Atherothrombosis may cause cerebral infarction in several ways. The most obvious is that an occlusive plaque or a thrombus formed on a plaque occupies the lumen of a major intracerebral vessel, such as the middle cerebral artery, and stops flow to the areas of the brain supplied by the vessel. A variation of this mechanism is one of occlusion by atherosclerosis of a more proximal vessel, such as the distal carotid artery. This may lead to infarction in the territory between major branches of the internal carotid circulation that are most susceptible to reduced blood flow—termed “borderzone,” or “end-arterial,” or less accurately, “watershed infarction,” depending on the richness of collateral vessels. Or, an atherothrombotic lesion in a proximal vessel may serve as the nidus for the formation of an embolus that manifests itself as a stroke in one of the territories of that vessel—called “artery-to-artery” embolism (cardioembolic stroke is more common). A separate mechanism pertains when an atherosclerotic plaque in a large vessel of the circle of Willis occludes the orifices of small penetrating vessels, most often the lenticulostriate branches of the middle cerebral artery or the thalamostriate vessels of the posterior cerebral artery, and cause small, or more confluent, strokes deep in the brain.
Whether plaque rupture plays a role in vessel occlusion or thrombus formation, as it does in the coronary artery, is not clear. In the carotid artery, Hosseini and coworkers found evidence of intraplaque hemorrhage using special MRI techniques and found these changes to be predictive of stroke in the distal distribution of the artery. Previous work by Fisher and Ojemann, cited in the references, involving the serial sectioning of carotid plaques removed at surgery, suggested otherwise. It is clear that the more severe the focal atheromata, the more likely a thrombotic complication will occur. Whether the complexity of a carotid artery plaque with ulcerations is an important component of stroke risk, for example, by originating small emboli, is not settled. Again, it is the high degree of stenosis, usually above 90 percent of the original lumen compromised, or a residual lumen of less than approximately 2 mm, of the carotid artery that is most likely to be associated with strokes in the distal territory of the vessel.
Atheromatous lesions may regress to some extent under the influence of diet and lipid-lowering drugs. Hennerici and colleagues followed a series of patients with carotid stenosis for a period of 18 months and observed spontaneous regression in nearly 20 percent of the lesions. In the large majority of cases, however, atherosclerosis is a progressive disease if the underlying risk factors, such as hyperlipidemia, smoking, diabetes, and hypertension, are not addressed.
The hemostatic elements, both clotting factors and platelets, which produce a thrombus within a vessel are complex and have been the object of intense study (see Furie and Furie for a discussion of this field). However, just as in the case of coronary artery disease, it is often the development and enlargement of the thrombus that acts as the final element in cerebral vascular occlusion and an ischemic stroke. It seems plausible, although not adequately studied, that the temporal profile of atherothrombotic stroke reflects this accretion of clot in a vessel. These biologic mechanisms have bearing on the treatment and prevention of stroke.