Like a hole in the head: Development, evolutionary implications and diseases of the cranial foramina.

Cranial foramina are holes in the skull through which nerves and blood vessels pass to reach both deep and superficial tissues. They are often overlooked in the literature; however they are complex structures that form within the developing cranial bones during embryogenesis and then remain open throughout life, despite the bone surrounding them undergoing constant remodelling. They are invaluable in assigning phylogeny in the fossil record and their size has been used, by some, to imply function of the nerve and/or blood vessel that they contained. Despite this, there are very few studies investigating the development or normal function of the cranial foramina. In this review, we will discuss the development of the cranial foramina and their subsequent maintenance, highlighting key gaps in the knowledge. We consider whether functional interpretations can be made from fossil material given a lack of knowledge regarding their contents and maintenance. Finally, we examine the significant role of malformation of foramina in congenital diseases such as craniosynostosis.

CNS-resident progenitors direct the vascularization of neighboring tissues.

Organ growth requires the coordinated invasion and expansion of blood vessel networks directed by tissue-resident cells and morphogenetic cues. A striking example of this intercellular communication is the vascularization of the central nervous system (CNS), which is driven by neuronal progenitors, including neuroepithelial cells and radial glia. Although the importance of neuronal progenitors in vascular development within the CNS is well recognized, how these progenitors regulate the vasculature outside the CNS remains largely unknown. Here we show that CNS-resident radial glia direct the vascularization of neighboring tissues during development. We find that genetic ablation of radial glia in zebrafish larvae leads to a complete loss of the bilateral vertebral arteries (VTAs) that extend along the ventrolateral sides of the spinal cord. Importantly, VTA formation is not affected by ablation of other CNS cell types, and radial glia ablation also compromises the subsequent formation of the peri-neural vascular plexus (PNVP), a vascular network that surrounds the CNS and is critical for CNS angiogenesis. Mechanistically, we find that radial glia control these processes via Vegfab/Vegfr2 signaling: vegfab is expressed by radial glia, and genetic or pharmacological inhibition of Vegfab/Vegfr2 signaling blocks the formation of the VTAs and subsequently of the PNVP. Moreover, mosaic overexpression of Vegfab in radial glia is sufficient to partially rescue the VTA formation defect in vegfab mutants. Thus, our findings identify a critical function for CNS-resident progenitors in the regulation of vascularization outside the CNS, serving as a paradigm for cross-tissue coordination of vascular morphogenesis and growth.

Early fetal development of the human vertebral artery especially at and above the occipitovertebral junction.

Little is known about the chronological changes that occur in the topographical anatomy of the fetal vertebral artery (VA), especially at and above the occipitovertebral junction. We histologically examined paraffin-embedded horizontal, sagittal and frontal sections of the heads of 25 human embryos and fetuses of crown-rump length 20-110 mm, corresponding to 6-15 weeks of gestation. At 6 weeks, the VA ran anterosuperiorly through a large intracranial subdural space filled with loose mesenchymal tissue. This intracranial course was distant from the brain stem, suggesting that the developing brain did not "guide" the VA. Before 8-9 weeks, the VA appeared to take an almost straight upward course at the occipitovertebral junction. Later, however, the atlanto-occipital joint growing along the mediolateral axis caused the VA to curve at the junction area. In specimens before 10 weeks, the terminal of the VA, or the origin of the basilar artery, was on the anterior side of the inferior olive and near the jugular foramen. The fetal posterior inferior cerebellar artery originated at the same caudal site distant from the primitive cerebellum. Later, the terminal or origin moved rostrally to the level of the pons. These findings indicate that the basic branching pattern of the VA-basilar artery is independent of the developing brain, whereas the arterial courses are secondarily "corrected" by the growing brain and atlanto-occipital joint.

Doppler changes in the vertebral, middle cerebral, and umbilical arteries in fetuses delivered after 34 weeks: relationship to severity of growth restriction.

OBJECTIVE: To determine the association between Doppler changes in the fetal vertebral (VA), middle cerebral (MCA), and umbilical arteries (UA) and severity of growth restriction (FGR) in fetuses delivered after 34 weeks. METHOD: Five hundred seventy-one Doppler examinations of the VA, MCA, and UA were performed between 26 and 41 weeks of gestation. Values were converted into multiples of the median and divided into birth weight (BW) categories: BW>P10(th) , BW

Doppler study of the fetal vertebral artery in small for gestational age fetuses with intrauterine growth restriction.

OBJECTIVES: The purposes of this study were to evaluate the Doppler resistive index of the fetal vertebral artery in small for gestational age (SGA) fetuses and to examine the ability of the vertebral artery resistive index in the diagnosis of intrauterine growth restriction (IUGR). METHODS: A total of 437 Doppler examinations of the vertebral and umbilical artery resistive indices were performed in 437 fetuses between 26 and 41 weeks' gestation. According to birth weight, fetuses were classified into 5 groups: 1, above the 10th percentile; 2, between the 10th and 5th percentiles; 3, between the 5th and 3rd percentiles; 4, below the 3rd percentile; and 5, below the 3rd percentile with an umbilical artery resistive index above the 95th percentile. Subsequently, vertebral artery resistive index values were converted into multiples of the median, and box and whisker charts were generated to evaluate differences. Finally, receiver operating characteristic curves were calculated to assess the accuracy of the vertebral artery resistive index for predicting IUGR and a low Apgar score. RESULTS: Compared to normally grown fetuses, vertebral artery resistive index values were lower in fetuses with birth weight below the 3rd percentile, and this difference was greater in fetuses with birth weight below the 3rd percentile and Doppler anomalies of the umbilical artery. The receiver operating characteristic analysis showed that the vertebral artery resistive index diagnosed SGA fetuses and low Apgar scores poorly. However, it performed better in cases of severe IUGR with high umbilical artery resistive index values. CONCLUSIONS: Preliminary data show that the vertebral artery resistive index diminishes in growth-restricted SGA fetuses. Doppler examination of the vertebral artery seems to identify a group of fetuses with brain sparing and severe IUGR.

Fetal vertebral artery Doppler reference values at 19-41 weeks of gestation.

OBJECTIVES: To establish Doppler reference values for the fetal vertebral artery resistance index (VA RI), pulsatility index (VA PI) and peak systolic velocity (VA PSV), and describe their normal ratios to the umbilical artery (UA) throughout the second and third trimester of pregnancy. METHODS: Between 19 and 41 weeks of gestation, 484 ultrasound examinations of the fetal VA and UA were performed on singleton pregnant women with uncomplicated pregnancies. The VA was examined at the anatomical point where the artery surrounds the lateral masses of the atlas between the first cervical vertebra and the occipital bone, and values were obtained for the VA RI, VA PI and VA PSV. The 10th, 50th and 90th percentiles were subsequently generated for these parameters and their ratios to the UA. RESULTS: The VA RI and VA PI reached their maximum values at the end of the second trimester. Both indexes subsequently decreased due to an increase in the diastolic flow. Conversely, the VA PSV values increased progressively until the end of gestation. As for the VA/UA ratios, the RI and PI were higher in the middle of the third trimester and decreased slightly afterwards. On the other hand, the PSV increased progressively until the end of pregnancy. CONCLUSIONS: The fetal VA can be visualized with Doppler ultrasound as early as 19 weeks' gestation. In this study, reference values of the VA RI, PI and PSV and their ratios to the UA during the second half of pregnancy have been provided for fetal research. However, future work is necessary to further explore the possible applications of VA Doppler examination in fetal medicine.

Sites of transition between functional systemic and cerebral arteries of rabbits occur at embryological junctional sites.

The vascular smooth muscle of cerebral blood vessels is relatively insensitive to sympathomimetic stimulation compared with muscle from systemic vessels. The transition in the vertebral artery occurs just rostral to the emergence of that artery from the foramen of the lateral process of the atlas and in the internal carotid artery just before it enters the carotid canal. These sites in the adult correspond to embryological junctions between segments of the vertebral and internal carotid arteries derived from the primitive dorsal aortas and their branches with vessels originating locally from the bilateral longitudinal neural arteries. Topographic patterns of vascular properties may in some cases be explained by the different sites of origin of their primordial mesodermal cells.

Proatlantal intersegmental artery: a review of normal and pathological features.

OBJECTS: Primitive carotid-vertebral and carotid-basilar anastomoses are formed early during human embryogenesis at approximately 24 days. From cephalic to caudal direction, these anastomoses are cranial extensions of the primitive internal carotid, trigeminal, otic, hypoglossal and proatlantal intersegmental arteries. MATERIALS AND METHODS: Normal and/or abnormal morphofunctional aspects of prenatal and postnatal forms of the proatlantal intersegmental artery, from the 24th day of gestation to postnatal eight decades, are described according to personal and literature data. Many (ab) normal carotid-vertebral anastomoses are also marked in differential diagnosis of the proatlantal intersegmental artery. CONCLUSIONS: The proatlantal intersegmental artery maintains the posterior circulation until the vertebral arteries are fully developed between the seventh and eighth gestational weeks. When this artery fails to obliterate, it becomes persistent one. The proatlantal intersegmental artery, most commonly, is an incidental finding or it may be of clinical significance in some patients.

Correlation between umbilical arterial pH values and fetal vertebral artery Doppler waveforms at the beginning of the second stage of labor: a pilot prospective study.

Objective: The aim of this study was to evaluate the association between umbilical arterial pH and fetal vertebral artery Doppler velocimetry waveforms measured at the beginning of the second stage of labor in physiological term pregnancies. Methods: This was a prospective cohort study of 250 pregnancies. The resistance index, pulsatility index, and peak systolic velocity were measured. The relationship between the fetal Doppler and the umbilical arterial pH was evaluated. A simple linear regression and a general linear model were used to explore possible correlations of Doppler parameters with fetal and neonatal outcome adjusted for confundents. Results: Umbilical arterial pH values were directly associated with vertebral artery pulsatility index. Fetuses with lower pulsatility index values were at increased risk of a subsequent diagnosis of pathological fetal heart rate tracing patterns (presence of decelerations or reduced variability according to FIGO criteria during the second stage of labor). We estimated a decrease in pulsatility index of 10% in those fetuses destined to show a pathological fetal heart rate tracing. Conclusion: Vertebral artery Doppler waveforms correlates with umbilical pH in normal pregnancies and is also a function of fetal heart rate patterns. If this proportional association would be demonstrated also for abnormal pH values, vertebral artery pulsatility index might be useful to evaluate fetal wellbeing in those cases of suspected hypoxia/academia.

Dual origin extracranial vertebral artery: case report and embryology.

Duplication of the vertebral artery origin is a rare vascular anomaly. The authors describe this finding in a patient who underwent neurointerventional treatment for a midbasilar aneurysm. The embryology and clinical significance is also presented.

Aberrant Right Vertebral Artery with a Diverticulum of Kommerell: Review of a Rare Aortic Arch Anomaly.

The normal aortic arch branching pattern is of a three-vessel arch with the vertebral arteries arising from the subclavian arteries. There are a variety of well-known symptomatic and asymptomatic aortic branching patterns widely reported in the literature. An anomalous right vertebral artery with a diverticulum of Kommerell is an extremely rare variant, with few other cases reported in the literature. Herein, we review the embryology of the aortic arch and vertebral artery, the various types of Kommerell's diverticula and the clinical significance of this anomaly.

Bilateral segmental agenesis of the vertebrobasilar junction: developmental and angiographic anatomy.

BACKGROUND AND PURPOSE: Bilateral vertebrobasilar junction agenesis is an exceptional anatomic variation. This article explores the angiographic characteristics of this variant and its embryologic mechanisms. MATERIALS AND METHODS: Two observations of bilateral agenesis of the vertebrobasilar junction are reported. A case of atheromatous disease of the vertebrobasilar junction is shown to highlight characteristics distinguishing such a lesion from the reported variant. RESULTS: In the 2 reported cases, the distal segment of both vertebral arteries (VAs) and the proximal portion of the basilar artery (BA) were absent. In addition, distal connections of the BA with the posterior cerebral arteries (PCA) were also lacking. As a consequence, the remaining portion of the BA was isolated from its usual sources of blood supply, which was provided by a persistent carotid-basilar anastomosis. CONCLUSION: The developmental mechanism underlying bilateral agenesis of the vertebrobasilar junction likely involves the anterior radicular artery of C1. This branch of the proatlantal artery normally becomes the adult distal VA and the proximal BA. The lack of cranial connection of the BA with the PCA may be secondary to the proximal vertebrobasilar agenesis and the resulting paucity of antegrade flow within the BA. Alternatively, the absence of both the proximal and distal connections of the BA could be the result of a similar, yet unknown, developmental mechanism. From a clinical standpoint, this vascular anomaly was discovered incidentally in our 2 patients, a finding consistent with the assumed congenital nature of the variant.

Carotid-vertebrobasilar Anastomoses with Reference to Their Segmental Property.

The primitive carotid-vertebrobasilar anastomoses are primitive embryonic cerebral vessels that temporarily provide arterial supply from the internal carotid artery to the longitudinal neural artery, the future vertebrobasilar artery in the hindbrain. Four types known are the trigeminal, otic, hypoglossal, and proatlantal intersegmental arteries. The arteries are accompanied by their corresponding nerves and resemble an intersegmental pattern. These vessels exist in the very early period of cerebral arterial development and rapidly involute within a week. Occasionally, persistence of the carotid to vertebrobasilar anastomosis is discovered in the adult period, and is considered as the vestige of the corresponding primitive embryonic vessel. The embryonic development and the segmental property of the primitive carotid-vertebrobasilar anastomoses are discussed. This is followed by a brief description of the persisting anastomoses in adults.

MR angiographic demonstration of bilateral duplication of the extracranial vertebral artery: unusual course and review of the literature.

Duplication of the vertebral artery is a rare developmental anomaly. Duplication and fenestration are terms often used incorrectly and interchangeably in the literature. To the best of our knowledge, this is the first report to describe bilateral duplication of the extracranial vertebral artery. Bilaterally, there are 2 separate origins of each vertebral artery from the corresponding subclavian artery, with one duplicated segment entering the C7 foramen transversarium bilaterally and the other segment entering the carotid space on either side. The duplicated vessels join together at C5-C6 disk level on the left and at C4-C5 disk level on the right before continuing as one vessel in the foramina transversaria on either side. Duplication is thought to represent failure of controlled regression of 2 intersegmental arteries and a segment of the primitive dorsal aorta. This case was discovered on a 2D time-of-flight and contrast-enhanced neck MR angiogram in an 83-year-old man with cognitive decline and appears as an incidental finding without obvious clinical implications.

A rare variation of the vertebral artery.

Variations of the vertebrobasilar arterial complex are important with regard to their potential clinical impact. We present an unusual case of the vertebral artery, in which the left vertebral artery in its ascent in the neck through the transverse foramina passed posteriorly between the transverse processes of C3 and C4 and supplied the posterior muscles of the neck without continuing intracranially. Albeit speculatively, we hypothesise that the variation of the vertebral artery reported here was caused by degeneration of the proximal portion of the left postcostal longitudinal anastomosis (i.e. C1 and C2 intersegmental arteries) in the context of a persistent third cervical intersegmental artery. Our case is unique in that the left vertebral artery terminated extracranially. Knowledge of the variations of the vertebrobasilar arterial complex is important for surgeons operating at the skull base, craniocervical junction, and cervical region, and for clinicians interpreting the imaging of this region.

Right proatlantal artery type I, right internal carotid occlusion, and left internal carotid stenosis: case report and review of the literature.

A 66-year-old man presented with right cerebellar infarction and ischemic lesions in the left dorsal thalamus and right upper parietal lobe. Angiography showed occlusion of the right internal carotid artery proximal to an ipsilateral proatlantal artery type I, 70% stenosis of the left internal carotid artery, and aplasia of both posterior communicating arteries. The carotid occlusion was successfully treated by thrombendarterectomy. Persistence of a proatlantal artery is a rare condition. In relation to the 38 literature reports on proatlantal arteries, this case demonstrates the clinical significance of a persistent proatlantal artery in the evolution of atypical ischemic cerebrovascular disease.

Dysplastic vertebral artery with paradoxical infarction.

A rare abnormality of the vertebral artery is described in a 63-year-old male. The right vertebral artery consisted of several minute endothelial lined channels which failed to perfuse at autopsy. The anterior spinal artery showed areas of muscular media dysplasia. These anomalies were associated with large posterior communicating arteries. The terminal event was precipitated by thrombotic occlusion of the left vertebral artery. The embryological aspect of these anomalies are discussed.

Segmental intervertebral anastomosis in subclavian steal.

Segmental intervertebral arterial connections originate from normal vascular channels which are commonly seen on selective vertebral arteriography. In subclavian steal, these vessels can hypertrophy and form important collateral pathways. The significance of their haemodynamic contributions may be assessed by their multiplicity and calibre. Lateral or oblique projections in addition to frontal visualization may be required to differentiate the various transcervical channels which lie either anterior or posterior to the vertebral bodies.

[Atypical termination of the vertebral artery and of the inferior posterior cerebellar artery (author's transl)]. / Eine atypische Bildung des Endabschnittes der Arteria vertebralis und der Arteriae cerebellares inferiores posteriores

A rare varient in the termination of the vertebral artery is described associated with a low origin of an unpaired inferior posterior cerebellar artery lying between C. 1 and C. 2. This is illustrated radiographically. An attempt is made to explain this radiologically and to classify it. Possible clinical significant of this anomaly, particularly in relation to subarachnoid haemorrhage, is discussed.

[The primitive otic artery, a very rare, persistent, primitive artery (author's transl)]. / Die Arteria primitiva otica, eine sehr seltene persistierende Primitivarterie.

A very rare carotid-basilar anastomosis, the primitive otic artery, is described. In the presence of hypoplasia of the vertebral and basilar arteries and dorsal interruption of the circle of Willis, an attempt is made to explain the situation embryologically and to discuss the disadvantages associated with this condition.