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Completeness of Circle of Willis in asymptomatic and symptomatic extracranial carotid disease/Kompletnost vilisovog poligona kod ekstrakranijalne karotidne bolesti bez simptoma i sa simptomima.

UDK 616.831-005:616.133-089.87


Circle of Willis (CoW) is the most significant collateral pathway in the presence of extracranial carotid disease. Collateralization with the opposite internal carotid artery (ICA) is conducted via anterior collateral segment of CoW (made of A1 segments of anterior cerebral artery--ACA and anterior communicating artery--AcomA). Collateralization with posterior cerebral circulation is achieved by posterior collateral segment of CoW, (made by PI segments of posterior cerebral artery--ACP) and posterior communicating artery--AcomP). Hypoplasia or occlusion of arteries forming the aforementioned collateral segments are common as variations of incomplete CoW are presented in one third to one half of population [1, 2]. An incomplete CoW becomes clinically significant in the setting of inadequate blood inflow in extracranial cerebrovascular disease [3] (Figure 1).

The blood flow through anterior and posterior segment of CoW increases in significant stenosis of extracranial segment of ICA due to a decreased inflow. Such a development of collateral flow depends on the patency of anterior and ipsilateral posterior collateral arterial pathway. Insufficient collateralization results in a decreased flow in the cerebral arteries, which increases the risk of neurological symptoms and cerebrovascular insult [4]. By recognizing the importance of collateral flow and finding patients at the highest risk of stroke we are able to treat such patients on time, before a disabling cerebrovascular event occurs [5].

Magnetic resonance angiography (MRA) has a significant role in examining CoW. It is a low risk procedure enabling in vivo studies which provide information on the patency and diameter of arteries, as well as on the functional morphology, and indirectly on hemodynamic changes of CoW [6-8].

This research has been aimed at determining whether an incomplete CoW (hypoplasia or occlusion of anterior or posterior collateral segment) is associated with neurological symptoms or ischemic lesion of brain parenchyma in the patients with significant extracranial carotid stenosis.

Material and Methods

The research was conducted as a prospective study comprising 211 patients who underwent surgical treatment of extracranial carotid disease at the Department of Vascular Surgery in Novi Sad, in the period from September 1st, 2013 to September 1st, 2014. Neurological examination was preoperatively performed on each patient by a qualified neurologist. The degree of stenosis was determined by duplex ultrasonography (DUS) according to the NASCET criteria using 5MHz linear transducer. Each patient underwent preoperative magnetic resonance imaging (MRI) and MRA examination on standardized magnetic resonance (MR) device GEHC SignaHDt 1.5T at the Center of Radiology, Clinical Center of Vojvodina. We analyzed two sequences: T2 sequence for visualization of cerebral parenchyma; 3D TOF sequence for the assessment of CoW morphology. Only the patients with unilateral carotid disease and no vertebral and basilar artery stenosis or occlusion were included. The control group consisted of 102 patients whose indications for MRI/MRA examination were other than extracranial cerebrovacular disease. The same sequences of MRI/MRA were analyzed in this group of patients by using the data base of Center of Radiology, Clinical Center of Vojvodina. This study was approved by the Ethics Committee of Clinical Center of Vojvodina in Novi Sad, Serbia (No 145/2013/2).

The selected participants were grouped according to the following criteria:

--The groups of the asymptomatic and symptomatic patients were formed regarding symptoms of extracranial carotid disease. "Pscudo asymptomatic patients" ("silent brain infarction" larger than 1 cm) were assigned to the symptomatic patient group.

--Regarding the CoW completeness the patients were assigned to the group of patients with complete CoW and the group of patients with incomplete CoW (occlusion or hypoplasia (less than 2 mm of diameter on 3D TOF MRA finding) of arteries forming anterior and/or ipsilateral posterior collateral segment regarding the side of significant carotid stenosis) as it is shown in Figure 1.


Out of 211 patients who were operated during the observed period, 133 were males and 78 were females, between the ages of 49 and 81 years (mean age being 69.3 years).

A hundred (47.3%) asymptomatic patients and 111 (52.7%) patients with symptomatic carotid stenosis or ischemic cerebral parenchymal lesion greater than 1 cm ("silent brain infarction") underwent surgery.

The total number of operated patients with the complete and with the incomplete CoW was 133 (63%) and 78 (37%), respectively. In the group of asymptomatic patients, the complete CoW was observed in 75% (75) of patients, while the disruption of anterior or ipsilateral posterior collateralization was found in 25% (25) of patients. Out of 111 patients with symptomatic carotid disease or silent brain infarction, 52.5% (58 patients) had the complete CoW, and 47.5% (53 patients) had the incomplete CoW. In the control group, 41% (42 patients) had the complete CoW and 59% (60 patients) had the incomplete CoW.

The difference in the occurrence of complete and incomplete CoW was shown to be statistically different between the patients with extracranial carotid disease and the control group of patients, there were more complete CoW in the group of patients with extracranial carotid disease (P = 0.0003 OR 2.4359 95% CI:1.5022 to 3.9498 z stat. 3.610)

The difference in the occurrence of complete and incomplete CoW was shown to be statistically different between the asymptomatic and symptomatic patients with extracranial carotid disease, there were more complete CoW in asymptomatic group of patients (P = 0.0146 OR 0.4906 95% CI: 0.2770 to 0.8688 z stat. 2.442) (Table 1).


The results of this study have shown that based on 3D TOF MRA findings, the frequency of CoW variety with complete anterior and posterior collateral segment in the patients with carotid disease is 63%, which is higher compared to the control group of patients free of extracranial carotid stenosis (41%). According to literature data, the frequency of complete CoW in the age-matched general population is about 35-50%. The causes of incompleteness of CoW are hypoplasia or aplasia of arteries forming it and with progression of atherosclerotic disease, stenosis and occlusion occur. That can be confirmed by 3D TOF MRA analy sis of diameter and patency of CoW collaterals in patients of different age [9]. In the patients with regular flow in the carotid and vertebral arteries, the collaterals of CoW are usually inactive, which can be confirmed by imaging methods and transcranial Doppler (TCD), with a high level of correlation. This correlation is explained by the fact that MRA 3D TOF sequence register flowing of the blood (speed of blood less than 5 cm/s is virtually not registered) providing not only morphological but also functional findings on CoW [10].

As already stated, in about one third of general population at certain age the CoW collaterals are completely developed, and in such persons a decreased flow in one carotid artery (e.g. occlusion or ligature) would be accompanied by a less severe hemodynamic disorder, and therefore a lower risk of significant neurological deficiency. In the remaining two thirds of population, CoW is a reserve whose activation depends on the potential of arteries to increase the flow (an important factor is affection of collaterals by atherosclerotic process), as the extracranial occlusive carotid disease gradually progresses. It has been proven that in the patients with significant extracranial carotid stenosis there is not only the collateral blood flow, but the collaterals have greater diameter as well, which indicates the capability of CoW adaptation on altered hemodynamics due to carotid stenosis or occlusion, which is called remodeling [11]. In case of unilateral carotid occlusive disease, the anterior collateral segment (ACA1, AcomA) made of arteries with constant diameter is crucial, while in case of bilateral occlusive carotid disease the posterior collateralization (ACPI, AcomP) develops, with the inflow from the vertebrobasilar arterial system. A more frequent occurrence of complete CoW in patients with extracranial carotid stenosis undergoing surgical treatment can be explained by two mechanisms: one is the gradual stimulation of CoW arteries to develop collateral flow due to decreased inflow, and the other one is "natural selection" as the patients with developed CoW collateralization tend to have mild neurological damage, and are therefore better qualified for the surgical treatment.

Considering the importance of collateral circulation in extracranial carotid disease, a compelling correlation between ischemic cerebral lesions or neurological symptoms and incompleteness of CoW would be expected. However, not all surveys have confirmed this correlation. To the contrary, certain studies have not proven a statistically significant difference in the occurrence of incomplete CoW in the patients with symptomatic carotid stenosis [11]. On the other hand, different studies have shown that the occurrence of ischemic lesions, especially hemodynamic "watershed" ischemic lesions is connected to the smaller diameter of anterior and posterior collaterals and their occlusion [12]. Moreover, rare randomized controlled studies have shown a protective effect of complete CoW in the symptomatic carotid patients on medicament treatment, as well as in surgically treated patients perioperatively and during the two-year follow up period [13]. According to certain authors, the disruption of anterior collaterals is an isolated risk factor for brain ischemia development, even in the absence of extracranial carotid disease (A1 hypoplasia syndrome), [14] while the disruption in the posterior collaterals has an impact on hemodynamics only in the presence of a carotid occlusive disease [15].

In our study, we have found the significant statistical correlation between neurological deficit or silent brain infarction and interruption in anterior or ipsilateral posterior collaterals of CoW in the patients with extracranial carotid stenosis undergoing surgical treatment. A high degree of statistical significance is a little surprising considering previous studies, and initial elimination of patients with severe neurological deficit, large ischemic areas and extensive changes on intracranial segments of ICA and cerebral arteries, in which even more frequent interruption of CoW collateralization is expected.

The shortcoming of this study and of similar studies as well lies in fact that CoW is presented with numerous variations and even more numerous classifications, which makes the assessment of CoW morphology more complicated. Such detailed classifications have little clinical usage, especially when analyzed in terms of extracranial carotid disease. We used complete/incomplete CoW classification, disregarding further divisions (i.e. on the anterior or posterior collateral segment incompleteness) as it was recently proposed by SMART study group [16]. However, this study did not prove completely the importance of complete CoW in prevention of ischemic stroke in asymptomatic carotid patients. However, in more recent study the complete CoW proved to be an independent predictor of good outcome after ischemic stroke [17].

It can be concluded that an incomplete CoW is a risk factor for neurological symptoms and cerebral ischemia in the patients with significant ICA stenosis, i.e. it contributes to their more frequent occurrence. The patients with interrupted anterior or posterior CoW collaterals who have not developed ischemic cerebral lesions or neurological symptoms are of special interest. Such asymptomatic patients accounted for 25% of participants in our study, and 12% of total number of treated patients. If we assume that those are asymptomatic patients with the increased risk for development of neurological symptoms, their timely treatment would probably have a significant impact on primary prevention of cerebrovascular infarction. Thus, these patients would have the most benefit from surgical treatment. Such an assumption emphasizes the surgical perspective of role of CoW in carotid disease, considering that previous studies have mostly been based on choice of surgical technique and intraoperative protection of cerebral ischemia in relation to morphology of CoW [18].


Incompleteness of circle of Willis is associated with a more frequent occurrence of neurological symptomatology or ischemic lesions of brain parenchyma in the operated patients with significant extracranial carotid stenosis

The control group without extracranial carotid stenosis had less developed collaterals of circe of Willis compared to the patients with extracranial carotid disease.

CoW     --circle of Willis
ICA     --internal carotid artery
ACA     --anterior cerebral artery
AcomA   --anterior communicating artery
ACP     --posterior cerebral artery
MRI     --magnetic resonance imaging
MRA     --magnetic resonance angiography
DUS     --duplex ultrasonography

DOI: 10.2298/MPNS1612351M


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[18.] Montisci R, Sanfilippo R, Bura R, Branca C, Piga M, Saba L. Status of the circle of Willis and intolerance to carotid cross-clamping during carotid endaterectomy. Eur J Vase Endovasc Surg. 2013; 45(2):107-12.

Rad je primljen 28. Ill 2016.

Recenziran 8. VII 2016.

Prihvacen za stampu 13. VIII2016.

BIBLID.0025-8105:(2016):LXIX: 11-12:351-355.


Clinical Center of Vojvodina, Novi Sad

Clinic for Vascular Surgery

Corresponding Author: Dr Vladimir Manojlovic, Klinika za vaskularnu hirurgiju, Klinicki centar Vojvodine, 21000 Novi Sad, Hajduk Veljkova 1-7, E-mail:

Caption: Figure 1. Clinically significant types of CoW: a. complete CoW; incomplete CoW presented by: b. interruption of anterior collaterals c. interruption of posterior collaterals; d. interruption of both anterior and posterior collaterals

Slika 1. Klinicki znacajni tipovi Vilisovog prstena: a. kompletan Vilisov prsten; nekompletan Vilisov prsten sa: b. prekidom prednjih kolaterala c. prekidom zadnjih kolaterala d. prekidom i prednjih i zadnjih kolaterala
Table 1. Frequency of complete and incomplete CoW in operated
patients with asymptomatic and symptomatic extracranial carotid
disease and control group.
Tabela 1. Ucestalost kompletnog i nekompletnog Vilisovog prstena kod
operisanih pacijenata sa asimptomatskom i simptomatskom karotidnom
bolesti i kod kontrolne grupe ispitanika

                                             All operated
                                             Svi operisani

All/Svi                                           211
Complete CoW/Kompletan Vilisov prsten          133 (63%)
Incomplete CoW/Nekompletan Vilisov prsten      78 (37%)


All/Svi                                        100 (47%)
Complete CoW/Kompletan Vilisov prsten          75 (75%)
Incomplete CoW/Nekompletan Vilisov prsten      25 (25%)


All/Svi                                       111 (53%)
Complete CoW/Kompletan Vilisov prsten         58 (52,5%)
Incomplete CoW/Nekompletan Vilisov prsten     53 (47,5%)

                                              Control group
                                             Kontrolna grupa

All/Svi                                            102
Complete CoW/Kompletan Vilisov prsten           42 (41%)
Incomplete CoW/Nekompletan Vilisov prsten       60 (59%)
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Article Details
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Title Annotation:Original study/Originalni naucni rad
Author:Manojlovic, Vladimir; Popovic, Vladan; Nikolic, Dragan; Milosevic, Dorde; Pasternak, Janko; Budakov,
Publication:Medicinski Pregled
Article Type:Report
Date:Nov 1, 2016
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