A systematic review of early neuroimaging and neurophysiological biomarkers for post-stroke mobility prognostication

BackgroundAccurate prognostication of mobility outcomes is essential to guide rehabilitation and manage patient expectations. The prognostic utility of neuroimaging and neurophysiological biomarkers remains uncertain when measured early post-stroke. This systematic review aimed to examine the prognostic capacity of early neuroimaging and neurophysiological biomarkers of mobility outcomes up to 24-months post-stroke. MethodsMEDLINE and EMBASE were searched from inception to June 2025. Cohort studies that reported neuroimaging or neurophysiological biomarkers measured [≤]14-days post-stroke and mobility outcome(s) assessed >14-days and [≤]24-months post-stroke were included. Biomarker analyses were classified by statistical analysis approach (association, discrimination/classification or validation). Magnitude of relevant statistical measures was used as the primary indicator of prognostic capacity. Risk of bias was assessed using the Quality in Prognostic Studies tool. Meta-analysis was not performed due to heterogeneity. ResultsTwenty reports from 18 independent study samples (n=2,160 participants) were included. Biomarkers were measured a median 7.5-days post-stroke, and outcomes were assessed between 1- and 12-months. Eighty-six biomarker analyses were identified (61 neuroimaging, 25 neurophysiological) and the majority used an association approach (88%). Few used discrimination/classification methods (11%), and only one conducted internal validation (1%); an MRI-based machine learning model which demonstrated excellent discrimination but still requires external validation. Structural and functional corticospinal tract integrity were frequently investigated, and most associations were small or non-significant. Lesion location and size were also commonly examined, but findings were inconsistent and often lacked magnitude reporting. Methodological limitations were common, including small sample sizes, moderate to high risk of bias, poor reporting of magnitudes, and heterogeneous outcome measures and follow-up time points. ConclusionsCurrent evidence provides limited support for early neuroimaging and neurophysiological biomarkers to prognosticate post-stroke mobility outcomes. Most analyses remain at the association stage, with minimal progress toward validation and clinical implementation. Advancing the field requires international collaboration using harmonized methodologies, standardised statistical reporting, and consistent outcome measures and timepoints. RegistrationURL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42022350771.