Developmental outcome of electroencephalographic findings in SYNGAP1 encephalopathy.

SYNGAP1 haploinsufficiency results in a developmental and epileptic encephalopathy (DEE) causing generalized epilepsies accompanied by a spectrum of neurodevelopmental symptoms. Concerning interictal epileptiform discharges (IEDs) in electroencephalograms (EEG), potential biomarkers have been postulated, including changes in background activity, fixation-off sensitivity (FOS) or eye closure sensitivity (ECS). In this study we clinically evaluate a new cohort of 36 SYNGAP1-DEE individuals. Standardized questionnaires were employed to collect clinical, electroencephalographic and genetic data. We investigated electroencephalographic findings, focusing on the cortical distribution of interictal abnormalities and their changes with age. Among the 36 SYNGAP1-DEE cases 18 presented variants in the SYNGAP1 gene that had never been previously reported. The mean age of diagnosis was 8 years and 8 months, ranging from 2 to 17 years, with 55.9% being male. All subjects had global neurodevelopmental/language delay and behavioral abnormalities; 83.3% had moderate to profound intellectual disability (ID), 91.7% displayed autistic traits, 73% experienced sleep disorders and 86.1% suffered from epileptic seizures, mainly eyelid myoclonia with absences (55.3%). A total of 63 VEEGs were revised, observing a worsening of certain EEG findings with increasing age. A disorganized background was observed in all age ranges, yet this was more common among older cases. The main IEDs were bilateral synchronous and asynchronous posterior discharges, accounting for ≥50% in all age ranges. Generalized alterations with maximum amplitude in the anterior region showed as the second most frequent IED (≥15% in all age ranges) and were also more common with increasing age. Finally, diffuse fast activity was much more prevalent in cases with 6 years or older. To the best of our knowledge, this is the first study to analyze EEG features across different age groups, revealing an increase in interictal abnormalities over infancy and adolescence. Our findings suggest that SYNGAP1 haploinsufficiency has complex effects in human brain development, some of which might unravel at different developmental stages. Furthermore, they highlight the potential of baseline EEG to identify candidate biomarkers and the importance of natural history studies to develop specialized therapies and clinical trials.

[Vitamin D in a pediatric population after the end of home lockdown: a prospective study]. / Vitamina D en pediatría tras el fin del confinamiento domiciliario: estudio prospectivo.

Home confinement during the onset of the SARS-CoV-2 pandemic decreased sunlight exposure, the main source of vitamin D in the body. OBJECTIVE: To evaluate the impact of SARS-CoV-2 confinement on 25-hydroxyvitamin D (25-OH-VD) levels in a pediatric population. PATIENTS AND METHODS: Observational study in a Spanish pediatric population between June and October 2020. 25-OH- VD levels were measured by electrochemiluminescence and several related variables were collected (anthropometry, sex, skin phototype, date, calcium level, inorganic phosphorus, parathormone, and alkaline phosphatase). The child's companion answered a survey that included the following aspects: access to open air in the house where the confinement took place, hours of sunlight per day received by the child after the end of the confinement, regular use of sunscreen with outdoor exposure, skin phototype of the child, type of milk the child usually drinks, 25-OH-VD supplementation intake, and if so, dosage and adherence to treatment. RESULTS: 123 children participated, mean age 8.15 years (95%CI 7.52-8.79), and 56.1% were female. The median 25-OH-VD was 27.70 ng/ml (RIC 22.7533.60), and 14% presented 25-OH-VD insufficiency (< 20 ng/ml). 25-OH-VD levels presented an ascending correlation slope as the date moved away from the end of confinement (Rho 0.467; p < 0.001), being related to sunshine hours (Rho 0.368; p < 0.001). 25-OH-VD levels were higher in patients with photoprotection (median 29.9 vs 23.5 ng/ml, p = 0.005), with differences according to skin phototype (p = 0.032), but were not related to age, weight z-score, height z-score, body mass index z-score, or the presence of a balcony or garden at home. CONCLUSION: The rate of 25-OH-VD insufficiency at the end of confinement was not higher than in previous studies. 25-OH-VD levels increased progressively in relation to the hours of sunlight exposure and to the summer months. Interestingly, 25-OH-VD levels were higher in children using phot.

Crisis neonatales y evolución a epilepsia en un hospital de tercer nivel / Neonatal seizures and progression to epilepsy in a tertiary hospital

Introducción Las convulsiones neonatales son un reto diagnóstico, dada la inmadurez del recién nacido. La mayoría son secundarias a un evento agudo. Un pequeño porcentaje constituye el inicio de una epilepsia. Objetivos Analizar a los neonatos ingresados en un hospital de tercer nivel con diagnóstico de crisis entre noviembre de 2009 y mayo de 2021, y su evolución posterior a epilepsia. Material y métodos. Se ha realizado un estudio observacional retrospectivo utilizando la base de datos del hospital. Se ha recogido la información de los neonatos con diagnóstico en el alta de ‘convulsiones’ o ‘encefalopatía hipóxico-isquémica moderada o grave’. Se analizaron distintas variables: etiología de las crisis, tipo, persistencia temporal, tratamiento y correlato electroclínico. Resultados De 165 pacientes, 55 presentaron crisis neonatales. En cuanto a la etiología, 43 pacientes (78%) tuvieron crisis secundarias a un evento agudo, de las cuales 19 (34%) fueron encefalopatías hipóxico-isquémicas, y 22 (40%), otras alteraciones agudas. En seis (11%) se encontró alteración genética. Trece pacientes (24%) evolucionaron a una epilepsia posterior, de los cuales siete presentaron una epilepsia sintomática, con un período de latencia tras el evento agudo en dos pacientes. Seis pacientes tuvieron epilepsia neonatal con crisis no provocadas. Veintidós (62%) mostraron correlato electroclínico. El 100% de las crisis confirmadas fueron focales. Todas las crisis se trataron. El fármaco de elección fue el fenobarbital. Conclusiones El diagnóstico de convulsiones neonatales requiere una alta sospecha clínica y una confirmación electroclínica. La mayoría tiene evolución favorable, pero un porcentaje constituye el inicio de una epilepsia, cuya identificación determinará su manejo terapéutico. (AU)

INTRODUCTION Given the immaturity of the newborn, neonatal seizures are a diagnostic challenge. Most of them are secondary to an acute event. A small percentage constitute the onset of epilepsy. AIMS. The aim was to analyse neonates with a diagnosis of seizures admitted to a tertiary hospital between November 2009 and May 2021, and their subsequent progression to epilepsy. Material and methods. A retrospective observational study was carried out using the hospital database. Information was collected on neonates with a discharge diagnosis of ‘seizures’ or ‘moderate or severe hypoxic-ischaemic encephalopathy’. Different variables were analysed: aetiology of the seizures, type, persistence over time, treatment and electroclinical correlates. RESULTS Of 165 patients, 55 presented neonatal seizures. As regards aetiology, 43 patients (78%) had seizures secondary to an acute event, of which 19 (34%) were hypoxic-ischaemic encephalopathies, and 22 (40%) had other acute disorders. Genetic alteration was found in six of them (11%). Thirteen patients (24%) progressed to subsequent epilepsy, of whom seven had symptomatic epilepsy, with a period of latency after the acute event in two patients. Six patients had neonatal epilepsy with unprovoked seizures. Twenty-two (62%) showed electroclinical correlates. All of the confirmed crises (100%) were focal. All the seizures were treated. The drug of choice was phenobarbital. CONCLUSIONS Diagnosis of neonatal seizures requires high clinical suspicion and electroclinical confirmation. Most of them progress favourably, but a percentage constitute the onset of epilepsy, the identification of which will determine their therapeutic management. (AU)

Predictors of autism spectrum disorder diagnosis in a spanish sample of preterm children with very low birthweight: A cross-sectional study.

Background and Aims: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a higher likelihood of being diagnosed in preterm populations. Likewise, low birthweight has also been connected with an increased likelihood of ASD. The objectives were to study the frequency and define the relationship between ASD, gestational age, birthweight, and growth percentiles for preterm children. Methods: A sample of preterm children with very low birthweight was selected from the Spanish population at 7-10 years old. Families were contacted from the hospital, and they were offered an appointment to conduct a neuropsychological assessment. The children who showed signs of ASD were referred to the diagnostic unit for differential diagnosis. Results: A total of 57 children completed full assessments, with 4 confirmed ASD diagnoses. The estimated prevalence was 7.02%. There were statistically significant weak correlations between ASD and gestational age (τb = -0.23), and birthweight (τb = -0.25), suggesting there is a higher likelihood of developing ASD for those born smaller or earlier in their gestation. Conclusion: These results could improve ASD detection and outcomes for this vulnerable population while also supporting and enhancing previous findings.

Effect of a Focused Social and Communication Intervention on Preterm Children with ASD: A Pilot Study.

While advances in intensive neonatal care have greatly improved survival rates among preterm infants, incidence of neurodevelopmental disorders in this group is still high, with autism spectrum disorder (ASD) being one of the most frequent. To this end, we conducted a social-communication intervention aimed at investigating efficacy in social-communicative skills. Eighteen children (preterm and full-term with ASD and preterm children) aged 18 through 20 months participated in the study. Our findings indicate that most participants in the intervention groups registered significant improvements in terms of socio-communicative skills, cognitive development, and language. Accordingly, these pilot data underscore the need for further research and implementation of early interventions in young preterm children with ASD.

Spanish Cultural Validation of the Modified Checklist for Autism in Toddlers, Revised.

The Modified Checklist for Autism in Toddlers-revised/follow-up (M-CHAT-R/F) was developed to reduce the number of cases requiring telephone verification. The aim of this study was to validate a Spanish version of the M-CHAT-R/F in the Spanish public health system. The M-CHAT-R/F was translated, culturally adapted, and then administered to 6625 children. Of the 39 positive screening cases, 15 children were diagnosed with autism spectrum disorder (ASD) and 24 with non-ASD disorders or delays. The sensitivity was 0.79 and specificity of 0.99. Positive and negative predictive values were 0.39 and 0.99, respectively. These results are similar to the English equivalent, though observed prevalence was lower. This study supports Spanish National Health System policy makers to consider a universal ASD screening program.

Trastorno del espectro autista y prematuridad: hacia un programa de cribado prospectivo / Autism spectrum disorder and prematurity: towards a prospective screening program

Introducción. La prevalencia de trastornos del espectro autista (TEA) comunicada en estudios actuales en grupos de riesgo como son los recién nacidos pretermino o con bajo peso al nacer, es más alta que en la población normal. Este hecho ha supuesto el incremento en los últimos anos de estudios de cribado que investigan posibles factores de riesgo de TEA en los recién nacidos pretermino y su trayectoria evolutiva. Objetivo. Exponer los resultados de los principales estudios de cribado de recién nacidos pretermino a fin de presentar recomendaciones de cribado en esta población de riesgo. Desarrollo. Los resultados de los estudios presentados sugieren la posibilidad de que la trayectoria del desarrollo sociocomunicativo y conductual de los recién nacidos pretermino difiera de lo esperado si su nacimiento se hubiera producido a término, lo que apoya el hecho de que se realicen programas de cribado basados en una monitorización evolutiva del desarrollo y se utilicen herramientas de cribado adaptadas a esta población de riesgo. Conclusión. Los menores prematuros son un grupo de riesgo que muestra características diferenciales para el cribado de TEA (AU)

Introduction. The prevalence of autism spectrum disorders (ASD) reported in current studies in risk groups such as preterm or low birth weight infants is higher than in the normal population. This fact has led to the increase in recent years of screening studies that investigate possible risk factors for ASD in preterm newborns and their developmental trajectory. Aim. To present the results of the main screening studies of preterm newborns in order to propose screening recommendations for this population at risk. Development. The results of the studies presented suggest the possibility that the trajectory of socio-communicative and behavioral development of preterm infants differed from what was expected if their birth had occurred at term. This supports the fact that screening programs are carried out based on developmental surveillance and that it is advisable to use screening tools adapted to this population at risk. Conclusion. Premature children are a risk group that shows differential characteristics for the screening of ASD (AU)

Crisis parainfecciosas: estudio retrospectivo multicéntrico / Para-infectious seizures: a retrospective multicentre study

INTRODUCCIÓN: Las crisis parainfecciosas son crisis convulsivas afebriles en el contexto de infecciones banales en niños sin afectación neurológica, siendo aún una patología poco conocida en nuestro medio. MÉTODOS: Estudio retrospectivo multicéntrico donde se incluye a pacientes con crisis única o múltiple en el contexto de una infección banal afebril, con desarrollo psicomotor normal. RESULTADOS: Se recogió a 38 pacientes (47% varones, 53% mujeres) en un periodo de 3 años (2012-2015) con edad media de 2,1 años. El 7,9% presentaba antecedentes de crisis febriles. La media de crisis por paciente fue de 2,2, siendo el 57,9% crisis tónico-clónicas generalizadas, con una duración media de 3,2 min. Se realizó electroencefalograma durante su ingreso al 73,7%. Se efectuó punción lumbar en un 34,2% (todas normales) y prueba de neuroimangen en el 36,9%, siendo la más realizada la RM craneal en el 21,1%, sin hallazgos patológicos. El proceso infeccioso más frecuente (68%) fue tener gastroenteritis aguda seguida de la infección respiratoria de vías altas (32%). El 63,2% no precisó medicación anticomicial. En urgencias el fármaco más usado fue el diazepam rectal. Posteriormente, debido a la agrupación de crisis, un 28,9% de los casos precisó administración de fármacos por vía intravenosa (el más usado fue el ácido valproico), manteniéndose en el 16% tratamiento antiepiléptico al alta. El 76,3% de los pacientes fue diagnosticado al alta de crisis parainfecciosas. CONCLUSIONES: Es fundamental el conocimiento de las crisis parainfecciosas, su diagnóstico clínico y evolución benigna, ya que su identificación evita la realización de pruebas complementarias y tratamientos innecesarios

INTRODUCTION: Para-infectious seizures are afebrile seizures that are associated with mild infections, and occur in children with no pre-existing neurological illness. They are still little known in our environment. METHODS: A multicentre retrospective study was conducted that included patients with normal psychomotor development and had presented with one or more seizures in the context of a mild afebrile infection. RESULTS: A total of 38 patients (47% male, 53% female) were included in the study over a period of three years (2012-2015). The mean age was 2.1 years. A previous history of febrile seizures was found in 7.9% of them. Mean number of seizures per patient was 2.2, with 57.9% of them being tonic-clonic seizures. The mean duration of seizures was 3.2minutes. An EEG was performed during admission in 73.7% of cases. Lumbar punctures were performed in 34.2% of cases. All were normal. Neuroimaging tests were carried out in 36.9% of cases. Brain MRI was the imaging test performed in most cases (21.1%), with no any pathological findings. The most frequent infection found was acute gastroenteritis (68%), followed by upper respiratory tract infection (32%). Almost two-thirds (63.2%) of patients did not require anticonvulsant medication. Rectal diazepam was the most frequently used drug in emergencies. Intravenous medication was required by 28.9% of patients due to repeated seizures. The most frequently used drug in the non-emergency setting was valproic acid. Anticonvulsant treatment was continued after discharge in 16% of patients. Para-infectious seizures was the diagnosis in 76.3% of cases when discharged. CONCLUSIONS: Knowledge of para-infectious seizures, their clinical diagnosis and benign course is crucial, as this would avoid further testing and unnecessary treatments

[Para-infectious seizures: A retrospective multicentre study]. / Crisis parainfecciosas: estudio retrospectivo multicéntrico.

INTRODUCTION: Para-infectious seizures are afebrile seizures that are associated with mild infections, and occur in children with no pre-existing neurological illness. They are still little known in our environment. METHODS: A multicentre retrospective study was conducted that included patients with normal psychomotor development and had presented with one or more seizures in the context of a mild afebrile infection. RESULTS: A total of 38 patients (47% male, 53% female) were included in the study over a period of three years (2012-2015). The mean age was 2.1 years. A previous history of febrile seizures was found in 7.9% of them. Mean number of seizures per patient was 2.2, with 57.9% of them being tonic-clonic seizures. The mean duration of seizures was 3.2minutes. An EEG was performed during admission in 73.7% of cases. Lumbar punctures were performed in 34.2% of cases. All were normal. Neuroimaging tests were carried out in 36.9% of cases. Brain MRI was the imaging test performed in most cases (21.1%), with no any pathological findings. The most frequent infection found was acute gastroenteritis (68%), followed by upper respiratory tract infection (32%). Almost two-thirds (63.2%) of patients did not require anticonvulsant medication. Rectal diazepam was the most frequently used drug in emergencies. Intravenous medication was required by 28.9% of patients due to repeated seizures. The most frequently used drug in the non-emergency setting was valproic acid. Anticonvulsant treatment was continued after discharge in 16% of patients. Para-infectious seizures was the diagnosis in 76.3% of cases when discharged. CONCLUSIONS: Knowledge of para-infectious seizures, their clinical diagnosis and benign course is crucial, as this would avoid further testing and unnecessary treatments.

Tratamiento con hormona de crecimiento en 2 pacientes con deleción 22q11.21 / Growth hormone treatment in 2 patients with 22q11.21 deletion syndrome

No disponible

[From early detection to early care: intervention strategies based on prospective screening]. / De la detección precoz a la atención temprana: estrategias de intervención a partir del cribado prospectivo.

INTRODUCTION. The challenge of early detection can be tackled from an evolutionary perspective. Early intervention treatments have shown themselves to be effective provided that they are applied systematically as part of the strategic planning of the treatment. AIMS. The aim of this study is to provide an updated review in response to the criticism targeted towards early detection and to offer some considerations on the intervention strategy. Our research is based on a review of the early care techniques that are commonly used within the field of autism and it intends to reflect the most significant aspects that can be deduced from the experiments and studies carried out to date. CONCLUSIONS. From the findings of the review it can be concluded that early detection may be more efficient if carried out within the framework of developmental surveillance, which also offers the opportunity to provide guidance on the child's development. Early care is an effective resource for attending to the needs of children with autism. Professionals have the duty to assess the work they do on available treatments with a reflexive, judicious attitude, taking into account the values and preferences of the families. Programmes must focus on the core symptoms and apply the active ingredients of the treatment.

TITLE: De la deteccion precoz a la atencion temprana: estrategias de intervencion a partir del cribado prospectivo.Introduccion. El reto de la deteccion precoz puede realizarse desde una perspectiva evolutiva. Los tratamientos de intervencion temprana han demostrado su eficacia siempre y cuando se apliquen sistematicamente en el marco de una planificacion estrategica del tratamiento. Objetivos. Proporcionar una revision actualizada para responder a las criticas a la deteccion precoz y aportar una reflexion sobre la estrategia de intervencion, basada en la revision de las tecnicas de atencion temprana usuales en el campo del autismo, reflejando los aspectos mas relevantes que se deducen de las experiencias y estudios llevados a cabo hasta el momento. Conclusiones. Tras la revision realizada se concluye que la deteccion precoz puede ser mas eficiente si se lleva a cabo en el marco de la vigilancia del desarrollo, que ademas ofrece la oportunidad de proporcionar orientacion sobre el desarrollo del menor. La atencion temprana constituye un recurso eficaz para atender las necesidades del menor con autismo. Los profesionales tienen la responsabilidad de evaluar el trabajo que hacen con una actitud reflexiva y critica sobre los tratamientos disponibles tomando en consideracion los valores y las preferencias de las familias. Los programas deben centrarse en los sintomas nucleares aplicando ingredientes activos del tratamiento.

De la detección precoz a la atención temprana: estrategias de intervención a partir del cribado prospectivo / From early detection to early care: intervention strategies based on prospective screening

Introducción. El reto de la detección precoz puede realizarse desde una perspectiva evolutiva. Los tratamientos de intervención emprana han demostrado su eficacia siempre y cuando se apliquen sistemáticamente en el marco de una planificación estratégica del tratamiento. Objetivos. Proporcionar una revisión actualizada para responder a las críticas a la detección precoz y aportar una reflexión sobre la estrategia de intervención, basada en la revisión de las técnicas de atención temprana usuales en el campo del autismo, reflejando los aspectos más relevantes que se deducen de las experiencias y estudios llevados a cabo hasta el momento. Conclusiones. Tras la revisión realizada se concluye que la detección precoz puede ser más eficiente si se lleva a cabo en el marco de la vigilancia del desarrollo, que además ofrece la oportunidad de proporcionar orientación sobre el desarrollo del menor. La atención temprana constituye un recurso eficaz para atender las necesidades del menor con autismo. Los profesionales tienen la responsabilidad de evaluar el trabajo que hacen con una actitud reflexiva y crítica sobre los tratamientos disponibles tomando en consideración los valores y las preferencias de las familias. Los programas deben centrarse en los síntomas nucleares aplicando ingredientes activos del tratamiento (AU)

Introduction. The challenge of early detection can be tackled from an evolutionary perspective. Early intervention treatments have shown themselves to be effective provided that they are applied systematically as part of the strategic planning of the treatment. Aims. The aim of this study is to provide an updated review in response to the criticism targeted towards early detection and to offer some considerations on the intervention strategy. Our research is based on a review of the early care techniques that are commonly used within the field of autism and it intends to reflect the most significant aspects that can be deduced from the experiments and studies carried out to date. Conclusions. From the findings of the review it can be concluded that early detection may be more efficient if carried out within the framework of developmental surveillance, which also offers the opportunity to provide guidance on the child’s development. Early care is an effective resource for attending to the needs of children with autism. Professionals have the duty to assess the work they do on available treatments with a reflexive, judicious attitude, taking into account the values and preferences of the families. Programmes must focus on the core symptoms and apply the active ingredients of the treatment (AU)