White Matter Integrity and Early Outcomes After Acute Ischemic Stroke


Chronic white matter structural injury is a risk factor for poor long-term outcomes after acute ischemic stroke (AIS). However, it is unclear how white matter structural injury predisposes to poor outcomes after AIS. To explore this question, in 42 AIS patients with moderate to severe white matter hyperintensity (WMH) burden, we characterized WMH and normal-appearing white matter (NAWM) diffusivity anisotropy metrics in the hemisphere contralateral to acute ischemia in relation to ischemic tissue and early functional outcomes. All patients underwent brain MRI with dynamic susceptibility contrast perfusion and diffusion tensor imaging within 12 h and at day 3–5 post stroke. Early neurological outcomes were measured as the change in NIH Stroke Scale score from admission to day 3–5 post stroke. Target mismatch profile, percent mismatch lost, infarct growth, and rates of good perfusion were measured to assess ischemic tissue outcomes. NAWM mean diffusivity was significantly lower in the group with early neurological improvement (ENI, 0.79 vs. 0.82 × 10−3, mm2/s; P = 0.02). In multivariable logistic regression, NAWM mean diffusivity was an independent radiographic predictor of ENI (β = − 17.6, P = 0.037). Median infarct growth was 118% (IQR 26.8–221.9%) despite good reperfusion being observed in 65.6% of the cohort. NAWM and WMH diffusivity metrics were not associated with target mismatch profile, percent mismatch lost, or infarct growth. Our results suggest that, in AIS patients, white matter structural integrity is associated with poor early neurological outcomes independent of ischemic tissue outcomes.

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This study is supported by the Statins Augment smalL Vessel function and improve stroke Outcomes (SALVO) study (NIH-NINDS 5R01NS082285).


The study was funded in part by the NIH-National Institute of Neurological Disorders and Stroke R01NS082285-01A1 (N.S.R.); National Institute of Biomedical Imaging and Bioengineering (P41EB015896); and American Heart Association 17CPOST33680102.

Author information




Mark Etherton: study concept and design, acquisition of data, analysis and interpretation of data, drafting, and critical revision of the manuscript.

Ona Wu: study concept and design, analysis and interpretation of data, critical revision of the manuscript for intellectual content.

Anne-Katrin Giese: analysis and interpretation of data, critical revision of the manuscript for intellectual content.

Arne Lauer; acquisition of data, critical revision of the manuscript for intellectual content.

Gregoire Boulouis: acquisition of data, critical revision of the manuscript for intellectual content.

Brittany Mills: acquisition of data.

Lisa Cloonan: acquisition of data.

Kathleen L. Donahue: acquisition of data.

William Copen: study concept and design, critical revision of the manuscript for intellectual content.

Pamela Schaefer: study concept and design, critical revision of the manuscript for intellectual content.

Natalia S. Rost: study concept and design, analysis and interpretation of data, critical revision of the manuscript for intellectual content.

Corresponding author

Correspondence to Mark R. Etherton.

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Conflict of Interest

Mark R. Etherton is in part supported by the American Heart Association (17CPOST33680102). Ona Wu is in part supported by NIH Health (P50NS051343, R01NS082285, R01NS086905) and NIBIB (P41EB015896). Anne-Katrin Giese reports no disclosures. Arne Lauer reports no disclosures. Gregoire Boulouis reports no disclosures. Brittany Mills reports no disclosures. Lisa Cloonan reports no disclosures. Kathleen L. Donahue reports no disclosures. William Copen reports no disclosures. Pamela Schaefer reports no disclosures. Natalia S. Rost is in part supported by the NIH-NINDS R01NS082285 and R01NS086905.

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Etherton, M.R., Wu, O., Giese, A. et al. White Matter Integrity and Early Outcomes After Acute Ischemic Stroke. Transl. Stroke Res. 10, 630–638 (2019). https://doi.org/10.1007/s12975-019-0689-4

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  • Ischemic stroke
  • Leukoaraiosis
  • Diffusion tensor imaging
  • Stroke outcomes