Brain correlates of spike and wave discharges in GLUT1 deficiency syndrome

Purpose To provide imaging biomarkers of generalized spike-and-wave discharges (GSWD) in patients with GLUT1 deficiency syndrome (GLUT1DS). Methods Eighteen GLUT1DS patients with pathogenetic mutation in SLC2A1 gene were studied by means of Video-EEG simultaneously recorded with functional MRI (VideoEEG-fMRI). A control group of sex and age-matched patients affected by Genetic Generalized Epilepsy (GGE) with GSWD were investigated with the same protocol. Within and between groups comparison was performed as appropriated. For GLUT1DS, correlations analyses between the contrast of interest and the main clinical measurements were provided. Results EEG during fMRI revealed interictal GSWD in 10 GLUT1DS patients. Group-level analysis showed BOLD signal increases at the premotor cortex and putamen. With respect to GGE, GLUT1DS patients demonstrated increased neuronal activity in the putamen, precuneus, cingulate cortex, SMA and paracentral lobule. Whole-brain correlation analyses disclosed a linear relationship between the GSWD-related BOLD changes and the levels of glycorrhachia at diagnosis over the sensory-motor cortex and superior parietal lobuli. Conclusion The BOLD dynamics related to GSWD in GLUT1DS are substantially different from typical GGE showing the former an increased activity in the premotor-striatal network and a decrease in the thalamus. The revealed hemodynamic maps might represent imaging biomarkers of GLUT1DS, being potentially useful for a precocious diagnosis of this genetic disorder

Case report: KETOLAND the psychoeducation program for ketogenic diet

Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a rare neurological disorder characterized by a wide spectrum of symptoms: epilepsy, movement disorders and neurocognitive impairment. The gold standard treatment for GLUT1DS are ketogenic dietary therapies (KDTs), specifically classical ketogenic diet (CKD). Despite the benefits, CKD often represents a challenge for patients and their families since meal preparation is extremely demanding and deviates a lot from normal diet. To assure an optimal compliance to CKD a psychological support for parents and patients with GLUT1DS is highly recommended. Specifically, a psychoeducational intervention that ameliorates the knowledge about the illness and its therapy improves treatment' s adherence and efficacy. The aim of this case report is to investigate the effectiveness of a psychoeducational program, partially implemented through telepsychology, based on the theoretical model of Cognitive Behavioral Play Therapy (CBPT) to support KDT knowledge and adherence in a patient with GLUT1DS who presented a worsening of her clinical picture due to a sparse knowledge of KDTs principles which determined a low adherence. Thus, with this case report we propose a model of intervention with psychoeducation in a patient with a complex chronic disease

Toward responsible clinical n-of-1 strategies for rare diseases

N-of-1 strategies can provide high-quality evidence of treatment efficacy at the individual level and optimize evidence-based selection of off-label treatments for patients with rare diseases. Given their design characteristics, n-of-1 strategies are considered to lay at the intersection between medical research and clinical care. Therefore, whether n-of-1 strategies should be governed by research or care regulations remains a debated issue. Here, we delineate differences between medical research and optimized clinical care, and distinguish the regulations which apply to either. We also set standards for responsible optimized clinical n-of-1 strategies with (off-label) treatments for rare diseases. Implementing clinical n-of-1 strategies as defined here could aid in optimized treatment selection for such diseases

Ketonemia variability through menstrual cycle in patients undergoing classic ketogenic diet

IntroductionKetogenic dietary therapies (KDT) are well-established, safe, non-pharmacologic treatments used for children and adults with drug-resistant epilepsy and other neurological disorders. Ketone bodies (KBs) levels are recognized as helpful to check compliance to the KDT and to attempt titration of the diet according to the individualized needs. KBs might undergo inter-individual and intra-individual variability and can be affected by several factors. Possible variations in glycemia and ketone bodies blood levels according to the menstrual cycle have not been systematically assessed yet, but this time window deserves special attention because of hormonal and metabolic related changes.MethodsThis study aims at searching for subtle changes in KBs blood level during menstrual cycle in female patients undergoing a stable ketogenic diet, by analyzing 3-months daily measurement of ketone bodies blood levels and glucose blood levels throughout the menstrual cycle.ResultsWe report the preliminary results on six female patients affected by GLUT1DS or drug resistant epilepsy, undergoing a stable classic ketogenic diet. A significant increase in glucose blood levels during menstruation was found in the entire cohort. As far as the ketone bodies blood levels, an inversely proportional trend compared to glycemia was noted.ConclusionExploring whether ketonemia variations might occur according to the menstrual cycle is relevant to determine the feasibility of transient preventive diet adjustments to assure a continuative treatment efficacy and to enhance dietary behavior support.Clinical trial registrationclinicaltrials.gov, identifier NCT05234411

Ketogenic dietary therapies in epilepsy: recommendations of the Italian League against Epilepsy Dietary Therapy Study Group

A stepwise increase in the utilization of ketogenic dietary therapies for drug-resistant epilepsy has been observed in Italy in the last decade, although it is still considered often underused in many centers when compared to other countries. The Dietary Therapy Study Group of the Italian League against Epilepsy proposes practical recommendations to improve shared knowledge and facilitate the application of ketogenic dietary therapies, optimizing its efficacy and tolerability. The experts involved (11 child neuropsychiatrists, two adult neurologists, one psychologist, one pharmacologist, one pediatric endocrinologist, one representative of patients' associations, and three dietitians and clinical nutritionists) responded to a survey on current clinical practice issues and were asked to discuss controversial topics related to supplementation, long-term maintenance, transition, and a multidisciplinary approach to ketogenic dietary therapies. Practical indications for patient selection, diet initiation, management, side effects prevention, and follow-up are provided

Utilización de metodologías activas de enseñanza para el aprendizaje de las matemáticas, centradas en el estudiante y desarrolladas en el espacio innovador de una hiperaula

La inauguración de la hiperaula de la Facultad de Educación-CFP (UCM) en abril de 2019 y su prioridad de uso para el Máster en Formación del Profesorado de Educación Secundaria, Bachillerato, Formación Profesional y Enseñanza de Idiomas durante el curso académico 2019-2020, supone un marco experimental absolutamente novedoso. Estas circunstancias permiten a la responsable del proyecto y a varios profesores participantes en el mismo, algunos de ellos docentes en el mencionado Máster y pertenecientes a diferentes Departamentos y Facultades de la UCM, así como a varios alumni y personal de administración y servicios implicados en el proyecto, utilizar este innovador espacio para la enseñanza de la asignatura de "Innovación docente e iniciación a la investigación educativa" (especialidad de matemáticas del Máster en Formación del Profesorado), empleando para ello metodologías activas de enseñanza centradas en el estudiante

A registry for Dravet syndrome: The Italian experience

Objectives: We describe the Residras registry, dedicated to Dravet syndrome (DS) and to other phenotypes related to SCN1A mutations, as a paradigm of registry for rare and complex epilepsies. Our primary objectives are to present the tools and framework of the integrative platform, the main characteristics emerging from the patient cohort included in the registry, with emphasis on demographic, clinical outcome, and mortality. / Methods: Standardized data of enrolled pediatric and adult patients were collected in 24 Italian expert centers and regularly updated at least on a yearly basis. Patients were prospectively enrolled, at registry starting, but historical retrospective data were also included. / Results: At present, 281 individuals with DS and a confirmed SCN1A mutation are included. Most patients have data available on epilepsy (n = 263) and their overall neurological condition (n = 255), based on at least one follow-up update. Median age at first clinical assessment was 2 years (IQR 0–9) while at last follow-up was 11 years (IQR 5–18.5). During the 7-year activity of the registry, five patients died resulting in a mortality rate of 1.84 per 1000-person-years. When analyzing clinical changes over the first 5-year follow-up, we observed a significant difference in cognitive function (P < 0.001), an increased prevalence of behavioral disorders including attention deficit (P < 0.001), a significant worsening of language (P = 0.001), and intellectual disability (P < 0.001). / Significance: The Residras registry represents a large collection of standardized national data for the DS population. The registry platform relies on a shareable and interoperable framework, which promotes multicenter high-quality data collection. In the future, such integrated platform may represent an invaluable asset for easing access to cohorts of patients that may benefit from clinical trials with emerging novel therapies, for drug safety monitoring, and for delineating natural history. Its framework makes it improvable based on growing experience with its use and easily adaptable to other rare and complex epilepsy syndromes

Knowledge Graphs Evolution and Preservation -- A Technical Report from ISWS 2019

One of the grand challenges discussed during the Dagstuhl Seminar "Knowledge Graphs: New Directions for Knowledge Representation on the Semantic Web" and described in its report is that of a: "Public FAIR Knowledge Graph of Everything: We increasingly see the creation of knowledge graphs that capture information about the entirety of a class of entities. [...] This grand challenge extends this further by asking if we can create a knowledge graph of "everything" ranging from common sense concepts to location based entities. This knowledge graph should be "open to the public" in a FAIR manner democratizing this mass amount of knowledge." Although linked open data (LOD) is one knowledge graph, it is the closest realisation (and probably the only one) to a public FAIR Knowledge Graph (KG) of everything. Surely, LOD provides a unique testbed for experimenting and evaluating research hypotheses on open and FAIR KG. One of the most neglected FAIR issues about KGs is their ongoing evolution and long term preservation. We want to investigate this problem, that is to understand what preserving and supporting the evolution of KGs means and how these problems can be addressed. Clearly, the problem can be approached from different perspectives and may require the development of different approaches, including new theories, ontologies, metrics, strategies, procedures, etc. This document reports a collaborative effort performed by 9 teams of students, each guided by a senior researcher as their mentor, attending the International Semantic Web Research School (ISWS 2019). Each team provides a different perspective to the problem of knowledge graph evolution substantiated by a set of research questions as the main subject of their investigation. In addition, they provide their working definition for KG preservation and evolution