Frontiers in Neurology (Sep 2021)

Excessive White Matter Hyperintensity Increases Susceptibility to Poor Functional Outcomes After Acute Ischemic Stroke

  • Sungmin Hong,
  • Anne-Katrin Giese,
  • Markus D. Schirmer,
  • Markus D. Schirmer,
  • Anna K. Bonkhoff,
  • Martin Bretzner,
  • Martin Bretzner,
  • Pamela Rist,
  • Adrian V. Dalca,
  • Adrian V. Dalca,
  • Robert W. Regenhardt,
  • Mark R. Etherton,
  • Kathleen L. Donahue,
  • Marco Nardin,
  • Steven J. T. Mocking,
  • Elissa C. McIntosh,
  • John Attia,
  • John Attia,
  • Oscar R. Benavente,
  • John W. Cole,
  • Amanda Donatti,
  • Christoph J. Griessenauer,
  • Christoph J. Griessenauer,
  • Laura Heitsch,
  • Laura Heitsch,
  • Lukas Holmegaard,
  • Katarina Jood,
  • Jordi Jimenez-Conde,
  • Jaume Roquer,
  • Steven J. Kittner,
  • Robin Lemmens,
  • Robin Lemmens,
  • Christopher R. Levi,
  • Christopher R. Levi,
  • Caitrin W. McDonough,
  • James F. Meschia,
  • Chia-Ling Phuah,
  • Arndt Rolfs,
  • Stefan Ropele,
  • Jonathan Rosand,
  • Jonathan Rosand,
  • Jonathan Rosand,
  • Tatjana Rundek,
  • Ralph L. Sacco,
  • Reinhold Schmidt,
  • Christian Enzinger,
  • Pankaj Sharma,
  • Pankaj Sharma,
  • Agnieszka Slowik,
  • Alessandro Sousa,
  • Tara M. Stanne,
  • Daniel Strbian,
  • Turgut Tatlisumak,
  • Turgut Tatlisumak,
  • Vincent Thijs,
  • Vincent Thijs,
  • Achala Vagal,
  • Johan Wasselius,
  • Johan Wasselius,
  • Daniel Woo,
  • Ramin Zand,
  • Patrick F. McArdle,
  • Bradford B. Worrall,
  • Ona Wu,
  • Christina Jern,
  • Arne G. Lindgren,
  • Arne G. Lindgren,
  • Jane Maguire,
  • Liisa Tomppo,
  • Polina Golland,
  • Natalia S. Rost,
  • The MRI-GENIE and GISCOME Investigators and the International Stroke Genetics Consortium,
  • Sungmin Hong,
  • Anne-Katrin Giese,
  • Markus D. Schirmer,
  • Anna K. Bonkhoff,
  • Martin Bretzner,
  • Pamela Rist,
  • Adrian V. Dalca,
  • Robert W. Regenhardt,
  • Mark R. Etherton,
  • Kathleen L. Donahue,
  • Marco Nardin,
  • Steven J. T. Mocking,
  • Elissa C. McIntosh,
  • John Attia,
  • Oscar R. Benavente,
  • John W. Cole,
  • Amanda Donatti,
  • Christoph J. Griessenauer,
  • Laura Heitsch,
  • Lukas Holmegaard,
  • Katarina Jood,
  • Jordi Jimenez-Conde,
  • Jaume Roquer,
  • Steven J. Kittner,
  • Robin Lemmens,
  • Christopher R. 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 Slowik,
  • Alessandro Sousa,
  • Tara M. Stanne,
  • Daniel Strbian,
  • Turgut Tatlisumak,
  • Vincent Thijs,
  • Achala Vagal,
  • Johan Wasselius,
  • Daniel Woo,
  • Ramin Zand,
  • Patrick F. McArdle,
  • Bradford B. Worrall,
  • Ona Wu,
  • Christina Jern,
  • Arne G. Lindgren,
  • Jane Maguire,
  • Liisa Tomppo,
  • Polina Golland,
  • Natalia S. Rost

DOI
https://doi.org/10.3389/fneur.2021.700616
Journal volume & issue
Vol. 12

Abstract

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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.

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