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.

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.

[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.

[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.