Reperfusion Failure after successful thrombectomy of large vessel occlusion (LVO) stroke: clinical and imaging evidence

Massimo Barbagallo^1,2*Malin Zahn^1,2Josua Zimmermann^3,4Robert Klövekorn^1,2Jeremia Held^1,2Bence Nemeth^5,6Benno Reolon^1,7Jacopo Bellomo^1,8Anne Schwarz⁹Janne Marieke Veerbeek¹⁰Christiaan Hendrik Bas Van Niftrik^1,11Martina Sebök^1,11Marco Piccirelli^1,7Lars Michels^1,7Andreas R Luft^1,12,2Zsolt Kulcsar^1,11Luca Regli^1,11Giuseppe Esposito^1,11Jorn Fierstra^1,11Patrick Thurner^1,7Tilman Schubert^1,7Susanne Wegener^1,2

• ¹Clinical Neuroscience Center, University of Zurich, Zürich, Switzerland
• ²UniversitatsSpital Zurich Neurologische Klinik, Zürich, Switzerland
• ³University Hospital Zürich, Zurich, Switzerland
• ⁴Lake Lucerne Institute AG, Vitznau, Switzerland
• ⁵Medizinische Universitat Wien Universitatsklinik fur Radiologie und Nuklearmedizin, Vienna, Austria
• ⁶Pazmany Peter Katolikus Egyetem Informacios Technologiai es Bionikai Kar, Budapest, Hungary
• ⁷UniversitatsSpital Zurich Klinik fur Neuroradiologie, Zürich, Switzerland
• ⁸University Hospital Zurich Department of Neurosurgery, Zürich, Switzerland
• ⁹Department of Neurology, David Geffen School of Medicine at University of California, Los Angeles, United States, Los Angeles, United States
• ¹⁰Clinic for Neurology and Neurorehabilitation, Cantonal Hospital of Lucerne, University Teaching and Research Hospital, and University of Lucerne, Switzerland, Lucerne, Switzerland
• ¹¹University Hospital Zurich Department of Neurosurgery, Zurich, Switzerland
• ¹²Cereneo Center for Neurology and Rehabilitation, Vitznau, Switzerland, Vitznau, Switzerland

Introduction Reperfusion failure (RF) describes a condition in which patients suffering a large vessel occlusion (LVO) stroke present insufficient tissue reperfusion and recovery despite optimal mechanical thrombectomy (MT) results. Approximately 50% of patients suffering from LVO are affected. Our current understanding of the underlying pathomechanisms is limited and mostly based on rodent models. The goal of this study was to further characterize RF by applying advanced multimodal hemodynamic imaging in stroke patients. Methods Patients from the IMPreST study with LVO stroke and successful recanalization (corresponding to thrombolysis in cerebral ischemia grade (TICI) 2b-3) were included. Follow-ups with blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) and non-invasive optimal vessel analysis (NOVA) were performed (<72hours, 7days and 90days). Demographic and clinical data (NIHSS and mRS) were collected. Results Of the 49 patients included in IMPreST, 18 patients met the inclusion criteria. Based on the perfusion weighted imaging (PWI) of the affected area compared to the contralateral side after MT, patients were stratified into three groups: hypoperfusion (n= 3), normalization (n= 8), and hyperperfusion (n= 7). The hyperperfusion group tended to show poorest clinical outcome (mRS 3months: 2.5 [Q1-Q3 2.0-3.0] vs. normalization: 1 [Q1-Q3 0.75-3.0], p=0.169) and had significantly lower BOLD-CVR values at visit one and two compared to hypoperfusion and normalization group, indicating impaired cerebrovascular reactivity (visit1 hyperperfusion group -0.01 [Q1-Q3 -0.02 – 0.07], normalization group 0.12 [0.09, 0.19], hypoperfusion group, 0.09 [0.09, 0.11] p=0.049, visit2 hyperperfusion group 0.07 [Q1-Q3 0.03-0.10], normalization group 0.17 [0.16, 0.18], hypoperfusion group 0.10 [0.09, 0.11], p= 0.014). Discussion We found three patterns of reperfusion after successful MT of LVO stroke: normalization, hypo- and hyperperfusion of the ischemic area on days at < 72h after stroke. There was substantial inhomogeneity in perfusion and clinical outcomes between the three groups. Next to poorest clinical outcome, the hyperperfusion-group showed poorest cerebrovascular reserve, reflecting findings of RF in rodent models. Thus, we suggest that RF includes both hypo- as well as hyperperfusion. Early detection using advanced imaging would allow a better identification of patients at risk for poor clinical outcome.