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1.
PLoS One ; 15(9): e0239477, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32956426

RESUMO

OBJECTIVE: Report maternal, fetal and neonatal complications associated with single intrauterine fetal death (sIUFD) in monochorionic twin pregnancies. DESIGN: Prospective observational study. SETTING: UK. POPULATION: 81 monochorionic twin pregnancies with sIUFD after 14 weeks gestation, irrespective of cause. METHODS: UKOSS reporters submitted data collection forms using data from hospital records. MAIN OUTCOME MEASURES: Aetiology of sIUFD; surviving co-twin outcomes: perinatal mortality, central nervous system (CNS) imaging, gestation and mode of delivery, neonatal outcomes; post-mortem findings; maternal outcomes. RESULTS: The commonest aetiology was twin-twin transfusion syndrome (38/81, 47%), "spontaneous" sIUFD (22/81, 27%) was second commonest. Death of the co-twin was common (10/70, 14%). Preterm birth (<37 weeks gestation) was the commonest adverse outcome (77%): half were spontaneous and half iatrogenic. Only 46/75 (61%) cases had antenatal CNS imaging, of which 33 cases had known results of which 7/33 (21%) had radiological findings suggestive of neurological damage. Postnatal CNS imaging revealed an additional 7 babies with CNS abnormalities, all born at <36 weeks, including all 4 babies exhibiting abnormal CNS signs. Major maternal morbidity was relatively common, with 6% requiring ITU admission, all related to infection. CONCLUSIONS: Monochorionic twin pregnancies with single IUD are complex and require specialist care. Further research is required regarding optimal gestation at delivery of the surviving co-twin, preterm birth prevention, and classifying the cause of death in twin pregnancies. Awareness of the importance of CNS imaging, and follow-up, needs improvement.


Assuntos
Morte Fetal , Gêmeos Monozigóticos , Adulto , Corioamnionite/epidemiologia , Feminino , Retardo do Crescimento Fetal/etiologia , Retardo do Crescimento Fetal/mortalidade , Transfusão Feto-Fetal/mortalidade , Transfusão Feto-Fetal/terapia , Idade Gestacional , Humanos , Incidência , Lactente , Mortalidade Infantil , Recém-Nascido , Nascimento Vivo , Masculino , Malformações do Sistema Nervoso/diagnóstico por imagem , Malformações do Sistema Nervoso/embriologia , Malformações do Sistema Nervoso/epidemiologia , Mortalidade Perinatal , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Redução de Gravidez Multifetal , Gravidez de Gêmeos , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Estudos Prospectivos , Transtornos Puerperais/epidemiologia , Reino Unido/epidemiologia
2.
Pediatrics ; 146(3)2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32820067

RESUMO

An 11-week-old unvaccinated, term Amish boy initially presented with poor feeding, microcephaly, failure to thrive, and developmental delays. His physical examination was significant for both weight and head circumference being less than the third percentile, and he was noted to have micrognathia, truncal hypotonia, and head lag. He was admitted to the pediatric hospital medicine service for further diagnostic evaluation. Laboratory studies assessing for endocrinological and metabolic etiologies yielded negative results, and imaging studies (including a chest radiograph, echocardiogram, and abdominal ultrasound) were normal. However, intracranial calcifications were noted on a head ultrasound. The etiology of his constellation of symptoms was initially thought to be infectious, but the ultimate diagnosis was not made until after discharge from the pediatric hospital medicine service.


Assuntos
Doenças Autoimunes do Sistema Nervoso/diagnóstico por imagem , Calcinose/diagnóstico por imagem , Microcefalia/diagnóstico por imagem , Hipotonia Muscular/diagnóstico por imagem , Malformações do Sistema Nervoso/diagnóstico por imagem , Doenças Autoimunes do Sistema Nervoso/sangue , Doenças Autoimunes do Sistema Nervoso/complicações , Calcinose/sangue , Calcinose/complicações , Cefalometria/métodos , Humanos , Lactente , Masculino , Microcefalia/sangue , Microcefalia/complicações , Hipotonia Muscular/sangue , Hipotonia Muscular/complicações , Malformações do Sistema Nervoso/sangue , Malformações do Sistema Nervoso/complicações
3.
Neurology ; 95(9): e1236-e1243, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32611640

RESUMO

OBJECTIVE: To assess the prevalence of brain MRI abnormalities in people with epilepsy in rural China and to compare it with that of individuals in the United Kingdom. METHODS: Brain MRI scans were obtained in people with epilepsy who participated in a rural community-based program in China between July 2010 and December 2012. Individual epileptogenic lesion types were reviewed and their associations with seizure control examined. The MRI findings were compared with 2 previous similar studies in the United Kingdom. RESULTS: Among the 597 individuals (58% male, median age 38 years) with MRI scans analyzed, 488 (82%) had active epilepsy. The MRI was abnormal in 389 individuals (65%), with potentially epileptogenic lesion in 224 (38%) and nonspecific abnormalities in 165 (28%), and 108 (18%) were potentially resectable. The potentially epileptogenic lesions were less frequently detected in children (<18 years old, 12 of 68, 18%) than in adults (212 of 529, 40%; p < 0.001). In people with potentially epileptogenic lesions, 67% (150 of 224) had failed ≥2 antiseizure medications. They had higher risk of uncontrolled epilepsy than those with normal MRI (risk ratio [RR] 1.25; p < 0.001) and those with nonspecific abnormality (RR 1.15; p = 0.002) after adjustment for age and sex. The diagnostic yield of MRI was similar to that reported in community- and hospital-based studies in the United Kingdom. CONCLUSIONS: More than one-third of people with chronic epilepsy in rural China have potentially epileptogenic lesions identifiable on brain MRI, with two-thirds fulfilling the definition of pharmacoresistance. These findings highlight the magnitude of the unmet needs for epilepsy surgery in China.


Assuntos
Encefalomalacia/epidemiologia , Epilepsia/epidemiologia , Gliose/epidemiologia , Malformações do Sistema Nervoso/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/epidemiologia , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Malformações Vasculares do Sistema Nervoso Central/epidemiologia , Criança , Pré-Escolar , China/epidemiologia , Epilepsia Resistente a Medicamentos , Encefalomalacia/diagnóstico por imagem , Epilepsia/diagnóstico por imagem , Feminino , Gliose/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Malformações do Sistema Nervoso/diagnóstico por imagem , Prevalência , População Rural , Esclerose , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologia , Reino Unido/epidemiologia , Adulto Jovem
4.
World Neurosurg ; 138: 461-467, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32200015

RESUMO

Caudal regression syndrome (CRS) represents a spectrum of clinical phenotypes with varying degrees of malformation of the lower body with involvement of structures deriving from all 3 layers of the trilaminar embryo. We review areas of active investigation in the diagnosis, etiology, epidemiology, and treatment of the disease with a focus on underlying genetics. CRS pathobiology is complex and multifactorial with a significant contribution from environmental factors as evidenced in twin studies. Contemporary genomic and genetic investigations in both human primary tissue and murine in vitro and in vivo models implicate various genes associated with caudal differentiation and neural cell migration in embryogenesis. A large number of identified targets center around the metabolic regulation of retinoic acid and its derivatives. Dysregulation of retinoic acid homeostasis has been associated with abnormal embryonic cell migration, differentiation, and organogenesis with resulting malformations and agenesis in both a laboratory and a clinical setting. There appears to be a significant overlap in potential genetic targets with CRS and other developmental syndromes with similar presentations, such as VACTERL (vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities) association. CRS represents a spectrum of caudal developmental abnormalities with treatment options limited to mild and moderate expressions of disease. Continued research is necessary to further clarify mechanisms of disease pathobiology and complex polygenetic and environmental interaction. Despite this, progress has been made in identifying genetic targets and downstream effectors contributing to preclinical and clinical progression.


Assuntos
Anormalidades Múltiplas/genética , Genômica , Deformidades Congênitas dos Membros/genética , Malformações do Sistema Nervoso/genética , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/diagnóstico por imagem , Anormalidades Múltiplas/patologia , Animais , Humanos , Deformidades Congênitas dos Membros/diagnóstico , Deformidades Congênitas dos Membros/diagnóstico por imagem , Deformidades Congênitas dos Membros/patologia , Malformações do Sistema Nervoso/diagnóstico , Malformações do Sistema Nervoso/diagnóstico por imagem , Malformações do Sistema Nervoso/patologia , Tretinoína/metabolismo
5.
World Neurosurg ; 138: 645-653, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31931232

RESUMO

BACKGROUND: The article uses ultrasound imaging standard section to examine the fetal central nervous system (CNS) in early pregnancy, combined with ultrasound imaging in the diagnosis of fetal CNS malformation in the middle and late pregnancy, to determine the feasibility of ultrasound imaging in the detection of CNS abnormalities in the first trimester of the fetus. METHODS: The article selected 2701 pregnant women from the Department of Ultrasound in our hospital from November 2012 to November 2016 to screen for the transparent layer of the fetal neck in early pregnancy, with a total of 2751 cases. The article uses Madison V20 and Madison XG color Doppler ultrasound diagnostic instruments, the probe frequency is measured from 2.0-3.5 MHz, grouped according to gestational age, the statistical section of the case is displayed, and the transparent layer of the neck value is used to count the ultrasound image during early pregnancy. The detection of the CNS malformation by the standard section examination and the sensitivity, specificity, positive predictive value, and negative predictive value of the diagnosis may affect the cause of the CNS display rate. RESULTS: The sensitivity, specificity, positive predictive value, and negative predictive value of the ultrasound standard section in the diagnosis of fetal CNS malformation in early pregnancy were 85.7%, 100%, 100%, and 99.9%, respectively. Through research, it is found that the use of ultrasound imaging standard section can effectively diagnose fetal CNS severe deformity in early pregnancy, and the detection rate of CNS malformation in early pregnancy is 85.7%. At the same time, the number of positive cases and CNS malformations in this group were few. CONCLUSIONS: The positive cases detected in early pregnancy were severe malformations of the CNS. The diagnosis of other CNS malformations in the fetus needs further study.


Assuntos
Feto/diagnóstico por imagem , Malformações do Sistema Nervoso/diagnóstico por imagem , Obstetrícia/métodos , Ultrassonografia Doppler em Cores/métodos , Ultrassonografia Pré-Natal/métodos , Feminino , Feto/anormalidades , Seguimentos , Humanos , Malformações do Sistema Nervoso/embriologia , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez
6.
Am J Obstet Gynecol ; 222(6): 615.e1-615.e9, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31930994

RESUMO

BACKGROUND: In 2014, the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Imaging Workshop consensus recommended that sonograms be offered routinely to all pregnant women. In the absence of another indication, this examination is recommended at 18-22 weeks of gestation. Studies of anomaly detection often focus on pregnancies at risk for anomalies and on the yield of detailed sonography, topics less applicable to counseling low-risk pregnancies about the benefits and limitations of standard sonography. The clinical utility of follow-up sonogram in low-risk pregnancies for the purpose of fetal anomaly detection has not been established. OBJECTIVE: The objective of the study was to evaluate the utility of follow-up standard sonography for anomaly detection among low-risk pregnancies in a nonreferred population. STUDY DESIGN: We performed a retrospective cohort study of singleton pregnancies that underwent standard sonography at 18-21 6/7 weeks of gestation from October 2011 through March 2018 with subsequent delivery of a live-born infant at our hospital. Pregnancies with indications for detailed sonography in our system were excluded to evaluate fetal anomalies first identified with standard sonography. Anomalies were categorized according to the European Registration of Congenital Anomalies and Twins (EUROCAT) system, with confirmation based on neonatal evaluation. Among those with no anomaly detected initially, we evaluated the rate of subsequent detection according to number of follow-up sonograms, gestational age at sonography, organ system(s) affected, and anomaly severity. Statistical analyses were performed using χ2 and a Mantel-Haenszel test. RESULTS: Standard sonography was performed in 40,335 pregnancies at 18-21 6/7 weeks, and 11,770 (29%) had at least 1 follow-up sonogram, with a second follow-up sonogram in 3520 (9%). Major abnormalities were confirmed in 387 infants (1%), with 248 (64%) detected initially and 28 (7%) and 5 (1%) detected on the first and second follow-up sonograms. Detection of residual anomalies on follow-up sonograms was significantly lower than detection on the initial standard examination: 64% on initial examination, 45% for first follow-up, and 45% for second follow-up (P < .01). A larger number of follow-up examinations were required per anomalous fetus detected: 163 examinations per anomalous fetus detected initially, 420 per fetus detected at the first follow-up examination, and 705 per fetus detected at the second follow-up sonogram (P < .01). The number of follow-up examinations to detect each additional anomalous fetus was not affected by gestational age (P = .7). Survival to hospital discharge was significantly lower for fetuses with anomalies detected on initial (88%) than for fetuses with anomalies undetected until delivery (90 of 91, 99%; P < .002). CONCLUSION: In a low-risk, nonreferred cohort with fetal anomaly prevalence of 1%, follow-up sonography resulted in detection of 45% of fetal anomalies that had not been identified during the initial standard sonogram. Significantly more follow-up sonograms were required to detect each additional anomalous fetus.


Assuntos
Anormalidades Congênitas/diagnóstico por imagem , Idade Gestacional , Guias de Prática Clínica como Assunto , Ultrassonografia Pré-Natal/métodos , Anormalidades Múltiplas/diagnóstico por imagem , Adulto , Doenças do Desenvolvimento Ósseo/congênito , Doenças do Desenvolvimento Ósseo/diagnóstico por imagem , Estudos de Coortes , Anormalidades Craniofaciais/diagnóstico por imagem , Anormalidades do Sistema Digestório/diagnóstico por imagem , Feminino , Cardiopatias Congênitas/diagnóstico por imagem , Humanos , Recém-Nascido , Malformações do Sistema Nervoso/diagnóstico por imagem , Gravidez , Segundo Trimestre da Gravidez , Anormalidades do Sistema Respiratório/diagnóstico por imagem , Estudos Retrospectivos , Ultrassonografia Pré-Natal/normas , Anormalidades Urogenitais/diagnóstico por imagem
7.
J Pediatr Orthop ; 40(5): e390-e393, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31834240

RESUMO

BACKGROUND: The association of scoliosis and congenital limb deficiency has been well described. However, the incidence of neural axis abnormalities in this population is not known. The ability to assess the neural axis by physical examination may be limited in patients with a limb deficiency. Although mobility of the spine is important for all children, it can be especially so in children with a limb deficiency. As spinal fusion in children with limb deficiency potentially has more functional impact, detecting reversible forms of scoliosis seems particularly important. METHODS: Retrospective review of children treated at 1 institution between 1990 and 2017 with both a diagnosis of a congenital limb deficiency, upper or lower, and scoliosis. Children were excluded if they had any neurological difference on history or physical examination, if they had sacral agenesis or spina bifida, or if their limb deficiency was related to trauma or early amniotic rupture sequence. RESULTS: Twenty-four children were identified, 11 with lower extremity deficiency, 14 with upper extremity deficiency with 1 having both. Fifteen children demonstrated neural axis abnormalities, 6 (40%) required neurosurgery. Five (45%) of 11 lower extremity deficiency children had MRI findings, 3 of these needing neurosurgery. Of the 14 upper extremity deficiency children, 10 had MRI changes, and 3 required neurosurgery. Eight children with congenital scoliosis, 5 had MRI findings, with 4 children requiring neurosurgery. The other 16 children had scoliosis without vertebral abnormalities, 10 had MRI findings, and 2 required neurosurgery. CONCLUSIONS: There is a high incidence of neural axis abnormalities (63%) in children with congenital limb deficiencies and scoliosis. A large portion of these require neurosurgical intervention. MRI should be considered soon after presentation in this population of children. LEVEL OF EVIDENCE: Level IV. DESIGN: Retrospective cohort.


Assuntos
Deformidades Congênitas dos Membros/complicações , Imagem por Ressonância Magnética , Malformações do Sistema Nervoso/diagnóstico por imagem , Escoliose/complicações , Encéfalo/anormalidades , Encéfalo/diagnóstico por imagem , Criança , Humanos , Malformações do Sistema Nervoso/cirurgia , Estudos Retrospectivos , Medula Espinal/anormalidades , Medula Espinal/diagnóstico por imagem
8.
Brain ; 143(1): 55-68, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31834374

RESUMO

MN1 encodes a transcriptional co-regulator without homology to other proteins, previously implicated in acute myeloid leukaemia and development of the palate. Large deletions encompassing MN1 have been reported in individuals with variable neurodevelopmental anomalies and non-specific facial features. We identified a cluster of de novo truncating mutations in MN1 in a cohort of 23 individuals with strikingly similar dysmorphic facial features, especially midface hypoplasia, and intellectual disability with severe expressive language delay. Imaging revealed an atypical form of rhombencephalosynapsis, a distinctive brain malformation characterized by partial or complete loss of the cerebellar vermis with fusion of the cerebellar hemispheres, in 8/10 individuals. Rhombencephalosynapsis has no previously known definitive genetic or environmental causes. Other frequent features included perisylvian polymicrogyria, abnormal posterior clinoid processes and persistent trigeminal artery. MN1 is encoded by only two exons. All mutations, including the recurrent variant p.Arg1295* observed in 8/21 probands, fall in the terminal exon or the extreme 3' region of exon 1, and are therefore predicted to result in escape from nonsense-mediated mRNA decay. This was confirmed in fibroblasts from three individuals. We propose that the condition described here, MN1 C-terminal truncation (MCTT) syndrome, is not due to MN1 haploinsufficiency but rather is the result of dominantly acting C-terminally truncated MN1 protein. Our data show that MN1 plays a critical role in human craniofacial and brain development, and opens the door to understanding the biological mechanisms underlying rhombencephalosynapsis.


Assuntos
Anormalidades Múltiplas/genética , Anormalidades Craniofaciais/genética , Deficiência Intelectual/genética , Transtornos do Desenvolvimento da Linguagem/genética , Malformações do Sistema Nervoso/genética , Transativadores/genética , Proteínas Supressoras de Tumor/genética , Anormalidades Múltiplas/diagnóstico por imagem , Adolescente , Artéria Basilar/anormalidades , Artéria Basilar/diagnóstico por imagem , Artérias Carótidas/anormalidades , Artérias Carótidas/diagnóstico por imagem , Vermis Cerebelar/anormalidades , Vermis Cerebelar/diagnóstico por imagem , Cerebelo/anormalidades , Cerebelo/diagnóstico por imagem , Criança , Pré-Escolar , Estudos de Coortes , Hibridização Genômica Comparativa , Anormalidades Craniofaciais/diagnóstico por imagem , Feminino , Fibroblastos/metabolismo , Humanos , Imageamento Tridimensional , Lactente , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação , Malformações do Sistema Nervoso/diagnóstico por imagem , Degradação do RNAm Mediada por Códon sem Sentido , Polimicrogiria/diagnóstico por imagem , Polimicrogiria/genética , RNA-Seq , Reação em Cadeia da Polimerase em Tempo Real , Síndrome , Tomografia Computadorizada por Raios X , Sequenciamento Completo do Exoma , Sequenciamento Completo do Genoma
9.
Ultraschall Med ; 40(6): 692-721, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31794996

RESUMO

Fetal neurosonography and the assessment of the posterior fossa have gained in importance during the last 2 decades primarily due to the development of high-resolution ultrasound probes and the introduction of 3 D sonography. The anatomical development of the posterior fossa can be visualized well with the newest ultrasound technologies. This allows better knowledge of the anatomical structures and helps with understanding of the development of malformations of the posterior fossa. In this article the longitudinal development of the posterior fossa structures will be reviewed. The embryologic description will be compared with ultrasound descriptions. These embryologic and anatomic illustrations form the basis for the screening and diagnosis of malformations of the posterior fossa. During the first trimester, screening for open spina bifida as well as cystic malformations of the posterior fossa is possible. In the second and third trimester, malformations of the posterior fossa can be subdivided into 3 groups: fluid accumulation in the posterior fossa (Dandy-Walker malformation, Blake's pouch cyst, mega cisterna magna, arachnoid cyst, vermian hypoplasia), decreased cerebellar biometrics (volume) (cerebellar hypoplasia, pontocerebellar hypoplasia) and suspicious cerebellar anatomy (Arnold-Chiari malformation, rhombencephalosynapsis, Joubert syndrome). This algorithm, in combination with knowledge of normal development, facilitates the diagnostic workup of malformations of the posterior fossa.


Assuntos
Fossa Craniana Posterior , Síndrome de Dandy-Walker , Malformações do Sistema Nervoso , Fossa Craniana Posterior/diagnóstico por imagem , Síndrome de Dandy-Walker/diagnóstico por imagem , Feminino , Humanos , Imagem por Ressonância Magnética , Malformações do Sistema Nervoso/diagnóstico por imagem , Gravidez , Ultrassonografia Pré-Natal
10.
Mol Genet Metab ; 128(4): 452-462, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31727539

RESUMO

Lethal neonatal encephalopathies are heterogeneous congenital disorders that can be caused by mitochondrial dysfunction. Biallelic large deletions in the contiguous ATAD3B and ATAD3A genes, encoding mitochondrial inner membrane ATPases of unknown function, as well as compound heterozygous nonsense and missense mutations in the ATAD3A gene have been recently associated with fatal neonatal cerebellar hypoplasia. In this work, whole exome sequencing (WES) identified the novel homozygous variant c.1217 T > G in ATAD3A, predicting a p.(Leu406Arg) substitution, in four siblings from a consanguineous family presenting with fatal neonatal cerebellar hypoplasia, seizures, axial hypotonia, hypertrophic cardiomyopathy, hepatomegaly, congenital cataract, and dysmorphic facies. Biochemical phenotypes of the patients included hyperlactatemia and hypocholesterolemia. Healthy siblings and parents were heterozygous for this variant, which is predicted to introduce a polar chain within the catalytic domain of ATAD3A that shortens its beta-sheet structure, presumably affecting protein stability. Accordingly, patient's fibroblasts with the homozygous variant displayed a specific reduction in ATAD3A protein levels associated with profound ultrastructural alterations of mitochondrial cristae and morphology. Our findings exclude the causative role of ATAD3B on this severe phenotype, expand the phenotypical spectrum of ATAD3A pathogenic variants and emphasize the vital role of ATAD3A in mitochondrial biogenesis.


Assuntos
ATPases Associadas a Diversas Atividades Celulares/genética , Cerebelo/anormalidades , Genes Recessivos , Predisposição Genética para Doença , Proteínas de Membrana/genética , Proteínas Mitocondriais/genética , Mutação , Malformações do Sistema Nervoso/genética , Malformações do Sistema Nervoso/patologia , ATPases Associadas a Diversas Atividades Celulares/química , Alelos , Substituição de Aminoácidos , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Criança , Pré-Escolar , Deficiências do Desenvolvimento/diagnóstico por imagem , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/patologia , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Lactente , Masculino , Proteínas de Membrana/química , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Proteínas Mitocondriais/química , Modelos Moleculares , Malformações do Sistema Nervoso/diagnóstico por imagem , Linhagem , Conformação Proteica , Relação Estrutura-Atividade , Ultrassonografia/métodos , Sequenciamento Completo do Exoma
11.
Laeknabladid ; 105(12): 547-553, 2019 Dec.
Artigo em Islandês | MEDLINE | ID: mdl-31782746

RESUMO

INTRODUCTION: The incidence of congenital anomalies of the central nervous system (CNS) in Iceland during 1992-2016 was examined along with timing of diagnosis, maternal residence, known risk factors and perinatal outcomes. MATERIAL AND METHODS: This was a retrospective study of all fe-tuses and newborns diagnosed with a CNS anomaly during the study period and their mothers. Information was obtained from the Icelandic Birth Registry and from maternal and neonatal medical records. Descriptive and inferential statistics were used in data analyzing. RESULTS: Annually, 3-12 cases of congenital CNS anomalies were diagnosed. Five year period incidence ranged from 1.4-2.4/1000 newborns, highest in 2012-2016. Over 89% were diagnosed -prenatally, of those 80% were terminated. The average gestational age at diagnosis of anencephaly was 19,3 weeks 1992-1996 vs. 11.6 weeks 2012-2016 (p=0,006). Urban area prenatal diagnosis was higher (94%) than rural (80%) (p=0.006). Known risk factors among mothers were uncommon, except for maternal obesity during the period 2012-2016 (23%). Of 57 live born children with CNS anomalies 37 (65%) were alive at the time of the study. CONCLUSION: The incidence of congenital anomalies of the CNS is stable and maternal risk factors are infrequent. Around 90% were diagnosed prenatally. Fetal anencephaly was diagnosed earlier at the end of the study period, after the introduction of a 11-14 week ultrasound scan in 2003, along with increased training among -healthcare professionals and improved ultrasound equipment. Higher prenatal detection rate in urban areas compared with rural may be explained by fewer ultrasound examinations being performed in less populated health districts, staff consequently receiving less training and experience and also with less advanced equipment.


Assuntos
Malformações do Sistema Nervoso/diagnóstico por imagem , Ultrassonografia Pré-Natal , Feminino , Idade Gestacional , Humanos , Islândia/epidemiologia , Incidência , Malformações do Sistema Nervoso/epidemiologia , Malformações do Sistema Nervoso/terapia , Obesidade Materna , Valor Preditivo dos Testes , Gravidez , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Serviços de Saúde Rural , Fatores de Tempo , Serviços Urbanos de Saúde
12.
Childs Nerv Syst ; 35(11): 2055-2069, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31289853

RESUMO

PURPOSE: Currently, the interest on craniosynostosis in the clinical practice is raised by their increased frequency and their genetic implications other than by the still existing search of less invasive surgical techniques. These reasons, together with the problem of legal issues, make the need of a definite diagnosis for a crucial problem, even in single-suture craniosynostosis (SSC). Although the diagnosis of craniosynostosis is primarily the result of physical examination, craniometrics measuring, and observation of the skull deformity, the radiological assessment currently plays an important role in the confirmation of the diagnosis, the surgical planning, and even the postoperative follow-up. On the other hand, in infants, the use of radiation or the need of sedation/anesthesia raises the problem to reduce them to minimum to preserve such a delicate category of patient from their adverse effects. METHODS, RESULTS AND CONCLUSIONS: This review aims at summarizing the state of the art of the role of radiology in craniosynostosis, mainly focusing on indications and techniques, to provide an update not only to pediatric neurosurgeons or maxillofacial surgeons but also to all the other specialists involved in their management, like neonatologists, pediatricians, clinical geneticists, and pediatric neurologists.


Assuntos
Craniossinostoses/diagnóstico por imagem , Procedimentos Neurocirúrgicos , Procedimentos Cirúrgicos Reconstrutivos , Cefalometria , Craniossinostoses/complicações , Craniossinostoses/cirurgia , Humanos , Imageamento Tridimensional , Lactente , Malformações do Sistema Nervoso/complicações , Malformações do Sistema Nervoso/diagnóstico por imagem , Radiografia , Tomografia Computadorizada por Raios X
13.
Handb Clin Neurol ; 162: 201-216, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31324311

RESUMO

As magnetic resonance imaging has been increasingly used to study brain injury and brain development in premature newborns, the prevalence of cerebellar abnormalities is increasingly recognized. The preterm cerebellum is highly vulnerable to a number of insults during its critical phase of growth and development throughout the period of prematurity and beyond. Direct cerebellar injury and additional factors such as supratentorial brain injury and glucocorticoid exposure adversely impact cerebellar growth and, consequently, increase the risk of neurodevelopmental disabilities. In this chapter the causes and consequences of cerebellar hypoplasia of prematurity are reviewed.


Assuntos
Doenças Cerebelares/congênito , Doenças Cerebelares/patologia , Cerebelo/anormalidades , Doenças do Prematuro/patologia , Malformações do Sistema Nervoso/patologia , Adulto , Animais , Doenças Cerebelares/etiologia , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Deficiências do Desenvolvimento/diagnóstico por imagem , Deficiências do Desenvolvimento/patologia , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Imagem por Ressonância Magnética , Malformações do Sistema Nervoso/diagnóstico por imagem , Gravidez
14.
Can J Neurol Sci ; 46(6): 760-761, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31352912

RESUMO

A 9-year-old female presented to neurology outpatient department of our hospital with complaints of recurrent generalized tonic-clonic seizures since birth and was being treated with anticonvulsants for the same. Patient also had complaints of giddiness and episodes of momentary loss of consciousness. There was history of twitching of left hemiface and eyelid during infancy, often associated with deviation of eyes to the left and groaning. The birth history was unremarkable. Family history revealed no known consanguinity. General examination revealed no dysmorphic features. Neurological examination revealed no cognitive deficits/signs to suggest cerebellar pathology. An electroencephalogram was done in view of her recurrent seizures, which was normal. Initial laboratory work-up was normal. The patient then underwent magnetic resonance imaging (MRI) brain, acquired with a 1.5-T unit (Siemens, Erlangen, Germany). MRI brain revealed hemihypertrophy of left cerebellar hemisphere with disorganized architecture, fissural malorientation with individual folia running vertically rather than horizontally with disorganized foliation, abnormal arborization of white matter predominantly involving mid and dorsal surface of left cerebellar hemisphere and a few suspicious areas of abnormal T2-hyperintense signal in subcortical white matter. Right cerebellar hemisphere and cerebellar vermis were normal. Corpus callosum was normal. Cerebral parenchyma was normal in signal intensity pattern with normal gray-white matter differentiation. Ventricular system was normal (Figures 1 and 2). Cerebellar malformations are uncommon and are usually associated with Dandy-Walker continuum, Joubert syndrome, rhombencephalosynapsis, lissencephaly, Fukuyama congenital muscular dystrophy, Walker-Warburg syndrome, muscle-eye-brain disease, congenital cytomegalovirus infection to name a few.1,2 Isolated unilateral cerebellar hemispheric dysplasia is exceedingly rare with only a few cases previously described in English literature. Cerebellar malformations are less adequately understood entity partly because of the complex cerebellar embryology and limited histologic studies of these disorders. Genes expressed in migration and maintenance of the Purkinje cells and/or in the generation and migration of granular cells when mutated will disrupt cerebellar migration and foliation and thus cause cerebellar malformation.3-5 Cerebellum is known to be a centre for motor learning, coordination, and higher cognitive functions. Clinical presentation of cerebellar malformations is highly variable and depends on the degree of cerebellar involvement, presence of associated cerebral involvement and the underlying disorders such as muscular dystrophy if any. Patel and Barkovich suggested an imaging-based classification of cerebellar malformations and classified the malformations broadly into two types, malformations with cerebellar hypoplasia and the ones with cerebellar dysplasia. Each of these was further classified into focal and diffuse.1 Demaerel gave a classification of abnormalities of cerebellar foliation and fissuration.2 Our index case with disorganized architecture, fissural malorientation and disorganized foliation of left cerebellar hemisphere associated with normal cerebellar vermis, corpus callosum, and absence of cerebral malformation falls into Type 2 category as per the classification by Demaerel.2 Treatment depends upon the severity of symptoms and the underlying disorder in case of syndromic malformations. Generally, treatment is symptomatic and supportive. Understanding of the basics of cerebellar embryology, knowledge of the imaging features, and clinical presentation aids in the precise diagnosis of this disorder and its optimal management.


Assuntos
Doenças Cerebelares/diagnóstico por imagem , Cerebelo/anormalidades , Malformações do Sistema Nervoso/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Criança , Deficiências do Desenvolvimento/diagnóstico por imagem , Feminino , Humanos , Imagem por Ressonância Magnética
15.
Pediatr Dev Pathol ; 22(6): 546-557, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31256740

RESUMO

OBJECTIVES: Central nervous system (CNS) anomalies are the second most frequent category of congenital anomalies after congenital heart defects (CHDs). In this study, the aim was to investigate the distribution of different CNS anomalies with associated anomalies and karyotype in a fetal autopsy population of terminated pregnancies over a 30-year period and to correlate the ultrasonographic diagnoses of CNS anomalies with autopsy findings. MATERIALS AND METHODS: This study includes 420 intact fetuses with CNS anomalies terminated at gestational ages 11+ 0 to 33+ 6 over a 30-year period from 1985 to 2014. An ultrasound (US) examination was performed at the National Centre for Fetal Medicine, St. Olavs Hospital, Trondheim. The autopsies were performed at the Department of Pathology at the same hospital or a collaborating hospital. The anomalies were subcategorized according to the classification by the World Health Organization. RESULTS: Neural tube defects such as anencephaly (22.4%, 107/477) and spina bifida (22.2%, 106/477) constituted the most common CNS anomalies, followed by congenital hydrocephalus (17.8%, 85/477). In total, the karyotype was abnormal in 21.0% of all termination of pregnancies (TOPs), with trisomy 18 as the most frequent abnormal karyotype. CHDs, skeletal anomalies, and urinary anomalies were the most common associated organ anomalies. Throughout the study period, there was full agreement between US and postmortem findings of CNS anomalies in 96.9% (407/420) of TOPs. CONCLUSION: In this study of autopsy findings of CNS anomalies in intact fetuses terminated after prenatal US diagnosis, neural tube defects were most common. About half of the fetuses had isolated serious CNS anomalies, while the other half were CNS anomalies associated with structural and/or chromosomal anomalies. The prenatal US diagnoses were in good concordance with autopsy findings. In particular, due to challenges of diagnoses made early in pregnancy, it is necessary to continue the validation practice.


Assuntos
Aborto Eugênico , Sistema Nervoso Central/anormalidades , Malformações do Sistema Nervoso/patologia , Ultrassonografia Pré-Natal , Anormalidades Múltiplas/diagnóstico por imagem , Anormalidades Múltiplas/embriologia , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/patologia , Sistema Nervoso Central/diagnóstico por imagem , Sistema Nervoso Central/patologia , Feminino , Humanos , Cariótipo , Masculino , Malformações do Sistema Nervoso/diagnóstico por imagem , Malformações do Sistema Nervoso/embriologia , Malformações do Sistema Nervoso/genética , Gravidez
16.
J Perinatol ; 39(8): 1072-1077, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31213636

RESUMO

Fetal Magnetic Resonance Imaging (MRI) is increasingly used in prenatal evaluations. OBJECTIVE: Identify common brain malformations on fetal MRI and evaluate perinatal course. METHODS: Fetal consultations from 10/2016 to 12/2017 reviewed. RESULTS: Hundred consultations were requested; 94 were completed. Findings included: posterior fossa malformations (19%), agenesis/dysgenesis of corpus callosum (15%), congenital aqueductal stenosis (CAS) (14%), ventriculomegaly (11%), isolated cortical malformations (8.5%), and holoprosencephaly (6%). Posterior fossa malformations were more likely to be associated with genetic conditions and cardiac malformations. Patients with CAS all required intensive care unit admission. Overall, few patients with congenital brain malformations required feeding or respiratory support at discharge. None had seizures as neonates except two with early epileptic encephalopathy syndromes. CONCLUSIONS: Even though long term neurological prognosis is poor for many conditions including high lifetime risk of epilepsy, most are discharged with no feeding or respiratory support. Seizures are rarely seen in the neonatal period.


Assuntos
Encéfalo/diagnóstico por imagem , Feto/diagnóstico por imagem , Imagem por Ressonância Magnética , Malformações do Sistema Nervoso/diagnóstico por imagem , Diagnóstico Pré-Natal , Agenesia do Corpo Caloso/diagnóstico por imagem , Agenesia do Corpo Caloso/embriologia , Encéfalo/anormalidades , Encéfalo/embriologia , Feto/anormalidades , Holoprosencefalia/diagnóstico por imagem , Holoprosencefalia/embriologia , Humanos , Hidrocefalia/diagnóstico por imagem , Hidrocefalia/embriologia , Recém-Nascido , Malformações do Sistema Nervoso/embriologia , Estudos Retrospectivos , Convulsões/etiologia
17.
Eur J Med Genet ; 62(8): 103704, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31207318

RESUMO

Whole exome sequencing undertaken in two siblings with delayed psychomotor development, absent speech, severe intellectual disability and postnatal microcephaly, with brain malformations consisting of cerebellar atrophy in the eldest affected and hypoplastic corpus callosum in the younger sister; revealed a homozygous intragenic deletion in VPS51, which encodes the vacuolar protein sorting-associated protein, one the four subunits of the Golgi-associated retrograde protein (GARP) and endosome-associated recycling protein (EARP) complexes that promotes the fusion of endosome-derived vesicles with the trans-Golgi network (GARP) and recycling endosomes (EARP). This observation supports a pathogenic effect of VPS51 variants, which has only been reported previously once, in a single child with microcephaly. It confirms the key role of membrane trafficking in normal brain development and homeostasis.


Assuntos
Encéfalo/fisiopatologia , Microcefalia/genética , Malformações do Sistema Nervoso/genética , Proteínas de Transporte Vesicular/genética , Encéfalo/diagnóstico por imagem , Criança , Endossomos/genética , Feminino , Humanos , Masculino , Microcefalia/diagnóstico por imagem , Microcefalia/fisiopatologia , Malformações do Sistema Nervoso/diagnóstico por imagem , Malformações do Sistema Nervoso/fisiopatologia , Transporte Proteico/genética , Rede trans-Golgi/genética
18.
BMJ Case Rep ; 12(5)2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31133547

RESUMO

Several genes located within the chromosome 8p11.21 region are associated with movement disorders including SLC20A2 and THAP1. SLC20A2 is one of four genes associated with primary familial brain calcification, a syndrome that also includes movement disorders, cognitive decline and psychiatric issues. THAP1 is associated with dystonia type 6, a dominantly inherited dystonia with variable expression. In addition, several reports in the French-Canadian population have described microdeletions within the 8p11.2 region presenting with dystonia-plus syndromes including brain calcifications. This case report describes a 12-year-old boy with brain calcifications and generalised dystonia associated with a deletion in the 8p11.2 region detected via single nucleotide polymorphism microarray. This report emphasises the importance of obtaining a microarray analysis in diagnosing movement disorders and suggests that this copy number variant may be an under-recognised cause of dystonia and brain calcifications.


Assuntos
Encefalopatias/genética , Encefalopatias/patologia , Distonia/diagnóstico , Malformações do Sistema Nervoso/genética , Proteínas Reguladoras de Apoptose , Calcinose/diagnóstico por imagem , Calcinose/patologia , Criança , Cromossomos Humanos Par 2/genética , Proteínas de Ligação a DNA , Distonia/genética , Deleção de Genes , Haploinsuficiência/genética , Heterozigoto , Humanos , Masculino , Análise em Microsséries/métodos , Transtornos dos Movimentos/genética , Malformações do Sistema Nervoso/diagnóstico por imagem , Malformações do Sistema Nervoso/patologia , Polimorfismo de Nucleotídeo Único , Proteínas Cotransportadoras de Sódio-Fosfato Tipo III
19.
Radiology ; 291(3): 814-818, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31116692

RESUMO

History A 1-year-old boy was referred for cochlear implant assessment after he received a diagnosis of bilateral profound sensorineural hearing loss at neonatal hearing screening shortly after birth. The child was born at term via uneventful delivery, and there was no history of familial hearing loss or maternal illness. Tympanic membranes were normal, and hearing loss was confirmed with auditory brainstem testing, which showed no response from either ear. Hearing aids were provided from 3 months of age, but no behavioral responses were noted when these were worn. He was also noted to have some mild developmental delay throughout his 1st year of life and was slow to crawl, roll over, and stand up. Physical examination showed no syndromic features or physical abnormalities. Ophthalmology confirmed normal vision and visual movements but bilateral anesthetic corneas. He had corneal abrasions due to minor repeated corneal trauma, and left-sided tarsorraphy was performed at 6 months. Facial nerve function, swallow, and voice quality were normal. To assess suitability for a cochlear implant, the patient underwent MRI of the temporal lobe and brain and thin-section CT of the temporal bones. The patient subsequently underwent left cochlear implantation.


Assuntos
Malformações do Sistema Nervoso , Tegmento Pontino , Implante Coclear , Perda Auditiva Neurossensorial/diagnóstico por imagem , Perda Auditiva Neurossensorial/cirurgia , Humanos , Lactente , Imagem por Ressonância Magnética , Masculino , Malformações do Sistema Nervoso/diagnóstico por imagem , Malformações do Sistema Nervoso/patologia , Tegmento Pontino/anormalidades , Tegmento Pontino/diagnóstico por imagem , Tegmento Pontino/patologia , Osso Temporal/diagnóstico por imagem , Lobo Temporal/diagnóstico por imagem , Tomografia Computadorizada por Raios X
20.
J Obstet Gynaecol Res ; 45(7): 1245-1250, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30932268

RESUMO

AIM: To explore the effectiveness of cavum septi pellucidi (CSP) width to anteroposterior cerebellar diameter (APCD) ratio as a diagnostic adjunct for prenatal diagnosis of trisomy 18. METHODS: Images of normal fetal brain within 15 and 35 weeks were stored in our center from 2016 to 2017. Images of aneuploid fetuses were retrospectively collected from 2004 to 2017. The transverse cerebellar diameter, APCD and CSP width were measured. CSP/APCD and APCD/transverse cerebellar diameter ratios were calculated and compared between euploid and aneuploid fetuses. RESULTS: One thousand and forty one fetuses were analyzed, including 817 euploid fetuses and 224 aneuploid fetuses (trisomy 21 117 cases, trisomy 18 82 cases, trisomy 13 9 cases, sex-linked 16 cases). No correlation had been found between both ratios and gestational weeks (P > 0.05). In aneuploid groups, means of ratios were both significantly different just between trisomy 18 group and euploid group (P < 0.05). The best area under the curve was shown by the CSP/APCD ratio. The cutoff value of CSP/APCD was 0.46 (sensitivity 87.0%, specificity 85.0%). CONCLUSION: A wide CSP or cerebellar hypoplasia warrants a more detailed ultrasound screening and genetic counseling. A larger CSP/APCD ratio alerts us to trisomy 18 syndrome, especially in cases with subtle anomalies.


Assuntos
Cerebelo/embriologia , Feto/diagnóstico por imagem , Indicadores Básicos de Saúde , Septo Pelúcido/embriologia , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Ultrassonografia Pré-Natal/estatística & dados numéricos , Adulto , Encéfalo/embriologia , Cerebelo/anormalidades , Cerebelo/diagnóstico por imagem , Deficiências do Desenvolvimento/diagnóstico por imagem , Feminino , Feto/patologia , Idade Gestacional , Humanos , Malformações do Sistema Nervoso/diagnóstico por imagem , Malformações do Sistema Nervoso/embriologia , Gravidez , Valores de Referência , Estudos Retrospectivos , Sensibilidade e Especificidade , Síndrome da Trissomía do Cromossomo 18/embriologia
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