Abstract
Background and purpose
Cerebral microbleeds (CMBs) are a possible predictor of symptomatic intracranial hemorrhage (sICH) and poor function outcome (PFO). We aimed to investigate the presence of CMBs on increased incidence of sICH and PFO in acute ischemic stroke patients receiving intravenous thrombolysis (IVT) treatment.
Methods
We searched PubMed, EMBASE, and Cochrane Library from 1 January 1997 to 13 May 2018, for relevant studies and calculated the pooled relative risk (RR) for the incidence of sICH and PFO in patients with CMBs versus those without after IVT.
Results
We included 2407 participants from nine studies. The cumulative sICH incidence was higher in patients with CMBs (6%, 95% CI 4–8%) than that in patients without CMBs (4%, 95% CI 2–6%) with pooled RR 1.51 (95% CI, 1.04–2.21; P = 0.031). Four studies including 1550 patients reported data on 3- to 6-month PFO. The cumulative PFO incidence was higher in patients with CMBs (53%, 95% CI 47–59%) than that in patients without CMBs (41%, 95% CI 36–46%) with pooled RR 1.25 (95% CI 1.11–1.41; P = 0.000).
Conclusions
The pretreatment CMBs were associated with increased incidence of sICH and PFO in acute ischemic stroke patients receiving IVT. However, it was not convincing enough to set the presence of CMBs as contraindication to IVT.
Similar content being viewed by others
References
Emberson J, Lees KR, Lyden P, Blackwell L, Albers G, Bluhmki E, Brott T, Cohen G, Davis S, Donnan G (2014) 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 384:1929–1935
Álvarez-Sabín J, Maisterra O, Santamarina E, Kase CS (2013) Factors influencing haemorrhagic transformation in ischaemic stroke. Lancet Neurol 12:689–705
Linn J (2015) Imaging of cerebral microbleeds. Clin Neuroradiol 25(suppl 2):167–175
Senior K (2002) Microbleeds may predict cerebral bleeding after stroke. Lancet 359(9308):769
Fisher M (2014) Cerebral microbleeds: where are we now? Neurology 83:1304–1305
Shoamanesh A, Yan S, Charidimou A (2015) New cerebral microbleeds and mechanism of post-thrombolysis remote intracerebral hemorrhage: “red meets white” revisited. Front Neurol 6:203
Kakuda W, Thijs VN, Lansberg MG, Bammer R, Wechsler L, Kemp S, Moseley ME, Marks MP, Albers GW (2005) Clinical importance of microbleeds in patients receiving IV thrombolysis. Neurology 65:1175–1178
Fiehler J, Albers GW, Boulanger JM, Derex L, Gass A, Hjort N, Kim JS, Liebeskind DS, Neumann-Haefelin T, Pedraza S, Rother J, Rothwell P, Rovira A, Schellinger PD, Trenkler J (2007) Bleeding risk analysis in stroke imaging before thrombolysis (BRASIL): pooled analysis of T2*-weighted magnetic resonance imaging data from 570 patients. Stroke 38:2738–2744
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 45:1684–1688
Turc G, Sallem A, Moulin S, Tisserand M, Machet A, Edjlali M, Baron JC, Leclerc X, Leys D, Mas JL, Cordonnier C, Oppenheim C (2015) Microbleed status and 3-month outcome after intravenous thrombolysis in 717 patients with acute ischemic stroke. Stroke 46:2458–2463
Dannenberg S, Scheitz JF, Rozanski M, Erdur H, Brunecker P, Werring DJ, Fiebach JB, Nolte CH (2014) Number of cerebral microbleeds and risk of intracerebral hemorrhage after intravenous thrombolysis. Stroke 45:2900–2905
Yan S, Jin X, Zhang X, Zhang S, Liebeskind DS, Lou M (2015) Extensive cerebral microbleeds predicts parenchymal haemorrhage and poor outcome after intravenous thrombolysis. J Neurol Neurosurg Psychiatry 86:1267–1272
Shoamanesh A, Kwok CS, Lim PA, Benavente OR (2013) Postthrombolysis intracranial hemorrhage risk of cerebral microbleeds in acute stroke patients: a systematic review and meta-analysis. Int J Stroke 8:348–356
Tsivgoulis G, Zand R, Katsanos AH, Turc G, Nolte CH, Jung S, Cordonnier C, Fiebach JB, Scheitz JF, Klinger-Gratz PP, Oppenheim C, Goyal N, Safouris A, Mattle HP, Alexandrov AW, Schellinger PD, Alexandrov AV (2016) Risk of symptomatic intracerebral hemorrhage after intravenous thrombolysis in patients with acute ischemic stroke and high cerebral microbleed burden: a meta-analysis. JAMA Neurol 73:675–683
Charidimou A, Shoamanesh A (2016) Clinical relevance of microbleeds in acute stroke thrombolysis: comprehensive meta-analysis. Neurology 87:1534–1541
Charidimou A, Turc G, Oppenheim C, Yan S, Scheitz JF, Erdur H, Klinger-Gratz PP, El-Koussy M, Takahashi W, Moriya Y, Wilson D, Kidwell CS (2017) Microbleeds, cerebral hemorrhage, and functional outcome after stroke thrombolysis: individual patient data meta-analysis. Stroke 48:2084–2090
Wang S, Lv Y, Zheng X, Qiu J, Chen HS (2017) The impact of cerebral microbleeds on intracerebral hemorrhage and poor functional outcome of acute ischemic stroke patients treated with intravenous thrombolysis: a systematic review and meta-analysis. J Neurol 264:1309–1319
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 (Clin Res ed) 350:g7647
Stang A (2010) Critical evaluation of the newcastle-ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25:603–605
Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560
Xian Y, Federspiel JJ, Grau-Sepulveda M, Hernandez AF, Schwamm LH, Bhatt DL, Smith EE, Reeves MJ, Thomas L, Webb L, Bettger JP, Laskowitz DT, Fonarow GC, Peterson ED (2016) Risks and benefits associated with prestroke antiplatelet therapy among patients with acute ischemic stroke treated with intravenous tissue plasminogen activator. JAMA Neurol 73:50–59
Funding
None of the authors received financial support for this manuscript.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflicts of interest
The study authors received no funding and report no conflicts of interest.
Ethical standards
All studies in this review have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Yan, J., Qiu, J., Wu, X. et al. Pretreatment cerebral microbleeds and symptomatic intracerebral hemorrhage post-thrombolysis: a systematic review and meta-analysis. J Neurol 267, 301–307 (2020). https://doi.org/10.1007/s00415-018-9156-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00415-018-9156-5