The anatomy of the arterial system supplying blood to the brain can influence the development of arterial disease such as aneurysms, dolichoectasia and atherosclerosis. As the arteries supplying blood to the brain develop during embryogenesis, variation in their anatomy may occur and this variation may influence the development of arterial disease. Angiogenesis, which occurs mainly by sprouting of parent arteries, is the first stage at which variations can occur. At day 24 of embryological life, the internal carotid artery is the first artery to form and it provides all the blood required by the primitive brain. As the occipital region, brain stem and cerebellum enlarge; the internal carotid supply becomes insufficient, triggering the development of the posterior circulation. At this stage, the posterior circulation consists of a primitive mesh of arterial networks that originate from projection of penetrators from the distal carotid artery and more proximally from carotid-vertebrobasilar anastomoses. These anastomoses regress when the basilar artery and the vertebral arteries become independent from the internal carotid artery, but their persistence is not uncommon in adults (e.g., persistent trigeminal artery). Other common remnants of embryological development include fenestration or duplication (most commonly of the basilar artery), hypoplasia (typically of the posterior communicating artery) or agenesis (typically of the anterior communicating artery). Learning more about the hemodynamic consequence that these variants may have on the brain territories they supply may help understand better the underlying physiopathology of cerebral arterial remodeling and stroke in patients with these variants.
A large proportion of strokes worldwide are caused by atherosclerosis affecting the arteries that supply blood to the brain.
The goal of this review is to describe the embryology of the arteries supplying blood to the brain, their anatomical variants and how these variants might relate to clinical outcomes.
The development of the vascular system in the embryo happens before the heart starts beating.
The internal carotid arteries (ICA) appear during the 3 mm embryonic stage (24 days) from the combination of the 3rd branchial arch arteries and the distal segments of the paired dorsal aortae (
The occipital lobe and brain stem growth is the initial stimulus for the formation of the posterior circulation, first with the BA and later with the vertebral arteries (VA).
At the 11-12 mm embryological stage (35 days), the development of the MCA is first identified as small buds originating proximal to the ACA on the anterior division of the primitive ICA.
The posterior aspect of the circle of Willis (CoW) is formed at earlier stages, when the fetal PCA turns into PCOMM, the adult PCA connects with the BA as branches from the fetal PCA fuse medially to form the distal end of the BA, and the PChA incorporates into the adult PCA.
As the cerebral vascular tree reaches its typical configuration, the multiple events that occur during the embryological stage might lead to a diverse spectrum of vascular anatomical variants.
Fenestrations of the cerebral arteries are congenital anomalies with a reported prevalence ranging from 0.3% to 28.0% depending on the study methods.
Cerebral arteries integrating the adult CoW vary in size. A ratio between certain arteries has been proposed to determine when an artery is smaller than expected. For example, the size of the PCOMM is one half of the size of the PCA, which itself is one half of the BA.
After reviewing the literature and synthesizing the data, we proposed a classification of cerebral variants into four groups: a) anomaly of a normally present artery, b) persistence of a normal embryonic artery, and c) visualization of normally hidden anastomoses.
The normal ICA can be divided into multiple segments based on its course. The first segment (i.e., cervical) begins at the CCA bifurcation and ends at entrance into the skull base via the carotid foramen. The second segment (i.e., ascending petrous) extends to the apex of the antero-medial curvature within petrous bone and ends with the origin of the carotico-tympanic artery. The third segment (i.e., horizontal petrous) ends at the skull base in the foramen
An aberrant ICA pathway occurs when the ICA deviates from its anatomical landmarks. The most commonly reported aberrant ICA involves the middle ear.
The most typical MCA variants include an accessory MCA or a duplicated MCA. Both are rare variants (
The A1 segment of the ACA is among the most frequent sites of anatomic variation in the CoW and it usually involves changes in the ACOMM. Some examples include duplication, azygous ACA, or accessory ACA.
Variants of the ACOMM are common variants in the CoW with a duplication prevalence of 18% and fenestrations in up to 21%.
One of the most common embryological variants of the BA is its fenestration, also known as segmental duplication (
In a large surgical series, variants involving the origin of the VA were not uncommon.
A fetal origin of the PCA is the most frequent variant involving this artery. It has been reported in between 13%-15% of the population, and it is typically described in only one PCA, but it can also occur in both PCA in up to 0.5% of the population.
A hypoplastic PCOMM is overall the most common arterial variant reported in the brain.
What causes embryonic arteries to persist in supplying the brain with blood is not entirely clear. In some instances, for example in the case of a persistent TA (see below), it has been noted that there is a delay in the PCOMM development, which would lead to an incomplete support to the distal BA and with it, to a persistent need for these inferior anastomoses to maintain the flow.
Persistent TA is the most common of the persistent carotid-vertebrobasilar anastomoses, with a reported prevalence of about 0.2% (0.1%-0.6%,
The prevalence of a persistent HA is 8 to 10 times less than the persistent TA with a reported prevalence of 0.02% to 0.10% (
When the ProA persists, one or both VA are typically hypoplastic.
Persistence of the otic artery is one of the rarest variants of the carotid-vertebrobasilar anastomoses, and it is usually described as arising from the petrous ICA, then passing through the internal auditory canal to later join the BA.
During embryogenesis, multiple connections occur between the ICA, the ECA and the posterior circulation. These anastomoses are not usually seen in conventional angiographic studies due to hemodynamic balance between the involved systems, but they can become visible in the setting of increased intracranial pressure or hemodynamically significant arterial stenoses.
The three main collaterals route between the OphA (itself a branch of the ICA) and the ECA system are the dorsal nasal artery (a branch of the facial artery), the supraorbital artery (a branch of the superficial temporal artery) and the internal maxillary artery (through proximal and distal branches).
The two main arteries involved in this anastomotic connections include the ascending pharyngeal artery and the internal maxillary artery (through its proximal and distal portions).
The most commonly cited anastomosis between the ECA and posterior circulation is the occipital artery, itself a remnant of the ProA.
Although many cerebral arterial variants may be asymptomatic, their recognition is important in patients with cerebrovascular disease and in those who undergo brain imaging for other purposes, as some of these variants might be pathological or turn pathological in a surgical setting.
There is a substantial interest in the "geometric risk" for atherosclerosis.
As discussed above, the primary goal of the developing cerebral arterial system in the embryo is to supply blood to support the rapid and asynchronic brain growth. As long as the flow is delivered, there should not be a deleterious immediate consequence to the brain or the vessel. This statement is supported by the fact that adult individuals who have persistence of fetal arterial configurations in the brains are typically asymptomatic. In the long term, however, individuals with arterial configurations consisting of decreased collaterals routes (e.g., lack of PCOMM or ACOMM) or coexistence of branching arteries with discrepant diameters (i.e., wide diameter ratios), may be at a higher risk of developing atherosclerosis in areas with chronic low or oscillating blood flow.
In the carotid bifurcation, intima thickening and atheromas rarely occur in the flow divider but are more common in the outer wall of the bifurcation, where low or oscillating wall shear stress is found.
In intracerebral arteries, the larger the interadventitial arterial diameter is, the greater the degree of stenosis noted. After adjustment for artery type (e.g., ICA vs. MCA vs. BA) and artery location (proximal vs. distal segments of the same artery), however, the strength of association between arterial size and stenosis decreases.
Whether the posterior circulation has a higher risk of developing atherosclerosis is unknown. The MCA is typically overrepresented in samples studying symptomatic intracranial large artery atherosclerosis, perhaps due to the likelihood of symp-toms upon plaque rupture or erosion in this location.
The prospective study of arterial remodeling is challenging. We are not aware of any longitudinal study primary focused on brain arterial anatomy that has included newborns or children and follow them into adulthood or late aging. Despite the absence of such a study, it can postulated that individuals born with an arterial geometry favorable for the development of atherosclerosis can more easily, upon the exposure to endothelial injury induced by traditional vascular risk factors, develop atherosclerosis. It should be noted, however, that the "geometric risk for atherosclerosis" is not
Hypoplastic arteries are probably the most common variants seen in adults. The significance of these variants and has not yet fully validated in population-based studies, but autopsy series have shown that hypoplastic arteries are more commonly found in patients who have had brain infarcts.
It is less well-established whether other variants mentioned here increase the risk of vascular disease. However, it seems important to be aware of the possibility of these variants when assessing an atypical pattern of stroke. For example, a single embolism through an azygous ACA can cause bilateral medial frontal strokes while extracranial carotid stenosis can cause a brain stem stroke through a persistent carotid-vertebrobasilar anastomosis.
Fenestrations and/or duplication of intracranial arteries have been associated with the development of brain saccular aneurysm.
Azygous ACA has been associated with saccular aneurysm in the same vessel. The hypothesis behind this association is that the increased flow resulting from the fuse A2 leads to progressive dilatation of the wall.
Congenital absence of the ICA and hypoplasia of the ICA needs to be distinguished from acquired stenosis.
A persistent TA has been associated with aneurysms of the CoW, carotid and VA agenesis, facial hemangiomas, PCOMM agenesis, moyamoya disease, and aortic arch vessel anomalies in up to 25% of the cases.
Surgeons unaware of VA variations can encounter fatal hemorrhage during operations such as thyroidectomy or excision of a pharyngeal diverticulum where he can accidentally tear the VA while attempting ligation of the inferior thyroid artery or may cause destruction of any adjacent important structures such as the brachial plexus, thoracic duct , CCA, jugular vein.
To Alperin noninvasive Diagnostics, Inc (Miami, FL) for the use of the 3D MRA volumetric analyses tool to obtain
To the Northern Manhattan Study (NOMAS) funded by NINDS R37 NS029993 (Sacco/Elkind) for allowing the use of MRI images reported in
To Brianna Avenia-Tapper for her editorial assistance.
The authors have no financial conflicts of interest.
This work was done while Mr. Menshawi was visiting research fellow at Columbia University Medical Center.