Validation of early prognostic data for recovery outcomes after stroke for future, higher yield trials (verify) - currently, 7 million US stroke survivors have significant disability, more than half…

Validation of early prognostic data for recovery outcomes after stroke for future, higher yield trials (verify) - currently, 7 million US stroke survivors have significant disability, more than half with residual motor deficits. Motor function, particularly of the upper extremity (UE), is critical for regaining independence after stroke. UE function largely depends on integrity of motor cortex and its descending fibers, collectively termed the corticomotor system (CMS). Validated, clinically relevant biomarkers that identify biologically distinct patient subgroups are critically needed, particularly for the often affected and functionally important CMS. Their absence is a major obstacle to developing and personalizing new recovery therapies, especially in the early days post- stroke. Presence or absence of motor evoked potential (MEP) responses to TMS and extent of MRI-measured acute lesion load involving corticospinal tract (CST) are ready for formal validation. Also, the predict recovery potential (prep)-2 prediction tool, which sequentially combines acute clinical information and MEP status, is primed for multi-site validation. Our current objective, well-aligned with strokenet's, is to validate the most biologically relevant and primed biomarkers of 90-day UE motor outcomes after ischemic stroke in the first large- scale, prospective, acute dataset of clinical, transcranial magnetic stimulation (TMS), and MRI measures. The central hypothesis is that patients have different UE outcomes depending on CMS function measured with TMS, and on CST injury measured with MRI. The proposed study, "validation of early prognostic data for recovery outcomes after stroke for future, higher yield trials" (verify), will collect data from 657 patients at 30 US sites to address the following specific aims. Aim 1: to externally validate the relationships that TMS and MRI biomarkers of CMS integrity acquired < 7 days after stroke have with UE motor impairment outcome at 90 days after ischemic stroke. Aim 2: to externally validate the PREP2 prediction tool used < 7 days after stroke to predict 90-day UE functional outcome for individual patients with ischemic stroke. Our multi-dimensional approach to UE motor outcomes is an innovative advance on previous biomarker studies, which were typically limited to predicting outcomes in one or two domains. We will comprehensively measure UE outcomes 90 days post-stroke in three domains of motor performance -impairment, function, and use - identified by the world health organization international classification of functioning, disability and health. Our cross-disciplinary team has established expertise in multicenter acute trials, neurophysiology, neuroimaging, and stroke recovery and rehabilitation. The results are expected to have a positive impact because biomarkers used in the acute stroke period to identify patient subgroups with distinct day-90 outcomes can aid stroke recovery trials and inform rehabilitation decision-making.