The hidden story of the fourth ventricular choroid plexus: the flower basket of an old anatomist…

…where ‘flower basket’ refers to the most lateral terminal part of the fourth ventricular choroid plexus (4V-CP), which protrudes through the foramina of Luschka, and the ‘old anatomist’ is the Bohemian, Vincent Alexander Bochdalek (1801–1883), who described, in addition to the normal and abnormal appearance of other anatomical structures, this particular region of the 4V-CP. I decided to dedicate this Editorial to the 4V-CP and, more generally, to the posterior fossa, in order to highlight that the more we look into this anatomical region the more we piece together the puzzle of its normal and abnormal development. One of the latest discoveries, emerging from research carried out postnatally and in animal models, is that the role of the 4V-CP is more important than previously realized in terms of both developmental function and diagnostic potential. It has been demonstrated that all choroid plexuses are actively involved in the development, homeostasis and repair of the central nervous system through the production of trophic and angiogenic factors, chemorepellents and carrier proteins, which are then released in the cerebrospinal fluid playing an important role in the control of neuronal differentiation1-4. At the same time, recent research, carried out in the fetus using high-resolution ultrasound, has revealed that the position of the 4V-CP plays a key role in the differential diagnosis of posterior fossa anomalies5, 6. Therefore, it seems that the evidence is piling up to support the need for detailed evaluation of the 4V-CP using high-resolution transvaginal neurosonography in all cases with suspected posterior fossa cystic malformation. This Editorial describes what is currently thought to be the normal anatomical development of the 4V-CP, the ability of high-resolution ultrasound to demonstrate the normal and abnormal development of this structure and the key role the position of the 4V-CP has been recently shown to have in the diagnosis of cystic abnormalities of the posterior fossa. The plica choroidea, which represents the first evidence of the 4V-CP, becomes evident by the 7th gestational week (crown–rump length of 18–20 mm)7, 8. This structure is thought to be the divide between the area membranacea anterior (or anterior membranous area) and the area membranacea posterior (or posterior membranous area). The latter leads to the development of the transient Blake's pouch which seems to become fenestrated at about 12–13 gestational weeks to form the foramen of Magendie9. The anterior membranous area is eventually incorporated into the 4V-CP, probably leading to the development of the tenia choroidea which anchors the developing 4V-CP to the walls of the fourth ventricle. The fourth ventricle is a wide, tent-shaped midline cavity located between the cerebellum and the brainstem. It is connected rostrally with the third ventricle through the aqueduct, caudally with the cisterna magna through the foramen of Magendie and laterally with the cerebellopontine angles through the foramina of Luschka10, 11. The timing of the appearance of the lateral foramina of Luschka is still in question, but the most supported theory is that it becomes evident only at about 26 gestational weeks12. The 4V-CP is described as a T-shaped structure with double vertical limbs and consists of two inverted L-shaped structures11, 13 (Figure 1a). The two paired longitudinal limbs are located on each side of the midline and extend to the foramen of Magendie and, in some cases (in the adult), protrude through it to the cisterna magna13. The two longitudinal limbs are juxtaposed and, in some cases, appear to merge at their end. The two transverse limbs extend laterally through the foramina of Luschka and reach the cerebellopontine fissures. The two terminal parts of the lateral segments, protruding through the foramina of Luschka, have been named Bochdalek's flower baskets (in German, Blumenkőrbchen) (Figure 1b)14, because their appearance resembles a basket of flowers. The study of the 4V-CP is easier at 12–14 gestational weeks, because the calvarium is still widely unossified. By using a transvaginal approach with a high-frequency (6–12 MHz) ultrasound transducer, and acquiring a lateral volume of the posterior fossa, as recommended by the guidelines of the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG)15, it is possible to demonstrate the whole 4V-CP using multiplanar imaging. At 12–14 weeks' gestation, the appearance of the 4V-CP is different from that described above, owing to the presence of the still imperforated Blake's pouch. Blake's pouch, which represents an outpouching of the roof of the fourth ventricle, mechanically bends and displaces laterally the two longitudinal limbs of the 4V-CP and, as a result, their appearance in the coronal plane resembles two brackets surrounding the round fourth ventricular outlet (Figure 2b). In a multiplanar image, it is possible to demonstrate simultaneously, in the midsagittal plane, the downward, oblique direction of the longitudinal limbs of the 4V-CP (Figure 2a), in the coronal plane, the diverging longitudinal limbs of the 4V-CP, embracing the superolateral part of Blake's pouch inlet, as well as the proximal part of the transverse limbs of the 4V-CP (Figure 2b) and, in the axial plane, the transverse limbs of the 4V-CP reaching laterally towards the lateral components of the rhombic lips (Figure 2c). Later in pregnancy, it becomes progressively more challenging to demonstrate the whole anatomy of the 4V-CP, in particular its transverse limbs, due to the fact that the cerebellopontine fissure, where Bochdalek's flower basket is located, is rather hidden by several anatomic structures, including the skull base. Nonetheless, the human sees only what he expects to see and not what is in front of his eyes and, as such, by becoming aware of the shape and position of the transverse limbs of the 4V-CP, it is possible to also demonstrate them in the second and early third trimesters of pregnancy (Figure 3). In the prenatal ultrasound community, the 4V-CP entered the diagnostic arena only after the description, by Tortori-Donati et al. in 199616, of Blake's pouch cyst (BPC) as a pathological entity distinct from mega cisterna magna in neonates. Subsequently, BPC was also demonstrated in the fetus17-19 and it was established that one of the fundamental distinctive diagnostic criteria of BPC is a normal size of the vermis, unlike that which is observed in vermian hypoplasia (VH) and Dandy–Walker malformation (DWM)17. However, in a small number of cases, sonographic assessment of vermian biometry is not able to differentiate between BPC and VH. There are two likely reasons for this. The first is that, in a significant number of studies20, 21, sonographic assessment of the posterior fossa was carried out transabdominally which is a major limitation because, by definition, the lower part of the posterior fossa is shadowed by the skull base20. The second reason is that, in a few instances, there might be significant overlap in the values of the brainstem–vermis angle and vermian biometry between VH and BPC, due to possible mild compression of the vermis by the cyst, if very large, in BPC5, 21. On the contrary, the assessment of the position of the 4V-CP has proved to be highly reliable in the differentiation of cystic abnormalities of the posterior fossa5, 6, 22. In a study published in this issue of the Journal, Volpe et al.6 demonstrated that the 4V-CP is located outside the cyst, distant from the vermian margin and inferolaterally displaced by the cyst, in fetuses with DWM, whereas it is located within the cyst and just below the vermis in fetuses with BPC. These new data confirm and expand our previous finding that the 4V-CP is always superolateral (i.e. up) in relation to the cyst inlet in fetuses with BPC and inferolateral (i.e. down) in relation to the cyst inlet in fetuses with DWM and VH5. The findings of Volpe et al. concord with the hypothesized differential pathogenesis of the two conditions. Therefore, it is now highly recommended to check the position of the 4V-CP both at 12–13 gestational weeks and in the second trimester, in order to carry out an accurate differential diagnosis between cystic abnormalities of the posterior fossa. An important technical note should be mentioned here. In both our study5 and that of Volpe et al.6, the data on the differential position of the 4V-CP in cystic vermian abnormalities were obtained using high-resolution three-dimensional transvaginal ultrasound. As also underlined in the recent ISUOG guidelines on fetal neurosonography15, it is crucial to use all these three tools, i.e. a high-frequency transducer, transvaginal approach and three-dimensional multiplanar imaging, in order to visualize adequately the 4V-CP and distinguish it from the lower part of the vermis (i.e. the uvula). In fact, it is all but impossible to distinguish the two structures on transabdominal ultrasound6, 20. This leads to the conclusion that most charts for vermian biometry based on transabdominal ultrasound have very likely overestimated the true size of the vermis, because the 4V-CP was often inadvertently included in the measurements. Hence, there is a strong need to reassess vermian biometry in pregnancy using transvaginal ultrasound and build new biometric charts that do not include the 4V-CP in the measurements. Data sharing not applicable - no new data generated.