Maternité et conduites addictives (enjeux et intérêts de l'addictologie de liaison en périnatalité)

Il n'existe pas de données actuellement en France sur la prévalence des conduites addictives en dehors des consommations de substances licites (alcool, tabac) chez les femmes enceintes, et ce malgré l'importance de ces conduites chez les femmes en âge de procréer, en particulier pour le cannabis et les troubles du comportement alimentaire. Une étude menée à la maternité du CHU de Nantes auprès de 300 femmes nous a en effet permis d établir la prévalence relativement élevée des conduites addictives chez les femmes enceintes. Or si la problématique des conduites addictives pendant la grossesse commence à être reconnue comme un problème de santé publique préoccupant, la prévention comme le repérage restent encore peu répandus sur l ensemble du territoire français. Les enjeux du repérage et de la prise en charge des conduites addictives chez les femmes enceintes sont pourtant multiples puisqu elles ont un impact non seulement sur le déroulement et l issue de la grossesse, sur le développement fœtal, en terme de conséquences néonatales, mais aussi sur le développement psychocomportemental de l enfant à long terme. De plus, les processus psychopathologiques en jeu dans les addictions, en particulier la problématique de séparation-individuation, font écho aux enjeux psychopathologiques propres au processus de maternalité et peuvent être à l origine de dysfonctionnements des interactions mère-enfant. Mais il s agit aussi d une population de femmes jeunes, dont la motivation au changement est facilitée par la grossesse et la préoccupation maternelle pour l enfant, et pour qui cette période de la vie peut être une opportunité particulièrement importante pour s engager dans des soins. L'intervention des équipes de liaison en addictologie dans les maternités est donc à développer, d une part pour former les équipes des maternités au repérage de l ensemble des conduites addictives chez les femmes enceintes, en particulier de l alcool et du cannabis, mais aussi des troubles des conduites alimentaires, et d autre part pour faciliter l accès de ces femmes à des soins spécifiques qui doivent pouvoir leur être systématiquement proposés. Dans tous les cas la prise en charge de ces grossesses à haut risque devra être multidisciplinaire, réunissant la sage-femme, le gynécologue-obstétricien, le médecin généraliste, le pédiatre, la puéricultrice, l'assistante sociale, l'addictologue et parfois le pédopsychiatre. Elle s'organisera au mieux dans le cadre d un réseau, pour permettre un étayage et un accompagnement attentif et offrir à la mère et à son bébé un cadre de soins contenant et sécurisant.NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

« La Pene de Lescun : une probable roca occupée aux XIIe et XIIIe siècles (Lescun, Pyrénées-Atlantiques) »

Un lot de mobilier métallique médiéval a été mis au jour par le biais de prospection électromagnétiques autorisées dans le secteur du Pont de Lescun, sur la commune du même nom. La nature de cet ensemble chronologiquement homogène a incité à une évaluation archéologique du site. Les sondages réalisés, s'ils n'ont pas permis la mise en évidence de structures bâties, ont en revanche confirmé l'occupation du site à l'époque médiévale, entre le milieu du XIIe et le milieu du XIIIe siècle. Au regard de la typologie du mobilier, de la position stratégique du site et des données historiques, il y a de fortes présomptions pour que la Pene de Lescun puisse être assimilée à une roca

In vitro and in vivo interactions between glioma and marrow isolated adult multilineage inducible (MIAMI) cells.

International audienceThe prognosis of patients with malignant glioma remains extremely poor despite surgery and improvements in radio- and chemo-therapies. We recently showed that marrow-isolated adult mutilineage inducible (MIAMI) cells, a subpopulation of human mesenchymal stromal cells (MSCs), can serve as cellular carriers of drug-loaded nanoparticles to brain tumors. However, the safety of MIAMI cells as cellular treatment vectors in glioma therapy must be evaluated, in particular their effect on glioma growth and their fate in a tumor environment. In this study, we showed that MIAMI cells were able to specifically migrate toward the orthotopic U87MG tumor model and did not influence its growth. In this model, MIAMI cells did not give rise to cells resembling endothelial cells, pericytes, cancer-associated fibroblasts (CAFs), or astrocytes. Despite these encouraging results, the effects of MIAMI cells may be glioma-dependent. MIAMI cells did not migrate toward the orthotopic Lab1 GB and they can induce the proliferation of other glioma cell lines in vitro. Furthermore, a fraction of MIAMI cells was found to be in a state of proliferation in the U87MG tumor environment. These findings indicate that the use of MIAMI cells as cellular treatment vectors for malignant tumors must be controlled. These cells may be used as “suicide vectors”: vectors for killing not only tumor cells but themselves

Les "GASC" (GBM-associated stromal cells): mise en évidence et rôle dans la croissance des cellules tumorales

National audienc

The different clinical facets of SYN1-related neurodevelopmental disorders

International audienceSynapsin-I (SYN1) is a presynaptic phosphoprotein crucial for synaptogenesis and synaptic plasticity. Pathogenic SYN1 variants are associated with variable X-linked neurodevelopmental disorders mainly affecting males. In this study, we expand on the clinical and molecular spectrum of the SYN1 -related neurodevelopmental disorders by describing 31 novel individuals harboring 22 different SYN1 variants. We analyzed newly identified as well as previously reported individuals in order to define the frequency of key features associated with these disorders. Specifically, behavioral disturbances such as autism spectrum disorder or attention deficit hyperactivity disorder are observed in 91% of the individuals, epilepsy in 82%, intellectual disability in 77%, and developmental delay in 70%. Seizure types mainly include tonic-clonic or focal seizures with impaired awareness. The presence of reflex seizures is one of the most representative clinical manifestations related to SYN1 . In more than half of the cases, seizures are triggered by contact with water, but other triggers are also frequently reported, including rubbing with a towel, fever, toothbrushing, fingernail clipping, falling asleep, and watching others showering or bathing. We additionally describe hyperpnea, emotion, lighting, using a stroboscope, digestive troubles, and defecation as possible triggers in individuals with SYN1 variants. The molecular spectrum of SYN1 variants is broad and encompasses truncating variants (frameshift, nonsense, splicing and start-loss variants) as well as non-truncating variants (missense substitutions and in-frame duplications). Genotype-phenotype correlation revealed that epileptic phenotypes are enriched in individuals with truncating variants. Furthermore, we could show for the first time that individuals with early seizures onset tend to present with severe-to-profound intellectual disability, hence highlighting the existence of an association between early seizure onset and more severe impairment of cognitive functions. Altogether, we present a detailed clinical description of the largest series of individuals with SYN1 variants reported so far and provide the first genotype-phenotype correlations for this gene. A timely molecular diagnosis and genetic counseling are cardinal for appropriate patient management and treatment

The broad phenotypic spectrum of PPP2R1A-related neurodevelopmental disorders correlates with the degree of biochemical dysfunction

Purpose Neurodevelopmental disorders (NDD) caused by protein phosphatase 2A (PP2A) dysfunction have mainly been associated with de novo variants in PPP2R5D and PPP2CA, and more rarely in PPP2R1A. Here, we aimed to better understand the latter by characterizing 30 individuals with de novo and often recurrent variants in this PP2A scaffolding A alpha subunit. Methods Most cases were identified through routine clinical diagnostics. Variants were biochemically characterized for phosphatase activity and interaction with other PP2A subunits. Results We describe 30 individuals with 16 different variants in PPP2R1A, 21 of whom had variants not previously reported. The severity of developmental delay ranged from mild learning problems to severe intellectual disability (ID) with or without epilepsy. Common features were language delay, hypotonia, and hypermobile joints. Macrocephaly was only seen in individuals without B55 alpha subunit-binding deficit, and these patients had less severe ID and no seizures. Biochemically more disruptive variants with impaired B55 alpha but increased striatin binding were associated with profound ID, epilepsy, corpus callosum hypoplasia, and sometimes microcephaly. Conclusion We significantly expand the phenotypic spectrum of PPP2R1A-related NDD, revealing a broader clinical presentation of the patients and that the functional consequences of the variants are more diverse than previously reported

The broad phenotypic spectrum of PPP2R1A-related neurodevelopmental disorders correlates with the degree of biochemical dysfunction

International audiencePurpose: Neurodevelopmental disorders (NDD) caused by protein phosphatase 2A (PP2A) dysfunction have mainly been associated with de novo variants in PPP2R5D and PPP2CA, and more rarely in PPP2R1A. Here, we aimed to better understand the latter by characterizing 30 individuals with de novo and often recurrent variants in this PP2A scaffolding Aα subunit.Methods: Most cases were identified through routine clinical diagnostics. Variants were biochemically characterized for phosphatase activity and interaction with other PP2A subunits.Results: We describe 30 individuals with 16 different variants in PPP2R1A, 21 of whom had variants not previously reported. The severity of developmental delay ranged from mild learning problems to severe intellectual disability (ID) with or without epilepsy. Common features were language delay, hypotonia, and hypermobile joints. Macrocephaly was only seen in individuals without B55α subunit-binding deficit, and these patients had less severe ID and no seizures. Biochemically more disruptive variants with impaired B55α but increased striatin binding were associated with profound ID, epilepsy, corpus callosum hypoplasia, and sometimes microcephaly.Conclusion: We significantly expand the phenotypic spectrum of PPP2R1A-related NDD, revealing a broader clinical presentation of the patients and that the functional consequences of the variants are more diverse than previously reported

The broad phenotypic spectrum of PPP2R1A-related neurodevelopmental disorders correlates with the degree of biochemical dysfunction

PURPOSE: Neurodevelopmental disorders (NDD) caused by protein phosphatase 2A (PP2A) dysfunction have mainly been associated with de novo variants in PPP2R5D and PPP2CA, and more rarely in PPP2R1A. Here, we aimed to better understand the latter by characterizing 30 individuals with de novo and often recurrent variants in this PP2A scaffolding Aα subunit. METHODS: Most cases were identified through routine clinical diagnostics. Variants were biochemically characterized for phosphatase activity and interaction with other PP2A subunits. RESULTS: We describe 30 individuals with 16 different variants in PPP2R1A, 21 of whom had variants not previously reported. The severity of developmental delay ranged from mild learning problems to severe intellectual disability (ID) with or without epilepsy. Common features were language delay, hypotonia, and hypermobile joints. Macrocephaly was only seen in individuals without B55α subunit-binding deficit, and these patients had less severe ID and no seizures. Biochemically more disruptive variants with impaired B55α but increased striatin binding were associated with profound ID, epilepsy, corpus callosum hypoplasia, and sometimes microcephaly. CONCLUSION: We significantly expand the phenotypic spectrum of PPP2R1A-related NDD, revealing a broader clinical presentation of the patients and that the functional consequences of the variants are more diverse than previously reported.status: Published onlin

DataSheet1_The different clinical facets of SYN1-related neurodevelopmental disorders.PDF

Synapsin-I (SYN1) is a presynaptic phosphoprotein crucial for synaptogenesis and synaptic plasticity. Pathogenic SYN1 variants are associated with variable X-linked neurodevelopmental disorders mainly affecting males. In this study, we expand on the clinical and molecular spectrum of the SYN1-related neurodevelopmental disorders by describing 31 novel individuals harboring 22 different SYN1 variants. We analyzed newly identified as well as previously reported individuals in order to define the frequency of key features associated with these disorders. Specifically, behavioral disturbances such as autism spectrum disorder or attention deficit hyperactivity disorder are observed in 91% of the individuals, epilepsy in 82%, intellectual disability in 77%, and developmental delay in 70%. Seizure types mainly include tonic-clonic or focal seizures with impaired awareness. The presence of reflex seizures is one of the most representative clinical manifestations related to SYN1. In more than half of the cases, seizures are triggered by contact with water, but other triggers are also frequently reported, including rubbing with a towel, fever, toothbrushing, fingernail clipping, falling asleep, and watching others showering or bathing. We additionally describe hyperpnea, emotion, lighting, using a stroboscope, digestive troubles, and defecation as possible triggers in individuals with SYN1 variants. The molecular spectrum of SYN1 variants is broad and encompasses truncating variants (frameshift, nonsense, splicing and start-loss variants) as well as non-truncating variants (missense substitutions and in-frame duplications). Genotype-phenotype correlation revealed that epileptic phenotypes are enriched in individuals with truncating variants. Furthermore, we could show for the first time that individuals with early seizures onset tend to present with severe-to-profound intellectual disability, hence highlighting the existence of an association between early seizure onset and more severe impairment of cognitive functions. Altogether, we present a detailed clinical description of the largest series of individuals with SYN1 variants reported so far and provide the first genotype-phenotype correlations for this gene. A timely molecular diagnosis and genetic counseling are cardinal for appropriate patient management and treatment.</p