Inherited SCN1A missense mutation in a Dravet Syndrome family: Neuropathological correlation, family screening and implications for adult carriers.

INTRODUCTION: Neuropathological findings in Dravet Syndrome (DS) are scarce, especially in adult patients, and often do not have a genetic confirmation. Additionally, the missense SCN1A pathogenic variant found has only been described as de novo mutation in previous literature. METHODS: We describe the clinical and genetic findings of a family (including three sisters and his father), using Sanger sequencing in the three sisters and in postmortem brain tissue in the father. The present study also shows the neuropathological findings of the father. RESULTS: Despite the presence of long term drug resistant epilepsy, starting with febrile seizures between 6 and 12 months of age, and intellectual disability (ID), the three sisters were diagnosed with DS in adulthood, identifying a missense SCN1A pathogenic variant in exon 20, previously described as de novo -p.Gly1332Glu (c .3995 G>A). The oldest sister had the most severe phenotype, with severe ID and wheel chair dependency, passing away at 52. The other two sisters had a moderate phenotype, being at the present seizure free, but with significant comorbidities, such as crouch gait and parkinsonism. Several relatives from the paternal path (including the father) presented epilepsy, but without ID. The father was diagnosed with Alzheimer´s Disease (AD) at 60, and because he donated his brain, the same variant was confirmed in postmortem study. Neither the MRI nor the histopathology showed specific morphological changes for DS, consistent with previous studies. CONCLUSIONS: This work supports the need to review the clinical and genetic spectra of DS in adults with epilepsy and unknown ID. The clinical consequences of this syndrome seem to have a functional rather than a structural basis, supported by the absence of specific neuropathological findings.

Differential levels of Neurofilament Light protein in cerebrospinal fluid in patients with a wide range of neurodegenerative disorders.

Cerebrospinal fluid (CSF) biomarkers are useful in the diagnosis and the prediction of progression of several neurodegenerative diseases. Among them, CSF neurofilament light (NfL) protein has particular interest, as its levels reflect neuroaxonal degeneration, a common feature in various neurodegenerative diseases. In the present study, we analyzed NfL levels in the CSF of 535 participants of the SPIN (Sant Pau Initiative on Neurodegeneration) cohort including cognitively normal participants, patients with Alzheimer disease (AD), Down syndrome (DS), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). We evaluated the differences in CSF NfL accross groups and its association with other CSF biomarkers and with cognitive scales. All neurogenerative diseases showed increased levels of CSF NfL, with the highest levels in patients with ALS, FTD, CBS and PSP. Furthermore, we found an association of CSF NfL levels with cognitive impairment in patients within the AD and FTD spectrum and with AD pathology in DLB and DS patients. These results have implications for the use of NfL as a marker in neurodegenerative diseases.

[Teaching in emergency medicine]. / Docencia en medicina de urgencias y emergencias.

The appropriate care of patients in emergency services can reach a level of complexity as to make a sound training necessary, which should be based on a medical specialty, as happens in the majority of the countries in our context. In Spain at present there is no regulated and homogeneous training in urgency and emergency medicine (UEM), either during the period of undergraduate training (in the form of a universally compulsory subject in the faculties of medicine) or during the postgraduate period (in the form of a medical specialty). In this respect, the definitive approval of the specialty in UEM is currently pending within the framework of a reform of the residence program that will evolve towards a core training program of specialties. Until thus occurs, the reality in Spain is that professionals who work in this care setting possess a heterogeneous training. As a result of this vacuum and the training needs of these professionals, a wide range of specific training proposals has been developed over the years in order to optimise the skills and abilities of the professionals who provide initial emergency care to the patient. A new generation of courses has been set underway using the new didactic methodologies of training, into which didactic tools of e-learning and robotic simulation have been incorporated.

Docencia en medicina de urgencias y emergencias / Teaching in emergency medicine

de urgencias y emergencias puede llegar a ser losuficientemente complejo como para requerir una sólidaformación que debiera estar sustentada en una especialidadmédica, como ocurre en la mayoría de paísesde nuestro entorno.En la actualidad, en España no existe una formaciónreglada y homogénea en medicina de urgencias y emergencias(MUE) ni durante el período de formación de pregrado(en forma de asignatura obligatoria de forma universalen las facultades de medicina) ni durante el períodode posgrado (en forma de especialidad médica). En estesentido, actualmente se está pendiente de la aprobacióndefinitiva de esta especialidad en MUE en el marco de unareforma del programa de residencia que evolucionará haciaun programa formativo troncal de especialidades. A laespera de ello, la realidad es que en España los profesionalesque desarrollan su labor en este ámbito asistencialposeen una formación heterogénea. Fruto de todo estevacío y de las necesidades formativas de estos profesionales,se ha desarrollado con los años un amplio abanicode propuestas formativas específicas para optimizar lashabilidades y destrezas de los profesionales que prestanla primera asistencia urgente a los pacientes.Una nueva generación de cursos se ha puesto enmarcha utilizando las nuevas metodologías didácticasde formación, en las que se incorporan herramientasdidácticas de e-learning y simulación robótica(AU)

The appropriate care of patients in emergency servicescan reach a level of complexity as to make a soundtraining necessary, which should be based on a medicalspeciality, as happens in the majority of the countriesin our context.In Spain at present there is no regulated and homogeneoustraining in urgency and emergency medicine(UEM), either during the period of undergraduate training(in the form of a universally compulsory subjectin the faculties of medicine) or during the postgraduateperiod (in the form of a medical speciality). In this respect,the definitive approval of the speciality in UEM iscurrently pending within the framework of a reform ofthe residence program that will evolve towards a coretraining program of specialities. Until thus occurs, thereality in Spain is that professionals who work in thiscare setting possess a heterogeneous training. As a resultof this vacuum and the training needs of these professionals,a wide range of specific training proposalshas been developed over the years in order to optimisethe skills and abilities of the professionals who provideinitial emergency care to the patient.A new generation of courses has been set underwayusing the new didactic methodologies of training,into which didactic tools of e-learning and roboticsimulation have been incorporated(AU)