Excessive White Matter Hyperintensity Increases Susceptibility to Poor Functional Outcomes After Acute Ischemic Stroke
Sung‐Min Hong, Anne‐Katrin Giese, Markus D. Schirmer, Anna K. Bonkhoff, Martin Bretzner, Pamela M. Rist, Adrian V. Dalca, Robert W. Regenhardt, Mark R. Etherton, Kathleen Donahue, Marco Nardin, Steven J. T. Mocking, Elissa C. McIntosh, John Attia, Oscar Benavente, John W. Cole, Amanda Donatti, Christoph J. Griessenauer, Laura Heitsch, Lukas Holmegaard, Katarina Jood, Jordi Jiménez-Conde, Jaume Roquer, Steven J. Kittner, Robin Lemmens, Christopher Levi, Caitrin W. McDonough, James F. Meschia, Chia‐Ling Phuah, Arndt Rolfs, Stefan Ropele, Jonathan Rosand, Tatjana Rundek, Ralph L. Sacco, Reinhold Schmidt, Christian Enzinger, Pankaj Sharma, Agnieszka Słowik, Alessandro Sousa, Tara M. Stanne, Daniel Strbian, Turgut Tatlisumak, Vincent Thijs, Achala Vagal, Johan Wassélius, Daniel Woo, Ramin Zand, Patrick F. McArdle, Bradford B. Worrall, Ona Wu, Christina Jern, Arne Lindgren, Jane Maguire, Liisa Tomppo, Polina Golland, Natalia S. Rost
Abstract
Objective: To personalize the prognostication of post-stroke outcome using MRI-detected cerebrovascular pathology, we sought to investigate the association between the excessive white matter hyperintensity (WMH) burden unaccounted for by the traditional stroke risk profile of individual patients and their long-term functional outcomes after a stroke. Methods: We included 890 patients who survived after an acute ischemic stroke from the MRI-Genetics Interface Exploration (MRI-GENIE) study, for whom data on vascular risk factors (VRFs), including age, sex, atrial fibrillation, diabetes mellitus, hypertension, coronary artery disease, smoking, prior stroke history, as well as acute stroke severity, 3- to−6-month modified Rankin Scale score (mRS), WMH, and brain volumes, were available. We defined the unaccounted WMH (uWMH) burden via modeling of expected WMH burden based on the VRF profile of each individual patient. The association of uWMH and mRS score was analyzed by linear regression analysis. The odds ratios of patients who achieved full functional independence (mRS < 2) in between trichotomized uWMH burden groups were calculated by pair-wise comparisons. Results: The expected WMH volume was estimated with respect to known VRFs. The uWMH burden was associated with a long-term functional outcome (β = 0.104, p < 0.01). Excessive uWMH burden significantly reduced the odds of achieving full functional independence after a stroke compared to the low and average uWMH burden [OR = 0.4, 95% CI: (0.25, 0.63), p < 0.01 and OR = 0.61, 95% CI: (0.42, 0.87), p < 0.01, respectively]. Conclusion: The excessive amount of uWMH burden unaccounted for by the traditional VRF profile was associated with worse post-stroke functional outcomes. Further studies are needed to evaluate a lifetime brain injury reflected in WMH unrelated to the VRF profile of a patient as an important factor for stroke recovery and a plausible indicator of brain health.