Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Intracranial large artery atherosclerosis

As'ad Ehtisham, MD, MBBS, FAHA
Cathy A Sila, MD
Section Editor
Scott E Kasner, MD
Deputy Editor
John F Dashe, MD, PhD


Atherosclerotic stenosis of the major intracranial arteries is an important cause of ischemic stroke. This topic focuses on the epidemiology, diagnosis, treatment, and prognosis of intracranial arterial stenosis. Other ischemic stroke subtypes are reviewed separately. (See "Etiology, classification, and epidemiology of stroke" and "Clinical diagnosis of stroke subtypes" and "Lacunar infarcts" and "Cryptogenic stroke".)


Atherosclerosis is a pathologic process that causes disease of the coronary, cerebral, and peripheral arteries. Multiple factors contribute to the pathogenesis of atherosclerosis, including endothelial dysfunction, inflammatory and immunologic factors, plaque rupture, and the traditional risk factors of hypertension, diabetes, dyslipidemia, and smoking. The first stage of atherosclerosis begins in childhood with the development of fatty streaks, followed by progression involving the development of fibrous plaques, fibrous caps, and advanced atheromatous lesions. (See "Pathogenesis of atherosclerosis".)

Atherosclerosis is the most common cause of in situ local disease within the large extracranial and intracranial arteries that supply the brain (picture 1 and image 1). Atherosclerotic narrowing of large intracranial arteries can lead to ischemic stroke or TIA by a variety of mechanisms (image 2), which include [1-3]:

In-situ thromboembolism leading most often to artery-to-artery embolism, and less often to hemodynamic insufficiency or to a combination of embolism and hemodynamic insufficiency [4]

Progression of luminal stenosis resulting in hemodynamic insufficiency


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Dec 8, 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Qureshi AI, Caplan LR. Intracranial atherosclerosis. Lancet 2014; 383:984.
  2. Holmstedt CA, Turan TN, Chimowitz MI. Atherosclerotic intracranial arterial stenosis: risk factors, diagnosis, and treatment. Lancet Neurol 2013; 12:1106.
  3. Bang OY. Intracranial atherosclerosis: current understanding and perspectives. J Stroke 2014; 16:27.
  4. Caplan LR, Hennerici M. Impaired clearance of emboli (washout) is an important link between hypoperfusion, embolism, and ischemic stroke. Arch Neurol 1998; 55:1475.
  5. Bos D, Portegies ML, van der Lugt A, et al. Intracranial carotid artery atherosclerosis and the risk of stroke in whites: the Rotterdam Study. JAMA Neurol 2014; 71:405.
  6. Ritz K, Denswil NP, Stam OC, et al. Cause and mechanisms of intracranial atherosclerosis. Circulation 2014; 130:1407.
  7. Hass WK, Fields WS, North RR, et al. Joint study of extracranial arterial occlusion. II. Arteriography, techniques, sites, and complications. JAMA 1968; 203:961.
  8. McGarry P, Solberg LA, Guzman MA, Strong JP. Cerebral atherosclerosis in New Orleans. Comparisons of lesions by age, sex, and race. Lab Invest 1985; 52:533.
  9. Moossy J. Cerebral infarction and intracranial arterial thrombosis. Necropsy studies and clinical implications. Arch Neurol 1966; 14:119.
  10. Sacco RL, Kargman DE, Gu Q, Zamanillo MC. Race-ethnicity and determinants of intracranial atherosclerotic cerebral infarction. The Northern Manhattan Stroke Study. Stroke 1995; 26:14.
  11. Naylor AR, Sandercock PA, Sellar RJ, Warlow CP. Patterns of vascular pathology in acute, first-ever cerebral infarction. Scott Med J 1993; 38:41.
  12. Wityk R, Lehman D, Klag M, et al. Racial differences in extracranial and intracranial atherosclerosis. Neurology 1995; Suppl 4:A461.
  13. Passero S, Rossi G, Nardini M, et al. Italian multicenter study of reversible cerebral ischemic attacks. Part 5. Risk factors and cerebral atherosclerosis. Atherosclerosis 1987; 63:211.
  14. Bogousslavsky J, Van Melle G, Regli F. The Lausanne Stroke Registry: analysis of 1,000 consecutive patients with first stroke. Stroke 1988; 19:1083.
  15. Qureshi AI, Safdar K, Patel M, et al. Stroke in young black patients. Risk factors, subtypes, and prognosis. Stroke 1995; 26:1995.
  16. Weisberg LA. Clinical characteristics of transient ischemic attacks in black patients. Neurology 1991; 41:1410.
  17. Gorelick PB, Caplan LR, Hier DB, et al. Racial differences in the distribution of anterior circulation occlusive disease. Neurology 1984; 34:54.
  18. Inzitari D, Hachinski VC, Taylor DW, Barnett HJ. Racial differences in the anterior circulation in cerebrovascular disease. How much can be explained by risk factors? Arch Neurol 1990; 47:1080.
  19. Wong KS, Li H. Long-term mortality and recurrent stroke risk among Chinese stroke patients with predominant intracranial atherosclerosis. Stroke 2003; 34:2361.
  20. Nishimaru K, McHenry LC Jr, Toole JF. Cerebral angiographic and clinical differences in carotid system transient ischemic attacks between American Caucasian and Japanese patients. Stroke 1984; 15:56.
  21. Feldmann E, Daneault N, Kwan E, et al. Chinese-white differences in the distribution of occlusive cerebrovascular disease. Neurology 1990; 40:1541.
  22. De Silva DA, Woon FP, Lee MP, et al. South Asian patients with ischemic stroke: intracranial large arteries are the predominant site of disease. Stroke 2007; 38:2592.
  23. White H, Boden-Albala B, Wang C, et al. Ischemic stroke subtype incidence among whites, blacks, and Hispanics: the Northern Manhattan Study. Circulation 2005; 111:1327.
  24. Liu LH, Caplan LR, Kwan E, et al. Racial differences in ischemic cerebrovascular disease: clinical and magnetic resonance angiographic correlations of white and Asian patients. J Stroke Cerebrovasc Dis 1996; 6:79.
  25. Gorelick PB, Caplan LR, Hier DB, et al. Racial differences in the distribution of posterior circulation occlusive disease. Stroke 1985; 16:785.
  26. Gorelick PB, Caplan LR, Langenberg P, et al. Clinical and angiographic comparison of asymptomatic occlusive cerebrovascular disease. Neurology 1988; 38:852.
  27. Williams AO, Resch JA, Loewenson RB. Cerebral atherosclerosis--a comparative autopsy study between Nigerian Negroes and American Negroes and Caucasians. Neurology 1969; 19:205.
  28. Arenillas JF, Molina CA, Chacón P, et al. High lipoprotein (a), diabetes, and the extent of symptomatic intracranial atherosclerosis. Neurology 2004; 63:27.
  29. Sacco RL, Kargman DE, Zamanillo MC. Race-ethnic differences in stroke risk factors among hospitalized patients with cerebral infarction: the Northern Manhattan Stroke Study. Neurology 1995; 45:659.
  30. Ingall TJ, Homer D, Baker HL Jr, et al. Predictors of intracranial carotid artery atherosclerosis. Duration of cigarette smoking and hypertension are more powerful than serum lipid levels. Arch Neurol 1991; 48:687.
  31. Rincon F, Sacco RL, Kranwinkel G, et al. Incidence and risk factors of intracranial atherosclerotic stroke: the Northern Manhattan Stroke Study. Cerebrovasc Dis 2009; 28:65.
  32. Wityk RJ, Lehman D, Klag M, et al. Race and sex differences in the distribution of cerebral atherosclerosis. Stroke 1996; 27:1974.
  33. Sirimarco G, Deplanque D, Lavallée PC, et al. Atherogenic dyslipidemia in patients with transient ischemic attack. Stroke 2011; 42:2131.
  34. Turan TN, Makki AA, Tsappidi S, et al. Risk factors associated with severity and location of intracranial arterial stenosis. Stroke 2010; 41:1636.
  35. de Bray JM, Joseph PA, Jeanvoine H, et al. Transcranial Doppler evaluation of middle cerebral artery stenosis. J Ultrasound Med 1988; 7:611.
  36. Rorick MB, Nichols FT, Adams RJ. Transcranial Doppler correlation with angiography in detection of intracranial stenosis. Stroke 1994; 25:1931.
  37. Arenillas JF, Molina CA, Montaner J, et al. Progression and clinical recurrence of symptomatic middle cerebral artery stenosis: a long-term follow-up transcranial Doppler ultrasound study. Stroke 2001; 32:2898.
  38. Dagirmanjian A, Ross JS, Obuchowski N, et al. High resolution, magnetization transfer saturation, variable flip angle, time-of-flight MRA in the detection of intracranial vascular stenoses. J Comput Assist Tomogr 1995; 19:700.
  39. Katz DA, Marks MP, Napel SA, et al. Circle of Willis: evaluation with spiral CT angiography, MR angiography, and conventional angiography. Radiology 1995; 195:445.
  40. Stock KW, Radue EW, Jacob AL, et al. Intracranial arteries: prospective blinded comparative study of MR angiography and DSA in 50 patients. Radiology 1995; 195:451.
  41. Bash S, Villablanca JP, Jahan R, et al. Intracranial vascular stenosis and occlusive disease: evaluation with CT angiography, MR angiography, and digital subtraction angiography. AJNR Am J Neuroradiol 2005; 26:1012.
  42. Feldmann E, Wilterdink JL, Kosinski A, et al. The Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) trial. Neurology 2007; 68:2099.
  43. Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) Trail Investigators. Stroke outcome and neuroimaging of intracranial atherosclerosis (SONIA): design of a prospective, multicenter trial of diagnostic tests. Neuroepidemiology 2004; 23:23.
  44. Röther J, Wentz KU, Rautenberg W, et al. Magnetic resonance angiography in vertebrobasilar ischemia. Stroke 1993; 24:1310.
  45. Sila CA. Personal communication. 2012.
  46. Samuels OB, Joseph GJ, Lynn MJ, et al. A standardized method for measuring intracranial arterial stenosis. AJNR Am J Neuroradiol 2000; 21:643.
  47. Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA 1995; 273:1421.
  48. Dion JE, Gates PC, Fox AJ, et al. Clinical events following neuroangiography: a prospective study. Stroke 1987; 18:997.
  49. Chimowitz MI, Lynn MJ, Howlett-Smith H, et al. Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis. N Engl J Med 2005; 352:1305.
  50. Mohr JP, Thompson JL, Lazar RM, et al. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med 2001; 345:1444.
  51. MILLIKAN CH, SIEKERT RG, SHICK RM. Studies in cerebrovascular disease. III. The use of anticoagulant drugs in the treatment of insufficiency or thrombosis within the basilar arterial system. Proc Staff Meet Mayo Clin 1955; 30:116.
  52. Chimowitz MI, Kokkinos J, Strong J, et al. The Warfarin-Aspirin Symptomatic Intracranial Disease Study. Neurology 1995; 45:1488.
  53. Prognosis of patients with symptomatic vertebral or basilar artery stenosis. The Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) Study Group. Stroke 1998; 29:1389.
  54. Thijs VN, Albers GW. Symptomatic intracranial atherosclerosis: outcome of patients who fail antithrombotic therapy. Neurology 2000; 55:490.
  55. Kasner SE, Lynn MJ, Chimowitz MI, et al. Warfarin vs aspirin for symptomatic intracranial stenosis: subgroup analyses from WASID. Neurology 2006; 67:1275.
  56. Zaidat OO, Klucznik R, Alexander MJ, et al. The NIH registry on use of the Wingspan stent for symptomatic 70-99% intracranial arterial stenosis. Neurology 2008; 70:1518.
  57. Wang T, Elam MB, Forbes WP, et al. Reduction of remnant lipoprotein cholesterol concentrations by cilostazol in patients with intermittent claudication. Atherosclerosis 2003; 171:337.
  58. Kwon SU, Cho YJ, Koo JS, et al. Cilostazol prevents the progression of the symptomatic intracranial arterial stenosis: the multicenter double-blind placebo-controlled trial of cilostazol in symptomatic intracranial arterial stenosis. Stroke 2005; 36:782.
  59. Chaturvedi S, Turan TN, Lynn MJ, et al. Risk factor status and vascular events in patients with symptomatic intracranial stenosis. Neurology 2007; 69:2063.
  60. Turan TN, Cotsonis G, Lynn MJ, et al. Relationship between blood pressure and stroke recurrence in patients with intracranial arterial stenosis. Circulation 2007; 115:2969.
  61. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014; 129:S1.
  62. Fiorella D, Woo HH. Emerging endovascular therapies for symptomatic intracranial atherosclerotic disease. Stroke 2007; 38:2391.
  63. Chimowitz MI, Lynn MJ, Derdeyn CP, et al. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med 2011; 365:993.
  64. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014; 45:2160.
  65. Centers for Medicare & Medicaid Services. Medicare coverage database. Decision memo for intracranial stenting and angioplasty (CAG-00085R5). www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?NCAId=214&ver=20&NcaName=Intracranial+Stenting+and+Angioplasty&DocID=CAG-00085R5&bc=gAAAAAgAIAAA& (Accessed on May 25, 2011).
  66. Higashida RT, Tsai FY, Halbach VV, et al. Transluminal angioplasty for atherosclerotic disease of the vertebral and basilar arteries. J Neurosurg 1993; 78:192.
  67. Clark WM, Barnwell SL, Nesbit G, et al. Safety and efficacy of percutaneous transluminal angioplasty for intracranial atherosclerotic stenosis. Stroke 1995; 26:1200.
  68. Touho H. Percutaneous transluminal angioplasty in the treatment of atherosclerotic disease of the anterior cerebral circulation and hemodynamic evaluation. J Neurosurg 1995; 82:953.
  69. Takis C, Kwan ES, Pessin MS, et al. Intracranial angioplasty: experience and complications. AJNR Am J Neuroradiol 1997; 18:1661.
  70. Marks MP, Marcellus M, Norbash AM, et al. Outcome of angioplasty for atherosclerotic intracranial stenosis. Stroke 1999; 30:1065.
  71. Connors JJ 3rd, Wojak JC. Percutaneous transluminal angioplasty for intracranial atherosclerotic lesions: evolution of technique and short-term results. J Neurosurg 1999; 91:415.
  72. Nahser HC, Henkes H, Weber W, et al. Intracranial vertebrobasilar stenosis: angioplasty and follow-up. AJNR Am J Neuroradiol 2000; 21:1293.
  73. Alazzaz A, Thornton J, Aletich VA, et al. Intracranial percutaneous transluminal angioplasty for arteriosclerotic stenosis. Arch Neurol 2000; 57:1625.
  74. Gress DR, Smith WS, Dowd CF, et al. Angioplasty for intracranial symptomatic vertebrobasilar ischemia. Neurosurgery 2002; 51:23.
  75. Gupta R, Schumacher HC, Mangla S, et al. Urgent endovascular revascularization for symptomatic intracranial atherosclerotic stenosis. Neurology 2003; 61:1729.
  76. Cruz-Flores S, Diamond AL. Angioplasty for intracranial artery stenosis. Cochrane Database Syst Rev 2006; :CD004133.
  77. Zaidat OO, Fitzsimmons BF, Woodward BK, et al. Effect of a balloon-expandable intracranial stent vs medical therapy on risk of stroke in patients with symptomatic intracranial stenosis: the VISSIT randomized clinical trial. JAMA 2015; 313:1240.
  78. Derdeyn CP, Chimowitz MI, Lynn MJ, et al. Aggressive medical treatment with or without stenting in high-risk patients with intracranial artery stenosis (SAMMPRIS): the final results of a randomised trial. Lancet 2014; 383:333.
  79. Fiorella D, Derdeyn CP, Lynn MJ, et al. Detailed analysis of periprocedural strokes in patients undergoing intracranial stenting in Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS). Stroke 2012; 43:2682.
  80. Lutsep HL, Lynn MJ, Cotsonis GA, et al. Does the Stenting Versus Aggressive Medical Therapy Trial Support Stenting for Subgroups With Intracranial Stenosis? Stroke 2015; 46:3282.
  81. Failure of extracranial-intracranial arterial bypass to reduce the risk of ischemic stroke. Results of an international randomized trial. The EC/IC Bypass Study Group. N Engl J Med 1985; 313:1191.
  82. Bogousslavsky J, Barnett HJ, Fox AJ, et al. Atherosclerotic disease of the middle cerebral artery. Stroke 1986; 17:1112.
  83. Sundt TM Jr, Whisnant JP, Piepgras DG, et al. Intracranial bypass grafts for vertebral-basilar ischemia. Mayo Clin Proc 1978; 53:12.
  84. Ausman JI, Diaz FG, de los Reyes RA, et al. Anastomosis of occipital artery to anterior inferior cerebellar artery for vertebrobasilar junction stenosis. Surg Neurol 1981; 16:99.
  85. Marzewski DJ, Furlan AJ, St Louis P, et al. Intracranial internal carotid artery stenosis: longterm prognosis. Stroke 1982; 13:821.
  86. Qureshi AI, Ziai WC, Yahia AM, et al. Stroke-free survival and its determinants in patients with symptomatic vertebrobasilar stenosis: a multicenter study. Neurosurgery 2003; 52:1033.
  87. Moufarrij NA, Little JR, Furlan AJ, et al. Basilar and distal vertebral artery stenosis: long-term follow-up. Stroke 1986; 17:938.
  88. Mazighi M, Tanasescu R, Ducrocq X, et al. Prospective study of symptomatic atherothrombotic intracranial stenoses: the GESICA study. Neurology 2006; 66:1187.
  89. Famakin BM, Chimowitz MI, Lynn MJ, et al. Causes and severity of ischemic stroke in patients with symptomatic intracranial arterial stenosis. Stroke 2009; 40:1999.
  90. Kasner SE, Chimowitz MI, Lynn MJ, et al. Predictors of ischemic stroke in the territory of a symptomatic intracranial arterial stenosis. Circulation 2006; 113:555.
  91. Williams JE, Chimowitz MI, Cotsonis GA, et al. Gender differences in outcomes among patients with symptomatic intracranial arterial stenosis. Stroke 2007; 38:2055.