La passion du réel

Je dois constater que l’histoire, dès mes premiers textes, occupe une place importante. Cependant il me semble qu’au fil des livres, ma posture a changé. Auparavant l’histoire n’était qu’un outil dans ma trousse de romancière. Dans Le Chasseur Zéro, mon premier roman, l’intention initiale est de donner voix aux angoisses de mort qui hantent les enfants. J’ai choisi l’épisode des kamikazes de la guerre du Pacifique dans la mesure où elle entrait en résonance avec cette angoisse, et m’offrait u..

Neurological aspects of hyperinsulinism-hyperammonaemia syndrome.

Hyperinsulinism-hyperammonaemia syndrome (HHS) is a rare cause of congenital hyperinsulinism, due to missense mutations in the GLUD1 gene, resulting in glutamate dehydrogenase (GDH) overactivity. The aim of this study was to document the spectrum of neurological disturbances associated with HHS and to identify possible phenotype-genotype correlations. We retrospectively analyzed the neurological outcomes of 22 consecutive patients (12 males, 10 females) aged from 18 months to 40 years and diagnosed with HHS. We analyzed demographic and clinical features and neuroradiological, biochemical, and genetic findings. Fourteen patients had childhood-onset epilepsy. Learning disability was found in 17 patients. Two patients had pyramidal involvement and one had generalized dystonia. Seizures were observed in 11 of 19 patients with documented GLUD1 mutations, and nine of these 11 patients had a mutation in the guanosine triphosphate (GTP) binding site. Our data demonstrate that neurological disorders in HHS are more frequent than previously thought and might suggest that mutations in the GTP binding site of GDH could be associated with more frequent epilepsy.Journal ArticleSCOPUS: ar.jFLWINinfo:eu-repo/semantics/publishe

Long-term Outcome in Neurozika: When Biological Diagnosis Matters

International audienceObjective: To characterize the full spectrum, relative frequency and prognosis of the neurological manifestations in Zika virus (ZIKV) postnatal infection. Background: Zika virus (ZIKV) postnatal infection has been associated with both central and peripheral neurological manifestations. The full spectrum, relative frequency and prognosis of these neurological manifestations have yet to be described. Design/Methods: We conducted an observational study in consecutive ZIKV-infected patients presenting with neurological manifestations during the French West Indies 2016 outbreak. Results: Eighty-eight patients, including six children, were enrolled. Ninety-five percent of all cases required hospitalization. Guillain-Barré syndrome was the most frequent manifestation (46.6%) followed by encephalitis or encephalomyelitis (20.5%), isolated single or multiple cranial nerve palsies (9.1%), other peripheral manifestations (6.8%), and stroke (1.1%). Fourteen patients (15.9%) including one child, developed a mixed disorder involving both the central and peripheral nervous system. Mechanical ventilation was required in 21 cases all of whom had ZIKV RNA in at least one biological fluid. Two adult patients died due to neuroZika. Clinical follow-up (median 14 months; interquartile range, 12-17) was available for 77 patients. Residual disability (modified Rankin scale ≥2) was identified in 19 (24.7%) patients, in 6 cases (7.8%), disability was severe (modified Rankin scale ≥4). Amongst patients with ZIKV RNA detected in one biological fluid, the risk of residual disability or death was higher (odd ratio, 9.97; CI, 1.22 to 81.21; P=0.032). Conclusions: NeuroZika spectrum represents a heterogenous group of clinical neurological manifestations. During an outbreak, clinicians should consider neuroZika in patients presenting with cranial nerve palsies and a mixed neurological disorder. Long-term sequelae are frequent in NeuroZika. ZIKV reverse-transcription PCR status at admission can inform prognosis and should therefore be taken into consideration in the management of hospitalised patients

Statin Use and Incidence of Parkinson's Disease in Women from the French E3N Cohort Study

International audienceBackground: Statins represent candidates for drug repurposing in Parkinson's disease (PD). Few studies examined the role of reverse causation, statin subgroups, and dose–response relations based on time-varying exposures. Objectives: We examined whether statin use is associated with PD incidence while attempting to overcome the limitations described previously, especially reverse causation. Method: We used data from the E3N cohort study of French women (follow-up, 2004–2018). Incident PD was ascertained using multiple sources and validated by experts. New statin users were identified through linked drug claims. We set up a nested case-control study to describe trajectories of statin prescriptions and medical consultations before diagnosis. We used time-varying multivariable Cox proportional hazards regression models to examine the statins–PD association. Exposure indexes included ever use, cumulative duration/dose, and mean daily dose and were lagged by 5 years to address reverse causation. Results: The case-control study (693 cases, 13,784 controls) showed differences in case-control trajectories, with changes in the 5 years before diagnosis in cases. Of 73,925 women (aged 54–79 years), 524 developed PD and 11,552 started using statins in lagged analyses. Ever use of any statin was not associated with PD (hazard ratio [HR] = 0.87, 95% confidence interval [CI] = 0.67–1.11). Alternatively, ever use of lipophilic statins was significantly associated with lower PD incidence (HR = 0.70, 95% CI = 0.51–0.98), with a dose–response relation for the mean daily dose (P-linear trend = 0.02). There was no association for hydrophilic statins. Conclusion: Use of lipophilic statins at least 5 years earlier was associated with reduced PD incidence in women, with a dose–response relation for the mean daily dose. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Societ

Temps croisés I

Les temps qui se croisent dans cet ouvrage se situent a plusieurs niveaux : ceux des histoires européenne et chinoise, de l'histoire ancienne et de la modernité la plus contemporaine, ceux aussi de l'histoire et de la littérature - notamment en Chine, ou les deux sont difficilement séparables. Ce livre reprend certaines des réflexions produites dans le cadre de l'« Université d'automne», un programme de formation, d'échanges et de recherche associant enseignants, chercheurs et étudiants, européens et chinois, qui se tient depuis plus de cinq ans a Shanghai. Les représentations du temps constituent l'axe privilégie de l'ouvrage, qui met notamment au jour la difficulté a parler le même langage, a s'entendre sur les mots mêmes : le passe est a comprendre entre histoire, mémoire et patrimoine ; l'avenir est fait de peurs et d'espérances, de régimes d'historicité aussi. L'histoire au musée, l'histoire dans la ville, l'histoire dans la littérature, le jeu des mémoires et des projections dans le futur, le rapport au progrès et ses remises en cause, tout cela en forme la trame. Que nous apprennent les maux de l'histoire, que nous disent les mots de la littérature ? Ce recueil tente de répondre a ces questions en un exercice a la fois inhabituel et peu conventionnel. Comme l'Université d'automne, il témoigne du dialogue intellectuel qui se développe entre chercheurs des deux mondes, européen et chinois

NeuroZika study, Lannuzel et al.

Supplementary figure S1 and supplementary Tables S1-

Movement disorders in valine métabolism diseases caused by HIBCH and ECHS1 deficiencies

International audienceBackground and purpose: HIBCH and ECHS1 genes encode two enzymes implicated in the critical steps of valine catabolism, 3-hydroxyisobutyryl-coenzyme A (CoA) hydrolase (HIBCH) and short-chainenoyl-CoA hydratase (ECHS1), respectively. HIBCH deficiency (HIBCHD) and ECHS1 deficiency (ECHS1D) generate rare metabolic dysfunctions, often revealed by neurological symptoms. The aim of this study was to describe movement disorders spectrum in patients with pathogenic variants in ECHS1 and HIBC.Methods: We reviewed a series of 18 patients (HIBCHD: 5; ECHS1D: 13) as well as 105 patients from the literature. We analysed the detailed phenotype of HIBCHD (38 patients) and ECHS1D (85 patients), focusing on MDs.Results: The two diseases have a very similar neurological phenotype, with an early onset before 10 years of age for three clinical presentations: neonatal onset, Leigh-like syndrome (progressive onset or acute neurological decompensation), and isolated paroxysmal dyskinesia. Permanent or paroxysmal MDs were recorded in 61% of HIBCHD patients and 72% of ECHS1D patients. Patients had a variable combination of either isolated or combined MD, and dystonia was the main MD. These continuous MDs included dystonia, chorea, parkinsonism, athetosis, myoclonus, tremors, and abnormal eye movements. Patients with paroxysmal dyskinesia (HIBCHD: 4; ECHS1D: 9) usually had pure paroxysmal dystonia with normal clinical examination and no major impairment in psychomotor development. No correlation could be identified between clinical pattern (especially MD) and genetic pathogenic variants.Conclusions: Movement disorders, including abnormal ocular movements, are a hallmark of HIBCHD and ECHS1D. MDs are not uniform; dystonia is the most frequent, and various types of MD are combined in single patient

La classe est ouverte, qu’est-ce que ça change ?

International audience« La classe est ouverte, qu'est-ce que ça change ? », Cahiers pédagogiques. n° 564, p. 44-46. Ce fichier comporte le manuscrit auteur avant modifications introduites par les éditeurs La « classe ouverte en activité ». Un pas vers la coéducation L'équipe du LéA Delaunay Grigny 91 1 Dans la salle des professeurs du Collège Sonia Delaunay de Grigny, en REP+ 2 , au milieu des années 2010, le constat est partagé : très peu de parents viennent aux réunions de rentrée, aux remises de bulletins, au café des parents... Rentrée 2016, ce problème est à l'ordre du jour d'une réunion de « concertation », ce temps de travail collectif qu'offre désormais la « refondation de l'éducation prioritaire » et qu'accompagnent deux nouvelles formatrices académiques. Des chercheurs participent à la réflexion dans le cadre d'une recherche collaborative, et plus précisément ici recherche-intervention (Mérini & Ponté, 2009), menée avec les professeurs volontaires de l'équipe du Collège. Chacun fait part de ses questions et pistes de travail. Un professeur d'histoire-géographie rapporte ses souvenirs d'une année d'enseignement aux États-Unis, où des parents venaient assister à des cours. Les collègues du premier degré racontent que les écoles primaires sont familières de l'invitation des parents en classe. Le nouveau référentiel de l'éducation prioritaire mentionne, sans plus de détails, la possibilité de « classes ouvertes en activité » : pourquoi ne pas l'expérimenter au collège ? Ouvrir la classe aux parents pour réfléchir à l'autonomie des élèves : croisement des regards et des représentations Comment présenter et mettre en oeuvre l'invitation des parents à assister à une heure de cours ? Face aux nombreuses questions que soulève ce projet, trois années de tâtonnements permettront de concevoir un dispositif ajusté aux préoccupations et conditions de travail spécifiques à notre collège. Cette couleur local

29 French adult patients with PMM2-congenital disorder of glycosylation: outcome of the classical pediatric phenotype and depiction of a late-onset phenotype

International audiencePMM2-CDG (formerly known as CDG Ia) a deficiency in phosphomannomutase, is the most frequent congenital disorder of glycosylation. The phenotype encompasses a wide range of neurological and non-neurological manifestations comprising cerebellar atrophy and intellectual deficiency. The phenotype of the disorder is well characterized in children but the long term course of the disease is unknown and the phenotype of late onset forms has not been comprehensively described. We thus retrospectively collected the clinical, biological and radiological data of 29 French PMM2-CDG patients aged 15 years or more with a proven molecular diagnosis (16 females and 13 males). In addition, thirteen of these patients were reexamined at the time of the study to obtain detailed information. 27 of the 29 patients had a typical PMM2-CDG phenotype, with infantile hypotonia, strabismus, developmental delay followed by intellectual deficiency, epilepsy, retinitis pigmentosa and/or visceral manifestations. The main health problems for these patients as teenagers and in adulthood were primary ovarian insufficiency, growth retardation, coagulation anomalies and thrombotic events, skeletal deformities and osteopenia/ osteoporosis, retinitis pigmentosa, as well as peripheral neuropathy. Three patients had never walked and three lost their ability to walk. The two remaining patients had a late-onset phenotype unreported to date. All patients (n = 29) had stable cerebellar atrophy. Our findings are in line with those of previous adult PMM2-CDG cohorts and points to the need for a multidisciplinary approach to the follow up of PMM2-CDG patients to prevent late complications. Additionally, our findings add weight to the view that PMM2-CDG may be diagnosed in teenage/adult patients with cerebellar atrophy, even in the absence of intellectual deficiency or non-neurological involvement

Phenotypic variability in ARCA2 and identification of a core ataxic phenotype with slow progression.

International audience: Autosomal recessive cerebellar ataxia 2 (ARCA2) is a recently identified recessive ataxia due to ubiquinone deficiency and biallelic mutations in the ADCK3 gene. The phenotype of the twenty-one patients reported worldwide varies greatly. Thus, it is difficult to decide which ataxic patients are good candidates for ADCK3 screening without evidence of ubiquinone deficiency. We report here the clinical and molecular data of 10 newly diagnosed patients from seven families and update the disease history of four additional patients reported in previous articles to delineate the clinical spectrum of ARCA2 phenotype and to provide a guide to the molecular diagnosis. First signs occurred before adulthood in all 14 patients. Cerebellar atrophy appeared in all instances. The progressivity and severity of ataxia varied greatly, but no patients had the typical inexorable ataxic course that characterizes other childhood-onset recessive ataxias. The ataxia was frequently associated with other neurological signs. Importantly, stroke-like episodes contributed to significant deterioration of the neurological status in two patients. Ubidecarenone therapy markedly improved the movement disorders, including ataxia, in two other patients. The 7 novel ADCK3 mutations found in the 10 new patients were two missense and five truncating mutations. There was no apparent correlation between the genotype and the phenotype. Our series reveals that the clinical spectrum of ARCA2 encompasses a range of ataxic phenotypes. On one end, it may manifest as a pure ataxia with very slow progressivity and, on the other end, as a severe infantile encephalopathy with cerebellar atrophy. The phenotype of most patients, however, lies in between. It is characterized by a very slowly progressive or apparently stable ataxia associated with other signs of central nervous system involvement. We suggest undergoing the molecular analysis of ADCK3 in patients with this phenotype and in those with cerebellar atrophy and a stroke-like episode. The diagnosis of patients with a severe ARCA2 phenotype may also be performed on the basis of biological data, i.e. low ubiquinone level or functional evidence of ubiquinone deficiency. This diagnosis is crucial since the neurological status of some patients may be improved by ubiquinone therapy