Retraso madurativo neurológico / Neurological maturation retardation

Introducción. Los primeros años de vida, esencialmente los primeros tres, están presididos por una serie de hechos anatomofuncionales que expresan el progresivo enriquecimiento de la conducta a través del proceso de maduración neurológica, expresado como el alcanzar en cada etapa del desarrollo el máximo nivel funcional a través del aprendizaje. Desarrollo. A partir de la experiencia personal, se abordan los principales aspectos conceptuales que definen la maduración neurológica tanto en los aspectos de la normalidad, es decir, sus límites, como sus desviaciones patológicas, precisando límites conceptuales del llamado retraso madurativo. Se analizan los conceptos de ‘niño de riesgo’, y su control neuroevolutivo y factores de pronóstico. Conclusiones. El fin último y primordial de todos los estudios longitudinales es la detección precoz de todas las anomalías neurológicas –incluido el retraso madurativo– que permita un tratamiento precoz, curativo o paliativo, evitando generar ‘falsos positivos’ y, si la patología neurológica queda definida como residual, establecer la ayuda al paciente y su entorno familiar para que ambos se adapten adecuadamente a esta situación (AU)

Introduction. The early years of life, more especially the first three, are dominated by a series of anatomical-functional facts that express the progressive enrichment of behaviour through the process of neurological maturation, which is expressed as reaching the maximum level of functioning at each stage of development as a result of a process of learning. Development. One’s personal experience is used to address the main conceptual aspects that define neurological maturation both in its normal aspects, that is to say, its limits, and its pathological deviations, and there is a need for conceptual limits of the so-called maturation retardation. The concepts of ‘risk child’ and his or her neurodevelopmental control and prognostic factors are analysed. Conclusions. The ultimate and primordial aim of any longitudinal study is the early detection of all the neurological anomalies, including maturation retardation, since this makes it possible to establish an early –either curative or palliative– treatment without producing ‘false positives’. At the same time, if the neurological pathology is defined as residual, help can also be established for the patient and his or her family so that both of them can adapt to the situation in a suitable manner (AU)

[Neurological maturation retardation]. / Retraso madurativo neurológico.

INTRODUCTION: The early years of life, more especially the first three, are dominated by a series of anatomical-functional facts that express the progressive enrichment of behaviour through the process of neurological maturation, which is expressed as reaching the maximum level of functioning at each stage of development as a result of a process of learning. DEVELOPMENT: One's personal experience is used to address the main conceptual aspects that define neurological maturation both in its normal aspects, that is to say, its limits, and its pathological deviations, and there is a need for conceptual limits of the so-called maturation retardation. The concepts of 'risk child' and his or her neurodevelopmental control and prognostic factors are analysed. CONCLUSIONS: The ultimate and primordial aim of any longitudinal study is the early detection of all the neurological anomalies, including maturation retardation, since this makes it possible to establish an early--either curative or palliative--treatment without producing 'false positives'. At the same time, if the neurological pathology is defined as residual, help can also be established for the patient and his or her family so that both of them can adapt to the situation in a suitable manner.

TITLE: Retraso madurativo neurologico.Introduccion. Los primeros años de vida, esencialmente los primeros tres, estan presididos por una serie de hechos anatomofuncionales que expresan el progresivo enriquecimiento de la conducta a traves del proceso de maduracion neurologica, expresado como el alcanzar en cada etapa del desarrollo el maximo nivel funcional a traves del aprendizaje. Desarrollo. A partir de la experiencia personal, se abordan los principales aspectos conceptuales que definen la maduracion neurologica tanto en los aspectos de la normalidad, es decir, sus limites, como sus desviaciones patologicas, precisando limites conceptuales del llamado retraso madurativo. Se analizan los conceptos de 'niño de riesgo', y su control neuroevolutivo y factores de pronostico. Conclusiones. El fin ultimo y primordial de todos los estudios longitudinales es la deteccion precoz de todas las anomalias neurologicas ­incluido el retraso madurativo­ que permita un tratamiento precoz, curativo o paliativo, evitando generar 'falsos positivos' y, si la patologia neurologica queda definida como residual, establecer la ayuda al paciente y su entorno familiar para que ambos se adapten adecuadamente a esta situacion.

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.

Recomendaciones sobre aspectos éticos de la investigación cualitativa en la salud / Recommendations on ethical aspects of qualitative research in health

Desde el punto de vista ético, la investigación cualitativa debe cumplir un conjunto de requisitos éticos que son comunes a cualquier tipo de investigación. Además, presenta una serie de problemas peculiares que son abordados en 13 recomendaciones que inciden principalmente en los siguientes puntos: la necesidad de que las relaciones entre el investigador y los sujetos participantes en la investigación se caractericen por la confianza mutua y la integridad profesional; la obligación de informar de las características de la investigación como un proceso abierto que podría hacer necesario solicitar un nuevo consentimiento o revisarlo durante el proceso de investigación; la exigencia de informar y verificar que el participante comprende la diferencia entre investigación y acto terapéutico. Los investigadores han de tener especial cuidado en la publicación de los resultados para mantener la confidencialidad y evitar estigmatización (AU)

From the ethical point of view, qualitative research must meet a set of ethical requirements that are common to any type of research. In addition, it presents a series of unique problems that are addressed in 13 recommendations that impact primarily on the following points: the need for relations between the researcher and the subjects participating in research should be characterized by mutual trust and professional integrity, the obligation to inform of the characteristics of research as an open process that could make it necessary to request a new consent form or review the existing consent form during the investigation process; the requirement to provide information and verify that the participant understands the difference between research and therapeutic act. Researchers should take special care when publishing the results to maintain patient confidentiality and to avoid stigmatization (AU)

[Relationship between migraine and atopy in childhood: a retrospective case-control study]. / Relación entre la migraña y la atopia en la infancia: estudio retrospectivo de casos y controles.

INTRODUCTION: Migraine is a common complaint in childhood. Atopy is the predisposition to the complaint of one or more of the following conditions: atopic dermatitis, rhinoconjunctivitis and asthma. AIM: To examine whether there is a relationship between atopy, taking into account each of its different variants, and migraine with or without aura. The practical application of knowing about this association includes improvement in the diagnosis of migraine, which is often difficult in children. SUBJECTS AND METHODS: We performed a retrospective case-control study of children (5-15 years old) with and without migraine; recruitment time: six months. Data evaluated included age, sex, questions from a questionnaire about atopy to measure prevalence, and medical diagnosis that appears in the patient's medical record and overall (intersection of the previous ones), among other things. A statistical analysis was performed. The odds ratio (OR) and the 95% confidence interval were both estimated. Confusion factors were studied. RESULTS: Altogether 216 children were analysed. The prevalence of atopic dermatitis (OR = 7.1; p < 0.01), rhinoconjunctivitis (OR = 7.3; p < 0.01) and allergic asthma (OR = 4.69; p < 0.01), as well as their previous and overall medical diagnoses, is significantly higher and more severe in children with migraine. Dermatitis and rhinitis are more commonly diagnosed in the cases with aura. CONCLUSIONS: The prevalence and the percentage of prior and overall diagnoses of the three atopic diseases are significantly higher in children with migraine.

Relación entre la migraña y la atopia en la infancia: estudio retrospectivo de casos y controles / Relationship between migraine and atopy in childhood: a retrospective case-control study

Introducción. La migraña es un padecimiento común en la infancia. La atopia es la predisposición al padecimiento de una o varias de las siguientes patologías: dermatitis atópica, rinoconjuntivitis y asma. Objetivo. Estudiar si existe una relación entre la atopia, valorando cada una de sus variantes y la migraña con o sin aura. El uso práctico de conocer esta asociación incluye la mejora en el diagnóstico de la migraña, con frecuencia difícil en niños. Sujetos y métodos. Estudio retrospectivo de casos y controles de niños (5-15 años) con migraña o sin ella; tiempo de reclutamiento: seis meses. Se evalúan edad, sexo, preguntas de un cuestionario sobre atopia para medir prevalencia, y diagnóstico médico constatable en su historial y global (intersección de los previos), entre otros datos. Se realiza un análisis estadístico. Se estima la odds ratio (OR) junto con el intervalo de confianza del 95%. Se estudian factores de confusión. Resultados. Se analizan 216 niños. La prevalencia de dermatitis atópica (OR = 7,1; p < 0,01), rinoconjuntivitis (OR = 7,3;p < 0,01) y asma alérgica (OR = 4,69; p < 0,01), así como su diagnóstico médico previo y global, es significativamente más alta y grave en los niños con migraña. Se observa más diagnóstico de dermatitis y rinitis en los casos con aura. Conclusiones. La prevalencia y el porcentaje de diagnóstico previo y global de las tres enfermedades atópicas son significativamente mayores en los niños con migraña (AU)

Introduction. Migraine is a common complaint in childhood. Atopy is the predisposition to the complaint of one or more of the following conditions: atopic dermatitis, rhinoconjunctivitis and asthma. Aim. To examine whether there is a relationship between atopy, taking into account each of its different variants, and migraine with or without aura. The practical application of knowing about this association includes improvement in the diagnosis of migraine, which is often difficult in children. Subjects and methods. We performed a retrospective case-control study of children (5-15 years old) with and without migraine; recruitment time: six months. Data evaluated included age, sex, questions from a questionnaire about atopy to measure prevalence, and medical diagnosis that appears in the patient’s medical record and overall (intersection of the previous ones), among other things. A statistical analysis was performed. The odds ratio (OR) and the 95% confidence interval were both estimated. Confusion factors were studied. Results. Altogether 216 children were analysed. The prevalence of atopic dermatitis (OR = 7.1; p < 0.01), rhinoconjunctivitis (OR = 7.3; p < 0.01) and allergic asthma (OR = 4.69; p < 0.01), as well as their previous and overall medical diagnoses, is significantly higher and more severe in children with migraine. Dermatitis and rhinitis are more commonly diagnosed in the cases with aura. Conclusions. The prevalence and the percentage of prior and overall diagnoses of the three atopic diseases are significantly higher in children with migraine (AU)

[Lennox-Gastaut syndrome in Spain: a descriptive retrospective epidemiological study]. / Síndrome de Lennox-Gastaut en España: estudio epidemiológico retrospectivo y descriptivo.

INTRODUCTION: Lennox-Gastaut syndrome (LGS) is one of the most severe epileptic syndromes in childhood. It is characterised by the presence of several types of seizures, a characteristic electroencephalographic trace and its frequent association with mental retardation. There are no accurate data on the epidemiology of LGS in Spain. AIM: To describe the epidemiological profile of LGS in Spain. PATIENTS AND METHODS: We conducted a retrospective epidemiological study of a series of 331 patients with LGS from 50 Spanish hospitals. Patients were considered to be cases of LGS if they had at least two of the three types of seizures that characterise LGS (axial tonic seizures, atypical absences and atonic seizures) and displayed slow diffuse intercritical spike-wave activity (lower than 3 Hz) in the electroencephalogram in wakefulness. RESULTS: The mean age of the patients was 18.2 +/- 13.5 years. Of the total sample, 62% were males and 97% had cognitive retardation. And 54% of cases had a symptomatic aetiology. The most frequent types of seizures were axial tonic (89%), followed by the atypical absent type (84%) and atonic seizures (69%). In all, 99% of patients were treated with polytherapy, the most commonly used drugs being valproic acid, lamotrigine and topiramate. CONCLUSIONS: The results of the study are in line with those from previous analyses carried out in populations with similar characteristics. The high percentage of LGS patients with cognitive retardation in this epileptic encephalopathy results in important family and social repercussions.

[The ethical aspects of population screening programme of rare diseases]. / Recomendaciones sobre los aspectos éticos de los programas de cribado de población para enfermedades raras.

The Committee on Ethics of the Instituto de Investigación de Enfermedades Raras (CEIIER) of the Spanish National Institute of Health Carlos III, presents this article dealing with ethical guidelines regarding the implementation of screening population programmes with special emphasis on genetic screening. After a critical review it has been addressed 24 recommendations concerning 14 topics: evaluation of the opportunity of the programme, including ethical analysis besides scientific evidences and cost/benefits issues; the need to differentiate between research and public health intervention and to built a specific and comprehensive programme; the creation of an interdisciplinary working group which control its implementation and prepare a protocol including justification, development, therapeutic or preventive actions and follow-up activities; the review of the programme by an independent Ethical committee; the guarantee of the voluntary, universal and equitable population access, which requires sufficient information on the programme and their specific relevant facts, as incidental detection of heterozygous state in minors in newborn screening and the relevance of non directive genetic counselling specially in prenatal screening offered to pregnant women; considerations regarding future uses of samples for research purposes; total quality and periodic programme evaluation; guarantee of personal data confidentiality and the conflict of interest statement of the members of all the Committees involved in the programme.

Recomendaciones sobre los aspectos éticos de los programas de cribado de población para enfermedades raras / The ethicals aspects of population screening programme of rare diseases

El Comité de Ética del Instituto de Investigación de EnfermedadesRaras (CEIIER) del Instituto de Salud Carlos III, dentro de lasactividades que desarrolla, ha preparado el presente documento derecomendaciones éticas con respecto a la puesta en marcha de programasde cribado de población, con especial referencia a los cribadosgenéticos. Basándose en una revisión crítica se han elaborado 24recomendaciones concernientes a 14 apartados que inciden principalmenteen los siguientes puntos: la evaluación de la pertinencia delprograma, incorporando al proceso el análisis ético, de las evidenciascientíficas y de la oportunidad de los costes; la necesidad de diferenciarentre investigación e intervención y de que el programa seaespecífico e integral; la creación de un grupo de trabajo interdisciplinarque controle su desarrollo y elabore un protocolo de programaque incluya su justificación, desarrollo y ejecución incluyendo lasactividades terapéuticas o preventivas y actividades de seguimiento;la revisión necesaria del programa por un Comité de Ética independiente;la garantía de acceso voluntario, universal y equitativo querequiere de la información sobre el programa y hechos específicos silos hubiera, como la detección accidental del estado heterocigoto enmenores en los programas de cribado neonatal y las necesidades deconsejo genético; la consideración del uso futuro de las muestrasremanentes; la calidad total y evaluación periódica del programa; lasgarantías de confidencialidad de los datos de carácter personal; ladeclaración de conflictos de intereses de los miembros de losComités implicados en el programa(AU)

The Committee on Ethics of the Instituto de Investigación deEnfermedades Raras (CEIIER) of the Spanish National Institute ofHealth Carlos III, presents this article dealing with ethical guidelinesregarding the implementation of screening population programmeswith special emphasis on genetic screening. After a critical review ithas been addressed 24 recommendations concerning 14 topics: evaluationof the opportunity of the programme, including ethical analysisbesides scientific evidences and cost/benefits issues; the need todifferentiate between research and public health intervention and tobuilt a specific and comprehensive programme; the creation of aninterdisciplinary working group which control its implementationand prepare a protocol including justification, development, therapeuticor preventive actions and follow-up activities; the review of theprogramme by an independent Ethical committee; the guarantee ofthe voluntary, universal and equitable population access, which requiressufficient information on the programme and their specific relevantfacts, as incidental detection of heterozygous state in minors innewborn screening and the relevance of non directive genetic counsellingspecially in prenatal screening offered to pregnant women; considerationsregarding future uses of samples for research purposes;total quality and periodic programme evaluation; guarantee of personaldata confidentiality and the conflict of interest statement of themembers of all the Committees involved in the programme(AU)

[Role of generic antiepileptic drugs in the treatment of childhood epilepsy]. / Papel de los fármacos antiepilépticos genéricos en el tratamiento de la epilepsia infantil.

The use of generic instead of trade mark antiepileptic drugs raises the question of cost/benefit risks. The efficacy and side effects of the generic AED should be similar to the trade mark drugs. Otherwise, the substitution is not justified despite the benefits of reduced cost if efficacy or side effects are not similar in order to avoid possible recurrence of seizures with potential health hazard consequences and legal action. The purpose of this paper is to review the scientific medical literature to determine the efficacy and side effects of generic and trademark antiepileptic drugs.

Papel de los fármacos antiepilépticos genéricos en el tratamiento de la epilepsia infantil / Role of generic antiepileptic drugs in the treatment of childhood epilepsy

La aparición de fármacos genéricos en el mercado, en sustitución de marcas registradas®, y las adecuadas regulaciones de las autoridades sanitarias en los distintos países ha condicionado hasta la actualidad una polémica sobre el riesgo costo/beneficio de tal sustitución en el paciente afecto de epilepsia. El binomio costo/beneficio debe dar por demostrado de manera clara que el paciente puede beneficiarse de tal sustitución sin correr riesgo alguno significativo. Por ello se valoran los distintos aportes en la literatura médica al respecto, que analizan estos riesgos y beneficios y en especial el hecho esencial de la bioequivalencia de ambas formulaciones, en especial en las situaciones de aquellos fármacos antiepilépticos de margen o índice terapéutico estrecho que hagan inviable la equivalencia de la biodisponibilidad del fármaco, la ausencia de repercusión clínica real en el paciente así como la evidencia que existe un beneficio económico claro al valorar el citado binomio riesgo/beneficio. La revisión efectuada señala la clara existencia de desventajas potenciales del cambio de un fármaco antiepiléptico (FAE) original de marca a un genérico como: distinta biodisponibilidad, bioequivalencia no demostrada, riesgo de reaparición de crisis en pacientes controlados y variabilidad de la respuesta de los FAE en el paciente epiléptico, imposible de predecir. Por ello se aconseja valorar la importancia de un fracaso terapéutico tras un cambio a genérico, en especial en casos de margen terapéutico estrecho, la biodisponibilidad permisible con valoración de la variabilidad individual del paciente, situación médico-legal de tal cambio y la realidad de los ahorros y costos potenciales derivados.

The use of generic instead of trade mark antiepileptic drugs raises the question of cost/benefit risks. The efficacy and side effects of the generic AED should be similar to the trade mark drugs. Otherwise, the substitution is not justified despite the benefits of reduced cost if efficacy or side effects are not similar in order to avoid possible recurrence of seizures with potential health hazard consequences and legal action. The purpose of this paper is to review the scientific medical literature to determine the efficacy and side effects of generic and trademark antiepileptic drugs.

[Ethics guidelines for the creation and use of registries for biomedical research purposes]. / Directrices éticas sobre la creación y uso de registros con fines de investigación biomédica.

The clinical information stored in registries and records of different types is a fundamental tool for biomedical research. Up until just a few years ago, hardly any limitations existed on the creation and use of epidemiological registries or the use of information from pre-existing records for research purposes. This situation has changed substantially due mainly to the growing importance current laws place upon the safeguarding of the privacy and confidentiality of personal data. Although the legal framework is already quite explicit, a certain degree of leeway exists for ethical debate and prudence advice for the purpose of conducting valid, useful research with this information which will also respect the rights of the subjects and the laws in force. These guidelines deal with those aspects which have been considered relevant from an ethical standpoint in the handling of records and registries for research-related purposes, including not only the use but also the creation proper of the registries. A total of twenty-four recommendations are provided, grouped into ten sections: warranting of the creation of registry, organization and definition of responsibilities, scientific validity of the research project, ethical requirements of the collections of anonymous and anonymized data, ethical requirements of the registries including personal data, uses of medical records for research purposes, use of historical records of deceased individuals, contact with the research subjects, notification of results and review by a Research Ethics Committee.

Directrices éticas sobre la creación y uso de registros con fines de investigación biomédica / Ethics guidelines for the creation and use of registries for biomedical research purposes

La información clínica almacenada en registros de diverso tipo constituye una herramienta fundamental para la investigación biomédica. Hasta hace pocos años la creación y uso de registros epidemiológicos, o la utilización de información procedente de registros pre-existentes con fines de investigación, apenas tenía limitaciones. Esta situación ha cambiado de modo sustancial debido básicamente a la creciente importancia que las leyes actuales conceden a la protección de la intimidad, la privacidad y la confidencialidad de los datos de carácter personal. Aunque el marco legal es ya muy explícito, hay un cierto espacio para la deliberación ética y el consejo prudente, al objeto de realizar con dicha información una investigación válida y útil y que, al mismo tiempo, respete los derechos de los sujetos y la legalidad vigente. En las presentes directrices se abordan aquellos aspectos que se han considerado relevantes desde un punto de vista ético en el manejo de registros con fines de investigación, incluyendo no sólo el uso sino la creación misma del registro. Se proporcionan 24 recomendaciones agrupadas en 10 apartados: justificación de la creación de un registro, organización y definición de responsabilidades, validez científica del proyecto de investigación, requisitos éticos de las colecciones de datos anónimos y de los registros anonimizados, requisitos éticos de los registros que contienen datos de carácter personal, usos de la historia clínica con fines de investigación, uso de registros históricos y de personas fallecidas, contacto con los sujetos de investigación, comunicación de resultados y revisión por un Comité de Ética de la Investigación (AU)

The clinical information stored in registries and records of different types is a fundamental tool for biomedical research. Up until just a few years ago, hardly any limitations existed on the creation and use of epidemiological registries or the use of information from pre-existing records for research purposes. This situation has changed substantially due mainly to the growing importance current laws place upon the safeguarding of the privacy and confidentiality of personal data. Although the legal framework is already quite explicit, a certain degree of leeway exists for ethical debate and prudence advice for the purpose of conducting valid, useful research with this information which will also respect the rights of the subjects and the laws in force. These guidelines deal with those aspects which have been considered relevant from an ethical standpoint in the handling of records and registries for research-related purposes, including not only the use but also the creation proper of the registries. A total of twenty-four recommendations are provided, grouped into ten sections: warranting of the creation of registry, organization and definition of responsibilities, scientific validity of the research project, ethical requirements of the collections of anonymous and anonymized data, ethical requirements of the registries including personal data, uses of medical records for research purposes, use of historical records of deceased individuals, contact with the research subjects, notification of results and review by a Research Ethics Committee (AU)

3-methylglutaconic aciduria type 4 manifesting as Leigh syndrome in 2 siblings.

The authors report the case of a pair of siblings with 3-methylglutaconic aciduria type 4 manifesting as Leigh syndrome. Disease progression was monitored from birth until the present. Both patients fulfilled the diagnostic criteria for Leigh syndrome along with increased urinary excretion of 3-methylglutaconic acid and 3-methylglutaric acid (biochemical markers of methylglutaric acid) in several determinations. No mitochondrial respiratory chain defects in muscle biopsy were detected. Although mitochondrial abnormalities are the most common known cause of Leigh syndrome, there have been several reports of links with nonmitochondrial metabolic disorders. Descriptions of 3-methylglutaric acid type 4 associated with Leigh syndrome are rare.

[Recommendations on the ethical aspects of specimen collections and human biobanks for biomedical research purposes]. / Recomendaciones sobre los aspectos éticos de las colecciones de muestras y bancos de materiales humanos con fines de investigación biomédica.

The collecting and storing of human biospecimens and associated data are a historical fact in medicine, but the biobank is a very recent concept. The advent of new technologies making it possible to store all types of specimens, including cells capable of staying alive outside the human body for an indefinite length of time, and to obtain scientific data of all types, including genetic information, has opened up a whole new realm of possibilities for research. All of the above has led to complex ethical issues coming to fore concerning the specimen donors, the researchers handling the specimens and society as a whole. This document is aimed at providing some recommendations to serve as a guideline and encourage responsible deliberation among all those involved, thus contributing to society's recognition and trust in the forthrightness of the research and the solidary end purposes thereof. A total of nineteen recommendations have been drafted concerning the following aspects: Biobank organization and operation, degree of specimen identification, data management guarantees, consent for taking part in research and for the incorporation of specimens into the biobank, the right to know and the right not to know, consent for transferring specimens to third parties, specimen harvesting in deceased individuals, management of the pre-existing biospecimen collections, title to and commercialization of specimens and research findings and resulting payback benefiting the community.

[Rett syndrome: 50 years' history of a still not well known condition]. / Síndrome de Rett: 50 años de historia de un trastorno aun no bien conocido.

Since it was first described by Andrea Rett 50 years ago, Rett syndrome (RS) has been the subject of further investigations, nonetheless it continues to be a not well known condition. Our own experience and an updated literature review on RS is presented. RS is a severe dominant X chromosome-linked neurodevelopmental disorder with a characteristic clinical picture that mostly occurs in girls, most of the cases are sporadic and genetically determined. The diagnosis of RS is made based on observation and clinical assessment. Main clinical features are mental retardation, behavioural changes, stereotypes, loss of speech and hand skills, gait apraxia, irregular breathing with hyperventilation while awake, and frequent seizures. The internationally established criteria are reviewed. RS is caused by mutations in MECP2 in the majority of cases, but a proportion of atypical cases may result from mutations in CDKL5, particularly the early onset seizure variant. However, the molecular pathogenesis of this disorder remains unclear, as well as the relation between the mutations in MECP2 and other neurodevelopmental disorders. Neuroimaging, neuropathological and biochemical findings in RS are reviewed. Besides symptomatic treatment, no therapeutic trials have shown effectiveness. Some perspectives in the treatment of RS have been provided by a recent work showing a phenotypic reversal by activation of MeCP2 expression in a mouse model.

Acute hemiparesis in a boy with type 1 diabetes.

Unlike the case in adult-onset diabetes, neurologic complications in children with type 1 diabetes are uncommon. We report a case of a 14-year-old boy with type 1 diabetes who presented at our emergency unit with acute hemiparesis and intense headache without hypoglycaemia. Two hours after onset, the symptoms had subsided. It is the intention of the authors to increase the awareness of this association, whose prognosis is almost invariably good.