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Integrity of normal-appearing white matter and functional outcomes after acute ischemic stroke
Mark R Etherton1, Ona Wu2, Pedro Cougo2
1From the J. Philip Kistler Stroke Research Center (M.R.E., O.W., P.C., A.-K.G., L.C., K.M.F., A.S.K., G.B., H.H.K., A.L., N.S.R.), Department of Neurology, and Athinoula A. Martinos Center for Biomedical Imaging (O.W.), Department of Radiology, Massachusetts General Hospital and Harvard Medical School; Division of Neurocritical Care and Emergency Neurology (J.R.), Department of Neurology and Center for Human Genetic Research, Massachusetts General Hospital, Boston; and Department of Neurology (K.L.F.), Rhode Island Hospital, Alpert Medical School of Brown University, Providence. metherton@partners.org.
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.
Insights
White matter integrity, measured by fractional anisotropy (FA), impacts long-term recovery after acute ischemic stroke (AIS). Lower FA in normal-appearing white matter is linked to worse functional outcomes at 90 days.
Area of Science:
- Neuroscience
- Radiology
- Neurology
Background:
- Acute ischemic stroke (AIS) significantly impacts long-term patient outcomes.
- White matter microstructural integrity is increasingly recognized as a crucial factor in brain health and recovery.
- Understanding the relationship between white matter changes and functional outcomes is vital for improving stroke care.
Purpose of the Study:
- To investigate the association between white matter microstructural integrity and cerebral tissue outcomes.
- To determine the effect of white matter integrity on long-term functional recovery after AIS.
- To explore specific white matter diffusion metrics and their correlation with stroke severity and outcomes.
Main Methods:
- Inclusion of consecutive AIS patients with brain MRI within 48 hours of symptom onset and 90-day modified Rankin Scale (mRS) scores.
- Measurement of acute infarct volume (DWIv) and white matter hyperintensity volume (WMHv).
- Calculation of median fractional anisotropy (FA) and other diffusivity metrics in normal-appearing white matter (NAWM) contralateral to the lesion, using regression models to assess associations.
Main Results:
- Among 305 AIS patients, admission stroke severity and small vessel stroke subtype were associated with infarct volume (DWIv).
- Diffusivity metrics were not independently associated with DWIv.
- However, decreased FA in contralesional NAWM was independently associated with worse 90-day mRS scores, alongside age, sex, NIHSS score, and DWIv.
Conclusions:
- Reduced FA in normal-appearing white matter contralateral to the infarct is linked to poorer functional outcomes (mRS) at 90 days post-stroke.
- These findings highlight the role of white matter integrity in stroke recovery.
- White matter microstructural integrity may be a significant predictor of functional recovery after AIS.