Pre-treatment cerebral microbleeds and intracranial hemorrhage in patients with ischemic stroke receiving endovascular therapy: a systematic review and meta-analysis

  • Xiumei Wu
  • Jiangzhi Yan
  • Huirong Ye
  • Jianting Qiu
  • Jian Wang
  • Yujie WangEmail author


Background and purpose

Predicting the risk of intracranial hemorrhage (ICH) is an important aspect for improving the efficacy and safety of endovascular therapy (EVT). We intended to perform a systematic review and meta-analysis to show whether pre-treatment cerebral microbleeds (CMBs) were associated with an increased incidence of ICH in patients with ischemic stroke receiving EVT.


We searched PubMed, EMBASE, Web of Science and Cochrane Library from their dates of inception to December 18, 2018, and also manually searched reference lists of relevant articles. Cumulative prevalence of CMBs and ICH was calculated. Relative risk and 95% confidence interval (CI) were calculated for the incidence of ICH in patients with CMBs versus those without after EVT.


Four studies involving 598 patients were included. The pooled prevalence of CMBs was 18% (95% CI 15–21%) and the pooled prevalence of ≥ 5 CMBs was 1% (95% CI 0–2%). The pooled incidence of ICH was 29% (95% CI 8–49%) in all patients, 25% (95% CI 5–45%) in those with CMBs and 29% (95% CI 8–50%) in those without CMBs. The pooled relative risk of ICH was 0.90 (95% CI 0.65–1.25, P = 0.528; I2 = 0%, P = 0.949) in patients with CMBs versus those without CMBs.


There is no evidence that pre-treatment CMBs were associated with an increased incidence of ICH in patients with ischemic stroke receiving EVT.


Endovascular procedures Cerebral microbleeds Intracerebral hemorrhage Stroke Meta-analysis 



None of the authors received financial support for this manuscript.

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical standards

The manuscript does not contain clinical studies or patient data.

Supplementary material

415_2019_9210_MOESM1_ESM.pdf (472 kb)
Supplementary material 1 (PDF 471 KB)


  1. 1.
    Sacks D, Baxter B, Campbell BCV, Carpenter JS, Cognard C, Dippel D, Eesa M, Fischer U, Hausegger K, Hirsch JA, Hussain MS, Jansen O, Jayaraman MV, Khalessi AA, Kluck BW, Lavine S, Meyers PM, Ramee S, Rufenacht DA, Schirmer CM, Vorwerk D (2018) Multisociety consensus quality improvement revised consensus statement for endovascular therapy of acute ischemic stroke. AJNR Am J Neuroradiol 39(6):E61–E76. CrossRefGoogle Scholar
  2. 2.
    Hong KS, Ko SB, Yu KH, Jung C, Park SQ, Kim BM, Chang CH, Bae HJ, Heo JH, Oh CW, Lee BC, Kim BT, Kim BS, Chung CS, Yoon BW, Rha JH (2016) Update of the Korean clinical practice guidelines for endovascular recanalization therapy in patients with acute ischemic stroke. J Stroke 18(1):102–113. CrossRefGoogle Scholar
  3. 3.
    Saver JL, Jahan R, Levy EI, Jovin TG, Baxter B, Nogueira RG, Clark W, Budzik R, Zaidat OO (2012) Solitaire flow restoration device versus the merci retriever in patients with acute ischaemic stroke (SWIFT): a randomised, parallel-group, non-inferiority trial. Lancet 380(9849):1241–1249. CrossRefGoogle Scholar
  4. 4.
    Phan K, Dmytriw AA, Maingard J, Asadi H, Griessenauer CJ, Ng W, Kewagamang K, Mobbs RJ, Moore JM, Ogilvy CS, Thomas AJ (2017) Endovascular thrombectomy alone versus combined with intravenous thrombolysis. World Neurosurg 108:850–858.e852. CrossRefGoogle Scholar
  5. 5.
    Leng X, Fang H, Leung TW, Mao C, Miao Z, Liu L, Wong KS, Liebeskind DS (2016) Impact of collaterals on the efficacy and safety of endovascular treatment in acute ischaemic stroke: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 87(5):537–544. CrossRefGoogle Scholar
  6. 6.
    Senior K (2002) Microbleeds may predict cerebral bleeding after stroke. Lancet 359(9308):769. CrossRefGoogle Scholar
  7. 7.
    Charidimou A, Krishnan A, Werring DJ, Rolf Jager H (2013) Cerebral microbleeds: a guide to detection and clinical relevance in different disease settings. Neuroradiology 55(6):655–674. CrossRefGoogle Scholar
  8. 8.
    Charidimou A, Kakar P, Fox Z, Werring DJ (2013) Cerebral microbleeds and recurrent stroke risk: systematic review and meta-analysis of prospective ischemic stroke and transient ischemic attack cohorts. Stroke 44(4):995–1001. CrossRefGoogle Scholar
  9. 9.
    Qiu J, Ye H, Wang J, Yan J, Wang J, Wang Y (2018) Antiplatelet therapy, cerebral microbleeds, and intracerebral hemorrhage: a meta-analysis. Stroke 49(7):1751–1754. CrossRefGoogle Scholar
  10. 10.
    Yan J, Qiu J, Wu X, Ge Y, Wang J, Wang Y (2018) Pretreatment cerebral microbleeds and symptomatic intracerebral hemorrhage post-thrombolysis: a systematic review and meta-analysis. J Neurol. Google Scholar
  11. 11.
    Kidwell CS, Saver JL, Villablanca JP, Duckwiler G, Fredieu A, Gough K, Leary MC, Starkman S, Gobin YP, Jahan R, Vespa P, Liebeskind DS, Alger JR, Vinuela F (2002) Magnetic resonance imaging detection of microbleeds before thrombolysis: an emerging application. Stroke 33(1):95–98CrossRefGoogle Scholar
  12. 12.
    Soo YO, Siu DY, Abrigo J, Yu S, Ng N, Ahuja AT, Wong LK, Leung TW (2012) Risk of intracerebral hemorrhage in patients with cerebral microbleeds undergoing endovascular intervention. Stroke 43(6):1532–1536. CrossRefGoogle Scholar
  13. 13.
    Kim HS, Lee DH, Ryu CW, Lee JH, Choi CG, Kim SJ, Suh DC (2006) Multiple cerebral microbleeds in hyperacute ischemic stroke: impact on prevalence and severity of early hemorrhagic transformation after thrombolytic treatment. AJR Am J Roentgenol 186(5):1443–1449. CrossRefGoogle Scholar
  14. 14.
    Shi ZS, Duckwiler GR, Jahan R, Tateshima S, Gonzalez NR, Szeder V, Saver JL, Kim D, Ali LK, Starkman S, Vespa PM, Salamon N, Villablanca JP, Vinuela F, Feng L, Loh Y, Liebeskind DS (2016) Mechanical thrombectomy for acute ischemic stroke with cerebral microbleeds. J Neurointerventional Surg 8(6):563–567. CrossRefGoogle Scholar
  15. 15.
    Gratz PP, El-Koussy M, Hsieh K, von Arx S, Mono ML, Heldner MR, Fischer U, Mattle HP, Zubler C, Schroth G, Gralla J, Arnold M, Jung S (2014) Preexisting cerebral microbleeds on susceptibility-weighted magnetic resonance imaging and post-thrombolysis bleeding risk in 392 patients. Stroke 45(6):1684–1688. CrossRefGoogle Scholar
  16. 16.
    Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart LA (2015) Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 350:g7647. CrossRefGoogle Scholar
  17. 17.
    Haji S, Planchard R, Zubair A, Graff-Radford J, Rydberg C, Brown RD Jr, Flemming KD (2016) The clinical relevance of cerebral microbleeds in patients with cerebral ischemia and atrial fibrillation. J Neurol 263(2):238–244. CrossRefGoogle Scholar
  18. 18.
    Wilson D, Ambler G, Shakeshaft C, Brown MM, Charidimou A, Al-Shahi Salman R, Lip GYH, Cohen H, Banerjee G, Houlden H, White MJ, Yousry TA, Harkness K, Flossmann E, Smyth N, Shaw LJ, Warburton E, Muir KW, Jager HR, Werring DJ (2018) Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2): a multicentre observational cohort study. Lancet Neurol 17(6):539–547. CrossRefGoogle Scholar
  19. 19.
    Hao Y, Zhang Z, Zhang H, Xu L, Ye Z, Dai Q, Liu X, Xu G (2017) Risk of intracranial hemorrhage after endovascular treatment for acute ischemic stroke: systematic review and meta-analysis. Interv Neurol 6(1–2):57–64. CrossRefGoogle Scholar
  20. 20.
    Campbell BC, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov L, Yassi N, Yan B, Dowling RJ, Parsons MW, Oxley TJ, Wu TY, Brooks M, Simpson MA, Miteff F, Levi CR, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Priglinger M, Ang T, Scroop R, Barber PA, McGuinness B, Wijeratne T, Phan TG, Chong W, Chandra RV, Bladin CF, Badve M, Rice H, de Villiers L, Ma H, Desmond PM, Donnan GA, Davis SM (2015) Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med 372(11):1009–1018. CrossRefGoogle Scholar
  21. 21.
    Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, Roy D, Jovin TG, Willinsky RA, Sapkota BL, Dowlatshahi D, Frei DF, Kamal NR, Montanera WJ, Poppe AY, Ryckborst KJ, Silver FL, Shuaib A, Tampieri D, Williams D, Bang OY, Baxter BW, Burns PA, Choe H, Heo JH, Holmstedt CA, Jankowitz B, Kelly M, Linares G, Mandzia JL, Shankar J, Sohn SI, Swartz RH, Barber PA, Coutts SB, Smith EE, Morrish WF, Weill A, Subramaniam S, Mitha AP, Wong JH, Lowerison MW, Sajobi TT, Hill MD (2015) Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 372(11):1019–1030. CrossRefGoogle Scholar
  22. 22.
    Jovin TG, Chamorro A, Cobo E, de Miquel MA, Molina CA, Rovira A, San Roman L, Serena J, Abilleira S, Ribo M, Millan M, Urra X, Cardona P, Lopez-Cancio E, Tomasello A, Castano C, Blasco J, Aja L, Dorado L, Quesada H, Rubiera M, Hernandez-Perez M, Goyal M, Demchuk AM, von Kummer R, Gallofre M, Davalos A (2015) Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med 372(24):2296–2306. CrossRefGoogle Scholar
  23. 23.
    Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, Albers GW, Cognard C, Cohen DJ, Hacke W, Jansen O, Jovin TG, Mattle HP, Nogueira RG, Siddiqui AH, Yavagal DR, Baxter BW, Devlin TG, Lopes DK, Reddy VK, du de Rochemont M, Singer R, Jahan OC R (2015) Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med 372(24):2285–2295. CrossRefGoogle Scholar
  24. 24.
    Fisher M, French S, Ji P, Kim RC (2010) Cerebral microbleeds in the elderly: a pathological analysis. Stroke 41(12):2782–2785. CrossRefGoogle Scholar
  25. 25.
    Hopewell S, McDonald S, Clarke M, Egger M (2007) Grey literature in meta-analyses of randomized trials of health care interventions. Cochrane Database Syst Rev (2):Mr000010.
  26. 26.
    Cheng AL, Batool S, McCreary CR, Lauzon ML, Frayne R, Goyal M, Smith EE (2013) Susceptibility-weighted imaging is more reliable than T2*-weighted gradient-recalled echo MRI for detecting microbleeds. Stroke 44(10):2782–2786. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Xiumei Wu
    • 1
  • Jiangzhi Yan
    • 1
  • Huirong Ye
    • 1
  • Jianting Qiu
    • 1
  • Jian Wang
    • 1
  • Yujie Wang
    • 1
    Email author
  1. 1.Cerebrovascular Disease Center, Department of Neurology, People’s HospitalChina Medical UniversityShenyangPeople’s Republic of China

Personalised recommendations