A pathological perspective on the natural history of cerebral atherosclerosis

Background The natural history of intracranial large artery atherosclerosis has been mainly described from lumen-based imaging studies, and much of what is reported to be known about atherosclerosis is derived from non-cerebral arteries. Aims To test the hypothesis that atherosclerosis is only partially represented by stenosis and that advanced atherosclerosis is more common that severe stenosis in noncardioembolic infarcts. Methods Cerebral large arteries from 196 autopsy cases were studied. The revised American Heart Association classification for atherosclerosis was used to determine the phenotype in each available artery. Cross-sectional lumen stenosis was obtained as defined by the Glagov's method. Results As age of cases increased, there was a progressive increment in the frequency of atherosclerotic lesions, rising from 5% of all arteries at age 20-40, to more than 40% at age 60 or older. Stenosis also increased with age: less than 3% of the arteries in those <= 50 years had >40% stenosis, while one out of five arteries in those >80 years had >40% stenosis. In most cases (80%), atherosclerosis and stenosis were directly related. However, one out of five cases with advanced atherosclerosis had <30% stenosis. In arteries supplying brain areas with noncardioembolic infarcts, the majority of segments exhibiting advanced atherosclerosis had lumen stenosis of <40%. Conclusion Although intracranial atherosclerosis is typically associated with stenosis, a substantial minority of cases shows advanced atherosclerosis in the absence of stenosis >40%. Definitions based solely on stenosis may underestimate the extent and role of intracranial large artery atherosclerosis.