Suchergebnisse

TOSCA; Everolimus; Estudi de seguretat post-autorització ; TOSCA; Everolimus; Estudio de seguridad posterior a la autorización ; TOSCA; Everolimus; Post-authorization safety study ; This non-interventional post-authorisation safety study (PASS) assessed the long-term safety of everolimus in patients with tuberous sclerosis complex (TSC) who participated in the TuberOus SClerosis registry to increase disease Awareness (TOSCA) clinical study and received everolimus for the licensed indications in the European Union. The rate of adverse events (AEs), AEs that led to dose adjustments or treatment discontinuation, AEs of potential clinical interest, treatment-related AEs (TRAEs), serious AEs (SAEs), and deaths were documented. One hundred seventy-nine patients were included in the first 5 years of observation; 118 of 179 patients had an AE of any grade, with the most common AEs being stomatitis (7.8%) and headache (7.3%). AEs caused dose adjustments in 56 patients (31.3%) and treatment discontinuation in nine patients (5%). AEs appeared to be more frequent and severe in children. On Tanner staging, all patients displayed signs of age-appropriate sexual maturation. Twenty-two of 106 female (20.8%) patients had menstrual cycle disorders. The most frequent TRAEs were stomatitis (6.7%) and aphthous mouth ulcer (5.6%). SAEs were reported in 54 patients (30.2%); the most frequent SAE was pneumonia (>3% patients; grade 2, 1.1%, and grade 3, 2.8%). Three deaths were reported, all in patients who had discontinued everolimus for more than 28 days, and none were thought to be related to everolimus according to the treating physicians. The PASS sub-study reflects the safety and tolerability of everolimus in the management of TSC in real-world routine clinical practice.

European reference network; Rare neurological diseases; Virtual healthcare ; Xarxa europea de referència; Malalties neurològiques rares; Assistència sanitària virtual ; Red europea de referencia; Enfermedades neurologicas raras; Asistencia sanitaria virtual ; While rare diseases (RDs) are by definition of low prevalence, the total number of patients suffering from an RD is high, and the majority of them have neurologic manifestations, involving central, peripheral nerve, and muscle. In 2017, 24 European Reference Networks (ERNs), each focusing on a specific group of rare or low-prevalence complex diseases, were formed to improve the care for patients with an RD. One major aim is to have "the knowledge travel instead of the patient," which has been put into practice by the implementation of the Clinical Patient Management System (CPMS) that enables clinicians to perform pan-European virtual consultations. The European Reference Network for Rare Neurological Diseases (ERN-RND) provides an infrastructure for knowledge sharing and care coordination for patients affected by a rare neurological disease (RND) involving the most common central nervous system pathological conditions. It covers the following disease groups: (i) Cerebellar Ataxias and Hereditary Spastic Paraplegias; (ii) Huntington's disease and Other Choreas; (iii) Frontotemporal dementia; (iv) Dystonia, (non-epileptic) paroxysmal disorders, and Neurodegeneration with Brain Iron Accumulation; (v) Leukoencephalopathies; and (vi) Atypical Parkinsonian Syndromes. At the moment, it unites 32 expert centers and 10 affiliated partners in 21 European countries, as well as patient representatives, but will soon cover nearly all countries of the European Union as a result of the ongoing expansion process. Disease expert groups developed and consented on diagnostic flowcharts and disease scales to assess the different aspects of RNDs. ERN-RND has started to discuss diagnostically unclear patients in the CPMS, is one of four ERNs that serve as foundation of ...

Neurodevelopmental disorders; AMPA; GluA2 ; Trastorns del neurodesenvolupament; AMPA; GluA2 ; Trastornos del neurodesarrollo; AMPA; GluA2 ; AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission. ; Supported by the Wellcome Trust (WT093205MA and WT104033AIA), Medical Research Council (H.H. and D.M.K.), European Community's Seventh Framework Programme (FP7/2007‐2013, under grant agreement No. 2012‐305121 to H.H.), Muscular Dystrophy Association (MDA), Muscular Dystrophy UK, The MSA Trust, Ataxia UK, The Sparkes Children's Medical Research Charity, The Great Ormond Street Hospital Charity, Rosetrees Trust, Brain Research UK, The UK HSP Society, The European Union's Horizon 2020 research and innovation programme Solve-RD project (No 779257), The Pakistan Council (Scholarship to HT), The National Natural Science Foundation of China (31671114, 81871079, 81330027, and 81525007 to H.G. and K.X.), the US National Institutes of Health (NIH grant R01MH101221 to E.E.E), the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) and the Biomedical Research Centre (BRC)

Cervell; Investigació pediàtrica ; Cerebro; Investigación pediátrica ; Brain; Paediatric research ; Preterm newborns with germinal matrix-intraventricular hemorrhage (GM-IVH) are at a higher risk of evidencing neurodevelopmental alterations. Present study aimed to explore the long-term effects that GM-IVH have on hippocampal subfields, and their correlates with memory. The sample consisted of 58 participants, including 36 preterm-born (16 with GM-IVH and 20 without neonatal brain injury), and 22 full-term children aged between 6 and 15 years old. All participants underwent a cognitive assessment and magnetic resonance imaging study. GM-IVH children evidenced lower scores in Full Intelligence Quotient and memory measures compared to their low-risk preterm and full-term peers. High-risk preterm children with GM-IVH evidenced significantly lower total hippocampal volumes bilaterally and hippocampal subfield volumes compared to both low-risk preterm and full-term groups. Finally, significant positive correlations between memory and hippocampal subfield volumes were only found in preterm participants together; memory and the right CA-field correlation remained significant after Bonferroni correction was applied (p = .002). In conclusion, memory alterations and both global and regional volumetric reductions in the hippocampus were found to be specifically related to a preterm sample with GM-IVH. Nevertheless, results also suggest that prematurity per se has a long-lasting impact on the association between the right CA-field volume and memory during childhood. ; This study was funded by the Spanish Ministry of Science, Innovation and Universities [P.I.: L. Zubiaurre-Elorza (PSI2017-83657-P)]. L. Fernández de Gamarra-Oca, S. Soria-Pastor, R. L. Zubiaurre-Elorza, and E. Solana hold fellowships from the Basque Government (PRE_2019_1_0105), the Spanish Ministry of Education and Science (AP2005-0047) and (AP2008-0935) and the Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona respectively. We would like to extend special thanks to the families and the children who participated in this study.