Nieuwe beeldvormingstechnieken in de voorspelling van de neurologische uitkomst van foetale hersenaandoeningen.
Year: 2025
Type: dissertation
Study design: Observational Study
Abstract: Processes dysregulating brain development in utero can cause specific congenital central nervous system (CNS) anomalies. The human brain develops rapidly in volume and complexity throughout gestation in a well-orchestrated, choreographed manner. Brain malformations result from aberrations in this chain of events, irrespective of the genetic, infectious, traumatic, ischemic, toxic, metabolic, or idiopathic trigger. Early detection of CNS anomalies and dedicated prenatal neuroimaging, currently performed with targeted neurosonography and prenatal MRI supported by genetic analysis, lead to improved parental counselling. Many of these malformations harbour underlying genetic abnormalities and are associated with poor neurodevelopmental outcomes and seizures. Some anomalies are even difficult for expert practitioners or even impossible to diagnose in utero. Many may only be detected late in pregnancy or after birth. Some cerebral anomalies have predictable outcomes, such as holoprosencephaly or spina bifida. However, for other conditions with a less predictable natural history such as mild ventriculomegaly, agenesis of the corpus callosum, and the Dandy-Walker continuum, parental counselling evokes more questions than clearcut answers. In the second chapter of this thesis, we aimed to improve the detection rate of corpus callosum abnormalities by using non-standard sonographic parameters in routinely acquired images during routine obstetric ultrasound scans. We were able to consistently identify and measure the pericallosal artery and its branches starting from 11 weeks of pregnancy. Our results showed a high accuracy in detecting the pericallosal vasculature in the first trimester. Furthermore, its presence and normal arrangement during the 11-14 week scan may be highly predictive of a normal corpus callosum development later in pregnancy. The mid-brain to falx ratio in the first trimester is a reliable and reproducible index, yet it has a low specificity and sensitivity in detecting agenesis of the corpus callosum. However, first-trimester mid-sagittal ultrasound images of the fetal head, such as they have been defined in the nuchal translucency screening program for chromosomal anomalies, hold the potential to identify a high-risk group for corpus callosum agenesis that may benefit from visualising the pericallosal artery from the first trimester and early second trimester onwards. In Chapter 3, we thoroughly and systematically investigated the clinical impact of developmental errors in the midbrain. The differentiation between isolated and non-isolated forms is crucial for conducting further neurological follow-up studies. Initially, we extensively examined a cohort of prenatally diagnosed cases of partial corpus callosum agenesis using neurosonography and fetal magnetic resonance imaging to describe its morphology and associated conditions. Non-isolated cases often present with genetic anomalies. Sonographic diagnosis of this condition requires improvement. Unlike in complete agenesis, indirect cranial signs often lack or are more subtle. Unfortunately, long-term perinatal outcome, even in isolated cases of partial corpus callosum agenesis, raises some concerns. Although 60% of prenatally diagnosed cases have a favourable outcome, they often experience mild to severe disabilities later in life, including speech disorders during school age, in addition to behavioural and motor deficits developing later on at school age. Today, we realise that partial agenesis of the corpus callosum harbours many conditions of heterogeneous origin. It may well be that etiological differentiation in large data sets may provide better insights intothe neurodevelopmental outcome of the different entities. Additionally, we assessed the long-term neurodevelopmental outcome in children identified with prenatal corpus callosum anomalies and aimed to address the discrepancies between pediatric and obstetrical counselling for corpus callosum anomalies. Isolated forms of corpus callosum anomalies were associated more frequently with impaired neurodevelopment compared to the existing literature. The existing fetal data could be more balanced, caused by a small number of prospective studies with few patients (less than 30 cases) and a mean follow-up of less than three years. This timeframe needs to be longer to investigate potential late-onset neurodevelopmental issues thoroughly. Consequently, predicting the overall outcome of corpus callosum anomalies in the prenatal setting is quite challenging, just relying on the outcomes of live-born children today. In our series, the normal outcome in isolated ACC and p-ACC cases was only 52.4% and 57.1%, respectively, which is notably lower than anticipated. Hence, parental counselling should be adjusted accordingly. In Chapter 4, we addressed prenatal imaging in fetal destructive brain pathology, focusing on congenital cytomegalovirus (cCMV) infection and intracranial haemorrhage. cCMV is the most common perinatal infection and a significant cause of sensorineural hearing loss, cerebral palsy, and neurodevelopmental disability. We could demonstrate that in primary seroconversion before 14 weeks of gestation and subsequent CMV PCR-negative amniotic fluid, late CMV infection rarely leads to sequelae. Nevertheless, after a mean follow-up of 4 years, mild audiological, visual, and neurodevelopmental impairment have been observed, unlike severe neonatal impairment. Therefore, parents with primary CMV infection before 14 weeks can be reassured after a negative CMVAF PCR. We further highlighted the need to largely explore all diagnostic modalities, such as amniocentesis, bi-weekly ultrasound and subsequent MRI, to capture the chronological progression and outcome of CMV-infected fetuses. We described a 95% sensitivity in detecting fetal brain abnormalities, and although most abnormalities are found early in the second trimester, new findings surface at subsequent scans. Nearly half (46%) of all patients with positive CMV PCR at 25 weeks progress to a severe clinical picture. For comparison, in 9% of patients only, the first abnormal signs were encountered by neurosonography just in the third trimester. In addition, the extremely high viral load in the amniotic fluid is considered a useful tool for prognostication, as there is a 75% chance for abnormal findings on neuro sonography and a 77% chance of abnormal outcomes. In a third small retrospective study, we evaluated the lamination pattern as a proxy for normal brain development before 28 weeks of gestation in fetuses with proven CMV infection by prenatal MRI and ultrasound. Focal disruption of lamination and an abnormal intermediate zone differentiated the severely affected CMV-infected foetuses from the non-affected ones. Finally, we reported on the perinatal mortality and postnatal morbidity of 48 fetuses with a prenatal diagnosis of intracranial haemorrhage (ICH) made in the late second or third trimester. Ventriculomegaly was the most common US finding for referral. Prenatal MRI adds to the initial ultrasound findings in 16.3%, revealing polymicrogyria or cortical dysplasia. A causal factor for ICH was found in 38.9%. In slightly more than half of the cases (52%), the pregnancy was interrupted upon parental request. Few data reports on the neurodevelopmental outcome in the case of prenatal ICH. MRI classification of detailed anatomical location, the extension of the lesion, and laterality of the parenchymal involvement are proposed as promising tools in the prediction of subsequent neurologic outcomes. In Chapter 5, we concluded that a virtual necropsy using NMR after pregnancy termination or neonatal death is as informative as a pathological investigation for brain anomalies. Virtual necropsy s accounts for a highly qualitative analysis of the brain, providing adequate insight into the individual fetal brain pathology for proper parental counselling in 97% of cases, particularly in instances of brain autolysis. Fusion imaging, which combines MRI and US images, has been successfully applied offline for the simultaneous visualisation and confirmation of in-utero brain pathology. Our study evaluated the clinical use of fusion imaging, data registration, matching, and volume navigation in cases of fetal brain pathology. Our findings indicate that the combination of real-time MRI and US images for fetal imaging and navigation is not only feasible but has the potential to facilitate a more comprehensive prenatal diagnosis. Additionally, fusion imaging serves as an effective educational tool for both MRI and US specialists, helping to improve their expertise in demonstrating anatomical details. While it may not reveal new findings beyond what can be observed by MRI or US separately, this technique significantly enriches the multidisciplinary assessment of conditions. Conclusion of this thesis: The limited prevalence of CNS anomalies significantly constrains training opportunities and the expertise of obstetricians. This thesis subscribes to the need to introduce cutting-edge imaging techniques to predict neurological outcomes of fetal brain disorders accurately. Parents confronted with prenatal CNS malformation should be referred promptly to a multidisciplinary consultation with leading experts in fetal neuroimaging (ultrasound and MRI), fetal neurology, and genetics. This proactive approach substantially enhances parental counselling and support.
Source: Lirias
Author: De Keersmaecker, Bart
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7112515870
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