Quantitative Signal Intensity in Fluid-Attenuated Inversion Recovery and Treatment Effect in the WAKE-UP Trial

BACKGROUND AND PURPOSE—Relative signal intensity of acute ischemic stroke lesions in fluid-attenuated inversion recovery (fluid-attenuated inversion recovery relative signal intensity [FLAIR-rSI]) magnetic resonance imaging is associated with time elapsed since stroke onset with higher intensities s...

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Veröffentlicht in:Stroke (1970) 2020-01, Vol.51 (1), p.209-215
Hauptverfasser: Cheng, Bastian, Boutitie, Florent, Nickel, Alina, Wouters, Anke, Cho, Tae-Hee, Ebinger, Martin, Endres, Matthias, Fiebach, Jochen B., Fiehler, Jens, Galinovic, Ivana, Puig, Josep, Thijs, Vincent, Lemmens, Robin, Muir, Keith W., Nighoghossian, Norbert, Pedraza, Salvador, Simonsen, Claus Z., Gerloff, Christian, Thomalla, Götz
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container_end_page 215
container_issue 1
container_start_page 209
container_title Stroke (1970)
container_volume 51
creator Cheng, Bastian
Boutitie, Florent
Nickel, Alina
Wouters, Anke
Cho, Tae-Hee
Ebinger, Martin
Endres, Matthias
Fiebach, Jochen B.
Fiehler, Jens
Galinovic, Ivana
Puig, Josep
Thijs, Vincent
Lemmens, Robin
Muir, Keith W.
Nighoghossian, Norbert
Pedraza, Salvador
Simonsen, Claus Z.
Gerloff, Christian
Thomalla, Götz
description BACKGROUND AND PURPOSE—Relative signal intensity of acute ischemic stroke lesions in fluid-attenuated inversion recovery (fluid-attenuated inversion recovery relative signal intensity [FLAIR-rSI]) magnetic resonance imaging is associated with time elapsed since stroke onset with higher intensities signifying longer time intervals. In the randomized controlled WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke Trial), intravenous alteplase was effective in patients with unknown onset stroke selected by visual assessment of diffusion weighted imaging fluid-attenuated inversion recovery mismatch, that is, in those with no marked fluid-attenuated inversion recovery hyperintensity in the region of the acute diffusion weighted imaging lesion. In this post hoc analysis, we investigated whether quantitatively measured FLAIR-rSI modifies treatment effect of intravenous alteplase. METHODS—FLAIR-rSI of stroke lesions was measured relative to signal intensity in a mirrored region in the contralesional hemisphere. The relationship between FLAIR-rSI and treatment effect on functional outcome assessed by the modified Rankin Scale (mRS) after 90 days was analyzed by binary logistic regression using different end points, that is, favorable outcome defined as mRS score of 0 to 1, independent outcome defined as mRS score of 0 to 2, ordinal analysis of mRS scores (shift analysis). All models were adjusted for National Institutes of Health Stroke Scale at symptom onset and stroke lesion volume. RESULTS—FLAIR-rSI was successfully quantified in stroke lesions in 433 patients (86% of 503 patients included in WAKE-UP). Mean FLAIR-rSI was 1.06 (SD, 0.09). Interaction of FLAIR-rSI and treatment effect was not significant for mRS score of 0 to 1 (P=0.169) and shift analysis (P=0.086) but reached significance for mRS score of 0 to 2 (P=0.004). We observed a smooth continuing trend of decreasing treatment effects in relation to clinical end points with increasing FLAIR-rSI. CONCLUSIONS—In patients in whom no marked parenchymal fluid-attenuated inversion recovery hyperintensity was detected by visual judgement in the WAKE-UP trial, higher FLAIR-rSI of diffusion weighted imaging lesions was associated with decreased treatment effects of intravenous thrombolysis. This parallels the known association of treatment effect and elapsing time of stroke onset.
doi_str_mv 10.1161/STROKEAHA.119.027390
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In the randomized controlled WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke Trial), intravenous alteplase was effective in patients with unknown onset stroke selected by visual assessment of diffusion weighted imaging fluid-attenuated inversion recovery mismatch, that is, in those with no marked fluid-attenuated inversion recovery hyperintensity in the region of the acute diffusion weighted imaging lesion. In this post hoc analysis, we investigated whether quantitatively measured FLAIR-rSI modifies treatment effect of intravenous alteplase. METHODS—FLAIR-rSI of stroke lesions was measured relative to signal intensity in a mirrored region in the contralesional hemisphere. The relationship between FLAIR-rSI and treatment effect on functional outcome assessed by the modified Rankin Scale (mRS) after 90 days was analyzed by binary logistic regression using different end points, that is, favorable outcome defined as mRS score of 0 to 1, independent outcome defined as mRS score of 0 to 2, ordinal analysis of mRS scores (shift analysis). All models were adjusted for National Institutes of Health Stroke Scale at symptom onset and stroke lesion volume. RESULTS—FLAIR-rSI was successfully quantified in stroke lesions in 433 patients (86% of 503 patients included in WAKE-UP). Mean FLAIR-rSI was 1.06 (SD, 0.09). Interaction of FLAIR-rSI and treatment effect was not significant for mRS score of 0 to 1 (P=0.169) and shift analysis (P=0.086) but reached significance for mRS score of 0 to 2 (P=0.004). We observed a smooth continuing trend of decreasing treatment effects in relation to clinical end points with increasing FLAIR-rSI. CONCLUSIONS—In patients in whom no marked parenchymal fluid-attenuated inversion recovery hyperintensity was detected by visual judgement in the WAKE-UP trial, higher FLAIR-rSI of diffusion weighted imaging lesions was associated with decreased treatment effects of intravenous thrombolysis. This parallels the known association of treatment effect and elapsing time of stroke onset.</description><identifier>ISSN: 0039-2499</identifier><identifier>EISSN: 1524-4628</identifier><identifier>DOI: 10.1161/STROKEAHA.119.027390</identifier><identifier>PMID: 31662118</identifier><language>eng</language><publisher>United States: American Heart Association, Inc</publisher><subject>Acute Disease ; Aged ; Brain Ischemia - diagnostic imaging ; Brain Ischemia - drug therapy ; Diffusion Magnetic Resonance Imaging ; Double-Blind Method ; Female ; Humans ; Male ; Middle Aged ; Statistics ; Stroke - diagnostic imaging ; Stroke - drug therapy ; Thrombolytic Therapy ; Tissue Plasminogen Activator - therapeutic use</subject><ispartof>Stroke (1970), 2020-01, Vol.51 (1), p.209-215</ispartof><rights>American Heart Association, Inc.</rights><rights>2020 American Heart Association, Inc.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4810-1a428b516a478380b2209a840c237a6ca3b5b64a4ea645494ce552a5989642cc3</citedby><cites>FETCH-LOGICAL-c4810-1a428b516a478380b2209a840c237a6ca3b5b64a4ea645494ce552a5989642cc3</cites><orcidid>0000-0001-8677-2447 ; 0000-0002-0909-8900 ; 0000-0002-3223-2071</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,3687,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31662118$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-04551489$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Cheng, Bastian</creatorcontrib><creatorcontrib>Boutitie, Florent</creatorcontrib><creatorcontrib>Nickel, Alina</creatorcontrib><creatorcontrib>Wouters, Anke</creatorcontrib><creatorcontrib>Cho, Tae-Hee</creatorcontrib><creatorcontrib>Ebinger, Martin</creatorcontrib><creatorcontrib>Endres, Matthias</creatorcontrib><creatorcontrib>Fiebach, Jochen B.</creatorcontrib><creatorcontrib>Fiehler, Jens</creatorcontrib><creatorcontrib>Galinovic, Ivana</creatorcontrib><creatorcontrib>Puig, Josep</creatorcontrib><creatorcontrib>Thijs, Vincent</creatorcontrib><creatorcontrib>Lemmens, Robin</creatorcontrib><creatorcontrib>Muir, Keith W.</creatorcontrib><creatorcontrib>Nighoghossian, Norbert</creatorcontrib><creatorcontrib>Pedraza, Salvador</creatorcontrib><creatorcontrib>Simonsen, Claus Z.</creatorcontrib><creatorcontrib>Gerloff, Christian</creatorcontrib><creatorcontrib>Thomalla, Götz</creatorcontrib><creatorcontrib>WAKE-UP (Efficacy and Safety of MRI-Based Thrombolysis inWake-Up Stroke Trial) investigators and administrative staff are as follows</creatorcontrib><creatorcontrib>on behalf of the WAKE-UP Investigators</creatorcontrib><title>Quantitative Signal Intensity in Fluid-Attenuated Inversion Recovery and Treatment Effect in the WAKE-UP Trial</title><title>Stroke (1970)</title><addtitle>Stroke</addtitle><description>BACKGROUND AND PURPOSE—Relative signal intensity of acute ischemic stroke lesions in fluid-attenuated inversion recovery (fluid-attenuated inversion recovery relative signal intensity [FLAIR-rSI]) magnetic resonance imaging is associated with time elapsed since stroke onset with higher intensities signifying longer time intervals. In the randomized controlled WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke Trial), intravenous alteplase was effective in patients with unknown onset stroke selected by visual assessment of diffusion weighted imaging fluid-attenuated inversion recovery mismatch, that is, in those with no marked fluid-attenuated inversion recovery hyperintensity in the region of the acute diffusion weighted imaging lesion. In this post hoc analysis, we investigated whether quantitatively measured FLAIR-rSI modifies treatment effect of intravenous alteplase. METHODS—FLAIR-rSI of stroke lesions was measured relative to signal intensity in a mirrored region in the contralesional hemisphere. The relationship between FLAIR-rSI and treatment effect on functional outcome assessed by the modified Rankin Scale (mRS) after 90 days was analyzed by binary logistic regression using different end points, that is, favorable outcome defined as mRS score of 0 to 1, independent outcome defined as mRS score of 0 to 2, ordinal analysis of mRS scores (shift analysis). All models were adjusted for National Institutes of Health Stroke Scale at symptom onset and stroke lesion volume. RESULTS—FLAIR-rSI was successfully quantified in stroke lesions in 433 patients (86% of 503 patients included in WAKE-UP). Mean FLAIR-rSI was 1.06 (SD, 0.09). Interaction of FLAIR-rSI and treatment effect was not significant for mRS score of 0 to 1 (P=0.169) and shift analysis (P=0.086) but reached significance for mRS score of 0 to 2 (P=0.004). We observed a smooth continuing trend of decreasing treatment effects in relation to clinical end points with increasing FLAIR-rSI. CONCLUSIONS—In patients in whom no marked parenchymal fluid-attenuated inversion recovery hyperintensity was detected by visual judgement in the WAKE-UP trial, higher FLAIR-rSI of diffusion weighted imaging lesions was associated with decreased treatment effects of intravenous thrombolysis. This parallels the known association of treatment effect and elapsing time of stroke onset.</description><subject>Acute Disease</subject><subject>Aged</subject><subject>Brain Ischemia - diagnostic imaging</subject><subject>Brain Ischemia - drug therapy</subject><subject>Diffusion Magnetic Resonance Imaging</subject><subject>Double-Blind Method</subject><subject>Female</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Statistics</subject><subject>Stroke - diagnostic imaging</subject><subject>Stroke - drug therapy</subject><subject>Thrombolytic Therapy</subject><subject>Tissue Plasminogen Activator - therapeutic use</subject><issn>0039-2499</issn><issn>1524-4628</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1uEzEUhS0EoqHwBgjNEhZT_D_2clSlpGqkQpuKpXXHcYjB8ZSxJ1XeHkdTsoSFZZ97v3Nt-SD0nuALQiT5fL-6u72Zt4u2SH2BacM0foFmRFBec0nVSzTDmOmacq3P0JuUfmKMKVPiNTpjREpKiJqh-G2EmH2G7Peuuvc_IoTqOmYXk8-HysfqKox-Xbe5lEbIbl26ezck38fqztm-nA8VxHW1GhzknYu5mm82zuajN29d9b29mdcPX0vfQ3iLXm0gJPfueT9HD1fz1eWiXt5-ub5sl7XliuCaAKeqE0QCbxRTuKMUa1AcW8oakBZYJzrJgTuQXHDNrROCgtBKS06tZefo0zR3C8E8Dn4Hw8H04M2iXZpjDXMhCFd6Twr7cWIfh_736FI2O5-sCwGi68dkKCNYSiUbXFA-oXboUxrc5jSbYHNMxZxSKVKbKZVi-_B8w9jt3Ppk-htDAdQEPPUhl8_9FcYnN5itg5C3_5vN_2EtkeOmvLymmGJMiqrLYoz9AUBqqI0</recordid><startdate>20200101</startdate><enddate>20200101</enddate><creator>Cheng, Bastian</creator><creator>Boutitie, Florent</creator><creator>Nickel, Alina</creator><creator>Wouters, Anke</creator><creator>Cho, Tae-Hee</creator><creator>Ebinger, Martin</creator><creator>Endres, Matthias</creator><creator>Fiebach, Jochen B.</creator><creator>Fiehler, Jens</creator><creator>Galinovic, Ivana</creator><creator>Puig, Josep</creator><creator>Thijs, Vincent</creator><creator>Lemmens, Robin</creator><creator>Muir, Keith W.</creator><creator>Nighoghossian, Norbert</creator><creator>Pedraza, Salvador</creator><creator>Simonsen, Claus Z.</creator><creator>Gerloff, Christian</creator><creator>Thomalla, Götz</creator><general>American Heart Association, Inc</general><general>American Heart Association</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0001-8677-2447</orcidid><orcidid>https://orcid.org/0000-0002-0909-8900</orcidid><orcidid>https://orcid.org/0000-0002-3223-2071</orcidid></search><sort><creationdate>20200101</creationdate><title>Quantitative Signal Intensity in Fluid-Attenuated Inversion Recovery and Treatment Effect in the WAKE-UP Trial</title><author>Cheng, Bastian ; Boutitie, Florent ; Nickel, Alina ; Wouters, Anke ; Cho, Tae-Hee ; Ebinger, Martin ; Endres, Matthias ; Fiebach, Jochen B. ; Fiehler, Jens ; Galinovic, Ivana ; Puig, Josep ; Thijs, Vincent ; Lemmens, Robin ; Muir, Keith W. ; Nighoghossian, Norbert ; Pedraza, Salvador ; Simonsen, Claus Z. ; Gerloff, Christian ; Thomalla, Götz</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4810-1a428b516a478380b2209a840c237a6ca3b5b64a4ea645494ce552a5989642cc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Acute Disease</topic><topic>Aged</topic><topic>Brain Ischemia - diagnostic imaging</topic><topic>Brain Ischemia - drug therapy</topic><topic>Diffusion Magnetic Resonance Imaging</topic><topic>Double-Blind Method</topic><topic>Female</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Statistics</topic><topic>Stroke - diagnostic imaging</topic><topic>Stroke - drug therapy</topic><topic>Thrombolytic Therapy</topic><topic>Tissue Plasminogen Activator - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cheng, Bastian</creatorcontrib><creatorcontrib>Boutitie, Florent</creatorcontrib><creatorcontrib>Nickel, Alina</creatorcontrib><creatorcontrib>Wouters, Anke</creatorcontrib><creatorcontrib>Cho, Tae-Hee</creatorcontrib><creatorcontrib>Ebinger, Martin</creatorcontrib><creatorcontrib>Endres, Matthias</creatorcontrib><creatorcontrib>Fiebach, Jochen B.</creatorcontrib><creatorcontrib>Fiehler, Jens</creatorcontrib><creatorcontrib>Galinovic, Ivana</creatorcontrib><creatorcontrib>Puig, Josep</creatorcontrib><creatorcontrib>Thijs, Vincent</creatorcontrib><creatorcontrib>Lemmens, Robin</creatorcontrib><creatorcontrib>Muir, Keith W.</creatorcontrib><creatorcontrib>Nighoghossian, Norbert</creatorcontrib><creatorcontrib>Pedraza, Salvador</creatorcontrib><creatorcontrib>Simonsen, Claus Z.</creatorcontrib><creatorcontrib>Gerloff, Christian</creatorcontrib><creatorcontrib>Thomalla, Götz</creatorcontrib><creatorcontrib>WAKE-UP (Efficacy and Safety of MRI-Based Thrombolysis inWake-Up Stroke Trial) investigators and administrative staff are as follows</creatorcontrib><creatorcontrib>on behalf of the WAKE-UP Investigators</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Stroke (1970)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cheng, Bastian</au><au>Boutitie, Florent</au><au>Nickel, Alina</au><au>Wouters, Anke</au><au>Cho, Tae-Hee</au><au>Ebinger, Martin</au><au>Endres, Matthias</au><au>Fiebach, Jochen B.</au><au>Fiehler, Jens</au><au>Galinovic, Ivana</au><au>Puig, Josep</au><au>Thijs, Vincent</au><au>Lemmens, Robin</au><au>Muir, Keith W.</au><au>Nighoghossian, Norbert</au><au>Pedraza, Salvador</au><au>Simonsen, Claus Z.</au><au>Gerloff, Christian</au><au>Thomalla, Götz</au><aucorp>WAKE-UP (Efficacy and Safety of MRI-Based Thrombolysis inWake-Up Stroke Trial) investigators and administrative staff are as follows</aucorp><aucorp>on behalf of the WAKE-UP Investigators</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Quantitative Signal Intensity in Fluid-Attenuated Inversion Recovery and Treatment Effect in the WAKE-UP Trial</atitle><jtitle>Stroke (1970)</jtitle><addtitle>Stroke</addtitle><date>2020-01-01</date><risdate>2020</risdate><volume>51</volume><issue>1</issue><spage>209</spage><epage>215</epage><pages>209-215</pages><issn>0039-2499</issn><eissn>1524-4628</eissn><abstract>BACKGROUND AND PURPOSE—Relative signal intensity of acute ischemic stroke lesions in fluid-attenuated inversion recovery (fluid-attenuated inversion recovery relative signal intensity [FLAIR-rSI]) magnetic resonance imaging is associated with time elapsed since stroke onset with higher intensities signifying longer time intervals. In the randomized controlled WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke Trial), intravenous alteplase was effective in patients with unknown onset stroke selected by visual assessment of diffusion weighted imaging fluid-attenuated inversion recovery mismatch, that is, in those with no marked fluid-attenuated inversion recovery hyperintensity in the region of the acute diffusion weighted imaging lesion. In this post hoc analysis, we investigated whether quantitatively measured FLAIR-rSI modifies treatment effect of intravenous alteplase. METHODS—FLAIR-rSI of stroke lesions was measured relative to signal intensity in a mirrored region in the contralesional hemisphere. The relationship between FLAIR-rSI and treatment effect on functional outcome assessed by the modified Rankin Scale (mRS) after 90 days was analyzed by binary logistic regression using different end points, that is, favorable outcome defined as mRS score of 0 to 1, independent outcome defined as mRS score of 0 to 2, ordinal analysis of mRS scores (shift analysis). All models were adjusted for National Institutes of Health Stroke Scale at symptom onset and stroke lesion volume. RESULTS—FLAIR-rSI was successfully quantified in stroke lesions in 433 patients (86% of 503 patients included in WAKE-UP). Mean FLAIR-rSI was 1.06 (SD, 0.09). Interaction of FLAIR-rSI and treatment effect was not significant for mRS score of 0 to 1 (P=0.169) and shift analysis (P=0.086) but reached significance for mRS score of 0 to 2 (P=0.004). We observed a smooth continuing trend of decreasing treatment effects in relation to clinical end points with increasing FLAIR-rSI. CONCLUSIONS—In patients in whom no marked parenchymal fluid-attenuated inversion recovery hyperintensity was detected by visual judgement in the WAKE-UP trial, higher FLAIR-rSI of diffusion weighted imaging lesions was associated with decreased treatment effects of intravenous thrombolysis. This parallels the known association of treatment effect and elapsing time of stroke onset.</abstract><cop>United States</cop><pub>American Heart Association, Inc</pub><pmid>31662118</pmid><doi>10.1161/STROKEAHA.119.027390</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0001-8677-2447</orcidid><orcidid>https://orcid.org/0000-0002-0909-8900</orcidid><orcidid>https://orcid.org/0000-0002-3223-2071</orcidid><oa>free_for_read</oa></addata></record>
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subjects Acute Disease
Aged
Brain Ischemia - diagnostic imaging
Brain Ischemia - drug therapy
Diffusion Magnetic Resonance Imaging
Double-Blind Method
Female
Humans
Male
Middle Aged
Statistics
Stroke - diagnostic imaging
Stroke - drug therapy
Thrombolytic Therapy
Tissue Plasminogen Activator - therapeutic use
title Quantitative Signal Intensity in Fluid-Attenuated Inversion Recovery and Treatment Effect in the WAKE-UP Trial
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