Skip to main content
AAN.com
Article
September 14, 2016

Clinical relevance of microbleeds in acute stroke thrombolysis
Comprehensive meta-analysis

October 11, 2016 issue
87 (15) 1534-1541

Abstract

Objective:

We performed a systematic review and meta-analysis to assess whether the presence of cerebral microbleeds (CMBs) on pretreatment MRI of patients with acute ischemic stroke treated with IV thrombolysis is associated with increased risk of symptomatic intracerebral hemorrhage (ICH) and poor functional outcome.

Methods:

We searched PubMed for relevant studies and calculated pooled odds ratios (OR) for symptomatic ICH and poor (i.e., modified Rankin Scale score >2) 3- to 6-month functional outcome using random effects models with DerSimonian-Laird weights among individuals with vs without CMBs.

Results:

Eight eligible studies including 2,601 stroke patients treated with IV thrombolysis were pooled in a meta-analysis. The cumulative CMBs prevalence was 24% (95% confidence interval [CI] 18%–30%). The pooled symptomatic ICH incidence was 5% (95% CI 4%–7%) among patients with CMBs and 3% (95% CI 2%–5%) in patients without CMBs. CMB presence was associated with higher risk of symptomatic ICH compared to patients without CMBs (OR 2.18; 95% CI 1.12–4.22; p = 0.021). Four studies (n = 1,665) reported data on 3- to 6-month poststroke functional outcome. The pooled incidence of poor functional outcome was 52% (95% CI 45%–59%) in patients with CMBs vs 41% (95% CI 35%–46%) in those without CMBs. Meta-analysis of these studies demonstrated OR for CMBs presence and adverse outcome to be 1.58 (95% CI 1.18–2.14; p = 0.002).

Conclusions:

CMBs are associated with greater symptomatic ICH risk and poor functional outcome in ischemic stroke patients undergoing thrombolytic therapy. In the absence of adjusted analyses and randomized evidence, this risk seems acceptable and should probably not discourage recanalization therapies in this patient population (Level B recommendation: nonrandomized Class IIa evidence).

Get full access to this article

View all available purchase options and get full access to this article.

Supplementary Material

File (1526.pdf)
File (table_e-1.pdf)

REFERENCES

1.
Emberson J, Lees KR, Lyden P, et al. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet 2014;384:1929–1935.
2.
Greenberg SM, Vernooij MW, Cordonnier C, et al. Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol 2009;8:165–174.
3.
Charidimou A, Shoamanesh A, Wilson D, et al. Cerebral microbleeds and postthrombolysis intracerebral hemorrhage risk updated meta-analysis. Neurology 2015;85:927–934.
4.
Yan S, Jin X, Zhang X, Zhang S, Liebeskind DS, Lou M. Extensive cerebral microbleeds predict parenchymal haemorrhage and poor outcome after intravenous thrombolysis. J Neurol Neurosurg Psychiatry 2015;86:1267–1272.
5.
Turc G, Sallem A, Moulin S, et al. Microbleed status and 3-month outcome after intravenous thrombolysis in 717 patients with acute ischemic stroke. Stroke 2015;46:2458–2463.
6.
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009;339:b2535.
7.
Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000;283:2008–2012.
8.
Cordonnier C, Al-Shahi Salman R, Wardlaw J. Spontaneous brain microbleeds: systematic review, subgroup analyses and standards for study design and reporting. Brain 2007;130:1988–2003.
9.
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177–188.
10.
Shen-Qiang Y, Ying-Ying M, Gen-Long Z, Sheng Z, Min L. Safety of intravenous thrombolysis in cerebral microbleeds patients with prior antiplatelet therapy [in Chinese]. Zhejiang Da Xue Xue Bao Yi Xue Ban 2015;44:618–624.
11.
Gratz PP, El-Koussy M, Hsieh K, et al. Preexisting cerebral microbleeds on susceptibility-weighted magnetic resonance imaging and post-thrombolysis bleeding risk in 392 patients. Stroke 2014;45:1684–1688.
12.
Dannenberg S, Scheitz JF, Rozanski M, et al. Number of cerebral microbleeds and risk of intracerebral hemorrhage after intravenous thrombolysis. Stroke 2014;45:2900–2905.
13.
Moriya Y, Takahashi W, Kijima C, et al. Predictors for hemorrhagic transformation with intravenous tissue plasminogen activator in acute ischemic stroke. Tokai J Exp Clin Med 2013;38:24–27.
14.
Kimura K, Aoki J, Shibazaki K, Saji N, Uemura J, Sakamoto Y. New appearance of extraischemic microbleeds on T2*-weighted magnetic resonance imaging 24 hours after tissue-type plasminogen activator administration. Stroke 2013;44:2776–2781.
15.
Fiehler J, Albers GW, Boulanger JM, et al. Bleeding risk analysis in stroke imaging before thrombolysis (BRASIL): pooled analysis of T2*-weighted magnetic resonance imaging data from 570 patients. Stroke 2007;38:2738–2744.
16.
Kakuda W, Thijs VN, Lansberg MG, et al. Clinical importance of microbleeds in patients receiving IV thrombolysis. Neurology 2005;65:1175–1178.
17.
Yan SQ, Wan JP, Guo Y, Lou M. Impact of cerebral microbleeds on outcomes of acute ischemic stroke treated with intravenous thrombolysis [in Chinese]. Zhejiang Da Xue Xue Bao Yi Xue Ban 2014;43:20–27.
18.
Pantoni L, Fierini F, Poggesi A. Thrombolysis in acute stroke patients with cerebral small vessel disease. Cerebrovasc Dis 2014;37:5–13.
19.
Curtze S, Melkas S, Sibolt G, et al. Cerebral computed tomography-graded white matter lesions are associated with worse outcome after thrombolysis in patients with stroke. Stroke 2015;46:1554–1560.
20.
The NINDS t-PA Stroke Study Group. Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke. Stroke 1997;28:2109–2118.
21.
Shi ZS, Duckwiler GR, Jahan R, et al. Mechanical thrombectomy for acute ischemic stroke with cerebral microbleeds. J Neurointerv Surg 2016;8:563–567.
22.
Mazya MV, Ahmed N, Ford GA, et al. Remote or extraischemic intracerebral hemorrhage: an uncommon complication of stroke thrombolysis: results from the safe implementation of treatments in stroke-international stroke thrombolysis register. Stroke 2014;45:1657–1663.
23.
Shoamanesh A, Kwok CS, Lim PA, Benavente OR. Postthrombolysis intracranial hemorrhage risk of cerebral microbleeds in acute stroke patients: a systematic review and meta-analysis. Int J Stroke 2013;8:348–356.
24.
Charidimou A, Nicoll JA, McCarron MO. Thrombolysis-related intracerebral hemorrhage and cerebral amyloid angiopathy: accumulating evidence. Front Neurol 2015;6:99.
25.
Ly JV, Rowe CC, Villemagne VL, et al. Cerebral beta-amyloid detected by Pittsburgh compound B positron emission topography predisposes to recombinant tissue plasminogen activator-related hemorrhage. Ann Neurol 2010;68:959–962.
26.
Charidimou A, Soo Y, Heo JH, Srikanth V, Consortium M.-M. A call for researchers to join the META-MICROBLEEDS Consortium. Lancet Neurol 2016;15:900.

Information & Authors

Information

Published In

Neurology®
Volume 87Number 15October 11, 2016
Pages: 1534-1541
PubMed: 27629086

Publication History

Received: February 25, 2016
Accepted: May 23, 2016
Published online: September 14, 2016
Published in print: October 11, 2016

Permissions

Request permissions for this article.

Disclosure

A. Charidimou reports no disclosures relevant to the manuscript. A. Shoamanesh is funded by the Marta an Owen Boris Chair in Stroke Research and Care. Go to Neurology.org for full disclosures.

Study Funding

No targeted funding reported.

Authors

Affiliations & Disclosures

Andreas Charidimou, MD, MSc (Neurology), PhD
From the Hemorrhagic Stroke Research Group (A.C.) and Harvard Medical School (A.C.), Massachusetts General Hospital, Boston; and Department of Medicine (Neurology) (A.S.), McMaster University and Population Health Research Institute, Hamilton, Canada.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Ashkan Shoamanesh, MD
From the Hemorrhagic Stroke Research Group (A.C.) and Harvard Medical School (A.C.), Massachusetts General Hospital, Boston; and Department of Medicine (Neurology) (A.S.), McMaster University and Population Health Research Institute, Hamilton, Canada.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Speaker Honoraria - Bayer HealthCare Pharmaceuticals
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Research stipend from Bayer HealthCare Pharmaceuticals for committee involvement within the NAVIGATE ESUS trial.
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Marta and Owen Boris Foundation Stroke Research Chair
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
For the International META-MICROBLEEDS Initiative
From the Hemorrhagic Stroke Research Group (A.C.) and Harvard Medical School (A.C.), Massachusetts General Hospital, Boston; and Department of Medicine (Neurology) (A.S.), McMaster University and Population Health Research Institute, Hamilton, Canada.

Notes

Correspondence to Dr. Charidimou: [email protected]
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

Author Contributions

A. Charidimou: study concept and design, systematic review, data extraction, data analysis, statistical analysis, writeup. A. Shoamanesh: study concept, systematic review, data extraction, critical revisions.

Metrics & Citations

Metrics

Citations

Download Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.

Cited By
  1. Risk factors for intracerebral hemorrhage in small-vessel disease and non-small-vessel disease etiologies—an observational proof-of-concept study, Frontiers in Neurology, 15, (2024).https://doi.org/10.3389/fneur.2024.1322442
    Crossref
  2. Impact of dementia status on intravenous thrombolysis and endovascular treatment for acute ischemic stroke: Retrospective study, Journal of the Neurological Sciences, 459, (122954), (2024).https://doi.org/10.1016/j.jns.2024.122954
    Crossref
  3. Outcomes of patients with cerebral microbleeds undergoing percutaneous coronary intervention and dual antiplatelet therapy, Heart and Vessels, (2024).https://doi.org/10.1007/s00380-024-02404-7
    Crossref
  4. The Study of Risk Factors and The Predict Model of Cerebral Microbleeds, Current Neurovascular Research, 20, 3, (377-389), (2023).https://doi.org/10.2174/1567202620666230710160809
    Crossref
  5. A Nested Attention Guided UNet++ Architecture for White Matter Hyperintensity Segmentation, IEEE Access, 11, (66910-66920), (2023).https://doi.org/10.1109/ACCESS.2023.3281201
    Crossref
  6. Imaging in Acute Anterior Circulation Ischemic Stroke: Current and Future, Neurointervention, 17, 1, (2-17), (2022).https://doi.org/10.5469/neuroint.2021.00465
    Crossref
  7. Cerebral Small Vessel Diseases and Outcomes for Acute Ischemic Stroke Patients after Endovascular Therapy, Journal of Clinical Medicine, 11, 23, (6883), (2022).https://doi.org/10.3390/jcm11236883
    Crossref
  8. Clinical Prediction Model for Screening Acute Ischemic Stroke Patients With More Than 10 Cerebral Microbleeds, Frontiers in Neurology, 13, (2022).https://doi.org/10.3389/fneur.2022.833952
    Crossref
  9. Detection, Diagnosis and Treatment of Acute Ischemic Stroke: Current and Future Perspectives, Frontiers in Medical Technology, 4, (2022).https://doi.org/10.3389/fmedt.2022.748949
    Crossref
  10. Association between cerebral microbleeds and inflammatory biomarkers in patients with ischemic stroke, The Egyptian Journal of Neurology, Psychiatry and Neurosurgery, 58, 1, (2022).https://doi.org/10.1186/s41983-022-00478-6
    Crossref
  11. See more
Loading...

View Options

Get Access

Login options

Check if you have access through your login credentials or your institution to get full access on this article.

Personal login Institutional Login
Purchase Options

The neurology.org payment platform is currently offline. Our technical team is working as quickly as possible to restore service.

If you need immediate support or to place an order, please call or email customer service:

  • 1-800-638-3030 for U.S. customers - 8:30 - 7 pm ET (M-F)
  • 1-301-223-2300 for customers outside the U.S. - 8:30 - 7 pm ET (M-F)
  • [email protected]

We appreciate your patience during this time and apologize for any inconvenience.

View options

Full Text

View Full Text

Full Text HTML

View Full Text HTML

Media

Figures

Other

Tables

Share

Share

Share article link

Share