Integrity of normal-appearing white matter and functional outcomes after acute ischemic stroke

Objective: To characterize the influence of white matter microstructural integrity on acute ischemic stroke (AIS) outcomes. Background: In AIS, white matter hyperintensity (WMH) burden is associated with worse tissue and functional outcomes. A growing body of evidence suggests that microstructural injury to normal appearing WM (NAWM) is also associated with clinical phenotypes and could impact stroke outcomes. We hypothesized that, in patients with AIS, diffusivity anisotropy metrics of NAWM microstructural integrity in the contralesional hemisphere will be predictive of acute ischemic tissue and long-term functional outcomes. Design/Methods: Consecutive AIS patients with brain MRI acquired within 48 hours of symptom onset and 3–6 month modified Rankin scale (mRS) score were included. Acute infarct volume on diffusion-weighted imaging (DWIv), and white matter hyperintensity volume (WMHv) on T2 FLAIR MRI were measured. Median fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) values were calculated in contralesional NAWM. Regression models were used to assess the association between diffusivity metrics and DWIv and mRS. Results: Among 319 AIS with DWIv and mRS, mean age was 64.9 ±15.9 years and 188 subjects (59%) were male. Median NIHSS was 3 (interquartile range [IQR] 1–9) and median normalized WMHv (nWMHv) was 6.34 cm3 (IQR 3.0– 12.7). Admission NIHSS (β 0.16, p Conclusions: Independent of WMH severity, FA decrease in NAWM contralateral to the acute infarct predicts worse mRS category at 90 days post-stroke. These data suggest that measuring white matter integrity has added value in prediction of functional outcome post-stroke. Disclosure: Dr. Etherton has nothing to disclose. Dr. Wu has received (royalty or license fee or contractual rights) payments from GE, Siemens, and Olea Medical. Dr. Cougo has nothing to disclose. Dr. Giese has nothing to disclose. Dr. Cloonan has nothing to disclose. Dr. Fitzpatrick has nothing to disclose. Dr. Kanakis has nothing to disclose. Dr. Boulouis has nothing to disclose. Dr. Karadeli has nothing to disclose. Dr. Lauer has nothing to disclose. Dr. Rosand has received personal compensation for activities with Pfizer as a member of the Data Safety Monitoring Board. Dr. Furie has received personal compensation for activities with Pfizer as a data safety and monitoring board member. Dr. Furie has received personal compensation in an editorial capacity for Up-To-Date and the Journal of Neurology, Neurosurgery & Psychiatry. Dr. Rost has received personal compensation for activities with Genzyme, Omniox, Broadview Ventures and CardioNet as a consult and Merck for serving on the clinical events committee. Dr. Rost has received personal compensation in an editorial capacity for Current Treatment Options in Cardiovascular Disease.