HISTOLOGICAL PrincipLES OF BRAIN ARTERIES

BAR and Neurological diseases SMALL VESSEL DISEASE Intima thickening of penetrating arteries occurred in 17% Microatheromas were exceedingly rare (< 2 %) Specimens from the BARS

BAR and Neurological diseases SMALL VESSEL DISEASE Specimens from the BARS

Wrong assumptions about brain arteries It is believed that the physiology of brain arteries is similar to systemic arteries of the same size. For example, it is believed that arteries are capable of accommodating an enlarging plaque by undergoing outward remodeling. Glagov et al. NEJM, 1987.

Assumptions about brain arteries However, there is no evidence to support that brain arteries have ability to dilate in the setting or an enlarging plaque. On the contrary, smaller (large) arteries have a lumen reduction that appears linearly related with the area of the plaque. Gutierrez et al. Atherosclerosis, 2014.

Assumptions about brain arteries Gutierrez et al. Atherosclerosis, 2014.

Assumptions about brain arteries Gutierrez et al. Atherosclerosis, 2014.

Assumptions about brain arteries Table 1. Arterial stenosis as determinant of the internal elastic lamina (IEL) proportion*   Arterial size (mm) Model 0 Beta coefficient (P-value) Model 1 Beta coefficient (P-value) Model 2 Model 3 All arteries N=1,400 1.09-7.29 0.44 (0.86) -1.85 (0.47) (0.48) -2.96 (0.14) By Quintiles First (lowest) 1.09-2.20 -24.6 (<0.0001) -28.01 -27.3 -23.65 (<0.001) Second 2.21-2.63 -1.12 (0.82) -0.53 (0.91) -0.28 (0.95) 1.23 (0.81) Third 2.63-3.10 -6.26 (0.21) -6.72 (0.19) -7.24 (0.15) -6.14 (0.23) Fourth 3.11-3.74 2.01 (0.57) 1.81 (0.63) 1.95 (0.60) 0.07 (0.98) Fifth (highest) 3.74-7.29 16.7 13.4 (0.006) 12.4 (0.003) 5.99 (0.13) Model 0: Univariate. Model 1: Adjusting for age, sex, and race/ethnicity. Model 2: Adjusting for age, sex, and race/ethnicity, hypertension, diabetes, dyslipidemia, and smoking. Model 3: Adjusting for age, sex, and race/ethnicity, hypertension, diabetes, dyslipidemia, smoking and arterial size and location. *Exponential transformation was used to achieve normalization. Gutierrez et al. Atherosclerosis, 2014.

Particularities OF THE BRAIN CIRCULATION The circle of Willis is an unique structure that influences arterial caliber and flow pattern depending on its configuration The brain autoregulates the flow by distal arterioles within a broad range to allow steady perfusion. The brain is a low-resistance system (similar to the kidney) which allows greater transmissibility of pulsatility to the brain Hassler, O. Acta anatomica, 1962 De Groot et al. PLoS One, 2006 Gutierrez et al. Atherosclerosis, 2014

Brain arterial disease is rarely focal Analyzing the spread of stenosis within each case disclosed arteries with minimal degrees of stenosis coexisting with arteries with a maximum stenosis that varied from 10 % to a maximum of 70%. The average difference between the lowest and highest degrees of stenosis among the arteries within each case was within 12 % suggesting a high degree of concordance in stenosis within individuals, however. Gutierrez et al. Int J Stroke, 2014.

Brain arterial disease is rarely focal Gutierrez et al. Int J Stroke, 2014.

Brain arterial disease is rarely focal For example, comparing the average stenosis from arteries in the anterior circulation to that of the posterior circulation demonstrated that their mean stenosis differed by < 5 % in 64% of the subjects, by 6 to 10% in 26 % and by 11 to 21 % in only 10 %. The average arterial stenosis of one hemisphere vs. the contralateral showed that both means were within 5% of each other in 75% of the cases, between 6-10 % in 19 %, and between 11 and 15% in only 6 % of the cases. Gutierrez et al. Int J Stroke, 2014.

Brain arterial disease is rarely focal Gutierrez et al. Int J Stroke, 2014.

Brain arterial disease is rarely focal The average difference in stenosis between proximal and distal segments of the same artery was between 4-5%. In only a minority of occasions (9%) the difference in stenosis between the proximal and distal portion of the same artery exceeded 10% and the maximum difference was never greater than 22 %. The concordance in stenosis within the same arterial segment increased as the average arterial stenosis increased. Gutierrez et al. Int J Stroke, 2014.

Brain arterial disease is rarely focal

Correlation Between Posterior Circulation Pathology With Anterior Circulation Pathology Roth et al. Stroke, 2017.

Extracranial atherosclerosis and the BAR score Gutierrez et al. Cerebrovasc Dis, 2016.

Circle of Willis anatomy and remodeling Compensatory dilatatory changes in ipsilateral downstream arteries is greater when collaterals are available Carotid atherosclerosis in one carotid was not associated with dilatatory changes in the VB system, however, when both carotid had evidence of disease (either cIMT, number of plaques or MCPT), there were increased arterials diameters in the posterior circulation. Gutierrez et al. Int J Stroke, 2014.

Atherosclerosis All that glitters is not gold. Similarly, all arterial disease is not atheromatous. Atheroma: "lump of gruel", from Greek ἀθήρα (athera), meaning "gruel")

Atherosclerosis Gruel Atheroma

Dolichoectasia & the creation of myths “The main etiologic factors of dolichoectasia are atherosclerosis, defects or destruction of the internal elastic, and hypertension”. AJNR, 2006 27: 1241-1244 Evidence 1: “The third case (out of five!) showed considerable atheroma and dilatation of the basilar artery, with aneurysm formation at its tip”

Dolichoectasia & the creation of myths Evidence 2: “Other authors agree with Dandy's conclusion that these changes "all are unquestionably of arteriosclerotic origin” and see in them a variant of this common arterial disease. This is also not correct. Therefore, we believe that the presence of arteriosclerosis is rather coincidental”