Genetic Heterogeneity Underlying Phenotypes with Early-Onset Cerebellar Atrophy.

Cerebellar atrophy (CA) is a frequent neuroimaging finding in paediatric neurology, usually associated with cerebellar ataxia. The list of genes involved in hereditary forms of CA is continuously growing and reveals its genetic complexity. We investigated ten cases with early-onset cerebellar involvement with and without ataxia by exome sequencing or by a targeted panel with 363 genes involved in ataxia or spastic paraplegia. Novel variants were investigated by in silico or experimental approaches. Seven probands carry causative variants in well-known genes associated with CA or cerebellar hypoplasia: SETX, CACNA1G, CACNA1A, CLN6, CPLANE1, and TBCD. The remaining three cases deserve special attention; they harbour variants in MAST1, PI4KA and CLK2 genes. MAST1 is responsible for an ultrarare condition characterised by global developmental delay and cognitive decline; our index case added ataxia to the list of concomitant associated symptoms. PIK4A is mainly related to hypomyelinating leukodystrophy; our proband presented with pure spastic paraplegia and normal intellectual capacity. Finally, in a patient who suffers from mild ataxia with oculomotor apraxia, the de novo novel CLK2 c.1120T>C variant was found. The protein expression of the mutated protein was reduced, which may indicate instability that would affect its kinase activity.

Telemedicina en neuropediatría / Telemedicine in pediatric neurology

El estrés que la pandemia de coronavirus ha producido en los servicios sanitarios, y la interferencia que ha ocasionado en la atención al resto de patologías y su seguimiento en consultas nos han llevado a impulsar e incorporar la telemedicina en nuestra práctica médica habitual. La telemedicina es la asistencia médica a distancia o no presencial, un nuevo método de administrar atención médica por parte de profesionales acreditados, que optimiza los recursos y aumenta su alcance. Un inconveniente para la teleneurología infantil es la necesidad para nuestros diagnósticos de una observación directa del niño y de una exploración en forma de juego. Principalmente en las etapas más infantiles, un paciente nuevo evaluado por telemedicina puede ser más difícil de diagnosticar y manejar y, por ello, algunos neuropediatras han optado por realizar sólo visitas de seguimiento, de manejo de medicamentos y de revisión de resultados. Pero la telemedicina tiene otros muchos beneficios: posibilidad de asesoramiento rápido, de coordinación interprofesional y de llegar donde y cuando la medicina clásica lo tiene más difícil. El objetivo de este artículo es revisar las posibles indicaciones de la telemedicina en neurología infantil, partiendo de la base de que nunca deberíamos demorar el diagnóstico de lo que tenga tratamiento, tanto en el momento actual como en una eventual situación de rebrote de la pandemia. El avance de la telemedicina dependerá de la implementación tecnológica, de resolver los problemas legales y de seguridad/privacidad, de sus resultados clínicos, y de la demanda y aceptación por los pacientes de estas visitas virtuales

The stress that the coronavirus pandemic has produced on the health services and the disruption it has caused in the care of other pathologies and their follow-up in outpatient visits have led us to promote and incorporate telemedicine in our routine medical practice. Telemedicine refers to remote or non-face-to-face medical attention, a new method of administering medical care by accredited professionals, which optimises resources and increases their scope. One drawback for child teleneurology is that our diagnoses require direct observation of the child and carrying out an examination as though playing a game. Mainly in the youngest stages, a new patient evaluated by telemedicine can be more difficult to diagnose and manage, and therefore some neuropaediatricians have chosen to carry out only follow-up visits, medication management and outcome reviews. Telemedicine, however, also has many benefits, such as the possibility of giving rapid advice, coordination among professionals and reaching the patient where and when it is difficult for classical medicine to do so. The aim of this article is to review the possible indications of telemedicine in child neurology, starting out from the fact that we should never delay the diagnosis of something that can be treated, both at the present time and in an eventual situation of resurgence of the pandemic. The advance of telemedicine will depend on the implementation of technology, on solving legal and security/privacy issues, on its clinical outcomes and on the extent to which patients demand and accept these virtual visits

Estado epiléptico eléctrico durante el sueño: estudio retrospectivo multicéntrico de 29 casos / Electrical status epilepticus during sleep: a retrospective multi-centre study of 29 cases

Introducción. El estado epiléptico eléctrico durante el sueño (ESES) es un síndrome epiléptico caracterizado por la presencia de descargas epilépticas tipo punta-onda lenta de manera muy persistente durante el sueño no REM. En la actualidad, el manejo de esta patología es heterogéneo y no hay estudios controlados con los tratamientos utilizados, ni se ha comprobado si éstos mejoran la evolución cognitiva de los pacientes. Pacientes y métodos. Se revisan los pacientes diagnosticados de ESES durante 15 años en cuatro centros hospitalarios, se recoge la presentación clínica, el manejo terapéutico y la evolución clínica, y se compara con la bibliografía. Resultados. Se seleccionaron 29 pacientes con ESES, 20 de ellos idiopático y 26 de ellos generalizado. Los fármacos con los que se consiguió mayor control de la actividad eléctrica fueron los corticoides/hormona adrenocorticotropa (ACTH), el clobazam y el levetiracetam. La mediana de duración del ESES en los casos primarios fue de seis meses, y en los secundarios, el doble. El 45% de los pacientes mantuvo un cociente intelectual normal y un 40% presentó en la evolución discapacidad cognitiva de diferente grado. Conclusiones. El pronóstico neuropsicológico evolutivo suele ser desfavorable y la evolución cognitiva parece estar en relación con la duración del ESES y el área donde esté concentrada la actividad epiléptica, lo que sugiere que el mal pronóstico, si se trata precozmente, se puede evitar. Los antiepilépticos más frecuentemente utilizados son el ácido valproico, la etosuximida y el levetiracetam, y en nuestra muestra también se utilizaron con frecuencia el clobazam y la lamotrigina. Los fármacos más eficaces para el control del ESES fueron los corticoides/ACTH, el clobazam y el levetiracetam (AU)

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

[Electrical status epilepticus during sleep: a retrospective multi-centre study of 29 cases]. / Estado epiléptico eléctrico durante el sueño: estudio retrospectivo multicéntrico de 29 casos.

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

TITLE: Estado epileptico electrico durante el sueño: estudio retrospectivo multicentrico de 29 casos.Introduccion. El estado epileptico electrico durante el sueño (ESES) es un sindrome epileptico caracterizado por la presencia de descargas epilepticas tipo punta-onda lenta de manera muy persistente durante el sueño no REM. En la actualidad, el manejo de esta patologia es heterogeneo y no hay estudios controlados con los tratamientos utilizados, ni se ha comprobado si estos mejoran la evolucion cognitiva de los pacientes. Pacientes y metodos. Se revisan los pacientes diagnosticados de ESES durante 15 años en cuatro centros hospitalarios, se recoge la presentacion clinica, el manejo terapeutico y la evolucion clinica, y se compara con la bibliografia. Resultados. Se seleccionaron 29 pacientes con ESES, 20 de ellos idiopatico y 26 de ellos generalizado. Los farmacos con los que se consiguio mayor control de la actividad electrica fueron los corticoides/hormona adrenocorticotropa (ACTH), el clobazam y el levetiracetam. La mediana de duracion del ESES en los casos primarios fue de seis meses, y en los secundarios, el doble. El 45% de los pacientes mantuvo un cociente intelectual normal y un 40% presento en la evolucion discapacidad cognitiva de diferente grado. Conclusiones. El pronostico neuropsicologico evolutivo suele ser desfavorable y la evolucion cognitiva parece estar en relacion con la duracion del ESES y el area donde este concentrada la actividad epileptica, lo que sugiere que el mal pronostico, si se trata precozmente, se puede evitar. Los antiepilepticos mas frecuentemente utilizados son el acido valproico, la etosuximida y el levetiracetam, y en nuestra muestra tambien se utilizaron con frecuencia el clobazam y la lamotrigina. Los farmacos mas eficaces para el control del ESES fueron los corticoides/ACTH, el clobazam y el levetiracetam.