Background: Increasing clinical and scientific attention is given to the transition of neurological stages from child to adult. Data on brain plasticity during adolescence is interesting for providing adequate evidence-based medical attention to neurological conditions in this population. Acquired aphasia is well described in adults and children, but not in adolescence. Objective: We describe a 5-year follow-up of language in three adolescent subjects with post-brain injury aphasia. Methods: We analysed and scored formal aspects of language three times, language hemispheric dominance twice with dichotic listening test and functional magnetic resonance imaging (fMRI) brain activation patterns that supported expressive and comprehensive language during the recovery period. Results: We found similarities to both paediatric and adult aphasia in these three adolescents. While the level of recovery resembled that of children with aphasia, a more efficient language rehabilitation occurred in those who remained with left hemispheric dominance in the chronic stage, as it is reported in adults. Conclusions: Our analysis and long-term follow-up provide data for a better understanding on how the injured brain matures during adolescence. More studies with larger samples will help to understand the function of the remaining networks and the recovery from injury in this particular age group.

Introducción Las redes sociales tienen un creciente potencial como herramienta educativa universitaria, pero existe poca evidencia sobre cuáles son las preferencias de los alumnos, y en qué condiciones prefieren utilizarlas. El objetivo de nuestro estudio ha sido identificar esas preferencias para favorecer un uso dirigido por el profesorado de Ciencias de la Salud. Métodos Hemos investigado las redes sociales preferidas de los alumnos del último curso del Grado de Medicina a través de un cuestionario online. Se ha realizado un análisis descriptivo de sus respuestas, y de relación estadística entre las mismas a través del cálculo de la chi-cuadrado. Resultados Han participado en el estudio un total de 147 alumnos, de una muestra de 220. Más del 80% consideraban que las redes sociales son una herramienta docente útil, y mostraban un interés moderado-máximo hacia el aprendizaje vehiculado a través de las mismas. De entre las redes sociales, las preferidas fueron Instagram y YouTube. Una mayoría desean recibir las «píldoras educativas» con una frecuencia moderada, y con contenido mixto (texto, imágenes, cuestionarios¿). Conclusión El uso de las redes sociales como herramienta docente suscita interés entre los alumnos, que se decantan por redes de contenido visual. Esta conectividad profesor-alumno podría favorecer el refuerzo de conceptos docentes y la comunicación bidireccional.

Dravet syndrome is a genetic encephalopathy characterized by severe epilepsy combined with motor, cognitive, and behavioral abnormalities. Current antiepileptic drugs achieve only partial control of seizures and provide little benefit on the patient's neurological development. In >80% of cases, the disease is caused by haploinsufficiency of the SCN1A gene, which encodes the alpha subunit of the Nav1.1 voltage-gated sodium channel. Novel therapies aim to restore SCN1A expression in order to address all disease manifestations. We provide evidence that a high-capacity adenoviral vector harboring the 6-kb SCN1A cDNA is feasible and able to express functional Nav1.1 in neurons. In vivo, the best biodistribution was observed after intracerebral injection in basal ganglia, cerebellum, and prefrontal cortex. SCN1A A1783V knockin mice received the vector at 5 weeks of age, when most neurological alterations were present. Animals were protected from sudden death, and the epileptic phenotype was attenuated. Improvement of motor performance and interaction with the environment was observed. In contrast, hyperactivity persisted, and the impact on cognitive tests was variable (success in novel object recognition and failure in Morris water maze tests). These results provide proof of concept for gene supplementation in Dravet syndrome and indicate new directions for improvement.

Early infantile epileptic encephalopathies (EIEEs) constitute a group of severe early onset epilepsies. Although still classified under syndromic clusters of clinical features, the genetic basis of several EIEEs leads to the definition of new types of epilepsies. We report a newborn male with seizures since his second day of life. The results of the first line diagnostic tests did not identify the cause of the seizures, which prompted a genetic study. A de novo KCNQ2 genomic variant that may explain the neonatal epileptic encephalopathy was found and led to more appropriate treatment. Genetic testing allows more specific treatment and more accurate prognosis, and also adds to the database of the phenotypes associated with the genomic variants.

Objective: To evaluate the capability of children with Dravet syndrome to generate brain gamma-oscillatory activity in response to auditory steady-state stimulation. Methods: Fifty-one subjects were included: 13 with Dravet syndrome with SCN1A gene alterations, 26 with non-Dravet epilepsies and 12 healthy controls. Responses to auditory steady-state stimulation elicited with a chirp-modulated tone between 1 and 120 Hz were collected in subjects and compared across groups. Results: Subjects with Dravet syndrome showed weak or no responses in the 1-120 Hz frequency range. Healthy controls showed oscillatory responses following the frequency of the modulation that were maximal in the low (30-70 Hz) and high (80-120) gamma-ranges both, in the power and inter-trial coherence estimates. Non-Dravet epileptic children showed differences in the auditory responses when compared with the healthy controls but were able to generate oscillatory evoked activities following the frequency-varying stimulation. Conclusions: The ability to generate brain gamma-oscillatory activity of children with Dravet in response to a chirp-modulated auditory stimulus is highly impaired, is not due to epilepsy and is consistent with the Nav1.1 channel dysfunction affecting interneuron activity seen in Dravet mouse models. Significance: The reported deficits in the brain oscillatory activity evoked by chirp modulated tones in children with Dravet is compatible with Dravet syndrome disease mechanisms and constitutes a potential biomarker for future disease-modifying interventions. (C) 2019 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

mportance: Clinical evidence supports effectiveness of cannabidiol for treatment-resistant seizures in Dravet syndrome, but this trial is the first to evaluate the 10-mg/kg/d dose. Objective: To evaluate the efficacy and safety of a pharmaceutical formulation of cannabidiol, 10 and 20 mg/kg/d, vs placebo for adjunctive treatment of convulsive seizures in patients with Dravet syndrome. Design, setting, and participants: This double-blind, placebo-controlled, randomized clinical trial (GWPCARE2) recruited patients from April 13, 2015, to November 10, 2017, with follow-up completed on April 9, 2018. Of 285 patients screened from 38 centers in the United States, Spain, Poland, the Netherlands, Australia, and Israel, 86 were excluded, and 199 were randomized. Patients were aged 2 to 18 years with a confirmed diagnosis of Dravet syndrome and at least 4 convulsive seizures during the 4-week baseline period while receiving at least 1 antiepileptic drug. Data were analyzed from November 16 (date of unblinding) to December 13 (date of final outputs), 2018, based on intention to treat and per protocol. Interventions: Patients received cannabidiol oral solution at a dose of 10 or 20 mg/kg per day (CBD10 and CBD20 groups, respectively) or matched placebo in 2 equally divided doses for 14 weeks. All patients, caregivers, investigators, and individuals assessing data were blinded to group assignment. Main outcomes and measures: The primary outcome was change from baseline in convulsive seizure frequency during the treatment period. Secondary outcomes included change in all seizure frequency, proportion with at least a 50% reduction in convulsive seizure activity, and change in Caregiver Global Impression of Change score. Results: Of 198 eligible patients (mean [SD] age, 9.3 [4.4] years; 104 female [52.5%]), 66 were randomized to the CBD10 group, 67 to the CBD20 group, and 65 to the placebo group, and 190 completed treatment. The percentage reduction from baseline in convulsive seizure frequency was 48.7% for CBD10 group and 45.7% for the CBD20 group vs 26.9% for the placebo group; the percentage reduction from placebo was 29.8% (95% CI, 8.4%-46.2%; P = .01) for CBD10 group and 25.7% (95% CI, 2.9%-43.2%; P = .03) for the CBD20 group. The most common adverse events were decreased appetite, diarrhea, somnolence, pyrexia, and fatigue. Five patients in the CBD20 group discontinued owing to adverse events. Elevated liver transaminase levels occurred more frequently in the CBD20 (n = 13) than the CBD10 (n = 3) group, with all affected patients given concomitant valproate sodium. Conclusions and relevance: Adjunctive cannabidiol at doses of 10 and 20 mg/kg/d led to similar clinically relevant reductions in convulsive seizure frequency with a better safety and tolerability profile for the 10-mg/kg/d dose in children with treatment-resistant Dravet syndrome. Dose increases of cannabidiol to greater than 10 mg/kg/d should be tailored to individual efficacy and safety. Trial registration: ClinicalTrials.gov Identifier: NCT02224703.

The growing interest in cannabidiol (CBD), specifically a pure form of CBD, as a treatment for epilepsy, among other conditions, is reflected in recent changes in legislation in some countries. Although there has been much speculation about the therapeutic value of cannabis-based products as an anti-seizure treatment for some time, it is only within the last two years that Class I evidence has been available for a pure form of CBD, based on placebo-controlled RCTs for patients with Lennox-Gastaut syndrome and Dravet syndrome. However, just as we are beginning to understand the significance of CBD as a treatment for epilepsy, in recent years, a broad spectrum of products advertised to contain CBD has emerged on the market. The effects of these products are fundamentally dependent on the purity, preparation, and concentration of CBD and other components, and consensus and standardisation are severely lacking regarding their preparation, composition, usage and effectiveness. This review aims to provide information to neurologists and epileptologists on the therapeutic value of CBD products, principally a purified form, in routine practice for patients with intractable epilepsy.

Importance Fenfluramine treatment may reduce monthly convulsive seizure frequency in patients with Dravet syndrome who have poor seizure control with their current stiripentol-containing antiepileptic drug regimens. Objective To determine whether fenfluramine reduced monthly convulsive seizure frequency relative to placebo in patients with Dravet syndrome who were taking stiripentol-inclusive regimens. Design, Setting, and Participants This double-blind, placebo-controlled, parallel-group randomized clinical trial was conducted in multiple centers. Eligible patients were children aged 2 to 18 years with a confirmed clinical diagnosis of Dravet syndrome who were receiving stable, stiripentol-inclusive antiepileptic drug regimens. Interventions Patients with 6 or more convulsive seizures during the 6-week baseline period were randomly assigned to receive fenfluramine, 0.4 mg/kg/d (maximum, 17 mg/d), or a placebo. After titration (3 weeks), patients' assigned dosages were maintained for 12 additional weeks. Caregivers recorded seizures via a daily electronic diary. Main Outcomes and Measures The primary efficacy end point was the change in mean monthly convulsive seizure frequency between fenfluramine and placebo during the combined titration and maintenance periods relative to baseline. Results A total of 115 eligible patients were identified; of these, 87 patients (mean [SD], age 9.1 [4.8] years; 50 male patients [57%]; mean baseline frequency of seizures, approximately 25 convulsive seizures per month) were enrolled and randomized to fenfluramine, 0.4 mg/kg/d (n = 43) or placebo (n = 44). Patients treated with fenfluramine achieved a 54.0% (95% CI, 35.6%-67.2%; P < .001) greater reduction in mean monthly convulsive seizure frequency than those receiving the placebo. With fenfluramine, 54% of patients demonstrated a clinically meaningful (>= 50%) reduction in monthly convulsive seizure frequency vs 5% with placebo (P < .001). The median (range) longest seizure-free interval was 22 (3.0-105.0) days with fenfluramine and 13 (1.0-40.0) days with placebo (P = .004). The most common adverse events were decreased appetite (19 patients taking fenfluramine [44%] vs 5 taking placebo [11%]), fatigue (11 [26%] vs 2 [5%]), diarrhea (10 [23%] vs 3 [7%]), and pyrexia (11 [26%] vs 4 [9%]). Cardiac monitoring demonstrated no clinical or echocardiographic evidence of valvular heart disease or pulmonary arterial hypertension. Conclusions and Relevance Fenfluramine demonstrated significant improvements in monthly convulsive seizure frequency in patients with Dravet syndrome whose conditions were insufficiently controlled with stiripentol-inclusive antiepileptic drug regimens. Fenfluramine was generally well tolerated. Fenfluramine may represent a new treatment option for Dravet syndrome.

Introduction. Dravet syndrome (DS) is a rare, drug resistant epilepsy that starts very early in life with febrile seizures followed by cognitive impairment and diverse seizure types. Aim. To generate evidence on the epidemiology of DS, its diagnosis, patient-flow, treatment and unmet needs from the perspective of Spanish experts. Development. A two-round Delphi study involving 19 physicians was conducted. Questionnaires were based on literature review and validated by clinical experts. Consensus was reached when topics were subject to routine clinical practice and individual experience, or the coefficient of variation among answers was <= 0.3. The estimated number of new DS patients is 73 per year. Prevalence is estimated to be between 348-540 patients. DS is mostly diagnosed in children. Survival varies from 5 to 60 years. There is no standardised follow-up of patients beyond the age of 18 and mortality rates are uncertain. No standard guidelines exist for diagnosing or treating DS. It takes 9 to 15 months to confirm the diagnosis and genetic testing is unevenly available. Valproic acid, clobazam, stiripentol and topiramate are commonly used. Poor efficacy and safety are the main reasons for treatment switch. Conclusions. The epidemiology of DS in Spain is not well known and several areas of unmet needs still exist. Experts' views offer a starting point for further research into the reality of DS in Spain. Epidemiological studies, consensus criteria, easy access to genetic testing, treatment options, training and research into quality of life aspects are highly needed.

Dravet Syndrome (DS) is an encephalopathy with epilepsy associated with multiple neuropsychiatric comorbidities. In up to 90% of cases, it is caused by functional happloinsufficiency of the SCN1A gene, which encodes the alpha subunit of a voltage-dependent sodium channel (Nav1.1). Preclinical development of new targeted therapies requires accessible animal models which recapitulate the disease at the genetic and clinical levels. Here we describe that a C57BL/6 J knock-in mouse strain carrying a heterozygous, clinically relevant SCN1A mutation (A1783V) presents a full spectrum of DS manifestations. This includes 70% mortality rate during the first 8 weeks of age, reduced threshold for heat-induced seizures (4.7 degrees C lower compared with control littermates), cognitive impairment, motor disturbances, anxiety, hyperactive behavior and defects in the interaction with the environment. In contrast, sociability was relatively preserved. Electrophysiological studies showed spontaneous interictal epileptiform discharges, which increased in a temperature-dependent manner. Seizures were multifocal, with different origins within and across individuals. They showed intra/inter-hemispheric propagation and often resulted in generalized tonic-clonic seizures. F-18-labelled flourodeoxyglucose positron emission tomography (FDG-PET) revealed a global increase in glucose uptake in the brain of Scn1a(WT/A1783V) mice. We conclude that the Scn1a(WT/A1783V) model is a robust research platform for the evaluation of new therapies against DS.

It is estimated that about 70 million people all over the world suffer from epilepsy, half of which are children, in whom the prevalence is around 0.5 to 0.8%. Although there are several therapies, the treatment of epilepsy is based mainly on drugs, which, depending on the year of coming onto the market are classified as first, second, or third generation. In this article, a description is presented on the main characteristics of the latest generation of anti-epileptic drugs (lacosamide, eslicarbazepine acetate, brivaracetam, perampanel, retigabine, everolimus and cannabidiol). These, with the exception of retigabine (is not yet on the market), are considered safe and effective in the paediatric population. Everolimus and cannabidiol have very specific indications (tuberous sclerosis, Dravet syndrome, and Lennox Gastaut syndrome), while the rest are indicated in the management of seizures of focal origin in children from 4 years-old. These new molecules have been developed in order to provide a pharmaceutical profile and tolerance superior to the previously available drugs, and it is forecast that as their use increases, their true potential and profile will widen. Furthermore, for the first time in Paediatric Epileptology, the extrapolation of the efficacy data in adults have been used (together with specific safety and pharmacokinetic studies in the paediatric population), in order to speed up their approval for use in the child population.

BACKGROUND: Cannabidiol has been used for treatment-resistant seizures in patients with severe early-onset epilepsy. We investigated the efficacy and safety of cannabidiol added to a regimen of conventional antiepileptic medication to treat drop seizures in patients with the Lennox-Gastaut syndrome, a severe developmental epileptic encephalopathy. METHODS: In this double-blind, placebo-controlled trial conducted at 30 clinical centers, we randomly assigned patients with the Lennox-Gastaut syndrome (age range, 2 to 55 years) who had had two or more drop seizures per week during a 28-day baseline period to receive cannabidiol oral solution at a dose of either 20 mg per kilogram of body weight (20-mg cannabidiol group) or 10 mg per kilogram (10-mg cannabidiol group) or matching placebo, administered in two equally divided doses daily for 14 weeks. The primary outcome was the percentage change from baseline in the frequency of drop seizures (average per 28 days) during the treatment period. RESULTS: A total of 225 patients were enrolled; 76 patients were assigned to the 20-mg cannabidiol group, 73 to the 10-mg cannabidiol group, and 76 to the placebo group. During the 28-day baseline period, the median number of drop seizures was 85 in all trial groups combined. The median percent reduction from baseline in drop-seizure frequency during the treatment period was 41.9% in the 20-mg cannabidiol group, 37.2% in the 10-mg cannabidiol group, and 17.2% in the placebo group (P=0.005 for the 20-mg cannabidiol group vs. placebo group, and P=0.002 for the 10-mg cannabidiol group vs. placebo group). The most common adverse events among the patients in the cannabidiol groups were somnolence, decreased appetite, and diarrhea; these events occurred more frequently in the higher-dose group. Six patients in the 20-mg cannabidiol group and 1 patient in the 10-mg cannabidiol group discontinued the trial medication because of adverse events and were withdrawn from the trial. Fourteen patients who received cannabidiol (9%) had elevated liver aminotransferase concentrations. CONCLUSIONS: Among children and adults with the Lennox-Gastaut syndrome, the addition of cannabidiol at a dose of 10 mg or 20 mg per kilogram per day to a conventional antiepileptic regimen resulted in greater reductions in the frequency of drop seizures than placebo. Adverse events with cannabidiol included elevated liver aminotransferase concentrations.

Aim. To know the current state of the approach of attention deficit hyperactivity disorder (ADHD) in neuropediatricians. Subjects and methods. A telematic survey was carried out to collect preliminary information on the interest, difficulties in the management and treatment of ADHD to the 437 fellowship of the Neuropediactric Spanish Society (SENEP). Results. Only 32.49% of the sent questionnaires were answered, with important geographic variability. 97.89% stated that 50% of their consultations were children with learning disabilities and ADHD. Regarding who started treatment for ADHD in their area, the majority answered that the neuropediatrician (57.97%), followed by the child psychiatrist (34.78%) and the primary care pediatrician (5.31%). The lack of a psycho-pedagogical study by the school (49.79%), followed by the lack of time in the consultation (29.11%), was cited as the greatest difficulty in the initial assessment of children with suspected ADHD. Concerning the difficulties in the follow-up, the biggest complaint was the lack of coordination between professionals, the school and parents. And, lastly, regarding the type of treatment use, most patients were on prolonged-release methylphenidate, a stable percentage using immediate release methylphenidate as a single or combined treatment, and in a lower range was the use of clonidine and atomoxetine, and an incipient use of lisdexamphetamine were observed. 80% of the patient showed adherence to pharmacological treatment after one year. Conclusions. It is necessary to advance in the training and continuous education of our neuropediatric specialists in ADHD and to homogenize the clinical practice and coordination with education system in the Spanish territory.

Gillespie syndrome (GS) is characterized by bilateral iris hypoplasia, congenital hypotonia, non-progressive ataxia, and progressive cerebellar atrophy. Trio-based exome sequencing identified de novo mutations in ITPR1 in three unrelated individuals with GS recruited to the Deciphering Developmental Disorders study. Whole-exome or targeted sequence analysis identified plausible disease-causing ITPR1 mutations in 10/10 additional GS-affected individuals. These ultra-rare protein-altering variants affected only three residues in ITPR1: Glu2094 missense (one de novo, one co-segregating), Gly2539 missense (five de novo, one inheritance uncertain), and Lys2596 in-frame deletion (four de novo). No clinical or radiological differences were evident between individuals with different mutations. ITPR1 encodes an inositol 1,4,5-triphosphate-responsive calcium channel. The homo-tetrameric structure has been solved by cryoelectron microscopy. Using estimations of the degree of structural change induced by known recessive- and dominant-negative mutations in other disease-associated multimeric channels, we developed a generalizable computational approach to indicate the likely mutational mechanism. This analysis supports a dominant-negative mechanism for GS variants in ITPR1. In GS-derived lymphoblastoid cell lines (LCLs), the proportion of ITPR1-positive cells using immunofluorescence was significantly higher in mutant than control LCLs, consistent with an abnormality of nuclear calcium si

Symptoms of inattention and hyperactivity are correlated with impaired sleep duration and quality; specifically, there is an association between ADHD symptoms and problems falling asleep and parasomnias, however, the current study does not address the nature and direction of causality. Children with ADHD and receiving methylphenidate had fewer sleep disorders, suggesting that, at least in some children, stimulant treatment is associated with improvement of some aspects of sleep. Shorter sleep duration in adolescents under pharmacological treatment for ADHD tended to result in more errors of omission, suggesting that it is important to promote good sleep habits in this population.

ntroduction: Electrical status epilepticus during sleep (ESES) is an epileptic syndrome characterised by the presence of very persistent slow spike-wave-type epileptic discharges during non-REM sleep. The management of this pathology, today, is heterogeneous and no controlled studies have been conducted with the treatments employed; similarly, whether or not they improve patients' cognitive development or not has still to be determined. Patients and methods: A review was carried out of the patients diagnosed with ESES at four hospitals over a period of 15 years; data concerning their clinical presentation, therapeutic management and clinical course were collected and compared with the literature. Results: Altogether 29 patients with ESES were detected, 20 of them idiopathic and 26 generalised. The drugs with which the greatest control of the electrical activity was achieved were corticoids/adrenocorticotropic hormone (ACTH), clobazam and levetiracetam. In the primary cases ESES lasted an average of six months and the duration was twice that time in the secondary cases. Findings showed that the intelligence quotient remained normal in 45% of patients and 40% presented differing degrees of cognitive disability in the course of the pathology. Conclusions: The developmental neuropsychological prognosis is usually unfavourable and the cognitive development seems to be related with the duration of ESES and the area where the epileptic activity is concentrated, which suggests that the poor prognosis can be avoided if treatment is established at an early stage. The antiepileptic drugs that are most commonly used are valproic acid, ethosuximide and levetiracetam, and in our milieu clobazam and lamotrigine were commonly employed. The most effective drugs for controlling ESES were corticoids/ACTH, clobazam and levetiracetam.

The majority of neuropsychological tests used to evaluate attention processes in children lack ecological validity. The AULA Nesplora (AULA) is a continuous performance test, developed in a virtual setting, very similar to a school classroom. The aim of the present study is to analyze the convergent validity between the AULA and the Continuous Performance Test (CPT) of Conners. The AULA and CPT were administered correlatively to 57 children, aged 6¿16 years (26.3% female) with average cognitive ability (IQ mean = 100.56, SD¿=¿10.38) who had a diagnosis of attention deficit/hyperactivity disorder (ADHD) according to DSM-IV-TR criteria. Spearman correlations analyses were conducted among the different variables. Significant correlations were observed between both tests in all the analyzed variables (omissions, commissions, reaction time, and variability of reaction time), including for those measures of the AULA based on different sensorial modalities, presentation of distractors, and task paradigms. Hence, convergent validity between both tests was confirmed. Moreover, the AULA showed differences by gender and correlation to Perceptual Reasoning and Working Memory indexes of the WISC-IV, supporting the relevance of IQ measures in the understanding of cognitive performance in ADHD. In addition, the AULA (but not Conners¿ CPT) was able to differentiate between ADHD children with and without pharmacological treatment for a wide range of measures related to inattention, impulsivit

The results obtained with the model show that buccal midazolam is more cost-effective than rectal diazepam due to a reduction in the need to call out ambulances and for stays in hospital, as well as an improved health-related quality of life.

Prolonged seizures and status epilepticus are common neurological medical emergencies. Early and appropriate treatment is essential to reduce morbidity and mortality. Most seizures occur in the community, so parents and caregivers must be prepared for their management. Benzodiazepines (BZD) are the first-line drugs used, with rectal diazepam (DZPr) being the most commonly used in pre-hospital treatment in Spain. In September 2011, the European Medicines Agency (EMA) authorized the use of oromucosal midazolam (MDZb) for the treatment of prolonged acute convulsive seizures in patients aged 3 months to <18 years. MDZb has a rapid onset, short duration of effect, and avoids first-pass hepatic metabolism. MDZb has shown to be at least as or more effective than DZPr to stop the seizures. Buccal administration is easier and more socially accepted, especially in adolescents and adults. It is a safe drug with similar effects to other BZD; MDZb improves the overall cost-effectiveness of seizures management

El desarrollo cognitivo en el síndrome de Dravet cursa con un enlentecimiento o estancamiento de las habilidades cognitivas durante la niñez. La clasificación del síndrome dentro de las encefalopatías epilépticas sugiere un papel importante de la actividad epileptiforme en la génesis de las alteraciones cognitivas. En esta revisión, se pone de manifiesto que el fenotipo epiléptico y la actividad crítica e intercrítica no explican por sí solas la evolución cognitiva en niños con síndrome de Dravet. Cambios sustanciales en el tratamiento, con repercusión sobre el desarrollo cognitivo, vendrán con probabilidad de la mano de terapias que actúen modificando directamente la fisiopatología del síndrome y no tanto sus consecuencias.

There is a need for more explicit guidance covering educational and healthcare settings, clearer information to parents and schools, and more systematic training to be made available to caregivers. This is to ensure that all children at risk of a prolonged convulsive seizure receive rescue medication in a timely manner, regardless of where their seizure occurs.

Dravet syndrome is an epileptic encephalopathy characterized by multiple types of seizures. We report the first case of musicogenic reflex seizures in a 7-year-old male with a mutation in the SCN1A gene causing Dravet syndrome. Reflex seizures have been reported in patients with Dravet syndrome provoked by body temperature elevation, looking at visual patterns, or under intermittent photic stimulation. The case we report widens the spectrum of reflex seizures recorded in patients with Dravet syndrome. Cortical hyperexcitability of genetic origin could explain the tendency of these patients to experience reflex seizures.

To date, our group has described 37 patients, of whom 27 have mutations in POLR3A and 10 in POLR3B, respectively. Altogether, our results further support the proposal that POLR3A and POLR3B mutations are a major cause of hypomyelinating leukodystrophies and suggest that POLR3A mutations are more frequent.

Dravet syndrome is a drug resistant epilepsy which starts in the first year of life with febrile seizures, followed by cognitive impairment and epilepsy with multiple seizure types. Diagnosis has been typically made at the age of three to four years, but earlier diagnosis is now possible as clinical features are better recognised and molecular diagnosis is available. PATIENTS AND METHODS: We studied a series of 14 children with Dravet syndrome or Dravet spectrum epilepsy. A screening test, developed by other authors to distinguish the febrile seizures in Dravet syndrome from febrile seizures from other origin, was applied to the clinical features of the seizures occurring during the first year of life in our patients. RESULTS: Clinical suspicion of Dravet spectrum epilepsy was possible in 100% of children in our series. Moreover, taking into consideration only the first seizure, 79% of patients scored sufficiently to detect Dravet syndrome. CONCLUSIONS: Dravet syndrome can be recognised during the first year of life. It is important that physicians are made aware of these clinical criteria capable to distinguish febrile seizures in Dravet syndrome from febrile seizures of other origin, and set up a protocol to collect appropriate data regarding febrile seizures occurring in the first year of life.

Kabuki syndrome (KS) comprises multiple congenital abnormalities and is characterized by a peculiar facial appearance, dermatoglyphic anomalies, mental retardation, skeletal abnormalities and postnatal growth retardation. We describe the case of a 23-month-old boy with the typical features of KS who had several malformations in the veins of the brain, which had not previously been described in patients with this syndrome. The MRI phlebogram of this patient showed that the vein of Galen was dilated and that it drained anomalously. The sinus rectus was abnormal and the longitudinal inferior venous sinus was absent. In view of this finding, together with the fact that structural brain abnormalities in KS are more frequent than in other congenital syndromes with multiple malformations, we propose that MRI be used in the diagnostic work-up of all patients with KS.

The phenotype of Dravet syndrome is now better defined and early detection is already possible. As a consequence, it is now possible to use more specific antiepileptic drugs and to avoid harmful treatments. The benefits of better and prompter control of seizures and earlier cognitive interventions need to be demonstrated in prospective studies of children diagnosed in their first year of life.