Neurodegeneration of the Substantia Nigra after Ipsilateral Infarct: MRI R2*Mapping and Relationship to Clinical Outcome

Background: The substantia nigra (SN) is suspected to be affected after remote infarction, in view of its large array of connections with the supratentorial brain. Whether secondary involvement of SN worsens overall clinical outcome after a supratentorial stroke has not previously been studied. Purpose: To assess longitudinal changes in SN R2* by using MRI in the setting of ipsilesional supratentorial infarct and the relationship of SN signal change to clinical outcome. Materials and Methods: Participants prospectively included from 2012 to 2015 were evaluated at 24-72 hours (baseline visit) and at 1 year with MRI to quantify R2*. The SN was segmented bilaterally to calculate an R2* asymmetry index (SN-AI); greater SN-AI indicated greater relative R2* in the ipsilateral compared with contralateral SN. The 95th percentile of R2* (hereafter, SN-AI 95) was compared according to infarct location with mixed linear regression models. We also conducted voxel-based comparisons of R2* and identified individual infarcted voxels associated with high SN-AI 95 through voxel-based lesion-symptom mapping. Multivariable regression models tested the association between SN-AI 95 and clinical scores. Results: A total of 181 participants were evaluated (127 men, 54 women; mean age 6 standard deviation, 64.2 years 6 13.1; 75 striatum infarcts, 106 other locations). Visual inspection, SN-AI 95, and average maps consistently showed higher SN R2* at 1 year if ipsilateral striatum was infarcted than if it was not (SN-AI 95, 4.25 vs 20.88; P < .001), but this was not observed at baseline. The striatal location of the infarct was associated with higher SN-AI 95 at 1 year independently from infarct volume, SN-AI 95 at baseline, microbleeds, age, and sex (beta = 4.99; P < .001). Voxel-based lesion-symptom mapping confirmed that striatum but also insula, internal capsule, and external capsule were associated with higher SN-AI 95 at 1 year. SN-AI 95 was an independent contributor of poor motor outcome (Box and Block Test, beta = 2.62 points; P = .01). Conclusion: In patients with stroke, greater substantia nigra R2*, likely reflective of greater iron content, can be observed at 1 year ipsilateral from remote infarcts of specific location, which is associated with worse motor function. (c) RSNA, 2019