Excessive White Matter Hyperintensity Increases Susceptibility to Poor Functional Outcomes After Acute Ischemic Stroke
Authors: Hong Sungmin , Giese Anne-Katrin , Schirmer Markus D. , Bonkhoff Anna K. , Bretzner Martin , Rist Pamela , Dalca Adrian V. , Regenhardt Robert W. , Etherton Mark R. , Donahue Kathleen L. , Nardin Marco , Mocking Steven J. T. , McIntosh Elissa C. , Attia John , Benavente Oscar R. , Cole John W. , Donatti Amanda , Griessenauer Christoph J. , Heitsch Laura , Holmegaard Lukas , Jood Katarina , Jimenez-Conde Jordi , Roquer Jaume , Kittner Steven J. , Lemmens Robin , Levi Christopher R. , McDonough Caitrin W. , Meschia James F. , Phuah Chia-Ling , Rolfs Arndt , Ropele Stefan , Rosand Jonathan , Rundek Tatjana , Sacco Ralph L. , Schmidt Reinhold , Enzinger Christian , Sharma Pankaj , Slowik Agnieszka , Sousa Alessandro , Stanne Tara M. , Strbian Daniel , Tatlisumak Turgut , Thijs Vincent , Vagal Achala , Wasselius Johan , Woo Daniel , Zand Ramin , McArdle Patrick F. , Worrall Bradford B. , Wu Ona , Jern Christina , Lindgren Arne G. , Maguire Jane , Tomppo Liisa , Golland Polina , Rost Natalia S. ,   The MRI-GENIE and GISCOME Investigators and the International Stroke Genetics Consortium
Published: September 2021

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 &lt; 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 &lt; 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 &lt; 0.01 and OR = 0.61, 95% CI: (0.42, 0.87), p &lt; 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.