Determining factors of better leptomeningeal collaterals: a study of 857 consecutive acute ischemic stroke patients

  • Stefania NannoniEmail author
  • Gaia Sirimarco
  • Carlo W. Cereda
  • Dimitris Lambrou
  • Davide Strambo
  • Ashraf Eskandari
  • Pascal J. Mosimann
  • Max Wintermark
  • Patrik Michel
Original Communication



In acute ischemic stroke (AIS) collaterals correlate with infarct size, recanalization rate and clinical outcome. We aimed to identify factors associated with better collateral status in a large series of AIS patients with middle cerebral artery (MCA) occlusion.


In the Acute STroke Registry and Analysis of Lausanne (ASTRAL) from 2003 to 2016, we identified all consecutive AIS with proximal MCA occlusion on CT-angiography performed < 24 h. Collaterals were scored from 0 (absent) to 3 (≥ 100%) and related to multiple demographic, clinical, metabolic and radiological variables in a multivariate regression analysis (MVA).


The 857 included patients had a median age of 72.3 years, 48.4% were female and median admission NIHSS was 16. Better collaterals were associated with younger age (OR 0.99; 95% CI 0.98–1.00), hemineglect (OR 1.35; 95% CI 1.03–1.76), absence of visual field defects (OR 0.64; 95% CI 0.46–0.90), eye deviation (OR 0.58; 95% CI 0.43–0.79) and decreased vigilance (OR 0.62; 95% CI 0.44–0.88). Better collaterals were also associated with dyslipidemia (OR 1.57; 95% CI 1.16–2.13), no previous statin use (OR 0.69; 95% CI 0.50–0.95), and lower creatinine levels (OR 0.99; 95% CI 0.99–1.00). On neuroimaging, better collaterals related to higher ASPECTS score (OR 1.27; 95% CI 1.20–1.35) and higher clot burden score (OR 1.09; 95% CI 1.03–1.14).


Younger age, dyslipidemia and lower creatinine levels were predictors of better collaterals in AIS patients from proximal MCA occlusions. Greater degree of collaterals related to lower stroke severity on admission. On neuroimaging, better collaterals were independently associated with minor early ischemic changes and lower clot burden. These data may add knowledge on pathophysiology of collaterals development and may help to identify patients with better collaterals for late or aggressive recanalization treatments.


Acute ischemic stroke Collateral circulation Computed tomography-angiography (CTA) Acute neuroimaging 



Acute ischemic stroke


Clot burden score


Middle cerebral artery



We thank Melanie Price Hirt for English language correction and editing. We thank Dr Federico Ricciardi from University College London for helpful suggestions on this manuscript.

Author contributions

SN studied the concept and design, helped in analysis and interpretation, and preparation of the article. GS, CWC and DS helped in interpretation of data and critical revision of the article for important intellectual content. DL carried out data analysis and interpretation and helped in preparation of the article. AE helped in data acquisition and analysis. PJM helped in radiological data acquisition and critical revision of the article for important intellectual content. MW contributed to the conception and design, and helped in the interpretation of radiological data. PM studied the concept and design, and helped in data acquisition, analysis and interpretation, critical revision of the article for important intellectual content, study supervision.


This project was supported by the European Academy of Neurology and the Swiss Heart Foundation.

Compliance with ethical standards

Conflicts of interest

In the last 3 years, Prof. P. Michel received research grants from the Swiss Heart Foundation, Boehringer Ingelheim and BMS through his institution; speaker fees from Boehringer Ingelheim, Bayer, Daiichi Sankyo, Medtronic and Amgen; honoraria from scientific advisory boards from Boehringer Ingelheim, Bayer, Pfizer and BMS and consulting fees from Medtronic, Astra-Zeneca and Amgen. His institution (CHUV), receives all of the support for stroke education and research. Dr. G. Sirimarco served on scientific advisory boards for Amgen and Daiichi Sankyo. Dr. C.W. Cereda received research grants from the Swiss Heart Foundation, Advisory Board of Research (EOC) and Boehringer Ingelheim in the last 3 years through his institution; honoraria from scientific advisory boards from Boehringer Ingelheim, Bayer and Pfizer. The other authors report no conflicts of interest.

Ethical standards

Collection, analysis and publication of data in ASTRAL was approved by the institution’s ethical commission.

Supplementary material

415_2018_9170_MOESM1_ESM.docx (53 kb)
Supplementary material 1 (DOCX 53 KB)


  1. 1.
    Liebeskind DS (2003) Collateral circulation. Stroke 34(9):2279–2284. CrossRefGoogle Scholar
  2. 2.
    Vagal A, Menon BK, Foster LD, Livorine A, Yeatts SD, Qazi E, d’Esterre C, Shi J, Demchuk AM, Hill MD, Liebeskind DS, Tomsick T, Goyal M (2016) Association Between CT angiogram collaterals and CT perfusion in the interventional management of stroke III trial. Stroke 47(2):535–538. CrossRefGoogle Scholar
  3. 3.
    Bang OY, Saver JL, Kim SJ, Kim GM, Chung CS, Ovbiagele B, Lee KH, Liebeskind DS (2011) Collateral flow predicts response to endovascular therapy for acute ischemic stroke. Stroke 42(3):693–699. CrossRefGoogle Scholar
  4. 4.
    Miteff F, Levi CR, Bateman GA, Spratt N, McElduff P, Parsons MW (2009) The independent predictive utility of computed tomography angiographic collateral status in acute ischaemic stroke. Brain 132(Pt 8):2231–2238. CrossRefGoogle Scholar
  5. 5.
    Menon BK, Qazi E, Nambiar V, Foster LD, Yeatts SD, Liebeskind D, Jovin TG, Goyal M, Hill MD, Tomsick TA, Broderick JP, Demchuk AM, Interventional Management of Stroke IIII (2015) Differential effect of baseline computed tomographic angiography collaterals on clinical outcome in patients enrolled in the interventional management of stroke III trial. Stroke 46(5):1239–1244. CrossRefGoogle Scholar
  6. 6.
    Ovbiagele B, Saver JL, Starkman S, Kim D, Ali LK, Jahan R, Duckwiler GR, Vinuela F, Pineda S, Liebeskind DS (2007) Statin enhancement of collateralization in acute stroke. Neurology 68(24):2129–2131. CrossRefGoogle Scholar
  7. 7.
    Lima FO, Furie KL, Silva GS, Lev MH, Camargo EC, Singhal AB, Harris GJ, Halpern EF, Koroshetz WJ, Smith WS, Yoo AJ, Nogueira RG (2010) The pattern of leptomeningeal collaterals on CT angiography is a strong predictor of long-term functional outcome in stroke patients with large vessel intracranial occlusion. Stroke 41(10):2316–2322. CrossRefGoogle Scholar
  8. 8.
    Menon BK, Smith EE, Coutts SB, Welsh DG, Faber JE, Goyal M, Hill MD, Demchuk AM, Damani Z, Cho KH, Chang HW, Hong JH, Sohn SI (2013) Leptomeningeal collaterals are associated with modifiable metabolic risk factors. Ann Neurol 74(2):241–248. Google Scholar
  9. 9.
    Malik N, Hou Q, Vagal A, Patrie J, Xin W, Michel P, Eskandari A, Jovin T, Wintermark M (2014) Demographic and clinical predictors of leptomeningeal collaterals in stroke patients. J Stroke Cerebrovasc Dis 23(8):2018–2022. CrossRefGoogle Scholar
  10. 10.
    Michel P, Odier C, Rutgers M, Reichhart M, Maeder P, Meuli R, Wintermark M, Maghraoui A, Faouzi M, Croquelois A, Ntaios G (2010) The Acute STroke Registry and Analysis of Lausanne (ASTRAL): design and baseline analysis of an ischemic stroke registry including acute multimodal imaging. Stroke 41(11):2491–2498. CrossRefGoogle Scholar
  11. 11.
    Tan JC, Dillon WP, Liu S, Adler F, Smith WS, Wintermark M (2007) Systematic comparison of perfusion-CT and CT-angiography in acute stroke patients. Ann Neurol 61(6):533–543. CrossRefGoogle Scholar
  12. 12.
    Stef van Buuren KG-O (2011) Multivariate imputation by chained equations in R. J Stat Softw 45(3):1–68Google Scholar
  13. 13.
    Faber JE, Zhang H, Lassance-Soares RM, Prabhakar P, Najafi AH, Burnett MS, Epstein SE (2011) Aging causes collateral rarefaction and increased severity of ischemic injury in multiple tissues. Arterioscler Thromb Vasc Biol 31(8):1748–1756. CrossRefGoogle Scholar
  14. 14.
    Kinnaird T, Stabile E, Zbinden S, Burnett MS, Epstein SE (2008) Cardiovascular risk factors impair native collateral development and may impair efficacy of therapeutic interventions. Cardiovasc Res 78(2):257–264. CrossRefGoogle Scholar
  15. 15.
    Moore SM, Zhang H, Maeda N, Doerschuk CM, Faber JE (2015) Cardiovascular risk factors cause premature rarefaction of the collateral circulation and greater ischemic tissue injury. Angiogenesis 18(3):265–281. CrossRefGoogle Scholar
  16. 16.
    Kornowski R (2003) Collateral formation and clinical variables in obstructive coronary artery disease: the influence of hypercholesterolemia and diabetes mellitus. Coron Artery Dis 14(1):61–64. CrossRefGoogle Scholar
  17. 17.
    Lee MJ, Bang OY, Kim SJ, Kim GM, Chung CS, Lee KH, Ovbiagele B, Liebeskind DS, Saver JL (2014) Role of statin in atrial fibrillation-related stroke: an angiographic study for collateral flow. Cerebrovasc Dis 37(2):77–84. CrossRefGoogle Scholar
  18. 18.
    Cheripelli BK, Huang X, McVerry F, Muir KW (2016) What is the relationship among penumbra volume, collaterals, and time since onset in the first 6 h after acute ischemic stroke? Int J Stroke 11(3):338–346. CrossRefGoogle Scholar
  19. 19.
    Campbell BC, Christensen S, Tress BM, Churilov L, Desmond PM, Parsons MW, Barber PA, Levi CR, Bladin C, Donnan GA, Davis SM, Investigators E (2013) Failure of collateral blood flow is associated with infarct growth in ischemic stroke. J Cereb Blood Flow Metab 33(8):1168–1172. CrossRefGoogle Scholar
  20. 20.
    Turk M, Zaletel M, Pretnar Oblak J (2016) Characteristics of cerebral hemodynamics in patients with ischemic leukoaraiosis and new ultrasound indices of ischemic leukoaraiosis. J Stroke Cerebrovasc Dis 25(4):977–984. CrossRefGoogle Scholar
  21. 21.
    Menon BK, Smith EE, Modi J, Patel SK, Bhatia R, Watson TW, Hill MD, Demchuk AM, Goyal M (2011) Regional leptomeningeal score on CT angiography predicts clinical and imaging outcomes in patients with acute anterior circulation occlusions. AJNR 32(9):1640–1645. CrossRefGoogle Scholar
  22. 22.
    Verdon V, Schwartz S, Lovblad KO, Hauert CA, Vuilleumier P (2010) Neuroanatomy of hemispatial neglect and its functional components: a study using voxel-based lesion-symptom mapping. Brain 133(Pt 3):880–894. CrossRefGoogle Scholar
  23. 23.
    Alves HC, Treurniet KM, Dutra BG, Jansen IGH, Boers AMM, Santos EMM, Berkhemer OA, Dippel DWJ, van der Lugt A, van Zwam WH, van Oostenbrugge RJ, Lingsma HF, Roos Y, Yoo AJ, Marquering HA, Majoie C, Investigators MCt (2018) Associations between collateral status and thrombus characteristics and their impact in anterior circulation stroke. Stroke 49(2):391–396. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Stefania Nannoni
    • 1
    Email author return OK on get
  • Gaia Sirimarco
    • 1
  • Carlo W. Cereda
    • 1
    • 2
  • Dimitris Lambrou
    • 1
  • Davide Strambo
    • 1
  • Ashraf Eskandari
    • 1
  • Pascal J. Mosimann
    • 3
  • Max Wintermark
    • 4
  • Patrik Michel
    • 1
  1. 1.Stroke Center, Neurology ServiceLausanne University HospitalLausanneSwitzerland
  2. 2.Stroke Center, Neurology ServiceNeurocenter of Southern Switzerland, Ospedale Civico di LuganoLuganoSwitzerland
  3. 3.Neuroradiology Division, Department of RadiologyInselspitalBernSwitzerland
  4. 4.Neuroradiology Division, Department of RadiologyStanford University and Medical CenterStanfordUSA

Personalised recommendations