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

Bastian Cheng (1) , Florent Boutitie (2) , Alina Nickel , Anke Wouters (3, 4, 5, 6) , Tae-Hee Cho (7, 8) , Martin Ebinger (9) , Matthias Endres (10) , Jochen Fiebach (10) , Jens Fiehler (1) , Ivana Galinovic (10) , Josep Puig (11, 12, 13) , Vincent Thijs (14, 15) , Robin Lemmens (3, 4, 5) , Keith Muir (16) , Norbert Nighoghossian (17, 18) , Salvador Pedraza (19) , Claus Simonsen , Christian Gerloff (1) , Götz Thomalla (1) , Amir Golsari , Anna Alegiani , Christoph Beck , Chi-Un Choe , Dieke Voget , Julia Hoppe , Julian Schröder , Michal Rozanski , Alexander Nave , Christian Wollboldt , Isabelle van Sloten , Jos Göhler , Juliane Herm , Jan Jungehülsing , Janos Lückl , Jan Kröber , Johannes Schurig , Luzie Koehler , Ludwig Schlemm , Michael Knops , Maria Roennefarth , Nils Ipsen , Peter Harmel , Rouven Bathe-Peters , Robert Fleischmann , Ramanan Ganeshan , Rohat Geran , Simon Hellwig , Sein Schmidt , Serdar Tütüncü , Thomas Krause , Verena Gramse , Joachim Röther , Peter Michels , Dominik Michalski , Johann Pelz , Andreas Schulz , Carsten Hobohm , Christopher Weise , Gesa Weise , Johannes Orthgieß , Katrin Pomrehn , Mirko Wegscheider , Anne Mueller , Michael Hennerici , Martin Griebe , Angelika Alonso , Alexandra Filipov , Annika Marzina , Bettina Anders , Christian Bähr , Carolin Hoyer , Christopher Schwarzbach , Claudia Weber , Eva Hornberger , Hans-Werner Pledl , Matti Klockziem , Markus Stuermlinger , Matthias Wittayer , Marc Wolf , Nadja Meyer , Philipp Eisele , Susanne Steinert , Tamara Sauer , Valentin Held , Peter Ringleb , Simon Nagel , Roland Veltkamp , Sönke Schwarting , Alexander Schwarz , Christoph Gumbinger , Christian Hametner , Hemasse Amiri , Jan Purrucker , Mareva Ciatipis , Oliver Menn , Sibu Mundiyanapurath , Simon Schieber , Tobias Kessler , Tilman Reiff , Verena Panitz , Oliver Singer , Christian Foerch , Arne Lauer , Anika Männer , Alexander Seiler , Damla Guerzoglu , Jan Schäfer , Katharina Filipski , Matthias Lorenz , Natalia Kurka , Pia Zeiner , Waltraud Pfeilschifter , Rainer Dziewas , Jens Minnerup , Christian Albiker , Martin Ritter , Matthias Seidel , Ralf Dittrich , Bernd Kallmünzer , Tobias Bobinger , Dominik Madzar , David Stark , Jochen Sembill , Kosmas Macha , Klemens Winder , Lorenz Breuer , Martin Koehrmann , Maximilian Spruegel , Stefan Gerner , Peter Kraft , Daniel Mackenrodt , Christoph Kleinschnitz , Ahmed Elhfnawy , Florian Heinen , Ignaz Gunreben , Sven Poli , Ulf Ziemann , Alexandra Gaenslen , Dennis Schlak , Florian Haertig , Francesca Russo , Hardy Richter , Matthias Ebner , Martin Ribitsch , Martin Wolf , Christian Weimar , Vesna Zegarac , Hsin-Chieh Chen , Katharina Althaus , Hermann Neugebauer , Eric Jüttler , Julia Meier , Sebastian Stösser , Volker Puetz , Ulf Bodechtel , Leif Ostergaard , Anette Møller , Dorte Damgaard , Kristina Hougaard Dupont , Marika Poulsen , Niels Hjort , Noelia Ruiz de Morales , Paul von Weitzel , Thomas Harbo , Jacob Marstrand , Andreas Hansen , Hanne Christensen , Karen Aegidius , Lise Jeppesen , Per Meden , Sverre Rosenbaum , Helle Iversen , Jakob Hansen , Lene Michelsen , Thomas Truelsen , Boris Modrau , Karsten Vestergaard , Lorenz Oppel , Aalborg Sygehus , Syd Aalborg , Bart Swinnen , Ide Smets , Jelle Demeestere , Laurens Dobbels , Raf Brouns , Ann de Smedt , Jacques Dekeyser , Laetita Yperzeele , Robbert- Jan van Hooff , Andre Peeters , Anne Dusart , Ana Etexberria , Bernard Hanseeuw , Frederic London , Jonathan Leempoel , Katharina Hohenbichler , Nadia Younan , Vicky Maqueda , Patrice Laloux , Beatrijs de Coene , Charlotte de Maeseneire , Gaetane Turine , Yves Vandermeeren , Nina de Klippel , Chris Willems , Isabel de Hollander , Peter Soors , Sylvia Hermans , Dimitri Hemelsoet , Philippe Desfontaines , Peter Vanacker , Matthieu Rutgers , Charlotte Druart , Dirk Peeters , Bart Bruneel , Evelien Vancaester , Frederik Vanhee , Guy Meersman , Paul Bourgeois , Patrick Vanderdonckt , Amandine Benoit , Laurent Derex , Laura Mechthouff , Nadia Berhoune , Thomas Ritzenthaler , Pierre Amarenco , Cristina Hobeanu , Elena Meseguer Gancedo , David Calvet , Alexandre Ladoux , Alexandre Machet , Catherine Lamy , Charles Mellerio , Catherine Oppenheim , Christine Rodriguez-Regent , Eric Bodiguel , Guillaume Turc , Julia Birchenall , Laurence Legrand , Ludovic Morin , Myriam Edjali-Goujon , Oliver Naggara , Soulliard Raphaelle , Sylvie Godon-Hardy , Valérie Domigo , Vincent Guiraud , Yves Samson , Anne Leger , Charlotte Rosso , Flore Baronnet-Chauvet , Sophie Crozier , Sandrine Deltour , Marion Yger , Igor Sibon , Pauline Renou , Sharmilla Sagnier , Mathieu Zuber , Ruben Tamazyan , Gilles Rodier , Nathalie Morel , Sandra Felix , Wilfried Vadot , Valerie Wolff , Adriana Aniculaesei , Bertrand Yalo , Daniela Bindila , Veronique Quenardelle , Karine Blanc-Lasserre , Emmanuelle Landrault , Ludovic Breynaert , Serkan Cakmak , Stéphane Peysson , Alain Viguier , Claire Lebely , Nicolas Raposo , Anne-Evelyne Vallet , Pauline Vallet , Sébastian Brugirard , Bharath Cheripelli , Dheeraj Kalladka , Fiona Moreton , Krishna Dani , Salwa El Tawil , Sankaranarayanan Ramachandran , Xuya Huang , Elisabeth Warburton , Nicholas Evans , Richard Perry , Bhavni Patel , Geoffrey Cloud , Anthony Pereira , Barry Moynihan , Caroline Lovelock , Lillian Choy , Usman Khan , Christine Roffe , Pippa Tyrell , Craig Smith , Anand Dixit , Stephen Louw , David Broughton , Ashit Shetty , Jason Appleton , Nikola Sprigg , Boris Raul Acosta , Cecile van Eendenburg , Joaquin Serena Leal , Maria Del Mar Castellanos Rodrigo , Mikel Terceno Izaga , Olga Belchí Guillamon , Juan Arenillas , Ana Calleja , Elisa Cortijo , Patricia Mulero , Natalia Pérez de la Ossa , Alicia Garrido , Alicia Martinez , Carlos García Esperón , Cristina Guerrero , David Carrera , Dolores Vilas , Elena Lopez-Cancio , Ernest Palomeras , Giuseppe Lucente , Meritxell Gomis , Irina Isern , Juan Becerra , Jose Hervas Vicente , Josep Sánchez , Laura Dorado , Laia Grau , Lourdes Ispierto , Luis Prats , Miriam Almendrote , María Hernández , Marta Jimenez , Manuel Lozano Sánchez , Monica Millán Torne , Silvia Presas , Xavier Ustrell , Anna Pellisé , Irene Navalpotro , Alain Luna , Wouter Schonewille , Paul Nederkoorn , Charles Majoie , Lucie van den Berg , Sophie van den Berg , Thomas Zonneveld , Michel Remmers , Franz Fazekas , Alexander Pichler , Simon Fandler , Thomas Gattringer , Johannes Mutzenbach , Jörg Weber , Elmar Höfner , Heinz Kohlfürst , Karin Weinstich , Lars Kellert , Anna Bayer-Karpinska , Christian Opherk , Frank Wollenweber , Matthias Klein , Tobias Neumann- Haefelin , Alexandra Pierskalla , Andreas Harloff , Jürgen Bardutzky , Florian Buggle , Jörg von Schrader , Rainer Kollmar , Josef Schill , Anna-Mareike Löbbe , Thierry Moulin , Benjamin Bouamra , Louise Bonnet , Emmanuel Touzé , Anne-Laure Bonnet , Emmanuel Touze , Julien Cogez , Lin Li , Sophie Guettier , Arindam Kar , Aravinth Sivagnanaratham , Olivia Geraghty , Urszula Bojaryn , Arumugam Nallasivan , Miguel Blanco Gonzales , Manuel Rodríguez-Yáñez , Jose Tembl , David Gorriz , Stefan Oberndorfer , Elisabeth Prohaska

1 UKE - Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg]
2 Biostatistiques santé
3 University Hospitals Leuven [Leuven]
4 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
5 VIB-KU-CCB - Leuven Center for Cancer Biology
6 Amsterdam UMC - Amsterdam University Medical Center
7 CarMeN - Cardiovasculaire, métabolisme, diabétologie et nutrition
8 HCL - Hospices Civils de Lyon
9 Tübingen University Hospital [Germany]
10 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
11 Hospital Dr Josep Trueta de Girona
12 UdG - Universitat de Girona
13 ISC - Instituto de Salud Carlos III [Madrid]
14 The Florey Institute of Neuroscience and Mental Health [Parkville, VIC, Australie]
15 Department of Neurology [Heidelberg, VIC, Australie]
16 Institute of Neurosciences and Psychology [Glasgow]
17 Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL]
18 CREATIS - Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé
19 Hospital Universitari de Girona Doctor Josep Trueta [Girona, Spain]

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.

Domaines: Statistiques [stat]

Bastian Cheng, Florent Boutitie, Alina Nickel, Anke Wouters, Tae-Hee Cho, et al.. Quantitative Signal Intensity in Fluid-Attenuated Inversion Recovery and Treatment Effect in the WAKE-UP Trial. Stroke, 2020, 51 (1), pp.209-215. ⟨10.1161/STROKEAHA.119.027390⟩. ⟨hal-04551489⟩