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Neuroradiology

, Volume 58, Issue 10, pp 961–967 | Cite as

Impact of leukoaraiosis on parenchymal hemorrhage in elderly patients treated with thrombolysis

  • Norbert Nighoghossian
  • Fatima Abbas
  • Tae-Hee Cho
  • Ana Filipa Geraldo
  • Vincent Cottaz
  • Elie Janecek
  • Laura Mechtouff
  • Magali Bischoff
  • Carlos El Khoury
  • Anne Marie Schott
  • Laurent Derex
  • Marc Hermier
  • Louis Guy Tisserand
  • Roxana Amelie
  • Leila Chamard
  • Yves BerthezeneEmail author
Diagnostic Neuroradiology

Abstract

Introduction

Severity of vascular damage of white matter may predict hemorrhagic transformation (HT). We assess the relationship between leukoaraiosis (LA) severity and the type of hemorrhagic transformation in elderly patients treated with thrombolysis.

Methods

We retrospectively analyzed the clinical data and pretreatment magnetic resonance imaging (MRI) of 180 consecutive ischemic stroke patients aged over 75 years. LA severity was graded according to the Fazekas scale, and acute diffusion-weighted-imaging (DWI) lesion volumes were semi-automatically outlined. Predictors of hemorrhagic infarction (HI) and parenchymal hemorrhage (PH) were identified using logistic regression analysis and exact multinomial logistic analysis.

Results

HT occurred in 31 patients (17 %). Baseline National Institute of Health Stroke Score (NIHSS; p = 0.008), severe LA (p = 0.02), and diffusion lesion volume (p = 0.02) were predictors of HT in univariable logistic regression. Adjusted to lesion volume and baseline NIHSS score, exact multinomial logistic analysis showed that severe LA was the only independent predictor of parenchymal hemorrhage (p = 0.03).

Conclusion

In elderly patients, LA severity better predicts parenchymal hemorrhage than infarct size.

Keywords

Magnetic resonance imaging Elderly Ischemic stroke Leucoaraiosis Thrombolysis 

Abbreviations

LA

Leukoaraiosis

WMH

White matter hyperintensity

HT

Hemorrhagic transformation

ICH

Intracerebral hemorrhage

HI

Hemorrhagic infarction

PH

Parenchymal hemorrhage

NIHSS

National Institute of Health Stroke Score

MRI

Magnetic resonance imaging

SVD

Small-vessel disease

CMBs

Cerebral microbleeds

tPA

Tissue plasminogen activator

Notes

Compliance with ethical standards

We declare that all human studies have been approved [data from a regional emergency stroke network health registry in the Rhône Valley, France—RESUVAL Stroke Network—with 5 stroke units (one academic stroke unit and 4 non-academic stroke units), covering a population of 3 million people authorized by the French Ministry of Healthcare, Registration number E-2012-069] and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. We declare that all patients gave informed consent prior to inclusion in this study.

Conflict of interest

We declare that we have no conflict of interest.

References

  1. 1.
    Bonita R, Anderson CS, Broad JB, Jamrozik KD, Stewart-Wynne EG, Anderson NE (1994) Stroke incidence and case fatality in Australasia. A comparison of the Auckland and Perth population-based stroke registers. Stroke 25:552–7CrossRefPubMedGoogle Scholar
  2. 2.
    Marini C, Baldassarre M, Russo T, De Santis F, Sacco S, Ciancarelli I et al (2004) Burden of first-ever ischemic stroke in the oldest old: evidence from a population-based study. Neurology 62:77–81CrossRefPubMedGoogle Scholar
  3. 3.
    Di Carlo A, Baldereschi M, Gandolfo C, Candelise L, Ghetti A, Maggi S et al (2003) Stroke in an elderly population: incidence and impact on survival and daily function. Italian Longitudinal Study on Aging. Cerebrovasc Dis 16:141–50CrossRefPubMedGoogle Scholar
  4. 4.
    Derex L, Nighoghossian N (2009) Thrombolysis, stroke-unit admission and early rehabilitation in elderly patients. Nat Rev Neurol 5:506–11CrossRefPubMedGoogle Scholar
  5. 5.
    Mishra NK, Ahmed N, Andersen G, Egido JA, Lindsberg PJ, Ringleb PA et al (2010) Thrombolysis in very elderly people: controlled comparison of SITS International Stroke Thrombolysis Registry and Virtual International Stroke Trials Archive. BMJ 23:341–c604Google Scholar
  6. 6.
    Emberson J, Lees KR, Lyden P, Blackwell L, Albers G, Bluhmki E et al (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(9958):1929–35CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    IST-3 collaborative group (2015) Association between brain imaging signs, early and late outcomes, and response to intravenous alteplase after acute ischaemic stroke in the third International Stroke Trial (IST-3): secondary analysis of a randomised controlled trial. Lancet Neurol 14(5):485–96CrossRefGoogle Scholar
  8. 8.
    Ringleb PA, Schwark C, Kohrmann M, Kulkens S, Juttler E, Hacke W et al (2007) Thrombolytic therapy for acute ischaemic stroke in octogenarians: selection by magnetic resonance imaging improves safety but does not improve outcome. J Neurol Neurosurg Psychiatry 78:690–3CrossRefPubMedGoogle Scholar
  9. 9.
    Singer OC, Humpich MC, Fiehler J, Albers GW, Lansberg MG, Kastrup A, for the MR Stroke Study Group Investigators et al (2008) Risk for symptomatic intracerebral hemorrhage after thrombolysis assessed by diffusion-weighted magnetic resonance imaging. Ann Neurol 63:52–60CrossRefPubMedGoogle Scholar
  10. 10.
    Lansberg MG, Thijs VN, Bammer R, Kemp S, Wijman CA, Marks MP et al (2007) DEFUSE Investigators. Risk factors of symptomatic intracerebral hemorrhage after tPA therapy for acute stroke. Stroke 38:2275–2278CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Jung S, Mono ML, Findling O, Fischer U, Galimanis A, Weck A et al (2012) White matter lesions and intra-arterial thrombolysis. J Neurol 7:1331–6CrossRefGoogle Scholar
  12. 12.
    Neumann-Haefelin T, Hoelig S, Berkefeld J, Fiehler J, Gass A, Humpich M et al (2006) Leukoaraiosis is a risk factor for symptomatic intracerebral hemorrhage after thrombolysis for acute stroke. Stroke 37:2463–2466CrossRefPubMedGoogle Scholar
  13. 13.
    Arsava EM, Rahman R, Rosand J, Lu J, Smith EE, Rost NS et al (2014) Severity of leukoaraiosis correlates with clinical outcome after ischemic stroke. Neurology 72:1403–1410CrossRefGoogle Scholar
  14. 14.
    Henninger N, Lin E, Baker SP, Wakhloo AK, Takhtani D, Moonis M (2012) Leukoaraiosis predicts poor 90-day outcome after acute large cerebral artery occlusion. Cerebrovasc Dis 33:525–531.15CrossRefPubMedGoogle Scholar
  15. 15.
    Pantoni L (2010) Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 9:689–701CrossRefPubMedGoogle Scholar
  16. 16.
    Fiehler J, Albers GW, Boulanger JM, Derex L, Gass A, Hjort N, Group MRSTROKE et al (2007) Bleeding Risk Analysis in Stroke Imaging before ThromboLysis (BRASIL): pooled analysis of T 2 *-weighted magnetic resonance imaging data from 570 patients. Stroke 38:2738–2744CrossRefPubMedGoogle Scholar
  17. 17.
    Dannenberg S, Scheitz JF, Rozanski M, Erdur H, Brunecker P, Werring DJ et al (2014) Number of cerebral microbleeds and risk of intracerebral hemorrhage after intravenous thrombolysis. Stroke 10:2900–5CrossRefGoogle Scholar
  18. 18.
    Gratz PP, El-Koussy M, Hsieh K, von Arx S, Mono ML, Heldner MR (2014) Preexisting cerebral microbleeds on susceptibility-weighted magnetic resonance imaging and post-thrombolysis bleeding risk in 392 patients. Stroke 6:1684–8CrossRefGoogle Scholar
  19. 19.
    Curtze S, Melkas S, Sibolt G, Haapaniemi E, Mustanoja S, Putaala J et al (2015) Cerebral computed tomography-graded white matter lesions are associated with worse outcome after thrombolysis in patients with stroke. Stroke 6:1554–60CrossRefGoogle Scholar
  20. 20.
    Curtze S, Haapaniemi E, Melkas S, Mustanoja S, Putaala J, Sairanen T et al (2015) White matter lesions double the risk of post-thrombolytic intracerebral hemorrhage. Stroke 8:2149–55CrossRefGoogle Scholar
  21. 21.
    Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL et al (1993) Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 24:35–41CrossRefPubMedGoogle Scholar
  22. 22.
    Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R et al (2013) Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol 8:822–38CrossRefGoogle Scholar
  23. 23.
    Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D et al (1998) Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet 352:1245–1251CrossRefPubMedGoogle Scholar
  24. 24.
    Hirji KF, Mehta CR, Patel NR (1987) Computing distributions for exact logistic regression. J Am Stat Assoc 82:1110–1117CrossRefGoogle Scholar
  25. 25.
    Kaffashian S, Tzourio C, Zhu YC, Mazoyer B, Debette S (2016) Differential effect of white-matter lesions and covert brain infarcts on the risk of ischemic stroke and intracerebral hemorrhage. Stroke 47(7):1923–1925Google Scholar
  26. 26.
    Whiteley WN, Slot KB, Fernandes P, Sandercock P, Wardlaw J (2012) Risk factors for intracranial hemorrhage in acute ischemic stroke patients treated with recombinant tissue plasminogen activator: a systematic review and meta-analysis of 55 studies. Stroke 43(11):2904–9.2CrossRefPubMedGoogle Scholar
  27. 27.
    Derex L, Hermier M, Adeleine P, Pialat JB, Wiart M, Berthezène Y et al (2005) Clinical and imaging predictors of intracerebral haemorrhage in stroke patients treated with intravenous tissue plasminogen activator. J Neurol Neurosurg Psychiatry 1:70–5CrossRefGoogle Scholar
  28. 28.
    Kahles T, Foerch C, Sitzer M, Schroeter M, Steinmetz H, Rami A et al (2005) Tissue plasminogen activator mediated blood–brain barrier damage in transient focal cerebral ischemia in rats: relevance of interactions between thrombotic material and thrombolytic agent. Vasc Pharmacol 43:254–259CrossRefGoogle Scholar
  29. 29.
    Albers GW, Thijs VN, Wechsler L, for the DEFUSE Investigators et al (2006) Magnetic resonance imaging profiles predict clinical response to early reperfusion: the Diffusion and Perfusion Imaging Evaluation For Understanding Stroke Evolution (DEFUSE) study. Ann Neurol 60:508–517CrossRefPubMedGoogle Scholar
  30. 30.
    Henninger N, LinE HDC, LehmanLL TD, Selim M et al (2013) Leukoaraiosis and sex predict the hyperacute ischemic core volume. Stroke 44:61–67CrossRefPubMedGoogle Scholar
  31. 31.
    Bivard A, Cheng X, Lin LT, Levi C, Spratt N, Kleinig T, O’Brien B, Butcher K et al (2016) Global white matter hypoperfusion on CT predicts larger infarcts and hemorrhagic transformation after acute ischemia. CNS Neurosci Ther 22(3):238–43CrossRefPubMedGoogle Scholar
  32. 32.
    Shoamanesh A, Kwok CS, Lim PA, Benavente OR (2013) Post-thrombolysis intracranial hemorrhage risk of cerebral microbleeds in acute stroke patients: a systematic review and meta-analysis. Int J Stroke 5:348–56CrossRefGoogle Scholar
  33. 33.
    Charidimou A, Shoamanesh A, Wilson D, Gang Q, Fox Z, Jäger HR, Benavente OR, Werring DJ (2015) Cerebral micro bleeds and postthrombolysis intracerebral hemorrhage risk: updated meta-analysis. Neurology 11:927–4CrossRefGoogle Scholar
  34. 34.
    Tsivgoulis G, Zand R, Katsanos AH, Turc G, Nolte CH, Jung S et al (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(6):675–83CrossRefPubMedGoogle Scholar
  35. 35.
    Seet RC, Rabinstein AA (2012) Symptomatic intracranial hemorrhage following intravenous thrombolysis for acute ischemic stroke: a critical review of case definitions. Cerebrovasc Dis 2:106–14CrossRefGoogle Scholar
  36. 36.
    Nogueira RC, Bor-Seng-Shu E, Saeed NP, Teixeira MJ, Panerai RB, Robinson TG (2016) Meta-analysis of vascular imaging features to predict outcome following intravenous rtPA for acute ischemic stroke. Front Neurol 7:77CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM et al (2016) Endovascular thrombectomy after large vessel ischaemic stroke: a meta-analysis of individual patient data from five randomized trials. Lancet 387(10029):1723–31CrossRefPubMedGoogle Scholar
  38. 38.
    Shi ZS, Loh Y, Liebeskind DS, Saver JL, Gonzalez NR, Tateshima S, Jahan R, Feng L, Vespa PM, Starkman S et al (2012) Leukoaraiosis predicts parenchymal hematoma after mechanical thrombectomy in acute ischemic stroke. Stroke 43(7):1806–11CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Norbert Nighoghossian
    • 1
  • Fatima Abbas
    • 2
  • Tae-Hee Cho
    • 1
  • Ana Filipa Geraldo
    • 3
  • Vincent Cottaz
    • 1
  • Elie Janecek
    • 3
  • Laura Mechtouff
    • 1
  • Magali Bischoff
    • 4
  • Carlos El Khoury
    • 4
  • Anne Marie Schott
    • 2
  • Laurent Derex
    • 1
  • Marc Hermier
    • 3
  • Louis Guy Tisserand
    • 3
  • Roxana Amelie
    • 3
  • Leila Chamard
    • 3
  • Yves Berthezene
    • 3
    Email author
  1. 1.Department of Stroke, Neurological HospitalUniversité Lyon 1LyonFrance
  2. 2.Pôle Information Médicale Evaluation RechercheHospices Civils de LyonLyonFrance
  3. 3.Department of Neuroradiology, Neurological HospitalUniversité Lyon 1Bron, LyonFrance
  4. 4.RESUVAL Stroke NetworkLyonFrance

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