RESUMO
Pyroglutamate amyloid beta3-42 (pGlu-Abeta3-42), a highly amyloidogenic and neurotoxic form of Abeta, is N-terminally truncated to form a pyroglutamate and has recently been proposed as a key target for immunotherapy. Optimized ACI-24, a vaccine in development for the treatment and prevention of Alzheimer's disease, focuses the antibody response on the first 15 N-terminal amino acids of Abeta (Abeta1-15). Importantly, clinical data with an initial version of ACI-24 incorporating Abeta1-15, established the vaccine's safety and tolerability with evidence of immunogenicity. To explore optimized ACI-24's capacity to generate antibodies to pGlu-Abeta3-42, pre-clinical studies were carried out. Vaccinating mice and non-human primates demonstrated that optimized ACI-24 was well-tolerated and induced an antibody response against Abeta1-42 as expected, as well as high titres of IgG reactive with pyroGlu-Abeta. Epitope mapping of the polyclonal response confirmed these findings revealing broad coverage of epitopes particularly for Abeta peptides mimicking where cleavage occurs to form pGlu-Abeta3-42. These data are in striking contrast to results obtained with other clinically tested Abeta targeting vaccines which generated restricted and limited antibody diversity. Taken together, our findings demonstrate that optimized ACI-24 vaccination represents a breakthrough to provide a safe immune response with a broader Abeta sequence recognition compared to previously tested vaccines, creating binders to pathogenic forms of Abeta important in pathogenesis including pGlu-Abeta3-42.
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INTRODUCTION: Cannabidiol (CBD) is one of the main components of the cannabis plant that has demonstrated anti-epileptic seizure effect. Following its clinical development, in September 2019 the European Medicines Agency approved its indication for the adjunctive therapy of epileptic seizures associated with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS), combined with clobazam (CLB), in patients of 2 years of age and older. AIM: To establish recommendations on the use of plant-derived highly purified CBD on which Spanish experts have reached consensus for the treatment of epilepsy in patients with DS and LGS based on their clinical experience and the scientific evidence. DEVELOPMENT: Consensus meeting with the participation of four Spanish neurologists and neuropediatric who are experts in epilepsy secondary to DS and LGS and with clinical experience in the use and management of CBD. They discussed on several topics, including posology (starting dose, dose escalation schema), efficacy (assessment of outcomes and indications for treatment withdrawal), and safety (evaluation, drug-drug interactions, adverse events management). CONCLUSIONS: In order to optimise CBD treatment, a slow dose escalation (= 4 weeks) is recommended until the maximum recommended dose or the desire effect is reached. It is also recommended that the concomitant antiseizure medications (ASMs) be reduced in case of adverse events due to interactions, and that the treatment continues for at least 6 months if it is well tolerated. The efficacy and safety of CBD must be assessed individually, considering the benefits and risks for individual patients.
TITLE: Cannabidiol para el tratamiento del síndrome de Lennox-Gastaut y del síndrome de Dravet: recomendaciones de expertos sobre su uso en la práctica clínica en España.Introducción. El cannabidiol (CBD) es uno de los componentes principales de la planta del cannabis que ha demostrado efecto ante las crisis epilépticas. Tras su desarrollo clínico, obtuvo su aprobación por la Agencia Europea del Medicamento en septiembre de 2019 para el tratamiento de las crisis epilépticas asociadas con el síndrome de Lennox-Gastaut (SLG) y el síndrome de Dravet (SD), en combinación con el clobazam (CLB), en pacientes a partir de los dos años. Objetivo. Establecer unas recomendaciones de manejo del CBD derivado de la planta altamente purificado consensuadas por expertos españoles en el tratamiento de la epilepsia para su uso en pacientes con SD y SLG, basándose en su experiencia clínica y en la evidencia científica. Desarrollo. Reunión de consenso de un grupo de cuatro neurólogos y neuropediatras españoles expertos en el manejo de la epilepsia asociada al SD y el SLG y con experiencia clínica en el uso de CBD. Se debatió sobre diferentes áreas, incluyendo la posología (dosis de inicio, pauta de escalada), la eficacia (valoración de resultados e indicaciones para la suspensión del tratamiento) y la seguridad (evaluación, interacciones entre fármacos, manejo de efectos adversos). Conclusiones. Para optimizar el tratamiento con CBD, se recomienda una pauta lenta de escalada de dosis (de cuatro semanas o más) hasta alcanzar la dosis máxima recomendada o el efecto deseado, reducir los fármacos anticrisis epilépticas concomitantes si aparecen efectos adversos por interacciones y mantener el tratamiento al menos seis meses si se tolera. La eficacia y la seguridad del CBD deben evaluarse de forma individual, considerando el beneficio y el riesgo para cada paciente.
Assuntos
Anticonvulsivantes/uso terapêutico , Canabidiol/uso terapêutico , Epilepsias Mioclônicas/tratamento farmacológico , Síndrome de Lennox-Gastaut/tratamento farmacológico , Guias de Prática Clínica como Assunto , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/efeitos adversos , Canabidiol/administração & dosagem , Canabidiol/efeitos adversos , Clobazam/administração & dosagem , Clobazam/uso terapêutico , Clonazepam/administração & dosagem , Clonazepam/uso terapêutico , Diazepam/administração & dosagem , Diazepam/uso terapêutico , Dioxolanos/administração & dosagem , Dioxolanos/uso terapêutico , Esquema de Medicação , Sinergismo Farmacológico , Quimioterapia Combinada , Humanos , Fenobarbital/administração & dosagem , Fenobarbital/uso terapêutico , Pirrolidinonas/administração & dosagem , Pirrolidinonas/uso terapêutico , Espanha , Triazóis/administração & dosagem , Triazóis/uso terapêutico , Ácido Valproico/administração & dosagem , Ácido Valproico/uso terapêuticoRESUMO
INTRODUCTION: Dravet syndrome (DS) is a rare, drug resistant epilepsy that starts very early in life with febrile seizures followed by cognitive impairment and diverse seizure types. AIM: To generate evidence on the epidemiology of DS, its diagnosis, patient-flow, treatment and unmet needs from the perspective of Spanish experts. DEVELOPMENT: A two-round Delphi study involving 19 physicians was conducted. Questionnaires were based on literature review and validated by clinical experts. Consensus was reached when topics were subject to routine clinical practice and individual experience, or the coefficient of variation among answers was <= 0.3. The estimated number of new DS patients is 73 per year. Prevalence is estimated to be between 348-540 patients. DS is mostly diagnosed in children. Survival varies from 5 to 60 years. There is no standardised follow-up of patients beyond the age of 18 and mortality rates are uncertain. No standard guidelines exist for diagnosing or treating DS. It takes 9 to 15 months to confirm the diagnosis and genetic testing is unevenly available. Valproic acid, clobazam, stiripentol and topiramate are commonly used. Poor efficacy and safety are the main reasons for treatment switch. CONCLUSIONS: The epidemiology of DS in Spain is not well known and several areas of unmet needs still exist. Experts' views offer a starting point for further research into the reality of DS in Spain. Epidemiological studies, consensus criteria, easy access to genetic testing, treatment options, training and research into quality of life aspects are highly needed.
TITLE: Determinacion de la epidemiologia, el flujo de pacientes y el tratamiento del sindrome de Dravet en España.Introduccion. El sindrome de Dravet (SD) es una epilepsia rara y resistente a los farmacos que comienza en etapas muy precoces de la vida con convulsiones febriles, seguidas de deterioro cognitivo y diversos tipos de crisis epilepticas. Objetivo. Generar datos objetivos sobre la epidemiologia del SD, su diagnostico, el flujo de pacientes, el tratamiento y las necesidades no cubiertas desde el punto de vista de expertos españoles. Desarrollo. Se efectuo un estudio Delphi de dos rondas en el que participaron 19 medicos. Los cuestionarios se basaron en una revision de la bibliografia y fueron validados por expertos clinicos. Se alcanzo consenso si los temas se referian a la practica clinica habitual y la experiencia individual, o si el coeficiente de variacion entre las respuestas era <= 0,3. El numero estimado de pacientes nuevos con SD es de 73 al año. La prevalencia se calcula entre 348 y 540 pacientes. El SD se diagnostica principalmente en niños. La supervivencia varia entre los 5 y los 60 años. No existe ningun seguimiento normalizado para los pacientes de mas de 18 años de edad, y las tasas de mortalidad son inciertas. No existen guias normalizadas para diagnosticar o tratar el SD. Se tarda de 9 a 15 meses en confirmar el diagnostico, y la disponibilidad de los analisis geneticos es irregular. Normalmente se utilizan el acido valproico, el clobazam, el estiripentol y el topiramato. La escasa eficacia y la seguridad son los motivos principales de los cambios de tratamiento. Conclusiones. La epidemiologia del SD en España es poco conocida, y sigue habiendo necesidades no cubiertas en algunas areas. Las opiniones de expertos suponen un punto de partida para poder investigar la realidad del SD en España. Los estudios epidemiologicos, los criterios de consenso, el acceso facil a las pruebas geneticas, las opciones de tratamiento, la formacion y la investigacion de la calidad de vida relacionada con la salud constituyen todos ellos aspectos muy necesarios.
Assuntos
Epilepsias Mioclônicas/epidemiologia , Adulto , Idade de Início , Anticonvulsivantes/uso terapêutico , Criança , Pré-Escolar , Consenso , Continuidade da Assistência ao Paciente , Técnica Delphi , Gerenciamento Clínico , Progressão da Doença , Resistência a Medicamentos , Epilepsias Mioclônicas/tratamento farmacológico , Epilepsias Mioclônicas/genética , Humanos , Lactente , Prevalência , Encaminhamento e Consulta , Espanha/epidemiologia , Morte Súbita do Lactente/etiologiaRESUMO
INTRODUCTION: Infantile cerebral palsy is a well-known condition, the prevalence of which has varied only slightly over the years. The most common subtype is spastic diplegia, and spasticity is the most disabling symptom. Its treatment involves a multidisciplinary intervention that includes rehabilitation, the use of drugs, and orthopaedic and nervous system surgery, where selective dorsal rhizotomy is a prominent procedure. AIM: To present a thorough review of the use, indication and long-term consequences of selective dorsal rhizotomy. DEVELOPMENT: It is a minimally invasive procedure aimed at reducing spasticity in the lower extremities in order to improve the ability to walk, lessen pain, facilitate care in everyday life and diminish the need for orthopaedic surgery. The literature contains a wide range of criteria for its use, and the main indication is spastic diplegia with the absence of dystonia. It is routinely performed in several countries, while we have no evidence of its application in ours. CONCLUSIONS: Following the literature review, we believe there is enough experience to state that selective dorsal rhizotomy is a safe and simple technique from which many patients with spasticity of the lower limbs secondary to infantile cerebral palsy can benefit in both the short and the long term.
TITLE: Rizotomia dorsal selectiva: revision bibliografica de esta tecnica para el tratamiento de la espasticidad en la paralisis cerebral infantil.Introduccion. La paralisis cerebral infantil conforma una entidad bien conocida cuya prevalencia ha variado poco a lo largo de los años. El subtipo mas comun es la diplejia espastica, y la espasticidad es el sintoma mas incapacitante. Para su tratamiento es preciso una intervencion multidisciplinar que auna rehabilitacion, uso de farmacos y cirugia ortopedica y del sistema nervioso, donde destaca la rizotomia dorsal selectiva. Objetivo. Mostrar una amplia revision del uso, indicaciones y consecuencias a largo plazo de la rizotomia dorsal selectiva. Desarrollo. Se trata de una intervencion minimamente invasiva dirigida a disminuir la espasticidad en las extremidades inferiores con el fin de mejorar la deambulacion, aminorar el dolor, facilitar los cuidados de la vida diaria y reducir la necesidad de cirugias ortopedicas. En la bibliografia hay una amplia variabilidad de criterios para su uso, y la principal indicacion es la diplejia espastica con ausencia de distonia. Diversos paises lo practican de forma rutinaria, mientras que en el nuestro no tenemos aun constancia de ello. Conclusiones. Tras la revision de la bibliografia consideramos que existe suficiente experiencia como para afirmar que la rizotomia dorsal selectiva es una tecnica segura y sencilla de la que muchos pacientes con espasticidad de las extremidades inferiores secundaria a paralisis cerebral infantil se pueden beneficiar a corto y largo plazo.
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Paralisia Cerebral/cirurgia , Rizotomia/métodos , Paralisia Cerebral/terapia , Criança , Pré-Escolar , Terapia Combinada , Medicina Baseada em Evidências , Seguimentos , Humanos , Laminectomia , Metanálise como Assunto , Limitação da Mobilidade , Espasticidade Muscular/cirurgia , Modalidades de Fisioterapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
AIM: To know the current state of the approach of attention deficit hyperactivity disorder (ADHD) in neuropediatricians. SUBJECTS AND METHODS: A telematic survey was carried out to collect preliminary information on the interest, difficulties in the management and treatment of ADHD to the 437 fellowship of the Neuropediactric Spanish Society (SENEP). RESULTS: Only 32.49% of the sent questionnaires were answered, with important geographic variability. 97.89% stated that 50% of their consultations were children with learning disabilities and ADHD. Regarding who started treatment for ADHD in their area, the majority answered that the neuropediatrician (57.97%), followed by the child psychiatrist (34.78%) and the primary care pediatrician (5.31%). The lack of a psycho-pedagogical study by the school (49.79%), followed by the lack of time in the consultation (29.11%), was cited as the greatest difficulty in the initial assessment of children with suspected ADHD. Concerning the difficulties in the follow-up, the biggest complaint was the lack of coordination between professionals, the school and parents. And, lastly, regarding the type of treatment use, most patients were on prolonged-release methylphenidate, a stable percentage using immediate release methylphenidate as a single or combined treatment, and in a lower range was the use of clonidine and atomoxetine, and an incipient use of lisdexamphetamine were observed. 80% of the patient showed adherence to pharmacological treatment after one year. CONCLUSIONS: It is necessary to advance in the training and continuous education of our neuropediatric specialists in ADHD and to homogenize the clinical practice and coordination with education system in the Spanish territory.
TITLE: Estado actual del enfoque del trastorno por deficit de atencion/hiperactividad en neuropediatria.Objetivo. Conocer el estado actual del enfoque del trastorno por deficit de atencion/hiperactividad (TDAH) entre los neuropediatras. Sujetos y metodos. Se realizo una encuesta telematica que recogia informacion preliminar sobre el interes, las dificultades en el manejo y el tratamiento del TDAH a los 437 socios de la Sociedad Española de Neurologia Pediatrica. Resultados. Respondio un 32,49% de los cuestionarios enviados, con una importante variabilidad geografica. El 97,89% afirmo que el 50% de sus consultas eran niños con trastornos de aprendizaje y TDAH. Respecto a quien iniciaba el tratamiento para el TDAH en su area, la mayoria contesto que el neuropediatra (57,97%), seguido del psiquiatra infantil (34,78%) y del pediatra de atencion primaria (5,31%). Respecto a las mayores dificultades para la valoracion inicial de los niños con sospecha de TDAH, se citaron la falta de un estudio psicopedagogico por parte de la escuela (49,79%), seguido de la falta de tiempo en la consulta (29,11%). Sobre las dificultades en el seguimiento, la mayor queja se produjo por la falta de coordinacion entre los profesionales, la escuela y los padres. Respecto a la medicacion, la mayoria de los pacientes se encontraba en tratamiento con algun tipo de metilfenidato de liberacion prolongada, un porcentaje estable utilizaba metilfenidato de liberacion inmediata como tratamiento unico o combinado, y se observo en un rango inferior el uso de clonidina y atomoxetina, y un incipiente uso de lisdexanfetamina. La adhesion al tratamiento farmacologico al año fue alrededor del 80%. Conclusiones. Es necesario avanzar en la capacitacion y educacion continua de nuestros especialistas neuropediatricos en el manejo del TDAH, y en homogeneizar la practica clinica y la coordinacion con educacion en el territorio español.
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Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Criança , Humanos , Neurologia , Pediatria , Padrões de Prática MédicaRESUMO
INTRODUCTION: The Children's Communication Checklist (CCC) by Bishop is a useful scale for evaluation of pragmatic verbal abilities in school children. The aim of the study is to ascertain the validity and reliability of the CCC in Spanish. SUBJECTS AND METHODS: Answers to the CCC items by parents of 360 children with normal intelligence were analyzed. There were five groups: 160 control children; 68 children with attention deficit hyperactivity disorder, 77 with procedural non-verbal disorder, 25 children with social communication disorder and 30 with autism spectrum disorder. Investigations included: factorial analysis in order to cluster checklist items, reliability analyses of the proposed scales and discriminant analysis to check whether the scale correctly classifies children with pragmatic verbal abilities. RESULTS: Seven factors were obtained (Kaiser-Meyer-Olkin: 0.852) with moderate similarity with those of the original scale: social relationships, interests, and five more that can be grouped into pragmatic verbal ability (conversational abilities, coherence-comprehension, empathy nonverbal communication and appropriateness). All factors are significantly correlated with each other in the control group, and the five that compose pragmatic verbal ability correlate with each other in the clinical groups (Pearson r). The scales have good reliability (Cronbach's alpha: 0.914). The questionnaire correctly classifies 98.9% of grouped cases with and without pragmatic disorder and 78% of subjects in their appropriate clinical group. Besides, the questionnaire allows to differentiate the pathologies according to the presence and intensity of the symptoms. CONCLUSIONS: This Spanish version of the CCC is highly valid and reliable. The proposed statistics can be used as normative-reference values.
TITLE: La adaptacion al castellano de la Children's Communication Checklist permite detectar las dificultades en el uso pragmatico del lenguaje y diferenciar subtipos clinicos.Introduccion. La Children's Communication Checklist (CCC) de Bishop es una prueba util para la valoracion de la pragmatica verbal en los escolares. El objetivo del trabajo es comprobar la fiabilidad y la validez de esta escala en castellano. Sujetos y metodos. Se analiza la CCC contestada por los padres de 360 niños/as de 4-12 años, con inteligencia normal, 160 controles y 200 de cuatro grupos clinicos: trastorno por deficit de atencion/hiperactividad (n = 68), trastorno de aprendizaje no verbal procedimental (n = 77), trastorno de la comunicacion social (n = 25) y trastornos del espectro autista de nivel 1 (n = 30). Se realizan analisis: factorial para agrupar los items del cuestionario, de fiabilidad de las nuevas escalas y discriminante para comprobar si clasifica bien a los afectos de dificultades en el uso del lenguaje. Resultados. Se obtienen siete factores (Kaiser-Meyer-Olkin: 0,852) con moderada similitud a las de la CCC original: relaciones sociales, intereses y otros cinco que constituyen pragmatica (habilidades conversacionales, coherencia-comprension, compenetracion, comunicacion no verbal y pertinencia). La correlacion es significativa entre todos ellos, en el grupo control, y entre los cinco que configuran pragmatica, en los grupos clinicos (r de Pearson). La fiabilidad de las escalas es buena (alfa de Cronbach: 0,914). El cuestionario clasifica bien al 98,9% de los casos agrupados con y sin trastorno pragmatico; y al 78% de los participantes en sus correspondientes grupos clinicos. Ademas, permite diferenciar las patologias segun la presencia e intensidad de los sintomas. Conclusiones. Esta version española de la CCC es altamente valida y fiable. Los estadisticos aportados pueden utilizarse como valores de referencia.
Assuntos
Lista de Checagem , Transtornos do Desenvolvimento da Linguagem/classificação , Transtornos do Desenvolvimento da Linguagem/diagnóstico , Criança , Pré-Escolar , Feminino , Humanos , Idioma , Masculino , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
Prolonged seizures and status epilepticus are common neurological medical emergencies. Early and appropriate treatment is essential to reduce morbidity and mortality. Most seizures occur in the community, so parents and caregivers must be prepared for their management. Benzodiazepines (BZD) are the first-line drugs used, with rectal diazepam (DZPr) being the most commonly used in pre-hospital treatment in Spain. In September 2011, the European Medicines Agency (EMA) authorized the use of oromucosal midazolam (MDZb) for the treatment of prolonged acute convulsive seizures in patients aged 3 months to <18 years. MDZb has a rapid onset, short duration of effect, and avoids first-pass hepatic metabolism. MDZb has shown to be at least as or more effective than DZPr to stop the seizures. Buccal administration is easier and more socially accepted, especially in adolescents and adults. It is a safe drug with similar effects to other BZD; MDZb improves the overall cost-effectiveness of seizures management.
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Benzodiazepinas/uso terapêutico , Convulsões/tratamento farmacológico , Estado Epiléptico/tratamento farmacológico , Criança , Serviços de Saúde Comunitária , Humanos , Estado Epiléptico/fisiopatologiaRESUMO
INTRODUCTION: The Practices in Emergency and Rescue medication For Epilepsy managed with Community administered Therapy (PERFECT™) Initiative was set up in 2011 to gain a better understanding of how prolonged convulsive seizures are managed, and rescue medication is administered, in out-of-hospital settings across Europe. This paper explores the initial research findings for Spain. MATERIAL AND METHODS: A review was made of existing clinical guidelines, guidance to schools, and relevant policy and legal frameworks, as well as a survey of 20 healthcare professionals who treat children with prolonged convulsive seizures in Spain. RESULTS: Existing clinical guidelines pertain mainly to the hospital setting, and contain very little information on how prolonged seizures should be managed outside of the hospital. Guidance for schools is unclear as to whether teachers are allowed to administer rescue medication to children, and there is no legal obligation for school staff to administer medication to children under their care. As a result of such uncertainty, whether or not children who experience prolonged seizures receive their rescue medication during school hours depends mostly on the resources and training available in each school. CONCLUSIONS: There is a need for more explicit guidance covering educational and healthcare settings, clearer information to parents and schools, and more systematic training to be made available to caregivers. This is to ensure that all children at risk of a prolonged convulsive seizure receive rescue medication in a timely manner, regardless of where their seizure occurs.
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Anticonvulsivantes/uso terapêutico , Convulsões/tratamento farmacológico , Criança , Hospitais , Humanos , Guias de Prática Clínica como Assunto , Instituições Acadêmicas , Espanha , Fatores de TempoRESUMO
INTRODUCTION: Dravet syndrome is a drug resistant epilepsy which starts in the first year of life with febrile seizures, followed by cognitive impairment and epilepsy with multiple seizure types. Diagnosis has been typically made at the age of three to four years, but earlier diagnosis is now possible as clinical features are better recognised and molecular diagnosis is available. PATIENTS AND METHODS: We studied a series of 14 children with Dravet syndrome or Dravet spectrum epilepsy. A screening test, developed by other authors to distinguish the febrile seizures in Dravet syndrome from febrile seizures from other origin, was applied to the clinical features of the seizures occurring during the first year of life in our patients. RESULTS: Clinical suspicion of Dravet spectrum epilepsy was possible in 100% of children in our series. Moreover, taking into consideration only the first seizure, 79% of patients scored sufficiently to detect Dravet syndrome. CONCLUSIONS: Dravet syndrome can be recognised during the first year of life. It is important that physicians are made aware of these clinical criteria capable to distinguish febrile seizures in Dravet syndrome from febrile seizures of other origin, and set up a protocol to collect appropriate data regarding febrile seizures occurring in the first year of life.
Assuntos
Epilepsia/diagnóstico , Convulsões Febris/diagnóstico , Resistência a Medicamentos , Epilepsia/tratamento farmacológico , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Convulsões Febris/tratamento farmacológicoRESUMO
INTRODUCTION: Alterations in SCN1A gene cause most cases of Dravet syndrome. This finding has increased scientific interest in the syndrome, helping to better define its clinical features and facilitating treatment. AIMS: To update the knowledge on Dravet syndrome and to discuss the role of the molecular studies in improving early detection and specific management of the syndrome. DEVELOPMENT: We review the current information on the causes, clinical and electrical characteristics, treatment and complications of Dravet syndrome. Special emphasis is made on early detection. CONCLUSIONS: The phenotype of Dravet syndrome is now better defined and early detection is already possible. As a consequence, it is now possible to use more specific antiepileptic drugs and to avoid harmful treatments. The benefits of better and prompter control of seizures and earlier cognitive interventions need to be demonstrated in prospective studies of children diagnosed in their first year of life.
Assuntos
Epilepsias Mioclônicas/diagnóstico , Biologia Molecular , Proteínas do Tecido Nervoso/genética , Convulsões Febris/diagnóstico , Canais de Sódio/genética , Anticonvulsivantes/uso terapêutico , Epilepsias Mioclônicas/tratamento farmacológico , Epilepsias Mioclônicas/genética , Epilepsias Mioclônicas/fisiopatologia , Humanos , Canal de Sódio Disparado por Voltagem NAV1.1 , Convulsões Febris/tratamento farmacológico , Convulsões Febris/genética , Convulsões Febris/fisiopatologia , SíndromeRESUMO
BACKGROUND/AIMS: An early, simple, and reliable marker for acute pancreatic allograft rejection is not available. Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) is an interleukin-6-dependent acute-phase positive protein that can act as an anti-inflammatory protein. We studied the response of the ITIH4 in pigs undergoing pancreas allotransplantation (PT) and evaluated this protein as a biomarker for acute graft rejection. METHODS: PT with enteric drainage of the exocrine secretion and systemic venous drainage was performed on 12 Landrace pigs. No immunosuppression was administered. Serum concentrations of glucose, amylase, lipase, insulin, C-peptide, and ITIH4 were determined daily. RESULTS: The response of ITIH4 to PT was early, intense, and prolonged, with 2 peaks in serum concentration. The first peak, which started on day 1 and reached maximum (around 6 mg/dL) on day 3, was attributed to the systemic acute phase response to surgical stress. The second peak, which exceeded the first peak and reached maximum (>8 mg/dL) on day 6, began when the recipients were still normoglycemic, and preceded onset of the diabetic state caused by acute graft rejection by an average of 4 days. CONCLUSION: Serum ITIH4 could help to predict subclinical acute graft rejection after PT in pigs.
Assuntos
alfa-Globulinas/metabolismo , Biomarcadores/sangue , Rejeição de Enxerto/sangue , Transplante de Pâncreas , Animais , Suínos , Transplante HomólogoRESUMO
INTRODUCTION: Children with epilepsy have a higher risk of suffering from cognitive and behavioural disorders, the intensity and repercussions of which may be more or less important. AIM: To examine the different factors, dependent on epilepsy, its cause or the treatment, which can affect the cognitive development of children with epilepsy. DEVELOPMENT: To this end, a review was carried out of the studies that have provided data about the causes of cognitive disorders in children with epilepsy, and we suggest which children with epilepsy are at greater risk of suffering cognitive disorders and how they must be treated. CONCLUSIONS: Children with epilepsy often experience cognitive and behavioural difficulties for the rest of their lives. Sometimes these problems can be avoided, or at least improved. Being familiar with them, together with their early detection and treatment must be priorities for neuropaediatricians who treat children with epilepsy.
Assuntos
Anticonvulsivantes/uso terapêutico , Transtornos do Comportamento Infantil/fisiopatologia , Transtornos Cognitivos/fisiopatologia , Cognição/fisiologia , Epilepsia/fisiopatologia , Epilepsia/psicologia , Idade de Início , Criança , Epilepsia/tratamento farmacológico , HumanosAssuntos
Craniossinostoses/diagnóstico , Imageamento Tridimensional , Humanos , Lactente , MasculinoRESUMO
The acute-phase protein (APP) response to an infection caused by Haemophilus parasuis, the etiological agent of Glässer's disease in pigs, was characterized measuring serum concentrations of pig major acute-phase protein (pig MAP), haptoglobin (HPT), C-reactive protein (CRP) and apolipoprotein A-I (ApoA-I) in colostrum-deprived pigs. They were divided into six experimental groups: non-immunized control group (I); immunized with a non-commercial bacterin (II); with an OMP-vaccine (III); with a sublethal dose (IV); and with two commercial bacterins (V and VI). All groups were challenged intratracheally with 5 × 10(9)CFU of H. parasuis 37 days after immunisation. The highest levels of the positive APPs (pig MAP, HPT and CRP) and the lowest levels of the negative APPs (ApoA-I) were observed in the animals that died as a consequence of the infection, both those in the non-immunized and in the immunized groups. However, the surviving animals (all of them in groups II, V and VI, two pigs in group III, and three in group IV) showed a minor variation in APP response, mainly on day 1 post-challenge (p.c.), and then tended to recover the initial values. APP response was still less pronounced in the groups of pigs previously immunized with bacterins. In conclusion, APP response can reflect Glässer-disease ongoing, showing a correlation between the severity and duration of the clinical signs and lesions and the magnitude of changes in the APP levels.
Assuntos
Proteínas de Fase Aguda/análise , Reação de Fase Aguda , Infecções por Haemophilus/veterinária , Vacinas Anti-Haemophilus/imunologia , Haemophilus parasuis/imunologia , Doenças dos Suínos/imunologia , Animais , Apolipoproteína A-I/sangue , Proteína C-Reativa/análise , Colostro , Infecções por Haemophilus/imunologia , Infecções por Haemophilus/metabolismo , Haptoglobinas/análise , Imunização/veterinária , Masculino , Suínos , Doenças dos Suínos/metabolismoRESUMO
Fatigue and lack of energy are frequent symptoms in children and adolescents. A diagnosis of chronic fatigue syndrome should be considered in children and adolescents who complain of chronic fatigue associated with other symptoms without a demonstrable physical cause. Lack of knowledge about this syndrome and late diagnosis may have a negative impact on the normal development of affected children and adolescents. Treatment should be based on a rehabilitation program with cognitive behavioral therapy and a gradual increase in activities.
Assuntos
Síndrome de Fadiga Crônica , Adolescente , Síndrome de Fadiga Crônica/diagnóstico , Síndrome de Fadiga Crônica/psicologia , Síndrome de Fadiga Crônica/terapia , Feminino , HumanosRESUMO
A total of 240 pigs, 74 days old, half boars and half females, were included in a trial designed to assess the effect of the stress caused by changes in the pattern of food administration on the concentration of acute phase proteins (APP) and productive performance parameters. Half of the animals (pigs fed ad libitum, AL group) had free access to feed, while the rest were fed following a disorderly pattern (DIS group), in which animals had alternating periods of free access to feed and periods of no feeding, when food was removed from the feeder. The periods of free access to feed (two daily periods of 2-h duration) were randomly assigned, and varied from day to day. Total feed supplied per day was identical in both groups, and exceeded the minimal amount required for animals of these ages. Pen feed intake, individual body weights and the main positive pig APP pig major acute phase protein (Pig-MAP), haptoglobin, serum amyloid A (SAA), C-reactive protein (CRP), and the negative APP apolipoprotein A-I (ApoA-I) and transtherytin were determined every 2 weeks during the period 76 to 116 days of age. Animals fed ad libitum had better average daily gain (ADG) than DIS animals in the whole experimental period (P < 0.01) but the differences in ADG were only produced in the two first experimental sub-periods (60 to 74 and 74 to 116 days of age), suggesting that the stress diminished when the animals get used to the DIS feeding. Interestingly differences in ADG between DIS and AL pigs were due to males, whereas no differences were observed between females. The same differences observed for ADG were found for APP. DIS males had higher Pig-MAP concentration than AL males at 74 and 116 days of age, lower ApoA-I concentration at 74 days of age and higher haptoglobin and CRP concentration at 116 days of age (P < 0.05). The results obtained in this trial show an inverse relationship between weight gain and APP levels, and suggest that APP may be biomarkers for the evaluation of distress and welfare in pigs.
RESUMO
In this work, apolipoprotein A-I (ApoA-I) was purified from pig sera. The responses of this protein after sterile inflammation and in animals infected with Actinobacillus pleuropneumoniae or Streptococcus suis were investigated. Decreases in the concentrations of ApoA-I, two to five times lower than the initial values, were observed at 2 to 4 days. It is concluded that ApoA-I is a negative acute-phase protein in pigs.
Assuntos
Infecções por Actinobacillus/imunologia , Apolipoproteína A-I/sangue , Inflamação/imunologia , Infecções Estreptocócicas/imunologia , Doenças dos Suínos/imunologia , Doenças dos Suínos/microbiologia , Infecções por Actinobacillus/microbiologia , Infecções por Actinobacillus/fisiopatologia , Actinobacillus pleuropneumoniae/patogenicidade , Sequência de Aminoácidos , Animais , Apolipoproteína A-I/química , Inflamação/etiologia , Inflamação/fisiopatologia , Dados de Sequência Molecular , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/fisiopatologia , Streptococcus suis/patogenicidade , Suínos , Doenças dos Suínos/fisiopatologia , TerebintinaRESUMO
INTRODUCTION AND DEVELOPMENT: Frontal lobe syndrome in adulthood is characterised by executive function deficits leading to altered behavioural control with difficulties in social interactions and in maintaining stable jobs and interpersonal relationships. Generalisation of this concept to children with early frontal lobe damage is not straightforward. There are complex interactions between the effects of the lesion itself and the effects in other interconnected regions, timing of lesion, how long it was since the lesion occurred to the time of evaluation, and how old the child is at examination. These facts lead to consider that there might be a number of 'frontal syndromes' in childhood rather than a unique one. We report 9 cases of children with early frontal lobe lesions who were followed up for an average of 10 years. CONCLUSION: A variety of different outcomes suggests that prognosis for these patients might be better that previously reported.
Assuntos
Transtornos Cognitivos , Lobo Frontal/patologia , Transtornos da Personalidade , Adulto , Fatores Etários , Criança , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/patologia , Transtornos Cognitivos/fisiopatologia , Lobo Frontal/fisiopatologia , Humanos , Testes Neuropsicológicos , Transtornos da Personalidade/diagnóstico , Transtornos da Personalidade/patologia , Transtornos da Personalidade/fisiopatologiaRESUMO
Reflex epilepsy includes a group of epileptic syndromes in which seizures are induced by a stimulus, either simple (visual, somatosensory, olfactory, auditory) or more complex (e.g., eating, thinking, reading). We document a case of reflex epilepsy in which focal seizures are triggered exclusively by gait. The patient is a young boy whose walking was impaired by abnormal motor phenomena on the left side. These phenomena were elicited by gait and were accompanied by a distinctive ictal pattern with centro-temporal discharges. After comparing this patient with others reported in the literature, we determined that he has an unusual type of reflex epilepsy for which we coined the term "gait epilepsy." This disorder must be considered when physicians are making a differential diagnosis in patients who have symptoms that suggest paroxysmal kinesigenic dystonia (PKD) or selective epileptic gait disorder.