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. 2017 May 2;88(18):1701-1708.
doi: 10.1212/WNL.0000000000003890. Epub 2017 Apr 5.

Integrity of Normal-Appearing White Matter and Functional Outcomes After Acute Ischemic Stroke

Free PMC article

Integrity of Normal-Appearing White Matter and Functional Outcomes After Acute Ischemic Stroke

Mark R Etherton et al. Neurology. .
Free PMC article


Objective: To characterize the effect of white matter microstructural integrity on cerebral tissue and long-term functional outcomes after acute ischemic stroke (AIS).

Methods: Consecutive AIS patients with brain MRI acquired within 48 hours of symptom onset and 90-day modified Rankin Scale (mRS) score were included. Acute infarct volume on diffusion-weighted imaging (DWIv) and white matter hyperintensity volume (WMHv) on T2 fluid-attenuated inversion recovery MRI were measured. Median fractional anisotropy (FA), mean diffusivity, radial diffusivity, and axial diffusivity values were calculated within normal-appearing white matter (NAWM) in the hemisphere contralateral to the acute lesion. Regression models were used to assess the association between diffusivity metrics and acute cerebral tissue and long-term functional outcomes in AIS. Level of significance was set at p < 0.05 for all analyses.

Results: Among 305 AIS patients with DWIv and mRS score, mean age was 64.4 ± 15.9 years, and 183 participants (60%) were male. Median NIH Stroke Scale (NIHSS) score was 3 (interquartile range [IQR] 1-8), and median normalized WMHv was 6.19 cm3 (IQR 3.0-12.6 cm3). Admission stroke severity (β = 0.16, p < 0.0001) and small vessel stroke subtype (β = -1.53, p < 0.0001), but not diffusivity metrics, were independently associated with DWIv. However, median FA in contralesional NAWM was independently associated with mRS score (β = -9.74, p = 0.02), along with age, female sex, NIHSS score, and DWIv.

Conclusions: FA decrease in NAWM contralateral to the acute infarct is associated with worse mRS category at 90 days after stroke. These data suggest that white matter integrity may contribute to functional recovery after stroke.


Figure 1
Figure 1. Image processing steps (here shown on 3T MRI of an acute stroke patient) of deriving NAWM masks in the contralesional hemisphere
Sample FLAIR image (A), acute DWI scan depicting ischemic stroke in the right frontal operculum (B), and representative WMH mask (red) and NAWM mask (blue) overlaid on FLAIR image (C). DWI = diffusion-weighted imaging; FLAIR = fluid-attenuated inversion recovery; NAWM = normal-appearing white matter; WM = white matter; WMH = white matter hyperintensity.
Figure 2
Figure 2. WMH and infarct volume as a function of stroke subtype
Box plots of normalized WMHv (A) and normalized DWIv (B) as a function of TOAST subtype. Plots include outliers for each subtype depicted as solid circles. CE = cardioembolic; DWI = diffusion-weighted imaging; DWIv = diffusion-weighted imaging volume; LA = large artery; SV = small vessel; TOAST = Trial of Org 10172 in Acute Stroke Treatment; WMH = white matter hyperintensity; WMHv = white matter hyperintensity volume.

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