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Cerebral hemorrhage after thrombolysis in stroke patients with unruptured intracranial aneurysms: a systemic review and meta-analysis

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Abstract

Background

For ischemic stroke patients with concomitant unruptured aneurysm, intravenous thrombolysis therapy (IVT) remains a disputable decision. We hence performed a meta-analysis to identify the related brain hemorrhage rate of unruptured aneurysms and the risk ratio for their rupture comparing to stroke patients who do not have aneurysms.

Methods

A comprehensive search was conducted to identify the studies from the online database from 2000 to September 1st, 2022. Cohort studies were included and assessed by Newcastle–Ottawa Scale (NOS) for quality. The research procedures were subjected to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Fixed-effects model was used based on the heterogeneity tests.

Results

In 10 eligible studies, 7238 ischemic stroke patients were screened, a total of 302 patients with 348 aneurysms were included. 10 studies were eligible for ICH rate analysis, 8 for SAH rate analysis and 7 for risk ratio of stroke patients with unruptured aneurysms. The pooled any ICH rate was 16% (95% CI 11–21%), symptomatic ICH rate was 4% (95% CI 1–7%, I2 = 0.00%, p = 0.90), and 0% (95% CI 0–1%) for aneurysm-related ICH. Subarachnoid hemorrhage was as low as 2% (95% CI 0–5%), while 0% (95% CI 0–2%) directly related to the aneurysm rupture. The risk ratio of ICH in stroke patients with aneurysms was 1.18 (95% CI 0.79–1.77). Additionally, the hemorrhage rate difference was not evident between saccular and fusiform aneurysms due to a lack of details.

Conclusions

IVT is unlikely to induce hemorrhage of pre-existing unruptured aneurysms in stroke patients. Further randomized control studies are warranted to validate these conclusions.

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Availability of supporting data

The clinical data used in this study can be provided via the corresponding authors upon reasonable request.

References

  1. Powers WJ, Rabinstein AA, Ackerson T et al (2019) 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 50(12):e344–e418. https://doi.org/10.1161/str.0000000000000211

    Article  PubMed  Google Scholar 

  2. Powers WJ, Rabinstein AA, Ackerson T et al (2018) Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 49(3):e46–e110. https://doi.org/10.1161/str.0000000000000158

    Article  PubMed  Google Scholar 

  3. Virta JJ, Strbian D, Putaala J, Korja M (2021) Risk of aneurysm rupture after thrombolysis in patients with acute ischemic stroke and unruptured intracranial aneurysms. Neurology 97(18):e1790–e1798. https://doi.org/10.1212/WNL.0000000000012771

    Article  PubMed  Google Scholar 

  4. Ding J, Han J, Jing Z, Jiang Y (2016) Is it dangerous to treat acute ischemic stroke by thrombolytic therapy in patients with comorbid intracranial aneurysms? Am J Emerg Med 34(3):636–642. https://doi.org/10.1016/j.ajem.2015.12.025

    Article  PubMed  Google Scholar 

  5. Chen F, Yan S, Jin X, Lin C, Cao J (2014) Post-thrombolysis hemorrhage risk of unruptured intracranial aneurysms. Eur Neurol 73(1–2):37–43. https://doi.org/10.1159/000366200

    Article  PubMed  Google Scholar 

  6. Chen H, Zeng X, Gao C, Cheng Y, Ren S, Zhao Q (2014) The safety among acute ischemic stroke patients with asymptomatic intracranial aneurysm after the administration of intravenous thrombolysis. Chin J Neurol 47(9):643–647. https://doi.org/10.3760/cma.j.issn.1006-7876.2014.09.009

    Article  Google Scholar 

  7. Bernardo F, Nannoni S, Strambo D, Bartolini B, Michel P, Sirimarco G (2019) Intravenous thrombolysis in acute ischemic stroke due to intracranial artery dissection: a single-center case series and a review of literature. J Thromb Thrombolysis 48(4):679–684. https://doi.org/10.1007/s11239-019-01918-6

    Article  CAS  PubMed  Google Scholar 

  8. Chiu WT, Hong CT, Chi NF, Hu CJ, Hu HH, Chan L (2017) The risk of intravenous thrombolysis-induced intracranial hemorrhage in Taiwanese patients with unruptured intracranial aneurysm. PLoS ONE 12(6):e0180021. https://doi.org/10.1371/journal.pone.0180021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Mowla A, Singh K, Mehla S, et al. Is acute reperfusion therapy safe in acute ischemic stroke patients who harbor unruptured intracranial aneurysm? Stroke. 2015;46(SUPPL. 1)American Heart Association/American Stroke Association 2015 International Stroke Conference and State-of-the-Science Stroke Nursing Symposium. Nashville, TN United States. (var.pagings)

  10. Zhang C-H, Li C, Wang Y-X et al (2015) Efficacy and safety of intravenous thrombolysis for the treatment of acute ischemic stroke patients with saccular intracranial aneurysms of a parts per thousand currency sign3 mm. Cell Biochem Biophys 72(3):889–893. https://doi.org/10.1007/s12013-015-0557-0

    Article  CAS  PubMed  Google Scholar 

  11. Zhang PL, Wang YX, Chen Y et al (2015) Analysis on the correlation factors for hemorrhagic transformation after intravenous thrombolytic therapy. Eur Rev Med Pharmacol Sci 19(6):1001–1008

    PubMed  Google Scholar 

  12. Goyal N, Tsivgoulis G, Zand R et al (2015) Systemic thrombolysis in acute ischemic stroke patients with unruptured intracranial aneurysms. Neurology 85(17):1452–1458. https://doi.org/10.1212/WNL.0000000000002068

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Mittal MK, Seet RC, Zhang Y, Brown RD Jr, Rabinstein AA (2013) Safety of intravenous thrombolysis in acute ischemic stroke patients with saccular intracranial aneurysms. J Stroke Cerebrovasc Dis 22(5):639–643. https://doi.org/10.1016/j.jstrokecerebrovasdis.2012.01.009

    Article  PubMed  Google Scholar 

  14. Sheth KN, Shah N, Morovati T, Hermann LD, Cronin CA (2012) Intravenous rt-PA is not associated with increased risk of hemorrhage in patients with intracranial aneurysms. Neurocrit Care 17(2):199–203. https://doi.org/10.1007/s12028-012-9734-9

    Article  CAS  PubMed  Google Scholar 

  15. Kim JT, Park MS, Yoon W, Cho KH (2012) Detection and significance of incidental unruptured cerebral aneurysms in patients undergoing intravenous thrombolysis for acute ischemic stroke. J Neuroimaging 22(2):197–200. https://doi.org/10.1111/j.1552-6569.2010.00560.x

    Article  PubMed  Google Scholar 

  16. Fugate JE, Rabinstein AA (2015) Absolute and relative contraindications to IV rt-PA for acute ischemic stroke. Neurohospitalist. 5(3):110–121. https://doi.org/10.1177/1941874415578532

    Article  PubMed  PubMed Central  Google Scholar 

  17. Sheth KN, Shah N, Morovati T, Hermann LD, Cronin CA. Intravenous RT-PA is not associated with increased risk of symptomatic hemorrhage in patients with intracranial aneurysms. Stroke. 2012;43(2 Meeting Abstracts)2012 International Stroke Conference and Nursing Symposium. New Orleans, LA United States. (var.pagings)

  18. Cumpston M, Li T, Page MJ, et al. Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Database Syst Rev. 2019;10:000142. https://doi.org/10.1002/14651858.Ed000142

  19. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ (Clinical research ed) 315(7109):629–634. https://doi.org/10.1136/bmj.315.7109.629

    Article  CAS  PubMed  Google Scholar 

  20. Duval S, Tweedie R (2000) Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 56(2):455–463. https://doi.org/10.1111/j.0006-341x.2000.00455.x

    Article  CAS  PubMed  Google Scholar 

  21. Rücker G, Schwarzer G, Carpenter JR, Binder H, Schumacher M (2011) Treatment-effect estimates adjusted for small-study effects via a limit meta-analysis. Biostatistics (Oxford, England) 12(1):122–142. https://doi.org/10.1093/biostatistics/kxq046

    Article  PubMed  Google Scholar 

  22. Virta JJ, Strbian D, Putaala J, Kaprio J, Korja M (2022) Characteristics and outcomes of thrombolysis-treated stroke patients with and without saccular intracranial aneurysms. Stroke 53(12):3616–3621. https://doi.org/10.1161/strokeaha.122.040151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Mowla A, Singh K, Mehla S et al (2015) Is acute reperfusion therapy safe in acute ischemic stroke patients who harbor unruptured intracranial aneurysm? Int J Stroke 10(A100):113–118. https://doi.org/10.1111/ijs.12616

    Article  PubMed  Google Scholar 

  24. Zhang CH, Li C, Wang YX et al (2015) Efficacy and safety of intravenous thrombolysis for the treatment of acute ischemic stroke patients with saccular intracranial aneurysms of <=3 mm. Cell Biochem Biophys 72(3):889–893. https://doi.org/10.1007/s12013-015-0557-0

    Article  CAS  PubMed  Google Scholar 

  25. Edwards NJ, Kamel H, Josephson SA (2012) The safety of intravenous thrombolysis for ischemic stroke in patients with pre-existing cerebral aneurysms a case series and review of the literature. Stroke 43(2):412–416. https://doi.org/10.1161/strokeaha.111.634147

    Article  CAS  PubMed  Google Scholar 

  26. (2000) Effect of intravenous recombinant tissue plasminogen activator on ischemic stroke lesion size measured by computed tomography. NINDS; The National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study Group. Stroke 31(12):2912–9. https://doi.org/10.1161/01.str.31.12.2912

  27. (1997) A systems approach to immediate evaluation and management of hyperacute stroke. Experience at eight centers and implications for community practice and patient care. The National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study Group. Stroke 28(8):1530–40. https://doi.org/10.1161/01.str.28.8.1530

  28. Hilkens NA, Algra A, Diener HC et al (2021) Balancing benefits and risks of long-term antiplatelet therapy in noncardioembolic transient ischemic attack or stroke. Stroke 52(10):3258–3265. https://doi.org/10.1161/strokeaha.120.031755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. van Gijn J, Kerr RS, Rinkel GJE (2007) Subarachnoid haemorrhage. Lancet 369(9558):306–318. https://doi.org/10.1016/s0140-6736(07)60153-6

    Article  PubMed  Google Scholar 

  30. Beneš V 3rd, Jurák L, Jedlička J, Dienelt J, Suchomel P (2019) Fatal intracranial aneurysm rupture after thrombolytic treatment for ischemic stroke: a case report and literature review. Acta Neurochir (Wien) 161(7):1337–1341. https://doi.org/10.1007/s00701-019-03931-3

    Article  PubMed  Google Scholar 

  31. Kim Y, Choi CH, Lee TH et al (2017) Endovascular stenting for symptomatic carotid dissection with hemodynamic insufficiency. World Neurosurg 102:598–607. https://doi.org/10.1016/j.wneu.2017.03.086

    Article  PubMed  Google Scholar 

  32. Glenn J, Strecker-McGraw M, McGraw I, Jabbar K, James NA, Stone CK (2017) Rupture of an occult intracranial mycotic aneurysm after intravenous thrombolysis with recombinant tissue plasminogen activator for acute ischemic stroke. J Emerg Med 53(5):717–721. https://doi.org/10.1016/j.jemermed.2017.08.032

    Article  PubMed  Google Scholar 

  33. Haji F, van Adel B, Avery M, Megyesi J, Young GB (2014) Intracranial aneurysm rupture following intravenous thrombolysis for stroke. Can J Neurol Sci 41(1):95–98. https://doi.org/10.1017/s0317167100016358

    Article  PubMed  Google Scholar 

  34. Rammos SK, Neils DM, Fraser K, Klopfenstein JD (2012) Anterior communicating artery aneurysm rupture after intravenous thrombolysis for acute middle cerebral artery thromboembolism: case report. Neurosurgery 70(6):E1603–E1607. https://doi.org/10.1227/NEU.0b013e31822e1097

    Article  PubMed  Google Scholar 

  35. Shi H, Wee CK, John S (2019) Post-thrombolysis rupture of small lenticulostriate aneurysms: a report of 2 consecutive cases. J Clin Neurosci 60:148–150. https://doi.org/10.1016/j.jocn.2018.10.087

    Article  PubMed  Google Scholar 

  36. Cai X, Han S, Feske SK, Chou SH (2013) Pearls and oy-sters: small but consequential: intracerebral hemorrhage caused by lenticulostriate artery aneurysm. Neurology 80(9):e89-91. https://doi.org/10.1212/WNL.0b013e31828406a2

    Article  PubMed  PubMed Central  Google Scholar 

  37. Heck O, Anxionnat R, Bracard S (2013) Pearls & oy-sters: small but consequential: intracerebral hemorrhage caused by lenticulostriate artery aneurysm. Neurology 81(21):1881. https://doi.org/10.1212/01.wnl.0000435757.50996.ae

    Article  PubMed  Google Scholar 

  38. Lama S, Dolati P, Sutherland GR (2014) Controversy in the management of lenticulostriate artery dissecting aneurysm: a case report and review of the literature. World Neurosurg 81(2):441.e1–7. https://doi.org/10.1016/j.wneu.2012.12.006

    Article  PubMed  Google Scholar 

  39. Figueroa-Sánchez JA, Caro-Osorio E, Martínez-Rodríguez HR, Herrera-Castro JC (2020) Diagnostic and therapeutic challenge in intracerebral hemorrhage due to aneurysm of distal lenticulostriate artery. Cir Cir 88(3):366–369. https://doi.org/10.24875/ciru.19001026. (Reto diagnóstico y terapéutico en la hemorragia intracerebral por aneurisma de la arteria lenticuloestriada distal)

    Article  PubMed  Google Scholar 

  40. Yaghi S, Willey JZ, Cucchiara B et al (2017) Treatment and outcome of hemorrhagic transformation after intravenous alteplase in acute ischemic stroke: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 48(12):e343–e361. https://doi.org/10.1161/str.0000000000000152

    Article  PubMed  Google Scholar 

  41. Kim H, Kang D, Kwon SU, Kim JS, Jeon S-B (2017) Aneurysmal subarachnoid hemorrhage following intravenous thrombolysis in acute ischemic stroke. J Neurocrit Care 10(2):107–111. https://doi.org/10.18700/jnc.170015

    Article  Google Scholar 

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Acknowledgements

None.

Funding

Dr. Dingke Wen is supported by the National Natural Science Foundation of China (No. 82201450). The sponsors had no role in the design or conduct of this research. Dr. Lu Ma received financial support from the National Key R&D Program of China (numbers 2018YFA 0108604 and 2018YFA0108603) and the Clinical Incubation Program of West China Hospital, SCU (2018HXFU008).

Author information

Author notes

  1. Dingke Wen, Yuqi Chen and Wei Zhu contributed equally and shared first authorship.

  2. Zongjun Peng and Lu Ma contributed equally and share senior authorship.

Authors and Affiliations

  1. Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China

    Dingke Wen, Yuqi Chen & Lu Ma

  2. West China Hospital, Sichuan University, Chengdu, Sichuan, China

    Wei Zhu

  3. Department of Neurosurgery, Sichuan Friendship Hospital, Chengdu, 610000, Sichuan, China

    Zongjun Peng

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  1. Dingke Wen
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Correspondence to Zongjun Peng or Lu Ma.

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Supplementary figure 1.

Publications bias assessment of studies reporting SAH data. (TIF 4441 kb)

Supplementary figure 2.

Publications bias assessment of studies reporting ICH cohort data. (TIF 4441 kb)

Supplementary file5 (DOCX 31 kb)

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Wen, D., Chen, Y., Zhu, W. et al. Cerebral hemorrhage after thrombolysis in stroke patients with unruptured intracranial aneurysms: a systemic review and meta-analysis. J Neurol 270, 1931–1944 (2023). https://doi.org/10.1007/s00415-022-11533-w

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