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

Background and objectivesIt 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.MethodsSeven 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.ResultsData 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).ConclusionsWithin 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

A composite robotic-based measure of upper limb proprioception

Abstract Background Proprioception is the sense of the position and movement of our limbs, and is vital for executing coordinated movements. Proprioceptive disorders are common following stroke, but clinical tests for measuring impairments in proprioception are simple ordinal scales that are unreliable and relatively crude. We developed and validated specific kinematic parameters to quantify proprioception and compared two common metrics, Euclidean and Mahalanobis distances, to combine these parameters into an overall summary score of proprioception. Methods We used the KINARM robotic exoskeleton to assess proprioception of the upper limb in subjects with stroke (N = 285. Mean days post-stroke = 12 ± 15). Two aspects of proprioception (position sense and kinesthetic sense) were tested using two mirror-matching tasks without vision. The tasks produced 12 parameters to quantify position sense and eight to quantify kinesthesia. The Euclidean and Mahalanobis distances of the z-scores for these parameters were computed each for position sense, kinesthetic sense, and overall proprioceptive function (average score of position and kinesthetic sense). Results A high proportion of stroke subjects were impaired on position matching (57%), kinesthetic matching (65%), and overall proprioception (62%). Robotic tasks were significantly correlated with clinical measures of upper extremity proprioception, motor impairment, and overall functional independence. Composite scores derived from the Euclidean distance and Mahalanobis distance showed strong content validity as they were highly correlated (r = 0.97–0.99). Conclusions We have outlined a composite measure of upper extremity proprioception to provide a single continuous outcome measure of proprioceptive function for use in clinical trials of rehabilitation. Multiple aspects of proprioception including sense of position, direction, speed, and amplitude of movement were incorporated into this measure. Despite similarities in the scores obtained with these two distance metrics, the Mahalanobis distance was preferred