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 (UE) 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 Determine whether stroke lesions in an UE 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 MCA 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 to 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.

Compensatory Relearning Following Stroke: Cellular and Plasticity Mechanisms in Rodents

“…Despite the importance of the striatum to learning, evidence of striatal participation on stroke recovery is lacking. In addition, the majority of basic stroke research studies does not fully address the role of striatal lesions and mechanisms (Edwardson et al, 2017).…”

Is Environmental Enrichment Ready for Clinical Application in Human Post-stroke Rehabilitation?

“…Stroke is a heterogeneous disorder, affecting both sexes at all points throughout the lifespan, causing damage in diverse brain regions and an array of functional impairments (Ramsey et al, 2017 ). In contrast, preclinical rodent studies of stroke typically utilize young adult, male rats, with cortical lesions that do not represent those most commonly observed in clinical studies (Edwardson et al, 2017 ). These factors hamper the translation of preclinical stroke treatments to clinical practice, and have led to concerted international efforts to better align preclinical and clinical experimental methodologies in stroke (Bernhardt et al, 2017a ; Corbett et al, 2017 ).…”

Recovery of upper limb function is greatest early after stroke but does continue to improve during the chronic phase: a two-year, observational study

“…It is important to complete observational studies that track recovery to establish whether there is a discrepancy between capacity and performance in the long-term. To date, longitudinal tracking of recovery has largely lacked investigation of natural recovery from an acute time point post stroke (first 7-to 14-days), long-term follow up of patients beyond 3-to 6-months post stroke, and characterisation of stroke variables such as lesion type and location that may modify or interact with observed recovery profiles [7].…”