Felix C Ng1,2, Nawaf Yassi1,3, Gagan Sharma1, Scott B Brown4, Mayank Goyal5, Charles B L M Majoie6, Tudor G Jovin7, Michael D Hill8, Keith W Muir9, Jeffrey L Saver10, Francis Guillemin11, Andrew M Demchuk8, Bijoy K Menon8, Luis San Roman12, Philip White13, Aad van der Lugt14, Marc Ribo15, Serge Bracard16, Peter J Mitchell17, Stephen M Davis1, Kevin N Sheth18, W Taylor Kimberly19, Bruce C V Campbell1. 1. Melbourne Brain Centre, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia (F.C.N., N.Y., G.S., S.M.D., B.C.V.C.). 2. Austin Health, Heidelberg, Australia (F.C.N.). 3. Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia (N.Y.). 4. Altair Biostatistics, St Louis Park, MN (S.B.B.). 5. Department of Radiology, University of Calgary, Foothills Hospital, AB, Canada (M.G.). 6. Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, location AMC, the Netherlands (C.B.L.M.M.). 7. Cooper Neurological Institute, Cooper University Health Care, Camden, NJ (T.G.J.). 8. Department of Clinical Neurosciences, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Foothills Hospital, AB, Canada (M.D.H., A.M.D., B.K.M.). 9. Institute of Neuroscience & Psychology, University of Glasgow, Queen Elizabeth University Hospital, United Kingdom (K.W.M.). 10. Department of Neurology and Comprehensive Stroke Center, David Geffen School of Medicine at the University of California, Los Angeles, California Stanford Stroke Center, Stanford University (J.L.S.). 11. Clinical Investigation Centre-Clinical Epidemiology INSERM 1433, University of Lorraine and University Hospital of Nancy, France (F.G.). 12. Department of Radiology, Hospital Clínic, Barcelona, Spain (L.S.R.). 13. Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom (P.W.). 14. Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands (A.v.d.L.). 15. Department of Neurology, Hospital Vall d'Hebron, Barcelona, Spain (M.R.). 16. Department of Diagnostic and Interventional Neuroradiology, Université de Lorraine, Inserm, IADI, CHRU Nancy, France (S.B.). 17. Department of Radiology, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia (P.J.M.). 18. Department of Neurology, Yale New Haven Hospital, CT (K.N.S.). 19. Center for Genomic Medicine and Department of Neurology, Massachusetts General Hospital, Boston (W.T.K.).
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.
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.