated with the same dose every two weeks. Results Fifty-three patients were treated: 20 women and 33 men, 24 in the CG and 29 in the LDG. The median age at diagnosis was 62 years [35.0–77.0]. No statistical difference was found in overall survival either for the CG or the LDG (P = 0.086) or among groups (P = 0.251), with even a trend toward improvement for LDG: 62 weeks [20–145] versus 73 weeks [18–178]. The median progression free survival was comparable: 19.5 weeks [6.0–54.0] for the CG and 15.0 weeks [0.0–134.0] for the LDG (P = 0.221). Bevacizumab was stopped either due to progression (45.1%) or toxicity (52.9%), without significant differences between doses but maybe less toxicities in the LDG (16.7% for toxicity in G1). Discussion Use of bevacizumab at progression at lower than usual doses seems to give the same results as the standard dose without giving additional toxicity.

BackgroundThe conventional dose rate of radiation therapy is 0.01–0.05 Gy per second. According to preclinical studies, an increased dose rate may offer similar anti-tumoral effect while dramatically improving normal tissue protection. This study aims at evaluating the early toxicities for patients irradiated with high dose rate pulsed proton therapy (PT).Materials and MethodsA single institution retrospective chart review was performed for patients treated with high dose rate (10 Gy per second) pulsed proton therapy, from September 2016 to April 2020. This included both benign and malignant tumors with ≥3 months follow-up, evaluated for acute (≤2 months) and subacute (>2 months) toxicity after the completion of PT.ResultsThere were 127 patients identified, with a median follow up of 14.8 months (3–42.9 months). The median age was 55 years (1.6–89). The cohort most commonly consisted of benign disease (55.1%), cranial targets (95.1%), and were treated with surgery prior to PT (56.7%). There was a median total PT dose of 56 Gy (30–74 Gy), dose per fraction of 2 Gy (1–3 Gy), and CTV size of 47.6 ml (5.6–2,106.1 ml). Maximum acute grade ≥2 toxicity were observed in 49 (38.6%) patients, of which 8 (6.3%) experienced grade 3 toxicity. No acute grade 4 or 5 toxicity was observed. Maximum subacute grade 2, 3, and 4 toxicity were discovered in 25 (19.7%), 12 (9.4%), and 1 (0.8%) patient(s), respectively.ConclusionIn this cohort, utilizing high dose rate proton therapy (10 Gy per second) did not result in a major decrease in acute and subacute toxicity. Longer follow-up and comparative studies with conventional dose rate are required to evaluate whether this approach offers a toxicity benefit.

Background Actionable fibroblast growth factor receptor 3 (FGFR3)–transforming acidic coiled-coil protein 3 fusions (F3T3) are found in approximately 3% of gliomas, but their characteristics and prognostic significance are still poorly defined. Our goal was to characterize the clinical, radiological, and molecular profile of F3T3 positive diffuse gliomas. Methods We screened F3T3 fusion by real-time (RT)-PCR and FGFR3 immunohistochemistry in a large series of gliomas, characterized for main genetic alterations, histology, and clinical evolution. We performed a radiological and radiomic case control study, using an exploratory and a validation cohort. Results We screened 1162 diffuse gliomas (951 unselected cases and 211 preselected for FGFR3 protein immunopositivity), identifying 80 F3T3 positive gliomas. F3T3 was mutually exclusive with IDH mutation (P < 0.001) and EGFR amplification (P = 0.01), defining a distinct molecular cluster associated with CDK4 (P = 0.04) and MDM2 amplification (P = 0.03). F3T3 fusion was associated with longer survival for the whole series and for glioblastomas (median overall survival was 31.1 vs 19.9 mo, P = 0.02) and was an independent predictor of better outcome on multivariate analysis. F3T3 positive gliomas had specific MRI features, affecting preferentially insula and temporal lobe, and with poorly defined tumor margins. F3T3 fusion was correctly predicted by radiomics analysis on both the exploratory (area under the curve [AUC] = 0.87) and the validation MRI (AUC = 0.75) cohort. Using Cox proportional hazards models, radiomics predicted survival with a high C-index (0.75, SD 0.04), while the model combining clinical, genetic, and radiomic data showed the highest C-index (0.81, SD 0.04). Conclusion F3T3 positive gliomas have distinct molecular and radiological features, and better outcome.

Background: Dalfampridine extended release (DAL) is a broad-spectrum voltage-gated potassium channel blocker that is indicated in multiple sclerosis to improve the nerve conduction of demyelinated axons. Seizures are a known side effect of DAL, which is contraindicated in patients with a history of epilepsy. Objective: Three cases of multiple sclerosis (MS) with de novo convulsive status epilepticus (CSE) probably related to dalfampridine administration are described. Methods: No patients had a history of seizures or renal impairment. Biological tests were normal. A brain magnetic resonance imaging (MRI) showed diffuse cortical and subcortical atrophy without active inflammatory lesions. Results: All three patients presented with CSE that was attributed to DAL and so was discontinued. Conclusion: These case reports illustrate that, aside from seizures, de novo CSE is a potential complication of MS patients treated with DAL.

Background Diffuse H3 K27M-mutant gliomas occur primarily in children but can also be encountered in adults. The aim of this study was to describe the characteristics of H3 K27M-mutant gliomas in adults. Methods We analyzed the characteristics of 21 adult H3 K27M-mutant gliomas and compared them with those of 135 adult diffuse gliomas without histone H3 and without isocitrate dehydrogenase (IDH) mutation (IDH/H3 wild type). Results The median age at diagnosis in H3 K27M-mutant gliomas was 32 years (range: 18-82 y). All tumors had a midline location (spinal cord n = 6, thalamus n = 5, brainstem n = 5, cerebellum n = 3, hypothalamus n = 1, and pineal region n = 1) and were IDH and BRAF-V600E wild type. The identification of an H3 K27M mutation significantly impacted the diagnosis in 3 patients (14%) for whom the histological aspect initially suggested a diffuse low-grade glioma and in 7 patients (33%) for whom pathological analysis hesitated between a diffuse glioma, ganglioglioma, or pilocytic astrocytoma. Compared with IDH/H3 wild-type gliomas, H3 K27M-mutant gliomas were diagnosed at an earlier age (32 vs 64 y, P < .001), always had a midline location (21/21 vs 21/130, P < .001), less frequently had a methylated MGMT promoter (1/21 vs 52/129, P = .002), and lacked EGFR amplification (0/21 vs 26/128, P = .02). The median survival was 19.6 months in H3 K27M-mutant gliomas and 17 months in IDH/H3 wild-type gliomas (P = .3). Conclusion In adults, as in children, H3 K27M mutations define a distinct subgroup of IDH wild-type gliomas characterized by a constant midline location, low rate of MGMT promoter methylation, and poor prognosis.

Objectifs Analyser les caracteristiques texturales (Radiomics) pour decrire une signature correlee aux mutations IDH et codeletion 1p/19q dans les gliomes de bas grade (classification OMS 2016, Figure 1 ). Evaluer l’impact des parametres d’acquisition sur les indices radiomiques. Materiels et methodes Les patients presentant un gliome de bas grade diagnostique au CHU de Nice entre 2009 et 2016 avec une imagerie FLAIR pre operatoire disponible ont ete inclus dans notre etude retrospective. Les donnees concernant le statut IDH, la codeletion 1p/19q, l’expression ATRX et les mutations type glioblastome moleculaire ont ete recueillies. Les sequences FLAIR, T2, T1 et T1 injectee ont ete normalisees en intensite (methode hybride WhiteStripes) et en resolution spatiale (Matlab SPM12), puis un contourage des tumeurs a ete realise avec positionnement de 6 VOI en substance blanche saine (logiciel LifeX). Quarante-huit indices de radiomiques ont ete extraits avec calcul du coefficient de Spearman entre index et realisation d’un test de Wilcoxon pour chaque tâche de classification. Resultats Trente-neuf patients ont ete inclus (16 astrocytomes IDH mutes, 13 astrocytomes IDH wild-type et 10 oligodendrogliomes, Tableau 1 ). Les correlogrammes sont presentes Figure 2 . Pour le statut IDH, 26 indices etaient discriminant sur l’ensemble des sequences (p Conclusion L’analyse radiomics pourrait permettre de quantifier a partir des donnees IRM une organisation tissulaire specifique au genotype IDH dans les gliomes de bas grade, mais necessite une poursuite des investigations sur une plus grande cohorte afin de valider une signature specifique.

ObjectiveMeningeal involvement in Immunoglobulin G (IgG)-4-related disease is rare and only described in case reports and series. Because a review into the disease is lacking, we present 2 cases followed by a literature review of IgG4-related hypertrophic pachymeningitis (IgG4-HP).MethodsTwo IgG4-HP cases were reported, one involving the spinal cord and responding to surgical management and a second involving the brain and responding to Rituximab therapy. We then review clinical cases and case-series of histologically proven IgG4-HP that were published in the PubMed-NCBI database.ResultsForty-two case reports and 5 case-series were studied (60 patients, 20 women). The median age was 53. Eighteen patients had systemic involvement and 24 had single-organ IgG4-HP. Fifty-five percent of patients had an elevated serum IgG4. Treatment was surgical in 20/53 cases. Steroid therapy and immunosuppressors were effective in 85% and more than 90% of the cases, respectively. The rate of disease relapse was 42.1% after steroid therapy was discontinued.Discussion/conclusionIgG4-HP is characterized by the lack of extra-neurologic organ-involvement and systemic signs. Histopathologic studies should be performed as it is crucial for diagnosis because serum markers are rarely informative. 18F-FDG positon tomography can be useful to characterize systemic forms. There is no specific CSF marker for IgG4-HP and the diagnostic value of CSF IgG4 levels needs to be studied with larger samples. We provide a treatment algorithm for IgG4-HP. Such treatment strategies rely on early surgery, steroids, and early immunosuppressive therapy to prevent neurologic complications.

International audience; Simultaneous execution of motor and cognitive tasks is embedded in the daily life of children. 53 children of 7-12 years and 22 adults (study 1), 20 healthy children and 20 children of 7-12 years with cerebral palsy (study 2) performed a Stroop-animal task simultaneously with a standing or a walking task in order to determine the attentional demand of postural control and locomotion. Dual-task cost decreased with advancing age in healthy children during balance. CP and healthy children were similarly affected by dual-task constraints during standing and walking. Children with diplegia were more affected by the DT during the postural task than children with hemiplegia. We found that adults could benefit from dual-tasking for standing. The integrated model of task prioritization might explain our results regarding postural reserve of each population.

Arthrogryposis multiplex congenita (AMC) consists of congenital joint contractures that affect at least two joints. There are two types: in the first, arthrogryposis is an additional sign in the context of various pathologies (neuromuscular diseases); in the second, it is the main and constant symptom. In the first type, the progression of the causal underlying disease must be considered. In the second type, there are two specific forms: Amyoplasia corresponds to a significant congenital absence of muscles (epigenetic disease or vascular origin) while distal arthrogryposis has a genetic component and is transmissible. The orthopedic surgeon's purpose, which is usually to enhance movement, is not appropriate for an arthrogryposis patient. One must keep in mind that without muscle, movement is impossible. The goal differs between the upper and lower limbs: for the upper limb, it is to allow grasping, and, if possible, to bring the hand to the mouth; for the lower limb, it is to ensure ambulation with plantigrade support, and the knees extended, which is the only stable position possible with little to no muscles. The rehabilitation, orthoses and/or surgical techniques are chosen to achieve this singular aim. While it may appear modest, it is crucial for patients. The goal is to achieve useful mobility, not maximum mobility. This multidisciplinary treatment, which evolves over time, must be explained to the family to get its adherence.

Jerome Barriere was inadvertently missing in the original version of this article. He has participated to the study design, protocol writing and inclusion of a significant number of patients.

Introduction La frequence d’administration du RTX dans la myasthenie est variable selon les equipes : taux de CD19 + , des LB-CD27 + , tous les 6 mois ou en cas de rechute clinique. Objectifs Etudier les sous-populations lymphocytaires (plasmablastes, transitionnels, switch, marginaux, doubles negatifs) afin de determiner si certains profils de repopulation permettraient de predire une rechute clinique avant la positivite des LB-CD27 + . Patients et Methodes Depuis 2015, 36 patients myastheniques ont ete traites par RTX avec une evaluation clinique (score myasthenique) et un dosage des parametres biologiques (CD19, CD27 + , precurseurs et sous-populations des LB-CD27 + ) tous les 3 mois. En cas de reemergence des LB-CD27 + (seuil de detection : 0,05 % PBMC), une cure d’entretien de RTX (1 g) est realisee. Resultats Un total de 36 patients sont evalues : âge moyen : 50 ans (18–84 ans ; 57 %de femmes). Mediane de repopulation des LB-CD27 + (et de retraitement) : 9 mois (2–24). Les antecedents d’immunosuppression (IS) n’influencent pas la duree de rechute biologique. Aucune emergence de sous populations de LB-CD27 + n’est predictive de la repopulation. Les LB-CD19 + sont toujours positifs avant la positivite des LB-CD27 + et ne sont pas predictifs de rechute. Discussion Le suivi des LB-CD27 + permet d’identifier des patients avec reemergence precoce (2 mois) et d’autres avec un espacement important des cures (24 mois), evitant des perfusions inutiles, des economies et une diminution de la toxicite sans rechute clinique. Les LCD27 transitionnels se positivent en cas de rechute precoce. L’ensemble des sous-populations se positive lors de rechute biologique tardive. Conclusion Les L-CD19 + ne sont pas un bon marqueur de suivi pour l’administration du RTX. Aucune sous-population de LB-CD27 + ne permet de mieux anticiper la rechute clinique.

Recent advances in the treatment of malignant gliomas have highlighted the fact that the appearance of new contrast-enhancing lesions on magnetic resonance imaging (MRI) is not always indicative of tumor recurrence. It has been suggested that transient seizure-related MRI changes could mimic disease progression (peri-ictal pseudoprogression [PIPG]). However, the clinical and MRI features associated with this situation have not been well described. Here, we consulted the databases of 6 institutions to identify patients with brain tumor who presented during the follow-up period transient MRI lesions wrongly suggesting tumor progression in a context of epileptic seizures. Ten patients were identified. All patients but 1 were long-term survivors who had initially been treated with radiotherapy. The PIPG episode occurred after a median interval of 11 years after radiotherapy. MRI features were highly similar across patients and consisted of transient focal cortical and/or leptomeningeal enhancing lesions that erroneously suggested tumor progression. All patients improved after adjustment of their antiepileptic drugs and transient oral corticosteroids, and MRI findings were normalized 3 months after the PIPG episode. Two patients demonstrated several seizure relapses with the same clinicoradiological pattern. After a median follow-up period of 3.5 years after the initial PIPG episode, only 1 patient presented with a tumor recurrence. In conclusion, in patients with brain tumor, especially in long-term survivors of radiotherapy, the appearance of new cortical and/or leptomeningeal contrast-enhancing lesions in a context of frequent seizures should raise the suspicion of PIPG. This phenomenon is important to recognize in order to avoid futile therapeutic escalation.

Bevacizumab is a monoclonal antibody, which neutralizes the effect of vascular endothelium growth factor (VEGF) allowing regression of tumour vessels and a decrease in the permeability of the blood-brain barrier. Already used in oncology as adjuvant treatment for certain metastatic cancers and in second line for high-grade gliomas, it has been recently used as a treatment of cerebral radionecrosis resisting conventional drug treatment and hyperbaric oxygen. This article presents three patients with cerebral radionecrosis and treated by monthly infusions of bevacizumab (10 mg/kg per month). The patients had developed cerebral radionecrosis after radiation therapy for a malignant brain tumour. The radionecrosis was proved by magnetic resonance imaging and spectroscopy. The first patient received only one perfusion of bevacizumab, as the development of a lymphopenia prevented the patient from continuing with the treatment. The second patient received four infusions, but the absence of improvement of the clinical symptoms and progression of the radiolesion led to discontinuation of the treatment. The third patient developed several severe side effects, a transient ischemic accident and a perforated corneal ulcer, resulting again in premature discontinuation of treatment. The development of severe side effects, combined with the absence of notable clinical and radiologic improvements resulting from the use of bevacizumab as a treatment resulted in the premature interruption of such treatment, in all three patients.

Introduction Le rituximab (RTX) a demontre son efficacite et sa tolerance dans la myasthenie generalisee (MG). L’evaluation de la rechute biologique, grâce a des marqueurs de suivi, n’est pas encore consensuelle. Objectifs Determiner les marqueurs de suivi, parmi le dosage sanguin des LBCD19 + CD27+, CD19+, rituximabemie et anticorps anti-rituximab, qui permettraient d’anticiper la rechute et l’administration d’un traitement par RTX. Methodes Depuis 2015, 39 patients myastheniques ont ete traites par RTX. Les patients ont recu une cure d’induction (1 g, j1–j15) puis en cas de reemergence des LBCD19 + CD 27+ (seuil de detection > 0,05 % PBMC), une cure d’entretien de RTX (1 g, j1) etait realisee. Une evaluation clinique (score myasthenique) et des prelevements biologiques (LBCD19+ methode standard, LBCD19 + CD27+ [MRD], rituximabemie et Ac anti-RTX) etaient effectues tous les 3 mois. Resultats Caracteristiques cliniques des patients : âge moyen : 54 ans (18–92 ans ; 59 % de femmes), 87 % ACanti-Rach, 2,5 % ACanti-Musk, 12,5 % ACanti-Titine ; moyenne de suivi : 21 mois (3–32), moyen du nombre de cures : 2,5, moyenne des intercures : 9,6 mois (5–14). Caracteristiques biologiques : moyenne des LBCD19 + CD 27+ au retraitement etait de 0,03 % (0,066–0,01), moyenne des LB-CD19+ au retraitement est de 51,6/mm3 (0–119), rituximabemie moyenne : 2,28 μg/mL (0–37,3). Discussion Nous confirmons que sur une moyenne de 21 mois de suivi, le dosage des LBCD19 + CD27+ est le marqueur biologique de rechute biologique le plus fiable, permettant d’eviter des perfusions inutiles, des economies et une diminution de la toxicite. Il n’y a pas eu de rechute clinique severe ni d’effet secondaire grave lors des espacements de cures. Conclusion Le suivi des LBCD19 + CD27+ est un marqueur biologique de rechute fiable et non correle aux LBCD19+. Les facteurs d’echappement au RTX sont en cours d’etude et seront discutes.

Introduction La maladie associee aux immunoglobulines (Ig) G4 (MAG4) est une entite fibro-inflammatoire multisystemique rare de plus en plus decrite. L’atteinte neurologique reste rare avec des manifestations hypophysaire et meningee preponderantes. Nous decrivons un cas de nevrite optique bilaterale et paralysie du III secondaire a une pachymeningite hypertrophique liee aux IgG4. Observation Un homme de 66 ans, polyvasculaire, se presentait aux urgences pour une baisse d’acuite visuelle bilaterale non douloureuse d’apparition subaigue. L’interrogatoire nous apprenait qu’il souffrait de cephalees chroniques pulsatiles depuis de nombreux mois. Il n’y avait ni fievre, ni perte de poids. L’examen physique retrouvait un ptosis et une mydriase reactive gauche avec baisse de l’acuite visuelle bilaterale a 5/10 a droite et 10/champ a fort grossissement. Le diagnostic de MAG4 pose, une corticotherapie a la posologie d’1 mg/kg/j apres assauts cortisoniques etait introduite mais ne permettait pas la regression des symptomes. A 12 mois, un traitement par rituximab a la posologie d’un gramme (J1–J15 puis entretien) etait utilise. A 15 mois de l’introduction de ce dernier, une amelioration clinico-radiologique etait constatee avec regression partielle des cephalees et recuperation d’une acuite visuelle a 10/10 a droite et Discussion La MAG4 est une entite fibro-inflammatoire caracterisee par des tumefactions, un infiltrat lympho-proliferatif dense, riche en plasmocytes IgG4, une fibrose storiforme et, frequemment, une elevation des concentrations seriques d’IgG4 qui permet d’orienter le diagnostic. L’approche diagnostique est complexe et requiert le recours a une analyse histologique afin d’eliminer tout processus neoplasique et/ou infectieux sous-jacent [1] . L’atteinte neurologique est volontiers caracterisee par une pachymeningite hypertrophique se revelant par des cephalees inhabituelles ou des phenomenes compressifs vasculaires ou neurologiques comme chez notre patient. L’atteinte meningee, lorsqu’elle est presente, est isolee dans 30 % des cas rendant le diagnostic difficile [2] . Seule la biopsie meningee permet d’etablir le diagnostic. De plus, l’elevation des IgG4 seriques semble dependante du nombre d’organes touches par la maladie expliquant ainsi sa frequente normalite au cours des atteintes neurologiques. Le LCR est rarement informatif. La MAG4 est la seconde cause de pachymeningite inflammatoire apres la granulomatose avec polyangeite. Les autres granulomatoses, y compris a BK et l’hypotension chronique du LCR sont les principaux diagnostics differentiels. Son traitement repose sur la corticotherapie en premiere intention. Il est frequent qu’un traitement immunosuppresseur d’epargne cortisonique soit prescrit et plusieurs cas rapportent l’efficacite des anticorps monoclonaux diriges contre le CD-20 [3] . Conclusion La pachymeningite liee a la MAG4 est une entite rare de la maladie. Cependant, cette manifestation, de plus en plus decrite, souleve certaines atypies qu’il convient de connaitre (atteinte neurologique isolee, absence de syndrome inflammatoire, IgG4 seriques normales et LCR peu informatif) afin de ne pas meconnaitre le diagnostic de cette pathologie curable et souvent corticosensible.

Encephalitis with anti-NMDA receptor antibodies is a recently-recognised form of paraneoplastic encephalitis characterized by a prodromal phase of unspecific illness with fever resembling viral disease, followed by memory loss, psychiatric features, seizures, disturbed consciousness, prominent abnormal movements and autonomic imbalance. Association with ovarian teratoma is common. Neurological outcome can be good, especially when surgery is performed at an early stage. Here, we report a case of anti-NMDA receptor encephalitis associated with ovarian teratoma presenting with inaugural complex partial status epilepticus. The nature of abnormal movements at early stages was unclear and abnormal movements were misinterpreted as the recurrence of partial epileptic seizures. Despite its rarity, all clinicians treating epilepsy and movement disorders should be familiar with anti-NMDA receptor encephalitis, that appears to be a very severe but curable disease.

Objective: Myasthenia gravis (MG) is an autoimmune neuromuscular disorder for which current therapies carry a high risk of side-effects and may be insufficient in stabilizing the clinical status. Many therapeutic options can be ruled, such as thymectomy, corticosteroids, azathioprine, cyclophosphamide, mycophenolate mofetil, methotrexate, intravenous immunoglobulin (IVIg) or less frequently plasmapheresis must be ruled. Methods: We followed prospectively six patients with MG who presented with a poor response to two or three lines of immunosuppressive conventional drugs associated with oral corticosteroids. All but one were acetylcholine receptor negative and three were anti-MuSK positive. IVIg did not improved the neurological status and all patient required high doses of cholinesterase inhibitors. Results: Rituximab was introduced with a mean follow-up of 1.5 years (375 mg/m2, days 1, 8, 15, 28 during the first month and then one dose every 2 months). After 2 years of follow-up, all patients stopped corticosteroids and tapered off cholinesterase inhibitors from 60 to 180 mg/day without severe infectious events. Conclusion: Rituximab, a chimeric IgG k monoclonal antibody that target CD20 is used for the treatment of relapsing/refractory CD20 positive low-grade non-Hodgkin’s lymphoma and other autoimmune neuromuscular diseases. Four previous short reports have described a good response of MG associated with lymphoma with rituximab. It appears to be a promising and effective drug for the treatment of MG without lymphoma, with a substantial benefit to the clinical status and good tolerability.

Resume Introduction Les criteres de de Seze et al. [Arch Neurol 64 (2007) 1426–32] permettent a priori, face a un episode inflammatoire aigu du SNC, de reperer les patients presentant une encephalomyelite aigue disseminee (EMAD). Nous avons applique ces criteres sur une serie de patients suivis au CHU de Nice dont l’histoire clinique initiale correspondait a un premier evenement demyelinisant aigu severe. Les patients âges de moins de 16 ans et ceux dont le tableau clinique initial se resumait a une NORB ou une myelite aigue transverse ont ete exclus de l’etude. Patients et methode Quatorze patients ont ete etudies retrospectivement : sept cas d’EMAD et sept cas de scleroses en plaques (SEP). La presentation initiale etait pseudotumorale pour cinq patients sur sept (71,4 %) du groupe SEP, ayant fait hesiter avec une EMAD. Nous trouvons une sensibilite de 85,7 % et une specificite de 71,4 % aux criteres de de Seze et al. Le manque de specificite vient des erreurs de classement des patients SEP a presentation pseudotumorale pour lesquels il existe deux faux positifs sur cinq. Les criteres de de Seze et al. representent une aide precieuse dans la demarche diagnostique d’un premier evenement demyelinisant. Conclusion Les resultats de notre etude suggerent que la presence d’un tableau initial pseudotumoral pourrait peut-etre constituer une limite a l’application de ces criteres.

Based on studies relating to anaplastic oligodendroglioma (OG) chemosensitivity and benefit of time to progression or overall survival, chemotherapy for pure OG has been proposed. Several studies have reported the efficacy of various chemotherapeutic agents in a small number of patients with low-grade gliomas, e.g. pure astrocytomas, OG or mixed histologies. The 5-year survival rate varies from 61% to 89% with a mean time to progression of 5 years. We report the outcome of 33 consecutive patients with pure low-grade OG diagnosed between 1990 and 2006 systematically treated for residual or non-removable tumor with PCV chemotherapy regimen as the front-line treatment after surgery. All the tumors were low grade (grade II) pure OG according to the WHO classification. All patients were symptomatic at presentation and underwent neurosurgical procedure for histological diagnosis. Response was evaluated by clinical assessment and brain magnetic resonance imaging. Twenty-one men and 12 women with a mean age at pathological diagnosis of 46.5 years were studied. The most common first symptom was partial epileptic seizure (73.7%). Six patients (18%) had initial gadolinium enhancement, associated with methoxyisobutyl (MIBI) hypermetabolism (P < 0.001). The resection was partial in seven cases (21%), and 26 patients (79%) had biopsy only. Eleven patients (36%) had a malignant transformation during the follow-up with a median time to progression of 19 months. Favorable prognostic factors were lack of contrast enhancement (P < 0.0001), and age

Resume Introduction La neurosarcoidose est une pathologie rare (5 cas pour 1 million d’habitants) et d’etiologie inconnue. L’atteinte neurologique est revelatrice de la sarcoidose dans 50 p. 100 des cas, et elle reste limitee au systeme nerveux dans 10 p. 100 des cas. Son polymorphisme clinique et iconographique rend son diagnostic difficile. La corticotherapie en premiere intention, puis les immunosuppresseurs classiques sont preconises, mais leurs contre-indications, leurs effets secondaires, et leurs toxicites ne sont pas negligeables. Lorsque la neurosarcoidose devient resistante aux traitements usuels, l’attitude therapeutique n’est pas codifiee. Le mycophenolate mofetil (MMF) est utilise dans de nombreuses pathologies neurologiques dysimmunitaires, avec des resultats tres satisfaisants et une bonne tolerance, mais aucun cas de neurosarcoidose traitee par MMF n’est actuellement rapporte. Cas clinique Nous rapportons l’observation de 2 patientes presentant une neurosarcoidose traitee par MMF et corticoides. Conclusion Une efficacite clinico-radiologique rapide et durable a pu etre notee, permettant une diminution progressive de la corticotherapie, avec une excellente tolerance clinique et biologique.

Resume Introduction Les patients atteints de SEP et originaires du Maghreb representent, a Nice, pres de 8 p. 100 des patients enregistres dans la base de donnees EDMUS. Patients et methodes Nous avons realise une etude descriptive retrospective de la population d’origine maghrebine (n = 76) atteinte de SEP, suivie dans le service de Neurologie du CHU de Nice et l’avons comparee a la population de SEP regionale (n = 968) issue de notre base de donnees EDMUS (European database on MS). L’analyse statistique nous a permis d’individualiser trois sous-groupes de patients, soumis a des facteurs environnementaux differents, selon le lieu de naissance ou l’âge a la migration, dont la comparaison revele des particularites pronostiques. Resultats Pour l’ensemble de la cohorte, les facteurs de mauvais pronostic sont : une forte proportion de sujets masculins, un premier evenement avec sequelles et une IRM initiale remplissant d’emblee les criteres de Barkhof. Concernant l’analyse en fonction des sous-groupes, les particularites pronostiques propres a chaque sous-groupe sont les suivantes : — les patients d’origine maghrebine nes en France ont un âge de debut precoce, un delai diagnostique et un intervalle libre entre les deux premieres poussees longs, presentent rapidement un syndrome cerebelleux et une forme secondairement progressive. — les patients ayant migre avant 15 ans ont un premier evenement monosymptomatique souvent visuel et avec sequelles et presentent rapidement un syndrome cerebelleux. — les patients ayant migre apres 15 ans ont un âge de debut tardif, un delai diagnostique et un intervalle libre entre les deux premieres poussees courts, un premier evenement monosymptomatique souvent moteur, medullaire ou du tronc cerebral, un syndrome cerebelleux et une forme secondairement progressive plus frequents. Ce sont les patients dont la progression du handicap est la plus rapide. Conclusion Notre travail confirme le profil evolutif plus severe de la maladie pour la cohorte maghrebine globale, comme dans les travaux disponibles dans la litterature. Differencier les patients en fonction du lieu de naissance et de l’âge a la migration est necessaire pour une prise en charge adaptee. L’instauration precoce d’un traitement de fond avec l’utilisation plus systematique et precoce des immunosuppresseurs doit etre discutee dans ces populations maghrebines.

Aims MET gene amplification is rare in glioblastoma (GBM) and represents a potential target for MET inhibitors. An immunohistochemical screening may be useful to identify MET amplification. The aim of our study was to establish how MET immunolabelling correlates with MET amplification. Methods Three cohorts including 108 GBM (cohort 1, prospective), 104 GBM (cohort 2, retrospective) and 52 GBM (cohort 3, prospective) were investigated for MET expression by immunohistochemistry. MET amplification was assessed by comparative genomic hybridization on microarray (CGH-array) in all cohorts and by fluorescent in situ hybridization (FISH) in cohorts 2 and 3. Active form of MET was assessed using p-MET (Y1349) immunohistochemistry. Results Diffuse MET amplification detectable by CGH-array was associated with diffuse, strong MET immunolabelling (four cases in cohort 1 and one case in cohort 2). Focal MET amplification detectable only by FISH was observed in small foci of strongly immunopositive cells in two GBM (cohort 2). In both cohorts, MET amplification was never detected in GBM devoid of strongly immunopositive cells. MET overexpression, observed in 23% of unamplified GBM, was associated with a predominant weak-to-moderate staining intensity and with necrosis (P < 0.005). p-MET was detected in all MET-amplified GBM and in perinecrotic areas of nonamplified GBM. A strong MET immunostaining intensity, at least focal and distant from necrosis, showed 100% sensitivity and 84% specificity for predicting MET amplification in cohort 3. Conclusions MET amplification is characterized by strongly immunopositive cells. Only GBM showing strong MET immunostaining is appropriate for the assessment of MET amplification.

Resume Introduction Le syndrome de Turcot est un syndrome clinique, presumant d’une susceptibilite genetique aux cancers, qui associe des tumeurs cerebrales primitives et une polypose colique familiale ou des cancers colo-rectaux. Observation Nous rapportons le cas d’une patiente âgee de 45 ans qui fut prise en charge en 1995 pour un astrocytome anaplasique selon la classification de l’OMS. Elle eut une sequence therapeutique complete des la presentation : chirurgie d’exerese complete, radiotherapie, chimiotherapie de premiere (nitroso-urees) et seconde lignes (sels de platine). La reprise de l’anamnese mit en evidence l’existence d’un cancer du colon chez son frere âge de 41 ans. Une analyse genetique de la patiente, realisee a la recherche d’un syndrome de Turcot, montra une mutation du gene hMSH2 , specifique du syndrome HNPCC (Human Non Polyposis Colorectal Cancer). La colonoscopie etait normale. La patiente deceda plus de 7 ans apres le diagnostic, d’une gliomatose cerebrale diffuse. Conclusion Le syndrome de Turcot doit etre recherche devant une histoire personnelle ou familiale evocatrice. II modifie la prise en charge du patient et de sa famille et est probablement sous-estime.

Nutritional factors and comedications are among the postulated causes of fatigue, a highly prevalent symptom in the multiple sclerosis (MS) population, with serious impact on patients’ quality of life. Deficiency of carnitine may play a role by reducing energy production through fatty acid oxidation and numerous MS therapies can induce fatigue syndrome. The aim of this prospective open-labelled study was to collect and study serum carnitine levels in MS patients with and without disease-modifying treatment-induced fatigue syndrome. We investigated whether restoration of the carnitine pool might improve treatment-induced fatigue in MS patients. In our study, there was no statistical difference in fatigue frequency between treated and untreated patients ( P=0.5). Matched to age, gender and treatments, carnitine levels were lower for MS treated patients compared to untreated MS patients ( P

Resume Les gliomes malins demeurent le probleme majeur de la neuro-oncologie, par leur frequence, leur gravite et les difficultes de traitement qu’ils posent. Les etapes de diagnostic clinique et neuroradiologique sont bien etablies et performantes ; la stabilite de ces acquis contraste avec le paradoxe des avancees de la recherche biologique qui demeurent sans consequence pratique, sinon de susciter une multitude de protocoles de recherche clinique. En neuropathologie des gliomes malins, les nouvelles methodes d’immunohistochimie et de genetique moleculaire font entrevoir les insuffisances des seuls aspects morphologiques au profit de criteres d’ontogenese cellulaire auquel le neuropathologue n’avait pas acces anterieurement. Ces donnees de biologie moleculaire et de genetique tumorale sont attendues en routine pour etablir des diagnostics precis guidant les strategies de traitement specifique de chaque type tumoral. En neurochirurgie, le lien entre l’etendue des exereses et la duree de survie a ete etabli et la chirurgie « optimale » aidee par les nouvelles technologies peroperatoires est devenu le temps essentiel du traitement initial et parfois de la recidive des gliomes. Surtout, le developpement des methodes de nanoneurochirurgie, d’implantation in situ d’agents cytotoxiques ou immunomodulateurs et les reponses obtenues par ces depots ouvrent un champ d’actions therapeutiques imaginees de longue date, mais demeurees virtuelles faute de disposer des technologies adequates de mise en œuvre. En radiotherapie, les methodes d’imagerie, les algorithmes de recalage conformationnel et de dosimetrie ont permis la reduction considerable des effets iatrogenes mais les resultats obtenus sont encore modestes et surtout transitoires. En chimiotherapie, les obstacles pharmacocinetiques, le faible nombre de molecules disponibles et les capacites innees ou acquises des systemes de chimioresistance et de reparation des lesions alkylantes sont retenus pour rendre compte de la mediocrite de l’apport objectif pour les patients, mais il y a espoir : des sous-groupes chimiosensibles peuvent etre identifies, de nouvelles molecules (fotemustine, temozolomide) et surtout les antagonistes des boucles de proliferation cellulaire, autocrines et paracrines, font envisager la mise a disposition des cliniciens de nouvelles associations et esperer des complementarites d’action. Enfin, les multiples possibilites de l’immunotherapie et des therapies geniques sont en exploration dans des etudes de phase I et II ; elles tentent de combler cette distance entre les connaissances acquises par la recherche fondamentale et les resultats obtenus en clinique. Au total, les gliomes malins demeurent d’un pronostic tres defavorable, mais les avancees des methodes diagnostiques et therapeutiques sont certaines ; des a present, quelques types tumoraux relevent de traitements specifiques qui montrent que ces nouvelles approches derivees des recherches en oncogenese sont possibles et valident les theories biologiques qui les sous-tendent.

Resume Introduction Certaines formes de sclerose en plaques ont une presentation en imagerie par resonance magnetique nucleaire troublante. Le diagnostic chez l’adolescent ou le jeune adulte est parfois difficile, surtout si l’interrogatoire retrouve un antecedent recent d’infection ou de vaccin. Observation Nous rapportons un cas de sclerose en plaques, particulier dans sa presentation radio-clinique, mimant une encephalite aigue disseminee. Le diagnostic differentiel clinique et radiologique avec une encephalomyelite et l’evolution en imagerie sous traitement immunosuppresseur sont discutes. Conclusion Le diagnostic differentiel entre une encephalomyelite aigue disseminee et une premiere poussee de sclerose en plaques peut etre difficile. L’imagerie apporte des indices importants pour discerner ces deux pathologies.

Resume Introduction Les meningites recurrentes aseptiques imposent souvent une enquete diagnostique difficile. Nous rapportons un cas de meningite aseptique recurrente associee a une cirrhose biliaire primitive. Cas clinique Une patiente de 37 ans presenta a 4 reprises des episodes meningitiques isoles avec hyperthermie. Le traitement par corticoides en intraveineuse etait efficace. Le bilan effectue retrouvait une fracture ancienne tympano-labyrinthique droite avec un rehaussement anormal du fond du conduit auditif interne en IRM, et un taux plasmatique significatif d’anticorps anti-mitochondries de type M2. Conclusion Le diagnostic retenu fut celui de meningite puriforme aseptique recurrente secondaire a un foyer inflammatoire non septique ORL dans un contexte auto-immun latent du a une cirrhose biliaire primitive. A notre connaissance, il constitue le premier cas de ce type rapporte dans la litterature.

INTRODUCTION: Magnetic resonance imaging (MRI) has transformed management of patients with multiple sclerosis. The exact contribution of brain MRI remains a subject of debate, but it is generally considered to provide a more specific and more sensitive outcome measure for monitoring purposes and for testing new therapies. The choice of MRI techniques, and measurement reproducibility for multiple sclerosis brain lesions are not defined with precision for routine practice. There are many sources of error when comparing successive images which can be overcome to some extent with repositioning and image processing techniques. METHODS: We evaluated the impact of image repositioning on treatment decision-making for twelve relapsing remitting patients. Brain MRIs were performed every three months for a one-year period. Two neurologists interpreted the non-repositioned and repositioned images giving their analysis of changes in the lesions visualized on the T2 sequences and their therapeutic decisions. RESULTS: For the first neurologist, analysis of the non-repositioned images yielded six patients whose lesions had worsened while for the repositioned images there were only three. For the second neurologist, four patients had more lesions with the non-repositioned images and only three with repositioning. The subjective interpretations were the same for the two neurologists when they used repositioned images. CONCLUSIONS: Comparison by two neurologists of non-repositioned and repositioned MRI, with no other image processing, affected the analysis and in certain cases propositions for treatment.

Resume Introduction Le cyclophosphamide est couramment utilise en traitement de fond des formes progressives de sclerose en plaques. L’objectif de cette etude a ete de chercher les facteurs predictifs d’une reponse au cyclophosphamide. Materiel et methodes Quarante-sept patients presentant une forme secondairement progressive et sept une forme primaire progressive ont recu des perfusions mensuelles de cyclophosphamide (750 mg/m2) et de methylprednisolone (500 mg). L’indication du traitement etait une aggravation du handicap avec une augmentation de l’EDSS d’au moins un point en un an due a la presence ou non de poussees surajoutees. Le critere d’evaluation du handicap etait le score EDSS a 6, 12, 24 mois et 5 ans. Resultats Pour les formes secondairement progressives, 91 p. 100 (43/47) des patients etaient stables ou ameliores a 12 mois, 65 p. 100 (26/40) a 24 mois et 22 p. 100 (5/23) a 5 ans. Pour les patients secondairement progressifs avec poussees surajoutees, le taux annuel de poussee passa de 0,81 l’annee avant le traitement a 0,48 pendant le traitement puis 0,12 l’annee suivante (p Conclusion Dans les formes progressives de sclerose en plaques, les patients avec une phase progressive d’apparition recente et une aggravation rapide du handicap repondent plus frequemment au cyclophosphamide, independamment de l’âge, du score de handicap initial ou de la presence de poussees surajoutees.

We collected 6 case-reports of symptomatric non removable low grade fibrillary astrocytoma of adults treated with a procarbazine-CCNU-vincristine chemotherapy regimen. All patients had drug-resistant epilepsy but brain imaging was stable. Total gross resection was rejected because of Volume or tumor location. After 4 to 7 cycles of chemotherapy, 2 patients had partial response and one minor response on brain MRI. All of them were seizure-free. Progression free survival was not reached at 5 Years. Up-front chemotherapy for low-grade astrocytomas may be useful and has to be prospectively evaluated.

Opinion/Feedback The Child and Family Hospital of Grenoble is one of the rare university hospitals in France to benefit from the presence of a physician specializing in rehabilitation medicine. This hospital includes both inpatient and outpatient units. During the temporary closure of one department, certain members of the rehabilitation unit were reassigned to the acute care wards of the pediatric department, including physical therapists, occupational therapists, and speech therapists. Over the course of one year, these therapists completed more than 150 interventions in this department, more than half of which were in the hematology and oncology ward. The most common requests were for speech therapy interventions to maintain and improve swallowing and feeding in the prolonged presence of a nasogastric tube as well as the prevention and follow-up for swallowing difficulties in brain tumor patients. The second most common request was for the assistance of an occupational therapist with wheelchair use, both to allow patients to sit upright early in good conditions and to analyze the conditions necessary for a patient to return home. The teamwork between the speech and occupational therapists is invaluable for patients learning to use voice synthesis software. Finally, care from a physical therapist allows for the maintenance of motor skills during oncological as well as orthopedic care. The data we report calls for the creation and systematic use of a rehabilitation medicine team in the pediatric oncology ward. Requests increased over the course of the year, showing that pediatricians became more and more aware of the benefits offered by these therapists. We observe that improvement is present regardless of the prognosis, from the beginning of treatment to the sometimes prolonged rehabilitation process, including situations of palliative care. The integration within the Child and Family Hospital allows for quick coordination that improves the quality of care. Improvement in quality of life is always observed by reducing patients’ hospital stays and allowing them to return home more quickly as well as expediting the process of choosing the most suitable form of rehabilitation.

Introduction Les traumatismes de l’epaule secondaires a des crises d’epilepsie sont rares mais leur impact fonctionnel et sur la qualite de vie est serieux. Objectifs Mieux caracteriser le mode de survenue des traumatismes de l’epaule induit par des crises d’epilepsie et le(s) type(s) de population(s) touchee(s). Patients et methodes Entre 2004 et juin 2015, nous avons collige, de maniere retrospective, les donnees des patients ayant presente un traumatisme de l’epaule a la suite d’une crise d’epilepsie. Nous avons recueilli des donnees demographiques, anamnestiques, et paracliniques pour plusieurs types de traumatismes et en particulier les luxations anterieures (LA), les luxations posterieures (LP) et les fractures sans luxation (FSL). Resultats Notre cohorte regroupait 73 patients (70 % d’hommes). Une LA etait retrouvee chez 30/73, une LP chez 33/73 et une FSL chez 10/73. L’âge moyen de survenue des LA etaient de 28,8 ans contre 49,5 ans dans le groupe LP ( p p = 0,0003). L’instabilite de l’epaule touchait majoritairement les patients avec LA. Les FSL concernaient des sujets plus âges et souvent secondairement a une chute. Discussion La phase tonique d’une crise generalisee favoriserait la LP par un mecanisme de flexion, rotation interne et adduction de l’epaule et l’asymetrie de contraction entre muscles rotateurs internes et externes de l’epaule. La LA serait favorisee par un mecanisme d’abduction, de rotation externe et de retropulsion survenant plus volontiers en phase clonique, et possiblement favorise par la mise en position laterale de securite (blocage de l’epaule). Conclusion Les crises d’epilepsie peuvent etre a l’origine de luxation anterieure ou posterieure sans qu’une chute en soit a l’origine. Les luxations anterieures predominent chez le jeune homme avec une EGI qui risque de developper une instabilite de l’epaule.

Introduction Le Rituximab (RTX) est un anticorps monoclonal antiCD20 qui a montre son efficacite et sa bonne tolerance dans la myasthenie generalisee (MG). Le schema d’administration est variable selon les equipes. Objectifs Evaluer l’interet du dosage sanguin des LB-CD27+ comme marqueur biologique de rechute de la MG dans le but d’adapter la frequence d’administration du RTX. Patients et methodes Depuis 2015, 32 patients myastheniques ont ete traites par RTX. Les patients recoivent une cure d’induction (1 g J1 et J15). Une evaluation clinique (score myasthenique) et des parametres biologiques (LB-CD19+, LB-CD27+, Rituximabemie et Ac anti-RTX) sont realises tous les 3 mois. En cas de reemergence des LB-CD 27+ (le seuil de detection est a 0,05 % PBMC), une cure d’entretient de RTX (1 g) est realisee. Resultats Trente-deux patients ont ete evalues : âge moyen de 52 ans (18–92 ans ; 53 % de femmes), 90 % Ac anti-Rach+, 3 % Ac anti-Musk+ et 12 % Ac anti-Titine. A l’induction, le score myasthenique moyen est de 70/100 (22/100–100/100). Quarante-quatre pour cent des patients avaient recu un ou plusieurs traitements immunosuppresseurs et 56 % etaient naifs de traitement de fond. Le delai moyen de reemergence des LB-CD27+ est de 7 mois (2–12) avec un score myasthenique moyen de 81/100 (56/100–100/100). Discussion Le suivi des LB-CD27+ a permis d’identifier des patients avec reemergence precoce (2 mois) et d’autres necessitant un espacement des cures jusqu’a un an, evitant ainsi des perfusions inutiles, des economies et une diminution de la toxicite. Il n’y a eu aucune rechute clinique severe lors des espacements de cures ni aucun effet secondaire grave. Conclusion Le suivi des LB-CD27+ permet une reduction du nombre de cures avec une bonne efficacite clinique. Ce marqueur sera d’autant plus interessant economiquement avec l’emergence des nouveaux anti-CD20.

Introduction La presence de troubles cognitifs au diagnostic a ete mise en evidence dans les gliomes de bas grade, particulierement au niveau des fonctions executives et de la memoire de travail. Objectifs Cette etude vise a investiguer l’evolution dans le temps et au decours du traitement chirurgical des capacites de memoire de travail chez les patients atteints de gliomes de bas grade. Patients et Methodes Vingt patients atteints de gliome de grade II selon l’OMS ont eu une evaluation pre et post-chirurgicale (16 operes en condition eveillee). Seize patients ont ete reevalues a 1 an et 13 a 2 ans. Ces 11 femmes et 9 hommes d’un niveau d’etude moyen de 12 ans et d’un âge moyen de 40 ans ont passe l’epreuve de la WAIS IV mesurant l’empan endroit (memoire a court terme) et l’empan inverse (memoire de travail). Resultats A l’inclusion, ils presentaient a l’empan inverse un z-score de 0,75 (±0,69). Pour 6 patients ce score etait inferieur a 1, dont 3 inferieurs a 1,5. Sur ces 6 patients, 4 se sont normalises en postoperatoire et 2 se sont ameliores ulterieurement. Sur les 20 patients, 5 se sont deteriores en postoperatoire, 10 sont restes stables et 5 se sont ameliores. A plus long terme, 9 se sont ameliores et 2 restent deficitaires. Discussion Les 2 patients restant deficitaires n’ont pas ete operes en condition eveillee. La deterioration potentielle de la memoire de travail suite a une exerese chirurgicale en condition eveillee est transitoire. Des recherches ulterieures s’interesseront a l’effet de la chimiotherapie. Conclusion L’exerese chirurgicale en condition eveillee peut permettre d’ameliorer a long terme les capacites de memoire de travail des patients atteints de gliomes de bas grade.

Summary Background The incidence of haematologic toxicity of valproate (VPA) ranges from 1% to 32%, and consists mainly of asymptomatic, dose-dependent thrombopenia. We describe a potentiation of haematologic side-effects of nitroso-urea (NU) when prescribed in association with VPA. Patients and methods We followed a cohort of 70 patients (58 men, 22 women, mean age: 56 years, range 20–75 years). Patients with high-grade gliomas were treated with up-front chemotherapy regimen consisting of fotemustine (d3: 100 mg/m2), cisplatin (dl–3: 33 mg/m2) and etoposide (dl–3: 75 mg/m2) followed by whole brain radiotherapy at progression. Sixty patients required anti-epileptic drugs (AED) for either a single, well-documented epileptic seizure, or immediatly initiated after neurosurgical procedures. AED included VPA (35 of 60), phenobarbital (PB) (17 of 60), carbamazepine (CBZ) (2 of 60) and phenytoin (PHT) (3 of 60). Two patients had both PB and CBZ and one PB and PHT. Results Haematologic toxicity (grade 3–4 thrombopenia, neutropenia or both) was observed in 37 of 70 (52.85%) patients. Among them 24 (65%) had VPA. Group C were patients treated with fotemustine alone with or without VPA (23 patients). Conclusion When prescribed in association with a fotemustine-cisplatin regimen, VPA treatment results in a three-fold higher incidence of reversible thrombopenia, neutropenia or both. Haematologic side-effects decrease after AED modification during the continued chemotherapy. This adverse event should be managed with caution.

Lower urinary tract dysfunctions (LUTD) are very common in Multiple Sclerosis (MS), have a significant social impact, while the organic impact is discussed. We studied urinary complications and their risk factors in our cohort of MS patients, in order to improve the management of LUTD in MS.Between 2004 and 2009, all patients affected by MS and managed for LUTD were included in a retrospective study. We studied the epidemiological data (age, gender), the clinical data (duration of MS, EDSS score, progression of MS) and the paraclinical data (urinary creatinine clearance, urine culture, urinary tract ultrasonography and in some cases urodynamic assessment and cystography). We then identified the urinary complications and their risk factors.Three hundred twenty eight patients, mean age 49.9 ± 12.3 years, with a MS for 14.3 ± 10 years on average and with a median EDSS score equal to 6 (1-9), were managed for LUTD. One hundred seventy eight (54%) patients developed one or more urinary complications. We identified duration of MS greater than 8.5 years and an EDSS above 7 as risk factors.Urinary complications are common in symptomatic MS, these results imply screening and specialized care to limit the impact on the quality of life but also to prevent urinary complications.

Objective We present a preliminary study of plantar pressure control with visual feedback in healthy volunteers by using internal or external focus attentional focalization. The objectives are to decrease the pressure under the right heel of 70%. Material/patients and methods Twenty healthy volunteers were randomized into 2 groups using either internal or external focus. Plantar pressures were recorded using 3 captors under each heel, on the heads of 1st and 5th metatarsals as well as under the calcanean tuberosity (Winshoe device, Medicapteurs C). Simultaneous visual feedback consisted of a graduated color scale through which each zone produced a color objective for requested alleviation. The order was different for each group, leading either to an external focus (“deforming the ground”) or internal focus (“press on the heel”). Measurements of walking speed as well as the number of steps were taken using photoelectric cells. Subjects were tested in 3 steps: (i) over 20 m of normal walking, (ii) tested after an order of internal or external focus, associated to a simultaneous visual feedback, and (iii) after 3 minutes of a single order. Results The subjects were able in every case to decrease the pressure on the heel; however, the goal of decreasing it by 70 ± 7% was achieved in only 10% to 20% of cases. There were no statistical differences across the 2 groups. We observed a retention/learning situation after the second step being able to decreased pressure even without feedback. The walking speed decreased in every case. Subjects were able to decrease pressure on the heel but the more refined objective to control this pressure was not achieved. Discussion–conclusion We discuss the relevance of the notice order and the type of visual feedback, which might have been too complex. The absence of difference between internal focus and external focus is difficult to interpret in this setting. The next step would be to test a higher number of human volunteers, and use hearing feedback.

Acute demyelinating encephalomyelitis (ADEM) is characterized by a severe inflammatory attack, frequently secondary to infectious events or vaccinations. To date, no clear criteria exist for ADEM, and the risk of subsequent evolution to multiple sclerosis (MS) remains unknown.To evaluate the risk of evolution to MS after a first episode of ADEM.Observational, retrospective case study.Thirteen French MS centers. Patients We retrospectively studied 60 patients with ADEM who were older than 15 years with no history suggestive of an inflammatory event who presented to MS centers from January 1, 1995, through December 31, 2005. We excluded 6 patients with multiphasic ADEM because this is a rare condition and somewhat difficult to classify. After a mean follow-up of 3.1 years (range, 1-10 years), the remaining 54 patients were then classified into 2 groups: monophasic ADEM (ADEM group) (n = 35) and clinically definite MS (MS group) (n = 19).Clinical, laboratory, magnetic resonance imaging, and follow-up data were evaluated for each group.Patients in the ADEM group more frequently had atypical symptoms of MS (26 of 35 [74%]) than patients with MS (8 of 19 [42%]) (P = .02). Oligoclonal bands were more frequently observed in the MS group (16 of 19 [84%]) than in the ADEM group (7 of 35 [20%]) (P.001). Patients in the ADEM group more frequently had gray matter involvement (21 of 35 [60%]) than those in the MS group (2 of 19 [11%]) (P.001). On the basis of these results, we consider that the presence of any 2 of the following 3 criteria could be used to differentiate patients with ADEM from those with MS in our cohort: atypical clinical symptoms for MS, absence of oligoclonal bands, and gray matter involvement. On this basis, 29 of the 35 patients in the ADEM group (83%) and 18 of the 19 patients in the MS group (95%) were classified in the appropriate category.Our study found some differences concerning the risk of evolution to clinically definite MS after a first demyelinating episode suggestive of ADEM. These findings led us to propose criteria that should now be tested in a larger, prospective cohort study.