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Differential Benefit of Collaterals for Stroke Patients Treated with Thrombolysis or Supportive Care

A Propensity Score Matched Analysis

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Abstract

Purpose

Leptomeningeal collaterals can slow down infarction growth; however, despite good collaterals in the DAWN and DEFUSE 3 trials, outcomes were devastating if reperfusion was not attempted. The aim of this study was to compare the influence of collaterals on morphological and functional outcome in patients with acute middle cerebral artery (MCA) stroke undergoing intravenous thrombolysis (IVT) vs. supportive care (non-IVT).

Methods

Out of 1639 consecutive patients examined with multiparametric computed tomography (CT) for suspected ischemic stroke, all patients with confirmed MCA stroke who did not undergo endovascular thrombectomy were selected. Propensity score matching (PSM) was used to match IVT and non-IVT treated patients for potential confounders including age, sex, National Institutes of Health Stroke Scale (NIHSS) score on admission, Alberta Stroke Program Early CT Score (ASPECTS), and occlusion site. Regression analysis after PSM was performed to identify independent associations.

Results

After PSM, 90 IVT patients were matched with 90 non-IVT patients. In multivariable regression analysis, a high regional leptomeningeal collateral (rLMC) score was independently associated with lower final infarction volume (FIV) in the IVT group (b = −0.472, p < 0.001) but not in the non-IVT group (b = −0.116, p = 0.327). The trichotomized rLMC scores predicted functional outcome in IVT treated patients (adjusted odds ratio, aOR = 4.57, 95% confidence interval, CI, 1.03–20.32, p = 0.046) but showed no independent association with outcome in the non-IVT group (aOR = 0.69, 95% CI 0.07–6.80, p = 0.753).

Conclusion

Good collaterals favored smaller FIV and good functional outcome in IVT treated patients but not in non-IVT treated patients. Good collateral flow may have limited prognostic value if IVT is not administered to attempt reperfusion

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References

  1. Liebeskind DS. Collateral circulation. Stroke. 2003;34:2279–84.

    Article  PubMed  Google Scholar 

  2. Bozzao L, Fantozzi LM, Bastianello S, Bozzao A, Fieschi C. Early collateral blood-supply and late parenchymal brain-damage in patients with middle cerebral-artery occlusion. Stroke. 1989;20:735–40.

    Article  CAS  PubMed  Google Scholar 

  3. Liebeskind DS. Collaterals in acute stroke: beyond the clot. Neuroimaging Clin N Am. 2005;15:553–73.

    Article  PubMed  Google Scholar 

  4. Shuaib A, Butcher K, Mohammad AA, Saqqur M, Liebeskind DS. Collateral blood vessels in acute ischaemic stroke: a potential therapeutic target. Lancet Neurol. 2011;10:909–21.

    Article  PubMed  Google Scholar 

  5. Leng X, Fang H, Leung TW, Mao C, Xu Y, Miao Z, Liu L, Wong KS, Liebeskind DS. Impact of collateral status on successful revascularization in endovascular treatment: a systematic review and meta-analysis. Cerebrovasc Dis. 2016;41:27–34.

    Article  PubMed  Google Scholar 

  6. 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.

    Article  CAS  PubMed  Google Scholar 

  7. Liebeskind DS. Collateral lessons from recent acute ischemic stroke trials. Neurol Res. 2014;36:397–402.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Sheth SA, Sanossian N, Hao Q, Starkman S, Ali LK, Kim D, Gonzalez NR, Tateshima S, Jahan R, Duckwiler GR, Saver JL, Vinuela F, Liebeskind DS; UCLA Collateral Investigators. Collateral flow as causative of good outcomes in endovascular stroke therapy. J Neurointerv Surg. 2016;8:2–7.

    Article  PubMed  Google Scholar 

  9. Wufuer A, Wubuli A, Mijiti P, Zhou J, Tuerxun S, Cai J, Ma J, Zhang X. Impact of collateral circulation status on favorable outcomes in thrombolysis treatment: a systematic review and meta-analysis. Exp Ther Med. 2018;15:707–18.

    Article  CAS  PubMed  Google Scholar 

  10. Rusanen H, Saarinen JT, Sillanpää N. Collateral circulation predicts the size of the infarct core and the proportion of salvageable penumbra in hyperacute ischemic stroke patients treated with intravenous thrombolysis. Cerebrovasc Dis. 2015;40:182–90.

    Article  CAS  PubMed  Google Scholar 

  11. Brunner F, Tomandl B, Hanken K, Hildebrandt H, Kastrup A. Impact of collateral circulation on early outcome and risk of hemorrhagic complications after systemic thrombolysis. Int J Stroke. 2014;9:992–8.

    Article  PubMed  Google Scholar 

  12. de Havenon A, Southerland AM. In large vessel occlusive stroke, time is brain … but collaterals are time. Neurology. 2018;90:153–4.

    Article  PubMed  Google Scholar 

  13. Campbell BC, Christensen S, Tress BM, Churilov L, Desmond PM, Parsons MW, Barber PA, Levi CR, Bladin C, Donnan GA, Davis SM; EPITHET Investigators. Failure of collateral blood flow is associated with infarct growth in ischemic stroke. J Cereb Blood Flow Metab. 2013;33:1168–72.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik RF, Bhuva P, Yavagal DR, Ribo M, Cognard C, Hanel RA, Sila CA, Hassan AE, Millan M, Levy EI, Mitchell P, Chen M, English JD, Shah QA, Silver FL, Pereira VM, Mehta BP, Baxter BW, Abraham MG, Cardona P, Veznedaroglu E, Hellinger FR, Feng L, Kirmani JF, Lopes DK, Jankowitz BT, Frankel MR, Costalat V, Vora NA, Yoo AJ, Malik AM, Furlan AJ, Rubiera M, Aghaebrahim A, Olivot JM, Tekle WG, Shields R, Graves T, Lewis RJ, Smith WS, Liebeskind DS, Saver JL, Jovin TG; DAWN Trial Investigators. 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 

  15. Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez S, McTaggart RA, Torbey MT, Kim-Tenser M, Leslie-Mazwi T, Sarraj A, Kasner SE, Ansari SA, Yeatts SD, Hamilton S, Mlynash M, Heit JJ, Zaharchuk G, Kim S, Carrozzella J, Palesch YY, Demchuk AM, Bammer R, Lavori PW, Broderick JP, Lansberg MG; DEFUSE 3 Investigators. 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 

  16. Barber PA, Demchuk AM, Zhang J, Buchan AM. Validity and reliability of a quantitative computed tomography score in predicting outcome of hyperacute stroke before thrombolytic therapy. ASPECTS Study Group. Alberta Stroke Programme Early CT Score. Lancet. 2000;355:1670–4.

    Article  CAS  PubMed  Google Scholar 

  17. Menon BK, Smith EE, Modi J, Patel SK, Bhatia R, Watson TW, Hill MD, Demchuk AM, Goyal M. Regional leptomeningeal score on CT angiography predicts clinical and imaging outcomes in patients with acute anterior circulation occlusions. AJNR Am J Neuroradiol. 2011;32:1640–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Sommer WH, Bollwein C, Thierfelder KM, Baumann A, Janssen H, Ertl-Wagner B, Reiser MF, Plate A, Straube A, von Baumgarten L. Crossed cerebellar diaschisis in patients with acute middle cerebral artery infarction: occurrence and perfusion characteristics. J Cereb Blood Flow Metab. 2016;36:743–54.

    Article  PubMed  Google Scholar 

  19. Thierfelder KM, Sommer WH, Baumann AB, Klotz E, Meinel FG, Strobl FF, Nikolaou K, Reiser MF, von Baumgarten L. Whole-brain CT perfusion: reliability and reproducibility of volumetric perfusion deficit assessment in patients with acute ischemic stroke. Neuroradiology. 2013;55:827–35.

    Article  PubMed  Google Scholar 

  20. Thierfelder KM, von Baumgarten L, Baumann AB, Meinel FG, Helck AD, Opherk C, Straube A, Reiser MF, Sommer WH. Penumbra pattern assessment in acute stroke patients: comparison of quantitative and non-quantitative methods in whole brain CT perfusion. PLoS ONE. 2014;9:e105413.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Padroni M, Bernardoni A, Tamborino C, Roversi G, Borrelli M, Saletti A, De Vito A, Azzini C, Borgatti L, Marcello O, d’Esterre C, Ceruti S, Casetta I, Lee TY, Fainardi E. Cerebral blood volume ASPECTS is the best predictor of clinical outcome in acute ischemic stroke: a retrospective, combined semi-quantitative and quantitative assessment. PLoS ONE. 2016;11:e147910.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Parsons MW, Pepper EM, Chan V, Siddique S, Rajaratnam S, Bateman GA, Levi CR. Perfusion computed tomography: prediction of final infarct extent and stroke outcome. Ann Neurol. 2005;58:672–9.

    Article  PubMed  Google Scholar 

  23. Brott T, Adams HP Jr, Olinger CP, Marler JR, Barsan WG, Biller J, Spilker J, Holleran R, Eberle R, Hertzberg V, Rorick M, Moomaw CJ, Walker M. Measurements of acute cerebral infarction—a clinical examination scale. Stroke. 1989;20:864–70.

    Article  CAS  PubMed  Google Scholar 

  24. Rankin J. Cerebral vascular accidents in patients over the Age of 60. II. Prognosis. Scott Med J. 1957;2:200–15.

    Article  CAS  PubMed  Google Scholar 

  25. D’Agostino RB. Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med. 1998;17:2265–81.

    Article  PubMed  Google Scholar 

  26. Rosenbaum PR, Rubin DB. Constructing a control-group using multivariate matched sampling methods that incorporate the propensity score. Am Stat. 1985;39:33–8.

    Article  Google Scholar 

  27. Caplan LR, Hennerici M. Impaired clearance of emboli (washout) is an important link between hypoperfusion, embolism, and ischemic stroke. Arch Neurol. 1998;55:1475–82.

    Article  CAS  PubMed  Google Scholar 

  28. Wang CX, Todd KG, Yang Y, Gordon T, Shuaib A. Patency of cerebral microvessels after focal embolic stroke in the rat. J Cereb Blood Flow Metab. 2001;21:413–21. https://doi.org/10.1097/00004647-200104000-00010.

    Article  CAS  PubMed  Google Scholar 

  29. Beard DJ, McLeod DD, Logan CL, Murtha LA, Imtiaz MS, van Helden DF, Spratt NJ. Intracranial pressure elevation reduces flow through collateral vessels and the penetrating arterioles they supply. A possible explanation for ‘collateral failure’ and infarct expansion after ischemic stroke. J Cereb Blood Flow Metab. 2015;35:861–72.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Pham M, Bendszus M. Facing time in ischemic stroke: an alternative hypothesis for collateral failure. Clin Neuroradiol. 2016;26:141–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Tan BY, Wan-Yee K, Paliwal P, Gopinathan A, Nadarajah M, Ting E, Venketasubramanian N, Seet RC, Chan BP, Teoh HL, Rathakrishnan R, Sharma VK, Yeo LL. Good intracranial collaterals trump poor Alberta stroke program early CT score for intravenous thrombolysis in anterior circulation acute ischemic stroke. Stroke. 2016;47:2292-8.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Lima FO, Furie KL, Silva GS, Lev MH, Camargo EC, Singhal AB, Harris GJ, Halpern EF, Koroshetz WJ, Smith WS, Nogueira RG. Prognosis of untreated strokes due to anterior circulation proximal intracranial arterial occlusions detected by use of computed tomography angiography. JAMA Neurol. 2014;71:151-7.

    Article  CAS  PubMed  Google Scholar 

  33. McDonald RJ, McDonald JS, Kallmes DF, Carter RE. Behind the numbers: propensity score analysis—a primer for the diagnostic radiologist. Radiology. 2013;269:640–5.

    Article  PubMed  Google Scholar 

  34. Stuart EA. Matching methods for causal inference: a review and a look forward. Stat Sci. 2010;25:1–21.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Weimar C, König IR, Kraywinkel K, Ziegler A, Diener HC; German Stroke Study Collaboration. Age and national institutes of health stroke scale score within 6 hours after onset are accurate predictors of outcome after cerebral ischemia—development and external validation of prognostic models. Stroke. 2004;35:158–62.

    Article  CAS  PubMed  Google Scholar 

  36. Weimar C, Ziegler A, König IR, Diener HC. Predicting functional outcome and survival after acute ischemic stroke. J Neurol. 2002;249:888–95.

    Article  PubMed  Google Scholar 

  37. Adams HP Jr, Davis PH, Leira EC, Chang KC, Bendixen BH, Clarke WR, Woolson RF, Hansen MD.. Baseline NIH Stroke Scale score strongly predicts outcome after stroke—a report of the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Neurology. 1999;53:126–31.

    Article  CAS  PubMed  Google Scholar 

  38. Medlin F, Amiguet M, Vanacker P, Michel P. Influence of arterial occlusion on outcome after intravenous thrombolysis for acute ischemic stroke. Stroke. 2015;46:126–31.

    Article  CAS  PubMed  Google Scholar 

  39. Jadhav AP, Diener HC, Bonafe A, Pereira VM, Levy EI, Baxter BW, Jovin TG, Nogueira RG, Yavagal DR, Cognard C, Purcell DD, Menon BK, Jahan R, Saver JL, Goyal M; SWIFT PRIME investigators. Correlation between clinical outcomes and baseline CT and CT angiographic findings in the SWIFT PRIME trial. AJNR Am J Neuroradiol. 2017;38:2270–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kunz WG, Fabritius MP, Sommer WH, Höhne C, Scheffler P, Rotkopf LT, Fendler WP, Sabel BO, Meinel FG, Dorn F, Ertl-Wagner B, Reiser MF, Thierfelder KM.. Effect of stroke thrombolysis predicted by distal vessel occlusion detection. Neurology. 2018;90:e1742–50.

    Article  PubMed  Google Scholar 

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Author Contributions

Conceived and designed the experiments: F. Schuler, W.G. Kunz, K.M. Thierfelder. Performed the experiments: F. Schuler, L.T. Rotkopf, M.P. Fabritius, K.M. Thierfelder, W.G. Kunz. Analyzed the data: F. Schuler, L.T. Rotkopf, W.G. Kunz, D. Apel. Wrote the manuscript: F. Schuler, L.T. Rotkopf, D. Apel, M.P. Fabritius, S. Tiedt, F.A. Wollenweber, L. Kellert, F. Dorn, T. Liebig, K.M. Thierfelder, W.G. Kunz.

Funding

W.G. Kunz received an institutional research grant from LMU Munich.

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Correspondence to Felix Schuler.

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F. Schuler, L.T. Rotkopf, D. Apel, M.P. Fabritius, S. Tiedt, F.A. Wollenweber, L. Kellert, F. Dorn, T. Liebig, K.M. Thierfelder and W.G. Kunz declare that they have no competing interests.

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Detailed CT examination protocols, analysis of subacute stroke complications and further statistical analysis including interaction terms.

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Schuler, F., Rotkopf, L.T., Apel, D. et al. Differential Benefit of Collaterals for Stroke Patients Treated with Thrombolysis or Supportive Care. Clin Neuroradiol 30, 525–533 (2020). https://doi.org/10.1007/s00062-019-00815-y

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  • DOI: https://doi.org/10.1007/s00062-019-00815-y

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