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The role of Human pegivirus (HPgV) in patients with encephalitis has been recently questioned. We present cases of 4 patients with similar clinical, biological, and radiological characteristics, including a past history of transplantation with long-term immunosuppression and a progressive course of severe and predominantly myelitis, associated in 3 cases with optic neuropathy causing blindness. Extensive workup was negative but analysis of the CSF by use of pan-microorganism DNA- and RNA-based shotgun metagenomics was positive for HPgV. This case series further supports the hypothesis of HPgV CNS infection and highlights the utility of metagenomic next-generation sequencing of CSF in immunocompromised patients.

SCOPUS: le.j, info:eu-repo/semantics/published

In multiple sclerosis (MS), immune cells invade the central nervous system and destroy myelin. Macrophages contribute to demyelination and myelin repair, and their role in each process depends on their ability to acquire specific phenotypes in response to external signals. Here, we assess whether defects in MS patient macrophage responses may lead to increased inflammation or lack of neuro-regenerative effects.To test this hypothesis, CD14+CD16- monocytes from MS patients and healthy controls were activated in vitro to obtain homeostatic-like, pro-inflammatory and pro-regenerative macrophages. Myelin phagocytic capacity and surface molecule expression of CD14, CD16 and HLA-DR were evaluated with flow cytometry. In parallel, macrophages were assessed through RNA sequencing and metabolomics.We observed that MS patient monocytes ex vivo recapitulate their preferential activation toward a CD16+ phenotype, a subset of pro-inflammatory cells present in MS lesions. Even in the absence of pro-inflammatory stimuli, MS patient macrophages exhibit a pro-inflammatory transcriptomic profile with higher levels of cytokine/chemokine suggesting increased recruitment capacities. Interestingly, MS patient macrophages exhibit a specific metabolic signature with a mitochondrial energy metabolism blockage resulting in a shift from oxidative phosphorylation to glycolysis. Furthermore, we observe a failure to up-regulate apoptosis effector genes in the pro inflammatory state suggesting a longer-lived pro-inflammatory macrophage population.Our results highlight an intrinsic defect of MS patient macrophages that provide evidence of innate immune cell memory in MS.

Objectives Establish recommendations for the management of UTIs in MS patients. Background Urinary tract infections (UTIs) are common during multiple sclerosis (MS) and are one of the most common comorbidities potentially responsible for deaths from urinary sepsis. Methods The recommendations attempt to answer three main questions about UTIs and MS. The French Group for Recommendations in MS (France4MS) did a systematic review of articles from PubMed and universities databases (01/1980–12/2019). The RAND/UCLA appropriateness method, which has been developed to synthesize the scientific literature and expert opinions on health care topics, was used for reaching a formal agreement. 26 MS experts worked on the full-text review and a group of 70 multidisciplinary health care specialists validated the final evaluation of summarized evidences. Results UTIs are not associated with an increased risk of relapse and permanent worsening of disability. Only febrile UTIs worsen transient disability through the Uhthoff phenomenon. Some immunosuppressive treatments increase the risk of UTIs in MS patients and require special attention especially in case of hypogammaglobulinemia. Experts recommend to treat UTIs in patients with MS, according to recommendations of the general population. Prevention of recurrent UTIs requires stabilization of the neurogenic bladder. In some cases, weekly oral cycling antibiotics can be proposed after specialist advice. Asymptomatic bacteriuria should not be screened for or treated systematically except in special cases (pregnancy and invasive urological procedures). Conclusion Physicians and patients should be aware of the updated recommendations for UTis and MS.

New techniques are needed to speed-up the identification and antimicrobial susceptibility testing (AST) of bacteria associated with bloodstream infections. Alfred 60/AST (Alifax®, Polverara, Italy) performs AST by light scattering directly from positive blood cultures.We evaluated Alfred 60/AST performances for 4 months. Each new episode of bacteraemia was included and AST were compared to either our rapid automated AST (Vitek® 2) or disk diffusion method. The discrepancies were investigated using Etest®. The time-to-result (TTR) was evaluated by comparing the blood volume inserted into Alfred 60/AST, i.e. 2 versus 7 blood drops. Taking into account the TTR, the workflow of positive blood cultures and the availability of AST results was studied in order to optimize the implementation of Alfred 60/AST.A total of 249 samples and 1108 antibiotics for AST were tested. After exclusion of unavailable results, 1008 antibiotics were analysed. 94.9% (n = 957/1008) of the antibiotics showed categorical agreement. There were 14 very major errors (VME), 24 major errors (ME) and 13 minor errors (mE). The VME were mostly related to clindamycin (64.3%) whereas meropenem and piperacillin-tazobactam constituted the major part (37.5% and 61.5%) of ME and mE respectively. Results were highly reliable for Enterobacterales and enterococci. The mean TTR ranged between 4.3 and 6.3 h and was statistically 20 min faster when applying the 7 blood drops protocol. We showed that Alfred 60/AST could give relievable results within working hours for positive blood culture which are flagged the same day between 12:00 am and 12:00 pm.Our study confirmed that Alfred 60/AST gives reliable AST results in a short period of time, especially for Enterobacterales and enterococci. AST could thus be easily obtained the same day of a positive blood culture. Clinical impact studies are mandatory to validate a 24/24 working.

Neurological localizations of sarcoidosis are heterogeneous and may affect virtually every part of the central or peripheral nervous system. They are often the inaugural manifestation of sarcoidosis. The diagnosis may be difficult due to the lack of extra-neurological localization. Diagnosis may be discussed in the presence of an inflammatory neurological disease, in particular in case of suggestive radiological or biological pattern. Cerebrospinal fluid analysis shows lymphocytic pleiocytosis, often with low glucose level. The diagnosis relies on a clinical, biological and radiological presentation consistent with neurosarcoidosis, the presence of non-caseating granuloma and exclusion of differential diagnoses. Screening for other localizations of sarcoidosis, in particular cardiac disease may be obtained during neurosarcoidosis. The treatment of neurosarcoidosis relies on corticosteroids although immunosuppressive drugs are usually added because of the chronic course of this condition and to limit the side effects of steroids. Treatments and follow-up may be prolonged because of the high rate of relapses.

Objectives To establish recommendations on immunization for patients with multiple sclerosis (MS). Background Vaccines have been suspected in the past to trigger MS and relapses. With the extension of the immunoactive treatment arsenal, other concerns have been raised more recently about an increased risk of infection or a decreased effectiveness of immunization in immunosuppressed patients. Methods The French Group for Recommendations into Multiple Sclerosis (France4MS) performed a systematic search of papers in Medline and other university databases (January 1975–June 2018). The RAND/UCLA appropriateness method was chosen to review the scientific literature and to formalize the degree of agreement among experts on 5 clinical questions related to immunization and MS. Readers from the steering committee conducted a systematic analysis, wrote a critical synthesis and prepared a list of proposals that were evaluated by a rating group of 28 MS experts. The final version of the recommendations was finally reviewed by a reading group of 110 health care professionals and classified as appropriate, inappropriate or uncertain. Results Neurologists should verify the vaccination status as soon as MS is diagnosed and before disease-modifying treatments (DMTs) are introduced. The French vaccination schedule applies to MS patients and seasonal influenza vaccination is recommended. In the case of treatment-induced immunosuppression, MS patients should be informed about the risk of infection and the vaccination standards of the French High Council of Health should be applied. Live attenuated vaccines are contra-indicated in patients recently treated with immunosuppressive drugs, including corticosteroids; other vaccines can be proposed whatever the treatment, but their effectiveness may be partly reduced with some drugs. Conclusion Physicians and patients should be aware of the updated recommendations for immunizations of patients with MS.

Background and purpose There are few clinico-radiological data on optic neuritis (ON) with myelin oligodendrocyte glycoprotein antibody (MOG-IgG). The objective was to characterize the clinico-radiological phenotype and outcome of patients with MOG-IgG-related ON. Methods The records of all adult patients admitted in three medical centres with MOG-IgG-associated ON who underwent orbital and brain magnetic resonance imaging (MRI) at the acute phase were reviewed. Spinal cord MRI within 1 month from the ON and all of the follow-up MRI were reviewed. Results Of 62 patients, 41.9% had bilateral ON and 66.2% optic disc swelling. On initial MRI, lesions were anterior (92%), extensive (63%) and associated with optic perineuritis (46.6%). Silent brain lesions were found in 51.8% of patients but were mainly non-specific (81%). Of 39 individuals with spinal MRI at onset, nine had abnormal findings (four were asymptomatic). Two symptomatic patients had longitudinally extensive myelitis with concurrent H-sign. At last follow-up, 5% of patients had visual acuity ≤0.1. Brain MRI remained unchanged in 41 patients (87%). Conclusions Our study supports a mostly benign ophthalmological course of MOG-IgG-associated ON, despite initially longitudinally extensive lesions and development of optic nerve atrophy on orbital MRI. Spinal MRI could be of interest in detecting silent suggestive lesions.

BACKGROUND AND PURPOSE Assessing patients' disability in multiple sclerosis (MS) requires time-consuming batteries of hospital tests. MSCopilot is a software medical device for the self-assessment of patients with MS (PwMS), combining four tests: walking, dexterity, cognition and low contrast vision. The objective was to validate MSCopilot versus the Multiple Sclerosis Functional Composite (MSFC). METHODS This multicentre, open-label, randomized, controlled, crossover study enrolled 141 PwMS and 76 healthy controls (HCs). All participants performed MSCopilot and MSFC tests at day 0. To assess reproducibility, 46 PwMS performed the same tests at day 30 ± 3. The primary end-point was the validation of MSCopilot versus MSFC for the identification of PwMS against HCs, quantified using the area under the curve (AUC). The main secondary end-point was the correlation of MSCopilot z-scores with MSFC z-scores. RESULTS In all, 116 PwMS and 69 HCs were analysed. The primary end-point was achieved: MSCopilot performance was non-inferior to that of MSFC (AUC 0.92 and 0.89 respectively; P = 0.3). MSCopilot and MSFC discriminated PwMS and HCs with 81% and 76% sensitivity and 82% and 88% specificity respectively. Digital and standard test scores were highly correlated (r = 0.81; P

Introduction Les maladies du spectre des neuromyelites optiques (neuromyelitis optica spectrum disorder, NMOSD) sont des maladies demyelinisantes auto-immunes du systeme nerveux central. Elles se manifestent par des episodes recidivants de myelites et de nevrite optique (NO). Le plus souvent, elles sont associees a la presence d’anticorps anti-aquaporine 4 (anti-AQP4). L’association d’une NMOSD anti-AQP4+ et d’une autre maladie auto-immune n’est pas exceptionnelle. En particulier, l’association avec le lupus systemique (LS) et le syndrome de Sjogren primaire (SS) a ete rapportee dans la litterature, sans que l’on sache si cette association avait un impact sur la prise en charge et le pronostic. L’objectif de l’etude etait d’analyser les caracteristiques cliniques, radiologiques, et le suivi a long terme des patients presentant une NMOSD avec anticorps anti-AQP4 associee a un LS et/ou un SS. Patients et methodes Il s’agissait d’une etude retrospective menee dans 4 centres. Les patients presentant une NMOSD avec anticorps anti-aquaporine 4 (criteres IPND 2015) et un LS (criteres EULAR/ACR 2019) ou un SS (criteres ACR/EULAR 2016) ont ete retrospectivement inclus. Les caracteristiques cliniques, biologiques et radiologiques en lien avec la NMOSD, le LS et/ou le SS ont ete recueillies a partir des dossiers medicaux. Lorsque cela etait possible, nous avons cherche la presence d’anticorps anti-AQP4 dans le serum des patients anterieurs aux premieres manifestations clniques de la NMOSD. Resultats Quinze patients presentant une NMOSD avec anticorps anti-AQP4 associee a un LS et/ou un SS (9 patients presentaient un LS, 5 patients un SS et 1 patients un LS associe a un SS) ont ete inclus. La duree de suivi mediane etait de 120 mois (4 a 336 mois) a partir du diagnostic de NMOSD. Quatorze patients (93 %) etaient des femmes et leur âge median lors de la premiere manifestation de NMOSD etait de 40 ans (11–56 ans). Le diagnostic de LS et/ou de SS precedait celui de NMOSD chez 10 patients (67 %) avec un delai median de 72 mois (4–168 mois). Le diagnostic de NMOSD etait concomitant de celui de LS et/ou SS chez 3 patients (20 %) et le precedait chez 2 patients (13 %). Les patients lupiques presentaient une atteinte cutaneo-articulaire dans 90 % des cas ; des cytopenies auto-immunes dans 30 % des cas, et une atteinte des sereuses ou une atteinte renale dans 30 % des cas chacun. Deux patients remplissaient les criteres de syndrome des anticorps anti-phospholipides. Tous les patients avaient des anticorps antinucleaires positifs, 13/15 des anticorps anti-ADN natif, 5/15 des anticorps anti-SS-A, 2/16 des anticorps anti-RNP, 1/15 des anticorps anti-SS-B, et 1/15 des anticorps anti-Sm. Le nombre moyen de poussees de NMOSD par patient etait de 2,7 (1–6). Les manifestations incluaient une atteinte medullaire dans 80 % des cas, une NO dans 60 % des cas, et une atteinte encephalique dans 33 % des cas (dont un syndrome de l’area postrema). Au diagnostic de NMOSD, les patients avec un LS et/ou SS prealable etaient traites par hydroxychloroquine dans 60 % des cas, prednisone dans 20 % des cas (tous a la dose de 5 milligrammes par jour), et azathioprine dans 10 % des cas. Les poussees de NMOSD n’etaient pas concomitantes de poussees de LS chez nos patients. Seul un patient a presente, lors de sa cinquieme poussee de NMOSD, une pericardite avec elevation du titre d’anticorps anti-ADN natifs. Les poussees de NMOSD etaient traitees par bolus de methylprednisolone dans 60 % des cas, par rituximab dans 49 % cas, par cyclophosphamide dans 12 % des cas, et par echanges plasmatiques dans 7 % des cas. Les molecules utilisees comme traitement d’entretien etaient le rituximab dans 60 % des cas, l’azathioprine dans 47 % des cas, et le mycophenolate mofetil dans 33 % des cas. Parmi nos 15 patients, 14 etaient en remission lors de la derniere consultation, apres une duree mediane de 33 mois (6–240 mois). Chez un patient, nous avons pu effectuer la recherche d’anticorps anti-AQP4 dans un serum preleve deux ans avant les manifestations cliniques de la NMOSD, recherche qui s’est averee positive. Conclusion Les NMOSD associees aux anti-AQP4 peuvent etre concomitantes d’un LS ou d’un SS, parfois peu severe, et peuvent survenir plusieurs annees apres le diagnostic de LS ou SS, et en dehors des poussees de ces dernieres. Par ailleurs, les anticorps anti-AQP4 pourraient apparaitre quelques annees avant le diagnostic de la NMOSD. L’impact clinique et therapeutique de cette constatation reste a preciser.

Introduction Le vaccin contre la fievre jaune est requis pour voyager en zone d’endemie de fievre jaune mais il est deconseille chez les patients atteints de sclerose en plaques (SEP) en raison du risque potentiel de poussees post-vaccinales mis en evidence dans une seule publication incluant 7 patients. Materiels et methodes Evaluer chez les patients SEP recurrentes-remittentes, ayant beneficie d’une vaccination fievre jaune, le risque de survenue d’une activite de la maladie dans les 12 mois suivant la vaccination. Dans cette etude retro-prospective et observationnelle exposes/non-exposes, chaque patient vaccine contre la fievre jaune apres le debut de la maladie SEP a ete apparie a 3 patients SEP sans historique de vaccination contre la fievre jaune et identifies par la base de donnees locale European Database for Multiple Sclerosis (EDMUS). Les criteres d’appariement etaient : l’âge et l’activite de la maladie avant vaccination. Le delai de survenue d’une poussee des exposes et non-exposes a ete analyse par un test log-rank. Un modele de Cox a estime les hazard ratio bruts et ajustes. Resultats Trente et un (20 F/11 H) patients vaccines ont ete inclus. L’âge moyen de debut de la maladie etait de 38 ans et la duree moyenne de la maladie avant la vaccination etait de 10,8 ans. Parmi les patients, 19,35 % avaient une activite clinique l’annee precedant la vaccination, l’Expanded Disability Status Scale (EDSS) moyen etait a 0,78 lors de la vaccination. La moitie des patients n’etaient pas traites pour le SEP au moment de la vaccination (51,6 %), 41,9 % d’entre eux avaient un traitement de 1re ligne et 6,4 % etaient traites par natalizumab. Les resultats complets de cette etude exposes/non-exposes seront disponibles fin fevrier. Conclusion La fievre jaune est une maladie grave potentiellement mortelle, pouvant etre contractee en zones d’endemie (Afrique subsaharienne et Amerique du Sud) et ne disposant pas de traitement. Le vaccin anti-amaril, tres efficace, est exige pour entrer sur le territoire de certains pays en zone d’endemie. Ce vaccin vivant attenue est contre-indique chez les patients traites par immunosuppresseurs. Les resultats de cette etude epidemiologique cas/temoin permettront de faire evoluer les pratiques et les recommandations vaccinales contre la fievre jaune et de conseiller au mieux les patients atteints de SEP se rendant en zone d’endemie.

Introduction L’absence de marqueur direct de poussees de Sclerose en plaques (SEP) dans le Systeme national des donnees de sante (SNDS) necessite le developpement d’algorithme complexe base essentiellement sur les hospitalisations et les episodes therapeutiques de forte dose de corticotherapie. Objectifs Evaluer la valeur predictive positive et negative (VPP et VPN) d’un algorithme complexe developpe pour identifier les poussees de SEP dans le SNDS comparativement au jugement de quatre experts neurologues. Methode Un tirage au sort a ete realise parmi les patients traites pour une SEP pour en selectionner 100 avec au moins une poussee d’apres l’algorithme et 100 patients sans poussee durant un suivi de 1 a 1,5 ans. L’ensemble des donnees de consommations de soins et d’hospitalisation de chaque patient a ete revu independamment par deux neurologues en aveugle de l’algorithme. Les cas discordants entre deux neurologues etaient revus collegialement afin d’obtenir un consensus. Resultats Parmi les 37 986 patients traites pour SEP identifies dans le SNDS entre juillet 2015 et decembre 2016, 9,6 % ont presente au moins une poussee d’apres l’algorithme. Parmi les patients selectionnes, les neurologues en ont confirme 95 avec poussee(s) et 96 sans poussee, soit une VPP de 95 % et une VPN de 96 %. Apres ajustement de l’algorithme en fonction des conclusions des neurologues, la VPP et la VPN etaient respectivement de 95,2 % et 100 %. Discussion La richesse des donnees du SNDS permet une vue holistique du patient dans l’ensemble du systeme de prise en charge, et rend possible la definition d’algorithmes de detection d’evenements complexes comme les poussees de SEP, mais aussi d’etudes de validation de ces algorithmes via la reconstitution de quasi-dossiers medicaux 100 % anonymises, permettant ensuite d’ajuster ces algorithmes afin d’ameliorer leur performance. Conclusion Les resultats montrent que l’algorithme presente permet une tres bonne identification des poussees de SEP dans le SNDS et pourra etre utilise pour de futures etudes observationnelles sur la SEP.

International audience; BACKGROUND AND PURPOSE: Neurosarcoidosis is a rare inflammatory disorder of unknown cause. The aim of this study was to evaluate the value of T/B lymphocyte population counts and the concentrations of the cytokines interleukin (IL) 6 and IL-10 in the cerebrospinal fluid (CSF) of neurosarcoidosis patients.METHODS: A retrospective study CSF biomarkers was conducted in patients with neurosarcoidosis who underwent CSF analysis between 2012 and 2017 as well as various control populations.RESULTS: Forty-three patients with neurosarcoidosis, 14 with multiple sclerosis (MS) and 48 with other inflammatory disorders were analyzed. The CSF IL-6 levels were higher in sarcoidosis patients than in MS patients (median 8 vs. 3 pg/ml, P = 0.006). The CSF CD4/CD8 ratio was higher in sarcoidosis patients than in MS patients and in patients with other inflammatory disorders (median 3.18 vs. 2.36 and 2.10, respectively, P = 0.008). The CSF IL-6 level was higher in patients with active neurosarcoidosis than in non-active neurosarcoidosis patients (median 13 vs. 3 pg/ml, P = 0.0005). In patients with neurosarcoidosis, a CSF IL-6 concentration >50 pg/ml was associated with a higher risk of relapse or progression-free survival (hazard ratio 3.60; 95% confidence interval 1.78-23.14). A refractory neurosarcoidosis patient was treated with an anti-IL-6 monoclonal antibody that produced a complete neurological response.CONCLUSIONS: The CSF CD4/CD8 ratio and IL-6 concentration are increased in neurosarcoidosis compared to MS and other inflammatory disorders. A CSF IL-6 concentration >50 pg/ml is associated with relapse or progression of neurosarcoidosis. IL-10 levels may be elevated in neurosarcoidosis.

Management of progressive multiple sclerosis (MS) is one of the main challenges of the new century. Based on our knowledge of pathophysiology, three therapeutic strategies are proposed: anti-inflammatory (ocrelizumab, siponimod…); remyelinating (opicinumab); and neuroprotective (high-dose biotin, ibudilast, simvastatin…). Nevertheless, despite recent promising positive clinical trials, new methodological approaches for therapeutic protocols with adaptable outcomes to assess progression are still needed.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system, whose incidental peak occurs around 30 years. This review focuses on epidemiologic, physiopathological, clinical and therapeutic characteristics of MS in elderly patients in two different situations: 1) late-onset MS (after 50 years), 2) aging in MS with young adult-onset. Epidemiologic studies established that MS occurs after 50 years in 5% of cases. As opposed to young adult-onset MS, late-onset MS is characterized by a predominant progressive course, a longer diagnosis delay, a higher prevalence of motor disability, while cognitive impairment is similar in terms of frequency and affected cognitive domains. Improvement of MS patients' global healthcare together with life expectancy increase has led to an increased number of elderly patients with MS, regardless of age at onset. Care providers must take into account the potential more frequent comorbidities in this specific population and pharmacological differences with younger subjects to adapt and optimize the risk/balance benefit of disease-modifying therapies.

Neurological localizations of sarcoidosis are heterogeneous and may affect virtually every part of the central or peripheral nervous system. They are often the inaugural manifestation of sarcoidosis. The diagnosis may be difficult due to the lack of extra-neurological localization. Diagnosis may be discussed in the presence of an inflammatory neurological disease, in particular in case of suggestive radiological or biological pattern. Cerebrospinal fluid analysis shows lymphocytic pleiocytosis, often with low glucose level. The diagnosis relies on a clinical, biological and radiological presentation consistent with neurosarcoidosis, the presence of non-caseating granuloma and exclusion of differential diagnoses. Screening for other localizations of sarcoidosis, in particular cardiac disease may be obtained during neurosarcoidosis. The treatment of neurosarcoidosis relies on corticosteroids although immunosuppressive drugs are usually added because of the chronic course of this condition and to limit the side effects of steroids. Treatments and follow-up may be prolonged because of the high rate of relapses.

Introduction Les atteintes neurologiques centrales au cours de la sarcoidose sont des manifestations rares et parfois inaugurales de la sarcoidose. Elles peuvent etre confondues avec de nombreuses autres affections inflammatoires, neurologiques ou infectieuses, responsables d’atteintes neurologiques. Leur diagnostic est particulierement difficile car les manifestations extra-neurologiques de la sarcoidose peuvent etre asymptomatiques et/ou discretes. Additionnellement, la prise en charge therapeutique est difficile avec des rechutes frequentes malgre des traitements qui associent le plus souvent corticotherapie et immunosuppresseurs. Nous avons donc mene une etude exploratoire sur l’interet de biomarqueurs du liquide cerebro-rachidien (LCR) a visee diagnostique et pronostique. Patients et methodes Nous avons prospectivement analyse le phenotypage des lymphocytes du LCR recueillis sur tube Transfix® et le dosage des interleukines (IL)-6 et 10 dans le LCR entre mars 2015 et novembre 2016, chez tous les patients ayant une neurosarcoidose definie ou suspectee, ainsi que chez des controles ayant une sclerose en plaques (SEP) definie ou une autre maladie neurologique inflammatoire diagnostiquee selon les criteres actuels. Les patients ayant une neurosarcoidose etaient consideres comme « actifs » au moment du prelevement si l’IRM montrait une prise de gadolinium ou si une pleiocytose etait observee dans le LCR et inactifs dans le cas contraire. Les patients avec une neurosarcoidose ont ensuite ete suivis a intervalles reguliers et la survenue de rechutes a ete notee. Resultats Sur la periode de l’etude, 192 patients ont ete inclus et ont eu au moins une determination du phenotypage lymphocytaire et dosage des IL-6 et 10 du LCR. Parmi eux, 83 ont ete exclus de l’analyse car le diagnostic final etait incertain : nous avons donc analyse les resultats chez 47 patients ayant une neurosarcoidose, 14 une SEP et 48 une autre maladie inflammatoire (neuro-lupus, neuro-Gougerot-Sjogren, tuberculose, neuro-Lyme, histiocytoses). Les dosages d’IL-6 et IL-10 etaient significativement plus eleves dans le groupe neurosarcoidose qu’au cours de la SEP (6,50 versus 3,00, p = 0,011 et 2,50 versus 2,00, p = 0,046 respectivement). Le ratio CD4/CD8 etait significativement plus eleve chez les patients ayant une neurosarcoidose qu’une SEP ou une autre maladie neurologique inflammatoire (3,44 versus 2,24 et 2,09 respectivement, p = 0,03). Le dosage de l’IL-6 etait significativement plus eleve chez les patients avec une neurosarcoidose active (mediane 9,00) que non active (mediane 3,00, p = 0,005). Chez les patients ayant une neurosarcoidose, un dosage d’IL-6 > 50 pg/mL etait associe avec une survie sans rechute ni progression moins longue (p = 0,005). Une rechute ou progression etait observee avec une mediane de 8 mois chez les patients ayant un dosage d’IL-6 > 50 pg/mL. Conclusion Les dosages d’IL-6 et IL-10 ainsi que le ratio CD4/CD8 du LCR sont des biomarqueurs diagnostiques qui aident a differencier les neurosarcoidoses des SEP. Le dosage d’IL-6 est plus eleve dans les neurosarcoidoses actives que non actives. Un dosage d’IL-6 dans le LCR eleve (> 50 pg/mL) est associe a un risque de rechute ou progression au cours des neurosarcoidoses et constitue donc un biomarqueur pronostique.

Introduction Lors de la derniere decennie, le traitement antiretroviral (TARV) a permis de reduire significativement le taux de mortalite ainsi que l’incidence des infections opportunistes. Cependant, il peut etre responsable d’un syndrome de reconstitution immunitaire dont les manifestations peuvent etre variables et severes et doivent etre connues des cliniciens. Le syndrome d’activation macrophagique est une manifestation possible et rare du syndrome d’immunoreconstitution. Observation En septembre 2016, un patient de 43 ans se presente avec une pneumonie a pneumocystis jiroveci complique d’un SDRA revelant une infection a VIH au stade SIDA avec un taux de CD4 a 13,4/μl et une charge virale a 835000 copies/mL. Une retinite et une colite a CMV sont egalement retrouvees et traitees. Une TARV (emcitabine-tenofovir, ritonavir et darunavir) est initiee le 10 octobre 2016. Un mois plus tard, le patient se presente aux urgences avec des douleurs abdominales diffuses, de la fievre et des sudations nocturnes. La prise de sang met en evidence une pancytopenie (hemoglobine a 7,8 g/dL, des plaquettes a 116,103/μl, des globules blancs a 1,42.103/μl, un taux de neutrophiles a 0,92.103/μl), une CRP a 62 mg/L, une ferritine a 2299 μg/L, des LDH a 431UI/L, une cytolyse hepatique, un taux de CD4 a 46/μl et une charge virale a 190000 copies/mL. Le scanner abdominal revele une panniculite mesenterique et une hepatosplenomegalie. Une ponction medullaire avec des images d’hemophagocytose est retrouvee ainsi qu’une amplification en chaine par polymerase (ACP) du virus epstein barr (EBV) dans le sang. La pyrexie, l’hepatosplenomegalie, la pancytopenie, l’hyperferritinemie et les images d’hemophagocytose dans la moelle permettent de poser le diagnostic de syndrome d’activation macrophagique (SAM) secondaire. Ni la fonction cytotoxique mediee par les cellules NK ou le recepteur soluble de l’IL2 (sCD25) n’ont pu etre mesures. Devant ce tableau et une ACP EBV fortement positive, la recherche d’une pathologie lymphomateuse est entreprise. Un TEP/CT indique la presence d’adenopathies hypermetaboliques mediastinales et mesenteriques ainsi qu’un hypermetabolisme splenique, hepatique et medullaire. Une biopsie ganglionnaire par laparoscopie est enfin realisee montrant une lymphadenite granulomateuse necrotique hautement suspecte d’une tuberculose active. Aucune pathologie lymphomateuse n’est mise en evidence. La survenue d’un syndrome d’activation macrophagique quelques semaines apres l’initiation d’un traitement antiretroviral ainsi que la chute de la charge virale font suspecter la presence d’un syndrome d’immunoreconstituion (SIR). Ce syndrome d’activation macrophagique serait secondaire a une maladie a EBV sans pathologie lymphomateuse retrouvee. Une infection tuberculeuse pourrait egalement etre a l’origine de ce syndrome d’activation macrophagique dont les etiologies peuvent parfois etre multiples [1] . Devant la pyrexie persistante et la degradation de l’etat general du patient un traitement antituberculeux est instaure suivi d’une bonne reponse clinique et biologique. Finalement, l’ ACP et la culture ne permettront pas de mettre la tuberculose en evidence. Quelques mois plus tard, le patient suivi en consultation realise un scanner abdominal de controle montrant de multiples masses disseminees. Une nouvelle biopsie est realisee et un lymphome de Burkitt est retrouve. Conclusion Les infections virales a herpes virus, virus de l’EBV en tete, seraient responsable de pres de la moitie des cas de SAM post infectieux [1] . Cependant, chez les patients VIH positifs, il semble que l’EBV ne puisse a lui seul etre responsable d’un syndrome d’activation macrophagique (exception faite d’une primo-infection) et doit faire systematiquement rechercher une autre pathologie sous-jacente comme un lymphome ou une tuberculose [2] .

Resume Introduction Le deficit multiple en acyl-CoA deshydrogenases (MADD) est une maladie hereditaire rare affectant l’oxydation des acides gras, et pouvant resulter du deficit de l’un des deux transporteurs d’electrons : electron transfer flavoprotein (ETF) ou electron transfer flavoprotein ubiquinone oxydoreductase (ETF-QO). Il se manifeste le plus souvent dans l’enfance ou chez l’adulte jeune, par une atteinte plurisytemique avec encephalopathie ou une atteinte musculaire. Observations Nous rapportons deux observations de patients adultes presentant un deficit en ETF-QO, confirme sur le plan moleculaire (gene ETFDH), revele par une faiblesse musculaire, avec une importante surcharge en lipides a la biopsie musculaire. L’un des patients avait presente un episode d’encephalopathie avec vomissements dix ans avant l’apparition des manifestations musculaires. Le diagnostic fut pose devant la presence d’anomalies caracteristiques du profil des acylcarnitines apres analyse par spectrometrie de masse en tandem. Une amelioration clinique spectaculaire fut obtenue apres instauration d’un traitement par riboflavine et L-carnitine chez les deux patients. Conclusion Le caractere traitable de cette affection doit conduire a envisager ce diagnostic en effectuant une etude du profil des acylcarnitines chez tout patient presentant une faiblesse musculaire inexpliquee.

Joint Bone Spine - In Press.Proof corrected by the author Available online since jeudi 30 juin 2016

Natalizumab (NZ), a humanized anti-α4 integrin monoclonal antibody, is used in the treatment of highly active multiple sclerosis (MS). Progressive multifocal leukoencephalopathy (PML) and rare cases of primary CNS lymphoma1 have been reported in NZ-treated patients, whereas severe relapses with MS reactivation are described after NZ discontinuation.

Background Disabled multiple sclerosis (MS) patients often need intervention of multiple specialists, resulting in a complex organization of care. How this multidisciplinary care should be organized and structured has not been studied. Objective The objective of this article is to address the effectiveness of an integrated multidisciplinary approach versus usual care in MS patients. Methods This is a prospective, randomized, controlled, monocentric clinical trial in MS patients. Two treatment strategies were compared: (i) an integrated multidisciplinary (IMD) approach, consisting of a half-day individually tailored comprehensive assessment in the MS clinic; and (ii) a standard care. The primary outcome was the impact of the strategy on quality of life (QoL) measured using the MSIS-29 scale at inclusion and after six months. Results Fifty MS patients were included. Median MSIS 29 score decreased over six months in the control group (−4.89) and increased in the IMD group (+2.00), with a significant difference between the two groups ( p = 0.03). However, in the multivariate analysis, after adjustment of HAD-D and INTERMED score, this difference was no longer significant. Conclusions This prospective, randomized study is the first attempt to evaluate the multidisciplinary approach in MS patients. The results show that, contrary to our expectations, an integrated multidisciplinary approach is not superior to usual care on QoL.

Resume Propos Il n'existe aucune recommandation sur la prise en charge de la fibrose retroperitoneale idiopathique (FRPI). L'objectif de cet article est de rechercher dans la litterature medicale recente les donnees issues d'essais cliniques ou de series de cas d'au moins dix patients permettant de proposer une prise en charge s'appuyant sur des donnees validees. Actualites et points forts Aucun essai therapeutique n'a ete retrouve. Huit publications de series de cas decrivent 177 patients : 45 ont recu un traitement chirurgical exclusif par ureterolyse, deux une desobstruction renale (endoscopie ou nephrostomie), 65 une corticotherapie seule et 64 une corticotherapie associee a une chirurgie. Dans 38 cas des immunosuppresseurs etaient associes aux corticoides. Un patient a ete traite par immunosuppresseur seul. Les doses et la duree de la corticotherapie varient selon les publications. Les criteres de jugement sont mal precises, et varient selon les auteurs. La duree du suivi est en mediane de 56 mois. Les taux de succes declares sont de 73 % pour la chirurgie seule, 86 % pour le traitement medical seul, 73 % pour l'association corticoides et chirurgies et 97 % pour l'association corticoides et immunosuppresseurs. Les donnees rapportees ne permettent pas d'estimer le poids des effets indesirables associes aux differentes options therapeutiques. Aucune publication concernant l'utilisation du tamoxifene et repondant aux criteres de selection de ce travail n'a ete retrouvee. Perspectives et projets L'analyse de la litterature des 20 dernieres annees montre que le traitement de la FRPI reste toujours empirique. Il n'y a pas de publications d'un niveau de preuve suffisant pour definir la strategie therapeutique optimale d'utilisation de la chirurgie, de la corticotherapie, des immunosuppresseurs et du tamoxifene. Seuls des essais therapeutiques prospectifs, dont aucun n'a ete realise a ce jour, permettront d'etablir le rapport benefice/risque des differentes options therapeutiques disponibles.

This chapter will deal with versatile biochips. The presented biochips are prepared by the microarray functionalization of gold surface from millimetric to micrometric scale via different electrochemical approaches. Interactions occurring on these functionalized surfaces are monitored using surface plasmon resonance imaging approaches. Different size of spots including hyphenated techniques will be used to study biological interactions from molecular (i.e., DNA, proteins (toxins), and sugars) to complex objects such as living cells. Applications of this approach will be illustrated by examples from different biological fields including DNA hybridization studies, antibody screening in patients’ samples, study of oligosaccharides–proteins interactions, and lymphocytes characterization and sorting. For each topic, optimized chemistry and optical developments will be specified.

Idiopathic intracranial hypertension (IH) occurs most commonly in women and overweight subjects. It must be reported associated to general diseases, like systemic lupus erythematosus (SLE).We report an observation of a patient with lupus complicated by glomerulonephritis and IH.A 29 years old woman, without overweight, was followed for a SLE with skin and arthritic involvement . Four years after onset, a renal complication appeared with severe nephrotic syndrome. Six weeks after, bilateral papillar oedema was discovered, revealing an IH, as the patient was treated by oral steroids at 1mg/kg/d and bimonthly intravenous cyclophosphamide. The patient was completely asymptomatic. Brain MRI with veino-RMN was normal, without cerebral venous thrombosis. Lumbar punction showed an elevated opening pressure of 30,5 cmH(2)0 but with normal cerebrospinal fluid (CSF) contents. Evacuation of 30 mL of CSF and immunosuppressive treatment allowed symptoms regression.Twenty-seven cases of IH associated to SLE with nephritis have been reported in literature. Young women are more frequently involved with in half of cases a diffuse proliferative glomerulonephritis. Predisposing factors, like anaemia, must be associated. IH allows SLE diagnose in more than the third of the cases. Then, SLE has to be searched as an etiology of IH, in particular in non-obese patients and when nephritis is associated.

Multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare genetic disease involving fatty acid oxidation. It is due to the deficiency of one of the two electron transporters: electron transfer flavoprotein (ETF) or electron transfer flavoprotein ubiquinone oxydoreductase (ETF-QO). Symptoms begin more often in childhood or in young adulthood with a multisystemic disease with encephalopathy or muscular weakness.We report here two adult cases with ETF-QO deficiency, confirmed by mutation analysis (ETFDH gene), revealed by a muscular weakness associated with muscle lipidosis. One of our patients presented an acute encephalopathy with vomiting ten years before the onset of muscular symptoms. The second patient exhibited a slowly progressive pelvic girdle muscle weakness. Diagnosis was established by characteristic abnormalities of acylcarnitine profile by tandem mass spectrometry. For both patients, a dramatic clinical improvement was observed under treatment with riboflavine and L-carnitine.Since it is a treatable disorder, this diagnosis must be considered by performing an acylcarnitine profile in all patients presenting with an unexplained muscular weakness.

Susac syndrome is a rare microangiopathy, responsible for small cerebral, retinal and cochlear infarcts. The classic clinical triad includes multiple neurologic signs (from headaches to coma), retinal branch occlusions and sensorineural hearing loss.We report a series of five patients with Susac syndrome followed in our department from 1997 to 2007.There were four women and one man (mean age at onset: 35.2 years). Clinical symptoms at onset were neurological (n=1), ophthalmological (n=1), auditory (n=1) and clinical triad (n=2). Neurologic symptoms included encephalopathy (n=2), headache (n=5), transient ischemic attacks (n=1). Brain MRI showed T2 lesions in the white and grey matter, corpus callosum and gadolinium-enhanced punctiform lesions. Cerebrospinal fluid contained an elevated protein level in three cases. Immunologic treatments (steroids [n=4], cylophosphamid [n=3], intravenous immunoglobulins [n=5]) associated with aspirin and/or oral anticoagulants, despite early relapses (n=2), led to dramatic clinical improvement (n=5).Due to its polymorphism the SS is difficult to diagnose when the clinical triad is lacking. In the absence of clinical trial and consensus treatment is empiric and based on supposed pathogenesis.

Nowadays it is quite easy to diagnose idiopathic retroperitoneal fibrosis (IRF), particularly with the help of medical imaging. However there is no guideline about the treatment.Looking for data about an evidence-based management.Screening of the database Medline. Titles and abstracts of articles published between 01/01/1985 and 31/12/2004 have been read to identify clinical trials and series about more than ten patients.No record of any therapeutic trials has been found. Eight series in total, which included 177 patients, were identified. Two of the patients have been treated by an ureteral desobstruction only (endoscopy or nephrostomy), 45 by surgery (ureterolysis), 65 by corticotherapy and 64 both by surgery and steroids. For 38 patients, immunosuppressive drugs were combined with corticotherapy (azathioprine, cyclophosphamide or D-penicillamine). According to the authors, doses and duration of corticotherapy varied. Median follow-up lasted 56 months. The outcome is satisfactory in 73% for surgery alone, 86% for medical treatment alone and 73% for both. The association between steroids therapy and immunosuppressive drugs is efficient in 97% of the cases. No clear data about side effects was mentioned.Treatment of the IRF is still empirical, based on surgery and corticotherapy. There is no guideline about the treatment strategy. Although tamoxifen has been proposed, efficacy evidence is lacking. Prospective multicenter studies will help us to progress in the management of the IRF.

BiCMOS associates high-speed circuits with the low power requirements of CMOS. Traditional BiCMOS circuits are mainly CMOS-based with bipolar buffers to improve driving capability and speed. Increased performance can be obtained with BiCMOS technology if CMOS/BiCMOS circuits are merged with an ECL (emitter-coupled logic) low swing circuit. Mixing of logic is possible if very-high-speed level translators for levels conversion are designed. The benefits of such an approach in 0.5- mu m BiCMOS technology have been estimated for the proposed ECL-to-CMOS-level convertor circuits. >

Background: Despite a growing use of rituximab (RTX) in neuromyelitis optica (NMO), data are lacking in patients with refractory NMO (RNMO), defined as cases with at least one relapse during immunosuppressive therapy. Objective: The purpose of this study was to assess RTX as a maintenance therapy in RNMO. Methods: Out of a total of 305 NMO cases from a population-based cohort, 21 RNMO patients received RTX during a mean follow-up period of 31 months. Results: After RTX, 11 patients (52.3%) were relapse free, meaning that 47.7% were refractory to RTX. The mean annualized relapse rate decreased from 1.3 to 0.4 ( pConclusions: RTX is an effective and well-tolerated treatment in RNMO. BMI could be a predictive factor for efficacy.