J Clin Neurol.  2005 Apr;1(1):1-7. 10.3988/jcn.2005.1.1.1.

Intracranial Atherosclerosis: Incidence, Diagnosis and Treatment

• Kim JS
• Kang DW
• Kwon SU

• KMID: 2287709
• DOI: http://doi.org/10.3988/jcn.2005.1.1.1

Abstract

Intracranial atherosclerosis is considered a cause of approximately 8% of all strokes in the western society. However, its frequency is much higher in Asian countries. In our hospital-based study, among the patients who had angiographic abnormalities, the frequency of intracranial atherosclerosis was approximately 70% far exceeding that of extratracranial atherosclerosis. Symptomatic atherosclerotic diseases were most often found in the middle cerebral artery. Generally, it has been shown that obesity and hyperlipidemia are related to extracranial diseases while advance hypertension is associated with intracranial diseases. However, these results have not always been replicated, and certain genetic factors may be related with the ethnic differences in the location of atherosclerosis. Recent studies using diffusion weighted MRI showed that the main mechanisms of stroke in patients with intracranial atherosclerosis are the branch occlusion, artery to artery embolism and both. The intracranial stenosis, especially symptomatic one, is not a static condition and may progress or regress in a relatively short period of time. Progressive stenosis of intracranial arteries is clearly related to the development of ischemic events. The annual risk of stroke relevant to the stenosed intracranial vessel is approximately 8%. In retrospective studies including ASID, anticoagulation was found to be superior to aspirin in reducing the stroke events. However, a recent prospective study failed to confirm the superiority of anticoagulation over aspirin in patients with intracranial stenosis. Moreover, anticoagulation resulted in excessive central nervous system bleeding as compared to aspirin. Because aspirin alone seems to be insufficient in the prevention of progression of intracranial stenosis, a combination of antiplatelets has been tried. Recently, we found that a combination of aspirin + cilostazol was superior to aspirin monotherapy in the prevention of progression of symptomatic intracranial stenosis. However, further studies are required to find out the best combination of antiplatelets for symptomatic intracranial stenosis. The effect of other atheroma stabilizers such as statins should also be properly evaluated. Angioplasty/stent is another important option for the relatively severe intracranial stenosis. According to previous studies, immediate success rate has reached up to 90%. If patients are carefully selected, and procedures done by experienced hand, angioplasty/stent can be of benefit especially in relatively young patients with proximal, short-segment, severe symptomatic stenosis. However, this procedure is not without complications or long-term re-stenosis. Further studies are required to elucidate the best therapeutic strategy in patients with intracranial atherosclerosis.

Keyword

Intracranial stenosis; Atherosclerosis; Diagnosis; Management

MeSH Terms

Arteries
Asian Continental Ancestry Group
Aspirin
Atherosclerosis
Central Nervous System
Constriction, Pathologic
Diagnosis*
Diffusion Magnetic Resonance Imaging
Embolism
Hand
Hemorrhage
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hyperlipidemias
Hypertension
Incidence*
Intracranial Arteriosclerosis*
Middle Cerebral Artery
Obesity
Plaque, Atherosclerotic
Stroke
Aspirin

Reference

1. Wityk RJ, Lehman D, Klag M, Coresh J, Ahn H, Litt B. Race and sex differences in the distribution of cerebral atherosclerosis. Stroke. 1996. 27:1974–1980.

2. Sacco RL, Kargman DE, Gu Q, Zamanillo MC. Race-ethnicity and determinants of intracranial atherosclerotic cerebral infarction. The Northern Manhatten Stroke Study. Stroke. 1995. 26:14–20.

3. Tomita T, Mihara H. Cerebral angiographic study on CVD in Japan. Angiology. 1972. 23:228–239.

4. Brust RW Jr. Patterns of cerebrovascular disease in Japanese and other population groups in Hawaii: An angiographic study. Stroke. 1975. 6:539–542.

5. Feldmann E, Daneault N, Kwan E, Ho KJ, Pessin MS, Langenberg P, et al. Chinese-white differences in the distribution of occlusive cerebrovascular disease. Neurology. 1990. 40:1541–1545.

6. Nagao T, Sadoshima S, Ibayashi S, Takeya Y, Fujishima M. Increase in extracrainal atherosclerotic carotid lesions in patients with brain ischemia in Japan: An angiographic study. Stroke. 1994. 25:766–770.

7. Leung SY, Ng THK, Yeun ST, Lauder IJ, Ho FCS. Pattern of cerebral atherosclerosis in Hong Kong Chinese. Stroke. 1993. 24:779–786.

8. Bang OY, Joo SY, Lee PH, Joo US, Lee JH, Joo IS, et al. The course of patients with lacunar infarcts and a parent arterial lesion: similarities to large artery vs small artery disease. Arch Neurol. 2004. 61:514–519.

9. Uehara T, Tabuchi M, Mori E. Risk factors for occlusive lesions of intracranial arteries in stroke-free Japanese. Eur J Neurol. 2005. 12:218–222.

10. Kim JS, Choi-Kwon S. Risk factors for stroke in different levels of cerebral arterial disease. Eur Neurol. 1999. 42:150–156.

11. Inzitari D, Hachinski VC, Taylor W, Barnett JM. Racial differences in the anterior circulation in cerebrovascular disease. Howe much can be explained by risk factors? Arch Neurol. 1990. 47:1080–1084.

12. Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) Trial Investigators. Stroke outcome and neuroimaging of intracranial atherosclerosis (SONIA): design of a prospective, multicenter trial of diagnostic tests. Neuroepidemiology. 2004. 23(1-2):23–32.

13. Lev MH, Farkas J, Rodriguez VR, Schwamm LH, Hunter GJ, Putman CM, et al. CT angiography in the rapid triage of patients with hyperacute stroke to intraarterial thrombolysis: accuracy in the detection of large vessel thrombus. J Comput Assist Tomogr. 2001. 25:520–528.

14. Samuels OB, Joseph GJ, Lynn MJ, Smith HA, Chimowitz MI. A standardized method for measuring intracranial arterial stenosis. Am J Neuroradiol. 2000. 21:643–646.

15. Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) Trial Investigators. Design, progress and challenges of a double-blind trial of warfarin versus aspirin for symptomatic intracranial arterial stenosis. Neuroepidemiology. 2003. 22:106–117.

16. Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation. 1995. 92:657–671.

17. Chen KY. A review of the pathological studies of the middle cerebral artery atherosclerosis. Proceeding for 1_st International Conference on Intracranial Athorosclerosis. 2004. Hong Kong: 15.

18. Klein IF, Lavallee PC, Schouman-Claeys E, Amarenco P. High-resolution MRI identifies basilar artery plaques in paramedian pontine infarct. Neurology. 2005. 64:551–552.

19. Wong KS, Gao S, Chan YL, Hansberg T, Lam WW, Droste DW, et al. Mechanisms of acute cerebral infarctions in patients with middle cerebral artery stenosis: a diffusion-weighted imaging and microemboli monitoring study. Ann Neurol. 2002. 52:74–81.

20. Adams HP Jr, Gross CE. Embolism distal to stenosis of the middle cerebral artery. Stroke. 1981. 12:228–229.

21. Caplan LR. Intracranial branch atheromatous disease: a neglected, understudied, and underused concept. Neurology. 1989. 39:1246–1250.

22. Cho AH, Kang DW, Kwon SU, Kim JS. Is 1.5 cm criteria for lacunar infarction still valid? In : International Stroke Conference 2005; New Orleans, USA.

23. Bang OY, Heo JH, Kim JY, Park JH, Huh K. Middle cerebral artery stenosis is a major clinical determinant in striatocapsular small, deep infarction. Arch Neurol. 2002. 59(2):259–263.

24. Lee DK, Cho AH, Kwon SU, Kim JS, Kang DW. Lesion patterns and mechanism of ischemia in atherosclerotic middle cerebral artery disease. 2004. In : The 2nd Korea-Japan Joint Stroke Symposim; Yokohama, Japan.

25. Akins PT, Pilgram TK, Cross DT 3rd, Moran CJ. Natural history of stenosis from intracranial atherosclerosis by serial angiography. Stroke. 1998. 29:433–438.

26. Arenillas JF, Molina CA, Montaner J, Abilleira S, Gonzalez-Sanchez MA, Alvarez-Sabin J. Progression and clinical recurrence of symptomatic middle cerebral artery stenosis: a long-term follow-up transcranial doppler ultrasound study. Stroke. 2001. 32:2898–2904.

27. Cho YJ. TOSS investigators. Progression of middle cerebral artery stenosis: symptomatic versus asymptomatic. In : International Stroke Conference 2005; New Orleans, USA.

28. Arenillas JF, Alvarez-Sabin J, Molina CA, Chacon P, Montaner J, Rovira A, et al. C-reactive protein predicts further ischemic events in first-ever transient ischemic attack or stroke patients with intracranial large-artery occlusive disease. Stroke. 2003. 34:2463–2468.

29. Arenillas JF, Álvarez-Sabin J, Montaner J, Rosell A, Molina CA, Rovira A, et al. Angiogenesis in Symptomatic Intracranial Atherosclerosis: Predominance of the Inhibitor Endostatin Is Related to a Greater Extent and Risk of Recurrence. Stroke. 2005. 36:92–97.

30. Chimowitz MI, Kokkinos J, Strong J, Brown MB, Levine SR, Silliman S, et al. The Warfarin-Aspirin Symptomatic Intracranial Disease Study. Neurology. 1995. 45:1488–1493.

31. Chimowitz M, Linn M, Hewlet-Smith H. Warfarin Aspirin Symptomatic Intracranial Disease trial: final results. Stroke. 2004. 35:235–241.

32. Mohr JP, Thompson JLP, Lazar RM, Levin B, Sacco RL, Furie KL, et al. the Warfarin-Aspirin Recurrent Stroke Study Group. A Comparison of Warfarin and Aspirin for the Prevention of Recurrent Ischemic Stroke. N Engl J Med. 2001. 345:1444–1145.

33. The EC/IC Bypass Study Group. Failure of extracranial-intracranial arterial bypass to reduce the risk of ischemic stroke: results of an international randomized trial. N Engl J Med. 1985. 313:1991–2000.

34. The Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001. 345:494–502.

35. Steinhubl SR, Berger PB, Mann JT 3rd, Fry ET, DeLago A, Wilmer C, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA. 2002. 288:2411–2420.

36. Diener HC, Cunha L, Forbes C, Sivenius J, Smets P, Lowenthal A. European Stroke Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci. 1996. 143:1–13.

37. Diener HC, Bogousslavsky J, Brass LM, Cimminiello C, Csiba L, Kaste M, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet. 2004. 364:331–337.

38. Strandness DE Jr, Dalman RL, Panian S, Rendell MS, Comp PC, Zhang P, et al. Effect of cilostazol in patients with intermittent claudication: a randomized, double-blind, placebo-controlled study. Vasc Endovascular Surg. 2002. 36:83–91.

39. Park SW, Lee CW, Kim HS, Lee NH, Nah DY, Hong MK, et al. Effects of cilostazol on angiographic restenosis after coronary stent placement. Am J Cardiol. 2000. 86:499–503.

40. Kwon SU, Cho YJ, Koo JS, Bae HJ, Lee YS, Hong KS, 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. (in press).

41. Wong KS, Li H, Lam WWM, Chan YL, Kay R. Progression of middle cerebral artery occlusive disease and its relationship with further vascular events after stroke. Stroke. 2002. 33:532–536.

42. Wong KS. Statin for the regression of cerebral artery stenosis study: new insights. Proceeding for 1^st International Conference on Intracranial Atherosclerosis. 2004. Hong Kong. 17.

43. Jiang WJ, Wang YJ, Du B, Wang SX, Wang GH, Jin M, et al. Stenting of Symptomatic M1 Stenosis of Middle Cerebral Artery: An Initial Experience of 40 Patients. Stroke. 2004. 35:1375–1380.

44. Kim JK, Ahn JY, Lee BH, Chung YS, Chung SS, Kim OJ, et al. Elective stenting for symptomatic middle cerebral artery stenosis presenting as transient ischaemic deficits or stroke attacks: short term arteriographical and clinical outcome. J Neurol Neurosurg Psychiatry. 2004. 75:847–851.

45. Lee JH, Kwon SU, Lee JH, Suh DC, Kim JS. Percutaneous transluminal angioplasty for symptomatic middle cerebral artery stenosis: long-term follow-up. Cerebrovasc Dis. 2003. 15:90–97.

46. Suh DC, Sung KB, Cho YS, Choi CG, Lee HK, Lee JH, et al. Transluminal angioplasty for middle cerebral artery stenosis in patients with acute ischemic stroke. AJNR. 1999. 20:553–558.

47. Gupta R, Schumacher HC, Mangla S, Meyers PM, Duong H, Khandji AG, et al. Urgent endovascular revascularization for symptomatic intracranial atherosclerotic stenosis. Neurology. 2003. 61:1729–1735.

48. The SSYLVIA Study Investigators. Stenting of Symptomatic Atherosclerotic Lesions in the Vertebral or Intracranial Arteries (SSYLVIA): Study Results. Stroke. 2004. 35:1388–1392.

49. Suh DC, Kim SJ, Lee DH, Choi CG, Lee JH, Kim HJ, et al. Outcome of endovascular treatment in symptomatic intracranial vascular stenosis. Kor J Radiol. 2005. 6:1–7.

50. JET Study Groups. Japanese EC-IC bypass surgery; the secondary interim analysis. Surg Cereb Stroke. 2002. 30:434–437.

51. Mizumura S, Nakagawara J, Takahashi M, Kumita S, Cho K, Nakajo H, et al. Three-dimensional display in staging hemodynamic brain ischemia for JET study: objective evaluation using SEE analysis and 3D-SSP display. Ann Nucl Med. 2004. 18:13–21.