Abstract
Background: Cerebral edema after large hemispheric infarction is associated with poor functional outcome and mortality. Net water uptake (NWU) quantifies the degree of hypoattenuation on unenhanced-computed tomography (CT) and is increasingly used to measure cerebral edema in stroke research. Hemorrhagic transformation and parenchymal contrast staining after thrombectomy may confound NWU measurements. We investigated the correlation of NWU measured postthrombectomy with volumetric markers of cerebral edema and association with functional outcomes. Methods: In a pooled individual patient level analysis of patients presenting with anterior circulation large hemispheric infarction (core 80-300 mL or Alberta Stroke Program Early CT Score ≤5) in the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke trials) data set, cerebral edema was defined as the volumetric expansion of the ischemic hemisphere expressed as a ratio to the contralateral hemisphere(rHV). NWU and midline-shift were compared with rHV as the reference standard on 24-hour follow-up CT, adjusted for hemorrhagic transformation and the use of thrombectomy. Association between edema markers and day 90 functional outcomes (modified Rankin Scale) was assessed using ordinal logistic regression. Results: Overall (n=144), there was no correlation between NWU and rHV (rs=0.055, P=0.51). In sub-group analyses, a weak correlation between NWU with rHV was observed after excluding patients with any degree of hemorrhagic transformation (rs=0.211, P=0.015), which further improved after excluding thrombectomy patients (rs=0.453, P=0.001). Midline-shift correlated strongly with rHV in all sub-group analyses (rs>0.753, P=0.001). Functional outcome at 90 days was negatively associated with rHV (adjusted common odds ratio, 0.46 [95% CI, 0.32-0.65]; P<0.001) and midline-shift (adjusted common odds ratio, 0.85 [95% CI, 0.78-0.92]; P<0.001) but not NWU (adjusted common odds ratio, 1.00 [95% CI, 0.97-1.03]; P=0.84), adjusted for age, baseline National Institutes of Health Stroke Scale, and thrombectomy. Prognostic performance of NWU improved after excluding patients with hemorrhagic transformation and thrombectomy (adjusted odds ratio, 0.90 [95% CI, 0.80-1.02]; P=0.10). Conclusions: NWU correlated poorly with conventional markers of cerebral edema and was not associated with clinical outcome in the presence of hemorrhagic transformation and thrombectomy. Measuring NWU postthrombectomy requires validation before implementation into clinical research. At present, the use of NWU should be limited to baseline CT, or follow-up CT only in patients without hemorrhagic transformation or treatment with thrombectomy.
| Original language | English |
|---|---|
| Pages (from-to) | 2628-2636 |
| Number of pages | 9 |
| Journal | Stroke |
| Volume | 53 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 1 Aug 2022 |
Bibliographical note
Funding Information:National Health and Medical Research Council of Australia, Heart Foundation of Australia, Royal Australasian College of Physician, Australian and New Zealand Association of Neurologist.
Funding Information:
F.C. Ng received grants from National Health and Medical Research Council and Heart Foundation. Dr Campbell received research support from National Health and Medical Research Council of Australia (GNT1043242 and GNT1035688), Royal Australasian College of Physicians, Royal Melbourne Hospital Foundation, National Heart Foundation, National Stroke Foundation of Australia, and unrestricted grant funding for the EXTEND-IA trial to the Florey Institute of Neuroscience and Mental Health from Covidien (Medtronic). Dr Majoie received research support from CVON/Dutch Heart Foundation, European Commission, TWIN foundation, Dutch Health Evaluation Program and Stryker (all paid to institution) and owns stock in Nico-lab, a company that focuses on the use of artificial intelligence for medical image analysis (modest). Dr Kimberly received research grants from National Institute of Neurological Disorders and Stroke, American Heart Association, Biogen, and NControl Therapeutics, and personal fees from Biogen and NControl Therapeutics, and has a patent pending (16/486 687 and PCT/US2018/018537) for a method and composition for treating a brain injury. Dr Menon is Member of the steering and executive committee for the ESCAPE trial, which received support from Covidien (Medtronic), was site principal investigator for the SOCRATES trial (sponsored by AstraZeneca), has received honoraria from Penumbra, has a provisional patent (62/086077) for triaging systems in ischemic stroke, and has research funding from Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Alberta Innovates—Health Solutions, and the Hotchkiss Brain Institute and the Faculty of Medicine, University of Calgary; shareholding from Circle NVI. Dr Demchuk received grant funding from Medtronic for the ESCAPE trial and personal fees from Medtronic; stock ownership from Circle NVI; patent to Circle NVI. Dr White received grant funding to University of Glasgow for the PISTE trial from Medtronic and Codman as well as grants from Stroke Association (TSA 2011/06) and National Institute of Health Research (NIHR) Health Technology Assessment programme (HTA 14.08.47), grants and personal fees from Microvention Terumo and personal fees from Stryker and Codman. Dr Demchuk received compensation from Boehringer Ingelheim, HLS Therapeutics Inc, NovaSignal and Medtronic for consultant services; compensation from Philips for data and safety monitoring services; Grant funding for REVASCAT trial. Dr Davis received Personal fees from Medtronic and Boehringer Ingelheim; compensation from AstraZeneca, Abbott Pharmaceuticals and Amgen for other services. Dr Brown received personal fees from Medtronic and the University of Calgary. Dr Muir received personal fees from Biogen, Bayer, for consultancy from Medtronic, personal feeds and nonfinancial support from Boehringer Ingelheim, personal fees from Daiichi Sankyo, Abbvie, ReNeuron. The University of Glasgow received grant support for the PISTE trial from Medtronic and Codman as well as grants from the Stroke Association (TSA 2011/06) and NIHR Health Technology Assessment programme (HTA 14 · 08 · 47). Dr van der Lugt received grants from the Dutch Heart Foundation, AngioCare BV, Medtronic/Covidien/EV3, MEDAC Gmbh/LAMEPRO, Penumbra, Top Medical/Concentric, Stryker and Cerenovus, Health Holland Top Sector Life Science & Health, Trombolytics Science LLC. Dr Goyal received Grants from Medtronic and Stryker, personal fees from Mentice, Medtronic, Stryker, Microvention and GE Healthcare; a patent systems and methods for diagnosing strokes (PCT/CA2013/000761) licensed to GE Healthcare. Dr Saver received compensation from Johnson & Johnson Health Care Systems Inc. for consultant services; Unpaid site investigator in multicentre trials sponsored by Covidien, Medtronic/Abbott, Stryker, and Neuravi/Abbott, for which the University of California received payments on the basis of clinical trial contracts for the number of subjects enrolled; reports receiving contracted hourly payments and travel reimbursement from Covidien, Medtronic/Abbott, Stryker, and Neuravi/Abbott, and stock options from Rapid Medical, for service on Trial Steering Committees, advising on rigorous trial design and conduct. The University of California has patent rights in retrieval devices for stroke. Dr Jovin reports Vizai; Personal fees for consultancy from Contego Medical, Cerenovus, Codman Neurovascular and Neuravi, holds stock in Silk Road, Anaconda, Route 92, FreeOx Biotech, Blockade and Corindus; stock options in Galazy Therapeutics, grants from Metronic; has acted as an unpaid consultant to Stryker as principal investigator of the DAWN trial; has acted as investor/advisor to Methinks. Dr Hill reports Medtronic LLC during the conduct of the study; grants from NoNO Inc, Boehringer Ingelheim, and Biogen Inc outside the submitted work; a patent to US Patent office Number: 62/086,077 issued and licensed; Stock owner in Pure Web Incorporated and CircleNVI, director of the Canadian Federation of Neurological Sciences, the Canadian Stroke Consortium and Circle NeuroVascular Inc, public grant support to the University of Calgary from Alberta Innovates Health Solutions, CIHR, Heart & Stroke Foundation of Canada, National Institutes of Neurological Disorders and Stroke; Brainsgate Ltd for consultant services. P.J. Mitchell reports unrestricted research grants to his institution from Codman Johnson and Johnson, Medtronic, and Stryker and has served as an unpaid consultant to Codman Johnson and Johnson; compensation from Stryker Corporation and Medtronic USA, Inc for other services; and compensation from Stryker Corporation for consultant services. Dr Sheth: Hyperfine to other; grants from Biogen to other; a patent pending for Stroke wearables licensed to Alva Health; grants from BARD to other; and grants from Novartis to other. Dr Ribo reports stock holdings in Anaconda Biomed and Methinks; compensation from Philips, Cerenovus, AptaTargets, Stryker Corporation and Medtronic MiniMed, Inc for consultant services. The other authors report no conflicts.
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