Continuous Electroencephalogram (cEEG) Findings and Neurodevelopmental Outcomes in Neonates with Congenital Heart Disease (CHD) at 12-24 Months of Age.

OBJECTIVE: This study aims to assess the role of continuous EEG (cEEG) background patterns and duration of cross-clamp time and cardiopulmonary bypass (CPB) in children with congenital heart disease (CHD) undergoing cardiac surgery and its correlation with abnormal neurodevelopmental outcomes at 12-24 months on Bayley Scales of Infant and Toddler Development (BSID-III). METHODS: This retrospective cohort study included infants with CHD and cEEG monitoring, who underwent surgery by 44 weeks gestational age. RESULTS: 34 patients were included, who were operated at median age - 7 days. Longer duration of cross- camp time was associated with poor language composite scores (LCS) (p value = 0.036). A significant association existed between severity of encephalopathy in 24-hour post-operative period and poor LCS (p value = 0.026). CONCLUSION: Majority of neonates with CHD have below average cognitive, language and motor composite scores on BSID-III. Longer duration of cross-clamp time and severity of encephalopathy during 24-hour post-operative EEG monitoring are associated with poor LCS.

Caregiver Perspective of Benefits and Side Effects of Anti-Seizure Medications in CDKL5 Deficiency Disorder from an International Database.

BACKGROUND AND OBJECTIVE: CDKL5 deficiency disorder presents as a challenging condition with early-onset refractory seizures, severe developmental delays, and a range of other neurological symptoms. Our study aimed to explore the benefits and side effects of anti-seizure medications (ASMs) in managing seizures among individuals with CDKL5 deficiency disorder, drawing on data from the International CDKL5 Disorder Database. METHODS: Data for this retrospective cohort study were obtained from the International CDKL5 Disorder Database, which contains responses from a baseline questionnaire administered between 2012 and 2022 and a follow-up questionnaire administered between 2018 and 2019. Families of eligible individuals were asked to provide information on ASMs that were previously and currently taken, the dose prescribed, the age at starting the medications, and the age at discontinuation for past medications. The outcome variables of interest were perceived seizure-related benefits for the current and past use of ASMs and caregiver-reported side effects. Rescue medications and infrequently used ASMs were excluded from the analysis. Descriptive statistics were used to summarise the characteristics of the study population. RESULTS: The study included 399 children and adults with CDKL5 deficiency disorder, descriptively analysing the perceived benefits and side effects of 23 unique ASMs based on caregiver reports. The study identified levetiracetam, topiramate, sodium valproate, vigabatrin, phenobarbital and clobazam as the most used ASMs. Notably, cannabidiol showed highly beneficial outcomes with few side effects, whereas levetiracetam and phenobarbital exhibited less favourable benefit-to-side-effect ratios. Dual therapy involving sodium valproate and levetiracetam was only used a small number (n = 5) of times but appeared effective in reducing seizure activity with relatively few side effects. Compared with monotherapy, polytherapy had a relatively higher likelihood of reported side effects than benefits. CONCLUSIONS: The study, leveraging a large sample size that exceeds that of previous research, emphasises the complex nature of seizure management in CDKL5 deficiency disorder. Our findings underscore the necessity of ongoing research to optimise treatment strategies, considering both the efficacy of seizure control and the potential for adverse effects. The study also points to the need for future investigations into the therapeutic potential of emerging treatments such as ganaxolone and the unresolved efficacy of cannabis products in seizure management.

CDKL5 Deficiency Disorder: Some Lessons Learned 20 Years After the First Description.

Loss of function variants in the Cyclin-dependent kinase-like 5 gene (CDKL5) causes CDKL5 deficiency disorder (CDD). Most cases of CDD are due to a de novo missense or truncating variants. The CDKL5 gene was discovered in 1998 as part of the genomic mapping of the chromosome Xp22 region that led to the discovery of the serine-threonine kinases STK9. Since then, there have been significant advancements in the description of the disease in humans, the understanding of the pathophysiology, and the management of the disease. There have been many lessons learned since the initial description of the condition in humans in 2003. In this article, we will focus on pathophysiology, clinical manifestations, with particular focus on seizures because of its relevance to the medical practitioners and researchers and guidelines for management. We finalize the manuscript with the voice of the parents and caregivers, as discussed with the 2019 meeting with the Food and Drug Administration.

Healthcare utilization and clinical characteristics of genetic epilepsy in electronic health records.

Understanding the clinical characteristics and medical treatment of individuals affected by genetic epilepsies is instrumental in guiding selection for genetic testing, defining the phenotype range of these rare disorders, optimizing patient care pathways and pinpointing unaddressed medical need by quantifying healthcare resource utilization. To date, a matched longitudinal cohort study encompassing the entire spectrum of clinical characteristics and medical treatment from childhood through adolescence has not been performed. We identified individuals with genetic and non-genetic epilepsies and onset at ages 0-5 years by linkage across the Cleveland Clinic Health System. We used natural language processing to extract medical terms and procedures from longitudinal electronic health records and tested for cross-sectional and temporal associations with genetic epilepsy. We implemented a two-stage design: in the discovery cohort, individuals were stratified as being 'likely genetic' or 'non-genetic' by a natural language processing algorithm, and controls did not receive genetic testing. The validation cohort consisted of cases with genetic epilepsy confirmed by manual chart review and an independent set of controls who received negative genetic testing. The discovery and validation cohorts consisted of 503 and 344 individuals with genetic epilepsy and matched controls, respectively. The median age at the first encounter was 0.1 years and 7.9 years at the last encounter, and the mean duration of follow-up was 8.2 years. We extracted 188,295 Unified Medical Language System annotations for statistical analysis across 9659 encounters. Individuals with genetic epilepsy received an earlier epilepsy diagnosis and had more frequent and complex encounters with the healthcare system. Notably, the highest enrichment of encounters compared with the non-genetic groups was found during the transition from paediatric to adult care. Our computational approach could validate established comorbidities of genetic epilepsies, such as behavioural abnormality and intellectual disability. We also revealed novel associations for genitourinary abnormalities (odds ratio 1.91, 95% confidence interval: 1.66-2.20, P = 6.16 × 10-19) linked to a spectrum of underrecognized epilepsy-associated genetic disorders. This case-control study leveraged real-world data to identify novel features associated with the likelihood of a genetic aetiology and quantified the healthcare utilization of genetic epilepsies compared with matched controls. Our results strongly recommend early genetic testing to stratify individuals into specialized care paths, thus improving the clinical management of people with genetic epilepsies.

Modification of a parent-report sleep scale for individuals with CDKL5 deficiency disorder: a psychometric study.

STUDY OBJECTIVES: Sleep difficulties are common in CDKL5 deficiency disorder (CDD), a developmental and epileptic encephalopathy (DEE). This study evaluated the factor structure of the Disorders of Initiating and Maintaining Sleep (DIMS), Disorders of Excessive Daytime Somnolence (DOES) and Sleep Breathing Disorders (SBD) domains of the Sleep Disturbance Scale for Children (SDSC) for CDD. METHODS: A cross-sectional psychometric study design was used. Data were collected for 125 individuals aged 3 years or older who attended a US Centers of Excellence clinic or registered with the International CDKL5 Disorder Database. RESULTS: The median age was 10.3 years (range 3.2 - 40.7 years) and 105 (84%) were female. Two of the three SBD items related were not observed by most respondents and analysis was restricted to the DIMS and DOES domains. Using all items in the initial confirmatory factor analysis, two items in the DIMS domain and one item in the DOES domain loaded poorly. After deleting these items and repeating the analysis, item loading (0.524-0.814) and internal consistency (DIMS: 0.78, DOES: 0.76) statistics were good. The square of the inter-domain correlation coefficient was 0.17, less than Average Variance Extracted values for both domains and indicating good discriminant validity. The Tucker-Lewis and Comparative Fit indices were slightly lower than the threshold of >0.9 for establishing goodness of fit. CONCLUSIONS: The modified DIMS and DOES domains from the SDSC could be suitable clinical outcome assessments of insomnia and related impairments in CDD and potentially other DEE conditions.

Atención primaria de salud en la enfermedad cerebrovascular / Primary health care in cerebrovascular disease

Se realiza un estudio retrospectivo-descriptivo para evaluar las acciones de salud que el Médico de la Familia realizó sobre los pacientes con enfermedad cerebrovascular y que fallecieron por ese motivo en el Área de Salud "Carlos Verdugo", Matanzas, durante los años 1994 y 1995. Se estudiaron 50 fallecidos en entrevista médico-familiar; se obtuvieron los datos de, edad, sexo y antecedentes patológicos personales que recogieron: enfermedades crónicas y factores de riesgo; dispensarización, que recogió número de controles realizados en los últimos 12 meses que precedieron a la defunción ya fueran en consultas, visitas de terreno y visitas integrales, así como el cumplimiento del tratamiento indicado. Se encontró que se dispensarizaron en el 100 porciento de los fallecidos la hipertensión arterial, la cardiopatía isquémica, la obesidad y la hiperlipidemia. El 72,4 porciento (12 fallecidos) recibió entre 1 y 3 controles en consultas. El 79,3 porciento (16 fallecidos) recibió entre 1 y 3 controles en visitas de terreno y el 100 porciento se controló entre 1 y 3 ocasiones en visitas integrales a la familia. Se concluyó que el cumplimiento del tratamiento indicado para la enfermedad cerebrovascular, los factores de riesgo y enfermedades crónicas no fue satisfactorio en el grupo estudiado. Se recomienda realizar un mayor número de controles en la atención primaria a los pacientes con enfermedad cerebrovascular sobre todo cuando en la dispensarización se encuentra la asociación hipertensión arterial, hábito de fumar y mayores de 65 años

Trastornos de conducta en el niño epiléptico: Su relación con los resultados escolares

Para conocer la influencia de los trastornos de conducta sobre los resultados escolares de niños epilépticos se estudiaron 30 niños con más de 1 año de evolución de la enfermedad y que asistían a escuelas de enseñaza primarias. En entrevistas a padres y maestros se recogió valoración sobre su conducta y los resultados académicos del último curso escolar y se realizó un test de concentración de la atención. Se halló que el 70 % refiere algún trastorno de conducta. Se observó una relación significativa entre los resultados escolares M y la hiperactividad (p < 0,05), las dificultades en la concentración (p < 0,025) y la distracción (p < 0,01). Se concluye en que los trastornos de conducta tienen una influencia negativa sobre los resultados escolares del niño epiléptico.

To know the influence of the behaviour disorders on the school results of the epileptic children, 30 of them with more than a year of evaluation and who attend primary school were studied. Information about their behavior and academic results was gathered by the interviews made to their parents and teachers. A test was conducted to check the concentration of attention. It was found that 70 % had some behavior disorder. A significant relation was observed among the bad marks and hyperactivity (p < 0.05), the difficulties in the concentration (p < 0.025), and the distraction (p < 0.01). It is concluded that the behavior disorders exert a negative influence on the academic results of the epileptic child.

Influencia de la medicación antiepiléptica sobre los resultados escolares de niños epilépticos

Con el objetivo de conocer la influencia de la medicación antiepiléptica sobre los resultados escolares se estudiaron 30 niños que padecen crisis epilépticas parciales y que asisten a escuelas primarias normales. En entrevista familiar se recogió: medicación antiepiléptica usada, dosis en sangre y resultados académicos del último curso escolar que se correlacionó con las variables estudiadas con el test de correlación múltiple. El 80 % (24 niños) recibió tratamiento en monoterapia y 6 (20 %) politerapia. La fenitoína correlacionó significativamente (p < 0,005) con los resultados escolares M. Existe relación de los niveles elevados de droga en sangre con los peores resultados académicos.

With the aim of knowing the influence of antiepileptic drug therapy on learning outcomes, 30 children with partial epileptic crisis that go to normal primary schools, were studied. These data were collected in family interviews: antiepileptic drug therapy used, dose in blood, and academic outcomes in the last school course correlated with the variables studied with the multiple correlation test. Twenty four children (80 %) received monotherapy treatment, and six (20 %) received politherapy. Phenytoin significantly correlated (p < 0.005) with M school outcomes. There is a relation of the increased drug levels in blood with the worst academic results.

Evaluación psicopedagógica de un grupo de niños epilépticos que asisten a escuelas primarias

Se estudiaron 30 niños que padecen crisis epilépticas parciales y que asisten a escuelas primarias normales, con el objetivo de conocer si presentan dificultades escolares y en qué asignaturas, para esto se realizó una evaluación psicopedagógica. Los resultados se compara-ron con un grupo control de 30 niños para lo cual se utilizó el test de comparación de medias. Se halló que 18 niños del grupo estudio (60 %) y 9 del grupo control (30 %) presentaron alguna dificultad en el cumplimiento de los objetivos del grado escolar, con una diferencia significativa entre los grupos de p < 0,001. Se concluye que las mayores dificultades escolares se encuentran en las áreas de Lectura y Español.

Thirty children with partial epileptic crisis that go to normal primary schools were studied, with the objective of knowing if they have learning difficulties, and in which subjects; with this purpose, a psychopedagogical assessment was carried out. Results were compared with a 30 children control group, and this was made through the mean comparison test. It was found that 18 children from the study group (60 %), and 9 from the control group (30 %) presented some difficulties in achieving the goals of the school grade with a significant difference between groups of p < 0,001. It is concluded that the highest learning difficulties are in the areas of Reading and Spanish.

Epilepsia en el nino: edad de inicio, tiempo de evolucion y situacion escolar. Su realcion con el rendimiento intelectual / Epilepsy in children: age of onset, time of evolution and school situation. Its relationship with the academic results

Se estudiaron 310 escolares epilepticos atendidos en el Instituto de Neurologia y Neurocirugia con edades entre 5 y 14 anos. Se les estudio rendimiento intelectual (test de inteligencia de Terman Merrill) clasificado segun la escala y se relaciono mediante el test de diferencias de medias con la edad de inicio de la enfermedad, el tiempo de evolucion y la situacion academica de cada ano. Se encontro que el grupo con retraso escolar difiere del que no lo tiene en cuanto a promedio alto (p < 0,01), promedio bajo, deficiente ligero y moderado (p < 0,0001( y deficiente severo (p < 0,001). Se concluye que entre los escolares epilepticos existen diferencias del rendimiento intelectual entre los que no tienen y los que tienen retraso escolar y entre los que tienen 5 o menos anos de evolucion de la enfermedad y los que tienen mas

Displasia septo-óptica o síndrome DeMorsier: presentación de 1 caso y revisión bibliográfica / Septo-optic dysplasia or DeMorsier's syndrome: a case report and bibliographic review

La displasia septo-óptica (DSO) o síndrome DeMorsier es un cuadro congénito de presentación poco frecuente, constituido por hipoplasia de 1 o más frecuentemente, de ambos nervios ópticos, ausencia de septum pellucidum y deficiencias hormonales. Se presenta una lactante de 6 meses de edad que es atendida porque la niña no mostraba interés visual y no sostenía la cabeza. Durante el embarazo su mamá tenía bajo peso corporal y padeció de infección urinaria en el último trimestre del embarazo. Durante los 2 primeros meses de vida presentó fiebre de hasta 38 º C sin que se pudiera identificar un proceso infeccioso como causante. En su examen neurológico se halló hipotonia generalizada de predominio axial con reflejos osteotendinosos presentes, nistagmus horizontal, estrabismo convergente, ausencia de reflejo visuopalpebral y en el fondo de ojo bilateralmente papilas muy pequeñas con imagen de doble contorno. El ultrasonido cerebral y la tomografía axial computadorizada (TAC) mostraron ausencia del septum pellucidum. La edad ósea se correspondió con 4 meses y se encontró deficiencia de la hormona del crecimiento con valores de 4 ng/L. Las manifestaciones clínicas de esta paciente se corresponden con la triada clásica del síndrome DeMorsier; hipoplasia del nervio óptico, agenesia del septum pellucidum y deficiencias hormonales, en este caso de hormona del crecimiento. Se presenta una actualización de esta enfermedad poco frecuente