Skip to main content
SpringerLink
Log in

Collateral Flow in Intracranial Atherosclerotic Disease

  • Review Article
  • Published:
Translational Stroke Research Aims and scope Submit manuscript

Abstract

Intracranial atherosclerotic disease (ICAD) is a major cause of ischemic stroke and transient ischemic attack (TIA) worldwide. The culprit of ICAD is frequently a high-grade intracranial atherosclerotic stenosis (ICAS) pertaining to the infarct territory, and by then, the ICAS is described as symptomatic. A high-grade ICAS may progressively limit cerebral perfusion downstream, demanding collateral compensation. Collateral circulation refers to the pre-existing and dynamic emergence of vascular channels that maintain and compensate for a failing principal vascular route. Collaterals through the Circle of Willis and leptomeningeal circulation are of utmost importance in this regard. In this article, we first discussed the epidemiology, stroke mechanisms, contemporary therapeutics, and prognosis of symptomatic ICAD. Then, we reviewed the collateral routes in ICAS, factors associated with recruitment and development of the collaterals and diagnostic imaging modalities in assessing the origin and function of collateral circulation. We discussed the associations between collateral circulation and clinical outcomes after acute reperfusion treatment in ICAD-related ischemic strokes with or without large vessel occlusion (LVO). We also conducted a systematic review and meta-analysis on the associations of collateral circulation with the risk of recurrent stroke and the functional outcome in symptomatic ICAS patients on medical treatment as secondary stroke prevention. Finally, we summarized current evidence in these aspects and proposed the future directions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data Availability

Data are available upon reasonable request to the corresponding author.

References

  1. Qureshi AI, Caplan LR. Intracranial atherosclerosis. Lancet. 2014;383:984–98.

    Article  Google Scholar 

  2. Leng X, Wong KS, Liebeskind DS. Evaluating intracranial atherosclerosis rather than intracranial stenosis. Stroke. 2014;45:645–51.

    Article  Google Scholar 

  3. Liebeskind DS. Collateral circulation. Stroke. 2003;34:2279–84.

    Article  Google Scholar 

  4. Lan L, Leng X, Ip V, Soo Y, Abrigo J, Liu H, et al. Sustaining cerebral perfusion in intracranial atherosclerotic stenosis: the roles of antegrade residual flow and leptomeningeal collateral flow. J Cereb Blood Flow Metab. 2020;40:126–34.

    Article  Google Scholar 

  5. Kern R, Steinke W, Daffertshofer M, Prager R, Hennerici M. Stroke recurrences in patients with symptomatic vs asymptomatic middle cerebral artery disease. Neurology. 2005;65:859–64.

    Article  CAS  Google Scholar 

  6. Tanaka M, Shimosegawa E, Kajimoto K, Kimura Y, Kato H, Oku N, et al. Chronic middle cerebral artery occlusion: a hemodynamic and metabolic study with positron-emission tomography. AJNR Am J Neuroradiol. 2008;29:1841–6.

    Article  CAS  Google Scholar 

  7. Liebeskind DS. Intracranial collateral routes and anastomoses in interventional neuroradilolgy. In: Hurst RW, Rosenwasser RH, editors. Neurointerventional Management: Diagnosis and Treatment. 2nd ed. CRC Press; 2012. p. 59–87.

    Chapter  Google Scholar 

  8. Lou X, Ma X, Liebeskind DS, Ma N, Tian C, Lyu J, et al. Collateral perfusion using arterial spin labeling in symptomatic versus asymptomatic middle cerebral artery stenosis. J Cereb Blood Flow Metab. 2019;39:108–17.

    Article  CAS  Google Scholar 

  9. Shi M, Leng X, Li Y, Chen Z, Cao Y, Chung T, et al. Genome sequencing reveals the role of rare genomic variants in Chinese patients with symptomatic intracranial atherosclerotic disease. Stroke Vas Neurol. 2021:svn-2021–001157.

  10. Leng X, Hurford R, Feng X, Chan KL, Wolters FJ, Li L, et al. Intracranial arterial stenosis in Caucasian versus Chinese patients with TIA and minor stroke: two contemporaneous cohorts and a systematic review. J Neurol Neurosurg Psychiatry. 2021;92:590–7.

    Article  Google Scholar 

  11. Leung S, Ng T, Yuen S, Lauder I, Ho F. Pattern of cerebral atherosclerosis in Hong Kong Chinese. Severity in intracranial and extracranial vessels. Stroke. 1993;24:779–86.

    Article  CAS  Google Scholar 

  12. Baker AB, Resch JA, Loewenson RB. Cerebral atherosclerosis in European populations: a preliminary report. Stroke. 1973;4:898–903.

    Article  CAS  Google Scholar 

  13. Wong KS, Huang YN, Yang HB, Gao S, Li H, Liu JY, et al. A door-to-door survey of intracranial atherosclerosis in Liangbei County. China Neurology. 2007;68:2031–4.

    Article  CAS  Google Scholar 

  14. Zhang S, Zhou Y, Zhang Y, Gao X, Zhang Q, Wang A, et al. Prevalence and risk factors of asymptomatic intracranial arterial stenosis in a community-based population of Chinese adults. Eur J Neurol. 2013;20:1479–85.

    CAS  Google Scholar 

  15. Wong KS, Ng PW, Tang A, Liu R, Yeung V, Tomlinson B. Prevalence of asymptomatic intracranial atherosclerosis in high-risk patients. Neurology. 2007;68:2035–8.

    Article  CAS  Google Scholar 

  16. Elmore EM, Mosquera A, Weinberger J. The prevalence of asymptomatic intracranial large-vessel occlusive disease: the role of diabetes. J Neuroimaging. 2003;13:224–7.

    Article  Google Scholar 

  17. Holmstedt CA, Turan TN, Chimowitz MI. Atherosclerotic intracranial arterial stenosis: risk factors, diagnosis, and treatment. Lancet Neurol. 2013;12:1106–14.

    Article  Google Scholar 

  18. Wong LK. Global burden of intracranial atherosclerosis. Int J Stroke. 2006;1:158–9.

    Article  Google Scholar 

  19. Hurford R, Wolters FJ, Li L, Lau KK, Küker W, Rothwell PM. Prevalence, predictors, and prognosis of symptomatic intracranial stenosis in patients with transient ischaemic attack or minor stroke: a population-based cohort study. Lancet Neurol. 2020;19:413–21.

    Article  Google Scholar 

  20. Ip B, Au L, Chan A, Fan F, Ip V, Ma SH, et al. Evolving ischemic stroke subtypes in 15 years: a hospital-based observational study. Int J Stroke. 2022;17:444–54.

    Article  Google Scholar 

  21. Gao S, Wang YJ, Xu AD, Li YS, Wang DZ. Chinese ischemic stroke subclassification Front Neurol. 2011;2:6.

    CAS  Google Scholar 

  22. Feng X, Chan KL, Lan L, Abrigo J, Liu J, Fang H, et al. Stroke mechanisms in symptomatic intracranial atherosclerotic disease: classification and clinical implications. Stroke. 2019;50:2692–9.

    Article  CAS  Google Scholar 

  23. Chimowitz MI, Lynn MJ, Howlett-Smith H, Stern BJ, Hertzberg VS, Frankel MR, et al. Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis. N Engl J Med. 2005;352:1305–16.

    Article  CAS  Google Scholar 

  24. Chimowitz MI, Lynn MJ, Derdeyn CP, Turan TN, Fiorella D, Lane BF, et al. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med. 2011;365:993–1003.

    Article  CAS  Google Scholar 

  25. Kleindorfer DO, Towfighi A, Chaturvedi S, Cockroft KM, Gutierrez J, Lombardi-Hill D, et al. 2021 Guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline from the American Heart Association/American Stroke Association. Stroke. 2021;52:e364–467.

    Article  Google Scholar 

  26. Wang Y, Wang Y, Zhao X, Liu L, Wang D, Wang C, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med. 2013;369:11–9.

    Article  CAS  Google Scholar 

  27. Zaidat OO, Fitzsimmons BF, Woodward BK, Wang Z, Killer-Oberpfalzer M, Wakhloo A, 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;313:1240–8.

    Article  CAS  Google Scholar 

  28. Alexander MJ, Zauner A, Chaloupka JC, Baxter B, Callison RC, Gupta R, et al. WEAVE Trial: final results in 152 on-label patients. Stroke. 2019;50:889–94.

    Article  Google Scholar 

  29. Alexander MJ, Zauner A, Gupta R, Alshekhlee A, Fraser JF, Toth G, et al. The WOVEN trial: Wingspan One-year Vascular Events and Neurologic Outcomes. J Neurointerv Surg. 2021;13:307–10.

    Article  Google Scholar 

  30. Wabnitz AM, Derdeyn CP, Fiorella DJ, Lynn MJ, Cotsonis GA, Liebeskind DS, et al. Hemodynamic markers in the anterior circulation as predictors of recurrent stroke in patients with intracranial stenosis. Stroke. 2019;50:143–7.

    Article  Google Scholar 

  31. Yaghi S, Prabhakaran S, Khatri P, Liebeskind DS. Intracranial atherosclerotic disease: mechanisms and therapeutic implications. Stroke. 2019;50:1286–93.

    Article  Google Scholar 

  32. Gui X, Wang L, Wu C, Wang H, Kong J. Prognosis of subtypes of acute large artery atherosclerotic cerebral infarction by evaluation of established collateral circulation. J Stroke Cerebrovasc Dis. 2020;29:105232.

    Article  Google Scholar 

  33. Caplan LR, Hennerici M. Impaired clearance of emboli (washout) is an important link between hypoperfusion, embolism, and ischemic stroke. Arch Neurol. 1998;55:1475–82.

    Article  CAS  Google Scholar 

  34. Caplan LR, Wong KS, Gao S, Hennerici MG. Is hypoperfusion an important cause of strokes? If so, how? Cerebrovasc Dis. 2006;21:145–53.

    Article  Google Scholar 

  35. Liebeskind DS, Cotsonis GA, Saver JL, Lynn MJ, Cloft HJ, Chimowitz MI, et al. Collateral circulation in symptomatic intracranial atherosclerosis. J Cereb Blood Flow Metab. 2011;31:1293–301.

    Article  Google Scholar 

  36. Heil M, Eitenmüller I, Schmitz-Rixen T, Schaper W. Arteriogenesis versus angiogenesis: similarities and differences. J Cell Mol Med. 2006;10:45–55.

    Article  CAS  Google Scholar 

  37. Liang M, Wang P, Ma Y, Zhang X, Gao J, Ma M, et al. New vessels formation in young strokes with isolated steno-occlusive MCA. Brain Behav. 2018;8:e01088.

    Article  Google Scholar 

  38. Kanazawa M, Takahashi T, Ishikawa M, Onodera O, Shimohata T, del Zoppo GJ. Angiogenesis in the ischemic core: a potential treatment target? J Cereb Blood Flow Metab. 2019;39:753–69.

    Article  CAS  Google Scholar 

  39. Xu YY, Li ML, Gao S, Hou B, Sun ZY, Zhou HL, et al. Non-moyamoya vessel network formation along steno-occlusive middle cerebral artery. Neurology. 2016;86:1957–63.

    Article  Google Scholar 

  40. Leng X, Lan L, Ip HL, Fan F, Ma SH, Ma K, et al. Translesional pressure gradient and leptomeningeal collateral status in symptomatic middle cerebral artery stenosis. Eur J Neurol. 2018;25:404–10.

    Article  CAS  Google Scholar 

  41. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) expert panel on detection evaluation and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001;285:2486–97.

    Article  Google Scholar 

  42. Menon BK, Smith EE, Coutts SB, Welsh DG, Faber JE, Goyal M, et al. Leptomeningeal collaterals are associated with modifiable metabolic risk factors. Ann Neurol. 2013;74:241–8.

    CAS  Google Scholar 

  43. Nannoni S, Sirimarco G, Cereda CW, Lambrou D, Strambo D, Eskandari A, et al. Determining factors of better leptomeningeal collaterals: a study of 857 consecutive acute ischemic stroke patients. J Neurol. 2019;266:582–8.

    Article  Google Scholar 

  44. Wiegers EJA, Mulder MJHL, Jansen IGH, Venema E, Compagne KCJ, Berkhemer OA, et al. Clinical and imaging determinants of collateral status in patients with acute ischemic stroke in MR CLEAN Trial and Registry. Stroke. 2020;51:1493–502.

    Article  Google Scholar 

  45. Sinha A, Stanwell P, Beran RG, Calic Z, Killingsworth MC, Bhaskar SMM. Stroke aetiology and collateral status in acute ischemic stroke patients receiving reperfusion therapy-a meta-analysis. Neurol Int. 2021;13:608–21.

    Article  Google Scholar 

  46. Higashida RT, Furlan AJ, Roberts H, Tomsick T, Connors B, Barr J, et al. Trial design and reporting standards for intra-arterial cerebral thrombolysis for acute ischemic stroke. Stroke. 2003;34:e109-137.

    Article  Google Scholar 

  47. Miteff F, Levi CR, Bateman GA, Spratt N, McElduff P, Parsons MW. The independent predictive utility of computed tomography angiographic collateral status in acute ischaemic stroke. Brain. 2009;132:2231–8.

    Article  Google Scholar 

  48. Tan IY, Demchuk AM, Hopyan J, Zhang L, Gladstone D, Wong K, et al. CT angiography clot burden score and collateral score: correlation with clinical and radiologic outcomes in acute middle cerebral artery infarct. AJNR Am J Neuroradiol. 2009;30:525–31.

    Article  CAS  Google Scholar 

  49. Maas MB, Lev MH, Ay H, Singhal AB, Greer DM, Smith WS, et al. Collateral vessels on CT angiography predict outcome in acute ischemic stroke. Stroke. 2009;40:3001–5.

    Article  Google Scholar 

  50. Menon BK, Smith EE, Modi J, Patel SK, Bhatia R, Watson TW, et al. Regional leptomeningeal score on CT angiography predicts clinical and imaging outcomes in patients with acute anterior circulation occlusions. AJNR Am J Neuroradiol. 2011;32:1640–5.

    Article  CAS  Google Scholar 

  51. Liu L, Ding J, Leng X, Pu Y, Huang LA, Xu A, et al. Guidelines for evaluation and management of cerebral collateral circulation in ischaemic stroke 2017. Stroke Vas Neurol. 2018;3:117–30.

    Article  Google Scholar 

  52. Cipolla MJ. Therapeutic induction of collateral flow. Transl Stroke Res. Published online ahead of print on 13 April 2022.

  53. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2019;50:e344–418.

    Article  Google Scholar 

  54. Leng X, Lan L, Liu L, Leung TW, Wong KS. Good collateral circulation predicts favorable outcomes in intravenous thrombolysis: a systematic review and meta-analysis. Eur J Neurol. 2016;23:1738–49.

    Article  CAS  Google Scholar 

  55. Leng X, Fang H, Leung TW, Mao C, Xu Y, Miao Z, et al. Impact of collateral status on successful revascularization in endovascular treatment: a systematic review and meta-analysis. Cerebrovasc Dis. 2016;41:27–34.

    Article  Google Scholar 

  56. Leng X, Fang H, Leung TWH, Mao C, Miao Z, Liu L, et al. Impact of collaterals on the efficacy and safety of endovascular treatment in acute ischemic stroke: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2016;87:537–44.

    Article  Google Scholar 

  57. Román LS, Menon BK, Blasco J, Hernández-Pérez M, Dávalos A, Majoie CBLM, et al. Imaging features and safety and efficacy of endovascular stroke treatment: a meta-analysis of individual patient-level data. Lancet Neurol. 2018;17:895–904.

    Article  Google Scholar 

  58. Guglielmi V, LeCouffe NE, Zinkstok SM, Compagne KCJ, Eker R, Treurniet KM, et al. Collateral circulation and outcome in atherosclerotic versus cardioembolic cerebral large vessel occlusion. Stroke. 2019;50(12):3360–8.

    Article  Google Scholar 

  59. Matusevicius M, Cooray C, Rand V-M, Nunes AP, Moreira T, Tassi R, et al. Stroke etiology and outcomes after endovascular thrombectomy: results from the SITS Registry and a meta-analysis. J Stroke. 2021;23:388–400.

    Article  Google Scholar 

  60. Zhang X, Zhang M, Ding W, Yan S, Liebeskind DS, Lou M. Distinct predictive role of collateral status on clinical outcome in variant stroke subtypes of acute large arterial occlusion. Eur J Neurol. 2018;25:293–300.

    Article  CAS  Google Scholar 

  61. Malhotra K, Liebeskind DS. Collaterals Ischemic Stroke Brain Hemorrhages. 2020;1:6–12.

    Article  Google Scholar 

  62. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151:264–9.

    Article  Google Scholar 

  63. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283:2008–12.

    Article  CAS  Google Scholar 

  64. Wells G, Shea B, O'Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 10 Jan 2022.

  65. Liebeskind DS, Cotsonis GA, Saver JL, Lynn MJ, Turan TN, Cloft HJ, et al. Collaterals dramatically alter stroke risk in intracranial atherosclerosis. Ann Neurol. 2011;69:963–74.

    Article  Google Scholar 

  66. Lau AY, Wong EH, Wong A, Mok VC, Leung TW, Wong KS. Significance of good collateral compensation in symptomatic intracranial atherosclerosis. Cerebrovasc Dis. 2012;33:517–24.

    Article  CAS  Google Scholar 

  67. Liu D, Li Y, Shi Z, Davis SM, Wong KS, Leung TW, et al. Presence of anterior temporal artery associates with good outcome in acute atherosclerotic M1-middle cerebral artery occlusion. Neuroradiology. 2014;56:1023–30.

    Article  Google Scholar 

  68. Wang Y, Zhao X, Liu L, Soo YO, Pu Y, Pan Y, et al. Prevalence and outcomes of symptomatic intracranial large artery stenoses and occlusions in China: the Chinese Intracranial Atherosclerosis (CICAS) Study. Stroke. 2014;45:663–9.

    Article  Google Scholar 

  69. Kim KM, Kang HS, Lee WJ, Cho YD, Kim JE, Han MH. Clinical significance of the circle of Willis in intracranial atherosclerotic stenosis. J Neurointerv Surg. 2016;8:251–5.

    Article  Google Scholar 

  70. Lee WJ, Jung KH, Ryu YJ, Kim JM, Lee ST, Chu K, et al. Utility of digital subtraction angiography-based collateral evaluation in medically treated acute symptomatic basilar artery stenosis. Eur J Neurol. 2017;24:1148–55.

    Article  Google Scholar 

  71. Shang WJ, Chen HB, Shu LM, Liao HQ, Huang XY, Xiao S, et al. The association between flair vascular hyperintensity and stroke outcome varies with time from onset. AJNR Am J Neuroradiol. 2019;40:1317–22.

    Article  CAS  Google Scholar 

  72. Wabnitz AM, Derdeyn CP, Fiorella DJ, Lynn MJ, Cotsonis GA, Liebeskind DS, et al. Hemodynamic markers in the anterior circulation as predictors of recurrent stroke in patients with intracranial stenosis. Stroke. 2019;50(1):143–7.

    Article  Google Scholar 

  73. Leung TW, Wang L, Zou X, Soo Y, Pu Y, Ip HL, et al. Plaque morphology in acute symptomatic intracranial atherosclerotic disease. J Neurol Neurosurg Psychiatry. 2021;92:370–6.

    Article  Google Scholar 

  74. Bang OY, Chung JW, Kim SK, Kim SJ, Lee MJ, Hwang J, et al. Therapeutic-induced hypertension in patients with noncardioembolic acute stroke. Neurology. 2019;93:e1955–63.

    Article  Google Scholar 

  75. Bornstein NM, Saver JL, Diener HC, Gorelick PB, Shuaib A, Solberg Y, et al. Sphenopalatine ganglion stimulation to augment cerebral blood flow: a randomized, sham-controlled trial. Stroke. 2019;50:2108–17.

    Article  Google Scholar 

  76. Lin WH, Xiong L, Han JH, Leung TWH, Soo YOY, Chen XY, et al. External counterpulsation augments blood pressure and cerebral flow velocities in ischemic stroke patients with cerebral intracranial large artery occlusive disease. Stroke. 2012;43:3007–11.

    Article  Google Scholar 

  77. Meng R, Asmaro K, Meng L, Liu Y, Ma C, Xi C, et al. Upper limb ischemic preconditioning prevents recurrent stroke in intracranial arterial stenosis. Neurology. 2012;79:1853–61.

    Article  Google Scholar 

  78. Gonzalez NR, Jiang H, Lyden P, Song S, Schlick K, Dumitrascu O, et al. Encephaloduroarteriosynangiosis (EDAS) revascularization for symptomatic intracranial atherosclerotic steno-occlusive (ERSIAS) Phase-II objective performance criterion trial. Int J Stroke. 2021;16:701–9.

    Article  Google Scholar 

Download references

Funding

This work was supported by the Kwok Tak Seng Centre for Stroke Research and Intervention.

Author information

Authors and Affiliations

  1. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Hong Kong SAR, China

    Xinyi Leng & Thomas W. Leung

Authors
  1. Xinyi Leng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas W. Leung
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

X.L. performed literature search and drafted the article; T.W.L. revised the article. All the authors have read and agreed to the final version of the manuscript.

Corresponding author

Correspondence to Thomas W. Leung.

Ethics declarations

Ethics Approval

Not applicable of this review article.

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 184 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Leng, X., Leung, T.W. Collateral Flow in Intracranial Atherosclerotic Disease. Transl. Stroke Res. 14, 38–52 (2023). https://doi.org/10.1007/s12975-022-01042-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12975-022-01042-3

Keywords

Search

Navigation