Oligoclonal bands increase the specificity of MRI criteria to predict multiple sclerosis in children with radiologically isolated syndrome

Background: Steps towards the development of diagnostic criteria are needed for children with the radiologically isolated syndrome to identify children at risk of clinical demyelination. Objectives: To evaluate the 2005 and 2016 MAGNIMS magnetic resonance imaging criteria for dissemination in space for multiple sclerosis, both alone and with oligoclonal bands in cerebrospinal fluid added, as predictors of a first clinical event consistent with central nervous system demyelination in children with radiologically isolated syndrome. Methods: We analysed an international historical cohort of 61 children with radiologically isolated syndrome (18 years), defined using the 2010 magnetic resonance imaging dissemination in space criteria (Ped-RIS) who were followed longitudinally (mean 4.2 4.7 years). All index scans also met the 2017 magnetic resonance imaging dissemination in space criteria. Results: Diagnostic indices (95% confidence intervals) for the 2005 dissemination in space criteria, with and without oligoclonal bands, were: sensitivity 66.7% (38.4\u201388.2%) versus 72.7% (49.8\u201389.3%); specificity 83.3% (58.6\u201396.4%) versus 53.9% (37.2\u201369.9%). For the 2016 MAGNIMS dissemination in space criteria diagnostic indices were: sensitivity 76.5% (50.1\u201393.2%) versus 100% (84.6\u2013100%); specificity 72.7% (49.8\u201389.3%) versus 25.6% (13.0\u201342.1%). Conclusions: Oligoclonal bands increased the specificity of magnetic resonance imaging criteria in children with Ped-RIS. Clinicians should consider testing cerebrospinal fluid to improve diagnostic certainty. There is rationale to include cerebrospinal fluid analysis for biomarkers including oligoclonal bands in planned prospective studies to develop optimal diagnostic criteria for radiologically isolated syndrome in children

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Long-term outcomes of CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) in a consecutive series of 12 patients.

BACKGROUND: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a central nervous system inflammatory disease. OBJECTIVE: To describe the disease course of CLIPPERS. DESIGN: A nationwide study was implemented to collect clinical, magnetic resonance imaging, cerebrospinal fluid, and brain biopsy specimen characteristics of patients with CLIPPERS. SETTING: Academic research. PATIENTS: Twelve patients with CLIPPERS. MAIN OUTCOME MEASURES: The therapeutic management of CLIPPERS was evaluated. RESULTS: Among 12 patients, 42 relapses were analyzed. Relapses lasted a mean duration of 2.5 months, manifested frequent cerebellar ataxia and diplopia, and were associated with a mean Expanded Disability Status Scale (EDSS) score of 4. Besides typical findings of CLIPPERS, magnetic resonance imaging showed brainstem mass effect in 5 patients, extensive myelitis in 3 patients, and closed ring enhancement in 1 patient. Inconstant oligoclonal bands were found on cerebrospinal fluid investigation in 4 patients, with an increased T-cell ratio of CD4 to CD8. Among 7 available brain biopsy specimens, staining was positive for perivascular CD4 T lymphocytes in 5 samples. Thirty-eight of 42 relapses were treated with pulse corticosteroid therapy, which led to improvement, with a mean residual EDSS score of 1.9 (range, 0-7). In 1 patient with untreated relapses, scores on the EDSS progressively increased to a score of 10 at death. Among 5 patients without long-term corticosteroid therapy, the mean annualized relapse rate was 0.5 (range, 0.25-2.8). Among 7 patients taking oral corticosteroids, no relapses occurred in those whose daily dose was 20 mg or higher. No progressive course of CLIPPERS was observed. Four patients with a final EDSS score of 4 or higher had experienced previous severe relapses (EDSS score, ≥5) and brainstem and spinal cord atrophy. CONCLUSIONS: CLIPPERS is a relapsing-remitting disorder without progressive forms. Long-term disability is correlated with the severity of previous relapses. Further studies are needed to confirm that prolonged corticosteroid therapy prevents further relapses.journal article2012 Julimporte

Education, apprentissage et connaissance (la formation des idées pédagogiques)

Depuis les débuts des sciences humaines à la fin du dix-huitième siècle, la pédagogie et la psychologie scientifiques se sont constituées conjointement autour des questions du développement et de l activité d apprentissage chez l enfant. Les notions d activité, de développement et d apprentissage ont permis d établir l hypothèse empiriste d une psychogenèse des facultés mentales dont l enfance attesterait naturellement à travers ses âges successifs. Les mouvements d éducation nouvelle, issus des thèses philosophiques et pédagogiques exprimées par Rousseau dans l Emile en 1762, ont pu donner sa dimension pratique à l idéal d une éducation négative fondée sur l activité de l enfant comme expression spontanée de ses forces vitales et spirituelles. Dans l entrecroisement d une métaphysique de l activité, d une conception libérale humaniste de l éducation, d une rationalité émancipatrice et de perspectives pédagogiques psychophysiologiques, peu à peu marquées par l évolutionnisme et l utilitarisme, sont nés les principaux paradigmes des pédagogies contemporaines : sensualistes, vitalistes, pragmatiques, fonctionnalistes, puis constructivistes. Dans cette recherche, nous avons analysé de façon archéologique et généalogique, à l instar de M. Foucault, les dispositifs philosophiques et épistémologiques convergents et opposés qui ont permis leur constitution. Il apparaît que Rousseau a non seulement écrit le programme de leur déploiement mais encore anticipé des contradictions que celui-ci allait rencontrer durant la crise institutionnelle ultérieure de la modernité.Since the beginning of human sciences at the end of the eighteenth century, scientific pedagogy and psychology were founded conjointly around questions of the development and learning activity in childhood. The ideas of activity, development and learning have allowed to establish the empiricist hypothesis of a psychogenesis of mental faculties that would be proven naturally by the successive phases of childhood. The movements of New Education, stemming from the philosophical and pedagogical theses expounded in Rousseau s Emile in 1762 have provided the ideal of a negative education founded on the activity of the child as spontaneous expression of his vital and spiritual forces with its practical dimension. It is in the intertwinent of a metaphysics of activity, a liberal and humanist conception of education, an emancipatory rationality, and pedagogical psycho-physiological perpectives marked increasingly by evolutionism and utilitarianism, that the principal paradigms of contemporary pedagogies were born : sensualist, vitalist, pragmatic, functionalist, and finaly constructivist. In the vein of M. Foucault this thesis proposes an archeological and genealogical analysis of the philosophical and epistemological apparatus or dispositives that, converging and diverging, made the formation of these pedagogies possible. It seems that Rousseau did not only write the program of their deployment, but also anticipated the contradictions that the latter would encounter during the subsequent institutional crisis of modernity.NANTERRE-PARIS10-Bib. élec. (920509901) / SudocSudocFranceF

Le théâtre en question

Leclerc Guy, Santini Pierre, Lassalle Jacques, Mnouchkine Ariane, Brassat Jean, Vincent Jean-Pierre. Le théâtre en question. In: Raison présente, n°14, Avril – Mai – Juin 1970. Le Tchad du nord au sud. pp. 101-116

Le système éducatif

En réponse à la crise que traverse le système éducatif français, a été votée en 2013 la loi sur la refondation de l’école. Elle offre, par certains de ses dispositifs, l’opportunité de reconstruire une culture professionnelle commune. Pour l’approfondissement des dynamiques en cours, cet ouvrage appréhende le système éducatif dans son contexte républicain et sous l’angle de l’économie mondialisée de la connaissance. Il a été rédigé par une équipe pluridisciplinaire et pluri-catégorielle. Le constat des dysfonctionnements est éclairé par une approche historique et comparative. L’institution peut être revivifiée par la mise en place de stratégies dialogiques, grâce à une approche anthropologique. Des préconisations en éducation, formation des enseignants, et dans le domaine de l’enseignement supérieur et de la recherche, sont faites en regard de la loi de 2013 et du nouveau référentiel de compétences des métiers de l’enseignement. Deux axes sont proposés : - une démarche émancipatrice inspirée par les mouvements d’éducation populaire et citoyenne ; - une démarche universitaire et institutionnelle portée par les sciences de l’éducation. Des alternatives opérationnelles, synthèses de ces deux démarches, apportent des perspectives concrètes d’application à court, moyen et long terme

Mapping of Spinocerebellar Ataxia 13 to Chromosome 19q13.3-q13.4 in a Family with Autosomal Dominant Cerebellar Ataxia and Mental Retardation

We examined a large French family with autosomal dominant cerebellar ataxia (ADCA) that was excluded from all previously identified spinocerebellar ataxia genes and loci. The patients—seven women and a 4-year-old boy—exhibited slowly progressive childhood-onset cerebellar gait ataxia associated with cerebellar dysarthria, moderate mental retardation (IQ 62–76), and mild developmental delays in motor acquisition. Nystagmus and pyramidal signs were also observed in some cases. This unique association of clinical features clearly distinguishes this new entity from other previously described ADCA. Cerebral magnetic-resonance imaging showed moderate cerebellar and pontine atrophy in two patients. We performed a genomewide search and found significant evidence for linkage to chromosome 19q13.3-q13.4, in an ∼8-cM interval between markers D19S219 and D19S553

First clinical inflammatory demyelinating events of the central nervous system in a population aged over 70 years: A multicentre study

International audienceFew data are available regarding patients with very late-onset inflammatory demyelinating events. (VLO-IDE).Objectives: The aim of this study was to describe the clinical, biological, and radiological characteristics and aetiological diagnosis of very late first inflammatory demyelinating events of the central nervous system.Methods: We conducted a national descriptive retrospective multicentre study on a case series of patients aged >70 years at the time of VLO-IDE. Patients were recruited from a national call on behalf of the 'Société Francophone de la Sclérose en Plaques' (French Multiple Sclerosis Society).Results: Twenty-five patients were referred (F:M sex ratio 2.1:1). The most frequent clinical impairment was a spinal cord deficit (23/25), usually severe (disability score, median EDSS 4.5 [2-9.5]). Spinal cord lesions were usually extensive, spanning at least three segments (11/25), and large brain lesions were also observed (lesions >20 mm in 6/25). The final aetiological diagnoses comprised multiple sclerosis (9/25), neuromyelitis optica spectrum disorders (7/25), neurosystemic lupus erythematosus (2/25), transverse myelitis without aetiological diagnosis (6/25) and optic neuritis (1/25).Conclusions: This study highlights a particular phenotype of first clinical inflammatory demyelinating events in predominantly female patients aged >70 years who have severe motor impairment with common longitudinal extensive myelitis and large and common very active radiological inflammatory lesions. Neuromyelitis optica spectrum disorders seem overrepresented

Natalizumab-PML survivors with subsequent MS treatment

International audienceObjective: To describe the clinico-radiologic outcome of MS patients with natalizumab-related progressive multifocal leukoencephalopathy (Nz-PML) surviving and receiving disease-modifying therapy (DMT). Methods: We describe clinical and radiologic evolution of Nz-PML survivors in an observational retrospective multicenter cohort to clarify the effect of different subsequent MS DMT strategies. Twenty-three patients from 11 centers were analyzed. Outcomes were (1) clinical efficacy of post-PML MS DMT, (2) radiologic efficacy of post-PML MS DMT, (3) radiologic evolution of PML lesion, and (4) disability progression. Results: There was no clinical worsening of PML symptoms with a stability of Expanded Disability Status Scale at the last follow-up. No relapse was reported with fingolimod and dimethyl fumarate. No radiologic worsening of Nz-PML lesion was observed at the end of the follow-up. Conclusion: In this large cohort of patients with Nz-PML, MS therapies given after Nz discontinuation were not associated with PML worsening. A larger cohort with longer follow-up will be necessary to confirm this therapeutic strategy