Atherosclerosis, or what is commonly referred to as “hardening of the arteries,” refers to a generalized deterioration of the arteries of the body. Each organ in the human body, such as the heart, kidney or brain, has its own blood supply, which is susceptible to all the diseases affecting the blood vessels throughout the body, as well as some unique disease features for each individual arterial system. This review will be limited to a discussion of atherosclerosis affecting the arteries within the brain.
The requirements of the brain for oxygen and nutrients, such as blood sugar (glucose), are enormous, consuming up to 15% to 20% of what the heart can deliver to the body. The brain, therefore, requires a robust blood supply and is exceptionally vulnerable to any interruption in blood flow. Nature has provided a unique system of blood flow to the brain. There are four major arteries, all providing blood flow to brain structures (two carotid arteries and two vertebral arteries). Once these vessels enter the brain, they divide in a manner such that all arteries are connected to each other through a system called the circle of Willis, named after Sir Thomas Willis, an anatomist living in the 1600’s, who first described this unique arrangement. Theoretically, blood flow to the brain can be maintained through this system even if one or more of the arteries becomes occluded, providing that all connections are developed between the vessels and at least one vessel is fully open. In reality, this is rarely achieved.
One other notable feature of the blood flow to the brain is its constant nature despite fluctuations in systemic blood pressure, a phenomenon called autoregulation. If your blood pressure drops, the vessels in the brain dilate to allow greater blood flow. Alternatively, if your blood pressure increases, the vessels in the brain constrict to avoid excessive blood flow. This mechanism functions to maintain relatively constant cerebral blood flow over a wide range of systemic blood pressures. Clearly, maintaining a reliable, constant flow of blood to the brain is a critical requirement for brain function and survival.
The arterial system within the brain is divided into two major arterial networks, the anterior and posterior vascular systems. The anterior system, arising from the internal carotid arteries, is comprised of the anterior cerebral artery, which supplies blood to the center of the brain, and the middle cerebral artery, which supplies the surface of the brain and a large portion of the deeper brain substance. The posterior vascular system arises from the two vertebral arteries, which fuse once they enter the skull to form the basilar artery. The vertebral – basilar arterial system supplies blood to the deepest brain structures, i.e., the brainstem and cerebellum. The basilar artery then divides into two posterior cerebral arteries, which supply blood to the back of the brain, the occipital lobes, where vision is located. Each arterial system, therefore, supplies specific brain structures, with specific neurological symptoms arising when a vessel becomes narrowed. Your neurologist uses the symptoms and findings observed while conducting a neurological exam to determine which vessel is involved. The assessment is further refined by neurodiagnostic imaging with MRI scanning of the brain, a MRA of the blood vessels and a carotid ultrasound.
Narrowing of an Intracranial Artery:
When a major intracranial artery (an artery inside the skull) becomes significantly narrow, the risk for circulation failure to an area of the brain and subsequent stroke increases, especially if the narrowing exceeds 50%. Either failure of blood flow across the area of narrowing, or dislodgment of pieces of blood clot that then flow downstream blocking distal arterial branches, are the main mechanisms of stroke in this clinical circumstance. The symptoms that arise depend on which brain systems (speech, vision, movement, sensation, etc.) are deprived of blood.
Narrowing of intracranial arteries as a cause of stroke is found in approximately 5% to 10% of stroke patients. Recurrent intracranial stroke has been estimated to be 7% to 40% annually. The best therapy for treatment of this problem, however, is somewhat controversial, although it is being clarified with recent and current research projects.
Medical Treatment for Intracranial Atherosclerosis
“Blood thinning” therapy
Two options exist for “thinning the blood” (which is a misnomer as these agents actually make the blood less likely to clot; the blood is just as thick as before treatment), antiplatelet and anticoagulant therapy.
Medication, such as aspirin, clopidogrel (Plavix), or a combination of aspirin and dipyridamole (Aggrenox), are the current primary choices of antiplatelet agents. An initial phase in the evolution of a clot is aggregation of platelets, small spherical bodies in the blood that initiate clotting. Antiplatelet drugs work by interfering with the initial phase of platelet aggregation markedly interfering with the clotting process. Anticoagulant medication is limited to a single drug, warfarin (Coumadin), for outpatient therapy. Warfarin works by interfering with the synthesis of clotting proteins in the liver by antagonizing vitamin K.
The relative risks and benefits of these two treatment approaches was assessed in a relatively recent research study (NEJM:2005;352:1305 – 1316), with an accompanying editorial. Basically, the research demonstrated that the risk of stroke over a 2-year period of time for symptomatic patients was 10% if the artery was less than 70% narrowed and nearly 20% if the artery was more than 70% narrowed. Treatment with aspirin and warfarin gave the same protection for stroke, but the warfarin group had a higher bleeding rate. The study was complex and the accompanying editorial gave several warnings in interpreting the results. Currently, aspirin is the drug of choice unless other complicating features exist.
Blood pressure control
Managing blood pressure is perhaps the most critical factor in prevention and treatment of intracranial atherosclerosis and stenosis. Hypertension accelerates the development of atherosclerosis leading to narrowing of the arteries, loss of the normal lining of the arteries and increased tendency for a clot to form, occluding the vessel. Studies have demonstrated that patients with high-normal blood pressure (130–139 systolic, and 85-89 diastolic) have twice the risk of a stroke or heart attack compared to patients with blood pressure of 120/80. Control of blood pressure is essential in the proper management of intracranial arterial narrowing.
Elevated cholesterol is a significant risk factor for stroke development. Studies demonstrate that for every approximately 40 mg increase in total blood cholesterol above normal, there is a 25% increased risk of stroke. The numbers vary from study to study, but the elevated risk persists in most, but not all, studies. Treatment with a cholesterol-lowering agent, therefore, is an essential element in the treatment of intracranial atherosclerosis.
It has been estimated that nearly 40% of all ischemic strokes can be attributed to the effects of diabetes, either alone or in combination with hypertension. The elevated risk reflects accelerated atherosclerosis, as well as the increased prevalence of additional risk factors in diabetic patients, i.e., central obesity, elevated cholesterol and hypertension. Close management of diabetes and associated risk factors are essential for proper management of intracranial arterial narrowing.
Smokers have an elevated risk of stroke estimated at twice the baseline rate, with smokers younger than 55 years old having a risk nearly 3 times higher than non-smokers. If you smoke, you significantly elevate your stroke risk. One simple suggestion: STOP.
Diet and weight management
Diets high in fruits and vegetables are associated with a lower stroke risk. This relationship is especially notable for green leafy vegetables, cruciferous vegetables (i.e., broccoli, cauliflower, etc.) and citrus fruit. There is a 6% reduction in the risk of stroke with each one serving of fruits and vegetables daily.
Weight management and reduction of obesity also reduces stroke risk. The elevated risk ranged from 75% to 150% for differing degrees of obesity. Abdominal obesity (defined by a waist circumference greater than 34 inches in a female and 40 inches in a male) showed an elevated risk of stroke in males, but not females. The body mass index (BMI), a measure which takes into account not just your weight but also height (weight in kg/height, in meters squared, for those who like formulas) showed an increased risk of stroke in women with BMI values greater than 27.
Physical activity of moderate to high levels may also protect against stroke for all ages, races, and gender. Since the artery is located within the skull, surgical options are limited.
Surgical Treatment for Intracranial Atherosclerosis
EC-IC bypass surgery: A type of bypass surgery called EC-IC bypass (extracranial–intracranial bypass surgery) was studied several years ago (1985). The procedure entails connecting an artery in the scalp to an artery in the brain. Basically, a reasonable sized artery from the scalp is connected through a hole in the skull to an appropriate vessel on the surface of the brain. This was generally offered when the internal carotid artery in the neck or the intracranial middle cerebral artery was occluded. A major study, however failed to demonstrate a difference in those who were operated on versus those patients treated medically. The procedure is performed only rarely at this time.
Angioplasty and stenting: Cerebral angioplasty and stenting are procedures which evolved from success in treating narrow arteries in the heart causing heart attacks. Progress in developing similar procedures for narrow arteries in the brain has been steady with new procedures, technological advances, improved stents and better imaging techniques now available.
The procedure involves threading a catheter through an artery in the groin (femoral artery) up to the carotid arteries in the neck. The catheter is then carefully advanced up into the head to the area of narrowing of the intracranial artery. A balloon type expansion of the catheter will widen the area of narrowing followed by placement of a stent, which provides a rigid scaffold to maintain vessel patency.
A successful angioplasty and stent placement allows improved blood flow to the brain, prevents platelet activation in the area of stenosis, allows for regrowth of the normal lining along the vessel wall, and prevents plaque rupture and occlusion of the vessel. Angioplasty and stenting are offered to patients who are unresponsive to medical treatment, have greater than 50% stenosis of an intracranial artery and have a favorable anatomical arrangement of the cerebral vasculature (i.e., no unusual congenital variation). There are several circumstances where angioplasty/stenting cannot be offered, including chronic complete occlusion of the vessel, severe neurological impairment from a stroke distal to the lesion, a major stroke in the previous 6 weeks, or a contraindication to dual antiplatelet agents (usually aspirin and clopidogrel) after the procedure.
Several studies have been published regarding the results of intracranial stenting. Without mentioning each individual study, generally the stents were placed successfully in most patients with a procedure-related stroke risk of around 7% to 10%. Unfortunately, re-stenosis occurred in a large number of patients (reports range from 7% to 40%). Clearly, further research and development will be required to perfect this therapeutic modality.
In summary, intracranial arterial narrowing is a significant cause of stroke. There are many treatment options to manage and prevent stroke in this setting with newer techniques being developed. Close management of risk factors, however, remains the single most effective measure to avoid stroke from any cause including intracranial stenosis.
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