Normal-Appearing White Matter Integrity Is a Predictor of Outcome After Ischemic Stroke.
Stroke. 2020-02-01; 51(2): 449-456
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Sagnier S(1)(2), Catheline G(1), Dilharreguy B(1), Linck PA(3), Coupé P(4), Munsch F(5), Bigourdan A(3), Debruxelles S(2), Poli M(2), Olindo S(2), Renou P(2), Rouanet F(2), Dousset V(3)(6), Berthoz S(1)(7), Tourdias T(3)(6), Sibon I(1)(2).
(1)From the UMR-5287-CNRS, Université de Bordeaux, EPHE PSL Research University, France (S.S., G.C., B.D., S.B., I.S.).
(2)CHU de Bordeaux, Unité Neuro-vasculaire, France (S.S., S.D., M.P., S.O., P.R., F.R., I.S.).
(3)CHU de Bordeaux, Neuroradiologie, France (P.-A.L., A.B., V.D., T.T.).
(4)UMR-5800-CNRS, Université de Bordeaux, LaBRI, Talence, France (P.C.).
(5)Beth Israel Deaconess Medical Center, Harvard University, Boston, MA (F.M.).
(6)INSERM-U862, Neurocentre Magendie, Bordeaux, France (V.D., T.T.).
(7)Département de Psychiatrie de l’Adolescent et du Jeune Adulte, Institut Mutualiste Montsouris, Paris, France (S.B.).
Background and Purpose- The aim of the present study was to evaluate the
relationship between normal-appearing white matter (NAWM) integrity and
postischemic stroke recovery in 4 main domains including cognition, mood, gait,
and dependency. Methods- A prospective study was conducted, including patients
diagnosed for an ischemic supratentorial stroke on a 3T brain MRI performed 24 to
72 hours after symptom onset. Clinical assessment 1 year after stroke included a
Montreal Cognitive Assessment, an Isaacs set test, a Zazzo cancelation task, a
Hospital Anxiety and Depression scale, a 10-meter walking test, and a modified
Rankin Scale (mRS). Diffusion tensor imaging parameters in the NAWM were computed
using FMRIB (Functional Magnetic Resonance Imaging of the Brain) Diffusion
Toolbox. The relationships between mean NAWM diffusion tensor imaging parameters
and the clinical scores were assessed using linear and ordinal regression
analyses, including the volumes of white matter hyperintensities, gray matter,
and ischemic stroke as radiological covariates. Results- Two hundred seven
subjects were included (66±13 years old; 67% men; median National Institutes of
Health Stroke Scale score, 3; interquartile range, 2-6). In the models including
only radiological variables, NAWM fractional anisotropy was associated with the
mRS and the cognitive scores. After adjusting for demographic confounders, NAWM
fractional anisotropy remained a significant predictor of mRS (β=-0.24; P=0.04).
Additional path analysis showed that NAWM fractional anisotropy had a direct
effect on mRS (β=-0.241; P=0.001) and a less important indirect effect mediating
white matter hyperintensity burden. Similar results were found with mean
diffusivity, axial diffusivity, and radial diffusivity. In further subgroup
analyses, a relationship between NAWM integrity in widespread white matter
tracts, mRS, and Isaacs set test was found in right hemispheric strokes.
Conclusions- NAWM diffusion tensor imaging parameters measured early after an
ischemic stroke are independent predictors of functional outcome and may be
additional markers to include in studies evaluating poststroke recovery.