RESUMO
Introducción: Las malformaciones del desarrollo cortical se deben a alteraciones en la migración del neuroblasto durante la formación de la corteza cerebral. Se desconoce su frecuencia en embarazos monocoriales. Objetivo: Reportar el caso de un embarazo monocorial con diagnóstico de malformación del desarrollo cortical en uno de los fetos y revisar la literatura referente a su diagnóstico y pronóstico. Método: Mujer de 19 años, embarazo monocorial biamniótico de 26 semanas, que acudió con estudio ecográfico y resonancia fetal que evidenció en uno de los fetos asimetría de los hemisferios cerebrales, hipoplasia de la cisura de Silvio izquierda con simplificación del patrón giral por focos de paquigiria y polimicrogiria, con confirmación posnatal de alteración en la migración neuronal asociada a hipoplasia vermiana. Resultados: Se encontraron en la literatura tres casos de embarazo múltiple monocorial con trastorno de la migración neuronal con recién nacidos vivos. Los hallazgos más comunes fueron microcefalia, lisencefalia e hipoplasia cerebelosa. Conclusiones: El diagnóstico prenatal del trastorno de la migración neuronal se realiza con ecografía y resonancia fetal. La más frecuente es la alteración de la migración neuronal tipo II. El pronóstico depende del tipo de alteración; sin embargo, la mayoría de los casos presentan trastornos epileptiformes con alteraciones del neurodesarrollo.
Introduction: Malformations of cortical development are the result from alterations in the neuroblast migration during the cerebral cortex formation. Its frequency in monochorial multiple pregnancies remains unknown. Objective: To report a case of monochorial multiple pregnancy with diagnosis of malformation of the cortical development in one of the fetuses. In addition, to review the literature regarding the diagnosis and prognosis of this entity. Method: A 19-year-old female with a monochorial diamniotic pregnancy of 26 weeks gestation, arrived with an ultrasound anatomy scan visit, and fetal magnetic resonance imaging, we detected asymmetry in the cerebral hemispheres one of the fetuses, hypoplasia of the left sulcus of Sylvius with simplification of the gyrus pattern due to clusters of pachygyria and polymicrogyria. Those findings were confirmed afterbirth, with a definite diagnosis of neuronal migration disorder associated with vermian hypoplasia. Results: Three cases of monochorial pregnancy with neuronal migration disorder with live newborn, common findings like microcephaly, lissencephaly and vermian hypoplasia. Conclusions: Prenatal diagnosis with neuronal migration disorder is done via ultrasound and magnetic resonance imaging. Neuronal migration disorders type II are the most common of them. Prognosis depends on the type of disorder; however, most patients have epileptiform activity and neurodevelopment impairment.
Assuntos
Humanos , Feminino , Gravidez , Adulto Jovem , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Gravidez de Gêmeos , Diagnóstico Pré-Natal , Prognóstico , Imageamento por Ressonância Magnética , Ecoencefalografia , UltrassonografiaRESUMO
The present article describes pathophysiological and clinical aspects of congenital malformations of the cerebral tissue (cortex and white matter) that cause epilepsy and very frequently require surgical treatment. A particular emphasis is given to focal cortical dysplasias, the most common pathology among these epilepsy-related malformations. Specific radiological and surgical features are also highlighted, so a thorough overview of cortical dysplasias is provided.
Assuntos
Epilepsia , Displasia Cortical Focal , Malformações do Desenvolvimento Cortical , Humanos , Malformações do Desenvolvimento Cortical/complicações , Epilepsia/etiologia , Córtex Cerebral/diagnóstico por imagem , Imageamento por Ressonância Magnética/efeitos adversosRESUMO
Zika virus (ZIKV) is a neurotropic teratogen that causes congenital Zika syndrome (CZS), characterized by brain and eye anomalies. Impaired gene expression in neural cells after ZIKV infection has been demonstrated; however, there is a gap in the literature of studies comparing whether the differentially expressed genes in such cells are similar and how it can cause CZS. Therefore, the aim of this study was to compare the differential gene expression (DGE) after ZIKV infection in neural cells through a meta-analysis approach. Through the GEO database, studies that evaluated DGE in cells exposed to the Asian lineage of ZIKV versus cells, of the same type, not exposed were searched. From the 119 studies found, five meet our inclusion criteria. Raw data of them were retrieved, pre-processed, and evaluated. The meta-analysis was carried out by comparing seven datasets, from these five studies. We found 125 upregulated genes in neural cells, mainly interferon-stimulated genes, such as IFI6, ISG15, and OAS2, involved in the antiviral response. Furthermore, 167 downregulated, involved with cellular division. Among these downregulated genes, classic microcephaly-causing genes stood out, such as CENPJ, ASPM, CENPE, and CEP152, demonstrating a possible mechanism by which ZIKV impairs brain development and causes CZS.
Assuntos
Microcefalia , Teratogênese , Infecção por Zika virus , Zika virus , Humanos , Zika virus/genética , Infecção por Zika virus/genética , Infecção por Zika virus/congênito , Microcefalia/genética , RNA-Seq , Regulação para Baixo , Proteínas de Ciclo Celular/genéticaRESUMO
Introdução: Durante o desenvolvimento do encéfalo há formação de sulcos e giros que podem sofrer alterações morfológicas similarmente ao nervo facial (NC VII) que possui funções sensitivas e motoras e sua lesão pode gerar prejuízos clínicos e estéticos. Na literatura há informações sobre essas estruturas em adultos, porém pouco definidas em fetos. Objetivo: Descrever os giros e sulcos e o trajeto do NC VII em cadáveres de fetos humanos. Métodos: Selecionou-se sete fetos humanos, de ambos os sexos, do acervo do Laboratório de Anatomia da UFMS CPTL. Realizou-se três etapas: avaliação da idade fetal, dissecação e descrição anatômica. O estudo foi aprovado pelo Comitê de Ética em Pesquisa, CAEE: 75069617.5.0000.5386 2022. Resultados: observou-se na face dorsolateral sulcos frontal superior e médio e pós-central, temporal superior e inferior, circular da ínsula e central da ínsula. Há giro pré-central, pós-central, temporais, superior inferior e médio. Na face medial há sulco do cíngulo duplo, paracentral, parieto occipital e giro frontal superior. Em todos os fetos, há o tronco do NC VII e seus ramos perfurando o parênquima da glândula parótida na região infratemporal antes da divisão em ramos pela face Conclusão: A topografia dos giros e sulcos dos fetos é fundamental para identificar precocemente malformações corticais. Somado a isso, o estudo morfológico do NC VII poderá fomentar estudos futuros, haja vista que são poucos os registros a respeito das características deste nervo em fetos.
Introduction: In the development of the brain there are grooves and gyri that undergo morphological changes, similarly the facial nerve (CN VII) has sensory and motor functions and its injury generates clinical and aesthetic damage. In the literature there is information about these structures in adults, but little defined in fetuses. Objective: To describe the gyri and sulci and the course of CN VII in fetal cadavers. Methods: Seven human fetuses of both sexes were selected from the collection of the Anatomy Laboratory of the UFMS CPTL. Three steps were performed: assessment of fetal age, dissection and anatomical description. The study was approved by the Research Ethics Committee, CAEE 75069617.5.0000.5386. Results: in the studied brains, superior and medium frontal and postcentral, superior and inferior temporal, insula circular and insula central grooves were observed on the dorsolateral surface. There are precentral, postcentral, temporal, superior, inferior, and middle gyrus. On the medial surface there is the double cingulate sulcus, paracentral, parieto occipital and superior frontal gyrus. In all fetuses, there is the trunk of CN VII and its branches piercing the parotid gland parenchyma in the infratemporal region before dividing into branches across the face. Conclusion: The topography of the gyri and sulcus of fetuses is essential for early identification of cortical malformations. Added to this, the morphological study of CN VII may encourage future studies, given that there are few records regarding the characteristics of this nerve in fetuses.
Introducción: En el desarrollo del cerebro existen surcos y circunvoluciones que sufren cambios morfológicos, de igual manera el nervio facial (NC VII) tiene funciones sensoriales y motoras y su lesión genera daño clínico y estético. En la literatura existe información sobre estas estructuras en adultos, pero poco definidas en fetos. Objetivo: Describir las circunvoluciones y surcos y el curso del NC VII en cadáveres fetales. Métodos: Siete fetos humanos, de ambos sexos, fueron seleccionados de la colección del Laboratorio de Anatomía de la UFMS CPTL. Se realizaron tres pasos: evaluación de la edad fetal, disección y descripción anatómica. El estudio fue aprobado por el Comité de Ética en Investigación, CAEE 75069617.5.0000.5386. Resultados: en los cerebros estudiados, se observaron surcos en la superficie dorsolateral frontal superior y medio y poscentral, temporal superior e inferior, insular circular e insular central. Hay circunvolución precentral, poscentral, temporal, superior, inferior y media. En la superficie medial se encuentra el doble surco cingulado, paracentral, parieto occipital y giro frontal superior. En todos los fetos, el tronco del NC VII y sus ramas perforan el parénquima de la glándula parótida en la región infratemporal antes de dividirse en ramas a lo largo de la cara. Conclusión: La topografía de las circunvoluciones y surcos de los fetos es fundamental para la identificación temprana de malformaciones corticales. Sumado a esto, el estudio morfológico del NC VII puede alentar futuros estudios, dado que existen pocos registros sobre las características de este nervio en fetos.
RESUMO
The Na+/K+- ATPase acts as an ion pump maintaining the essential plasma membrane potential in all mammalian cell types, and is essential for many cellular functions. There are four α isoforms (α1, α2, α3 and α4) with distinct expression patterns, kinetic properties and substrate affinity. The α2-isoform is encoded by ATP1A2 and evidence supports its utmost importance in Cl- homeostasis in neurons, and in the function of respiratory neurons at birth. Monallelic pathogenic variants in ATP1A2 are associated with familial hemiplegic migraine type 2 (FHM2) and on rare occasions with alternating hemiplegia of childhood 1 (AHC1). To date, no instances of biallelic loss of function variants have been reported in humans. However, Atp1a2 homozygous loss of function knockout mice (α2-/- mice) show severe motor deficits, with lack of spontaneous movements, and are perinatally lethal due to absent respiratory activity. In this report we describe three newborns from two unrelated families, who died neonatally, presenting in utero with an unusual form of fetal hydrops, seizures and polyhydramnios. At birth they had multiple joint contractures (e.g. arthrogryposis), microcephaly, malformations of cortical development, dysmorphic features and severe respiratory insufficiency. Biallelic loss of function variants in ATP1A2, predicted to be pathogenic were found on whole exome sequencing. We propose that this is a distinctive new syndrome caused by complete absence of Na+/K+- ATPase α2-isoform expression.
Assuntos
Artrogripose/genética , Hidropisia Fetal/genética , Microcefalia/genética , Enxaqueca com Aura/genética , ATPase Trocadora de Sódio-Potássio/genética , Alelos , Animais , Artrogripose/patologia , Criança , Feminino , Predisposição Genética para Doença , Humanos , Hidropisia Fetal/patologia , Recém-Nascido , Mutação com Perda de Função/genética , Masculino , Camundongos , Microcefalia/patologia , Enxaqueca com Aura/patologia , Fenótipo , Gravidez , Isoformas de Proteínas/genética , Sequenciamento do ExomaRESUMO
Epilepsies are chronic neurological diseases that affect approximately 2% of the world population. In addition to being one of the most frequent neurological disorders, treatment for patients with epilepsy remains a challenge, because a proportion of patients do not respond to the antiseizure medications that are currently available. This results in a severe economic and social burden for patients, families, and the healthcare system. A characteristic common to all forms of epilepsy is the occurrence of epileptic seizures that are caused by abnormal neuronal discharges, leading to a clinical manifestation that is dependent on the affected brain region. It is generally accepted that an imbalance between neuronal excitation and inhibition generates the synchronic electrical activity leading to seizures. However, it is still unclear how a normal neural circuit becomes susceptible to the generation of seizures or how epileptogenesis is induced. Herein, we review the results of recent proteomic studies applied to investigate the underlying mechanisms leading to epilepsies and how these findings may impact research and treatment for these disorders.
RESUMO
Las malformaciones del desarrollo cortical son entidades relacionadas con la interrupción en el proceso de formación cortical secundarias a diferentes etimologías y se asocian con morbilidad neurológica significativa, incluyendo discapacidad intelectual, epilepsia severa y trastorno motor. El desarrollo de nuevas secuencias diagnósticas por resonancia magnética, y la implementación de su uso durante el periodo fetal permitió mejorar la identificación, caracterización y clasificación las malformaciones del desarrollo cortical. La resonancia magnética constituye uno de los pilares en el estudio de estos pacientes, sobre todo si se plantea como tratamiento de la epilepsia el quirúrgico.
Abstract Malformations of cortical development result from disruptions of the complex process of development of the cerebral cortex secondary to different etiologies. They are associated with significant neurological morbidity including sever epilepsy, developmental delay, and motor dysfunction. Currently, the development of new sequences of magnetic resonance imaging as well as their application during pregnancy have improved the identification, topography, and classification of these malformations. Magnetic resonance imaging is one of the cornerstones of the work-up of patients with epilepsy, especially when neurological treatment is contemplated.
Assuntos
Gravidez , Diagnóstico por Imagem , Transtornos do NeurodesenvolvimentoRESUMO
Medically intractable epilepsy is a clinical condition of concern that arises when a patient with epilepsy suffers seizures, despite a trial of two or more antiepileptic drugs (AEDs) suitable for the type of epilepsy that are prescribed at maximum tolerated doses, does not achieve control of seizures. This diagnosis could be related to cortical dysplasias. We report the case of a 5-year-old girl with a previous normal neurological development and no family history of epilepsy who presented with focal-type seizures at age 4. She started treatment by taking different AEDs for seizure control. She continued having frequent seizures that sometimes progressed to generalized seizures and status epilepticus. After a focal cortical resection performed in the area where interictal spikes were detected, the pathology confirmed a type IIb cortical dysplasia as the cause of the epilepsy. This article discusses cortical dysplasias as a cause of pharmacoresistant epilepsy and its treatment.
RESUMO
Las malformaciones del desarrollo cortical originan un grupo de patologías, que cursan con diversas manifestaciones las cuales marcan un grado de minusvalía significativo en quienes las padecen. La Lisencefalia es una de las alteraciones de la migración neuronal caracterizada por una corteza cerebral de superficie lisa o con pocas circunvoluciones. Este trastorno está frecuentemente asociado a epilepsias de difícil manejo. Se presenta el caso de un paciente masculino de 18 meses de edad con diagnóstico de Lisencefalia quien cursa con convulsiones tónicas generalizadas desde los 8 meses de edad. Se le realizó TAC de cráneo simple y resonancia magnética de cerebro para confirmar el diagnóstico y se dio manejo farmacológico a las convulsiones.
Malformations of cortical development originate a group of pathologies that involve diverse manifestations that mark a significant degree of disability in those who suffer from. The Lissencephaly is one of alterations in neuronal migration characterized by a smooth surface or with few convolutions in the cerebral cortex. This disorder is often associated with difficult management Epilepsies. We report the case of a male patient from 18 months of age with a diagnosis of Lissencephaly, who presents generalized tonic seizures from 8 months of age. Was performed a simple skull CT and brain magnetic resonance to confirm the diagnosis and the pharmacological management was given to seizures.
Assuntos
Humanos , Lactente , Córtex Cerebral , Epilepsia , Malformações do Desenvolvimento Cortical , Lisencefalia , Convulsões , Crânio , Espectroscopia de Ressonância Magnética , Diagnóstico , Cérebro , Malformações do Desenvolvimento Cortical do Grupo IIRESUMO
Introducción: Las últimas técnicas de análisis de RM funcional permiten medir el cambio espontáneo de la señal BOLD en reposo. Los métodos de análisis derivados de estos estudios se dividen en: mapas de conectividad funcional y conectividad cerebral por grafos. Un grafo permite representar cualquier sistema compuesto de elementos interconectados. Este enfoque es, en teoría, aplicable a cualquier escala, modalidad o cantidad de información neurocientífica. Objetivo: Presentar los resultados de la implementación de un algoritmo para analizar la conectividad funcional por teoría de grafos. Materiales: Resonador de 1,5 T para obtener imágenes con información en T1 volumétricas, para capturar la información estructural, y EPI con información en T2, para capturar la señal BOLD en reposo, de 19 individuos sanos y 1 paciente con epilepsia con diagnóstico imaginológico de displasia cortical. Se les solicitó permanecer despiertos, con los ojos cerrados, evitando pensar en algo particular. Los estudios fueron preprocesados y luego analizados mediante un grafo construido a partir de 8196 vóxeles de la corteza cerebral. Resultados: El enfoque permite obtener imágenes que codifican el patrón de correlación que tiene la señal BOLD en un vóxel con todos los otros vóxeles en la corteza cerebral. Este enfoque es replicable. Conclusiones: Se ha presentado un enfoque para analizar la conectividad funcional por teoría de grafos que permite cuantificar el grado de correlación de la señal BOLD en una muestra de vóxeles de la corteza cerebral y se ha presentado cómo cambia el patrón de correlación en un caso de epilepsia del lóbulo frontal.
Introduction: The latest analysis techniques of functional magnetic resonance enable to measure the spontaneous change of the BOLD signal during rest periods. The analysis and presentation methods which derive from the information obtained from these studies are divided in two approaches: functional connectivity at rest and functional connectivity using graph theory. A graph enables the representation of any system composed of interconnected elements. This approach is applicable to any scale, modality or quantity of neuroscientific data. Objective: To present the results of the implementation of one algorithm for the analysis of functional connectivity using graph theory. Materials and methods: The use of a 1.5 T magnetic resonator to obtain T1 volumetric images, in order to capture the structural information and the use of EPI with information in T2 in order to capture the BOLD signal at rest, in 19 healthy patients and 1 patient with epilepsy with a imaging diagnosis of cortical dysplasia. The patients were awake during the acquisition. Their eyes were closed, and they avoided specific thoughts. The studies are preprocessed using the approach reported in the literature and are analyzed with graphs using 8196 points of the cerebral cortex. Results: The presented approach enables to obtain images which encode the correlation pattern in the BOLD signal in a single. Meanwhile,the other voxels are in the cerebral cortex. This approach is replicable with other patients. Conclusions: An approach has been presented in order to analyze functional connectivity using graph theory. This enables to quantify the degree of correlation of a BOLD signal, in a voxel sample from the cerebral cortex. This approach also indicates how the correlation pattern changes in case of frontal lobe epilepsy.
Assuntos
Humanos , Epilepsia , Imageamento por Ressonância Magnética , Malformações do Desenvolvimento CorticalRESUMO
Malformations of cortical development (MCD) result from disruptions in the complex process of the human brain cortex formation and are highly associated to severe epilepsy, neurodevelopmental delay and motor dysfunction. Nowadays, magnetic resonance imaging (MRI) is the cornerstone of the work-up of patients with epilepsy and modern advanced imaging techniques have improved not only our ability to detect and characterize cortical malformations, but also in identifying associated functional abnormalities that are far beyond the structural visualized lesions. Herein, we address the most currently used classifications of MCD and make a concise review of the embryological process of cortical development. Our main goal is to summarize recent advances and new trends in diagnostic imaging techniques concerning MCD. Thereafter, follows a brief discussion of specific disorders and their radiological features.
As malformações do desenvolvimento cortical (MDC) resultam de distúrbios no complexo processo do desenvolvimento do córtex cerebral humano e estão comumente associadas a epilepsia severa e disfunções neuropsicomotoras. Atualmente, as imagens por ressonância magnética (RM) são a pedra angular no manejo de pacientes com epilepsia e modernas técnicas avançadas de imagem melhoraram não só a nossa capacidade de detectar e caracterizar as malformações corticais, mas também levaram ao reconhecimento de anomalias funcionais associadas que estão muito além das lesões estruturais visibilizadas. Abordaremos as classificações mais utilizadas de MDC e revisaremos a embriologia do desenvolvimento cortical. Nosso principal objetivo é destacar os avanços recentes e as novas tendências em técnicas de diagnóstico por imagens relacionadas às MDC. Em seguida, faremos uma breve discussão sobre alguns transtornos específicos e suas características radiológicas.
Assuntos
Feminino , Humanos , Masculino , Córtex Cerebral/anormalidades , Diagnóstico por Imagem/métodos , Epilepsia/etiologia , Malformações do Desenvolvimento Cortical/etiologia , Córtex Cerebral/embriologia , Coristoma/diagnóstico , Coristoma/etiologia , Giro do Cíngulo/anormalidades , Giro do Cíngulo/embriologia , Malformações do Desenvolvimento Cortical/diagnósticoRESUMO
Malformations of cortical development (MCD) have been increasingly identified. The purpose of this presentation is to review the current knowledge of the MCD. Before we address this issue, we will briefly present a review of cortical development. The second part of this presentation will address the most important MCD. Finally, the last part of this presentation will address the correlation between MCD and epilepsy.
As malformações do desenvolvimento cortical (MDC) são cada vez mais identificadas e diagnosticadas. O propósito desta apresentação é rever o conhecimento recente sobre as MDC. Antes de abordarmos o assunto em questão, apresentaremos brevemente uma revisão sobre a formação cortical. A seguir, abordaremos as principais entidades compreendidas dentro da classificação das MDC e, finalmente, resumiremos a correlação entre MDC e epilepsia.