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Delving Into the Significance of Brain’s Collateral Circulation in the Era of Revascularization Therapy

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Abstract

Purpose of review

This narrative review summarized the major studies focusing on the association between revascularization therapies (intravenous thrombolysis and endovascular thrombectomy) and collateral circulation status in terms of outcome and safety. Our aim is to elucidate, drawing upon the latest scientific evidence, the pivotal role that collateral circulation plays in shaping the prognosis and potential therapeutic in patients with ischemic stroke.

Recent findings

The data currently available suggest that pre-treatment assessment of collateral circulation may be crucial, as a good collateral circulation status appears to be associated with better outcomes in terms of both early revascularization and long-term disability. There is limited literature about the assessment of collateral circulation prior to acute reperfusion therapy.

Summary

The role of the intracranial collateral circulation is gaining increasing attention in the field of ischemic stroke, both in terms of outcome prognosis and therapeutic interventions. These findings need to be confirmed by more structured randomized controlled trials (RCTs), but they suggest that investigating therapeutic strategies to maintain and support collateral circulation may represent the future of ischemic stroke therapy.

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References and Recommended Readings

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Saini V, Guada L, Yavagal DR. Global epidemiology of stroke and access to acute ischemic stroke interventions. Neurol. 2021;97:S6–16.

    Google Scholar 

  2. Mosconi MG, Paciaroni M. Treatments in ischemic stroke: current and future. Eur Neurol. 2022;85:349–66.

    Article  CAS  PubMed  Google Scholar 

  3. Leira EC, Muir KW. EXTEND trial. Stroke. 2019;50:2637–9.

    Article  PubMed  Google Scholar 

  4. Berge E, et al. European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke. Eur Stroke J. 2021;6:I–LXII.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Goyal M, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet Lond Engl. 2016;387:1723–31.

    Article  Google Scholar 

  6. Turc G, et al. European Stroke Organisation (ESO) - European Society for Minimally Invasive Neurological Therapy (ESMINT) guidelines on mechanical thrombectomy in acute ischemic stroke. J Neurointerventional Surg. 2019. https://doi.org/10.1136/neurintsurg-2018-014569.

    Article  Google Scholar 

  7. Nogueira RG, et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med. 2018;378:11–21.

    Article  PubMed  Google Scholar 

  8. Uniken Venema SM, Dankbaar JW, van der Lugt A, Dippel DWJ, van der Worp HB. Cerebral collateral circulation in the era of reperfusion therapies for acute ischemic stroke. Stroke. 2022;53:3222–34.

    Article  PubMed  Google Scholar 

  9. Baron J-C. The core/penumbra model: implications for acute stroke treatment and patient selection in 2021. Eur J Neurol. 2021;28:2794–803.

    Article  PubMed  Google Scholar 

  10. Mangiardi M, et al. The pathophysiology of collateral circulation in acute ischemic stroke. Diagn Basel Switz. 2023;13:2425.

    CAS  Google Scholar 

  11. Seyman E, et al. The collateral circulation determines cortical infarct volume in anterior circulation ischemic stroke. BMC Neurol. 2016;16:206.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Silvestre J-S, Smadja DM, Lévy BI. Postischemic revascularization: from cellular and molecular mechanisms to clinical applications. Physiol Rev. 2013;93:1743–802.

    Article  CAS  PubMed  Google Scholar 

  13. Sheth SA, Liebeskind DS. Imaging evaluation of collaterals in the brain: physiology and clinical translation. Curr Radiol Rep. 2014;2:29.

    Article  PubMed  Google Scholar 

  14. Kortman HGJ, et al. 4D-CTA in neurovascular disease: a review. AJNR Am J Neuroradiol. 2015;36:1026–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ginsberg MD. The cerebral collateral circulation: relevance to pathophysiology and treatment of stroke. Neuropharmacology. 2018;134:280–92.

    Article  CAS  PubMed  Google Scholar 

  16. de Havenon A, et al. Association of collateral blood vessels detected by arterial spin labeling magnetic resonance imaging with neurological outcome after ischemic stroke. JAMA Neurol. 2017;74:453–8. https://doi.org/10.1001/jamaneurol.2016.4491.

  17. Tetteh G, et al. A deep learning approach to predict collateral flow in stroke patients using radiomic features from perfusion images. Front Neurol. 2023;14:1039693.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Wardlaw JM, et al. Accuracy of automated computer-aided diagnosis for stroke imaging: a critical evaluation of current evidence. Stroke. 2022;53:2393–403.

    Article  PubMed  Google Scholar 

  19. Seners P, et al. Incidence and predictors of early recanalization after intravenous thrombolysis: a systematic review and meta-analysis. Stroke. 2016;47:2409–12.

    Article  CAS  PubMed  Google Scholar 

  20. Christoforidis GA, et al. Predictors of hemorrhage following intra-arterial thrombolysis for acute ischemic stroke: the role of pial collateral formation. Am J Neuroradiol. 2009;30:165–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Bang OY, et al. Collateral flow averts hemorrhagic transformation after endovascular therapy for acute ischemic stroke. Stroke. 2011;42:2235–9.

    Article  PubMed  Google Scholar 

  22. Angermaier A, et al. CT-angiographic collateralization predicts final infarct volume after intra-arterial thrombolysis for acute anterior circulation ischemic stroke. Cerebrovasc Dis Basel Switz. 2011;31:177–84.

    Article  CAS  Google Scholar 

  23. Nicoli F, de Micheaux PL, Girard N. Perfusion-weighted imaging-derived collateral flow index is a predictor of MCA M1 recanalization after i.v. thrombolysis. AJNR Am J Neuroradiol. 2013;34:107–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Calleja AI, et al. Collateral circulation on perfusion-computed tomography-source images predicts the response to stroke intravenous thrombolysis. Eur J Neurol. 2013;20:795–802.

    Article  CAS  PubMed  Google Scholar 

  25. • Zhang S, et al. The velocity of collateral filling predicts recanalization in acute ischemic stroke after intravenous thrombolysis. Sci Rep. 2016;6:27880. This retrospective analysis evaluate the impact of pretreatment quality of collaterals, involving velocity and extent of collateral filling, on recanalization after intravenous thrombolysis . The study was performed of 66 patients with acute middle cerebral artery (MCA) M1 segment occlusion who underwent MR perfusion (MRP) imaging before IVT. The extent of collateral filling was assessed according to the Alberta Stroke Program Early CT (ASPECT) score on temporally fused maximum intensity projections (tMIP). The authors showed that when recanalization was achieved, hemorrhagic transformation occurred more frequently in patients with slow collaterals than those with rapid collaterals.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. •• Wufuer A, et al. Impact of collateral circulation status on favorable outcomes in thrombolysis treatment: a systematic review and meta-analysis. Exp Ther Med. 2018;15:707–18. This meta-analysis included a total of 29 studies involving 4053 patients. The study concludes that assessing collateral circulation and penumbra area before thrombolytic therapy can help identify AIS patients who may benefit from treatment. Good collateral circulation is associated with improved outcomes, including functional recovery, reduced hemorrhagic complications, and lower mortality.

    CAS  PubMed  Google Scholar 

  27. • 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. In this meta-analysis were screened full-text articles published since 2000 focused on the overall effect sizes of good versus poor collateral status. Compared with poor pre-treatment collateral status, good collaterals showed a beneficial effect over the primary outcome of a favorable functional outcome at 3 or 6 months [RR, 2.45; 95% confidence interval, 1.94-3.09; P < 0.001] in acute ischaemic stroke patients receiving IVT treatment.

    Article  CAS  PubMed  Google Scholar 

  28. Galego O, et al. Collateral pial circulation relates to the degree of brain edema on CT 24 hours after ischemic stroke. Neuroradiol J. 2018;31:456–63.

    Article  PubMed  PubMed Central  Google Scholar 

  29. •• Seners P, et al. Better collaterals are independently associated with post-thrombolysis recanalization before thrombectomy. Stroke. 2019;50:867–72. This recent French study suggest that collateral imaging may be valuable in identifying patients who are more likely to benefit from IVT before thrombectomy, emphasizing the potential role of advanced imaging for personalized stroke therapy.

    Article  PubMed  Google Scholar 

  30. Kim SJ, et al. A novel magnetic resonance imaging approach to collateral flow imaging in ischemic stroke. Ann Neurol. 2014;76:356–69.

    Article  PubMed  Google Scholar 

  31. Zaidat OO, et al. Recommendations on angiographic revascularization grading standards for acute ischemic stroke: a consensus statement. Stroke. 2013;44:2650–63.

    Article  PubMed  PubMed Central  Google Scholar 

  32. • Weiss D, et al. Systematic evaluation of computed tomography angiography collateral scores for estimation of long-term outcome after mechanical thrombectomy in acute ischaemic stroke. Neuroradiol J. 2019;32:277–86. The study found very good inter-rater reliability for Modified Tan, Miteff, and Opercular Index Score ratio, and substantial reliability for Maas. The study concluded that computed tomography angiography scores are valuable for estimating functional outcomes after mechanical thrombectomy and are reliable across readers. The more complex scores, Maas and Miteff, demonstrated the best performance in predicting favorable outcomes.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Yeo LLL, et al. Assessment of intracranial collaterals on CT angiography in anterior circulation acute ischemic stroke. Am J Neuroradiol. 2015;36:289–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Seker F, et al. Collateral scores in acute ischemic stroke : a retrospective study assessing the suitability of collateral scores as standalone predictors of clinical outcome. Clin Neuroradiol. 2020;30:789–93.

    Article  PubMed  Google Scholar 

  35. Tan BYQ, et al. Good intracranial collaterals trump poor ASPECTS (Alberta Stroke Program Early CT Score) for intravenous thrombolysis in anterior circulation acute ischemic stroke. Stroke. 2016;47:2292–8.

    Article  PubMed  Google Scholar 

  36. Copelan A, et al. Opercular index score: a CT angiography-based predictor of capillary robustness and neurological outcomes in the endovascular management of acute ischemic stroke. J Neurointerventional Surg. 2017;9:1179–86.

    Article  Google Scholar 

  37. Al-Ali F, et al. The capillary index score in the IMS I. II trials Stroke J Cereb Circ. 2014;45:1999–2003.

    Article  Google Scholar 

  38. •• Liebeskind DS, et al. Collaterals at angiography and outcomes in the Interventional Management of Stroke (IMS) III trial. Stroke. 2014;45:759–64. The IMS-3 is the largest prospective study evaluating the prognostic value of collateral circulation prior to thrombectomy, involving a significant number of patients. The findings indicate a substantial correlation between collateral circulation, the modified Rankin Scale (mRS), the National Institutes of Health Stroke Scale (NIHSS), and the Alberta Stroke Program Early CT Score (ASPECTS).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Albers GW, et al. Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging. N Engl J Med. 2018;378:708–18.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Saver JL, et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015;372:2285–95.

    Article  CAS  PubMed  Google Scholar 

  41. • El Nawar R, et al. Higher annual operator volume is associated with better reperfusion rates in stroke patients treated by mechanical thrombectomy: the ETIS registry. JACC Cardiovasc Interv. 2019;12:385–91. This study aimed to determine whether individual operator characteristics affect reperfusion and procedural complication rates in mechanical thrombectomy (MT) for acute ischemic stroke (AIS). The study included 1,541 patients with anterior and posterior AIS (mean age 67 years, median NIHSS 16). he data indicate that the annual volume of MT procedures performed by an operator positively impacts successful reperfusion rates in AIS patients, but it does not affect clinical outcomes or complication rates.

    Article  PubMed  Google Scholar 

  42. Liebeskind DS, et al. Collateral circulation in thrombectomy for stroke after 6 to 24 hours in the DAWN trial. Stroke. 2022;53:742–8.

    Article  PubMed  Google Scholar 

  43. Liebeskind DS, Jahan R, Nogueira RG, Zaidat OO, Saver JL. Impact of collaterals on successful revascularization in solitaire FR with the intention for thrombectomy. Stroke J Cereb Circ. 2014;45:2036–40.

    Article  Google Scholar 

  44. Anadani M, et al. Endovascular therapy of anterior circulation tandem occlusions: pooled analysis from the TITAN and ETIS registries. Stroke. 2021;52:3097–105.

    Article  PubMed  Google Scholar 

  45. •• Leng X, et al. Impact of collaterals on the efficacy and safety of endovascular treatment in acute ischaemic stroke: a systematic review and meta-analysis. J Neurol Neurosurg Psych. 2016;87:537–44. This recent meta-analysis encompasses 39 studies and demonstrates that patients with robust collateral circulation undergoing thrombectomy have a threefold higher likelihood of achieving a favorable functional outcome at 3 months.

    Article  Google Scholar 

  46. Bornstein NM, et al. An injectable implant to stimulate the sphenopalatine ganglion for treatment of acute ischaemic stroke up to 24 h from onset (ImpACT-24B): an international, randomised, double-blind, sham-controlled, pivotal trial. Lancet Lond Engl. 2019;394:219–29.

    Article  CAS  Google Scholar 

  47. Malhotra K, et al. Association of statin pretreatment with collateral circulation and final infarct volume in acute ischemic stroke patients: a meta-analysis. Atherosclerosis. 2019;282:75–9.

    Article  CAS  PubMed  Google Scholar 

  48. Charriaut-Marlangue C, et al. Inhaled nitric oxide reduces brain damage by collateral recruitment in a neonatal stroke model. Stroke. 2012;43:3078–84.

    Article  CAS  PubMed  Google Scholar 

  49. Terpolilli NA, et al. Inhalation of nitric oxide prevents ischemic brain damage in experimental stroke by selective dilatation of collateral arterioles. Circ Res. 2012;110:727–38.

    Article  CAS  PubMed  Google Scholar 

  50. van den Berg SA, et al. Prehospital transdermal glyceryl trinitrate in patients with presumed acute stroke (MR ASAP): an ambulance-based, multicentre, randomised, open-label, blinded endpoint, phase 3 trial. Lancet Neurol. 2022;21:971–81.

    Article  PubMed  Google Scholar 

  51. Desai SM, Jha RM, Linfante I. Collateral circulation augmentation and neuroprotection as adjuvant to mechanical thrombectomy in acute ischemic stroke. Neurol. 2021;97:S178–84.

    Google Scholar 

  52. de Havenon A, et al. Results from DEFUSE 3: good collaterals are associated with reduced ischemic core growth but not neurologic outcome. Stroke. 2019;50:632–8.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Rao VL, et al. Collateral status contributes to differences between observed and predicted 24-h infarct volumes in DEFUSE 3. J Cereb Blood Flow Metab. 2020;40:1966–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Author information

Author notes

  1. Marilena Mangiardi, Sergio Soeren Rossi, Adriano Bonura, and Gianmarco Iaccarino contributed equally to this work and share first authorship.

Authors and Affiliations

  1. Department of Stroke Unit, San Camillo-Forlanini Hospital, Rome, Italy

    Marilena Mangiardi MD, Sabrina Anticoli MD & Francesca Romana Pezzella MD

  2. Sapienza University Rome, Rome, Italy

    Marilena Mangiardi MD

  3. Unit of Neurology, Neurophysiology, Neurobiology, Department of Medicine, Campus Bio-Medico University, Rome, Neurobiology, Italy

    Sergio Soeren Rossi MD, Adriano Bonura MD & Gianmarco Iaccarino MD

  4. Neurology Division, S. Maria Goretti Hospital, Latina, Italy

    Michele Alessiani MD

  5. Department of Neuroradiology and Interventional Neuroradiology, San Camillo-Forlanini Hospital, Rome, Italy

    Gianluca De Rubeis MD & Enrico Pampana MD

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  1. Marilena Mangiardi MD
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Contributions

Conceptualization: M.M., S.S.R., B.A.; methodology: M.M., S.S.R., B.A., G.I.; validation: M.M., F.R.P., A.M.; investigation: M.M., S.S.R., G.I.; Fig. 1 prepared by B.A.; Table 1 prepared by S.S.R., B.A., G.I.; writing—original draft preparation: M.M., S.S.R., B.A., G.I.; writing—review and editing: M.M.; supervision: A.S., P.E., F.R.P., G.DR. All authors reviewed the manuscript.

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Correspondence to Marilena Mangiardi MD.

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Mangiardi, M., Rossi, S.S., Bonura, A. et al. Delving Into the Significance of Brain’s Collateral Circulation in the Era of Revascularization Therapy. Curr Treat Options Neurol (2024). https://doi.org/10.1007/s11940-024-00794-7

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