Pathophysiology of symptoms from carotid atherosclerosis
- Karen L Furie, MD, MPH
Karen L Furie, MD, MPH
- Chair and Professor of Neurology
- Alpert Medical School of Brown University
The symptoms and pathologic substrate of carotid artery atherosclerotic occlusive disease were first described by C Miller Fisher in 1951 . He related atherosclerotic disease at the carotid bifurcation to ischemic symptoms in the ipsilateral eye and brain. The modern era has seen an extraordinary expansion in our approach to the diagnosis and management of patients with carotid artery stenosis.
Stroke, due to atherothrombosis of the extracranial carotid arteries, is caused by a combination of factors involving the blood vessels, the clotting system, and hemodynamics. This interaction explains the mechanism of ischemic stroke in patients with carotid atheroma which may be due to artery-to-artery embolism or low cerebral blood flow.
The classification of symptomatic status of the internal carotid artery, the mechanism of symptom production, and the associated physical signs are reviewed here. Other issues, such as the methods for evaluating carotid stenosis and therapies available for the treatment of carotid artery disease, are discussed separately. (See "Evaluation of carotid artery stenosis" and "Overview of secondary prevention of ischemic stroke" and "Management of symptomatic carotid atherosclerotic disease" and "Management of asymptomatic carotid atherosclerotic disease".)
MECHANISM OF SYMPTOMS
Carotid atherosclerosis is usually most severe within 2 cm of the bifurcation of the common carotid artery, and predominantly involves the posterior wall of the vessel. The plaque encroaches on the lumen of the internal carotid artery and often extends caudally into the common carotid artery. An hourglass configuration to the stenosis typically develops with time.
Regardless of their location, carotid plaques were associated with an increased risk of stroke in an observational study of older adult men and women  and an increased risk of mortality in an observational study of older adult men . In addition to a reduction in vessel diameter induced by the enlarging plaque, thrombus can become superimposed on the atheroma which will further increase the degree of stenosis. Thus, the mechanism of stroke may be embolism of the thrombotic material or low flow due to the stenosis with inadequate collateral compensation [1,4-8].To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- FISHER M. Occlusion of the internal carotid artery. AMA Arch Neurol Psychiatry 1951; 65:346.
- Hollander M, Bots ML, Del Sol AI, et al. Carotid plaques increase the risk of stroke and subtypes of cerebral infarction in asymptomatic elderly: the Rotterdam study. Circulation 2002; 105:2872.
- Störk S, van den Beld AW, von Schacky C, et al. Carotid artery plaque burden, stiffness, and mortality risk in elderly men: a prospective, population-based cohort study. Circulation 2004; 110:344.
- FISHER CM. Concerning recurrent transient cerebral ischemic attacks. Can Med Assoc J 1962; 86:1091.
- Fisher CM, Karnes WE. Local embolism. J Neuropathol Exp Neurol 1965; 24:174.
- Kistler JP, Ropper AH, Heros RC. Therapy of ischemic cerebral vascular disease due to atherothrombosis (1). N Engl J Med 1984; 311:27.
- Kistler JP, Ropper AH, Heros RC. Therapy of ischemic cerebral vascular disease due to atherothrombosis. (2). N Engl J Med 1984; 311:100.
- Mohr JP. Transient ischemic attacks and the prevention of strokes. N Engl J Med 1978; 299:93.
- FISHER CM. Observations of the fundus oculi in transient monocular blindness. Neurology 1959; 9:333.
- Delcker A, Diener HC, Wilhelm H. Source of cerebral microembolic signals in occlusion of the internal carotid artery. J Neurol 1997; 244:312.
- Liberman AL, Zandieh A, Loomis C, et al. Symptomatic Carotid Occlusion Is Frequently Associated With Microembolization. Stroke 2017; 48:394.
- Duncan GW, Pessin MS, Mohr JP, Adams RD. Transient cerebral ischemic attacks. Adv Intern Med 1976; 21:1.
- Fields WS, Lemak NA. Joint study of extracranial arterial occlusion. X. Internal carotid artery occlusion. JAMA 1976; 235:2734.
- Furlan AJ, Whisnant JP, Baker HL Jr. Long-term prognosis after carotid artery occlusion. Neurology 1980; 30:986.
- Dyken ML, Klatte E, Kolar OJ, Surgeon C. Complete occlusion of common or internal carotid arteries. Clinical significance. Arch Neurol 1974; 30:343.
- Hedera P, Bujdáková J, Traubner P. Effect of collateral flow patterns on outcome of carotid occlusion. Eur Neurol 1995; 35:212.
- Kleiser B, Widder B. Course of carotid artery occlusions with impaired cerebrovascular reactivity. Stroke 1992; 23:171.
- Reinhard M, Schwarzer G, Briel M, et al. Cerebrovascular reactivity predicts stroke in high-grade carotid artery disease. Neurology 2014; 83:1424.
- Takaya N, Yuan C, Chu B, et al. Association between carotid plaque characteristics and subsequent ischemic cerebrovascular events: a prospective assessment with MRI--initial results. Stroke 2006; 37:818.
- Kerwin WS, Hatsukami T, Yuan C, Zhao XQ. MRI of carotid atherosclerosis. AJR Am J Roentgenol 2013; 200:W304.
- Young VE, Sadat U, Gillard JH. Noninvasive carotid artery imaging with a focus on the vulnerable plaque. Neuroimaging Clin N Am 2011; 21:391.
- Kakkos SK, Griffin MB, Nicolaides AN, et al. The size of juxtaluminal hypoechoic area in ultrasound images of asymptomatic carotid plaques predicts the occurrence of stroke. J Vasc Surg 2013; 57:609.
- Millon A, Mathevet JL, Boussel L, et al. High-resolution magnetic resonance imaging of carotid atherosclerosis identifies vulnerable carotid plaques. J Vasc Surg 2013; 57:1046.
- Bauer RB, Meyer JS, Fields WS, et al. Joint study of extracranila arterial occlusion. 3. Progress report of controlled study of long-term survival in patients with and without operation. JAMA 1969; 208:509.
- Hatsukami TS, Ferguson MS, Beach KW, et al. Carotid plaque morphology and clinical events. Stroke 1997; 28:95.
- Steinke W, Hennerici M, Rautenberg W, Mohr JP. Symptomatic and asymptomatic high-grade carotid stenoses in Doppler color-flow imaging. Neurology 1992; 42:131.
- Carr S, Farb A, Pearce WH, et al. Atherosclerotic plaque rupture in symptomatic carotid artery stenosis. J Vasc Surg 1996; 23:755.
- Fisher M, Blumenfeld AM, Smith TW. The importance of carotid artery plaque disruption and hemorrhage. Arch Neurol 1987; 44:1086.
- Milei J, Parodi JC, Alonso GF, et al. Carotid rupture and intraplaque hemorrhage: immunophenotype and role of cells involved. Am Heart J 1998; 136:1096.
- Lovett JK, Rothwell PM. Site of carotid plaque ulceration in relation to direction of blood flow: an angiographic and pathological study. Cerebrovasc Dis 2003; 16:369.
- Li ZY, Howarth SP, Tang T, Gillard JH. How critical is fibrous cap thickness to carotid plaque stability? A flow-plaque interaction model. Stroke 2006; 37:1195.
- Yilmaz A, Lipfert B, Cicha I, et al. Accumulation of immune cells and high expression of chemokines/chemokine receptors in the upstream shoulder of atherosclerotic carotid plaques. Exp Mol Pathol 2007; 82:245.
- Thrysøe SA, Oikawa M, Yuan C, et al. Longitudinal distribution of mechanical stresses in carotid plaques of symptomatic patients. Stroke 2010; 41:1041.
- Cicha I, Wörner A, Urschel K, et al. Carotid plaque vulnerability: a positive feedback between hemodynamic and biochemical mechanisms. Stroke 2011; 42:3502.
- Hermus L, Lefrandt JD, Tio RA, et al. Carotid plaque formation and serum biomarkers. Atherosclerosis 2010; 213:21.
- Mallat Z, Nakamura T, Ohan J, et al. The relationship of hydroxyeicosatetraenoic acids and F2-isoprostanes to plaque instability in human carotid atherosclerosis. J Clin Invest 1999; 103:421.
- Rudd JH, Warburton EA, Fryer TD, et al. Imaging atherosclerotic plaque inflammation with [18F]-fluorodeoxyglucose positron emission tomography. Circulation 2002; 105:2708.
- Saam T, Hetterich H, Hoffmann V, et al. Meta-analysis and systematic review of the predictive value of carotid plaque hemorrhage on cerebrovascular events by magnetic resonance imaging. J Am Coll Cardiol 2013; 62:1081.
- Gupta A, Baradaran H, Schweitzer AD, et al. Carotid plaque MRI and stroke risk: a systematic review and meta-analysis. Stroke 2013; 44:3071.
- Hosseini AA, Kandiyil N, Macsweeney ST, et al. Carotid plaque hemorrhage on magnetic resonance imaging strongly predicts recurrent ischemia and stroke. Ann Neurol 2013; 73:774.
- Altaf N, Kandiyil N, Hosseini A, et al. Risk factors associated with cerebrovascular recurrence in symptomatic carotid disease: a comparative study of carotid plaque morphology, microemboli assessment and the European Carotid Surgery Trial risk model. J Am Heart Assoc 2014; 3:e000173.
- Polak JF, O'Leary DH, Kronmal RA, et al. Sonographic evaluation of carotid artery atherosclerosis in the elderly: relationship of disease severity to stroke and transient ischemic attack. Radiology 1993; 188:363.
- Babikian VL, Hyde C, Pochay V, Winter MR. Clinical correlates of high-intensity transient signals detected on transcranial Doppler sonography in patients with cerebrovascular disease. Stroke 1994; 25:1570.
- Spagnoli LG, Mauriello A, Sangiorgi G, et al. Extracranial thrombotically active carotid plaque as a risk factor for ischemic stroke. JAMA 2004; 292:1845.
- North American Symptomatic Carotid Endarterectomy Trial Collaborators, Barnett HJM, Taylor DW, et al. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 1991; 325:445.
- Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA 1995; 273:1421.
- Fisher M, Paganini-Hill A, Martin A, et al. Carotid plaque pathology: thrombosis, ulceration, and stroke pathogenesis. Stroke 2005; 36:253.
- Kwee RM, van Oostenbrugge RJ, Prins MH, et al. Symptomatic patients with mild and moderate carotid stenosis: plaque features at MRI and association with cardiovascular risk factors and statin use. Stroke 2010; 41:1389.
- Pickett CA, Jackson JL, Hemann BA, Atwood JE. Carotid bruits and cerebrovascular disease risk: a meta-analysis. Stroke 2010; 41:2295.
- Davies KN, Humphrey PR. Do carotid bruits predict disease of the internal carotid arteries? Postgrad Med J 1994; 70:433.
- Roederer GO, Langlois YE, Jager KA, et al. The natural history of carotid arterial disease in asymptomatic patients with cervical bruits. Stroke 1984; 15:605.
- Chambers BR, Norris JW. Outcome in patients with asymptomatic neck bruits. N Engl J Med 1986; 315:860.
- Meissner I, Wiebers DO, Whisnant JP, O'Fallon WM. The natural history of asymptomatic carotid artery occlusive lesions. JAMA 1987; 258:2704.
- Shorr RI, Johnson KC, Wan JY, et al. The prognostic significance of asymptomatic carotid bruits in the elderly. J Gen Intern Med 1998; 13:86.
- Wolf PA, Kannel WB, Sorlie P, McNamara P. Asymptomatic carotid bruit and risk of stroke. The Framingham study. JAMA 1981; 245:1442.
- Sauvé JS, Thorpe KE, Sackett DL, et al. Can bruits distinguish high-grade from moderate symptomatic carotid stenosis? The North American Symptomatic Carotid Endarterectomy Trial. Ann Intern Med 1994; 120:633.
- Caplan, LR. Diagnosis and the clinical encounter. In: Caplan's Stroke: A Clinical Approach, 4th ed, Saunders, Philadelphia 2009. p.64.
- Suwanwela N, Can U, Furie KL, et al. Carotid Doppler ultrasound criteria for internal carotid artery stenosis based on residual lumen diameter calculated from en bloc carotid endarterectomy specimens. Stroke 1996; 27:1965.
- Can U, Furie KL, Suwanwela N, et al. Transcranial Doppler ultrasound criteria for hemodynamically significant internal carotid artery stenosis based on residual lumen diameter calculated from en bloc endarterectomy specimens. Stroke 1997; 28:1966.
- Persoon S, Kappelle LJ, Klijn CJ. Limb-shaking transient ischaemic attacks in patients with internal carotid artery occlusion: a case-control study. Brain 2010; 133:915.
- MECHANISM OF SYMPTOMS
- Transient ischemic attacks
- Total carotid artery occlusion
- Impaired vasoreactivity
- PLAQUE MORPHOLOGY AND PATHOLOGY
- Plaque ulceration and rupture
- Intraplaque hemorrhage
- Plaque emboli
- Clinicopathologic correlates
- CLINICAL MANIFESTATIONS
- Carotid bruit
- Ischemic symptoms
- INFORMATION FOR PATIENTS