Corrigendum: Intrafamilial variability in SLC6A1-related neurodevelopmental disorders.

[This corrects the article DOI: 10.3389/fnins.2023.1219262.].

Intrafamilial variability in SLC6A1-related neurodevelopmental disorders.

Introduction: Phenotypic spectrum of SLC6A1-related neurodevelopmental disorders (SLC6A1-NDD) includes intellectual disability (ID), autistic spectrum disorders (ASD), epilepsy, developmental delay, beginning from early infancy or after seizure onset, and other neurological features such as hypotonia and movement disorders. Data on familial phenotypic heterogeneity have been rarely reported, thus in our study we aimed to investigate intrafamilial phenotypic variability in families with SLC6A1 variants. Methods: We collected clinical, laboratory and genetic data on 39 individuals, including 17 probands, belonging to 13 families harboring inherited variants of SLC6A1. Data were collected through an international network of Epilepsy and Genetic Centers. Results: Main clinical findings in the whole cohort of 39 subjects were: (a) epilepsy, mainly presenting with generalized seizures, reported in 71% of probands and 36% of siblings or first/second-degree relatives. Within a family, the same epilepsy type (generalized or focal) was observed; (b) ID reported in 100% and in 13% of probands and siblings or first/second-degree relatives, respectively; (c) learning disabilities detected in 28% of the SLC6A1 carriers, all of them were relatives of a proband; (d) around 51% of the whole cohort presented with psychiatric symptoms or behavioral disorders, including 82% of the probands. Out of the 19 patients with psychiatric symptoms, ASD were diagnosed in 40% of them; (e) neurological findings (primarily tremor and speech difficulties) were observed 38.5% of the whole cohort, including 10 probands. Our families harbored 12 different SLC6A1 variants, one was a frameshift, two stop-gain, while the remaining were missense. No genotype-phenotype associations were identified. Discussion: Our study showed that first-or second-degree relatives presented with a less severe phenotype, featuring mainly mild intellectual and/or learning disabilities, at variance with the probands who suffered from moderate to severe ID, generalized, sometimes intractable, epileptic seizures, behavioral and psychiatric disorders. These findings may suggest that a proportion of individuals with mild SLC6A1-NDD might be missed, in particular those with an older age where genetic testing is not performed. Further studies on intrafamilial phenotypic variability are needed to confirm our results and possibly to expand the phenotypic spectrum of these disorders and benefit genetic counseling.

Celia's Encephalopathy (BSCL2-Gene-Related): Current Understanding.

Seipin, encoded by the BSCL2 gene, is a protein that in humans is expressed mainly in the central nervous system. Uniquely, certain variants in BSCL2 can cause both generalized congenital lipodystrophy type 2, upper and/or lower motor neuron diseases, or progressive encephalopathy, with a poor prognosis during childhood. The latter, Celia's encephalopathy, which may or may not be associated with generalized lipodystrophy, is caused by the c.985C >T variant. This cytosine to thymine transition creates a cryptic splicing zone that leads to intronization of exon 7, resulting in an aberrant form of seipin, Celia seipin. It has been proposed that the accumulation of this protein, both in the endoplasmic reticulum and in the nucleus of neurons, might be the pathogenetic mechanism of this neurodegenerative condition. In recent years, other variants in BSCL2 associated with generalized lipodystrophy and progressive epileptic encephalopathy have been reported. Interestingly, most of these variants could also lead to the loss of exon 7. In this review, we analyzed the molecular bases of Celia's encephalopathy and its pathogenic mechanisms, the clinical features of the different variants, and a therapeutic approach in order to slow down the progression of this fatal neurological disorder.

Transición de la epilepsia del niño al adulto. Dificultades en un objetivo no demorable / Transition from child to adult epilepsy. Difficulties with an objective that cannot be delayed

La atención pediátrica de un proceso crónico se ve limitada por el momento a partir del cual el seguimiento clínico y terapéutico debe continuarlo el especialista del área con dedicación al adulto. El retraso de la transición de la pediatría a la medicina del adulto puede originarse por causas familiares o del paciente, o bien por el profesional que diagnosticó la enfermedad. La primera emana de la incertidumbre ante lo desconocido, más intensa cuanto mayor ha sido la dificultad diagnóstica y terapéutica, al temer que el paciente se desestabilice. La segunda atañe al especialista pediátrico, que creó lazos de dependencia con el paciente por las dificultades del proceso, e incluso por el deseo de no perder protagonismo en el mismo. Demorar la transición genera problemas perjudiciales para el niño, pues superada la adolescencia mantendrá una nociva dependencia familiar y del pediatra, retrasando el necesario conocimiento de la propia enfermedad y de las limitaciones que pueden condicionarle, e impidiéndole desarrollar mecanismos para enfrentarse a su realidad vital. Más adelante, cuando llega el necesario paso a la medicina del adulto, aflora la inmadurez, que incrementa las dificultades por desconocer tanto la enfermedad como los signos de alarma, revelando inseguridad en las situaciones que vayan apareciendo. El problema se soluciona con un cambio lento y progresivo, que debe coordinarse en consultas mixtas atendidas por especialistas pediátricos y de adultos. En esta publicación se analiza esta problemática y se revisan las soluciones aconsejadas para su mejor desarrollo

Paediatric care of a chronic process is limited by the moment when the clinical and therapeutic follow-up must be continued by a specialist from the area for adults. The delay in the transition from paediatrics to adult medicine can be due to causes attributable to the patient or his/her relatives, or the professional who diagnosed the disease. The former arises from the uncertainty of facing the unknown, which becomes more intense when the diagnosis and treatment have been difficult, as there is a fear of upsetting the stability of the patient. The latter concerns the paediatric specialist, who created ties of dependence with the patient due to the difficulties involved in the process, and perhaps even owing to a wish to avoid playing a less important role in it. Delaying the transition gives rise to problems that are detrimental for the child, because after adolescence there will still be a harmful dependence on the family and the paediatrician, which will delay the necessary knowledge of their own illness and of the limitations that can condition them. As a result this can prevent them from developing mechanisms for coming to terms with the reality of their own life situation. Later on, when it comes to taking the necessary step into adult medicine, immaturity appears, which increases the difficulties due to a lack of knowledge of both the disease and the tell-tale signs of alarm, revealing insecurity in the different situations that arise. The problem can be solved by a slow progressive change which must be coordinated in mixed outpatient departments with the presence of specialists for both paediatric and adult patients. This publication offers an analysis of this problem and a review of the solutions recommended to implement them in the best possible way

Pseudotumor cerebri in kaposiform lymphangiomatosis: a case report and pathogenetic hypothesis.

CASE REPORT: A 4-year-old boy with kaposiform lymphangiomatosis (KLA) developed progressive headaches and papilloedema and was diagnosed with pseudotumor cerebri initially treated with acetazolamide. Clinical deterioration prompted placement of a ventriculoperitoneal shunt. After the surgery, the child's condition has markedly improved. DISCUSSION AND CONCLUSIONS: A network of intracranial lymphatics is presently being investigated. Neuroimaging excluded KLA infiltration of the skull and/or meninges, leaving as the most plausible explanation for the child's pseudotumor cerebri the existence of an increase in intracranial venous pressure by venous compression at the thorax. To our knowledge, our case constitutes the first report of pseudotumor cerebri occurring in the context of KLA.

Nivel formativo sobre trastornos del espectro autista (TEA) entre los pediatras de atención hospitalaria / Level of training in autistic spectrum disorders among hospital paediatricians

Introducción: La formación en trastornos del espectro autista (TEA) por parte de los pediatras es esencial para su diagnóstico precoz. Sin embargo, son escasos los estudios que han cuantificado este conocimiento, por lo que el objetivo principal es determinar el nivel formativo sobre TEA entre pediatras de atención hospitalaria en diferentes comunidades e identificar aspectos a mejorar. Material y métodos: Un total de 157 pediatras de atención hospitalaria de 3 comunidades autónomas completó el cuestionario online sobre TEA, estructurado en 3 partes (sociodemográfico, nivel formativo y opinión). Los datos fueron analizados con SPSS (versión 15). Resultados La media ± desviación estándar de puntuaciones en el cuestionario fue 20,34±2,43 (puntuación máxima posible: 23). Un 65% puntúa en todos los dominios igual o superior a la media. Los conceptos menos conocidos son: patrones restringidos de conducta, concepto general TEA y comorbilidades posibles. No hay diferencias estadísticamente significativas en cuanto a las puntuaciones entre diferentes grupos de pediatras según variables sociodemográficas. Un 64% de los pediatras opina que su conocimiento sobre TEA es limitado. Destaca un desconocimiento importante sobre la disponibilidad de recursos, presente en todas las comunidades estudiadas. Conclusiones Existe un adecuado nivel general de conocimientos sobre TEA entre los pediatras, pero un deficiente conocimiento en la parte práctica del manejo de estos pacientes y en la coordinación entre los diferentes equipos que participan en el cuidado de estos. Los esfuerzos deberían centrarse en lograr una buena comunicación entre estos equipos y en mantener actualizados los conocimientos sobre TEA a todos los niveles (AU)

Background: Training in autistic spectrum disorders is crucial in order to achieve an early diagnosis. However, the number of papers describing this training is limited. This study describes this level of knowledge among paediatricians from tertiary care hospitals in different regions of Spain and detects areas that need improvement. Material and method: A total of one hundred and fifty-seven (157) paediatricians working in tertiary healthcare hospitals located in three different regions in Spain consented to complete an online questionnaire divided in three sections (socio-demographic, knowledge about childhood autism, and opinion). Data were analysed using SPSS version 15. Results: The total mean score of participating paediatricians in the questionnaire was 20.34 (± 2.43 SD) out of a total possible score of 23. Approximately two-thirds (65%) of paediatricians scored more or equal to the mean score. The knowledge gap was found to be higher with symptoms of repetitive behaviour patterns, concept of autism, and comorbidity, with no statistical significance. There were no differences in paediatrician scores within different socio-demographic groups. Just under two-thirds (64%) of paediatricians subscribed to the opinion that their own knowledge about autism is limited, and there is a significant lack of knowledge about facilities in every region. Conclusions: There is a sufficient level of knowledge about autism among paediatricians in tertiary healthcare, although a lack of awareness about the management of these patients, with poor coordination between the different specialists that are involved in their treatment. Efforts should focus on achieving a better coordination between these specialists, and update the knowledge gaps identified (AU)

[Level of training in autistic spectrum disorders among hospital paediatricians]. / Nivel formativo sobre trastornos del espectro autista (TEA) entre los pediatras de atención hospitalaria.

BACKGROUND: Training in autistic spectrum disorders is crucial in order to achieve an early diagnosis. However, the number of papers describing this training is limited. This study describes this level of knowledge among paediatricians from tertiary care hospitals in different regions of Spain and detects areas that need improvement. MATERIAL AND METHOD: A total of one hundred and fifty-seven (157) paediatricians working in tertiary healthcare hospitals located in three different regions in Spain consented to complete an online questionnaire divided in three sections (socio-demographic, knowledge about childhood autism, and opinion). Data were analysed using SPSS version 15. RESULTS: The total mean score of participating paediatricians in the questionnaire was 20.34 (± 2.43 SD) out of a total possible score of 23. Approximately two-thirds (65%) of paediatricians scored more or equal to the mean score. The knowledge gap was found to be higher with symptoms of repetitive behaviour patterns, concept of autism, and comorbidity, with no statistical significance. There were no differences in paediatrician scores within different socio-demographic groups. Just under two-thirds (64%) of paediatricians subscribed to the opinion that their own knowledge about autism is limited, and there is a significant lack of knowledge about facilities in every region. CONCLUSIONS: There is a sufficient level of knowledge about autism among paediatricians in tertiary healthcare, although a lack of awareness about the management of these patients, with poor coordination between the different specialists that are involved in their treatment. Efforts should focus on achieving a better coordination between these specialists, and update the knowledge gaps identified.

[The importance of sleep problems in children with headache and other neurodevelopmental disorders in neuropaediatric services]. / Importancia de los problemas de sueño en los niños con cefalea y otros trastornos del neurodesarrollo en las consultas de neuropediatria.

INTRODUCTION: Sleep disorders are common in children with neurological disorders. The aim of this study is to know the opinion of neuropediatricians and the prevalence of these disturbances in Spain. PATIENTS AND METHODS: Multicenter cross-sectional study (12 Spanish hospitals, 15 researchers). BEARS survey was collected in three groups: A (2-5 years), (6-12 years), and C (> 12 years). The opinion of neuropediatricians was also collected. RESULTS: 939 questionnaires were filled. The main results in groups B and C were ADHD (32.4% and 30.1% respectively) and headache (25.1% and 27.6% respectively), whereas in group A neurodevelopmental disorders (32.4%) and epilepsy (21.4%) were the main diagnoses. Disturbances in at least one area of sleep were found in 92% of children in group A (n = 209, mean 3 years), 64.2% in group B (n = 534, mean 9.4 years) and 58.2% in group C (n = 196, mean 13.7 years). Sixty-one surveys were answered by neuropediatricians (16.75% of the total sent), estimating that less than a quarter of the patients (24.5%) suffered. Even, up to 23% of doctors claimed that the prevalence of sleep disorders was < 10%. CONCLUSIONS: 58-92% of parents-patients under follow up at a neuropediatrician office in Spain have some degree of disturbed sleep. Although most neurologists emphasize the importance of an early diagnosis and treatment of sleep disorders in children with neurological disorders, its frequency is often underestimated (risk of underdiagnosis).

TITLE: Importancia de los problemas de sueño en los niños con cefalea y otros trastornos del neurodesarrollo en las consultas de neuropediatria.Introduccion. Los trastornos de sueño son frecuentes en niños con trastornos neurologicos. El objetivo del estudio es conocer la opinion de los neuropediatras y su prevalencia real en España. Pacientes y metodos. Estudio transversal multicentrico (12 hospitales españoles, 15 investigadores). Se administro la encuesta Bedtime, Excesive Daytime Sleepiness, Awakenings, Regularity, Sleep-Disordered Breathing (BEARS) y se definieron tres grupos: A (2-5 años), B (6-12 años) y C (> 12 años). Asimismo, se recogio la opinion de neuropediatras de la Sociedad Española de Neuropediatria mediante una encuesta anonima. Resultados. Se recogieron 939 encuestas. Los principales motivos de consulta en los grupos B y C fueron trastorno por deficit de atencion/hiperactividad (32,4% y 30,1%, respectivamente) y cefalea (25,1% y 27,6%, respectivamente), y en el grupo A, los trastornos del neurodesarrollo (32,4%) y la epilepsia (21,4%). Al menos un area del sueño alterada se encontro en el 92,9% de niños del grupo A (n = 209; media: 3 años), en el 64,2% del grupo B (n = 534; media: 9,4 años) y en el 58,2% del grupo C (n = 196; media: 13,7 años). Se recibieron 61 encuestas respondidas por los neuropediatras (16,75% de las enviadas), quienes estimaban que los trastornos del sueño afectaban a menos de una cuarta parte de sus pacientes (24,5%), y hasta un 23% afirmo que la prevalencia era inferior al 10%. Conclusion. El 58-92% de los padres-pacientes que acuden a consultas de neuropediatria refiere tener algun aspecto del sueño alterado. Aunque la mayoria de los neuropediatras subraya la importancia de un diagnostico y tratamiento de los trastornos de sueño de los niños con trastornos neurologicos, se suele infraestimar su frecuencia e importancia.

Importancia de los problemas de sueño en los niños con cefalea y otros trastornos del neurodesarrollo en las consultas de neuropediatría / The importance of sleep problems in children with headache and other neurodevelopmental disorders in neuropaediatric services

Introducción. Los trastornos de sueño son frecuentes en niños con trastornos neurológicos. El objetivo del estudio es conocer la opinión de los neuropediatras y su prevalencia real en España. Pacientes y métodos. Estudio transversal multicéntrico (12 hospitales españoles, 15 investigadores). Se administró la encuesta Bedtime, Excesive Daytime Sleepiness, Awakenings, Regularity, Sleep-Disordered Breathing (BEARS) y se definieron tres grupos: A (2-5 años), B (6-12 años) y C (> 12 años). Asimismo, se recogió la opinión de neuropediatras de la Sociedad Española de Neuropediatría mediante una encuesta anónima. Resultados. Se recogieron 939 encuestas. Los principales motivos de consulta en los grupos B y C fueron trastorno por déficit de atención/hiperactividad (32,4% y 30,1%, respectivamente) y cefalea (25,1% y 27,6%, respectivamente), y en el grupo A, los trastornos del neurodesarrollo (32,4%) y la epilepsia (21,4%). Al menos un área del sueño alterada se encontró en el 92,9% de niños del grupo A (n = 209; media: 3 años), en el 64,2% del grupo B (n = 534; media: 9,4 años) y en el 58,2% del grupo C (n = 196; media: 13,7 años). Se recibieron 61 encuestas respondidas por los neuropediatras (16,75% de las enviadas), quienes estimaban que los trastornos del sueño afectaban a menos de una cuarta parte de sus pacientes (24,5%), y hasta un 23% afirmó que la prevalencia era inferior al 10%. Conclusión. El 58-92% de los padres-pacientes que acuden a consultas de neuropediatría refiere tener algún aspecto del sueño alterado. Aunque la mayoría de los neuropediatras subraya la importancia de un diagnóstico y tratamiento de los trastornos de sueño de los niños con trastornos neurológicos, se suele infraestimar su frecuencia e importancia (AU)

Introduction. Sleep disorders are common in children with neurological disorders. The aim of this study is to know the opinion of neuropediatricians and the prevalence of these disturbances in Spain. Patients and methods. Multicenter cross-sectional study (12 Spanish hospitals, 15 researchers). BEARS survey was collected in three groups: A (2-5 years), (6-12 years), and C (> 12 years). The opinion of neuropediatricians was also collected. Results. 939 questionnaires were filled. The main results in groups B and C were ADHD (32.4% and 30.1% respectively) and headache (25.1% and 27.6% respectively), whereas in group A neurodevelopmental disorders (32.4%) and epilepsy (21.4%) were the main diagnoses. Disturbances in at least one area of sleep were found in 92% of children in group A (n = 209, mean 3 years), 64.2% in group B (n = 534, mean 9.4 years) and 58.2% in group C (n = 196, mean 13.7 years). Sixty-one surveys were answered by neuropediatricians (16.75% of the total sent), estimating that less than a quarter of the patients (24.5%) suffered. Even, up to 23% of doctors claimed that the prevalence of sleep disorders was < 10%. Conclusions. 58-92% of parents-patients under follow up at a neuropediatrician office in Spain have some degree of disturbed sleep. Although most neurologists emphasize the importance of an early diagnosis and treatment of sleep disorders in children with neurological disorders, its frequency is often undesestimated (risk of underdiagnosis) (AU)

Enfermedad de Hirayama en pediatría: aportación de un caso clínico y revisión de la bibliografía / Hirayama disease in paediatrics: a clinical case report and review of the literature

Introducción. La enfermedad de Hirayama es una rara atrofia muscular juvenil que afecta a varones jóvenes de origen asiático, con atrofia muscular habitualmente de una de las extremidades superiores de progresión lenta con estabilización posterior. Se diagnostica por estudios electromiográficos/electroneurográficos con velocidad de conducción (EMG/ENG-VC), y por resonancia magnética (RM) medular en posición neutra y en flexión cervical. El tratamiento se basa en el collarín cervical y cirugía (casos graves). Son muy pocos los estudios realizados en edad pediátrica. Caso clínico. Niña de 7 años, con atrofia de la musculatura de la mano y el antebrazo izquierdos, de dos años de evolución. En EMG/ENG-VC presenta signos de denervación crónica muy grave en los miótomos correspondientes a C7, C8 y D1 izquierdos, con conservación de amplitudes de potenciales sensitivos evocados, congruentes con mielopatía cervical. La RM medular cervical en posición neutra muestra un resultado normal en ese nivel. Posteriormente, por la sospecha dirigida de enfermedad de Hirayama, se realiza una nueva RM medular cervical en posición neutra y en flexión, que muestra asimetría en el tamaño y morfología de los cordones anteriores medulares en C6/C7, hiperseñal en el asta anterior homolateral e ingurgitación del plexo venoso epidural posterior. Con el diagnóstico de enfermedad de Hirayama se inicia tratamiento con collarín cervical para evitar la progresión del daño. Conclusiones. Se presenta un caso de enfermedad de Hirayama peculiar por las características epidemiológicas, con la finalidad de difundir esta entidad en nuestro medio, cuyo diagnóstico precoz permite un tratamiento eficaz, y se revisan los estudios realizados en edad pediátrica (AU)

Introduction. Hirayama disease is a rare children’s muscular atrophy that affects young Asian males, with muscular atrophy usually in one of the upper limbs that progresses slowly and later stabilises. It is diagnosed by means of electromyographic/ electroneurographic with conduction speed studies (EMG/ENG-CS) and by magnetic resonance imaging (MRI) of the spinal cord in a neutral position and with cervical flexion. Treatment is based on the cervical collar and surgery (severe cases). Very few studies have been conducted on patients at the paediatric age. Case report. We report the case of a 7-year-old girl with atrophy of the muscles of the left hand and forearm, and a disease history of two years. The EMG/ENG-CS scans presented signs of very severe chronic denervation in the myotomes of C7, C8 and T1 on the left side, with conservation of the amplitudes of sensory evoked potentials, consistent with cervical myelopathy. Results of an MRI scan of the cervical spinal cord in a neutral position were normal at that level. Later, owing to suspicions pointing towards Hirayama disease, a new MRI scan of the cervical spinal cord was performed in a neutral position and in flexion. This second scan showed asymmetry in the size and morphology of the anterior funiculi of the spinal cord at C6/C7, hypersignal in the homolateral anterior horn and ingurgitation of the posterior epidural venous plexus. With a diagnosis of Hirayama disease, treatment is started with a cervical collar in order to prevent the damage from getting worse. Conclusions. This case of Hirayama disease is peculiar due to its epidemiological characteristics and is presented here with the aim of making this entity more widely known in our milieu. If diagnosed at an early stage, treatment is effective, and the studies conducted on children at the paediatric age are reviewed (AU)

[Hirayama disease in paediatrics: a clinical case report and review of the literature]. / Enfermedad de Hirayama en pediatría: aportación de un caso clínico y revisión de la bibliografía.

INTRODUCTION: Hirayama disease is a rare children's muscular atrophy that affects young Asian males, with muscular atrophy usually in one of the upper limbs that progresses slowly and later stabilises. It is diagnosed by means of electromyographic/electroneurographic with conduction speed studies (EMG/ENG-CS) and by magnetic resonance imaging (MRI) of the spinal cord in a neutral position and with cervical flexion. Treatment is based on the cervical collar and surgery (severe cases). Very few studies have been conducted on patients at the paediatric age. CASE REPORT: We report the case of a 7-year-old girl with atrophy of the muscles of the left hand and forearm, and a disease history of two years. The EMG/ENG-CS scans presented signs of very severe chronic denervation in the myotomes of C7, C8 and T1 on the left side, with conservation of the amplitudes of sensory evoked potentials, consistent with cervical myelopathy. Results of an MRI scan of the cervical spinal cord in a neutral position were normal at that level. Later, owing to suspicions pointing towards Hirayama disease, a new MRI scan of the cervical spinal cord was performed in a neutral position and in flexion. This second scan showed asymmetry in the size and morphology of the anterior funiculi of the spinal cord at C6/C7, hypersignal in the homolateral anterior horn and ingurgitation of the posterior epidural venous plexus. With a diagnosis of Hirayama disease, treatment is started with a cervical collar in order to prevent the damage from getting worse. CONCLUSIONS: This case of Hirayama disease is peculiar due to its epidemiological characteristics and is presented here with the aim of making this entity more widely known in our milieu. If diagnosed at an early stage, treatment is effective, and the studies conducted on children at the paediatric age are reviewed.

TITLE: Enfermedad de Hirayama en pediatria: aportacion de un caso clinico y revision de la bibliografia.Introduccion. La enfermedad de Hirayama es una rara atrofia muscular juvenil que afecta a varones jovenes de origen asiatico, con atrofia muscular habitualmente de una de las extremidades superiores de progresion lenta con estabilizacion posterior. Se diagnostica por estudios electromiograficos/electroneurograficos con velocidad de conduccion (EMG/ENG-VC), y por resonancia magnetica (RM) medular en posicion neutra y en flexion cervical. El tratamiento se basa en el collarin cervical y cirugia (casos graves). Son muy pocos los estudios realizados en edad pediatrica. Caso clinico. Niña de 7 años, con atrofia de la musculatura de la mano y el antebrazo izquierdos, de dos años de evolucion. En EMG/ENG-VC presenta signos de denervacion cronica muy grave en los miotomos correspondientes a C7, C8 y D1 izquierdos, con conservacion de amplitudes de potenciales sensitivos evocados, congruentes con mielopatia cervical. La RM medular cervical en posicion neutra muestra un resultado normal en ese nivel. Posteriormente, por la sospecha dirigida de enfermedad de Hirayama, se realiza una nueva RM medular cervical en posicion neutra y en flexion, que muestra asimetria en el tamaño y morfologia de los cordones anteriores medulares en C6/C7, hiperseñal en el asta anterior homolateral e ingurgitacion del plexo venoso epidural posterior. Con el diagnostico de enfermedad de Hirayama se inicia tratamiento con collarin cervical para evitar la progresion del daño. Conclusiones. Se presenta un caso de enfermedad de Hirayama peculiar por las caracteristicas epidemiologicas, con la finalidad de difundir esta entidad en nuestro medio, cuyo diagnostico precoz permite un tratamiento eficaz, y se revisan los estudios realizados en edad pediatrica.

Complicaciones neurológicas en población infantil con leucemia / Neurological complications in the population of children with leukaemia

Introducción. La leucemia es el cáncer más frecuente en edad pediátrica. Su tasa de curación es del 80% con quimioterapia intensiva, que mejora la supervivencia, pero que también aumenta la frecuencia de efectos adversos, incluyendo los neurológicos. Objetivos. Describir la frecuencia y características de las complicaciones neurológicas (CN) en pacientes con leucemia aguda linfoide (LAL) y leucemia aguda mieloide (LAM), e identificar los factores asociados a su presencia, la tasa de morbilidad neurológica y la supervivencia. Pacientes y métodos. Estudio retrospectivo de las CN presentes durante el tratamiento y seguimiento de los pacientes con LAL y LAM entre 1997 y 2012 por la unidad de oncohematología infantil. Variables analizadas: datos demográficos, diagnóstico oncológico, tratamiento y CN. Resultados. Se incluyó un total de 157 pacientes, 145 sin infiltración de sistema nervioso central al diagnóstico y ocho con infiltración (tasa de CN del 14 y 12%, respectivamente). Las CN más frecuentes fueron: neuropatías (31%), alteración del nivel de conciencia (27%), convulsiones (22%) y cefalea (12%). Un 40% de los pacientes con CN ha presentado secuelas, pero ninguno ha fallecido como consecuencia de la CN. Se han detectado más CN en el grupo de edad menor de 6 años con LAL de alto grado, en niveles de gravedad más altos y en pacientes que habían recibido trasplante de precursores hematopoyéticos, todas ellas con diferencias estadísticamente significativas. Conclusiones. Las complicaciones neurológicas son frecuentes en los pacientes con leucemia aguda, en especial en aquellos con estadio de riesgo alto (sobre todo si son menores de 6 años) y trasplante de precursores hematopoyéticos. La mortalidad asociada es baja (AU)

Introduction. Leukaemia is the most frequent type of cancer at the paediatric age. The cure rate is 80% with intensive chemotherapy, which improves survival but also often increases the frequency of adverse side effects, including those of a neurological nature. Aims. To describe the frequency and characteristics of the neurological complications (NC) in patients with acute lymphoid leukaemia (ALL) and acute myeloid leukaemia (AML), as well as to identify factors associated to their presence, neurological morbidity and survival rate. Patients and methods. A retrospective study was conducted of the NC present in patients with ALL and AML between 1997 and 2012 treated and followed up by the child onco-haematology unit. The following variables were analysed: demographic data, oncological diagnosis, treatment and NC. Results. Altogether 157 patients were included, 145 without infiltration of the central nervous system at diagnosis and eight with infiltration (rate of NC of 14% and 12%, respectively). The most frequent NC were: neuropathies (31%), altered levels of consciousness (27%), convulsions (22%) and headache (12%). Forty per cent of the patients with NC presented sequelae but none of them died as a consequence of the NC. More NC were detected in the age group of children aged under 6 years with high-degree ALL, at higher levels of severity and in patients who had received a haematopoietic stem-cell transplant, all of them with statistically significant differences. Conclusions. Neurological complications are common in patients with acute leukaemia, especially in those at a high-risk stage (above all if they are under the age of 6 years) and with haematopoietic stem-cell transplant. The associated mortality rate is low (AU)

[Neurological complications in the population of children with leukaemia]. / Complicaciones neurológicas en población infantil con leucemia.

INTRODUCTION: Leukaemia is the most frequent type of cancer at the paediatric age. The cure rate is 80% with intensive chemotherapy, which improves survival but also often increases the frequency of adverse side effects, including those of a neurological nature. AIMS: To describe the frequency and characteristics of the neurological complications (NC) in patients with acute lymphoid leukaemia (ALL) and acute myeloid leukaemia (AML), as well as to identify factors associated to their presence, neurological morbidity and survival rate. PATIENTS AND METHODS: A retrospective study was conducted of the NC present in patients with ALL and AML between 1997 and 2012 treated and followed up by the child onco-haematology unit. The following variables were analysed: demographic data, oncological diagnosis, treatment and NC. RESULTS: Altogether 157 patients were included, 145 without infiltration of the central nervous system at diagnosis and eight with infiltration (rate of NC of 14% and 12%, respectively). The most frequent NC were: neuropathies (31%), altered levels of consciousness (27%), convulsions (22%) and headache (12%). Forty per cent of the patients with NC presented sequelae but none of them died as a consequence of the NC. More NC were detected in the age group of children aged under 6 years with high-degree ALL, at higher levels of severity and in patients who had received a haematopoietic stem-cell transplant, all of them with statistically significant differences. CONCLUSIONS: Neurological complications are common in patients with acute leukaemia, especially in those at a high-risk stage (above all if they are under the age of 6 years) and with haematopoietic stem-cell transplant. The associated mortality rate is low.

TITLE: Complicaciones neurologicas en poblacion infantil con leucemia.Introduccion. La leucemia es el cancer mas frecuente en edad pediatrica. Su tasa de curacion es del 80% con quimioterapia intensiva, que mejora la supervivencia, pero que tambien aumenta la frecuencia de efectos adversos, incluyendo los neurologicos. Objetivos. Describir la frecuencia y caracteristicas de las complicaciones neurologicas (CN) en pacientes con leucemia aguda linfoide (LAL) y leucemia aguda mieloide (LAM), e identificar los factores asociados a su presencia, la tasa de morbilidad neurologica y la supervivencia. Pacientes y metodos. Estudio retrospectivo de las CN presentes durante el tratamiento y seguimiento de los pacientes con LAL y LAM entre 1997 y 2012 por la unidad de oncohematologia infantil. Variables analizadas: datos demograficos, diagnostico oncologico, tratamiento y CN. Resultados. Se incluyo un total de 157 pacientes, 145 sin infiltracion de sistema nervioso central al diagnostico y ocho con infiltracion (tasa de CN del 14 y 12%, respectivamente). Las CN mas frecuentes fueron: neuropatias (31%), alteracion del nivel de conciencia (27%), convulsiones (22%) y cefalea (12%). Un 40% de los pacientes con CN ha presentado secuelas, pero ninguno ha fallecido como consecuencia de la CN. Se han detectado mas CN en el grupo de edad menor de 6 años con LAL de alto grado, en niveles de gravedad mas altos y en pacientes que habian recibido trasplante de precursores hematopoyeticos, todas ellas con diferencias estadisticamente significativas. Conclusiones. Las complicaciones neurologicas son frecuentes en los pacientes con leucemia aguda, en especial en aquellos con estadio de riesgo alto (sobre todo si son menores de 6 años) y trasplante de precursores hematopoyeticos. La mortalidad asociada es baja.

Crisis febriles complejas: ¿debemos cambiar nuestro modo de actuación? / Complex febrile crises: should we change the way we act?

Introducción. Las convulsiones febriles son una de las causas más frecuentes de consulta. Hasta ahora, los pacientes con convulsiones febriles complejas (CFC) deben ingresar, dado el mayor porcentaje de epilepsia y complicaciones agudas descrito clásicamente. En la actualidad hay estudios que apoyan ser menos invasivos en el abordaje de estos pacientes. Objetivo. Describir las características de los pacientes ingresados por CFC y proponer un nuevo protocolo de actuación. Pacientes y métodos. Análisis retrospectivo de historias clínicas de ingresados por CFC (enero de 2010-diciembre de 2013). Se ofrecen datos epidemiológicos, clínicos, pruebas complementarias y evolución. Resultados. Las CFC suponían un 4,2% de los ingresos de neuropediatría (n = 67). Edad media al evento: 25 meses. El 47% tenía antecedentes familiares patológicos, y el 31%, antecedentes personales de convulsión febril previa. En el 54% de los pacientes, la CFC duró menos de cinco minutos; hubo recurrencia, la mayoría con un total de dos crisis y durante el primer día (las CFC por recurrencia son las más frecuentes). De las pruebas complementarias realizadas, ninguna de ellas sirvió como apoyo diagnóstico en el momento agudo. Durante su seguimiento, cinco pacientes presentaron complicaciones. Los pacientes con antecedentes familiares de convulsiones febriles presentan mayor riesgo de epilepsia o recurrencia (p =0,02), sin diferencias significativas respecto a la edad, número de crisis, intervalo de fiebre, estado epiléptico o tipo de CFC. Conclusiones. Las CFC no asocian mayores complicaciones agudas; las exploraciones complementarias no permiten discriminar precozmente a los pacientes de riesgo. Su ingreso podría evitarse en ausencia de otros signos clínicos y limitarse a casos seleccionados (AU)

Introduction. Febrile seizures are one of the most frequent reasons why patients visit the healthcare specialist. Up until now, patients with complex febrile seizures (CFS) have been hospitalised, bearing in mind the higher percentages of epilepsy and acute complications that were classically reported. Today there are studies that back the idea of being less invasive in the management of these patients. Aims. To describe the characteristics of patients hospitalised due to CFS and to propose a new protocol to be followed in dealing with such cases Patients and methods. The medical records of patients hospitalised because of CFS (January 2010-December 2013) were analysed retrospectively. Epidemiological and clinical data are presented, together with information from complementary tests and about development. Results. CFS account for 4.2% of all neuropaediatric cases of admittance to hospital in (67 patients). Mean age at the time of the event: 25 months. A pathological family history existed in 47% of cases, and 31% had a previous personal history of febrile seizures. The CFS lasted less than five minutes in 54% of patients; there were also recurrences, most of them with a total of two crises and during the first day (CFS due to recurrence are the most frequent). None of the complementary tests that were carried out were of any use as a diagnostic aid during the acute phase. During their follow-up, five patients presented complications. Patients with a family history of febrile seizures presented a higher risk of epilepsy or recurrence (p = 0.02), with no significant differences as regards age, number of seizures, febrile interval, epileptic status or type of CFS. Conclusions. The CFS are not associated with greater acute complications, and the complementary examinations do not allow high-risk patients to be distinguished at an early stage. Hospitalising them could be avoided in the absence of other clinical signs and symptoms, and thus be limited to selected cases (AU)

Efficacy and tolerability of lacosamide in the concomitant treatment of 130 patients under 16 years of age with refractory epilepsy: a prospective, open-label, observational, multicenter study in Spain.

BACKGROUND: The safety and effectiveness of lacosamide, an antiepileptic drug (AED) that selectively enhances the slow inactivation of voltage-gated sodium channels without affecting rapid inactivation, has been demonstrated in randomized, double-blind, placebo-controlled trials in adults with focal epileptic seizures. Although lacosamide is approved for use in patients over 16 years of age, limited clinical experience exists for younger patients. OBJECTIVE: To assess the efficacy and tolerability of lacosamide in children with refractory epilepsy. DesignMethods: The trial was a prospective, open-label, observational, multicenter study. A total of 130 patients aged less than 16 years (range 6 months to 16 years) with refractory epilepsy who had initiated treatment with lacosamide were enrolled at 18 neuropediatric units in hospitals across Spain. Patients with a variety of etiologies were enrolled, including those with partial epilepsies and symptomatic, generalized epilepsy syndromes. Lacosamide (VIMPAT®; UCB Pharma SA, Brussels, Belgium) was primarily administered once every 12 hours as an oral solution or as an oral tablet, with an initial dose of 1-2 mg/kg/day in the majority of cases. The majority of patients were also receiving stable concomitant therapy with ≥1 other AED. Treatment response to lacosamide was determined by assessing the change in seizure frequency after 3 months of lacosamide therapy. Responders were defined as patients who achieved a seizure frequency reduction of >50%. Tolerability was assessed by the reporting of adverse effects, laboratory testing, and electroencephalography recordings. RESULTS: Lacosamide was dosed at a mean of 6.80 ± 2.39 mg/kg/day. After 3 months of lacosamide therapy, 62.3% of patients achieved a >50% reduction in seizure frequency, with complete seizure suppression being reported in 13.8% of patients. Adverse effects occurred in 39 patients (30%), but no dose-response relationship was observed in terms of these events. In ten patients, instability, difficulty walking, an inability to relate to subjective elements, and blurred vision or dizziness were reported. A total of 13 patients discontinued treatment - in five of these patients, symptom intensity remained unchanged despite dose reduction, which led to treatment discontinuation. The symptoms were markedly different in each patient, preventing determination of a causal factor(s). CONCLUSIONS: The results of this study provide preliminary evidence for the efficacy of lacosamide in children with refractory epilepsy. Further evaluation in a randomized, controlled trial is needed to validate the efficacy in this population and to fully investigate the adverse effects described here. We recommend an initial dose of 1-2 mg/kg/day, uptitrated to 6-9 mg/kg/day over 4-6 weeks.

Síndrome de Angelman y temor a andar. ¿Involución psicomotriz? / Angelman syndrome and fear of walking. Psychomotor involution?

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[Cases of video electroencephalogram: differential diagnosis in newborn infants]. / Casos de videoelectroencefalograma: diagnostico diferencial en el recien nacido.

This study addresses a number of general considerations on epilepsies and epileptic syndromes that develop in the neonatal period. The chronological limits of this stage of maturation are set out and the pathophysiology of the convulsive phenomenon during that period are briefly analysed. Furthermore, the differences that exist as a result of the incipient level of maturity of the newborn infant's central nervous system with regard to other ages, and obviously adults, are highlighted. Likewise, reference is made to the percentage values of this pathology, which even vary depending on the gestational age. The clinical expression has a personality that is very different from the other stages of maturation in children, with four predominant manifestations: subtle, tonic, clonic and myoclonic seizures, which have been universally accepted since they were first reported by Volpe. Epilepsies in the newborn infant are not sufficiently well differentiated in the different classifications of epilepsies and epileptic syndromes that have appeared in recent years, although they could well be, since they display enough significance and individuality for that to be so. Three clinical cases are reported, with the aid of video electroencephalographic findings, to illustrate some of the possible neonatal epileptic manifestations.

Casos de videoelectroencefalograma: diagnóstico diferencial en el recién nacido / Cases of video electroencephalogram: differential diagnosis in newborn infants

Resumen. Se exponen las consideraciones generales sobre las epilepsias y síndromes epilépticos que se desarrollan en el período neonatal, marcando los límites cronológicos de esta etapa madurativa y analizando sucintamente la fisiopatología del fenómeno convulsivo durante él, remarcando las diferencias existentes con otras edades y obviamente con el adulto, como consecuencia del incipiente nivel madurativo del sistema nervioso central del recién nacido. Asimismo, se hace referencia a los valores porcentuales de esta patología, que varía incluso en dependencia de la edad gestacional. La expresividad clínica tiene una personalidad muy diferenciada respecto al resto de las etapas madurativas del niño, aceptándose cuatro manifestaciones predominantes: las crisis sutiles, tónicas, clónicas y mioclónicas, aceptadas universalmente desde que fueron descritas por Volpe. Las epilepsias del recién nacido no se encuentran suficientemente diferenciadas en las diferentes clasificaciones de las epilepsias y síndromes epilépticos aparecidas a lo largo de los últimos años, aunque tienen el suficiente significado e individualidad como para que así fuera. Se presentan tres casos clínicos, con soporte videoelectroencefalográfico, para ilustrar algunas de las posibles manifestaciones epilépticas neonatales (AU)

Summary. This study addresses a number of general considerations on epilepsies and epileptic syndromes that develop in the neonatal period. The chronological limits of this stage of maturation are set out and the pathophysiology of the convulsive phenomenon during that period are briefly analysed. Furthermore, the differences that exist as a result of the incipient level of maturity of the newborn infant’s central nervous system with regard to other ages, and obviously adults, are highlighted. Likewise, reference is made to the percentage values of this pathology, which even vary depending on the gestational age. The clinical expression has a personality that is very different from the other stages of maturation in children, with four predominant manifestations: subtle, tonic, clonic and myoclonic seizures, which have been universally accepted since they were first reported by Volpe. Epilepsies in the newborn infant are not sufficiently well differentiated in the different classifications of epilepsies and epileptic syndromes that have appeared in recent years, although they could well be, since they display enough significance and individuality for that to be so. Three clinical cases are reported, with the aid of video electroencephalographic findings, to illustrate some of the possible neonatal epileptic manifestations (AU)