RESUMEN
Malformations of cortical development (MCDs) are structural abnormalities that disrupt the normal process of cortical development in utero. MCDs include microcephaly with simplified gyral pattern/microlyssencephaly, hemimegalencephaly, focal cortical dysplasia, lissencephaly, heterotopia, polymicrogyria, and schizencephaly. The debut of MCD can be with pharmacoresistant epilepsy, developmental delay, neurologic deficits, or cognitive impairment. The diagnostic pathway for MCDs is complex owing to wide variations in presentation and etiology. Although the definitive diagnosis of MCD depends on histopathology, neuroimages have an important role in this process. Furthermore, knowing the disturbance of the molecular pathway involved is important. Increased understanding of the molecular biology and recent advances in genetic testing have caused rapid growth in the knowledge of the genetic causes of MCDs, allowing for information on prognosis, recurrence risk, and prediction of treatment outcomes.
Las malformaciones del desarrollo cortical (MDC) son alteraciones estructurales que interrumpen el proceso normal de desarrollo cortical in utero. Se incluyen la microcefalia, con patrón giral simplificado/microlisencefalia, hemimegalencefalia, displasia cortical focal, lisencefalia, heterotopía, polimicrogiria y esquizencefalia. Se presentan con epilepsia farmacorresistente, retraso del desarrollo, déficit neurológico o compromiso cognitivo. El diagnóstico es complejo debido a la amplia variedad en su presentación y etiología. Aunque el diagnóstico definitivo es por anatomía patológica, las neuroimágenes cumplen un rol fundamental. Además, es sumamente importante conocer la alteración en el mecanismo molecular involucrado en la fisiopatogenia de la malformación. El creciente desarrollo de la biología molecular y de los estudios genéticos han mejorado el conocimiento de las causas genéticas de las MDC. Esto permitirá mejorar el pronóstico, consejo genético y probablemente las opciones terapéuticas.
Asunto(s)
Malformaciones del Desarrollo Cortical , Humanos , Malformaciones del Desarrollo Cortical/genética , Malformaciones del Desarrollo Cortical/diagnóstico , Malformaciones del Desarrollo Cortical/diagnóstico por imagen , Imagen por Resonancia Magnética , Corteza Cerebral/anomalías , Corteza Cerebral/embriologíaRESUMEN
The cell-intrinsic mechanisms underlying the decision of a stem/progenitor cell to either proliferate or differentiate remain incompletely understood. Here, we identify the transmembrane protein Lrig1 as a physiological homeostatic regulator of FGF2-driven proliferation and self-renewal of neural progenitors at early-to-mid embryonic stages of cortical development. We show that Lrig1 is expressed in cortical progenitors (CPs), and its ablation caused expansion and increased proliferation of radial/apical progenitors and of neurogenic transit-amplifying Tbr2+ intermediate progenitors. Notably, our findings identify a previously unreported EGF-independent mechanism through which Lrig1 negatively regulates neural progenitor proliferation by modulating the FGF2-induced IL6/Jak2/Stat3 pathway, a molecular cascade that plays a pivotal role in the generation and maintenance of CPs. Consistently, Lrig1 knockout mice showed a significant increase in the density of pyramidal glutamatergic neurons placed in superficial layers 2 and 3 of the postnatal neocortex. Together, these results support a model in which Lrig1 regulates cortical neurogenesis by influencing the cycling activity of a set of progenitors that are temporally specified to produce upper layer glutamatergic neurons.
Asunto(s)
Janus Quinasa 2 , Glicoproteínas de Membrana , Ratones Noqueados , Células-Madre Neurales , Neurogénesis , Neuronas , Factor de Transcripción STAT3 , Transducción de Señal , Animales , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética , Janus Quinasa 2/metabolismo , Células-Madre Neurales/metabolismo , Células-Madre Neurales/citología , Ratones , Neurogénesis/genética , Neuronas/metabolismo , Neuronas/citología , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Proliferación Celular , Corteza Cerebral/metabolismo , Corteza Cerebral/citología , Corteza Cerebral/embriología , Diferenciación Celular , Factores de Crecimiento de Fibroblastos/metabolismo , Proteínas del Tejido NerviosoRESUMEN
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.
Asunto(s)
Humanos , Femenino , Embarazo , Adulto Joven , Malformaciones del Desarrollo Cortical/diagnóstico por imagen , Embarazo Gemelar , Diagnóstico Prenatal , Pronóstico , Imagen por Resonancia Magnética , Ecoencefalografía , UltrasonografíaRESUMEN
BACKGROUND: Limited information exists in the prenatal literature regarding the neuroimaging features of fetal hemimegalencephaly. SUMMARY: This report describes ultrasound and magnetic resonance imaging (MRI) findings in a second-trimester fetus with an isolated, severe form of hemimegalencephaly. The most prominent imaging findings included unilateral enlarged cerebral hemisphere and ipsilateral ventriculomegaly causing cerebral asymmetry, midline shift, and macrocephaly. Abnormal cortical development imaging signs were also evident. A literature review encompassing 23 reports describing 36 cases, including ours, is presented. KEY MESSAGES: Characteristic ultrasound findings for the diagnosis of hemimegalencephaly are not always apparent prenatally. Asymmetric ventriculomegaly emerges as the most common but nonspecific presenting feature during routine second- or third-trimester ultrasound scans. Subsequent high-resolution prenatal neurosonography and fetal MRI facilitate definitive prenatal diagnosis, showcasting associated features primarily related to cortical migration, differentiation, and maturation. Postnatally, the prognosis is poor due to intractable seizures, hemiplegia, and progressive neurodevelopmental delay.
Asunto(s)
Hemimegalencefalia , Hidrocefalia , Malformaciones del Sistema Nervioso , Embarazo , Femenino , Humanos , Hemimegalencefalia/patología , Ultrasonografía Prenatal/métodos , Diagnóstico Prenatal/métodos , Feto/patología , Hidrocefalia/patología , Imagen por Resonancia Magnética/métodos , NeuroimagenRESUMEN
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.
Asunto(s)
Epilepsia , Displasia Cortical Focal , Malformaciones del Desarrollo Cortical , Humanos , Malformaciones del Desarrollo Cortical/complicaciones , Epilepsia/etiología , Corteza Cerebral/diagnóstico por imagen , Imagen por Resonancia Magnética/efectos adversosRESUMEN
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.
Asunto(s)
Microcefalia , Teratogénesis , Infección por el Virus Zika , Virus Zika , Humanos , Virus Zika/genética , Infección por el Virus Zika/genética , Infección por el Virus Zika/congénito , Microcefalia/genética , RNA-Seq , Regulación hacia Abajo , Proteínas de Ciclo Celular/genéticaRESUMEN
Diabetic rat embryos have increased cortical neurogenesis and neuron maturation, and their offspring presented altered neuron polarity, lamination, and diminished neuron excitability. The FOXP2 overexpression results in higher cortical neurogenesis by increasing the transition of radial glia to the intermediate progenitor. Similarly, histamine through H1-receptor activation increases cortical neuron differentiation. Indeed, blocking the H1-receptor by the systemic administration of chlorpheniramine to diabetic pregnant rats prevents increased neurogenesis. Here, we explore the relationship between the H1-receptor and FOXP2 on embryo neurogenesis from diabetic dams. Through qRT-PCR, Western blot, immunohistofluorescence, and flow cytometry, we showed an increased FOXP2 expression and nuclear localization, a reduced Nestin expression and -positive cells number, and a higher PKCα expression in the cortical neuroepithelium of fourteen-day-old embryos from diabetic rats. Interestingly, this scenario was prevented by the chlorpheniramine systemic administration to diabetic pregnant rats at embryo day twelve. These data, together with the bioinformatic analysis, suggest that higher H1-receptor activity in embryos under high glucose increases FOXP2 nuclear translocation, presumably through PKCα phosphorylation, impairing the transition of radial glia to intermediate progenitor and increasing neuron differentiation in embryos of diabetic rats.
Asunto(s)
Diabetes Mellitus Experimental , Células-Madre Neurales , Animales , Femenino , Embarazo , Ratas , Clorfeniramina/metabolismo , Diabetes Mellitus Experimental/metabolismo , Factores de Transcripción Forkhead/metabolismo , Histamina/metabolismo , Células-Madre Neurales/metabolismo , Neurogénesis/fisiología , Proteína Quinasa C-alfa/metabolismo , Telencéfalo/metabolismo , Receptores Histamínicos H1RESUMEN
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.
RESUMEN
Infections during pregnancy can seriously damage fetal neurodevelopment by aberrantly activating the maternal immune system, directly impacting fetal neural cells. Increasing evidence suggests that these adverse impacts involve alterations in neural stem cell biology with long-term consequences for offspring, including neurodevelopmental disorders such as autism spectrum disorder, schizophrenia, and cognitive impairment. Here we review how maternal infection with viruses such as Influenza A, Cytomegalovirus, and Zika during pregnancy can affect the brain development of offspring by promoting the release of maternal pro-inflammatory cytokines, triggering neuroinflammation of the fetal brain, and/or directly infecting fetal neural cells. In addition, we review insights into how these infections impact human brain development from studies with animal models and brain organoids. Finally, we discuss how maternal infection with SARS-CoV-2 may have consequences for neurodevelopment of the offspring.
Asunto(s)
Trastorno del Espectro Autista , COVID-19 , Virosis , Infección por el Virus Zika , Virus Zika , Animales , Trastorno del Espectro Autista/etiología , Encéfalo , Citocinas , Femenino , Embarazo , SARS-CoV-2 , Virosis/complicacionesRESUMEN
OBJECTIVE: We aimed to better characterize the magnetic resonance imaging (MRI) findings of mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE), a rare clinicopathological entity associated with pharmacoresistance recently described in patients with frontal lobe epilepsy. METHODS: We studied 12 patients who underwent epilepsy surgery and whose surgical specimens showed histopathological findings of MOGHE, characterized by preserved cortical lamination, blurred gray-white matter interface due to increased number of oligodendrocytes, and heterotopic neurons in the white matter. The age at MRI evaluation ranged from 11 to 58 years, except for one 4.5-year-old patient. RESULTS: Following a detailed MRI analysis using an in-house protocol, we found abnormalities in all cases. The lesion was circumscribed in the frontal lobe in six (50%) and in the temporal lobe in three (25%) patients. In the remaining three patients (25%), the lesion was multilobar (frontotemporal and temporoparieto-occipital). Cortical thickening was mild in all patients, except in the 4.5-year-old patient, who had pronounced cortical thickening and white matter blurring. We also identified cortical/subcortical hyperintense T2/fluid-attenuated inversion recovery signal associated with gray/white matter blurring in all but one patient. When present, cleft cortical dimple, and deep sulci aided in localizing the lesion. Overall, the MRI findings were like those in focal cortical dysplasia (FCD) Type IIa. Surgical outcome was excellent in five patients (Engel Class I in 25% and II in 17%). The remaining seven patients (58%) had worthwhile seizure reduction (Engle Class III). Incomplete lesion resection was significantly associated with worse outcomes. SIGNIFICANCE: MRI findings associated with MOGHE are similar to those described in FCD Type IIa. Although more frequent in the frontal lobe, MOGHE also occurred in the temporal lobe or involved multiple lobes. Multilobar or extensive MOGHE MRI lesions are associated with less favorable surgical outcomes. Because this is a rare condition, multicenter studies are necessary to characterize MOGHE further.
Asunto(s)
Epilepsia del Lóbulo Frontal/diagnóstico por imagen , Epilepsia del Lóbulo Frontal/patología , Malformaciones del Desarrollo Cortical/diagnóstico por imagen , Oligodendroglía/patología , Adolescente , Adulto , Edad de Inicio , Niño , Preescolar , Estudios de Cohortes , Epilepsia Refractaria/diagnóstico por imagen , Epilepsia Refractaria/patología , Epilepsia Refractaria/cirugía , Electroencefalografía , Epilepsia del Lóbulo Frontal/cirugía , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Malformaciones del Desarrollo Cortical/cirugía , Persona de Mediana Edad , Neuronas/patología , Procedimientos Neuroquirúrgicos , Tomografía de Emisión de Positrones , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To construct international ultrasound-based standards for fetal cerebellar growth and Sylvian fissure maturation. METHODS: Healthy, well nourished pregnant women, enrolled at < 14 weeks' gestation in the Fetal Growth Longitudinal Study (FGLS) of INTERGROWTH-21st , an international multicenter, population-based project, underwent serial three-dimensional (3D) fetal ultrasound scans every 5 ± 1 weeks until delivery in study sites located in Brazil, India, Italy, Kenya and the UK. In the present analysis, only those fetuses that underwent developmental assessment at 2 years of age were included. We measured the transcerebellar diameter and assessed Sylvian fissure maturation using two-dimensional ultrasound images extracted from available 3D fetal head volumes. The appropriateness of pooling data from the five sites was assessed using variance component analysis and standardized site differences. For each Sylvian fissure maturation score (left or right side), mean gestational age and 95% CI were calculated. Transcerebellar diameter was modeled using fractional polynomial regression, and goodness of fit was assessed. RESULTS: Of those children in the original FGLS cohort who had developmental assessment at 2 years of age, 1130 also had an available 3D ultrasound fetal head volume. The sociodemographic characteristics and pregnancy/perinatal outcomes of the study sample confirmed the health and low-risk status of the population studied. In addition, the fetuses had low morbidity and adequate growth and development at 2 years of age. In total, 3016 and 2359 individual volumes were available for transcerebellar-diameter and Sylvian-fissure analysis, respectively. Variance component analysis and standardized site differences showed that the five study populations were sufficiently similar on the basis of predefined criteria for the data to be pooled to produce international standards. A second-degree fractional polynomial provided the best fit for modeling transcerebellar diameter; we then estimated gestational-age-specific 3rd , 50th and 97th smoothed centiles. Goodness-of-fit analysis comparing empirical centiles with smoothed centile curves showed good agreement. The Sylvian fissure increased in maturation with advancing gestation, with complete overlap of the mean gestational age and 95% CIs between the sexes for each development score. No differences in Sylvian fissure maturation between the right and left hemispheres were observed. CONCLUSION: We present, for the first time, international standards for fetal cerebellar growth and Sylvian fissure maturation throughout pregnancy based on a healthy fetal population that exhibited adequate growth and development at 2 years of age. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Asunto(s)
Cerebelo/embriología , Acueducto del Mesencéfalo/embriología , Desarrollo Fetal , Gráficos de Crecimiento , Ultrasonografía Prenatal , Adulto , Brasil , Cerebelo/crecimiento & desarrollo , Acueducto del Mesencéfalo/crecimiento & desarrollo , Preescolar , Femenino , Edad Gestacional , Humanos , India , Lactante , Recién Nacido , Italia , Kenia , Estudios Longitudinales , Masculino , Embarazo , Resultado del Embarazo , Estándares de Referencia , Reino UnidoRESUMEN
BACKGROUND: Lissencephaly is a brain malformation characterized by smooth and thickened cerebral surface, which may result in structural epilepsy. Lissencephaly is not common in veterinary medicine. Here, we characterize the first cases of lissencephaly in four Shih Tzu dogs, including clinical presentations and findings of magnetic resonance imaging of lissencephaly and several concomitant brain malformations. CASE PRESENTATION: Early-onset acute signs of forebrain abnormalities were observed in all dogs, which were mainly cluster seizures and behavioral alterations. Based on neurological examination, the findings were consistent with symmetrical and bilateral forebrain lesions. Metabolic disorders and inflammatory diseases were excluded. Magnetic resonance imaging for three dogs showed diffuse neocortical agyria and thickened gray matter while one dog had mixed agyria and pachygyria. Other features, such as internal hydrocephalus, supracollicular fluid accumulation, and corpus callosum hypoplasia, were detected concomitantly. Antiepileptic drugs effectively controlled cluster seizures, however, sporadic isolated seizures and signs of forebrain abnormalities, such as behavioral alterations, central blindness, and strabismus persisted. CONCLUSIONS: Lissencephaly should be considered an important differential diagnosis in Shih Tzu dogs presenting with early-onset signs of forebrain abnormalities, including cluster seizures and behavioral alterations. Magnetic resonance imaging was appropriate for ante-mortem diagnosis of lissencephaly and associated cerebral anomalies.
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Anticonvulsivantes/uso terapéutico , Enfermedades de los Perros/diagnóstico por imagen , Epilepsia/veterinaria , Lisencefalia/veterinaria , Animales , Enfermedades de los Perros/congénito , Enfermedades de los Perros/diagnóstico , Perros , Epilepsia/tratamiento farmacológico , Epilepsia/etiología , Femenino , Lisencefalia/complicaciones , Lisencefalia/diagnóstico , Lisencefalia/diagnóstico por imagen , Imagen por Resonancia Magnética/veterinaria , MasculinoRESUMEN
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.
Asunto(s)
Artrogriposis/genética , Hidropesía Fetal/genética , Microcefalia/genética , Migraña con Aura/genética , ATPasa Intercambiadora de Sodio-Potasio/genética , Alelos , Animales , Artrogriposis/patología , Niño , Femenino , Predisposición Genética a la Enfermedad , Humanos , Hidropesía Fetal/patología , Recién Nacido , Mutación con Pérdida de Función/genética , Masculino , Ratones , Microcefalia/patología , Migraña con Aura/patología , Fenotipo , Embarazo , Isoformas de Proteínas/genética , Secuenciación del ExomaRESUMEN
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.
RESUMEN
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.
Asunto(s)
Embarazo , Diagnóstico por Imagen , Trastornos del NeurodesarrolloRESUMEN
Evaluar la efectividad de las estrategias existentes para la prevención de la ambliopía en pacientes menores de 18 años. o Evaluar la efectividad de las estrategias existentes para la detección temprana en pacientes menores de 18 años.
Asunto(s)
Humanos , Preescolar , Niño , Adolescente , Ambliopía/diagnóstico , Ambliopía/terapia , Ambliopía/prevención & control , Diagnóstico PrecozRESUMEN
Abstract Objective: This study aimed to critically review the literature available regarding the Zika virus outbreak in Brazil and its possible association with microcephaly cases. Sources: Experts from Instituto do Cérebro do Rio Grande do Sul performed a critical (nonsystematic) literature review regarding different aspects of the Zika virus outbreak in Brazil, such as transmission, epidemiology, diagnostic criteria, and its possible association with the increase of microcephaly reports. The PubMed search using the key word “Zika virus” in February 2016 yielded 151 articles. The manuscripts were reviewed, as well as all publications/guidelines from the Brazilian Ministry of Health, World Health Organization and Centers for Disease Control and Prevention (CDC – United States). Summary of findings: Epidemiological data suggest a temporal association between the increased number of microcephaly notifications in Brazil and outbreak of Zika virus, primarily in the Brazil's Northeast. It has been previously documented that many different viruses might cause congenital acquired microcephaly. Still there is no consensus on the best curve to measure cephalic circumference, specifically in preterm neonates. Conflicting opinions regarding the diagnosis of microcephaly (below 2 or 3 standard deviations) that should be used for the notifications were also found in the literature. Conclusion: The development of diagnostic techniques that confirm a cause–effect association and studies regarding the physiopathology of the central nervous system impairment should be prioritized. It is also necessary to strictly define the criteria for the diagnosis of microcephaly to identify cases that should undergo an etiological investigation.
Resumo Objetivos: O objetivo deste estudo foi realizar uma revisão crítica da literatura sobre o surto de vírus Zika no Brasil e sua possível associação com casos de microcefalia. Fonte de dados: Especialistas em áreas afins do Instituto do Cérebro do Rio Grande do Sul realizaram uma revisão crítica (não sistemática) da literatura sobre o vírus Zika, suas formas de transmissão, a epidemia no Brasil, critérios diagnósticos e a possível associação com os casos crescentes de microcefalia. O uso da palavra chave “Zika virus” na base de dados do PubMed em fevereiro de 2016, retorna 151 publicações. Estes textos foram revisados assim como todas as publicações e recomendações do Ministério da Saúde, Organização Mundial da Saúde e Centro de Controle de Doenças (CDC – USA). Síntese dos dados: Os dados epidemiológicos sugerem uma relação temporal entre aumento da notificação de casos de microcefalia e o surto de vírus Zika, principalmente no Nordeste do Brasil. Agentes virais comprovadamente podem ser causadores de microcefalia congênita adquirida. Não existe um consenso sobre a melhor curva de perímetro cefálico a ser utilizada, principalmente nos prematuros. Assim como também existem divergências sobre a definição de microcefalia (abaixo de 2 ou 3 desvios padrões) a ser padronizada nas notificações. Conclusão: Deve-se priorizar o desenvolvimento de técnicas diagnósticas que confirmem uma relação causa–efeito e estudos sobre mecanismos da patogênese da infecção pelo Zika no sistema nervoso central. Também é necessário definir e universalizar os critérios diagnósticos para a identificação dos casos de microcefalia que devem ser submetidos à investigação etiológica.
Asunto(s)
Humanos , Animales , Femenino , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Infección por el Virus Zika/epidemiología , Microcefalia/epidemiología , Microcefalia/virología , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/virología , Brasil/epidemiología , Brotes de Enfermedades , Aedes , Virus Zika/aislamiento & purificación , Infección por el Virus Zika/diagnóstico , Insectos Vectores , Microcefalia/diagnósticoRESUMEN
OBJECTIVE: This study aimed to critically review the literature available regarding the Zika virus outbreak in Brazil and its possible association with microcephaly cases. SOURCES: Experts from Instituto do Cérebro do Rio Grande do Sul performed a critical (nonsystematic) literature review regarding different aspects of the Zika virus outbreak in Brazil, such as transmission, epidemiology, diagnostic criteria, and its possible association with the increase of microcephaly reports. The PubMed search using the key word "Zika virus" in February 2016 yielded 151 articles. The manuscripts were reviewed, as well as all publications/guidelines from the Brazilian Ministry of Health, World Health Organization and Centers for Disease Control and Prevention (CDC - United States). SUMMARY OF FINDINGS: Epidemiological data suggest a temporal association between the increased number of microcephaly notifications in Brazil and outbreak of Zika virus, primarily in the Brazil's Northeast. It has been previously documented that many different viruses might cause congenital acquired microcephaly. Still there is no consensus on the best curve to measure cephalic circumference, specifically in preterm neonates. Conflicting opinions regarding the diagnosis of microcephaly (below 2 or 3 standard deviations) that should be used for the notifications were also found in the literature. CONCLUSION: The development of diagnostic techniques that confirm a cause-effect association and studies regarding the physiopathology of the central nervous system impairment should be prioritized. It is also necessary to strictly define the criteria for the diagnosis of microcephaly to identify cases that should undergo an etiological investigation.
Asunto(s)
Microcefalia/epidemiología , Microcefalia/virología , Complicaciones Infecciosas del Embarazo/epidemiología , Infección por el Virus Zika/epidemiología , Aedes , Animales , Brasil/epidemiología , Brotes de Enfermedades , Femenino , Humanos , Recién Nacido , Insectos Vectores , Microcefalia/diagnóstico , Embarazo , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/virología , Virus Zika/aislamiento & purificación , Infección por el Virus Zika/diagnósticoRESUMEN
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.
RESUMEN
Cortical GABAergic interneurons constitute an extremely diverse population of cells organized in a well-defined topology of precisely interconnected cells. They play a crucial role regulating inhibitory-excitatory balance in brain circuits, gating sensory perception, and regulating spike timing to brain oscillations during distinct behaviors. Dysfunctions in the establishment of proper inhibitory circuits have been associated to several brain disorders such as autism, epilepsy, and schizophrenia. In the rodent adult cortex, inhibitory neurons are generated during the second gestational week from distinct progenitor lineages located in restricted domains of the ventral telencephalon. However, only recently, studies have revealed some of the mechanisms generating the heterogeneity of neuronal subtypes and their modes of integration in brain networks. Here we will discuss some the events involved in the production of cortical GABAergic neuron diversity with focus on the interaction between intrinsically driven genetic programs and environmental signals during development.