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OBJECTIVES: To describe the prenatal neuroimaging spectrum of rhombencephalosynapsis (RES) and criteria for its classification according to the severity of vermian anomaly. METHODS: In this multicenter retrospective study of fetuses with RES between 2002 and 2020, the medical records and brain ultrasound and magnetic resonance images were evaluated comprehensively to determine the severity of the vermian anomaly and the presence of associated brain findings. RES was classified, according to the pattern of vermian agenesis and the extent of the fusion of the hemispheres, as complete RES (complete absence of the vermis) or partial RES (further classified according to the part of the vermis that was missing and, consequently, the region of hemispheric fusion, as anterior, posterior, severe or mixed RES). Findings were compared between cases with complete and those with partial RES. RESULTS: Included in the study were 62 fetuses with a gestational age ranging between 12 and 37 weeks. Most had complete absence of the vermis (complete RES, 77.4% of cases), a 'round-shaped' cerebellum on axial views (72.6%) and a transverse cerebellar diameter (TCD) < 3rd centile (87.1%). Among the 22.6% of cases with partial RES, 6.5% were classified as severe partial, 6.5% as partial anterior, 8.1% as partial mixed and 1.6% as partial posterior. Half of these cases presented with normal or nearly normal cerebellar morphology and 28.5% had a TCD within the normal limits. Infratentorially, the fourth ventricle was abnormal in 88.7% of cases overall, and anomalies of the midbrain and pons were frequent (93.5% and 77.4%, respectively). Ventriculomegaly was observed in 80.6% of all cases, being more severe in cases with complete RES than in those with partial RES, with high rates of parenchymal and septal disruption. CONCLUSIONS: This study provides prenatal neuroimaging criteria for the diagnosis and classification of RES, and identification of related features, using ultrasound and magnetic resonance imaging. According to our findings, a diagnosis of RES should be considered in fetuses with a small TCD (severe cerebellar hypoplasia) and/or a round-shaped cerebellum on axial views, during the second or third trimester, especially when associated with ventriculomegaly. Partial RES is more common than previously thought, but presents an extreme diagnostic challenge, especially in cases with normal or nearly-normal cerebellar morphobiometric features. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
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Anomalías Múltiples/diagnóstico por imagen , Vermis Cerebeloso/anomalías , Cerebelo/anomalías , Anomalías del Ojo/diagnóstico por imagen , Enfermedades Renales Quísticas/diagnóstico por imagen , Malformaciones del Sistema Nervioso/diagnóstico por imagen , Neuroimagen , Diagnóstico Prenatal/métodos , Retina/anomalías , Rombencéfalo/anomalías , Anomalías Múltiples/embriología , Adulto , Vermis Cerebeloso/diagnóstico por imagen , Vermis Cerebeloso/embriología , Cerebelo/diagnóstico por imagen , Cerebelo/embriología , Anomalías del Ojo/embriología , Femenino , Edad Gestacional , Humanos , Enfermedades Renales Quísticas/embriología , Imagen por Resonancia Magnética , Imagen Multimodal , Malformaciones del Sistema Nervioso/embriología , Embarazo , Retina/diagnóstico por imagen , Retina/embriología , Estudios Retrospectivos , Rombencéfalo/diagnóstico por imagen , Rombencéfalo/embriología , Índice de Severidad de la Enfermedad , Ultrasonografía PrenatalRESUMEN
BACKGROUND AND PURPOSE: Antibodies to myelin oligodendrocyte glycoprotein (MOG) have been identified in both children and adults with demyelination, with a strong association with bilateral or recurrent optic neuritis (ON). However, the full clinical spectrum of this newly described condition is unknown. We sought to describe non-ON inflammatory ophthalmological presentations such as uveitis and optic perineuritis in the context of MOG antibody seropositivity. METHODS: Using a live cell-based assay analysed by flow cytometry, we identified seropositive patients referred for MOG antibody testing in Australasia between 2014 and 2017. We identified four MOG antibody-positive patients with non-ON inflammatory ophthalmological presentations and present their detailed clinical information in this case series. RESULTS: Three patients had uveitis either in association with, or remote from, ON. One patient had optic perineuritis and peripheral ulcerative keratitis. We describe the presentation, examination, investigation findings and clinical course of these four patients. CONCLUSIONS: Recognition of these novel clinical associations may expand the clinical spectrum of MOG antibody-associated presentations. An expedited diagnosis may guide the management of these complex patients.
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Autoanticuerpos/inmunología , Glicoproteína Mielina-Oligodendrócito/inmunología , Neuritis Óptica/diagnóstico , Uveítis/diagnóstico , Adulto , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuritis Óptica/inmunología , Uveítis/inmunologíaRESUMEN
BACKGROUND AND PURPOSE: Clusters of acute limb weakness in paediatric patients have been linked to outbreaks of non-polio enteroviruses, termed acute flaccid myelitis (AFM). Outside these clusters, in countries where polio is not endemic, this poliomyelitic-like illness is rare in childhood and its natural history is not well defined. We describe presenting features, investigation findings and long-term outcome of a series of children with AFM. METHODS: This was a retrospective cohort study. RESULTS: Eight children (six females) aged 3 months to 8 years (median age 5 years) met case criteria. Initial symptoms were pain (n = 7) followed by limb weakness with hypotonia (n = 8). Flaccid paralysis occurred in only three patients. Two had cranial nerve dysfunction. Magnetic resonance imaging of the spinal cord demonstrated grey matter involvement particularly affecting the anterior cord, with longitudinally extensive changes in three children. Cerebrospinal fluid examination showed pleocytosis in six children with raised cerebrospinal fluid protein in five. Nerve conduction and electromyography findings were consistent with a motor neuronopathy. Residual deficits were common, with moderate to severe weakness seen in five patients. Median follow-up was 28 months (range 17-108 months, 30.4 patient years in total). CONCLUSIONS: Acute flaccid myelitis is an uncommon condition in childhood with a high rate of significant long-term morbidity. AFM should be considered in children presenting with acute limb pain and weakness.
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Mielitis/diagnóstico , Parálisis/diagnóstico , Médula Espinal/diagnóstico por imagen , Niño , Preescolar , Electrodiagnóstico , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Mielitis/diagnóstico por imagen , Mielitis/patología , Conducción Nerviosa/fisiología , Parálisis/diagnóstico por imagen , Parálisis/patología , Estudios Retrospectivos , Médula Espinal/patologíaRESUMEN
BACKGROUND AND PURPOSE: Pathogenic variants in the ACTA2 gene cause a distinctive arterial phenotype that has recently been described to be associated with brain malformation. Our objective was to further characterize gyral abnormalities in patients with ACTA2 pathogenic variants as per the 2020 consensus recommendations for the definition and classification of malformations of cortical development. MATERIALS AND METHODS: We performed a retrospective, multicentric review of patients with proved ACTA2 pathogenic variants, searching for the presence of malformations of cortical development. A consensus read was performed for all patients, and the type and location of cortical malformation were noted in each. The presence of the typical ACTA2 arterial phenotype as well as demographic and relevant clinical data was obtained. RESULTS: We included 13 patients with ACTA2 pathogenic variants (Arg179His mutation, n = 11, and Arg179Cys mutation, n = 2). Ninety-two percent (12/13) of patients had peri-Sylvian dysgyria, 77% (10/13) had frontal dysgyria, and 15% (2/13) had generalized dysgyria. The peri-Sylvian location was involved in all patients with dysgyria (12/12). All patients with dysgyria had a characteristic arterial phenotype described in ACTA2 pathogenic variants. One patient did not have dysgyria or the characteristic arterial phenotype. CONCLUSIONS: Dysgyria is common in patients with ACTA2 pathogenic variants, with a peri-Sylvian and frontal predominance, and was seen in all our patients who also had the typical ACTA2 arterial phenotype.
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Malformaciones del Sistema Nervioso , Actinas/genética , Humanos , Mutación , Fenotipo , Estudios RetrospectivosRESUMEN
BACKGROUND AND PURPOSE: Zhu-Tokita-Takenouchi-Kim syndrome is a severe multisystem malformation disorder characterized by developmental delay and a diverse array of congenital abnormalities. However, these currently identified phenotypic components provide limited guidance in diagnostic situations, due to both the nonspecificity and variability of these features. Here we report a case series of 7 individuals with a molecular diagnosis of Zhu-Tokita-Takenouchi-Kim syndrome, 5 ascertained by their presentation with the neuronal migration disorder, periventricular nodular heterotopia. MATERIALS AND METHODS: Individuals with a molecular diagnosis of Zhu-Tokita-Takenouchi-Kim syndrome were recruited from 2 sources, a high-throughput sequencing study of individuals with periventricular nodular heterotopia or from clinical diagnostic sequencing studies. We analyzed available brain MR images of recruited individuals to characterize periventricular nodular heterotopia distribution and to identify the presence of any additional brain abnormalities. RESULTS: Pathogenic variants in SON, causative of Zhu-Tokita-Takenouchi-Kim syndrome, were identified in 7 individuals. Brain MR images from these individuals were re-analyzed. A characteristic set of imaging anomalies in addition to periventricular nodular heterotopia was identified, including the elongation of the pituitary stalk, cerebellar enlargement with an abnormally shaped posterior fossa, rounding of the caudate nuclei, hippocampal malformations, and cortical anomalies including polymicrogyria or dysgyria. CONCLUSIONS: The recurrent neuroradiologic changes identified here represent an opportunity to guide diagnostic formulation of Zhu-Tokita-Takenouchi-Kim syndrome on the basis of brain MR imaging evaluation.
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Encefalopatías , Discapacidad Intelectual , Heterotopia Nodular Periventricular , Humanos , Encéfalo/patología , Imagen por Resonancia Magnética , Encefalopatías/patología , Discapacidad Intelectual/patologíaRESUMEN
BACKGROUND: Next generation sequencing studies have revealed an ever-increasing number of causes for genetic disorders of central nervous system white matter. A substantial number of disorders are identifiable from their specific pattern of biochemical and/or imaging findings for which single gene testing may be indicated. Beyond this group, the causes of genetic white matter disorders are unclear and a broader approach to genomic testing is recommended. AIM: This study aimed to identify the genetic causes for a group of individuals with unclassified white matter disorders with suspected genetic aetiology and highlight the investigations required when the initial testing is non-diagnostic. METHODS: Twenty-six individuals from 22 families with unclassified white matter disorders underwent deep phenotyping and genome sequencing performed on trio, or larger, family groups. Functional studies and transcriptomics were used to resolve variants of uncertain significance with potential clinical relevance. RESULTS: Causative or candidate variants were identified in 15/22 (68.2%) families. Six of the 15 implicated genes had been previously associated with white matter disease (COL4A1, NDUFV1, SLC17A5, TUBB4A, BOLA3, DARS2). Patients with variants in the latter two presented with an atypical phenotype. The other nine genes had not been specifically associated with white matter disease at the time of diagnosis and included genes associated with monogenic syndromes, developmental disorders, and developmental and epileptic encephalopathies (STAG2, LSS, FIG4, GLS, PMPCA, SPTBN1, AGO2, SCN2A, SCN8A). Consequently, only 46% of the diagnoses would have been made via a current leukodystrophy gene panel test. DISCUSSION: These results confirm the importance of broad genomic testing for patients with white matter disorders. The high diagnostic yield reflects the integration of deep phenotyping, whole genome sequencing, trio analysis, functional studies, and transcriptomic analyses. CONCLUSIONS: Genetic white matter disorders are genetically and phenotypically heterogeneous. Deep phenotyping together with a range of genomic technologies underpin the identification of causes of unclassified white matter disease. A molecular diagnosis is essential for prognostication, appropriate management, and accurate reproductive counseling.
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Leucoencefalopatías , Sustancia Blanca , Flavoproteínas , Pruebas Genéticas/métodos , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Leucoencefalopatías/diagnóstico por imagen , Leucoencefalopatías/genética , Proteínas Mitocondriales , Fenotipo , Monoéster Fosfórico Hidrolasas , Tubulina (Proteína) , Sustancia Blanca/diagnóstico por imagenRESUMEN
AIM: To identify the genetic aetiology of a distinct leukoencephalopathy causing acute neurological regression in infancy with apparently complete clinical recovery. METHODS: We performed trio whole genome sequencing (WGS) to determine the genetic basis of the disorder. Mitochondrial function analysis in cultured patient fibroblasts was undertaken to confirm the pathogenicity of candidate variants. RESULTS: The patient presented at 18 months with acute hemiplegia and cognitive regression without obvious trigger. This was followed by clinical recovery over 4 years. MRI at disease onset revealed bilateral T2 hyperintensity involving the periventricular and deep white matter and MR spectroscopy of frontal white matter demonstrated a lactate doublet. Lactate levels and mitochondrial respiratory chain enzyme activity in muscle, liver and fibroblasts were normal. Plasma glycine was elevated. The MRI abnormalities improved. WGS identified compound heterozygous variants in BOLA3: one previously reported (c.136C>T, p.Arg46*) and one novel variant (c.176G>A, p.Cys59Tyr). Analysis of cultured patient fibroblasts demonstrated deficient pyruvate dehydrogenase (PDH) activity and reduced quantity of protein subunits of mitochondrial complexes I and II, consistent with BOLA3 dysfunction. Previously reported cases of multiple mitochondrial dysfunctions syndrome 2 (MMDS2) with hyperglycinaemia caused by BOLA3 mutations have leukodystrophy with severe, progressive neurological and multisystem disease. CONCLUSIONS: We report a novel phenotype for MMDS2 associated with apparently complete clinical recovery and partial resolution of MRI abnormalities. We have identified a novel disease-causing variant in BOLA3 validated by functional cellular studies. Our patient's clinical course broadens the phenotypic spectrum of MMDS2 and highlights the potential for some genetic leukoencephalopathies to spontaneously improve.
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The ability to temporarily maintain relevant information in mind in the presence of interference or distracting information, also called working memory (WM), is critical for higher cognitive functions and cognitive development. In typically developing (TD) children, WM is underpinned by a fronto-parietal network of interacting left and right brain regions. Developmental absence (agenesis) of the corpus callosum (AgCC) is a congenital brain malformation resulting from disruption of corpus callosum formation. This study aims to investigate functional organisation of WM in children and adolescents with AgCC using functional magnetic resonance imaging (fMRI). Nine children with AgCC and a comparison group of sixteen TD children aged 8-17 years completed an fMRI WM paradigm designed to enable investigation of different WM processes, i.e., encoding, maintenance and retrieval. We found that AgCC children recruited globally similar brain regions as the TD comparison group during the WM task, despite significant disparity in brain development, i.e., bilateral occipito-frontal activations during verbal encoding, and bilateral fronto-parietal executive control network during retrieval. However, compared to their TD peers, children with AgCC seemed less able to engage lateralised brain systems specialised for particular memory material (i.e. less supramarginal activations for verbal material and less fusiform activations for face processing) and particular memory process (i.e. absence of right-predominant activations during retrieval). Group differences in the pattern of activation might also reflect different cognitive strategies to cope with competition in processing resources with different susceptibility to concurrent tasks (verbal vs visual), such as differential recruitment of associative visual areas and executive prefrontal regions in the AgCC compared with the TD group depending on the concurrent task completed during maintenance. This study provides a first step towards a better understanding of functional brain networks underlying higher cognitive functions in children with AgCC.
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Agenesia del Cuerpo Calloso/complicaciones , Agenesia del Cuerpo Calloso/diagnóstico por imagen , Mapeo Encefálico , Imagen por Resonancia Magnética , Trastornos de la Memoria/diagnóstico por imagen , Trastornos de la Memoria/etiología , Adolescente , Niño , Femenino , Lateralidad Funcional , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Movimiento , Oxígeno/sangre , Estadísticas no Paramétricas , Factores de Tiempo , Aprendizaje VerbalRESUMEN
The LIS1 gene was cloned following the study of children with lissencephaly and cytogenetic abnormalities involving chromosome 17p, however, the role of the LIS1 protein in normal cortical development is not precisely defined. LIS1 is a component of evolutionarily conserved intracellular multiprotein complexes and recent literature shows that these complexes are essential, not only for neuronal migration, but they might also be fundamental components of the machinery for cell proliferation and intracellular transport.
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Proteínas Portadoras/biosíntesis , Movimiento Celular/fisiología , Corteza Cerebral/anomalías , Corteza Cerebral/metabolismo , Proteínas Asociadas a Microtúbulos/biosíntesis , 1-Alquil-2-acetilglicerofosfocolina Esterasa , Animales , Proteínas Portadoras/genética , Humanos , Proteínas Asociadas a Microtúbulos/genética , Neuronas/citología , Neuronas/metabolismoRESUMEN
Subcortical band heterotopia (SBH) comprises part of a spectrum of phenotypes associated with classical lissencephaly (LIS). LIS and SBH are caused by alterations in at least two genes: LIS1 (PAFAH1B1) at 17p13.3 and DCX (doublecortin) at Xq22.3-q23. DCX mutations predominantly cause LIS in hemizygous males and SBH in heterozygous females, and we have evaluated several families with LIS male and SBH female siblings. In this study, we performed detailed DCX mutation analysis and genotype-phenotype correlation in a large cohort with typical SBH. We screened 26 sporadic SBH females and 11 LIS/SBH families for DCX mutations by direct sequencing. We found 29 mutations in 22 sporadic patients and 11 pedigrees, including five deletions, four nonsense mutations, 19 missense mutations and one splice donor site mutation. The DCX mutation prevalence was 84.6% (22 of 26) in sporadic SBH patients and 100% (11 of 11) in SBH pedigrees. Maternal germline mosaicism was found in one family. Significant differences in genotype were found in relation to band thickness and familial vs sporadic status.
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Encéfalo/anomalías , Proteínas Asociadas a Microtúbulos , Neuropéptidos/genética , Estudios de Cohortes , ADN/química , ADN/genética , Análisis Mutacional de ADN , Compensación de Dosificación (Genética) , Proteínas de Dominio Doblecortina , Proteína Doblecortina , Femenino , Genotipo , Mutación de Línea Germinal , Humanos , Masculino , Mosaicismo , Mutación , Fenotipo , Cromosoma X/genéticaRESUMEN
BACKGROUND: Classical lissencephaly is a disorder of neuroblast migration with most patients having mutations of either the LIS1 or DCX genes. Most patients with lissencephaly secondary to LIS1 mutations have a severe malformation consisting of generalized agyria and pachygyria. However, increasing experience suggests that the phenotypic spectrum is wider than previously thought. METHODS: The authors describe the clinical and imaging features and mutation data of the five known patients with missense mutations of the LIS1 gene and emphasize one patient with normal intelligence. RESULTS: Patients with a missense mutation of the LIS1 gene have a wider and milder spectrum of cortical malformations and clinical sequelae compared with patients with other mutation types. CONCLUSION: Milder and more variable phenotypes seen in patients with missense mutations of LIS1 are likely a consequence of suboptimal function of the mutant LIS1 protein, rather than complete loss of function of this protein. The authors suggest that the few patients found thus far with missense mutations of LIS1 results from an underascertainment of patients with more subtle malformations and that abnormalities of the LIS1 gene may account for a greater spectrum of neurologic problems in childhood than has previously been appreciated.
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Encefalopatías/genética , Encefalopatías/patología , Encéfalo/anomalías , Encéfalo/patología , Inteligencia/genética , Proteínas Asociadas a Microtúbulos/genética , Mutación Missense/genética , 1-Alquil-2-acetilglicerofosfocolina Esterasa , Niño , Preescolar , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , FenotipoRESUMEN
OBJECTIVE: To determine the types, relative frequencies, clinical features, and MRI characteristics of malformations of cortical development (MCD) occurring in a cohort of children referred to a tertiary pediatric center. METHODS: Original MR images were reviewed by two investigators, who were blinded to clinical details, to determine the elemental imaging features of each malformation and to label these malformations according to an existing system of classification. Clinical information was collected by a review of hospital records. RESULTS: A total of 109 children with MCD were identified. There were 58 boys and 51 girls, age 8 days to 18 years at initial imaging (mean age, 5 years). Seizures were present in 75%, developmental delay or intellectual disability in 68%, abnormal neurologic findings in 48%, and congenital anomalies apart from the CNS malformation in 18%. The main malformations identified were heterotopic gray matter (19%), cortical tubers (17%), focal cortical dysplasia (16%), polymicrogyria (16%), agyria/pachygyria (15%), schizencephaly/cleft (5%), transmantle dysplasia (5%), and hemimegalencephaly (4%). Eight patients had features of more than one malformation. Most lesions were multilobar (47%), with the frontal lobe being the most common lobe involved (78%). A total of 68% of patients had other cerebral malformations including ventricular dilatation or dysmorphism (46%) and abnormalities of the corpus callosum (29%). CONCLUSIONS: This study illustrates the spectrum of MCD in a pediatric cohort and highlights some of the differences between pediatric and adult patients. Patients with MCD presenting in childhood have a wider spectrum of malformations and more varied, often more severe, clinical manifestations. The lesions are frequently multifocal or generalized and many are associated with noncortical developmental brain anomalies.
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Encefalopatías/patología , Encéfalo/anomalías , Encéfalo/patología , Preescolar , Epilepsia/patología , Femenino , Humanos , Imagen por Resonancia Magnética , MasculinoRESUMEN
Disorders of the development of the human cortex are recognized as significant causes of mental retardation, epilepsy, and congenital neurologic deficits. These malformations may be restricted to the brain or may be one component of a generalized malformation syndrome. Through the efforts of several groups, a large number of human cortical malformations have been identified and classified. Studies of informative families and sporadic patients with specific chromosomal rearrangements or deletions have demonstrated a genetic basis for many of these disorders. Subsequent work has facilitated a precise genetic diagnosis and provided insight into the molecular basis of some of these malformations. This review will discuss four cortical malformation syndromes, which are known or likely to have an X-linked inheritance pattern: bilateral periventricular nodular heterotopia, X-linked lissencephaly/subcortical band heterotopia, X-linked lissencephaly with abnormal genitalia, and X-linked bilateral perisylvian polymicrogyria.
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Encefalopatías/genética , Corteza Cerebral/anomalías , Ligamiento Genético , Cromosoma X/genética , Encefalopatías/patología , Encefalopatías/fisiopatología , Corteza Cerebral/patología , Corteza Cerebral/fisiopatología , Asesoramiento Genético , Humanos , Anomalías Urogenitales/genética , Anomalías Urogenitales/fisiopatologíaRESUMEN
We describe cortical malformations in two siblings who also had features of Adams-Oliver syndrome (AOS, MIM 100300). The parents were first cousins and showed no signs of either disorder, suggesting autosomal recessive inheritance. Psychomotor delay was present in both sibs, and cerebral imaging was indicative of polymicrogyria (PMG). One sib had aplasia cutis congenita of the scalp and transverse limb defects, and the other had short fingers and toes and also developed lymphedema of the right leg. CNS abnormalities and lymphatic abnormalities are rare manifestations of AOS, and we suggest that these sibs have a rare variant of AOS with probable recessive inheritance.
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Anomalías Múltiples/diagnóstico , Encéfalo/anomalías , Deformidades Congénitas de las Extremidades/diagnóstico , Encéfalo/diagnóstico por imagen , Niño , Preescolar , Consanguinidad , Femenino , Genes Recesivos , Humanos , Lactante , Recién Nacido , Imagen por Resonancia Magnética , Masculino , Cuero Cabelludo/anomalías , Síndrome , Tomografía Computarizada por Rayos XRESUMEN
Childhood stroke is uncommon and may require extensive evaluation to elucidate an underlying cause. A 9-year-old boy had clinical and magnetic resonance imaging (MRI) features of an ischemic event in the left middle cerebral artery territory. Magnetic resonance angiography (MRA) revealed beading of the left middle cerebral artery, consistent with irregular blood flow secondary to turbulence or luminal narrowing. Conventional angiography of the cerebral vessels confirmed the findings of cerebral MRA and raised further the suspicion of fibromuscular dysplasia (FMD). MRA of the renal vessels was subsequently performed, revealing beading of the left renal artery and confirming the diagnosis of FMD. MRA, a rapid and less invasive technique associated with far less morbidity and mortality as compared with conventional angiography, may prove to be as sensitive as conventional angiography in detecting the changes of FMD. MRA of the renal arteries should be performed with initial cranial MRI and MRA in children who present with cerebral infarction of possible vascular origin. This may obviate the need to perform further investigations and may make early diagnosis possible at the first MRI scan and under a single general anesthetic.
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Trastornos Cerebrovasculares/diagnóstico , Displasia Fibromuscular/diagnóstico , Angiografía por Resonancia Magnética , Niño , Humanos , Masculino , Arteria RenalRESUMEN
BACKGROUND AND PURPOSE: Bilateral posterior PNH is a distinctive complex malformation with imaging features distinguishing it from classic bilateral PNH associated with FLNA mutations. The purpose of this study was to define the imaging features of posterior bilateral periventricular nodular heterotopia and to determine whether associated brain malformations suggest specific subcategories. MATERIALS AND METHODS: We identified a cohort of 50 patients (31 females; mean age, 13 years) with bilateral posterior PNH and systematically reviewed and documented associated MR imaging abnormalities. Patients were negative for mutations of FLNA. RESULTS: Nodules were often noncontiguous (n = 28) and asymmetric (n = 31). All except 1 patient showed associated developmental brain abnormalities involving a spectrum of posterior structures. A range of posterior fossa abnormalities affected the cerebellum, including cerebellar malformations and posterior fossa cysts (n = 38). Corpus callosum abnormalities (n = 40) ranged from mild dysplasia to agenesis. Posterior white matter volume was decreased (n = 22), and colpocephaly was frequent (n = 26). Most (n = 40) had associated cortical abnormalities ranging from minor to major (polymicrogyria), typically located in the cortex overlying the PNH. Abnormal Sylvian fissure morphology was common (n = 27), and hippocampal abnormalities were frequent (n = 37). Four family cases were identified-2 with concordant malformation patterns and 2 with discordant malformation patterns. CONCLUSIONS: The associations of bilateral posterior PNH encompass a range of abnormalities involving brain structures inferior to the Sylvian fissures. We were unable to identify specific subgroups and therefore conceptualize bilateral posterior PNH as a continuum of infrasylvian malformations involving the posterior cerebral and hindbrain structures.
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Encefalopatías/patología , Ventrículos Laterales/anomalías , Imagen por Resonancia Magnética , Malformaciones del Desarrollo Cortical/patología , Heterotopia Nodular Periventricular/patología , Adolescente , Adulto , Anciano , Corteza Cerebral/anomalías , Niño , Preescolar , Estudios de Cohortes , Proteínas Contráctiles/genética , Cuerpo Calloso/patología , Femenino , Enfermedades Fetales/genética , Enfermedades Fetales/patología , Filaminas , Hipocampo/anomalías , Humanos , Lactante , Recién Nacido , Ventrículos Laterales/patología , Masculino , Proteínas de Microfilamentos/genética , Persona de Mediana Edad , Heterotopia Nodular Periventricular/genética , Embarazo , Rombencéfalo/anomalías , Hermanos , Gemelos Monocigóticos , Adulto JovenRESUMEN
In contrast to malformations, cerebellar disruptions have attracted little interest in the literature. We draw attention for the first time to the hypothesis that cerebellar clefts are residual changes following a prenatal cerebellar insult, and represent disruptions. We reviewed the clinical records and MR findings of six patients with a cerebellar cleft, two of whom also had prenatal MRI at 24 weeks of gestation. The clefts were located in the left cerebellar hemisphere in five cases, in the right in one patient. Other typical findings included disorderly alignment of the cerebellar folia and fissures, irregular gray/white matter junction, and abnormal arborization of the white matter in all patients. The cerebellar cleft extended into the fourth ventricle in three cases, and in two children cystic cortical lesions were seen. Supratentorial schizencephaly was found in two patients. In two patients there was a documented fetal cerebellar hemorrhage at 24 weeks of gestation. We conclude that cerebellar clefts are residual changes resulting from a prenatal cerebellar insult and consequently represent disruptions rather than primary malformations. The supratentorial findings are also in agreement with an acquired lesion. The outcome in these children was variable, mainly depending of the presence of supratentorial lesions.
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Cerebelo/anomalías , Dilatación Patológica/etiología , Enfermedades Fetales/diagnóstico , Diagnóstico Prenatal/métodos , Niño , Preescolar , Dilatación Patológica/diagnóstico , Femenino , Edad Gestacional , Humanos , Procesamiento de Imagen Asistido por Computador , Lactante , Hemorragias Intracraneales/complicaciones , Hemorragias Intracraneales/patología , Imagen por Resonancia Magnética , Masculino , Malformaciones del Desarrollo Cortical/complicaciones , Malformaciones del Desarrollo Cortical/patología , EmbarazoRESUMEN
Disorders of cortical development are a significant cause of epilepsy, developmental delay and congenital neurological deficits in children of all ages. Disruption of neuronal proliferation, differentiation, migration and organization during the middle trimester are recognized as the basis of most of these disorders. With advances in magnetic resonance imaging and increasing recognition of the characteristic radiological appearance of these lesions, a variety of lesions are now described. Furthermore, detailed clinical and genetic studies have lead to the recognition of clinicopathological syndromes of cortical maldevelopment with specific modes of inheritance. Our understanding of these disorders is increasing rapidly and will continue to do so with improvements in neuroimaging, advances in developmental neurobiology and heightened clinician awareness.