Search Results (12)

Objectives: The increasing use of fetal MRI has increased the diagnosis of posterior fossa malformations, yet the long-term neurodevelopmental outcomes of affected fetuses remain unclear. This study aims to examine the long-term neurodevelopmental outcomes of fetuses with structural posterior fossa malformation diagnosed on fetal MRI. Methods: A historical cohort study was conducted at a single tertiary referral center, including fetuses diagnosed with structural posterior fossa malformations and apparently healthy fetuses who underwent fetal brain MRI between 2011 and 2019. Maternal, pregnancy, and newborn characteristics were compared between groups, alongside long-term neurodevelopmental outcomes using the Vineland Adaptive Behavior Scales II (VABS-II) questionnaire. This included an extensive assessment of malformation types, additional structural, genetic, or neurodevelopmental anomalies, and outcomes. Results: A total of 126 fetuses met the inclusion criteria, of which 70 were apparently healthy fetuses, and 56 had structural posterior fossa malformations. Among the latter, 18 pregnancies were terminated, 4 resulted in neonatal death, and 11 were lost to follow-up. No significant differences were found in the overall neurodevelopmental outcomes between fetuses with structural posterior fossa malformation (93.4 ± 19.0) and apparently healthy fetuses (99.8 ± 13.8). Motor skills scores were lower among fetuses with structural posterior fossa malformations (87.7 ± 16.5 vs. 99.3 ± 17.2, p = 0.01) but remained within the normal range. Conclusion: Fetuses with structural posterior fossa malformations may exhibit normal long-term neurodevelopmental outcomes if no additional anomalies are detected during thorough prenatal screening that includes proper sonographic, biochemical and genetic screening, as well as fetal MRI. Further research with larger cohorts and longer-term assessments is recommended to validate these findings and support clinical decision-making. Full article

Background/Objective: The accurate diagnosis of congenital central nervous system abnormalities is critical to pre- and postnatal prognostication and management. When an abnormality is found in the posterior fossa of the fetal brain, parental counseling is challenging because of the wide spectrum of clinical and neurodevelopmental outcomes in patients with Dandy–Walker (DW) spectrum posterior malformations. The objective of this study was to evaluate the utility of biometric measurements obtained from fetal magnetic resonance imaging (MRI) to facilitate the prenatal differentiation of Dandy–Walker (DW) spectrum malformations, including vermian hypoplasia (VH), Blake’s pouch cyst (BPC), and classic Dandy–Walker malformation (DWM). Methods: This retrospective single-center study evaluated 34 maternal–infant dyads referred for fetal MRI evaluation of suspected DW spectrum malformations identified on antenatal ultrasound. Radiologists took posterior fossa measurements, including the vermis anteroposterior (AP) diameter, vermis height (VH), and tegmento–vermian angle (TVA). The posterior fossa, fourth ventricle, and cisterna magna were classified as normal, large, or dilated. The postnatal imaging findings were evaluated for concordance. The acquired values were compared between the groups and with normative data. The genetic testing results are reported when available. Results: A total of 27 DW spectrum fetal MRI cases were identified, including 7 classic DWMs, 14 VHs, and 6 BPCs. The TVA was significantly higher in the DWM group compared with the VH and BPC groups (p < 0.001). All three groups had reduced AP vermis measurements for gestational age compared with normal fetal brains, as well as differences in the means across the groups (p = 0.002). Conclusions: Biometric measurements derived from fetal MRI can effectively facilitate the prenatal differentiation of VH, BPC, and classic DWM when assessing DW spectrum posterior fossa lesions. Standardizing biometric measurements may increase the diagnostic utility of fetal MRI and facilitate improved antenatal counseling and clinical decision-making. Full article

This retrospective cohort study analyzed 7870 pregnant women, including 2269 with confirmed Zika virus (ZIKV) infection and 5601 without Zika infection, along with their fetuses and newborns. Data were sourced from multiple databases in the state of Rio de Janeiro, Brazil. A propensity score model was employed to control confounding factors and stratify outcomes by pregnancy trimester. Among ZIKV+ pregnant women, 49 cases of congenital microcephaly or congenital nervous system (CNS) abnormalities were identified (2.16%, or 193.9 cases in 10,000 live births), whereas 44 cases were identified among ZIKV− women (0.78%, or 71.4 cases in 10,000 live births). Multivariable analysis yielded an odds ratio of 2.46 (95% CI 1.30–4.64) overall, with 4.29 (95% CI 1.93–9.53) in the first trimester, 5.29 (95% CI 1.08–25.95) in the second trimester, and 0.68 (95% CI 0.21–2.14) in the third trimester. The most frequent findings among ZIKV+ cases included intracranial calcifications, ventriculomegaly, posterior fossa malformations, reduced brain volume, corpus callosum malformations, cortex dysplasia, lissencephaly, and pachygyria. Ophthalmologic abnormalities were detected in 55.5% of cases, and brainstem auditory evoked potential anomalies were reported in 33.3%. ZIKV infection can result in structural or functional anomalies. Given the absence of specific treatment for congenital Zika syndrome (CZS), clinical care should prioritize monitoring and managing neurological, motor, auditory, visual, and orthopedic disorders in all children with in utero ZIKV exposure, especially during the first and second trimesters of pregnancy. Full article

Background: In patients with Chiari 1.5 malformation (CM1.5), a more aggressive disease course and an increased association with craniovertebral junction (CVJ) anomalies has been suggested. The best management of this subgroup of patients is not clearly defined, also due to the lack of specific series elucidating this anomaly’s peculiar characteristics. Methods: We evaluated a series of 33 patients (25 females, 8 males; mean age at surgery: 13 years) fulfilling the criteria for Chiari 1.5 diagnosis who underwent posterior fossa decompression and duraplasty (PFDD) between 2006 and 2021. Results: Headache was present in all children, five presented central apnea, five had dysphagia, and three had rhinolalia. Syringomyelia was present in 19 (58%) children. Twenty patients (61%) showed various CVJ anomalies, but only one child presented instability requiring arthrodesis. The mean tonsil displacement below the foramen magnum was 19.9 mm (range: 12–30), without significant correlation with the severity of symptoms. Syringomyelia recurred or was unchanged in three patients, and one needed C1–C2 fixation. The headache disappeared in 28 children (84%). Arachnoid opening and tonsil coagulation or resection was necessary for 19 children (58%). Conclusions: In our pediatric CM series, the need for tonsil resection or coagulation was higher in CM1.5 children due to a more severe crowding. Full article

Background: Developmental and epileptic encephalopathies (DEE) encompass a group of rare diseases with hereditary and genetic causes as well as acquired causes such as brain injuries or metabolic abnormalities. The phosphofurin acidic cluster sorting protein 2 (PACS2) is a multifunctional protein with nuclear gene expression. The first cases of the recurrent c.625G>A pathogenic variant of PACS2 gene were reported in 2018 by Olson et al. Since then, several case reports and case series have been published. Methods: We performed a systematic review of the PUBMED and SCOPUS databases using Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Our search parameters included DEE66 with a pathogenic PACS2 gene p.Glu209Lys mutation published cases to which we added our own clinical experience regarding this pathology. Results: A total of 11 articles and 29 patients were included in this review, to which we added our own experience for a total of 30 patients. There was not a significant difference between sexes regarding the incidence of this pathology (M/F: 16/14). The most common neurological and psychiatric symptoms presented by the patients were: early onset epileptic seizures, delayed global development (including motor and speech delays), behavioral disturbances, limited intellectual capacity, nystagmus, hypotonia, and a wide-based gait. Facial dysmorphism and other organs’ involvement were also frequently reported. Brain MRIs evidenced anomalies of the posterior cerebellar fossa, foliar distortion of the cerebellum, vermis hypoplasia, white matter reduction, and lateral ventricles enlargement. Genetic testing is more frequent in children. Only 4 cases have been reported in adults to date. Conclusions: It is important to maintain a high suspicion of new pathogenic gene variants in adult patients presenting with a characteristic clinical picture correlated with radiologic changes. The neurologist must gradually recognize the distinct evolving phenotype of DEE66 in adult patients, and genetic testing must become a scenario with which the neurologist attending adult patients should be familiar. Accurate diagnosis is required for adequate treatment, genetic counseling, and an improved long-term prognosis. Full article

Background and Objectives: The present study aims to provide prenatal 2-dimensional ultrasonographic (2D-US) nomograms of the normal cerebellar area. Materials and Methods: This is a prospective cross-sectional analysis of 252 normal singleton pregnancies, ranging from 13 to 39 weeks of gestation. The operator performed measurements of the fetal cerebellar area in the transverse plane using 2D-US. The relationship between cerebellar area and gestational age (GA) was determined through regression equations. Results: A significant, strong positive correlation was investigated between the cerebellar area with GA (r-value = 0.89), and a positive correlation indicates that with increasing GA, the cerebellar area increased in all the participants of the study. Several 2D-US nomograms of the normal cerebellar area were provided, and an increase of 0.4% in the cerebellar area each week of GA was reported. Conclusions: We presented information on the typical dimensions of the fetal cerebellar area throughout gestation. In future studies, it could be evaluated how the cerebellar area changes with cerebellar abnormalities. It should be established if calculating the cerebellar area in addition to the routine transverse cerebellar diameter may help in discriminating posterior fossa anomalies or even help to identify anomalies that would otherwise remain undetected. Full article

A rare, uncommon disorder called PHACE(S) (P-posterior fossa anomalies, H-hemangioma, A-arterial anomalies, C-cardiac anomalies, E-eye anomalies, and S-sternal cleft) of unknown etiology was rarely reported. Children are susceptible to developing PHACE(S) syndrome from the moment they are born. It may be challenging for a physician to appropriately diagnose and treat children with PHACE due to the multifaceted nature of the disease and the extensive range of consequences that may be associated with it. A one-month-old newborn girl was admitted to hospital with extensive, multiple facial infantile hemangiomas, ulceration of the lower lip hemangioma-like lesion, cardiovascular, sternal, and neurological concomitant malformations. Five days following the initial application of the medication, systemic treatment with propranolol and topical treatment with silver sulfadiazine produced their first noticeable benefits. The lip ulceration was mostly healed and facial hemangioma started to regress. The regression continued under therapy and this effect persists for 6 months since Propranolol therapy ended. No cardiovascular or neurological clinical events have been registered during follow-up. The present case has three peculiarities: (1) high number of facial hemangiomas; (2) presence of subependymal cyst not yet reported in the literature associated with PHACE syndrome; and (3) lack of cardiovascular events during therapy knowing that these events frequently appear in PHACE syndrome patients. Full article

Brain abnormalities detected in fetal life are being increasingly recognized. Child neurologists are often involved in fetal consultations, and specific fetal neurology training has been implemented in many countries. Pediatric neurologists are asked to examine the data available and to contribute to the definition of the long-term outcomes. Ventriculomegaly, posterior fossa malformations, and agenesis/dysgenesis of corpus callosum are among the most common reasons for antenatal neurological consultations. Fetuses with central nervous system and extra-CNS anomalies should ideally be managed in secondary/tertiary hospitals where obstetricians who are experts in fetal medicine and pediatric specialists are available. Obstetricians play a critical role in screening, performing detailed neurosonography, and referring to other specialists for additional investigations. Clinical geneticists are frequently asked to propose diagnostic tests and counsel complex fetal malformations whose phenotypes may differ from those during postnatal life. Advances in fetal MRI and genetic investigations can support the specialists involved in counseling. Nevertheless, data interpretation can be challenging, and it requires a high level of expertise in a multidisciplinary setting. Postnatally, child neurologists should be part of an integrated multidisciplinary follow-up, together with neonatologists and pediatricians. The neurodevelopmental outcomes should be assessed at least up to school age. Children should be evaluated with formal tests of their gross motor, cognitive, language, fine motor/visuo-perceptual skills, and their behavior. In this perspective, fetal neurology can be regarded as the beginning of a long journey which continues with a prolonged, structured follow-up, support to the families, and transition to adult life. A review of the most common conditions is presented, along with the long-term outcomes and a proposal of the neurodevelopmental follow-up of children with CNS malformation which are diagnosed in uterus. Full article

This paper describes the contemporary state of knowledge regarding processes that regulate normal development of the embryonic–fetal central nervous system (CNS). The processes are described according to the developmental timetable: dorsal induction, ventral induction, neurogenesis, neuronal migration, post-migration neuronal development, and cortical organization. We review the current literature on CNS malformations associated with these regulating processes. We specifically address neural tube defects, holoprosencephaly, malformations of cortical development (including microcephaly, megalencephaly, lissencephaly, cobblestone malformations, gray matter heterotopia, and polymicrogyria), disorders of the corpus callosum, and posterior fossa malformations. Fetal ventriculomegaly, which frequently accompanies these disorders, is also reviewed. Each malformation is described with reference to the etiology, genetic causes, prenatal sonographic imaging, associated anomalies, differential diagnosis, complimentary diagnostic studies, clinical interventions, neurodevelopmental outcome, and life quality. Full article

Fetal magnetic resonance imaging (MRI) has become a widely used tool in clinical practice, providing increased accuracy in prenatal diagnoses of congenital abnormalities of the brain, allowing for more accurate prenatal counseling, optimization of perinatal management, and in some cases fetal intervention. In this article, a brief description of how fetal ultrasound (US) and fetal MRI are used in clinical practice will be followed by an overview of the most common reasons for referral for fetal MRI of the brain, including ventriculomegaly, absence of the cavum septi pellucidi (CSP) and posterior fossa anomalies. Full article

Background and Objectives: A rare case of cor triatriatum sinistrum in combination with anomalies in the atrial septum and in the right atrium of a 60-year-old female body donor is described here. Materials and Methods: In addition to classical dissection, ultrasound and magnetic resonance imaging, computer tomography and cinematic rendering were performed. In a reference series of 59 regularly formed hearts (33 men, 26 women), we looked for features in the left and right atrium or atrial septum. In addition, we measured the atrial and ventricular wall thickness in 15 regularly formed hearts (7 men, 8 women). Results: In the case described, the left atrium was partly divided into two chambers by an intra-atrial membrane penetrated by two small openings. The 2.5 cm-high membrane originated in the upper level of the oval fossa and left an opening of about 4 cm in diameter. Apparently, the membrane did not lead to a functionally significant flow obstruction due to the broad intra-atrial communication between the proximal and distal chamber of the left atrium. In concordance with this fact, left atrial wall thickness was not elevated in the cor triatriatum sinistrum when compared with 15 regularly formed hearts. In addition, two further anomalies were found: 1. the oval fossa was deepened and arched in the direction of the left atrium; 2. the right atrium showed a membrane-like structure at its posterior and lateral walls, which began at the lower edge of the oval fossa. It probably corresponds to a strongly developed eustachian valve (valve of the inferior vena cava). Conclusions: The case described suggests that malformations in the development of the atrial septum and in the regression of the valve of the right sinus vein are involved in the pathogenesis of cor triatriatum sinistrum. Full article

A syndrome of multiple paragangliomas/pheochromocytomas, somatostatinoma, and polycythemia due to somatic mosaic gain-of-function mutation of EPAS1, encoding HIF-2α, was previously described. HIF-2α has been implicated in endochondral and intramembranous ossification. Abnormal bone growth of the skull base may lead to Chiari malformation type I. We report two cases of EPAS1 gain-of-function mutation syndrome with Chiari malformation and developmental skull base anomalies. Patients were referred to the Section on Medical Endocrinology, Eunice Kennedy Shriver NICHD, NIH for evaluation of recurrent and metastatic paragangliomas or pheochromocytoma. The syndrome was confirmed genetically by identification of the functional EPAS1 gain-of-function mutation in the resected tumors and circulating leukocytes. Both patients were confirmed for characteristics of EPAS1 gain-of-function mutation syndrome by complete blood count (CBC), plasma biochemistry, and computed tomography (CT) of the abdomen and pelvis. Chiari malformation type I and abnormal bony development of the posterior fossa was found on MRI and CT of the head. The present study implicates EPAS1 mutations in abnormal posterior fossa development resulting in Chiari malformation type I. Full article