Wardlaw, Joanna

Mair, Grant

2018-03-19T12:23:23Z

2018-03-19T12:23:23Z

2017-12-01

Among patients presenting acutely with ischaemic stroke who are being considered for intravenous thrombolysis, prompt brain imaging is used to exclude contraindications to treatment (chiefly haemorrhagic stroke or other conditions mimicking stroke) rather than to identify which patients are more or less likely to benefit from thrombolysis. For example, it is unclear whether the presence or absence of arterial obstruction on imaging should be used to guide thrombolysis treatment decisions. In this thesis I explore methods of imaging arterial patency among patients presenting acutely with ischaemic stroke and look for associations between these early imaging findings, response to intravenous thrombolysis and functional outcome six-months after stroke onset. I primarily use data from the Third International Stroke Trial (IST-3), the largest ever randomised-controlled trial testing the use of intravenous alteplase for the acute treatment of ischaemic stroke. I begin by summarising the main features of stroke, covering techniques for imaging the brain and for imaging arterial patency, and post-stroke outcomes. Next I describe two literature reviews which I compiled to increase my understanding of the topic with particular reference to imaging arterial patency. This is followed by a summary of IST-3. Then I describe the general methods I used to address my thesis aims exploring relationships between imaging characteristics of arterial patency, treatment with intravenous alteplase and functional outcome after ischaemic stroke. Specifically, I investigated the following imaging features: - The hyperattenuating artery sign (HAS), which is a non-contrast enhanced CT finding thought to be indicative of acute arterial obstruction by thrombus or embolus - Arterial patency or obstruction as demonstrated using contrast enhanced CT and MR angiographic imaging. In addition to providing better characterisation of the HAS and a better understanding of how angiography helps to assess ischaemic stroke patients, I found that arterial obstruction (however this is identified on imaging) is associated with more severe stroke at baseline and worse functional outcome six months after stroke. I also prove that intravenous alteplase is effective in the presence of arterial obstruction, counter to a widely held concern that it may not be effective in this context. Most of my work has been published in peer reviewed journals. My work should give front line clinicians greater confidence to use intravenous alteplase for the treatment of ischaemic stroke associated with arterial obstruction on imaging, but more work is needed to better understand the implications of apparently normal arterial patency on imaging among patients with ischaemic stroke.

http://hdl.handle.net/1842/28864

en

The University of Edinburgh

Mair G. Lack of flow on time-of-flight MR angiography does not always indicate occlusion. BJR Case Reports 2016; 2(1):http://dx.doi.org/10.1259/bjrcr.20150187.

Mair G and Wardlaw JM. Imaging of acute stroke prior to treatment: Current practice and evolving techniques. British Journal of Radiology 2014;87:20140216

Mair G, von Kummer R, Morris Z, von Heijne A, Bradey N, Cala L, Peeters A, Farrall AJ, Adami A, Potter G, Cohen G, Sandercock PAG, Lindley RI and Wardlaw JM for the IST-3 Collaborative Group. Effect of alteplase on the CT hyperdense artery sign and outcome after ischemic stroke. Neurology 2016;86:1-8

Mair G, Boyd E, Chappell FM, von Kummer R, Lindley R, Sandercock PAG et al. Sensitivity and specificity of the Hyperdense Artery Sign for arterial occlusion in acute ischemic stroke. Stroke 2015; 46:102-107.

Mair G, von Kummer R, Lindley RI, Sandercock PAG, Wardlaw JM. Effect of X-ray attenuation of arterial obstructions on intravenous thrombolysis and outcome after ischemic stroke. PLOS ONE 2015;10:e0145683.

Mair G, Boyd EV, Chappell FM, von Kummer R, Lindley RI, Sandercock P, Wardlaw JM, The IST-3 Collaborative Group. Sensitivity and specificity of the hyperdense artery sign for arterial obstruction in acute ischemic stroke. Stroke 2015;46:102-7.

Mair G, von Kummer R, Adami A, White PM, Adams ME, Yan B, Demchuk AM, Farrall AJ, Sellar RJ, Ramaswamy R, Mollison D, Boyd EV, Rodrigues MA, Samji K, Baird AJ, Cohen G, Sakka E, Palmer J, Perry D, Lindley R, Sandercock PAG, Wardlaw JM, The IST-3 Collaborative Group. Observer reliability of CT angiography in the assessment of acute ischaemic stroke: data from the Third International Stroke Trial. Neuroradiology. 2015;57:1–9.

Mair G, Wardlaw JM, Sandercock P, Lindley R, von Kummer R. Combining CT angiography with non-contrast CT to predict infarct on follow up CT in acute ischaemic stroke. Substudy analysis of imaging from the Third International Stroke Trial (IST-3). Cerebrovascular Diseases 2013;35(Suppl 3):237 (Abst.15)

Mair G, Wardlaw JM, Sandercock P, Lindley R, von Kummer R, Farrall AJ. Association of non-contrast CT and CT angiography with baseline clinical deficit and functional outcome. Substudy analysis of imaging from the Third International Stroke Trial (IST-3). Cerebrovascular Diseases 2013;35(Suppl 3):405 (Abst.226)

Mair G, von Kummer R, Adami A, White PM, Adams ME, Yan B, Demchuk AM, Farrall AJ, Sellar RJ, Sakka E, Palmer J, Perry D, Lindley RI, Sandercock PAG and Wardlaw JM and for the IST-3 Collaborative Group. Arterial Obstruction on Computed Tomographic or Magnetic Resonance Angiography and Response to Intravenous Thrombolytics in Ischemic Stroke. Stroke 2017;48:353-360

Mair G, von Kummer R, Adami A, White PM, Adams M, Yan B et al. Observer reliability of CT Angiography in the assessment of acute ischaemic stroke: Data from the Third International Stroke Trial. Neuroradiology 2015; 57(1):1-9.

Mair G, von Kummer R, Morris Z, von HA, Bradey N, Cala L et al. Effect of alteplase on the CT hyperdense artery sign and outcome after ischemic stroke. Neurology 2016; 86(2):118-125.

Mair G, von Kummer R, Adami A, White PM, Adams ME, Yan B et al. Arterial Obstruction on Computed Tomographic or Magnetic Resonance Angiography and Response to Intravenous Thrombolytics in Ischemic Stroke. Stroke 2016.

Mair G, Wardlaw JM, Sandercock P, Lindley RI, von Kummer R, Farrall AJ. Association of non-contrast CT and CT angiography with baseline clinical deficit and functional outcome. Substudy analysis of imaging from the Third International Stroke Trial (IST-3). Cerebrovasc Dis 2013; 35(suppl3):405.

Mair G, Wardlaw JM, von Kummer R, Sandercock P. Response to thrombolysis treatment in ischemic stroke patients with and without arterial occlusion on computed tomographic angiography: the Third International Stroke Trial. Stroke 2014; 45(suppl1):Abst.A6.

Wardlaw JM, Carpenter T, Sakka E, Mair G, Cohen G, Shuler K et al. Imaging perfusion deficits, arterial patency and thrombolysis safety and efficacy in acute ischaemic stroke. An observational study of the effect of advanced imaging methods in The Third International Stroke Trial (IST-3), a randomised controlled trial. Efficacy Mech Eval 2014; 10.3310/eme01010.

ischaemic stroke

imaging

thrombolysis

Imaging intracranial arterial patency and intravenous thrombolysis in acute ischaemic stroke

Thesis or Dissertation

Doctoral

MD Doctor of Medicine