RESUMO
Neuronal migration disorders (NMDs) are a heterogeneous group of conditions caused by the abnormal migration of neuroblasts in the developing brain and nervous system, resulting in severe developmental impairment, intractable epilepsy and intellectual disability (Spalice et al. 2009). To date, many genes have been identified as the leading cause of migration defects, i.e. agyria/pachygyria, polymicrogyria, heterotopias, agenesis of the corpus callosum and agenesis of the cranial nerves (Spalice et al. 2009). Here, we present a patient with early infantile epileptic encephalopathy (Ohtahara syndrome) with seizure onset on the first dayof life, severe developmental delay and an abnormal brain MRI with excessive folding of small, fused gyri and bilateral perisylvian polymicrogyria, suggestive of neuronal migration disorder. To clarify the unknown aetiology, we conducted whole-exome sequencing, which detected a de novo missense variant (c.5308A>T; p.(Met1770Leu)) in the SCN2A gene. This is a report of SCN2A gene variant identified in a patient with neuronal migration disorder which could further expand the phenotypic spectrum of these genetic disorders.
Assuntos
Mutação , Canal de Sódio Disparado por Voltagem NAV1.2/genética , Neuroimagem , Fenótipo , Espasmos Infantis/diagnóstico , Espasmos Infantis/genética , Sequência de Aminoácidos , Diagnóstico Diferencial , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Malformações do Desenvolvimento Cortical do Grupo II/diagnóstico , Neuroimagem/métodosRESUMO
Focal cortical dysplasia is a common cause of medically refractory epilepsy in infancy and childhood. We report a neonate with seizures occurring within the first day of life. Continuous video-EEG monitoring led to detection of left motor seizures and a right frontal EEG seizure pattern. Brain MRI revealed a lesion within the right frontal lobe without contrast enhancement. The patient was referred for epilepsy surgery due to drug resistance to vitamin B6 and four antiepileptic drugs. Lesionectomy was performed at the age of two and a half months, and histopathological evaluation confirmed the diagnosis of focal cortical dysplasia type IIb (FCD IIb). The patient is free of unprovoked seizures without medication (Engel Class I) and is normally developed at 36 months after surgery. The case study demonstrates that FCD IIb may cause seizures within the first day of life and that epilepsy surgery can be successfully performed in medically intractable patients with a clearly identifiable seizure onset zone within the first three months of life. Although radical surgery such as hemispherectomy and multi-lobar resections are over-represented in early infancy, this case also illustrates a favourable outcome with a more limited resection in this age group.
Assuntos
Epilepsia Resistente a Medicamentos/cirurgia , Malformações do Desenvolvimento Cortical do Grupo II/cirurgia , Pré-Escolar , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/etiologia , Epilepsia Resistente a Medicamentos/fisiopatologia , Eletroencefalografia , Feminino , Humanos , Imageamento por Ressonância Magnética , Malformações do Desenvolvimento Cortical do Grupo II/complicações , Malformações do Desenvolvimento Cortical do Grupo II/diagnósticoRESUMO
Neuronal migration disorders are a clinically and genetically heterogeneous group of malformations of cortical development, frequently responsible for severe disability. Despite the increasing knowledge of the molecular mechanisms underlying this group of diseases, their genetic diagnosis remains unattainable in a high proportion of cases. Here, we present the results of 38 patients with lissencephaly, periventricular heterotopia and subcortical band heterotopia from Argentina. We performed Sanger and Next Generation Sequencing (NGS) of DCX, FLNA and ARX and searched for copy number variations by MLPA in PAFAH1B1, DCX, POMT1, and POMGNT1. Additionally, somatic mosaicism at 5% or higher was investigated by means of targeted high coverage NGS of DCX, ARX, and PAFAH1B1. Our approach had a diagnostic yield of 36%. Pathogenic or likely pathogenic variants were identified in 14 patients, including 10 germline (five novel) and 4 somatic mutations in FLNA, DCX, ARX and PAFAH1B1 genes. This study represents the largest series of patients comprehensively characterized in our population. Our findings reinforce the importance of somatic mutations in the pathophysiology and diagnosis of neuronal migration disorders and contribute to expand their phenotype-genotype correlations.
Assuntos
Mutação em Linhagem Germinativa , Malformações do Desenvolvimento Cortical do Grupo II/genética , Estudos de Coortes , Variações do Número de Cópias de DNA , Feminino , Genótipo , Humanos , Masculino , Malformações do Desenvolvimento Cortical do Grupo II/diagnóstico , Fenótipo , Adulto JovemRESUMO
OBJECTIVE: Focal cortical dysplasia (FCD) type IIb is a cortical malformation characterized by cortical architectural abnormalities, dysmorphic neurons, and balloon cells. It has been suggested that FCDs are caused by somatic mutations in cells in the developing brain. Here, we explore the possible involvement of somatic mutations in FCD type IIb. METHODS: We collected a total of 24 blood-brain paired samples with FCD, including 13 individuals with FCD type IIb, 5 with type IIa, and 6 with type I. We performed whole-exome sequencing using paired samples from 9 of the FCD type IIb subjects. Somatic MTOR mutations were identified and further investigated using all 24 paired samples by deep sequencing of the entire gene's coding region. Somatic MTOR mutations were confirmed by droplet digital polymerase chain reaction. The effect of MTOR mutations on mammalian target of rapamycin (mTOR) kinase signaling was evaluated by immunohistochemistry and Western blotting analyses of brain samples and by in vitro transfection experiments. RESULTS: We identified four lesion-specific somatic MTOR mutations in 6 of 13 (46%) individuals with FCD type IIb showing mutant allele rates of 1.11% to 9.31%. Functional analyses showed that phosphorylation of ribosomal protein S6 in FCD type IIb brain tissues with MTOR mutations was clearly elevated, compared to control samples. Transfection of any of the four MTOR mutants into HEK293T cells led to elevated phosphorylation of 4EBP, the direct target of mTOR kinase. INTERPRETATION: We found low-prevalence somatic mutations in MTOR in FCD type IIb, indicating that activating somatic mutations in MTOR cause FCD type IIb.
Assuntos
Encéfalo/patologia , Malformações do Desenvolvimento Cortical do Grupo II/genética , Mutação/genética , Serina-Treonina Quinases TOR/genética , Adolescente , Adulto , Criança , Feminino , Células HEK293 , Humanos , Masculino , Malformações do Desenvolvimento Cortical/diagnóstico , Malformações do Desenvolvimento Cortical/genética , Malformações do Desenvolvimento Cortical do Grupo II/diagnósticoAssuntos
Epilepsias Parciais/diagnóstico , Lobo Frontal/patologia , Lobo Frontal/fisiopatologia , Malformações do Desenvolvimento Cortical do Grupo II/diagnóstico , Malformações do Desenvolvimento Cortical do Grupo II/patologia , Criança , Diagnóstico Diferencial , Eletroencefalografia , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Malformações do Desenvolvimento Cortical do Grupo II/fisiopatologia , Malformações do Desenvolvimento Cortical do Grupo II/cirurgia , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
OBJECTIVE: A post-spike slow wave (PSS) as part of a spike and slow wave is presumably related to inhibition of epileptic activity. In this study, we evaluated dynamic changes of PSS power toward seizure onset in patients with focal cortical dysplasia (FCD) type II. METHODS: We collected data from 10 pediatric patients with FCD type II, who underwent invasive monitoring with subdural grids. The PSS were averaged based on spike-triggering in 30s epochs during both interictal and preictal periods. We quantitatively measured and compared PSS power and distribution between interictal and preictal periods, both within and outside the seizure onset zone (SOZ). RESULTS: PSS power was significantly higher in all areas during preictal period compared with interictal period. During preictal period, PSS power within SOZ was significantly higher than outside SOZ. From interictal to preictal period, the number of electrodes with high power PSS significantly increased within SOZ and decreased outside SOZ. CONCLUSIONS: Toward seizure onset, PSS power increased in all areas, predominantly within SOZ, and became confined into SOZ in a subset of FCD type II patients. SIGNIFICANCE: Preictal PSS power increase and confinement into SOZ accompany transition to seizures.
Assuntos
Potenciais de Ação , Ondas Encefálicas , Malformações do Desenvolvimento Cortical do Grupo II/diagnóstico , Malformações do Desenvolvimento Cortical do Grupo II/fisiopatologia , Convulsões/diagnóstico , Convulsões/fisiopatologia , Potenciais de Ação/fisiologia , Adolescente , Ondas Encefálicas/fisiologia , Criança , Pré-Escolar , Eletroencefalografia/tendências , Feminino , Humanos , Masculino , Malformações do Desenvolvimento Cortical do Grupo II/complicações , Estudos Retrospectivos , Convulsões/complicaçõesRESUMO
Disruption of neuronal migration in humans is associated with a wide range of behavioral and cognitive outcomes including severe intellectual disability, language impairment, and social dysfunction. Furthermore, malformations of cortical development have been observed in a number of neurodevelopmental disorders (e.g. autism and dyslexia), where boys are much more commonly diagnosed than girls (estimates around 4 to 1). The use of rodent models provides an excellent means to examine how sex may modulate behavioral outcomes in the presence of comparable abnormal neuroanatomical presentations. Initially characterized by Rosen et al. 2012, the BXD29- Tlr4(lps-2J) /J mouse mutant exhibits a highly penetrant neuroanatomical phenotype that consists of bilateral midline subcortical nodular heterotopia with partial callosal agenesis. In the current study, we confirm our initial findings of a severe impairment in rapid auditory processing in affected male mice. We also report that BXD29- Tlr4(lps-2J) /J (mutant) female mice show no sparing of rapid auditory processing, and in fact show deficits similar to mutant males. Interestingly, female BXD29- Tlr4(lps-2J) /J mice do display superiority in Morris water maze performance as compared to wild type females, an affect not seen in mutant males. Finally, we report new evidence that BXD29- Tlr4(lps-2J) /J mice, in general, show evidence of hyper-social behaviors. In closing, the use of the BXD29- Tlr4(lps-2J) /J strain of mice - with its strong behavioral and neuroanatomical phenotype - may be highly useful in characterizing sex independent versus dependent mechanisms that interact with neural reorganization, as well as clinically relevant abnormal behavior resulting from aberrant neuronal migration.
Assuntos
Comportamento Animal , Malformações do Desenvolvimento Cortical do Grupo II/diagnóstico , Animais , Modelos Animais de Doenças , Retroalimentação Sensorial , Feminino , Masculino , Malformações do Desenvolvimento Cortical do Grupo II/genética , Malformações do Desenvolvimento Cortical do Grupo II/patologia , Aprendizagem em Labirinto , Camundongos , Camundongos Transgênicos , Malformações do Sistema Nervoso/genética , Fenótipo , Índice de Gravidade de Doença , Fatores Sexuais , Comportamento SocialRESUMO
Subependymal heterotopia (SEH) is a neuronal migration disorder characterized by nodules of gray matter along the lateral ventricular walls and often associated with other brain malformations. We present two cases of SEH associated with ventriculomegaly and cerebellar abnormalities diagnosed by fetal magnetic resonance imaging (MRI) at 20 and 23 weeks' gestation respectively. Fetal MRI findings of this association of abnormalities have never been reported in literature. This report emphasizes the role of fetal MRI in recognition of subependymal heterotopia and other associated brain anomalies at early age of gestation along with its importance for a more targeted counseling and management strategies.
Assuntos
Encefalopatias/diagnóstico , Encéfalo/anormalidades , Doenças Fetais/diagnóstico , Malformações do Desenvolvimento Cortical do Grupo II/diagnóstico , Adulto , Cerebelo/anormalidades , Feminino , Humanos , Hidrocefalia/diagnóstico , Imageamento por Ressonância Magnética/métodos , Diagnóstico Pré-Natal/métodosRESUMO
De novo mutations in the TUBA1A gene are responsible for a wide spectrum of neuronal migration disorders, ranging from lissencephaly to perisylvian pachygyria. Recently, one family with polymicrogyria (PMG) and mutation in TUBA1A was reported. Hence, the purpose of our study was to determine the frequency of TUBA1A mutations in patients with PMG and better define clinical and imaging characteristics for TUBA1A-related PMG. We collected 95 sporadic patients with non-syndromic bilateral PMG, including 54 with perisylvian PMG and 30 PMG with additional brain abnormalities. Mutation analysis of the TUBA1A gene was performed by sequencing of PCR fragments corresponding to TUBA1A-coding sequences. Three de novo missense TUBA1A mutations were identified in three unrelated patients with PMG representing 3.1% of PMG and 10% of PMGs with complex cerebral malformations. These patients had bilateral perisylvian asymmetrical PMG with dysmorphic basal ganglia cerebellar vermian dysplasia and pontine hypoplasia. These mutations (p.Tyr161His; p.Val235Leu; p.Arg390Cys) appear distributed throughout the primary structure of the alpha-tubulin polypeptide, but their localization within the tertiary structure suggests that PMG-related mutations are likely to impact microtubule dynamics, stability and/or local interactions with partner proteins. These findings broaden the phenotypic spectrum associated with TUBA1A mutations to PMG and further emphasize that additional brain abnormalities, that is, dysmorphic basal ganglia, hypoplastic pons and cerebellar dysplasia are key features for the diagnosis of TUBA1A-related PMG.
Assuntos
Malformações do Desenvolvimento Cortical do Grupo II/genética , Malformações do Desenvolvimento Cortical/genética , Tubulina (Proteína)/genética , Sequência de Aminoácidos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Malformações do Desenvolvimento Cortical/diagnóstico , Malformações do Desenvolvimento Cortical do Grupo II/diagnóstico , Dados de Sequência Molecular , Mutação de Sentido Incorreto , Linhagem , Estrutura Terciária de Proteína , Tubulina (Proteína)/química , Tubulina (Proteína)/metabolismoRESUMO
Objetivo: Presentar 16 pacientes con esquisencefalia y afectación neurológica recalcando sus características clínicas y de imagen.Material y métodos: Son 16 pacientes, 8 varones y 8 mujeres, todos ellos con edades por debajo de los 3 años al hacerse el diagnóstico de esquisencefalia. En dos casos el diagnóstico se hizo prenatalmente y, en los otros 14, a lo largo de los cinco primeros años de vida. El diagnóstico se hizo por tomografía computarizada (TC) en un caso y por RM tridimensional (RM3D) con un aparato de 1,5 T en los otros casos. Los motivos de la consulta fueron retraso psicomotor, trastornos motores y/o crisis epilépticas en la mayoría de los pacientes. Resultados: La esquisencefalia era de labios abiertos bilaterales en 5 pacientes (dos de ellos por citomegalia durante la gestación), labios abiertos unilaterales en 2 pacientes, 8 mostraban esquisencefalia unilateral de labios cerrados y 1 tenía esquisencefalia de labios abiertos en un lado y cerrados en otro. En dos pacientes se diagnosticó infección prenatal por citomegalovirus y en otros dos se diagnosticó malformación cerebral central prenatal por ecografía rutinaria durante la gestación. Todos los pacientes presentaban algún tipo de deficiencia motriz uni o bilateral. Ocho pacientes padecían crisis epilépticas (50%) parciales en todos los casos y solo en uno de ellos se generalizaban. Este último caso fue el único en el que las crisis no llegaron a ser controladas. Todos los pacientes presentaban algún tipo de deficiencia motriz, generalmente benigna, unilateral (hemiparesia) o bilateral (tetraparesia). Conclusión: La RM3D es muy importante para el diagnóstico de la esquisencefalia ya que permite ver la capa de polimicrogiria que tapiza los labios de la malformación y, por ello, la diferenciación con las cavidades porencefálicas (AU)
Objective: To present 16 patients with schizencephaly and neurological involvement, and analyse their characteristics and neuroimages. Material and methods:The study included 16 patients, 8 males and 8 females, all of whom were diagnosed with schizencephaly at less than 3 years of age; 2 patients were diagnosed prenatally. Schizencephaly was identified by computerized tomography (CT) in 1 patient and by MR or three-dimensional MR (3DMR) with a 1.5tesla apparatus in the others. Most patients were referred for evaluation because of psychomotor delay, motor disabilities and/or seizures. Results: Five patients had bilateral schizencephaly with open lips (2 of them had suffered intrauterine cytomegalovirus infections); 2 showed unilateral schizencephaly with separated lips, 8 presented unilateral schizencephaly with fused lips, and 1 had schizencephaly with open lips on one side and fused lips on the other. Prenatal cytomegalovirus infection was diagnosed in 2 patients. A cerebral malformation that affected the midline was diagnosed by routine ultrasound studies in 2 patients. Eight patients (50%) presented with seizures that were focal, except for one patient who showed secondary generalisation. The latter was the only patient whose disease was refractory to complete seizure control with antiepileptic medication. All patients had some degree of motor deficit, which was either unilateral (hemiparesis) or bilateral (tetraparesis). Conclusion:3D MR imaging was very important in diagnosing of schizencephaly in our patients because it showed the polymicrogyria that covered the area of the cleft and permitted us to rule out porencephaly. Neuronal migration disorders such as heterotopias and, more frequently, cortical dysplasias, were observed in several patients. Half of the patients had epilepsy which was controlled with antiepileptic medication, except in 1 patient (AU)
Assuntos
Humanos , Cérebro/anormalidades , Malformações do Desenvolvimento Cortical/diagnóstico , Malformações do Desenvolvimento Cortical do Grupo II/diagnóstico , Espectroscopia de Ressonância MagnéticaAssuntos
Hipóxia Encefálica/complicações , Convulsões/etiologia , Anticonvulsivantes/uso terapêutico , Diagnóstico Diferencial , Eletroencefalografia , Humanos , Hipóxia-Isquemia Encefálica/diagnóstico , Recém-Nascido , Infecções/diagnóstico , Hemorragias Intracranianas/diagnóstico , Malformações do Desenvolvimento Cortical do Grupo II/diagnóstico , Convulsões/diagnóstico , Convulsões/tratamento farmacológico , Convulsões/fisiopatologiaRESUMO
We present six patients from five unrelated families with a condition originally described by Van Maldergem et al and provide follow-up studies of the original patient. The phenotype comprises a distinctive facial appearance that includes blepharophimosis, maxillary hypoplasia, telecanthus, microtia and atresia of the external auditory meatus, intellectual disability, digital contractures and skeletal anomalies together with subependymal and subcortical neuronal heterotopia. Affected patients typically have neonatal hypotonia, chronic feeding difficulties and respiratory problems. In our cohort, we have observed one instance of sibling recurrence and parental consanguinity in three of the families, indicating that autosomal recessive inheritance is likely.
Assuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Craniofaciais/diagnóstico , Deformidades Congênitas do Pé/diagnóstico , Genes Recessivos , Deformidades Congênitas da Mão/diagnóstico , Deficiência Intelectual/diagnóstico , Instabilidade Articular/diagnóstico , Malformações do Desenvolvimento Cortical do Grupo II/diagnóstico , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/patologia , Criança , Pré-Escolar , Consanguinidade , Anormalidades Craniofaciais/genética , Anormalidades Craniofaciais/patologia , Diagnóstico Diferencial , Feminino , Deformidades Congênitas do Pé/genética , Deformidades Congênitas do Pé/patologia , Deformidades Congênitas da Mão/genética , Deformidades Congênitas da Mão/patologia , Humanos , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Instabilidade Articular/genética , Instabilidade Articular/patologia , Cariótipo , Masculino , Malformações do Desenvolvimento Cortical do Grupo II/genética , Malformações do Desenvolvimento Cortical do Grupo II/patologia , LinhagemAssuntos
Deleção Cromossômica , Cromossomos Humanos Par 4/genética , Hipocalcemia/genética , Malformações do Desenvolvimento Cortical do Grupo II/genética , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Mapeamento Cromossômico , Hibridização Genômica Comparativa , Epilepsia/diagnóstico , Feminino , Genoma Humano , Humanos , Lactente , Recém-Nascido , Malformações do Desenvolvimento Cortical do Grupo II/diagnóstico , Malformações do Desenvolvimento Cortical do Grupo II/patologia , Mucinas/genética , Proteínas e Peptídeos Salivares/genética , UltrassonografiaRESUMO
A magnetic resonance (MR) diffusion tensor imaging (DTI) study was performed in a newborn with bilateral subependymal heterotopia (SE). White matter fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) were compared to values obtained in four newborns with moderate perinatal asphyxia and normal MRI findings. The reduction of FA and increase of AD and RD in the newborn with SE were the in vivo late expression of alterations in the intermediate zone, with an underlying arrest of neuronal migration.
Assuntos
Imagem de Tensor de Difusão , Epilepsia/complicações , Epilepsia/diagnóstico , Doenças Fetais/diagnóstico , Malformações do Desenvolvimento Cortical do Grupo II/complicações , Malformações do Desenvolvimento Cortical do Grupo II/diagnóstico , Fibras Nervosas Mielinizadas/patologia , Adulto , Feminino , Humanos , Recém-Nascido , GravidezAssuntos
Malformações do Desenvolvimento Cortical do Grupo II/diagnóstico , Nevo Sebáceo de Jadassohn/diagnóstico , Encéfalo/patologia , Pré-Escolar , Humanos , Imageamento por Ressonância Magnética , Masculino , Malformações do Desenvolvimento Cortical do Grupo II/complicações , Nevo Sebáceo de Jadassohn/complicaçõesRESUMO
PURPOSE: Diffusion tensor imaging provides better understanding of pathophysiology of congenital anomalies, involving central nervous system. This study was aimed to specify the pathogenetic mechanism of heterotopia, proved by diffusion tensor imaging, and establish new findings of heterotopia on fractional anisotropy maps. MATERIALS AND METHODS: Diffusion-weighted imaging data from 11 patients (M : F = 7 : 4, aged from 1 to 22 years, mean = 12.3 years) who visited the epilepsy clinic and received a routine seizure protocol MRI exam were retrospectively analyzed. Fractional anisotropy (FA) maps were generated from diffusion tensor imaging of 11 patients with heterotopia. Regions of interests (ROI) were placed in cerebral cortex, heterotopic gray matter and deep gray matter, including putamen. ANOVA analysis was performed for comparison of different gray matter tissues. RESULTS: Heterotopic gray matter showed signal intensities similar to normal gray matter on T1 and T2 weighted MRI. The measured FA of heterotopic gray matter was higher than that of cortical gray matter (0.236 +/- 0.011 vs. 0.169 +/- 0.015, p < 0.01, one way ANOVA), and slightly lower than that of deep gray matter (0.236 +/- 0.011 vs. 0.259 +/- 0.016, p < 0.01). CONCLUSION: Increased FA of heterotopic gray matter suggests arrested neuron during radial migration and provides better understanding of neurodevelopment.
Assuntos
Imagem de Tensor de Difusão/métodos , Malformações do Desenvolvimento Cortical do Grupo II/patologia , Adolescente , Adulto , Anisotropia , Movimento Celular , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Malformações do Desenvolvimento Cortical do Grupo II/diagnóstico , Malformações do Desenvolvimento Cortical do Grupo II/etiologiaRESUMO
Migration disorders (MD) are increasingly recognized as an important cause of epilepsy and developmental delay. Up to 25 % of children with refractory epilepsy have a cortical malformation. MD encompass a wide spectrum with underlying genetic etiologies and clinical manifestations. Research regarding the delineation of the genetic and molecular basis of these disorders has provided greater insight into the pathogenesis of not only the malformation but also the process involved in normal cortical development. Diagnosis of MD is important since patients who fail three antiepileptic medications are less likely to have their seizures controlled with additional trials of medications and therefore epilepsy surgery should be considered. Recent improvements in neuroimaging have resulted in a significant increase in the recognition of MD. Findings can be subdivided in disorders due to abnormal neurogenesis, neuronal migration, neuronal migration arrest and neuronal organization resulting in different malformations like microcephaly, lissencephaly, schizencephaly and heterotopia. The examination protocol should include T 1-w and T 2-w sequences in adequate slice orientation. T 1-w turbo-inversion recovery sequences (TIR) can be helpful to diagnose heterotopia. Contrast agent is needed only to exclude other differential diagnoses.
Assuntos
Imageamento por Ressonância Magnética , Malformações do Desenvolvimento Cortical/diagnóstico , Córtex Cerebral/patologia , Criança , Pré-Escolar , Coristoma/classificação , Coristoma/diagnóstico , Coristoma/genética , Epilepsia/classificação , Epilepsia/diagnóstico , Epilepsia/genética , Feminino , Humanos , Lactente , Recém-Nascido , Lisencefalia/classificação , Lisencefalia/diagnóstico , Lisencefalia/genética , Malformações do Desenvolvimento Cortical/classificação , Malformações do Desenvolvimento Cortical/genética , Malformações do Desenvolvimento Cortical do Grupo II/classificação , Malformações do Desenvolvimento Cortical do Grupo II/diagnóstico , Malformações do Desenvolvimento Cortical do Grupo II/genética , Gravidez , Diagnóstico Pré-Natal , Prognóstico , Sensibilidade e EspecificidadeRESUMO
Schizencephaly is a rare neuromigrational/organizational disorder characterized by the development of cerebral clefts, which are typically associated with neurological sequelae including seizures, motor disturbances, and cognitive dysfunction. Although there are multiple case reports of schizencephaly and associated neurological sequelae, primarily in children, the literature regarding neuropsychological manifestations of schizencephaly is limited. This article reviews the case of a woman diagnosed with bilateral schizencephaly at age 29. Neuropsychological testing revealed intact intelligence and memory functioning. However, impairments were noted in attention, executive functioning, expressive language skills, visual-spatial abilities, and bilateral manual motor skills, all of which were adversely impacting her functional abilities (e.g., ability to be gainfully employed). Given the potential variability in deficits associated with schizencephaly, this case demonstrates the utility of neuropsychological evaluation for understanding cognitive and functional consequences of bilateral schizencephaly.
Assuntos
Encéfalo/anormalidades , Encéfalo/fisiopatologia , Malformações do Desenvolvimento Cortical/diagnóstico , Malformações do Desenvolvimento Cortical/fisiopatologia , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Malformações do Desenvolvimento Cortical do Grupo II/diagnóstico , Malformações do Desenvolvimento Cortical do Grupo II/fisiopatologia , Testes NeuropsicológicosRESUMO
UNLABELLED: Disorders of neuronal migration are a heterogeneous group of disorders of nervous system development. One of the most frequent disorders is lissencephaly, characterized by a paucity of normal gyri and sulci resulting in a 'smooth brain'. There are two pathologic subtypes: classical and cobblestone. Six different genes could be responsible for this entity (LIS1, DCX, TUBA1A, VLDLR, ARX, RELN), although co-delection of YWHAE gene with LIS1 could result in Miller-Dieker Syndrome. Heterotopia is defined as a cluster of normal neurons in abnormal locations, and divided into three main groups: periventricular nodular heterotopia, subcortical heterotopia and marginal glioneural heterotopia. Genetically, heterotopia is related to Filamin A (FLNA) or ADP-ribosylation factor guanine exchange factor 2 (ARFGEF2) genes mutations. Polymicrogyria is described as an augmentation of small circonvolutions separated by shallow enlarged sulci; bilateral frontoparietal form is characterized by bilateral, symmetric polymicrogyria in the frontoparietal regions. Bilateral perisylvian polymicrogyria results in a clinical syndrome manifested by mild mental retardation, epilepsy and pseudobulbar palsy. Gene mutations linked to this disorder are SRPX2, PAX6, TBR2, KIAA1279, RAB3GAP1 and COL18A1. Schizencephaly, consisting in a cleft of cerebral hemisphere connecting extra-axial subaracnoid spaces and ventricles, is another important disorder of neuronal migration whose clinical characteristics are extremely variable. EMX2 gene could be implicated in its genesis. Focal cortical dysplasia is characterized by three different types of altered cortical laminations, and represents one of most severe cause of epilepsy in children. TSC1 gene could play a role in its etiology. CONCLUSION: This review reports the main clinical, genetical and neuroradiological aspects of these disorders. It is hoped that accumulating data of the development mechanisms underlying the expanded network formation in the brain will lead to the development of therapeutic options for neuronal migration disorders.