Congenital Anomalies Of Central Nervous System Research Articles

Demographic and clinical characteristics of central nervous system congenital anomalies: A one year review of cases managed at UDUTH Sokoto

Background: The spectrum of CNS congenital anomalies varies from one geographical location to another across the globe. This essentially can be solitary or multiple and can be cranial, spinal, combination of both cranial and spinal or others. The understanding of their distribution in each location could determine local workforce and facility needs and as well guide in the areas of sub specialization. Objective: The aim of this study is to document the pattern of CNS congenital anomalies cases that had surgical intervention, at the Usmanu Danfodiyo University Teaching Hospital, Sokoto. Methods: A cross-sectional, retrospective hospital based study from January, 2021 to December, 2021 of all patients with CNS congenital anomalies who had surgical intervention at the Neurosurgery Department, Usmanu Danfodiyo University Teaching Hospital, Sokoto, Nigeria. Results: A total of 49 cases presented to our facility and had surgical interventions for central nervous system congenital anomaly. Of those 49 cases with CNS Congenital anomalies, there were 25 (51.0%) males and 24(48.98%) females, with a male-to-female ratio of 1.04: 1. The median age was 185 days, with age range of 2– 364days. Overall, the most commonly diagnosed neurosurgical CNS congenital anomalies in order of decreasing frequency were Congenital hydrocephalus 20 (40.82%), Myelomeningocele 14 (28.57%), Encephalocele 10 (20.41%), combination of Hydrocephalus associated with myelomeningocele 8(16.33%), Meningocele 3(6.12%), Lipomeningocele 1( 2.00%), Dandy walker malformation 1( 2.00%) , and Dandy variant1(2.00%) . Conclusions: NTDs (Myelomeningocele, Meningocele and lipomeningocele) were the most common CNS anomalies (55.10%). However, congenital hydrocephalus, Myelomeningocele, Encephalocele, Hydrocephalus + MM, and Meningocele are common in our environment in decreasing frequency. Though, Lipomeningocele, Dandy walker malformation and dandy variant are relatively rare. Understanding of this distribution may guide service expansion and workforce needs, inspire sub specialization as well as direct research and government policy in this community.

Trends of Neonatal Hypoxic-Ischemic Encephalopathy Prevalence and Associated Risk Factors in the United States, 2010 to 2018

ABSTRACT Neonatal hypoxic ischemic encephalopathy (HIE) is one of the most common causes of neonatal morbidity and mortality worldwide. It has an overall mortality rate ranging from 15% to 25%, with up to 50% of survivors developing long-term neurological disabilities. Therapeutic hypothermia (TH) has been the only effective treatment for moderate to severe HIE in neonates ≥35 weeks of gestation. Infants with mild HIE previously had been excluded from studies, but a recent study reported approximately 16% developed a disability at 18 to 22 months of age. Despite treatment, up to 29% of neonates with HIE still develop adverse outcomes. To decrease the prevalence of neonatal HIE, prevention is key and a better understanding of associated maternal, perinatal, and neonatal risk factors is needed. The aim of this study was to assess trends of HIE prevalence and use of TH, mortality, and clinical neonatal outcomes. This was a cross-sectional analysis using National Inpatient Sample data sets from 2010 to 2018. Included were newborn infants diagnosed with HIE or asphyxia, who were ≥35 weeks of gestation and had a birth weight ≥2500 g. Excluded were those with congenital heart disease, congenital central nervous system anomalies, congenital lung anomalies, congenital abdominal wall defects, gastroschisis or omphalocele, multiple congenital anomalies, common syndromes, and chromosomal disorders. Of the 32,180,617 infants included in the analysis, 31,249,100 were term infants (>35 weeks). The prevalence of all degrees of HIE for term infants was approximately 0.1%. There was a modest increase from 0.093% during the years 2010 and 2012 up to 0.097% during 2016 and 2018. Approximately 21% of cases were managed with TH. More infants with moderate HIE received TH than those with severe HIE (29.9% vs 19.9%; P < 0.01). Fewer infants with mild or unspecified HIE received TH than those with severe HIE (17.7% and 17.3%, respectively; P < 0.01). From 2010 to 2018, the use of TH increased overall and within each grade of HIE (P < 0.01). The mortality rate was higher in term infants with all degrees of asphyxia than the general population (10.8% vs 0.06%; P < 0.01). Over time, the mortality rate in term infants decreased from 12.3% in 2010 to 8.3% in 2018 (P < 0.01). The analysis included 931,517 were late preterm infants (35–36 weeks of gestation). The combined prevalence for all grades of HIE was 0.23% and did not change significantly over the years. Approximately 21% of late preterm infants were managed with TH. More infants with moderate HIE received TH than those with severe HIE (26.9% vs 20.1%). Fewer infants with mild HIE received TH (13.2%), and no significant difference was observed in infants with unspecified HIE compared with those with severe HIE (18.7% vs 20.1%). The use of TH increased has increased in late preterm infants over the years. The strongest factors associated with HIE were placental infarction or insufficiency, placental abruption, and cord prolapse. Female infant sex, maternal Hispanic ethnicity, and maternal Asian race were associated with lower risk of HIE. In conclusion, HIE prevalence remained essentially the same at 1 per 1000 live births. Use of TH increased, and mortality decreased over time. The strongest factors associated with HIE were placental factors.

HCMV Infection Reduces Nidogen-1 Expression, Contributing to Impaired Neural Rosette Development in Brain Organoids.

Human cytomegalovirus (HCMV) is a leading cause of birth defects in humans. These birth defects include microcephaly, sensorineural hearing loss, vision loss, and cognitive impairment. The process by which the developing fetus incurs these neurological defects is poorly understood. To elucidate some of these mechanisms, we have utilized HCMV-infected induced pluripotent stem cells (iPSCs) to generate in vitro brain organoids, modeling the first trimester of fetal brain development. Early during culturing, brain organoids generate neural rosettes. These structures are believed to model neural tube formation. Rosette formation was analyzed in HCMV-infected and mock-infected brain organoids at 17, 24, and 31 days postinfection. Histological analysis revealed fewer neural rosettes in HCMV-infected compared to mock-infected organoids. HCMV-infected organoid rosettes incurred multiple structural deficits, including increased lumen area, decreased ventricular zone depth, and decreased cell count. Immunofluorescent (IF) analysis found that nidogen-1 (NID1) protein expression in the basement membrane surrounding neural rosettes was greatly reduced by virus infection. IF analysis also identified a similar downregulation of laminin in basement membranes of HCMV-infected organoid rosettes. Knockdown of NID1 alone in brain organoids impaired their development, leading to the production of rosettes with increased lumen area, decreased structural integrity, and reduced laminin localization in the basement membrane, paralleling observations in HCMV-infected organoids. Our data strongly suggest that HCMV-induced downregulation of NID1 impairs neural rosette formation and integrity, likely contributing to many of HCMV's most severe birth defects. IMPORTANCE HCMV infection in pregnant women continues to be the leading cause of virus-induced neurologic birth defects. The mechanism through which congenital HCMV (cCMV) infection induces pathological changes to the developing fetal central nervous system (CNS) remains unclear. Our lab previously reproduced identified clinical defects in HCMV-infected infants using a three dimensional (3D) brain organoid model. In this new study, we have striven to discover very early HCMV-induced changes in developing brain organoids. We investigated the development of neural tube-like structures, neural rosettes. HCMV-infected rosettes displayed multiple structural abnormalities and cell loss. HCMV-infected rosettes displayed reduced expression of the key basement membrane protein, NID1. We previously found NID1 to be specifically targeted in HCMV-infected fibroblasts and endothelial cells. Brain organoids generated from NID1 knockdown iPSCs recapitulated the structural defects observed in HCMV-infected rosettes. Findings in this study revealed HCMV infection induced early and dramatic structural changes in 3D brain organoids. We believe our results suggest a major role for infection-induced NID1 downregulation in HCMV-induced CNS birth defects.

Causes of death in children with congenital Zika syndrome in Brazil, 2015 to 2018: A nationwide record linkage study.

Children with congenital Zika syndrome (CZS) have severe damage to the peripheral and central nervous system (CNS), greatly increasing the risk of death. However, there is no information on the sequence of the underlying, intermediate, immediate, and contributing causes of deaths among these children. The aims of this study are describe the sequence of events leading to death of children with CZS up to 36 months of age and their probability of dying from a given cause, 2015 to 2018. In a population-based study, we linked administrative data on live births, deaths, and cases of children with CZS from the SINASC (Live Birth Information System), the SIM (Mortality Information System), and the RESP (Public Health Event Records), respectively. Confirmed and probable cases of CZS were those that met the criteria established by the Brazilian Ministry of Health. The information on causes of death was collected from death certificates (DCs) using the World Health Organization (WHO) DC template. We estimated proportional mortality (PM%) among children with CZS and among children with non-Zika CNS congenital anomalies (CA) by 36 months of age and proportional mortality ratio by cause (PMRc). A total of 403 children with confirmed and probable CZS who died up to 36 months of age were included in the study; 81.9% were younger than 12 months of age. Multiple congenital malformations not classified elsewhere, and septicemia unspecified, with 18 (PM = 4.5%) and 17 (PM = 4.2%) deaths, respectively, were the most attested underlying causes of death. Unspecified septicemia (29 deaths and PM = 11.2%) and newborn respiratory failure (40 deaths and PM = 12.1%) were, respectively, the predominant intermediate and immediate causes of death. Fetuses and newborns affected by the mother's infectious and parasitic diseases, unspecified cerebral palsy, and unspecified severe protein-caloric malnutrition were the underlying causes with the greatest probability of death in children with CZS (PMRc from 10.0 to 17.0) when compared to the group born with non-Zika CNS anomalies. Among the intermediate and immediate causes of death, pneumonitis due to food or vomiting and unspecified seizures (PMRc = 9.5, each) and unspecified bronchopneumonia (PMRc = 5.0) were notable. As contributing causes, fetus and newborn affected by the mother's infectious and parasitic diseases (PMRc = 7.3), unspecified cerebral palsy, and newborn seizures (PMRc = 4.5, each) were more likely to lead to death in children with CZS than in the comparison group. The main limitations of this study were the use of a secondary database without additional clinical information and potential misclassification of cases and controls. The sequence of causes and circumstances involved in the deaths of the children with CZS highlights the greater vulnerability of these children to infectious and respiratory conditions compared to children with abnormalities of the CNS not related to Zika.

Comparative study between 1st and 2nd trimester screening for neural tube defects using US markers and maternal serum alpha fetoportein

Background; Neural tube defects, the commonest central nervous system congenital anomalies, are a heterogeneous group of malformations resulting from failure of normal neural tube closure. Aim and objectives; to assess the potential value of combined maternal serum alpha-fetoprotein and ultrasound markers at 11-13weeks of gestation in early screening for fetal neural tube defects in comparison to the standard second trimester screening of neural tube defects. Subjects and methods; This prospective study will be conducted at the Prenatal Diagnosis and Fetal Medicine Department – National Research Centre and Obstetrics and Gynecology Department in Kasr Al Ainy Teaching Hospital. Result; Number of patients with MSAFP ≥ 2.0 MoM in the study population was 50 (25%). Number of patients with MSAFP < 2.0 MoM in the study population was 150 (75%). Conclusion; Combined maternal serum alpha-fetoprotein and ultrasound markers at 11-13 weeks of gestation can be used as early screening for fetal neural tube defects as well as the standard second trimester screening of neural tube defects, the second trimester ultrasound is more sensitive than that of the first trimester for the diagnoses of neural tube defects.

Pattern of Congenital Central Nervous System Anomalies Among Newborns at A Regional Special Care Baby Unit (SCBU) in Makurdi, North Central Nigeria

Background: Congenital anomalies of the central nervous system (CNS) are important causes of childhood mortality, chronic illness and disability. They have significant implications for childhood growth and development particularly in resource limited settings. Areview of their occurrence is valuable to instituting preventive and curative health care services.Objective: To document the pattern of congenital CNS anomalies in our practice Subjects and Method: A retrospective study of all neonatal admissions with congenital anomalies of the CNS (Patients) admitted into the Special Care Baby Unit (SCBU) of Benue State University Teaching Hospital (BSUTH) in Makurdi-Nigeria, between June 2013 andJanuary 2016. The anomalies were classified according to the ICD 10 Classification. Other parameters assessed were: age at admission, gestational age at delivery, family history of congenital anomalies, maternal age, social class, history of ante natal care, and admission outcome.Results: A total of 73 (9.3%) out of the admitted 785 neonates had congenital anomalies and majority (28, 38.4%) were of the CNS. The affected patients had a male preponderance (20, 71.4%). Myelomeningocele was the commonest CNS anomaly (20, 71.4 %). Poor antenatal care, lack of periconceptional folic acid (pFA) intake, late folic acid supplementation, low socio economic class, and late presentation were all associated with the incidence of congenital CNS anomalies. The patients had a neonatal mortality rate of 7.1% over the study period of 30 months (2.8% per year).Conclusion: Congenital CNS anomalies were the predominant congenital anomalies, and myelomeningocele was the commonest. The study underscores the need to institute a comprehensive healthcare programme for the prevention and management of congenital anomalies of the CNS in our practice.

Evaluation of prenatal central nervous system anomalies: obstetric management, fetal outcomes and chromosome abnormalities

ObjectiveTo study the outcomes of fetuses who were diagnosed with central nervous system (CNS) anomalies during prenatal period and to describe the obstetric management of those pregnancies.MethodsIn this retrospective study, fetuses who were detected to have central nervous system anomalies by prenatal ultrasound from January 2010 to December 2019 were recruited. Data regarding prenatal diagnosis and obstetric outcomes were retrieved from maternal and paediatric records. The prognosis of fetuses who were born alive was classified based on their neurodevelopmental outcome within two years of life.ResultsThere were a total of 365 fetuses with CNS anomalies within the 10-year study period, with a mean gestational age of 24.65±7.37 weeks at diagnosis. Ventriculomegaly (23.36%) was the commonest CNS anomalies seen. 198 (54.20%) of these fetuses had associated extra-CNS anomalies, with cardiovascular being the most common system involved. Fetal karyotyping was performed in 111 pregnancies, with chromosomal aberrations detected in 53 (49.07%) cases and culture failure in 3 cases. Majority of the chromosomal abnormalities were Edward syndrome (trisomy 18) and Patau syndrome (trisomy 13). Fetuses with congenital CNS anomalies and abnormal chromosomal karyotyping were more likely to be diagnosed earlier by prenatal ultrasound and tend to have poorer obstetric and neurocognitive prognosis. Prenatally, 86 (23.56%) of the cases were lost to follow up and likely to deliver elsewhere. Among the 279 cases whom their pregnancy outcomes were available, 139 (49.82%) pregnancies resulted in live births, 105 (37.63%) pregnancies were electively terminated, while the remaining 35 (12.54%) pregnancies ended in spontaneous loss. The decision of termination of pregnancy largely depends on mean diagnostic gestational age, presence of chromosomal aberrations and abnormal amniotic fluid volume in those fetuses. Two years after delivery, only 75 (53.96%) children out of 139 live births were still alive, 43 (30.93%) died and 21 (15.11%) cases were lost to follow-up. 32 (23.02%) children with prenatally diagnosed CNS anomalies had normal neurodevelopmental outcome. The presence of multiple CNS anomalies and involvement of extra-CNS anomalies indicated a poorer neurodevelopmental prognosis.ConclusionLess than 50% of fetuses with prenatally diagnosed CNS anomalies resulted in live births. Even if they survive till delivery, 36.45% of them passed away within 2 years and 62.79% of children who survived till 2 years old had neurodevelopmental disability.

Four-dimensional ultrasound in the diagnosis of intrauterine central nervous system anomalies: four dimensional in CNS congenital anomalies

Background Central nervous system (CNS) anomalies are an important factor of neonatal deaths. Three-dimensional (3D)/4D ultrasound (US) has an advantage over the conventional 2D US as it provides additional multiple options like multiplanar view, tomographic view, and surface rendering view leading to accurate diagnosis of fetal congenital anomalies. Aim The aim of this study was to evaluate the role of the 4D US in the diagnosis of in utero congenital CNS anomalies. Patients and methods The current study was conducted on 30 pregnant women with suspected congenital CNS anomalies by 2D US in Tanta University Hospitals. All the patients were subjected to 2D and 4D US examination in cases with suspected anomalies by 2D US. Results Out of 30 anomalies, two (6.5%) anomalies were lobar holoprosencephaly; six (20%) anomalies were anencephaly, three (10%) anomalies were exencephaly, one (3.5%) anomaly was aqueductal stenosis, three (10%) anomalies were chiari malformation with its two types I and II, and three (10%) anomalies were Dandy–Walker. Three anomalies were hydranencephaly (10%), three (10%) meningocele, one (3.5%) spina bifida, and two cases were obstructive hydrocephalus distal to the 4th ventricle (obstruction of foramen of luschka and magendie) (6.5%). As regards brain anomalies, sensitivity of 4D US=96.4%, specificity of 4D US=100%, positive predictive value=100%, negative predictive value=50.0%, and accuracy=96%. So, 4D US is more superior to 2D US in demonstrating anomalies of the CNS (through multiplanar view and tomographic views), which may affect the postnatal outcome. 4D US offers precise demonstration of normal and abnormal fetal structures through its different modes, so it helps in accurate prenatal diagnosis of CNS anomalies. Conclusion 4D US is considered now an important diagnostic tool in fetal medicine as it provides many advanced diagnostic options such as multiplanar view or tomographic imaging, volume calculation, and surface rendering mode, which aided in early diagnosis of fetal anomalies and improved postnatal outcome.

Comparative Study between the Role of Two dimensional and Three dimensional Ultrasound in Assessment of Fetal Central Nervous System Congenital Anomalies

ABSTRACT Objective: This study aimed to evaluate the role of three dimensional (3D) ultrasound compared with two dimensional (2D) ultrasound in diagnosis of fetal central nervous system congenital malformations. Patients and Methods: this Prospective study was performed on total 100 patients with gestational age from 18 weeks to 24 weeks who underwent 2D ultrasound then examined by 3D ultrasound at Obstetrics and Gynecology Department, Bab el-Sheria, Al-azhar University Hospital. Results: Statistical analysis revealed that the most common neurological malformations detected were Holoprosencephaly and Anencephaly which had significant high agreement between 2D and 3D regarding their diagnosis. There was significant agreement between 2D and 3D regarding the congenital fetal spinal and cranial malformations. The 2D and 3D ultrasound provided equal diagnostic information in microcephaly while 3D US provided more diagnostic information than 2D US for Choroid plexus cyst, agenesis of the corpus callosum and spina bifida. Our study revealed that the 3D US was superior to 2D US in identifying small cranial malformations as choroid plexus cyst and the spine e.g Spina bifida. Conclusion: In comparison with 2D US, 3D US improves the diagnostic capability by illustrating more diagnostic details in evaluation of malformations of the fetus, especially in visualization of fetal malformations of the small cranial anomalies and spina bifida . In addition to 2D US, 3D US is a valuable adjunct in prenatal detection of anomalies.

Value of pre- and postnatal magnetic resonance imaging in the evaluation of congenital central nervous system anomalies.

Fetal MRI and neonatal MRI of the central nervous system (CNS) are complementary tools that can help to accurately counsel and direct the management of children with anomalies of the central nervous system. Postnatal MRI can add to fetal MRI by allowing for monitoring of changes in the severity of disease, better delineation of a suspected prenatal anomaly, evaluation for secondary pathologies related to the primary diagnosis, and surgical management direction. In this review we discuss the roles of fetal and neonatal MRI in the diagnosis and treatment of congenital anomalies of the CNS through a series of case examples and how both are important in patient management.

Congenital CNS malformations in pediatric autopsy and surgical specimen

Aim: The aim of the present study was to analyze congenital central nervous system (CNS) malformations from paediatric autopsies and from surgical specimens, to recognise, record, categorise the congenital CNS malformations and to study its association with various maternal and fetal factors. Materials and Methods: This is both prospective (June 2009 to May 2011) and retrospective study conducted during period of two and half decades i.e. from 1987 to May 2011 in a tertiary care hospital. Cases were selected from both pediatric autopsies and surgical specimens as per inclusion and exclusion criteria. Pediatric autopsy was conducted as per standard protocol after obtaining consent from parents. Results: Out of 3492 pediatric autopsies, the CNS malformations were seen in 58 cases and out of 5639 pediatric surgical specimens, 85 were of CNS anomalies. In autopsy study neural tube defects (NTD), 20 cases (34.48%) were the most common followed by congenital hydrocephalus, 14 cases (24.14%). In surgical specimen study all were NTD except for one neuroenteric cyst. Conclusion: Neural tube defects were the most common CNS anomalies; majority of which could be surgically treated. CNS anomalies are associated with preterm births, low birth weight and younger maternal age.Although radiological investigations have high sensitivity in diagnosing CNS malformations, autopsy findings are essential to arrive at a definitive diagnosis.

Management of Neural Tube Defect: A Single-Center Experience

Objective: Neural tube defects are a heterogeneous and complex group of congenital central nervous system anomalies involving that involve the failed closure of the vertebral column. The spinal cord is frequently affected, and neural tube defects substantially increase the risk of disability and death within the first year of life. Neural malformations are often associated with abnormalities in other organ systems. This study presents our clinical experiences regarding the development and comorbidities of infants with neural tube defect and compares them with the literature.
 Materials and Methods: This retrospective study included 47 patients (24 females, 23 males) who underwent surgical treatment for neural tube defect in the neurosurgery department of Sivas Cumhuriyet University Faculty of Medicine Training and Research Hospital between 2000 and 2020.
 Results: Of the 47 patients, 34 (72.34%) had myelomeningocele and 13 (27.65%) had meningocele. Lesion location was thoracolumbar in 38 patients (80.85%), lumbar in 5 (10.63%), lumbosacral in 3 (6.38%), and cervical in 1 patient (2.12%). Twenty-seven patients (57.44%) underwent ventriculoperitoneal shunting due to hydrocephalus. Thirty patients (63.82%) had Chiari malformation type II, 13 (27.65%) had cranial anomalies, and 1 (2.12%) had Down syndrome. In 9 patients, the conus medullaris terminated at or below the L3 vertebral body (19.14%). Two patients (4.25%) died.
 Conclusion: Because of their multidimensional nature, neural tube defects have various effects on individuals, families, society, and the field of medicine. This study represents a small group of patients with neural tube defects. Cases should be included from other centers to compile more comprehensive data about patients with neural tube defects in Turkey.

The Spectrum of Congenital Central Nervous System Anomalies Among Stillborn: An Autopsy Based Study

Background:Congenital central nervous system (CNS) anomalies are the structural or functional abnormalities of the brain and spinal cord that occur during the intrauterine developmental process.Purpose:The present study aims to detect the prevalence of congenital CNS anomalies among stillborn fetuses, the association between congenital anomalies and maternal factors, and also the association between autopsy and ultrasound findings.Methods:This study was conducted on 50 stillborn fetuses, obtained from the Department of Obstetrics and Gynecology at JSS Medical College and Hospital, Mysuru. The fetuses were fixed in 10% formalin and autopsies were performed as per the standard fetal autopsy protocol. The congenital CNS anomalies were studied in detail.Results:CNS anomalies were the most common congenital anomalies observed. Out of the total 50 stillborn fetuses studied, CNS anomalies were found in 17 fetuses and their occurrence was more common among male stillborn than females. Meningomyelocele was the most common anomaly, followed by anencephaly. The other anomalies documented were meningocele, encephalocele, meningoencephalocele, agenesis of the corpus callosum, craniorachischisis, bifid cerebellum with hypoplastic vermis, holoprosencephaly, and sirenomelia.Fisher’s exact test showed a significant association between maternal hypothyroidism and congenital CNS anomalies (P < .05). The autopsy confirmed the ultrasound findings in 40 (80%) fetuses. There were significant additional findings observed in seven (14%) fetal autopsies and ultrasound diagnosis completely changed in three (6%) cases, after the final autopsy procedure.Conclusion:The fetal autopsy is the single most directly evident investigation, which gives information that changes or significantly improves the clinical diagnosis. A multidisciplinary holistic approach toward pregnancy will help to detect any kind of abnormality in the fetus and thus to take a timely decision toward the management.

Investigation of copeptin levels in foetal congenital central nervous system anomalies

Copeptin has been shown to be associated with central nervous system pathologies. The aim of this study was to investigate the relationship between serum CCP levels and central nervous system (CNS) anomalies. In this case-control study, those at 9–14 weeks of gestation serum levels of copeptin, were assessed in pregnant women whose foetuses subsequently developed CNS anomalies (group 1: n = 60) and compared with gestational age-matched pregnant women who exhibited normal pregnancy outcomes (group 2: n = 48). The mean copeptin levels were 1.58 ± 0.40 ng/mL and 1.11 ± 0.36 ng/mL in the CNS anomalies and control groups, respectively (p < .0001). An increased level of copeptin independently predicts development of CNS anomalies, suggesting that copeptin can be used for prediction and discrimination of CNS anomalies in normal pregnancies at 9–14 weeks of gestation. Impact statement What is already known on this subject? There is no test or method to diagnose CNS anomalies in the first trimester of pregnancy. This study presents the first and new information on the relationship between serum copeptin levels and central nervous system anomalies in pregnant women whose foetuses subsequently developed CNS anomalies. What do the results of this study add? I have strongly demonstrated differences in maternal CPP levels between CNS anomalous pregnancies and healthy controls. What are the implications of these findings for clinical practice and/or further research? It has been thought that copeptin appears to be an ideal marker for central nervous system anomaly prediction at 9–14 weeks of gestational age and if confirmed in larger prospective studies. Finally, these results could not be used as parameters for prenatal CNS screening. Advanced studies, well-structured and conducted on larger populations are needed to investigate the issue further.

Pre- and Postnatal Diagnosis of Congenital Central Nervous System Anomalies in Iceland in 1992-2016

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. 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. 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. 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.

Congenital central nervous system anomalies: Ten-year single center experience on a challenging issue in perinatal medicine

Objective:Our goal was to highlight the prenatal diagnosis and management of central nervous system (CNS) anomalies through sharing our clinic’s experience.Material and Methods:We evaluated prenatal findings and postnatal outcomes of neonates who had a CNS anomaly diagnosis in our clinic over a ten-year period. A total of 183 cases with various CNS anomalies were included in the study. Birth or termination preferences of mothers were recorded in all cases, and postnatal diagnosis concordance and prognosis after surgical procedures were evaluated in mothers who chose to continue the pregnancy.Results:The mean maternal age was 28.2±5.5 years, mean gravida was 2.2±1.3, and the mean gestational age at diagnosis was 30.5±5.5 weeks. Seventy-five out of 183 (41%) patients chose to terminate their pregnancy. Twenty babies (26.6%) in the termination of pregnancy group had additional anomalies. One hundred eight patients gave birth at our institution. The mean birth weight was 3060±647.5 g, the mean gestational week at delivery was 37.9±1.7 weeks, and mean APGAR score (5th minute) was 8.8±2.3. Four neonates died on the postpartum first day. The postnatal diagnosis of 60 of the 108 (55.5%) patients who gave birth was concordant with the prenatal diagnosis, and 32 of the 108 (29.6%) babies underwent surgical interventions.Conclusion:CNS anomalies have a broad spectrum and variable prognoses. This study highlights the limitations of prenatal diagnoses, and the need for parents to have this information in order to determine the course of their pregnancy and prepare themselves for the postnatal challenging treatment/rehabilitation process.

Human Cytomegalovirus Compromises Development of Cerebral Organoids.

Congenital human cytomegalovirus (HCMV) infection causes a broad spectrum of central and peripheral nervous system disorders, ranging from microcephaly to hearing loss. These ramifications mandate the study of virus-host interactions in neural cells. Neural progenitor cells are permissive for lytic infection. We infected two induced pluripotent stem cell (iPSC) lines and found these more primitive cells to be susceptible to infection but not permissive. Differentiation of infected iPSCs induced de novo expression of viral antigens. iPSCs can be cultured in three dimensions to generate cerebral organoids, closely mimicking in vivo development. Mock- or HCMV-infected iPSCs were subjected to a cerebral organoid generation protocol. HCMV IE1 protein was detected in virus-infected organoids at 52 days postinfection. Absent a significant effect on organoid size, infection induced regions of necrosis and the presence of large vacuoles and cysts. Perhaps more in parallel with the subtler manifestations of HCMV-induced birth defects, infection dramatically altered neurological development of organoids, decreasing the number of developing and fully formed cortical structure sites, with associated changes in the architectural organization and depth of lamination within these structures, and manifesting aberrant expression of the neural marker β-tubulin III. Our observations parallel published descriptions of infected clinical samples, which often contain only sparse antigen-positive foci yet display areas of focal necrosis and cellular loss, delayed maturation, and abnormal cortical lamination. The parallels between pathologies present in clinical specimens and the highly tractable three-dimensional (3D) organoid system demonstrate the utility of this system in modeling host-virus interactions and HCMV-induced birth defects.IMPORTANCE Human cytomegalovirus (HCMV) is a leading cause of central nervous system birth defects, ranging from microcephaly to hearing impairment. Recent literature has provided descriptions of delayed and abnormal maturation of developing cortical tissue in infected clinical specimens. We have found that infected induced pluripotent stem cells can be differentiated into three-dimensional, viral protein-expressing cerebral organoids. Virus-infected organoids displayed dramatic alterations in development compared to those of mock-infected controls. Development in these organoids closely paralleled observations in HCMV-infected clinical samples. Infection induced regions of necrosis, the presence of larger vacuoles and cysts, changes in the architectural organization of cortical structures, aberrant expression of the neural marker β-tubulin III, and an overall reduction in numbers of cortical structure sites. We found clear parallels between the pathologies of clinical specimens and virus-infected organoids, demonstrating the utility of this highly tractable system for future investigations of HCMV-induced birth defects.

Added Value of Fetal Magnetic Resonance Imaging in Diagnosis of Central Nervous System Congenital Anomalies in Egyptian Population

CNS anomalies are the second most frequent type of congenital anomalies. It is important to diagnose them as early as possible due to poor outcome. The aim of the study is to assess the role of magnetic resonance imaging in evaluation of congenital anomalies of central nervous system. This study included 80 pregnant women with suspected congenital CNS anomalies. All patients had been examined by 2D ultrasound and MRI. The majority of anomalies in the current study were anencephaly, hydrocephalus with aqueductal stenosis and Chiari malformation . Twenty percentage of brain anomalies was associated with meningioceles. A significant difference was detected in both aqueductal stenosis and dandy walker as regards history of consanguinity. The results were compared with post natal clinical assessment and MRI. It is concluded that fetal MRI is becoming an increasingly important tool in diagnosis of brain abnormalities suspected on the basis of family history or fetal sonography (with equivocal data), with continuing improvements in technology for better improvement of postnatal outcome. BPD = Biparietal diameter, CNS = Central nervous system, EFW = Expected fetal body weight, FL = Femur length, FOV = Field of view, MRI = Magnetic resonance imaging, N= Number, SD = Standard deviation, Ssfp= Steady-state free percession, ST= Slice thickness, TE =time of echo, TR=time of repetition, T2WI=T2 weighted image, US=ultrasound.

Congenital central nervous system anomalies: the 10-year single center experience on a challenging issue in perinatal medicine

Congenital central nervous system anomalies: the 10-year single center experience on a challenging issue in perinatal medicine

The prevalence and pattern of central nervous system anomalies in a neonatal unit in a tertiary hospital in Jos, north-central Nigeria

Background: Congenital anomalies are an important cause of neonatal deaths, chronic illness, and disability and are most common in low- and middle-income countries. Central nervous system (CNS) congenital anomalies are one of the most common abnormalities. Information on the burden and types of CNS anomalies will facilitate health system planning and an efficient allocation of scarce resources. We determined the prevalence and pattern of CNS congenital anomalies in a neonatal unit in Jos, north-central Nigeria. Materials and Methods: A retrospective descriptive study of all neonates admitted with CNS congenital anomalies into the neonatal unit of Jos University Teaching Hospital (JUTH) from October 2013 to September 2016 was conducted. Results: One hundred and fifty-five (14.8%) of the 1046 babies admitted during the period had congenital anomalies. Twenty-seven babies (14 males and 13 females) had CNS anomalies giving a prevalence rate of 2.6%. CNS anomalies constituted 17.4% of the 155 babies admitted with congenital anomalies. All 27 (100%) of the babies were born outside the teaching hospital, with 13 (48.2%) of them delivered at home. Neural tube defects (NTDs) were the most common CNS malformations (26; 96.3% of the CNS anomalies). Talipes equinovarus was the most common associated anomaly (6; 22.2% of the babies). Conclusion: The prevalence of CNS anomalies among admitted neonates in the JUTH is high. NTDs were the most common CNS anomalies, with myelomeningocele being the single most common disorder.