Historical Review

The development of surgery on the extracranial cerebrovascular circulation was dependent on three principal factors: (1) recognition of the pathologic relationship between extracranial cerebrovascular disease and subsequent cerebral infarction, (2) the introduction of cerebral angiography to identify lesions before the patient’s death, and (3) the development of vascular surgical techniques that could be applied to the extracranial vessels once the anatomic patterns of disease were understood and described.

The earliest report linking cervical carotid artery disease to stroke is credited to Savory,¹ who in 1856 described a young woman with left monocular symptoms in combination with a right hemiplegia and dysesthesia. Postmortem examination demonstrated an occlusion of the cervical portion of the left internal carotid artery, along with bilateral subclavian artery occlusions. In 1875, Gowers reported a similar case,² and subsequent reports of individual cases were made by Chiari in 1905,³ Guthrie and Mayou in 1908,⁴ and Cadwater in 1912.⁵ By 1914, Hunt,⁶ in an important publication, emphasized the relationship between extracranial carotid artery disease and stroke. He also described the phenomenon of intermittent cerebral symptoms associated with partial occlusion and used the term cerebral intermittent claudication as a characterizing analogy. Hunt also pointed out that the clinicopathologic observations in patients with stroke were hampered by the fact that routine autopsies did not include examination of the cervical carotid arteries (as is often the case today because of the desire to maintain access to the external carotid artery for the mortician). He emphasized that no examination of cerebral infarction can be considered complete without examination of the neck vessels.⁶

The next major step in the evolution of the management of extracranial cerebrovascular disease came with the development of carotid angiography by Moniz in 1927.⁷ By 1937, Moniz and colleagues had described four cases of internal carotid occlusion diagnosed by angiography.⁸ In 1938, Chao and colleagues added two more cases,⁹ and by 1951, Johnson and Walker had collected from the world literature a total of 101 cases of occlusion of the cervical carotid artery diagnosed by angiography.¹⁰ Despite these early observations, the medical world was still slow to appreciate the relationship between extracranial cerebrovascular disease and cerebral symptoms, as emphasized by the fact that when cerebral angiography came into common use for neurologic diagnosis in the 1950s and 1960s, only the intracranial vessels were included on radiographs films. The area of the carotid bifurcation was seldom examined. By the late 1950s, patients with hemiplegia were still commonly receiving diagnoses of a middle cerebral artery thrombosis, without consideration of the carotid bifurcation as a source of the problem.

The next major steps in the evolution of understanding came from reports by Fisher in 1951 and 1954.^11,12 Fisher reemphasized the relationship between extracranial arterial occlusive disease and cerebral symptoms. He also pointed out that the lesion could be either total occlusion or stenosis. His most important observation, however, was that the disease was often localized to a short segment of the carotid artery, and he predicted that surgical correction might be possible if patients could be identified in the early stages of the clinical syndrome. Fisher stated, “It is even conceivable that some day vascular surgery will find a way to bypass the occluded portion of the artery during the period of ominous fleeting symptoms. Anastomosis of the external carotid artery or one of its branches with the internal carotid artery above the area of narrowing should be feasible.”

The surgical phase of understanding and managing extracranial cerebrovascular disease probably began in 1951, but it was not reported in the literature until 1955. This early report by Carrea and colleagues¹³ from Buenos Aires described their experience with the management of a patient with carotid artery stenosis. They resected the diseased internal carotid artery and performed an anastomosis between the external carotid artery and the distal internal carotid, as predicted earlier by Fisher.¹¹ In 1953, Strully and coworkers¹⁴ attempted a thromboendarterectomy of a totally thrombosed internal carotid artery. This attempt was unsuccessful, but the authors suggested that thromboendarterectomy should be technically feasible before thrombosis occurred, as long as the internal carotid artery is patent distally. The first carotid endarterectomy was probably performed by DeBakey and colleagues in an operation done on August 7, 1953, but it was not actually written up until 1959 and then reviewed in 1975.^15,16 The report that was most important in calling the world’s attention to the feasibility of carotid artery reconstruction came from Eastcott and associates.¹⁷ Their operation was performed on May 19, 1954, on a patient who was having hemispheric transient ischemic attacks (TIAs) with demonstrable disease at the carotid bifurcation; they used direct, end-to-end anastomosis between the common carotid artery and the internal carotid artery distal to the atherosclerotic lesion.

Although operations on the carotid artery were in the early phase of development, surgical attack was also considered feasible on occlusive lesions of the major arch vessels. In 1956, Davis and colleagues¹⁸ reported their experience with endarterectomy of the innominate artery performed on a patient on March 20, 1954. In 1957, Warren and Triedman reported the second case.¹⁹

By this time, the stage was set for the explosive development of an aggressive surgical approach to managing extracranial cerebrovascular disease as a means of preventing or treating cerebral infarction.

Thompson,²⁰ in his 1996 Willis lecture, related in great detail the history of surgery to prevent stroke. Those interested in the definitive history will be rewarded by reading this excellent paper.

Natural History of Extracranial Arterial Occlusive Disease

Therapy aimed at the prevention of cerebral infarction must be compared with the natural history of the disease process. The prognosis for a patient with extracranial arterial occlusive disease differs, depending on the presence or absence of symptoms. When a permanent neurologic deficit is present, the outlook worsens, thus underscoring the importance of prevention. A thorough understanding of the natural history of the disease is essential to formulating a rational and effective therapeutic program. The physician needs to be familiar with the expected results of each available option. This implies that no single alternative is applicable to all situations and that individualization is the key to effective prevention.

In the United States, approximately 600,000 people suffer a first stroke each year. In 200,000 of these cases, death follows, but at any one time approximately 1 million stroke victims are alive and disabled. In 1976, the annual direct and indirect cost of stroke was estimated at $7,363,784,000.²¹ Nearly 30 years later, with inflation and the accelerating cost of medical care, this cost has probably quadrupled. The incalculable morbidity of the affected individual adds further to the magnitude of this problem. Prevention remains the most plausible alternative.

The initial mortality of an ischemic stroke ranges from 15% to 33%.^22–24 Survivors remain at an inordinately high risk of subsequent stroke, estimated between 4.8% and 20% per year.^25,26 This implies that half of patients will experience a second event within 5 years.^23,27,28 The average recurrent stroke rate reported in the literature is between 6% and 12% each year. The most common cause of death in patients with extracranial arterial occlusive disease is myocardial infarction (MI). In an analysis of 535 stroke victims, however, the leading cause of death was recurrent stroke, as opposed to the expected myocardial mortality.²⁶

Since 1973, public health statistics have documented an accelerating decline in stroke mortality.²⁹ Stroke used to be considered the third leading cause of death in the United States. The American Heart and Stroke Association recently reported that stroke has now dropped to the fourth leading cause of death. The reasons for this are multifactorial but include successful efforts at primary prevention including surgical intervention and treatment of carotid bifurcation lesions, improved medical management, and better care of the patient with acute stroke, often in specialized centers. This reduction in stroke mortality has led to the erroneous assumption that a decline has also occurred in stroke incidence, which is not the case.

In 1989, Wolf and colleagues³⁰ reported the epidemiologic data from the Framingham Study to the 14th International Joint Conference on Stroke and Cerebral Circulation. They reviewed the experience from three successive decades, beginning in 1953. A decline in stroke fatality in both men and women was observed. However, the 10-year prevalence of stroke actually rose, and the incidence of stroke in men rose from 5.7% to 7.6% to 7.9%, without any apparent change in women. The authors postulated that falling case fatality rates might have resulted from changes in diagnostic criteria, a lessening in stroke severity, or improved care of stroke patients.

Harmsen and colleagues³¹ reviewed the stroke incidence and fatality in Gothenburg, Sweden, between 1971 and 1987. They noted that the stroke incidence remained the same during that interval, but the stroke fatality rate declined in both sexes. This was more marked for intracerebral hemorrhage and subarachnoid hemorrhage than for infarction. They concluded that the decline in stroke fatality rates might have been related to a decrease in smoking or better management of blood pressure. They could not explain why no corresponding decline in stroke incidence occurred.

Finally, Moden and Wagener³² examined the epidemiologic aspects of stroke based on death certificate information available from the National Center for Health Statistics’ compressed mortality file for all 50 states and the District of Columbia for the period 1968 to 1988. They noted a decline in stroke mortality that continued through the 1970s and 1980s, whereas morbidity remained constant and possibly even increased. They noted similar morbidity and mortality rates in both sexes. They concluded that the observed decrease in stroke mortality rates resulted from improved survival rather than a decline in incidence.³²

A variety of reasons for the decline in stroke mortality have been postulated, including the more aggressive treatment of hypertension. No one has suggested that the decline of stroke mortality might be related to the increasing use of carotid endarterectomy, as illustrated in Figure 18-1. Although this is not proof of a relationship, a possible relationship cannot be discounted.

FIGURE 18-1 The declining incidence of stroke-related death from 1968 to 1981 is compared with the accelerated frequency with which carotid endarterectomy was performed during the same period.

Two clinical syndromes deserve special emphasis because of their dismal natural history. Stroke in evolution is also known as progressing stroke or incomplete stroke; it is an acute neurologic deficit of modest degree that within hours or days progresses to a major cerebral infarct. This can happen in a sequential series of acute exacerbations or in a pattern of waxing and waning signs and symptoms over hours or days, with incomplete recovery eventually leading to a major fixed neurologic deficit. Crescendo transient ischemic attacks is the pattern that allows complete recovery between ischemic events, suggesting repeated frequent embolization from a point arterial source in the affected territory.

In a review of the literature, Mentzer and colleagues³³ identified 263 reported cases of stroke in evolution managed conservatively. Twenty-three percent had complete resolution or mild neurologic deficit on follow-up. Sixty-two percent had a moderate to severe deficit in the early recovery phase. The overall mortality was 14.5%. In their own series, 26 patients with stroke in evolution were treated conservatively. Mortality was 15%, but, more importantly, 66% suffered moderate to severe permanent neurologic deficits, with only five patients recovering completely or experiencing only mild neurologic dysfunction. These results are compared with a series of 17 patients operated on emergently for stroke in evolution. None of these patients had worsening of the preoperative neurologic deficit, four (24%) remained unchanged, and 12 (70%) had complete recovery.³³

In 1972, Millikan reviewed the natural history of patients with progressing stroke.³⁴ Of 204 patients, 12% were normal at 14 days, 7% had developed moderate to severe neurologic deficits, and 14% had died. Thus, stroke in evolution treated conservatively carries a poor prognosis. More than half of patients develop a severe permanent neurologic deficit within a few days of the onset, and approximately 15% die as a result. Only 10% to 20% recover full or partial neurologic function.³⁴

Patients who experience TIAs are also at a higher risk of developing a stroke. In the Mayo Clinic population study,³⁵ 118 patients with TIAs were monitored as a control group without therapy. The stroke rates at 1, 3, and 5 years were 23%, 37%, and 45%, respectively. Most permanent deficits occurred during the first year. This represents a sixteenfold increased risk of stroke compared with an age- and sex-adjusted population. The Oxfordshire project reported an actuarial risk of stroke during the first year after the onset of TIAs to be 11% to 16%.³⁶ For each subsequent year, the rate was 5% to 9% per year. Some series have reported lower figures,^37,38 but the average reported in the literature is on the order of 30% to 35% at 5 years, or 10% the first year and 6% each year thereafter.

Finally, Toole³⁹ noted that cerebral infarction in TIA patients goes unrecognized by either patient or physician surprisingly often. These lesions are now identified by better neuroimaging techniques, and there is now evidence to suggest that TIAs are actually small strokes.³⁹ If a TIA is actually a small stroke, the implied benignity of TIAs must be reexamined, and it may be equally important to prevent TIAs. This consideration is further strengthened by the observations of Grigg and colleagues,⁴⁰ who correlated cerebral infarction and atrophy as a function of TIAs and percentage of stenosis. They graded carotid stenosis in symptomatic patients from A (no stenosis) to E (occlusion). In patients with amaurosis fugax, the incidence of cerebral infarction rose from 2% in patients with stenosis grades A, B, and C to 40% in grade D and 58% in grade E. The incidence of atrophy increased in parallel, from 10% in grade A to 30% in grade E.

The natural history of asymptomatic patients with significant extracranial or arterial occlusive disease is difficult to predict accurately. Most studies that have addressed this problem used the presence of a cervical bruit as the sole criterion for inclusion. This inevitably includes patients without significant occlusive disease and omits others without cervical bruit but with high-risk lesions in the extracranial circulation.

As noninvasive studies developed, detection of hemodynamically significant lesions in the carotid system improved. Kartchner and McRae monitored 1130 patients who either were asymptomatic or had nonhemispheric symptoms.⁴¹ The mean interval was 24 months. Of 303 patients with hemodynamically significant lesions, 11.9% had strokes at 2 years. The group with negative noninvasive studies had a much lower stroke rate, on the order of 3% over the same follow-up period. Busuttil and colleagues⁴² noted an unfavorable trend toward higher stroke rates in asymptomatic patients with hemodynamically significant lesions in the carotid bifurcation.

In a report by Roederer and colleagues,⁴³ 167 asymptomatic patients with cervical bruits were monitored with serial duplex scanning regardless of the degree of stenosis at the time of presentation. During follow-up, 10 patients became symptomatic. The development of symptoms was accompanied by disease progression in 80% of patients. By life-table analysis, the annual rate of symptom occurrence was 4%; however, the presence of progression graded at 80% stenosis was highly correlated with the development of either total occlusion of the internal carotid artery or new symptoms. Thus, 89% of the symptoms were preceded by progression of the lesion to greater than 80% stenosis. Progression of a lesion to more than 80% stenosis was an important warning sign, because it carried a 35% risk of ischemic symptoms or internal carotid occlusion within 6 months and a 46% risk at 12 months. Conversely, only 1.5% of the lesions that remained at less than 80% stenosis developed such a complication. These data suggest that careful follow-up with repeated noninvasive evaluation is of great assistance in determining the appropriate management of asymptomatic carotid lesions.⁴³

In an analysis of 294 asymptomatic and nonhemispheric patients submitted to cerebrovascular testing, Moore and colleagues⁴⁴ found a 15% stroke incidence during the first 2 years in patients with greater than 50% stenosis. In contrast, there was a 3% stroke incidence at 2 years in patients with 1% to 49% stenosis. The difference was found to be statistically significant (p < 0.05). The 5-year cumulative stroke incidence was 21% with greater than 50% stenosis, 14% with 1% to 49% stenosis, and 9% in patients with no noninvasive evidence of carotid artery disease.

Chambers and Norris⁴⁵ monitored a group of 500 asymptomatic patients with noninvasive studies and clinical evaluation. They identified two high-risk groups: those with stenosis greater than 75%, and those who showed disease progression between studies. For patients with greater than 75% stenosis, the 1-year neurologic event rate (TIA and stroke) was 22%. The 1-year stroke rate alone was 5%. In a later publication,⁴⁶ the authors continued to note that neurologic events correlated with an increasing percentage of stenosis as well as disease progression between test intervals. In the study viewed over 5 years, the annual average neurologic event rate was 10% to 15%, with the highest event rate occurring within the first year of diagnosis. Finally, the incidence of silent cerebral infarction as documented by computed tomography (CT) was studied in the same patient population. The authors noted a 10% incidence of cerebral infarction among patients with mild (35% to 50%) stenosis, 17% with moderate (50% to 75%) stenosis, and 30% in patients with severe (>75%) stenosis. The authors concluded that silent cerebral infarction might be an indication for carotid endarterectomy in asymptomatic patients.⁴⁷

Although the natural history of asymptomatic carotid stenosis remains controversial, studies using serial noninvasive cerebrovascular testing have concluded that an increased risk of stroke exists ipsilateral to a 50% or greater carotid artery stenosis. These lesions appear to carry a risk of subsequent stroke on the order of 4% per year. In addition, progression of the disease carries an even higher risk of stroke, with lesions causing greater than 80% stenosis carrying a 35% risk of subsequent symptoms or carotid occlusion at 2 years.

Other studies have suggested that the composition of the plaque influences the stroke risk of carotid artery lesions. In one analysis, 297 patients with carotid stenosis greater than 75% at the time of initial study were at higher risk than peers without significant narrowing or development of symptoms ipsilateral to the lesion.⁴⁸ Even those patients with less than 75% stenosis were at greater risk if the associated plaque was less organized (i.e., soft). This was determined by B-mode ultrasonography, which was used to classify plaques as dense, calcified, or soft. A definite trend toward higher risk was seen in plaques of lower density. Only 10% of those patients with calcified plaque in significantly stenotic vessels developed symptoms, whereas 92% of patients with soft plaques and tight stenosis developed symptoms within the first 3 years of follow-up.⁴⁸ The morphology of the atherosclerotic plaque, as documented by B-mode ultrasonography, is emerging as one of the more important factors associated with embolic potential and stroke risk. Two studies have concluded that a heterogeneous plaque carries an increased risk of stroke and is a variable independent from carotid stenosis alone.^49,50

More recently, attempts have been made to better characterize the asymptomatic patient who is at higher risk for a cerebral ischemic event in order to identify subgroups of patients who would benefit from carotid endarterectomy compared to patients with carotid stenosis who are at low risk for an ischemic event. In addition to percent stenosis and plaque composition, two factors have been identified as being associated with increased stroke risk in the asymptomatic patient. These factors include the presence of silent brain infarction as seen on a screening CT scan and silent brain embolic signals as documented using transcranial Doppler. Kakkos and colleagues⁵¹ studied 821 patients with CT scans. In patients with 60% to 99% stenosis and without silent brain infarction on CT, the annual rate of TIA and stroke was 1.3%. In patients with silent brain infarction, the annual event rate was 4.4%, suggesting that this subgroup of patients might benefit from carotid endarterectomy, leaving the low-risk group free from an unnecessary intervention.⁵¹ Markus and colleagues⁵² evaluated 467 asymptomatic patients with high-grade carotid stenosis in a multicenter study. Transcranial Doppler identified 77 patients with embolic signals. The annual risk of TIA and stroke was 7.13% in patients with embolic signals compared to 3.04% in patients without embolic signals. For ipsilateral stroke alone, the hazard ratio was 6.37. These findings suggest that screening for silent brain emboli is another method for identifying a high-risk group who are more likely to benefit from intervention.⁵²

The embolic potential of ulcerated carotid lesions has been well documented.^53–55 Patients who experience symptoms from these lesions probably have the same prognosis as patients with occlusive lesions. Whether the former patient group responds more favorably to platelet antiaggregants remains to be determined. Moore and coworkers⁵⁶ first pointed out that asymptomatic patients with significant ulceration in a carotid plaque in the absence of stenosis appear to be at higher risk of stroke.⁵⁶ In a subsequent report, they expanded their series to 153 patients with asymptomatic, nonstenotic ulcerative lesions in the carotid bifurcation. Patients with deep (grade B) or complex (grade C) ulcerations received follow-up and were found to have a stroke rate of 4.5% and 7.5% each year, respectively.⁵⁷ Other reports have suggested a similar stroke risk for complex ulcerations in the carotid bulb. However, a much lower stroke risk was reported for deep (grade B) ulcerations, with no significant added risk of stroke observed in these patients. Controversy still exists about deep ulcerations without complex morphology. However, agreement exists that complex ulcerations in the carotid bulb increase the risk of stroke in asymptomatic patients.⁵⁸

The presence of an asymptomatic hemodynamically significant stenosis may increase the risk of stroke during major surgery. Kartchner and McRae reported their experience with 234 patients, 41 of whom had evidence of significant carotid artery stenosis by oculoplethysmography.⁵⁹ Seven postoperative strokes developed in the group with positive criteria (17%), whereas postoperative cerebral infarction developed in 2 of 192 patients (1%) with negative noninvasive studies. The mechanisms of stroke and the territory involved were not specifically reported. This high incidence of permanent neurologic deficits led the authors to conclude that prophylactic carotid endarterectomy should be considered in patients with hemodynamically significant carotid stenosis who are undergoing a major cardiovascular procedure.⁶⁰

Other series have reported results to the contrary.^60–63 Using noninvasive vascular evaluation and, in one series, angiography, patients with 50% or greater stenosis in the carotid bifurcation were compared with patients who had lesser degrees of stenosis undergoing cardiovascular surgery. No increased incidence of perioperative strokes was found in patients with positive criteria. Most of these investigators, however, excluded preocclusive stenosis in their considerations. Lesions causing 90% or greater stenosis were excluded from these series and were subjected to prophylactic endarterectomy before cardiovascular operation.

Cardiac surgeons have long been concerned about the presence of carotid stenosis in patients who will be undergoing cardiopulmonary bypass. Their concern is that during bypass there will be a decrease in pump perfusion pressure and a corresponding and unacceptable drop in cerebral blood flow. In fact, the opposite occurs. Von Reutern and colleagues⁶⁴ used transcranial Doppler ultrasonography to study middle cerebral artery blood flow before and during cardiopulmonary bypass in patients with and without carotid artery disease. Surprisingly, middle cerebral artery blood flow actually increased during cardiopulmonary bypass. Although the increase was not as great in patients with carotid artery disease, it was clearly an increase over baseline. This observation should dispel concern about the potential drop in cerebral blood flow in patients with carotid stenosis while using the pump.

Patients with a combination of severe carotid stenosis and symptomatic coronary artery disease represent a cohort that is at high risk of death, MI, and stroke. Brener and colleagues⁶⁵ performed an extensive literature review that examined complications associated with different treatment strategies. Patients who underwent staging with carotid endarterectomy first had a high cardiac morbidity and mortality. Patients who had coronary bypass first had a higher stroke morbidity. The data suggested that combined or simultaneous coronary artery bypass grafting and carotid endarterectomy might reduce overall morbidity and mortality. However, evidence from retrospective reviews was not sufficiently compelling to make a definitive recommendation.⁶⁵ Consensus exists that this is an appropriate topic for a prospective, randomized trial.

The natural history of extracranial arterial occlusive disease cannot be complete without a consideration of the natural history of frequently associated conditions such as coronary artery disease, hypertension, and diabetes. MI remains the most frequent cause of death in these patients. Including these variables in the equation when one is formulating a treatment plan for a particular patient is therefore important. The goal of therapy should be the prevention of a permanent neurologic deficit. When deciding on the most effective way to achieve this, one must consider the life expectancy of the patient and the inherent risk of each particular form of therapy.

Pathology of Extracranial Arterial Occlusive Disease

The pathology of cerebrovascular disease of extracranial origin can be divided into flow-restrictive lesions and lesions with embolic potential. Each of these can be further subdivided into occlusive and aneurysmal lesions. All entities that have been described as etiologic in extracranial disease fall within these categories.

Atherosclerosis

By far the most common lesion found in patients with extracranial cerebrovascular disease is an atherosclerotic plaque in the carotid bifurcation. This can produce symptoms by reducing blood flow to the hemisphere supplied or, more commonly, by releasing embolic material. Emboli can be composed of clot, platelet aggregates, or cholesterol debris.

The carotid bifurcation appears to be susceptible to the development of atherosclerotic plaques.⁶⁶ Frequently, severe changes at the carotid bifurcation occur with minimal or no changes present in the common or internal carotid artery.⁶⁷ Several investigators have proposed conflicting theories based on hemodynamic observations in various models. High shear stress and fluctuations in shear stress,⁶⁸ disordered or turbulent flow, flow separation, and high and low flow velocity have all been implicated.^69–72 Which of these mechanisms is responsible for plaque formation is not known. Zarins and colleagues⁷³ used a model of the human carotid bifurcation under steady flow and compared its hemodynamics with those of cadaver specimens. They concluded that carotid lesions localize in regions of low flow velocity and flow separation rather than in regions of high velocity and increased shear stress. They used their model to explain the propensity of the outer wall of the carotid sinus opposite the flow divider to develop atherosclerotic plaques (Figure 18-2). This may have further clinical implications, in that an enlarged carotid bulb after endarterectomy may create a region of reduced flow velocity and increased boundary layer separation, which may favor recurrent plaque deposition.

FIGURE 18-2 The common carotid artery bifurcation, the most common site for atherosclerotic plaque deposition, is located on the wall opposite the divider. ECA, External carotid artery; ICA, internal carotid artery.

Once the initial intimal injury is produced by these forces, platelet deposition, smooth muscle cell proliferation, and the slow accumulation of lipoproteins are involved in the reparative process (Figure 18-3). These eventually lead to plaque formation, which further alters the hemodynamics of the system and favors further injury.

FIGURE 18-3 Microscopic section of an atherosclerotic plaque removed from the carotid bifurcation. Notice the fibrointimal proliferation with cholesterol cleft formation. Thrombotic material is adherent to the luminal surface of the plaque.

The contribution of platelets to atheroma development can take several forms.⁷⁴ Platelets may adhere to one another, to the diseased vessel, or both; this can lead to thrombus formation. This process may narrow the vessel lumen, or the thrombus may dislodge, resulting in distal embolization. Vasoactive substances stored in granules within the platelet may be released, causing vasospasm and further contributing to compromise of the arterial lumen. The platelets’ interaction with collagen, exposed in an injured intima, may include elaboration of a smooth muscle growth factor that can lead to intimal thickening. The activation of enzymes in platelets, by their contact with collagen, initiates the production of highly active prostaglandins. The production of thromboxane A₂ represents the final common pathway of platelet response to diverse stimuli.⁷⁵ This substance is a potent stimulant of platelet aggregation and a powerful vasoconstrictor and is believed to be important in the pathophysiology of plaque formation or the development of symptoms from an already established atheroma.

Hemorrhage into a plaque may also play a significant role in the development of symptoms from an atherosclerotic lesion. Imbalances in wall tension secondary to asymmetrical deposition of plaques can lead to sudden plaque fracture and intraplaque hemorrhage.⁷⁶ These can lead to sudden expansion of the atheroma, with acute restriction of flow or breakdown of the intimal surface and concomitant embolization. An alternative mechanism for sudden intraplaque hemorrhage may be related to an increase in neovascularity within the plaque substance. Hypertension may be responsible for precipitating rupture of neovascular vessels, leading to intraplaque hemorrhage and expansion.⁷⁷ This process may be responsible for a large number of symptomatic lesions. In a prospective evaluation of 79 atheromatous plaques removed from 69 patients undergoing carotid endarterectomy, 49 of 53 (92.5%) symptomatic patients had evidence of intramural hemorrhage.⁷⁸ In contrast, only 7 of 26 (27%) asymptomatic patients showed recent or acute intraplaque hemorrhage. Rupture of an atherosclerotic plaque with intraluminal release of atheromatous debris has also been correlated with acute stroke and internal carotid occlusion in an autopsy study.⁷⁹

Coils and Kinks

Coils and kinks of the extracranial system on occasion have been associated with fibromuscular dysplasia.⁸³ More commonly, these are due to embryologic events and changes that occur in the aging process. Neurologic manifestations from these anomalies have been reported in children⁸⁷ and in adults.^88–90 Embryologically, the internal carotid artery is derived from the third aortic arch and the dorsal aortic root. In the early stages of development, a normally occurring kink is straightened as the heart and great vessels descend in the mediastinum. Failure of this process may account for the occurrence of coils and loops in children and for its bilaterality in approximately 50% of cases.⁹⁰

In adults, kinking of the extracranial vessels is almost always associated with atherosclerosis. In the aging process, loss of elasticity of the vessel wall occurs, which, in combination with lateral stresses, causes elongation between fixed points—the skull and the thoracic inlet. This produces bowing, with the eventual formation of coils and kinks. Between 5% and 16% of patients submitted for angiographic evaluation have coiling or kinking of one of the extracranial vessels.^88,90 Kinking of the artery is more likely to produce symptoms because of either flow reduction or concomitant plaque formation with distal embolization. Kinking is considered to be an angle of less than 90 degrees between arterial segments (Figure 18-4). Flow restriction is unlikely to exist in the absence of this configuration. This acute angulation is more likely to occur when the head is turned to the ipsilateral side.⁸⁷ In other cases, contralateral rotation, neck flexion, and extension may exaggerate the abnormality, leading to markedly reduced flow. A history of TIAs associated with head motion should lead the clinician to suspect the presence of a kink. Abnormal pulsations in the neck, sometimes suggesting an aneurysmal dilatation, may be present on physical examination. Secondary arteriosclerotic changes can occur because of abnormal flow patterns that predispose to plaque formation and ulceration, accounting for the development of neurologic symptoms. Rarely is the vertebral circulation affected by a kink.⁸⁸

FIGURE 18-4 A, Selective left carotid arteriogram demonstrating a kink of the internal carotid artery. Note the angulation of less than 90 degrees and the paucity of contrast material beyond the kink. B, Operative appearance of the internal carotid artery kink. C, Operative appearance of the internal carotid artery after connection of the kink by mobilization and segmental resection of the common carotid artery. The carotid bifurcation is pulled down, and an end-to-end anastomosis is constructed.

Radiation Therapy Injury

External cervical radiation therapy is recognized as a cause of accelerated atherosclerotic changes in the extracranial circulation. Experimentally, atherosclerotic lesions similar to the naturally occurring ones can be produced in the abdominal aorta in dogs by x-ray and electron beam radiation.¹⁰³ Injury to the endothelial cell, ground substance, elastic lamina, and smooth muscle appears to alter the vessel wall, increasing its permeability to circulating lipids and impairing its ability to repair elastic tissue, leading to the formation of a plaque characterized by fibrosis, fatty infiltration, and intimal destruction.¹⁰⁴ These changes can occur months to years after completion of therapy. Lesions occur in locations unusual for atherosclerosis (Figure 18-5). Blowout of the affected carotid artery may occur, but this is more frequent when surgery is combined with radiation in treating cervical malignancies. Hyperlipidemia and hypercholesterolemia appear to predispose patients receiving radiation therapy to the development of these accelerated changes.¹⁰⁵ Endarterectomy of the affected segments is difficult but can be performed safely.^104,106

FIGURE 18-5 A, Arch angiogram demonstrating carotid artery disease secondary to external cervical radiation. Note complete occlusion of the right common carotid artery. Multiple stenoses are in the left common carotid artery, an unusual site for primary atherosclerosis. B, Operative appearance of the lesion secondary to external radiation. C, Intimectomy specimen of the lesion produced by external cervical radiation.

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