Background: Anatomic variants of the circle of Willis (CW) are commonly observed in healthy subjects. Genetic and environmental factors influencing these variants remain unclear. Our aim was to assess the genetic and environmental background affecting variant CW phenotypes. Methods: A total of 122 adult healthy twins from the Hungarian Twin Registry (39 monozygotic (MZ) and 22 dizygotic (DZ) pairs, average age 49.7 ± 13.4 years) underwent Time-of-Flight magnetic resonance angiography and transcranial Doppler sonography. We investigated the anterior and posterior CW according to morphological categories. Prevalence and concordance rates of CW variants were calculated. MZ twins discordant for CW variants were analyzed for cardiovascular risk factors and altered blood flow. Results: Complete CW (45.0%) and bilaterally absent posterior communicating artery (PCoA) (22.5%) were the most prevalent variants in the anterior and posterior CW, respectively. There was no significant difference regarding the prevalence of variants across zygosity except for bilaterally hypoplastic PCoA (p = .02). DZ concordance was higher compared to MZ twins regarding morphological categories of the CW. Cardiovascular risk factors were not significantly associated with variant CW in MZ twins discordant to CW morphology. Flow parameters did not differ significantly among MZ twins discordant to CW variants. Conclusion: CW variants may not be determined by substantial genetic effects and are not influenced by altered blood flow in healthy individuals. Further investigations are needed to identify potential environmental factors affecting these variants.

Introduction: Impaired collateral circulation can lead to stroke during carotid endarterectomy. Carotid stump pressure (CSP) is used as a surrogate measure of collateral flow. The objective was to determine whether anatomical features obtained from digital subtraction angiography correlate with CSP during temporary internal carotid artery occlusion. The second objective was to use these features in combination to predict CSP. Methods: Digital subtraction angiographies from 102 patients obtained before endarterectomy were reviewed for anatomical variables including: degree of ipsilateral and contralateral carotid artery stenosis; patency of the anterior communicating artery; presence of cross-flow into ipsilateral middle cerebral artery branches; and size (< or ≥1 mm calibre) of the ipsilateral proximal anterior cerebral (A1), the contralateral A1, and the ipsilateral posterior communicating arteries. At surgery, systemic mean arterial pressure (MAP) and CSP were recorded. Multiple regression analysis was used to assess for anatomical features significantly associated with CSP. A “predicted CSP” equation was applied to 54 subsequent patients and correlated with measured CSP. Results: Variables correlating with CSP included MAP (p=0.001); the presence of severe contralateral carotid stenosis (p=0.002); patency of the anterior communicating artery (p=0.013); and the size of the contralateral A1 segment (p=0.029). Angiographic cross-flow, ipsilateral A1 size, and ipsilateral posterior communicating artery size were not significant. Predicted CSP correlated significantly with measured CSP (p<0.0001; R2=0.34). Conclusions: Anatomical features and systemic MAP are associated with carotid stump pressure during internal carotid artery occlusion and account for a significant amount of its variation.

Introduction: The Circle of Willis (CoW) is the most effective collateral circulation to the brain during internal carotid artery (ICA) occlusion. Carotid stump pressure (CSP) is an established surrogate measure of the cerebral collateral circulation. This study aims to use hemodynamic and computed tomography angiography measurements to determine the strongest influences upon the dependent variable, CSP. These findings could help clinicians noninvasively assess the adequacy of the collateral circulation and facilitate surgical risk assessment in an outpatient setting. Methods: CSP and mean arterial pressure were measured during carotid endarterectomy or during carotid balloon test occlusion in 92 patients. Intracranial arterial diameters were measured on computed tomography angiography at 16 different locations. Univariate and multivariate analyses were used to determine the key factors associated with CSP. In a subgroup of individuals (n=27) with severe (>70% North American Symptomatic Carotid Endarterectomy Trial) contralateral stenosis or occlusion, the same analysis was performed. Results: The contralateral anterior cerebral artery proximal to anterior communicating artery (A1) of the CoW had the strongest influence upon CSP, followed by the mean arterial pressure, the contralateral ICA diameter, and the anterior communicating artery diameter (R2=0.364). In the subgroup with high-grade contralateral ICA stenosis, the ipsilateral posterior communicating artery exerted the strongest influence (R2=0.620). Conclusions: During ICA occlusion, the anterior CoW dominates in preserving collateral flow, especially the contralateral A1 segment. In individuals with high-grade contralateral carotid stenosis, the posterior communicating artery calibre becomes a dominant influence. The most favourable anatomy consists of large contralateral A1 and anterior communicating arteries, and no contralateral carotid stenosis.

Thomas Willis [1621-1675] was not the first to describe the circle of vessels at the base of the brain that bears his name, but it was he who first recognised its functional significance in maintaining cerebral perfusion even after one of its feeding vessels was completely closed. Although Willis made many astute, original clinical observations (concerning myasthenia gravis, paracusis, restless legs syndrome and diabetes mellitus) his reputation suffered because he was an inveterate theorist in an age that frowned on hypotheses. Nonetheless he is now recognised as one of the earliest neuropsychiatrists who attempted to understand and explain mental illness, as he encountered it in his daily practice, in terms of brain dysfunction more than 300 years ago.