RESUMEN
INTRODUCCIÓN: La epilepsia es un desorden neurológico crónico caracterizado por crisis convulsivas recurrentes, y constituye uno de los trastornos neurológicos con mayor prevalencia global. Una de las etiologías que ha cobrado mayor relevancia en el último tiempo es la autoinmunidad, la que ha venido a dar explicación a muchos casos de epilepsia idiopática o refractaria a tratamientos convencionales. MÉTODOS: Se realizó una búsqueda avanzada asociada a filtros en la plataforma PubMed con los términos "epilepsy" y "autoimmunity". Se seleccionaron 17 artículos de un total de 98 publicados desde el año 2010 en adelante, y que aportaban mas datos desde la fisiopatología. RESULTADOS: En base a la literatura, se describen los principales mecanismos de autoinmunidad que generan epilepsia entre los destacan generación de auto-anticuerpos, desregulación del perfil de citoquinas y pérdida del control de linfocitos T autorreactivos, fenómenos que redundan en neuroinflamación y que se originan en el contexto de infecciones, síndromes paraneoplásicos, autoinmunidad materna transferida a hijos, encefalitis autoinmune, entre otras. CONCLUSIONES: En los últimos años ha habido grandes avances en la comprensión de la epilepsia autoinmune, sin embargo, aún queda mucho por comprender. Pese a lo prometedor que es el descubrimiento de anticuerpos, existen muchos casos de epilepsia con seronegatividad, o casos con la presencia de anticuerpos, pero no la epilepsia autoinmune. Cabe destacar que se debe precisar mecanismos diagnósticos eficaces y específicos que permitan generar protocolos terapéuticos atingentes y resolutivos.
Epilepsy is a neurological chronic disorder which is characterized by recurrent seizures and constitutes one of the most prevalent neurological disorders worldwide. One of the etiologies that has gained a lot of strength is autoimmunity, which has explained a lot of cases of idiopathic epilepsy or epilepsies refractory to common treatment. METHODS: An advanced search was made in the PubMed platform using filters with the terms "epilepsy" and "autoimmunity", showing 98 publications from 2010 onwards, leaving only 17 selected articles because of their pathophysiological information. RESULTS: Based on the literature, we described the main mechanisms of autoimmunity as a cause of epilepsy, standing out the ones related to auto-antibodies production, cytokines disregulation and autoreactive T lymphocytes control alteration, phenomenons related to neuroinflammation that arise from the context of infections, paraneoplastic syndromes, maternal autoimmunity transmitted to their babies, autoimmune encephalitis, etc. CONCLUSIONS: Great advances has been made on the understanding of autoimmune epilepsy in the last years, but despite this there's a lot that we need to comprehend. Although how promising was the discovery of antibodies there's still a lot of seronegative cases or cases with antibodies but without the epilepsy. It is worth mentioning that it becomes necessary to establish efficient and specific diagnostic mechanisms that allow us to create suitable and resolutive therapeutic protocols.
Asunto(s)
Humanos , Autoinmunidad , Epilepsia/inmunología , Convulsiones/inmunología , Epilepsia/etiología , AnticuerposAsunto(s)
Antígenos Helmínticos , Calcinosis/diagnóstico por imagen , Cysticercus/inmunología , Lóbulo Frontal/diagnóstico por imagen , Neurocisticercosis/diagnóstico por imagen , Convulsiones/diagnóstico por imagen , Corticoesteroides/uso terapéutico , Adulto , Animales , Anticonvulsivantes/uso terapéutico , Calcinosis/complicaciones , Calcinosis/inmunología , Calcinosis/parasitología , Cysticercus/patogenicidad , Electroencefalografía , Femenino , Lóbulo Frontal/inmunología , Lóbulo Frontal/parasitología , Humanos , Inyecciones Intravenosas , Neurocisticercosis/complicaciones , Neurocisticercosis/inmunología , Neurocisticercosis/parasitología , Neuroimagen , Convulsiones/complicaciones , Convulsiones/inmunología , Convulsiones/parasitologíaRESUMEN
Among autoimmune encephalitides, a prevalent group are those associated with antibodies against the N-Methyl-D-aspartate receptor, which present with behavior abnormalities, psychosis, seizures and abnormal movements. A new variant, mediated by antibodies against the GABA-A receptor, was recently described. We report a 66-years-old female with this form of encephalitis whose main manifestation was the presence of severe seizures leading to status epilepticus. The patient had a good response to immunomodulatory therapy with intravenous methylprednisolone, azathioprine and anticonvulsants. The laboratory tests initially detected anti-thyroid peroxidase antibodies which lead to the misdiagnosis of Hashimoto Encephalitis, which was ruled out after the detection of antibodies against GABA-A receptor. No malignancy was detected.
Asunto(s)
Humanos , Femenino , Anciano , Receptores de GABA/inmunología , Encefalitis/inmunología , Enfermedad de Hashimoto/inmunología , Convulsiones/inmunología , Imagen por Resonancia Magnética , Encefalitis/diagnóstico por imagen , Enfermedad de Hashimoto/diagnóstico por imagen , Anticuerpos/inmunologíaRESUMEN
Epilepsy is a disorder that affects 1-2% of the population and a significant percentage of these patients do not respond to anticonvulsant drugs available in the market suggesting the need to investigate new pharmacological treatments. Several studies have shown that inflammation occurs during epileptogenesis and may contribute to the development and progression of epilepsy, demonstrating increased levels of pro-inflammatory interleukins in animal models and human patients. The objective of this study was to evaluate the effect of non-steroidal anti-inflammatory diclofenac sodium on the severity of seizures and levels of pro-inflammatory interleukins in animals with kindling model induced by PTZ. The kindling model was induced by injections of subconvulsant doses of PTZ (20mg/kg) in alternated days for 15days of treatment. The animals were divided into four groups: control group given saline, group treated with diazepam (2mg/kg) and groups treated with diclofenac sodium (5 and 10mg/kg). After treatment the open field tests was conducted. The severity of seizures was evaluated by the Racine scale. We evaluated the levels of IL-1ß, IL-6 and TNF-α in the blood, hippocampus and cortex of animals. The treatment with diclofenac sodium, in the PTZ induced kindling model, decreased severity of seizures and interleukin-6 and TNF-α levels in the hippocampus of animals treated with doses of 5 and 10mg/kg. New studies are needed to investigate a new therapeutic approach in the treatment of epilepsy with this anti-inflammatory non-steroidal drug.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Anticonvulsivantes/farmacología , Diclofenaco/farmacología , Convulsiones/tratamiento farmacológico , Convulsiones/inmunología , Animales , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/inmunología , Diazepam/farmacología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Epilepsia/tratamiento farmacológico , Epilepsia/inmunología , Hipocampo/efectos de los fármacos , Hipocampo/inmunología , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Excitación Neurológica , Masculino , Actividad Motora/efectos de los fármacos , Ratas Wistar , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Early malnutrition in life has permanent consequences on brain development and has been suggested to influence seizure susceptibility. Despite malnutrition is not a direct cause of seizures, we hypothesize that malnutrition may modulate inflammatory response and result in cerebral vulnerability to seizures. In this study, we provide evidence that malnutrition may increase susceptibility to seizures in the postnatal period by interleukin-1ß (IL-1ß) in the hippocampus. Malnourished rats were maintained on a nutritional deprivation regimen from postnatal day 1 (P1) to P10. From P7 to P10, the threshold to seizures induced by flurothyl was used as an index of seizure susceptibility. ELISA and western blot was performed to evaluate levels of IL-1ß, IL-1R1, PSD-95 and synapsin. The role of inflammation in the changes of seizure threshold was studied with inhibitors of IL-1ß and IL-1R1. A significant decrease in body weight and seizure threshold was observed in postnatal malnourished rats. Early malnutrition modulates inflammation by high levels of IL-1ß in hippocampus and in serum. Furthermore, our malnutrition paradigm induced an increase in corticosterone levels. Injection of IL-1ß and IL-1R1 inhibitors before seizure induction augments seizure threshold in malnourished rats similar to nourished group. Malnutrition did not change PSD-95 and synapsin expression in the hippocampus. We suggest that malnutrition-induced inflammation might contribute to seizure susceptibility in the postnatal period. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1150-1159, 2016.
Asunto(s)
Hipocampo/crecimiento & desarrollo , Hipocampo/inmunología , Interleucina-1beta/metabolismo , Desnutrición/inmunología , Convulsiones/inmunología , Animales , Animales Recién Nacidos , Western Blotting , Corticosterona/sangre , Corticosterona/metabolismo , Homólogo 4 de la Proteína Discs Large , Ensayo de Inmunoadsorción Enzimática , Flurotilo , Hipocampo/efectos de los fármacos , Factores Inmunológicos/farmacología , Interleucina-1beta/antagonistas & inhibidores , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Privación Materna , Proteínas de la Membrana/metabolismo , Modelos Animales , Receptores Tipo I de Interleucina-1/antagonistas & inhibidores , Receptores Tipo I de Interleucina-1/metabolismo , Convulsiones/prevención & control , Sinapsinas/metabolismoRESUMEN
Among autoimmune encephalitides, a prevalent group are those associated with antibodies against the N-Methyl-D-aspartate receptor, which present with behavior abnormalities, psychosis, seizures and abnormal movements. A new variant, mediated by antibodies against the GABA-A receptor, was recen-tly described. We report a 66-years-old female with this form of encephalitis whose main manifestation was the presence of severe seizures leading to status epilepticus. The patient had a good response to immunomodulatory therapy with intravenous methylprednisolone, azathioprine and anticonvulsants. The laboratory tests initially detected anti-thyroid peroxidase antibodies which lead to the misdiagnosis of Hashimoto Encephalitis, which was ruled out after the detection of antibodies against GABA-A receptor. No malignancy was detected.
Asunto(s)
Encefalitis/inmunología , Enfermedad de Hashimoto/inmunología , Receptores de GABA-A/inmunología , Anciano , Anticuerpos/inmunología , Encefalitis/diagnóstico por imagen , Femenino , Enfermedad de Hashimoto/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Convulsiones/inmunologíaRESUMEN
INTRODUÇÃO: O absenteísmo-doença, enquanto falta ao trabalho justificada por licença médica, é um importante indicador das condições de saúde dos trabalhadores. Em geral, características sociodemográficas e ocupacionais situam-se entre os principais fatores associados ao absenteísmo-doença. A administração pública é responsável por 21,8% dos empregos formais no Brasil. Esta população permite o estudo de uma grande variedade de categorias profissionais. OBJETIVO: Analisar o perfil e os indicadores de absenteísmo-doença entre servidores municipais de Goiânia, no Estado de Goiás, Brasil. Métodos: Estudo transversal das licenças certificadas para tratamento de saúde superiores a três dias, de todos os servidores, desde janeiro de 2005 a dezembro de 2010. Foram calculadas as prevalências, utilizando como critérios o número de indivíduos, os episódios e os dias de afastamento. RESULTADOS: Foram concedidas 40.578 licenças certificadas para tratamento de saúde a 13.408 servidores numa população média anual de 17.270 pessoas, o que resultou em 944.722 dias de absenteísmo. A prevalência acumulada de licença no período foi de 143,7%, com média anual de 39,2% e duração de 23 dias por episódio. A prevalência acumulada de absenteísmo-doença foi maior entre mulheres (52,0%) com idade superior a 40 anos (55,9%), com companheiro (49,9%), de baixa escolaridade (54,4%), profissionais de educação (54,7%), > 10 anos de serviço (61,9%) e múltiplos vínculos profissionais (53,7%). Os grupos de diagnósticos (CID-10) com as maiores prevalências acumuladas de licenças foram os do capítulo de transtornos mentais (26,5%), doenças osteomusculares (25,1%) e lesões (23,6%). CONCLUSÕES: Os indicadores de absenteísmo-doença expressam a magnitude desse fenômeno no serviço público e podem auxiliar no planejamento das ações de saúde do trabalhador, priorizando os grupos ocupacionais mais vulneráveis. .
BACKGROUND: Sickness absence, as work absenteeism justified by medical certificate, is an important health status indicator of the employees and, overall, sociodemographic and occupational characteristics are among the main factors associated with sickness absence. Public administration accounts for 21.8% of the formal job positions in Brazil. This population allows the study of a wide range of professional categories. OBJECTIVE: To assess the profile and indicators of sickness absence among public workers from the municipality of Goiania, in the State of Goiás, Brazil. METHODS: A cross-sectional study on certified sick leaves, lasting longer than three days, of all civil servants from January 2005 to December 2010. Prevalence rates were calculated using as main criteria the number of individuals, episodes and sick days. RESULTS: 40,578 certified sick leaves were granted for health treatment among 13,408 public workers, in an annual average population of 17,270 people, which resulted in 944,722 days of absenteeism. The cumulative prevalence of sick leave for the period was of 143.7%, with annual average of 39.2% and duration of 23 days per episode. The cumulative prevalence of sickness absence was higher among women (52.0%), older than 40 years old (55.9%), with a partner (49.9%), low schooling (54.4%), education professionals (54.7%), > 10 years of service (61.9%), and with multiple work contracts (53.7%). Diagnoses groups (ICD-10) with higher cumulative prevalence of sick leaves were those with mental disorders (26.5%), musculoskeletal diseases (25.1%), and injuries (23.6%). CONCLUSIONS: Indicators of sickness absence express the magnitude of this phenomenon in the public sector and can assist in planning health actions for the worker, prioritizing the most vulnerable occupational groups. .
Asunto(s)
Animales , Masculino , Ratas , Factor H de Complemento , Citocinas/inmunología , Neuroglía/inmunología , Convulsiones/inmunología , Factores de Edad , Sistema de Transporte de Aminoácidos X-AG/inmunología , Sistema de Transporte de Aminoácidos X-AG/fisiología , Astrocitos/efectos de los fármacos , Astrocitos/inmunología , Astrocitos/fisiología , Western Blotting , Clusterina/inmunología , Citocinas/efectos de los fármacos , Citocinas/fisiología , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades/inmunología , Técnica del Anticuerpo Fluorescente , Hipocampo/inmunología , Hipocampo/fisiología , Inmunohistoquímica , Inflamación/inmunología , Ácido Kaínico , Microglía/efectos de los fármacos , Microglía/inmunología , Microglía/fisiología , Neuroglía/efectos de los fármacos , Distribución Aleatoria , Ratas Sprague-Dawley , Índice de Severidad de la Enfermedad , Convulsiones/inducido químicamente , Convulsiones/fisiopatología , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/inmunología , Regulación hacia Arriba/fisiologíaAsunto(s)
Autoanticuerpos/sangre , Ataxia Cerebelosa/diagnóstico , Ataxia Cerebelosa/inmunología , Glutamato Descarboxilasa/inmunología , Convulsiones/inmunología , Vitíligo/inmunología , Ataxia Cerebelosa/sangre , Ataxia Cerebelosa/complicaciones , Diagnóstico Diferencial , Femenino , Humanos , Enfermedades de la Tiroides/sangre , Enfermedades de la Tiroides/diagnóstico , Enfermedades de la Tiroides/inmunología , Vitíligo/sangre , Vitíligo/diagnóstico , Adulto JovenRESUMEN
Twelve hundred children with convulsions when feverish were studied during a period of five years. Among them 52 subjects (4.33%) developed nonfebrile seizures after a period of eight months to five years from the first febrile convulsion (group A). Twenty-three children had neither afebrile seizures nor EEG abnormalities during the period of observation (group B). The two groups were comparable for age of the first febrile convulsion onset, sex, and socioeconomic status. None had risk factors for subsequent epilepsy or clinical signs of congenital cytomegalovirus infection. The isolation rate of CMV from urine was 53.84% in patients of group A, 26.09% in children of group B, and 26.83% in healthy control children. Twelve CMV-positive children from group A were followed for one to more than three years. In five of seven children with persisting EEG abnormalities, cytomegaloviruria was still present 13 to 41 months after the first isolation, whereas none of five patients with normal electroencephalograms had viruria after a comparable period. We found that CMV-positive children generally lacked cell-mediated immunity to the virus, whereas CMV-negative patients had positive reactions. Our data suggest a correlation between persistence of neurologic abnormalities and CMV excretion in children with nonfebrile seizures and CMV infection.