Comparison of prenatal central nervous system abnormalities with postmortem findings in fetuses following termination of pregnancy and clinical utility of postmortem examination

Objectives In this study, we aimed to compare prenatal ultrasound (USG) and postmortem examination findings of central nervous system (CNS) abnormalities in fetuses following termination of pregnancy (TOP). Methods A total of 190 fetuses with USG-confirmed fetal CNS abnormalities of terminated pregnancies between January 2001 and January 2017 were retrospectively analyzed and USG and postmortem examination findings were compared. Results The most frequent CNS abnormalities were acrania/anencephaly (n=45, 24%), spina bifida (n=43, 23%), and ventriculomegaly (n=35, 18%). In 144 of the 190 (76%) cases, there was total agreement between USG and postmortem examination diagnosis. Postmortem examination provided minor findings which did not change the major clinical diagnosis in two (1%) cases with spina bifida and ventriculomegaly. In six (3%) cases, the diagnosis changed after postmortem examination. In 25 of the 190 (13%) cases with multiple abnormalities as evidenced by USG, CNS abnormality was unable to be confirmed at postmortem examination. Conclusions Our study results show an overall high agreement (76%) between USG and postmortem examination findings for CNS malformations. Due to autolysis and fluid structure, USG-confirmed CNS diagnosis cannot be always confirmed by postmortem examination. This potential discrepancy should be explained to patients before considering TOP. Postmortem examination is the gold standard to confirm prenatal diagnosis.

Zika Virus: A New Therapeutic Candidate for Glioblastoma Treatment

Glioblastoma (GBM) is the most aggressive among the neurological tumors. At present, no chemotherapy or radiotherapy regimen is associated with a positive long-term outcome. In the majority of cases, the tumor recurs within 32–36 weeks of initial treatment. The recent discovery that Zika virus (ZIKV) has an oncolytic action against GBM has brought hope for the development of new therapeutic approaches. ZIKV is an arbovirus of the Flaviviridae family, and its infection during development has been associated with central nervous system (CNS) malformations, including microcephaly, through the targeting of neural stem/progenitor cells (NSCs/NPCs). This finding has led various groups to evaluate ZIKV’s effects against glioblastoma stem cells (GSCs), supposedly responsible for GBM onset, progression, and therapy resistance. While preliminary data support ZIKV tropism toward GSCs, a more accurate study of ZIKV mechanisms of action is fundamental in order to launch ZIKV-based clinical trials for GBM patients.

Profile of congenital defects in foetuses: incidence and risk factors: a prospective observational study

Background: Perinatal outcome is one of the major indicators of evaluating health care system of a country. Congenital defects form important components of this parameter. The aim of the study was to determine the risk factors associated with congenital malformations in foetuses.Methods: All antenatal mothers whose foetuses were detected to have congenital defects on ultrasonography irrespective of period of gestation were enrolled for the study.Results: Eighty-six pregnant women with prenatally diagnosed fetal anomalies were enrolled for the study, out of which, 87.2% (N=75) belonged to 20-30 years age group. Majority of the subjects were educated till secondary school. Compared to primigravidae, the incidence of malformations was significantly higher in the multigravida group (69.8% vs 30.2% respectively). Thirty-eight (44.2%) mothers with malformed foetuses missed folic acid intake during early pregnancy. Only 40% mothers had prior history of abortions. Smoking was seen in 9% of subjects with malformations. Seven (8.3%) mothers had previous history of malformations and 5 (5.8%) reported a family history of malformations. Consanguineous marriage was observed in 4.7% of couples. Oligohydramnios or anhydramnios was associated with 11.6% foetuses, while polyhydramnios was seen in 53.5%. CNS malformations were seen in 57% of foetus, followed by genitourinary system malformations (9.2%).Conclusions: Tertiary level hospitals need to be upgraded with a dedicated multidisciplinary team of foetal medicine to cater to medical, clinical, surgical, preventive and therapeutic needs of malformed foetuses.

Characteristics of the Central Nervous System Malformations Presented in Trisomy 13: A single-center Experience in Recognizing the Phenotype and Genotype

BACKGROUND: Patients who are diagnosed with trisomy 13 (Patau syndrome) are known to have a poor prognosis. It has been hypothesized that such poor outcomes are suspected to be attributed to their central nervous system (CNS)-malformations and cardiac-malformations. This study was conducted at Division of Neuropediatric, Department of Neurosurgery, Faculty of Medicine, Universitas Padjadjaran – Dr. Hasan Sadikin Hospital, Bandung (2012–2018). AIM: This study aimed to describe clinical characteristics and karyotype findings in patients who were diagnosed with Patau syndrome and treated at our center. Since Indonesia is still categorized as a lower middle-income country with limited resources, we expected that this study would provide a clinical reference on how a congenital disease with chromosomal abnormalities is confirmed. CASE PRESENTATION: Our cases indicate that CNS malformations are likely to be the cause of indirect mortality of patients’ early period of life. The median survival in our study is 7 days, while the longest survival is 30 days. The major cause of death is apnea, which found in 4 of 5 diagnosed infants. One patient died of severe infection. In most cases, where CNS malformations were observed microcephaly with sloping forehead, Dandy–Walker syndrome, lobar or alobar holoprosencephaly and ventriculomegaly were identified, as well as neural tube defects (NTDs) were identified, such as spina bifida and meningoencephalocele. CNS malformations, such as holoprosencephaly, may be associated with episodes characterized by temporary cessation of spontaneous breathing (apnea) as direct cause of mortality. CONCLUSION: We conclude that early treatment in Patau syndrome patient in our center should be focused on more life-threatening problem caused by CNS malformations than NTDs defects, such defects could be managed electively.

Further evidence for POMK as candidate gene for WWS with meningoencephalocele

Background Walker-Warburg syndrome (WWS) is a rare form of alpha-dystroglycanopathy characterized by muscular dystrophy and severe malformations of the CNS and eyes. Bi-allelic pathogenic variants in POMK are the cause of a broad spectrum of alpha-dystroglycanopathies. POMK encodes protein-O-mannose kinase, which is required for proper glycosylation and function of the dystroglycan complex and is crucial for extracellular matrix composition. Results Here, we report on male monozygotic twins with severe CNS malformations (hydrocephalus, cortical malformation, hypoplastic cerebellum, and most prominently occipital meningocele), eye malformations and highly elevated creatine kinase, indicating the clinical diagnosis of a congenital muscular dystrophy (alpha-dystroglycanopathy). Both twins were found to harbor a homozygous nonsense mutation c.640C>T, p.214* in POMK, confirming the clinical diagnosis and supporting the concept that POMK mutations can be causative of WWS. Conclusion Our combined data suggest a more important role for POMK in the pathogenesis of meningoencephalocele. Only eight different pathogenic POMK variants have been published so far, detected in eight families; only five showed the severe WWS phenotype, suggesting that POMK-associated WWS is an extremely rare disease. We expand the phenotypic and mutational spectrum of POMK-associated WWS and provide evidence of the broad phenotypic variability of POMK-associated disease.

Aberrant Oligodendrogenesis in Down Syndrome: Shift in Gliogenesis?

Down syndrome (DS), or trisomy 21, is the most prevalent chromosomal anomaly accounting for cognitive impairment and intellectual disability (ID). Neuropathological changes of DS brains are characterized by a reduction in the number of neurons and oligodendrocytes, accompanied by hypomyelination and astrogliosis. Recent studies mainly focused on neuronal development in DS, but underestimated the role of glial cells as pathogenic players. Aberrant or impaired differentiation within the oligodendroglial lineage and altered white matter functionality are thought to contribute to central nervous system (CNS) malformations. Given that white matter, comprised of oligodendrocytes and their myelin sheaths, is vital for higher brain function, gathering knowledge about pathways and modulators challenging oligodendrogenesis and cell lineages within DS is essential. This review article discusses to what degree DS-related effects on oligodendroglial cells have been described and presents collected evidence regarding induced cell-fate switches, thereby resulting in an enhanced generation of astrocytes. Moreover, alterations in white matter formation observed in mouse and human post-mortem brains are described. Finally, the rationale for a better understanding of pathways and modulators responsible for the glial cell imbalance as a possible source for future therapeutic interventions is given based on current experience on pro-oligodendroglial treatment approaches developed for demyelinating diseases, such as multiple sclerosis.

Myelomeningocele with Associated Anomalies – Case Report and Literature Review

Myelomeningocele is a common defect of the development of the neural tube. It is a complex congenital malformation of the central nervous system (CNS) that can be associated with other concurrent anomalies. We report on a case of lumbar myelomeningocele with concomitant CNS malformations we followed up over a period of 15 years. A concise literature review has also been performed. The current report illustrates that the myelomeningocele is a complex anomaly that is commonly associated with a variety of other CNS malformations such as hydrocephalus and Chiari malformation. It may follow chronic progressive course with exacerbation of clinical symptoms in the long term. Patients that have undergone surgical correction of this spinal defect should be closely monitored over a long period of time because of the possibility of clinical deterioration of the concomitant anomalies such as hydrocephalus, Chiari malformation and siryngomyelia.