Diagnostic accuracy of fetal choroid plexus length to head biometry ratio at 11 to 13 weeks for open spina bifida.

BACKGROUND: Open spina bifida is a major congenital anomaly with an estimated incidence of <1 in 1000. The diagnosis of open spina bifida is usually made during the second trimester, but first-trimester detection rate of spina bifida is increasingly reported. Recently, the mean choroid plexus length to occipitofrontal diameter ratio was reported to be increased in fetuses with open spina bifida. The ratio reflects the so-called dry brain effect caused by cerebrospinal fluid leakage and expansion of the choroid plexus into the lateral ventricles. The mean choroid plexus length to occipitofrontal diameter ratio appears to be a promising tool for early detection of open spina bifida, but its diagnostic accuracy is yet to be determined in a large cohort. OBJECTIVE: This study aimed to assess the predictive accuracy of mean choroid plexus length to occipitofrontal diameter ratio recorded at 11 to 13 weeks' gestation for the detection of open spina bifida. STUDY DESIGN: This was a retrospective cohort of patients treated in a tertiary referral center. Fetuses in which open spina bifida was detected at 16 to 24 weeks' gestation and normal fetuses were included in the cohort. Biparietal diameter and occipitofrontal diameter were measured in an axial view. The length of choroid plexus was measured along its longest diameter in the same plane. Ultrasound images were examined offline, and the operator was blinded to the clinical diagnosis. The predictive accuracy was evaluated using the area under the curve and positive and negative predictive values. RESULTS: We included 3300 pregnant women, of whom 24 (0.73%) had the fetuses affected by open spina bifida. The area under the curve values were 0.921 for mean choroid plexus length to occipitofrontal diameter ratio and 0.933 for its multiple of the median. Mean choroid plexus length to biparietal diameter ratio indicated similar results, with area under the curve values of 0.928 and 0.931 for raw ratio and multiple of the median ratio models, respectively. The optimal cutoffs of the mean choroid plexus to occipitofrontal diameter ratio and multiple of the median ratios were 0.662 and 1.263, respectively. The optimal mean choroid plexus to occipitofrontal diameter ratio and multiple of the median ratio cutoffs provided a positive predictive value of 90.9% and a negative predictive value of 99.6%. The number of affected spinal segments was significantly higher in fetuses with a ratio above 0.662 (P=.022). CONCLUSION: The mean choroid plexus length to occipitofrontal diameter ratio at 11 to 13 weeks' gestation is a promising tool for the prenatal detection of open spina bifida.

Interstitial Adipocytes in the Beagle Dog and New Zealand White Rabbit Choroid Plexus.

The choroid plexus (CP) produces cerebrospinal fluid and has epithelial, interstitial, and vascular compartments. The CP is a potential site of toxicity, and recognizing the normal microanatomy in different animal models is important for the pathologist. In preclinical studies with beagle dog and New Zealand white rabbits, we observed variable numbers of adipocytes in the CP interstitium of control and xenobiotic-treated animals. The adipocytes were unilocular and consistent morphologically with white adipose tissue. There was a striking variability in the number of adipocytes; however, the presence of adipocytes was not associated with other microscopic findings that would suggest a pathologic process. The morphology of adipocytes was reminiscent of what is observed normally in the interstitium of other tissues like skeletal muscle, bone marrow, and the subcutis. Therefore, we propose that the interstitial adipocytes not be recorded as a finding in preclinical studies unless the adipocytes are altered spontaneously (ie, lipoma) or after xenobiotic treatment.

Hindbrain morphometry and choroid plexus position in differential diagnosis of posterior fossa cystic malformations.

OBJECTIVE: To assess the differential diagnostic significance of a series of quantitative and qualitative variables of the cerebellar vermis in fetuses with posterior fossa cystic malformation, including Dandy-Walker malformation (DWM), vermian hypoplasia (VH) and Blake's pouch cyst (BPC). METHODS: This was a retrospective study of confirmed cases of DWM, VH and BPC, diagnosed at the Fetal Medicine and Surgery Unit of the Federico II University between January 2005 and June 2013 or the Fetal Medicine and Surgery Unit of G. Gaslini Hospital between July 2013 and September 2017. All included cases had good-quality three-dimensional (3D) volume datasets of the posterior fossa, acquired by transvaginal ultrasound through the posterior fontanelle. The midsagittal view of the posterior fossa was the reference view for the study. We assessed brainstem-tentorium angle and brainstem-vermis angle (BVA), as well as craniocaudal (CCVD) and anteroposterior (APVD) vermian diameters and vermian area (VA), which were normalized by biparietal diameter (BPD) to take into account gestational age (CCVD/BPD × 100, APVD/BPD × 100 and VA/BPD × 100, respectively). Finally, the position of the fourth ventricular choroid plexus (4VCP) was defined as normal ('up') or abnormal ('down'), relative to the roof/cyst inlet of the fourth ventricle. RESULTS: We analyzed 67 fetuses with posterior fossa malformations (24 cases of DWM, 13 of VH and 30 of BPC). The mean gestational age at diagnosis was 23.6 weeks. Regardless of gestational age, the BVA differed significantly between the three groups, and the VA/BPD was able to differentiate between VH and BPC. In differentiating between VH and BPC, the greatest areas under the receiver-operating characteristics curve were those for VA/BPD ratio. The 4VCP position was down in all cases of DWM and VH, while it was up in all cases of BPC. CONCLUSIONS: Our data support the concept that VA/BPD ratio and 4VCP position may be used to differentiate between DWM, VH and BPC in the fetus. In our series, the position of the 4VCP had the highest accuracy, but a larger number of VH cases should be evaluated to confirm that an up position of the 4VCP indicates BPC while a down position indicates DWM or VH. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Surgical anatomy of lateral recess in paediatric auditory brainstem implant patients and its clinical correlates including grades of flocculus.

INTRODUCTION: Auditory brainstem implant (ABI), a standard technique in treatment of profound sensorineural hearing loss in patients with neurofibromatosis 2, is now being increasingly employed in children with congenital bilateral sensorineural hearing loss, as in Michele's deformity. A detailed knowledge of the relevant surgical anatomy of the lateral recess and its anatomical landmarks including the flocculus, the choroid plexus and the root entry zones of facial-vestibulocochlear and glossopharyngeal-vagus nerve complexes and their anatomical variants is mandatory, as it is the conduit for electrode array placement. The placement of electrode may be eased or impeded by these variations. MATERIALS AND METHODS: Thirty-two children with congenital bilateral hearing loss underwent surgery through retromastoid suboccipital approach for placement of auditory brainstem implant. The preoperative anatomy was reviewed in detail during procedure and again later in the operative videos. RESULTS: The flocculus was classified into four grades based on its anatomy and relations. Among these, grade II (11 children) was the commonest while grade IV (five children) was least common. Choroid plexus was variable in size across grades of flocculus. Difficulty in defining the anatomy was significantly more (p value = 0.003) in the group with higher grade flocculus (grade III and IV) than in lower grade flocculus (grade I and II). CONCLUSION: The flocculus in these patients is classifiable into one of the four grades and the surgical nuances such as difficulty in defining the anatomy for placement of ABI are dependent on the characteristics exhibited by the floccular anatomy and relations.

The choroid plexus in health and in disease: dialogues into and out of the brain.

This article brings the choroid plexus into the context of health and disease. It is remarkable that the choroid plexus, composed by a monolayer of epithelial cells that lie in a highly vascularized stroma, floating within the brain ventricles, gets so little attention in major physiology and medicine text books and in the scientific literature in general. Consider that it is responsible for producing most of the about 150mL of cerebrospinal fluid that fills the brain ventricles and the subarachnoid space and surrounds the spinal cord in the adult human central nervous system, which is renewed approximately 2-3 times daily. As such, its activity influences brain metabolism and function, which will be addressed. Reflect that it contains an impressive number of receptors and transporters, both in the apical and basolateral sides of the epithelial cells, and as such is a key structure for the communication between the brain and the periphery. This will be highlighted in the context of neonatal jaundice, multiple sclerosis and Alzheimer's disease. Realize that the capillaries that irrigate the choroid plexus stroma do not possess tight junctions and that the blood flow to the choroid plexus is five times higher than that in the brain parenchyma, allowing for a rapid sensing system and delivery of molecules such as nutrients and metals as will be revised. Recognize that certain drugs reach the brain parenchyma solely through the choroid plexus epithelia, which has potential to be manipulated in diseases such as neonatal jaundice and Alzheimer's disease as will be discussed. Without further notice, it must be now clear that understanding the choroid plexus is necessary for comprehending the brain and how the brain is modulated and modulates all other systems, in health and in disease. This review article intends to address current knowledge on the choroid plexus, and to motivate the scientific community to consider it when studying normal brain physiology and diseases of the central nervous system. It will guide the reader through several aspects of the choroid plexus in normal physiology, in diseases characteristic of various periods of life (newborns-kernicterus, young adults-multiple sclerosis and the elder-Alzheimer's disease), and how sex-differences may relate to disease susceptibility.

Morphometry and microsurgical anatomy of Bochdalek's flower basket and the related structures of the cerebellopontine angle.

BACKGROUND: Bochdalek's flower basket (Bfb) is the distal part of the horizontal segment of the fourth ventricle's choroid plexus protruding through the lateral aperture (foramen of Luschka). The microsurgical anatomy of the cerebellopontine angle, fourth ventricle and its inner choroid plexus is well described in the literature, but only one radiological study has investigated the Bfb so far. The goal of the present study was to give an extensive morphometric analysis of the Bfb for the first time and discuss the surgically relevant anatomical aspects. METHOD: Forty-two formalin-fixed human brains (84 cerebellopontine angles) were involved in this study. Photomicrographs with scale bars were taken in every step of dissection to perform further measurements with Fiji software. The lengths and widths of the Bfb, rhomboid lip and lateral aperture of the fourth ventricle as well as the related neurovascular and arachnoid structures were measured. The areas of two sides were compared with paired t-tests using R software. Significance level was set at p < 0.05. RESULTS: Protruding choroid plexus was present in 77 cases (91.66%). In 6 cases (7.14%), the Bfb was totally covered by the rhomboid lip, and in one case (1.19%), it was absent. The mean width of the Bfb was 6.618 mm (2-14 mm), the mean height 5.658 mm (1.5-14 mm) and mean area 25.80 mm2 (3.07-109.83 mm2). There was no statistically significant difference between the two sides (p = 0.1744). The Bfb was in contact with 20 AICAs (23.80%), 6 PICAs (7.14%) and 39 vestibulocochlear nerves (46.42%). Arachnoid trabecules, connecting the lower cranial nerves to the Bfb or rhomboid lip, were found in 57 cases (67.85%). CONCLUSIONS: The Bfb is an important landmark during various surgical procedures. Detailed morphology, dimensions and relations to the surrounding neurovascular structures are described in this study. These data are essential for surgeons operating in this region.

The choroid plexus: a comprehensive review of its history, anatomy, function, histology, embryology, and surgical considerations.

INTRODUCTION: The role of the choroid plexus in cerebrospinal fluid production has been identified for more than a century. Over the years, more intensive studies of this structure has lead to a better understanding of the functions, including brain immunity, protection, absorption, and many others. Here, we review the macro- and microanatomical structure of the choroid plexus in addition to its function and embryology. METHOD: The literature was searched for articles and textbooks for data related to the history, anatomy, physiology, histology, embryology, potential functions, and surgical implications of the choroid plexus. All were gathered and summarized comprehensively. CONCLUSION: We summarize the literature regarding the choroid plexus and its surgical implications.

First trimester screening for holoprosencephaly with choroid plexus morphology ('butterfly' sign) and biparietal diameter.

OBJECTIVE: The aim of this study was to determine whether choroid plexus morphology ('butterfly' sign) and biparietal diameter (BPD) are effective sonographic screening tools for holoprosencephaly (HPE) in the first trimester. METHODS: An axial view of the fetal head was obtained routinely to determine the presence of the 'butterfly' sign in pregnancies presenting for sonographic screening at 11-13 weeks of gestation. The same view was also used to obtain BPD measurements. The definitive diagnosis of HPE was established by the sonographic demonstration of an anterior cerebral monoventricular cavity and thalamic fusion. RESULTS: During a 9-year study period, 11 068 live fetuses were screened. There were 11 cases of HPE (prevalence 1/1006); all of them were detected by demonstration of an absent 'butterfly' sign with no false-positive cases. The BPD was less than the 5th percentile in 40% of the cases. CONCLUSIONS: The 'butterfly' sign appears to be a highly sensitive marker for HPE in the first trimester. On the other hand, BPD measurements had a lower sensitivity, implying that microcephaly is not a prominent first-trimester feature in these cases. Incorporation of the 'butterfly' sign into the first trimester anatomy scan is simple and can facilitate the identification of the vast majority of fetuses with HPE in the first trimester.

Molecular heterogeneity in the choroid plexus epithelium: the 22-member γ-protocadherin family is differentially expressed, apically localized, and implicated in CSF regulation.

The choroid plexus (CP) epithelium develops from the ependyma that lines the ventricular system, and plays a critical role in the development and function of the brain. In addition to being the primary site of CSF production, the CP maintains the blood-CSF barrier via apical tight junctions between epithelial cells. Here we show that the 22-member γ-protocadherin (γ-Pcdh) family of cell adhesion molecules, which we have implicated previously in synaptogenesis and neuronal survival, is highly expressed by both CP epithelial and ependymal cells, in which γ-Pcdh protein localization is, surprisingly, tightly restricted to the apical membrane. Multi-label immunostaining demonstrates that γ-Pcdhs are excluded from tight junctions, basolateral adherens junctions, and apical cilia tufts. RT-PCR analysis indicates that, as a whole, the CP expresses most members of the Pcdh-γ gene family. Immunostaining using novel monoclonal antibodies specific for single γ-Pcdh proteins shows that individual epithelial cells differ in their apically localized γ-Pcdh repertoire. Restricted mutation of the Pcdh-γ locus in the choroid plexus and ependyma leads to significant reductions in ventricular volume, without obvious disruptions of epithelial apical-basal polarity. Together, these results suggest an unsuspected role for the γ-Pcdhs in CSF production and demonstrate a surprising molecular heterogeneity in the CP epithelium.

Bochdalek's flower basket: applied neuroimaging morphometry and variants of choroid plexus in the cerebellopontine angles.

INTRODUCTION: Protrusions of fourth ventricular choroid plexus through the foramina of Luschka are called 'Bochdalek's flower basket' (BochFB). The bulbous terminal expansions (cornucopiae) extend into the cerebellopontine angle (CPA) cisterns. We studied and reviewed the normal imaging anatomy, morphometry and anatomical variants of BochFB. METHODS: We retrospectively analysed normal brain imaging findings on axial pre- and post-contrast CT scans and enhanced axial T1-weighted MRIs of 200 patients. We assessed BochFB for: (a) calcification, (b) lateral extension, (c) enhancement pattern, (d) cornucopiae shape, (e) symmetry and (f) proximity to tortuous vertebral arteries and morphometry of cornucopiae size and length of BochFB limbs. RESULTS: BochFB calcification was found in 38 % of patients aged over 51 years. Lateral extension of BochFB into the CPA cistern was prominent in 75 % on CT and 96 % on MRI. The mean length of these extensions was 23.6 mm. BochFB enhanced strongly in 47 % on CT and 66 % on MRI. The BochFB cornucopiae were bulbous in 51 % on CT and 54 % on MRI. The mean width of bulbous cornucopiae was 3.5 mm. Bilateral BochFB symmetry was found in 71 % on CT and 80 % on MRI. Six to 8 % of tortuous left vertebral arteries were close to BochFB. CONCLUSION: The cornucopiae are particularly well demonstrated on post-contrast MRI. However several sources of error in image interpretation may arise when imaging the normal BochFB on routine head CT and MRI. Difficulties in analysis arise especially on CT because of physiologic calcification, asymmetry, and the bulbous cornucopiae being mistaken for aneurysms.

Demonstration of fourth ventricular choroid plexus on neonatal cranial ultrasonography.

The choroid plexus of the fourth ventricle can be identified on neonatal cranial US via the mastoid fontanelle, particularly when transducers of high frequency are used. Its presence as a normal, echogenic structure might not be appreciated by all sonographers. It should not be mistaken for vermian hemorrhage or clotted blood within the fourth ventricle or cisterna magna.

Choroid plexus: normal size criteria on neuroimaging.

PURPOSE: The lack of a well-recognized normal size criterion for the choroid plexus makes small or diffuse choroid plexus pathologies difficult to recognize. The purpose of this study was to determine the normal size of the choroid plexus in the pediatric population utilizing magnetic resonance imaging (MR) and ultrasound (US). As volume measurement across multiple slices is a laborious process, we wanted to propose a simple clinical tool that is easy to use, reproducible, and quick to obtain measurements. METHODS: This study retrospectively evaluated choroid plexus size in 90 children between the ages of 0 and 16. To determine the choroid plexus thickness, a total of 97 studies (71 MRIs and 26 Ultrasounds) were reviewed, from children without any signs of choroid plexus pathology; 6 measurements were taken from MR studies, and 3 measurements were taken from US studies. Averages and ranges of choroid plexus thickness were computed across age groups and gender. RESULTS: Across all ages, the mean choroid plexus thickness in the lateral ventricles was found to be 3.4, 3.3, and 3.1 mm in the axial, coronal, and sagittal views; 3.2 mm in the temporal horns; 2.5 mm in the fourth ventricle with the lateral limb of the choroid plexus in the fourth ventricle measuring 11.3 mm in length. No trends were observed with respect to age subgroups or gender. CONCLUSION: Choroid plexus thickness on average was 3.2 mm in the lateral ventricles and 2.5 mm in the fourth ventricle.

Epithelial pathways in choroid plexus electrolyte transport.

A stable intraventricular milieu is crucial for maintaining normal neuronal function. The choroid plexus epithelium produces the cerebrospinal fluid and in doing so influences the chemical composition of the interstitial fluid of the brain. Here, we review the molecular pathways involved in transport of the electrolytes Na+, K+, Cl-, and HCO3(-)across the choroid plexus epithelium.

Fetal brain asymmetry: in utero sonographic study of normal fetuses.

OBJECTIVE: The objective of the study was to evaluate the magnitude of normal fetal brain asymmetry. STUDY DESIGN: This was a prospective study. Normal fetuses between 19-28 weeks of gestation were studied. The cerebral atria, occipital cortex, and hemispheres in both sides were measured. The difference between each side was evaluated and was correlated with sex, head biometry, and estimated weight. RESULTS: Four hundred six fetuses were studied. Mean atrial width was larger in the males and on the left side (5.2% and 6.5%, respectively). Mean cortical width was 2.6% larger in males but 5.5% thinner on the left side. Mean hemisphere width was larger in males and on the left side (2.3% and 1.5%, respectively). The atria and the cortex presented an inverse relationship regarding fetal growth parameters. CONCLUSION: Brain asymmetry represents normal fetal brain developmental phenomena. It is sex dependent and lateralized in most cases to the left. Lateralization was more accentuated in males.

Choroid plexus and the blood-cerebrospinal fluid barrier in disease.

The choroid plexus (CP) forming the blood-cerebrospinal fluid (B-CSF) barrier is among the least studied structures of the central nervous system (CNS) despite its clinical importance. The CP is an epithelio-endothelial convolute comprising a highly vascularized stroma with fenestrated capillaries and a continuous lining of epithelial cells joined by apical tight junctions (TJs) that are crucial in forming the B-CSF barrier. Integrity of the CP is critical for maintaining brain homeostasis and B-CSF barrier permeability. Recent experimental and clinical research has uncovered the significance of the CP in the pathophysiology of various diseases affecting the CNS. The CP is involved in penetration of various pathogens into the CNS, as well as the development of neurodegenerative (e.g., Alzheimer´s disease) and autoimmune diseases (e.g., multiple sclerosis). Moreover, the CP was shown to be important for restoring brain homeostasis following stroke and trauma. In addition, new diagnostic methods and treatment of CP papilloma and carcinoma have recently been developed. This review describes and summarizes the current state of knowledge with regard to the roles of the CP and B-CSF barrier in the pathophysiology of various types of CNS diseases and sets up the foundation for further avenues of research.

Improving Choroid Plexus Segmentation in the Healthy and Diseased Brain: Relevance for Tau-PET Imaging in Dementia.

Recent studies have revealed the possible role of choroid plexus (ChP) in Alzheimer's disease (AD). T1-weighted MRI is the modality of choice for the segmentation of ChP in humans. Manual segmentation is considered the gold-standard technique, but given its time-consuming nature, large-scale neuroimaging studies of ChP would be impossible. In this study, we introduce a lightweight segmentation algorithm based on the Gaussian Mixture Model (GMM). We compared its performance against manual segmentation as well as automated segmentation by Freesurfer in three separate datasets: 1) patients with structural MRIs enhanced with contrast (n = 19), 2) young healthy subjects (n = 20), and 3) patients with AD (n = 20). GMM outperformed Freesurfer and showed high similarity with manual segmentation. To further assess the algorithm's performance in large scale studies, we performed GMM segmentations in young healthy subjects from the Human Connectome Project (n = 1,067), as well as healthy controls, mild cognitive impairment (MCI), and AD patients from the Alzheimer's Disease Neuroimaging Initiative (n = 509). In both datasets, GMM segmented ChP more accurately than Freesurfer. To show the clinical importance of accurate ChP segmentation, total AV1451 (tau) PET binding to ChP was measured in 108 MCI and 32 AD patients. GMM was able to reveal the higher AV1451 binding to ChP in AD compared with MCI. Our results provide evidence for the utility of the GMM in accurately segmenting ChP and show its clinical relevance in AD. Future structural and functional studies of ChP will benefit from GMM's accurate segmentation.

Central neurocytoma originating in third ventricle with expansion into the cerebral aqueduct and fourth ventricle: Case report and review of literature.

BACKGROUND: Central Neurocytomas (CNs) are rare brain tumors, making up less than 1% of all primary tumors within the CNS. They are commonly located in the lateral ventricles, and often present with visual changes and symptoms of obstructive hydrocephalus. Histopathology shows characteristics similar to ependymomas and oligodendrogliomas, however tumor cells display neuronal differentiation, and immunohistochemical stains typically for synaptophysin. Gross total resection is the most important prognostic indicator of survival. CASE DESCRIPTION: We describe the case of a 48-year-old male with a CN originating in the third ventricle with expansion through the cerebral aqueduct into the fourth ventricle. He presented with bi-frontal headaches, imaging revealed an avidly enhancing tumor occupying the inferior third ventricle, cerebral aqueduct, with expansion into the fourth ventricle. An interhemispheric craniotomy with a transcallosal transchoroidal approach to the third ventricle was performed, this provided a trajectory that paralleled the long axis of the tumor. Postoperative imaging confirmed a near total resection with linear residual enhancement on the anterior wall of the fourth ventricle. Intensity modulated radiotherapy was performed, 7-month follow-up imaging was clean. CONCLUSION: CNs are rare brain tumors, most commonly located within the lateral ventricles. We describe a rare case of a CN spanning from the third ventricle into the cerebral aqueduct and fourth ventricle. To our knowledge, this is only the fourth reported case of such a tumor. Surgical approach must be carefully selected, as gross total resection is the most important prognostic indicator.

Surgical anatomy and surgical approaches to the lateral ventricles.

This study focuses on the surgical approaches to intraventricular tumors which have developed within the cavity of the lateral ventricle. The first section is dedicated to embryology and describes the wrapping of the telencephalic vesicles around the thalamus and the morphogenesis of basal nuclei and commissures. In the second section, the anatomy of the lateral ventricles is described, along with their arterial and venous vasculature, their relationship with the eloquent cortical areas and cortical sulci, and their relationship with white matter fascicles, especially the optic radiations. In the third part, the main surgical approaches to the frontal horn, to the ventricular atrium and to the temporal horn are detailed.