Stroke Lesions in a Large Upper Limb Rehabilitation Trial Cohort Rarely Match Lesions in Common Preclinical Models

Abstract

Background. Stroke patients with mild-moderate upper extremity motor impairments and minimal sensory and cognitive deficits provide a useful model to study recovery and improve rehabilitation. Laboratory-based investigators use lesioning techniques for similar goals. Objective. To determine whether stroke lesions in an upper extremity rehabilitation trial cohort match lesions from the preclinical stroke recovery models used to drive translational research. Methods. Clinical neuroimages from 297 participants enrolled in the Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE) study were reviewed. Images were characterized based on lesion type (ischemic or hemorrhagic), volume, vascular territory, depth (cortical gray matter, cortical white matter, subcortical), old strokes, and leukoaraiosis. Lesions were compared with those of preclinical stroke models commonly used to study upper limb recovery. Results. Among the ischemic stroke participants, median infarct volume was 1.8 mL, with most lesions confined to subcortical structures (61%) including the anterior choroidal artery territory (30%) and the pons (23%). Of ICARE participants, <1% had lesions resembling proximal middle cerebral artery or surface vessel occlusion models. Preclinical models of subcortical white matter injury best resembled the ICARE population (33%). Intracranial hemorrhage participants had small (median 12.5 mL) lesions that best matched the capsular hematoma preclinical model. Conclusions. ICARE subjects are not representative of all stroke patients, but they represent a clinically and scientifically important subgroup. Compared with lesions in general stroke populations and widely studied animal models of recovery, ICARE participants had smaller, more subcortically based strokes. Improved preclinical-clinical translational efforts may require better alignment of lesions between preclinical and human stroke recovery models.