Observational Study of Neuroimaging Biomarkers of Severe Upper Limb Impairment After Stroke

Kathryn S. Hayward, Jennifer K. Ferris, Keith R. Lohse, Michael R. Borich, Alexandra Borstad, Jessica M. Cassidy, Steven C. Cramer, Sean P. Dukelow, Sonja E. Findlater, Rachel L. Hawe, Sook Lei Liew, Jason L. Neva, Jill C. Stewart, Lara A. Boyd

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


BACKGROUND AND OBJECTIVES: It is difficult to predict post-stroke outcome for people with severe motor impairment, as both clinical tests and corticospinal tract (CST) microstructure may not reliably indicate severe motor impairment. Here, we test whether imaging biomarkers beyond the CST relate to severe upper limb impairment post-stroke by evaluating white matter microstructure in the corpus callosum (CC). In an international, multisite hypothesis-generating observational study we determined if: a) CST asymmetry index can differentiate between individuals with mild-moderate and severe upper limb impairment; and b) CC biomarkers relate to upper limb impairment within individuals with severe impairment post-stroke. We hypothesised that CST asymmetry index would differentiate between mild-moderate and severe impairment, but CC microstructure would relate to motor outcome for individuals with severe upper limb impairment.

METHODS: Seven cohorts with individual diffusion imaging and motor impairment (Fugl Meyer-Upper Limb) data were pooled. Hand-drawn regions-of-interest were used to seed probabilistic tractography for CST (ipsilesional/contralesional) and CC (prefrontal/premotor/motor/sensory/posterior) tracts. Our main imaging measure was mean fractional anisotropy. Linear mixed-effect regression explored relationships between candidate biomarkers and motor impairment, controlling for observations nested within cohorts, as well as age, sex, time post-stroke and lesion volume.

RESULTS: Data from 110 individuals (30 mild-moderate, 80 with severe motor impairment) were included. In the full sample, greater CST asymmetry index (i.e., lower fractional anisotropy in the ipsilesional hemisphere, p<.001) and larger lesion volume (p=.139) were negatively related to impairment. In the severe subgroup, CST asymmetry index was not reliably associated with impairment across models. Instead, lesion volume and CC microstructure explained impairment in the severe group beyond CST asymmetry index (p's<.010).

CONCLUSIONS: Within a large cohort of individuals with severe upper limb impairment, CC microstructure related to motor outcome post-stroke. Our findings demonstrate that CST microstructure does relate to upper limb outcome across the full range of motor impairment but was not reliably associated within the severe subgroup. Therefore, CC microstructure may provide a promising biomarker for severe upper limb outcome post-stroke, which may advance our ability to predict recovery in people with severe motor impairment after stroke.

Original languageEnglish (US)
Pages (from-to)E402-E413
Issue number4
StatePublished - Jul 26 2022

Bibliographical note

Funding Information:
M.R. Borich: NIH K12 HD055931. A. Borstad: AHA-Scientist Development Grant—PI Lynne Gauthier, ALB Co-I. L.A. Boyd: CIHR MOP-106651; Heart and Stroke Foundation of Canada/Centre for Stroke Recovery. J.C. Stewart: NIH R03 HD087481 and American Heart Association 15SDG24970011. J. M. Cassidy: NIH R00 HD091375, T32 AR047752-11A1. S.C. Cramer: NIH grants: K24 HD074722, R01 NS059909. S. Dukelow: CIHR MOP-106662. K.S. Hayward: NHMRC 1088449, MSFHR 11590. S.L. Liew: NIH grants: R01 NR105591, K01 HD091283.

Funding Information:
The Florey Institute of Neuroscience and Mental Health acknowledges strong support from the Victorian Government and in particular funding from an Operational Infrastructure Support Grant. Coauthor Sonja E. Findlater, PhD, died March 12, 2019.

Publisher Copyright:
© American Academy of Neurology.


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