Search

Objective: To formulate a classification system for foetal cortical formation abnormalities (CFAs) based on in utero magnetic resonance (iuMR) appearances and trial it in 356 cases., Methods: This retrospective study included all cases of foetal CFA diagnosed between 2000 and 2017 from seven centres in Italy and UK. All of the studies were reviewed by a panel of paediatric neuroradiologists experienced in iuMR with the aid of an algorithm designed to categorise the abnormalities., Results: Consensus expert review confirmed 356 foetuses with CFA and the first level of classification distinguished bilateral CFA (229/356-64%) from unilateral CFA (127/356-36%) cases with sub-classification of the bilateral cases into asymmetric (65/356-18%) and symmetric (164/356-46%) involvement. There was a statistically significant excess of foetuses with small head size, e.g. 17% of the cohort had a bi-parietal diameter < 3rd centile. There was a small but statistically significant excess of males in the cohort. Further categorisation was made on fine anatomical structure., Conclusions: It is often not possible to classify foetal CFA using the principles and nomenclature used in paediatric neuroradiology. We have created a classification system for foetal CFA based on the analysis of 356 cases and believe that this will assist future research designed to correlate ante-natal and post-natal imaging features and understand the clinical sequelae of CFA described in utero., Key Points: • We describe a morphological classification system of foetal brain cortical formation abnormalities that can be used in clinical practice. • This classification system can be used in future research studies to evaluate the long-term imaging and clinical outcomes of foetal brain cortical formation abnormalities in 17- to 38-week gestational age range. • The practical value of the work is in providing a framework and language to look for imaging clues that may differentiate between different CFA in further studies.

Methods: From the generally accepted data on the morphogenesis of the brain, the principles for the classification of brain malformations are given, and the salient features of each malformation which may be considered as independent from the developmental stage and therefore practical for MR imaging in the fetus after mid-gestation, are discussed., Results and Discussion: However, the correlation with the clinical results in 150 cases of malformations out of a series of more than 1,000 cases of MR fetal brain imaging, demonstrates that beside the main, well-defined malformative entities, a significant degree of uncertainty remains. As the indication of further imaging is mainly based on the ultrasonographic findings, cases that are not identified as abnormal by US are not submitted to MRI (partial commissural agenesis and malformations of cortical development). A striking discrepancy exists between the findings of US and those of MRI, in the specific instance of the disorders of the posterior fossa (cystic malformations versus mega cisterna magna versus cerebellar defects), which may be only partly corrected by the use of strict anatomic criteria. Similar difficulties are observed for the diagnosis of nondestructive microcephaly., Conclusion: Long-term prospective longitudinal clinical-radiological studies of these groups of patients are needed.

Introduction: It has been recognized that the morphological fetal CNS findings detected in early development are not always the final features: occasionally they may not be determined in diagnosis and may change developmentally or chronologically during the fetal life in utero., Discussion: Certain factors of the fetal chronology of CNS anomalies can cause irreversible changes during fetal life. These include: significant delay in the neuronal maturation process in fetal hydrocephalus developed in clinico-embryological stage II of the Perspective Classification of Congenital Hydrocephalus (PCCH), secondary neural injury in the intactly developing spinal cord above the neural placode in fetuses with spina bifida aperta (myeloschisis), histological "evolution" of tumors or dysgenetic CNS, and deformity of the normally developed intracranial or intraspinal CNS structures. Considering the current status of fetal surgery in general and technical advances promising improved outcomes, fetal neurosurgery can also be applied to the above-mentioned progressive pathology or pathophysiology in the fetal CNS. However, since the failure of the first trial of fetal neurosurgery in the 1980s, the prerequisites have still not been clarified. In order to use advanced neurosurgery techniques in the management of fetal CNS anomalies, these prerequisites have to be established.

Introduction: The sophistication of prenatal brain imaging (US, MRI) has awakened interest in fetal neuropathology and changed the concept of brain malformations, defined until recently through descriptive terms and considered as senseless accidents of development. Usually, most CNS malformations are documented from a clinical and radiological point of view. However, only a detailed neuropathological study permits their exact phenotype to be established, which is instrumental for a precise diagnosis and cause analysis., Discussion: After pregnancy termination for fetal malformations (or prenatal death) full autopsy and frozen tissue storage for DNA analysis are mandatory. The delay between death and autopsy should be limited because of the rapid autolysis of brain tissue. Detailed neuropathological and cause analysis have made it clear that each brain malformation is phenotypically "unique" and causally heterogeneous. Molecular studies have shown that mutations in different genes involved in a signaling pathway may result in a similar malformation. In addition, signaling pathways may be a possible target of toxic agents, which will mimic the genetic causes of malformations. These findings have raised growing interest in the early patterning of the developing nervous system in humans and its molecular controlling pathways. Consequently, brain malformations are now evaluated with special regard to their mechanism and cause analysis, considering fetal, maternal, and placental pathology. The predictive value of this multidisciplinary approach is now well demonstrated and has led, in some conditions, to gene identification, which is crucial for genetic counseling. It permits a prenatal molecular diagnosis as early as the 10-12th gestational week on chorionic villus sampling.

Introduction: Each of the processes involved in the development of the central nervous system is under genetic control and some mutations are responsible for severe malformations. For example, holoprosencephaly is associated with HPE genes, hydrocephalus with L1-CAM and lissencephaly with LIS-1., Discussion: Molecular genetics has brought new insights into the etiology and pathogenesis of nervous system malformations and has provided new tools for accurate prenatal diagnosis.