Cortical N-acetylaspartate concentrations are impacted in chronic stroke but do not relate to motor impairment: A magnetic resonance spectroscopy study.

Jennifer K Ferris,Kaitlin J Attard,Brian Greeley,Irene M Vavasour,Jason L Neva,Katie P Wadden,Kathryn S Hayward,Lara A Boyd,Alex L Mackay

doi:10.1002/hbm.25421

Abstract

Magnetic resonance spectroscopy (MRS) measures cerebral metabolite concentrations, which can inform our understanding of the neurobiological processes associated with stroke recovery. Here, we investigated whether metabolite concentrations in primary motor and somatosensory cortices (sensorimotor cortex) are impacted by stroke and relate to upper‐extremity motor impairment in 45 individuals with chronic stroke. Cerebral metabolite estimates were adjusted for cerebrospinal fluid and brain tissue composition in the MRS voxel. Upper‐extremity motor impairment was indexed with the Fugl‐Meyer (FM) scale. N‐acetylaspartate (NAA) concentration was reduced bilaterally in stroke participants with right hemisphere lesions (n = 23), relative to right‐handed healthy older adults (n = 15; p = .006). Within the entire stroke sample (n = 45) NAA and glutamate/glutamine (GLX) were lower in the ipsilesional sensorimotor cortex, relative to the contralesional cortex (NAA: p < .001; GLX: p = .003). Lower ipsilesional NAA was related to greater extent of corticospinal tract (CST) injury, quantified by a weighted CST lesion load (p = .006). Cortical NAA and GLX concentrations did not relate to the severity of chronic upper‐extremity impairment (p > .05), including after a sensitivity analysis imputing missing metabolite data for individuals with large cortical lesions (n = 5). Our results suggest that NAA, a marker of neuronal integrity, is sensitive to stroke‐related cortical damage and may provide mechanistic insights into cellular processes of cortical adaptation to stroke. However, cortical MRS metabolites may have limited clinical utility as prospective biomarkers of upper‐extremity outcomes in chronic stroke.

Highlights

Upper-extremity motor impairments are a significant source of chronic disability after stroke (Veerbeek, Kwakkel, van Wegen, Ket, & Heymans, 2011)
Magnetic resonance spectroscopy (MRS) is an attractive technique to investigate cortical changes poststroke, as it quantifies the concentration of cerebral metabolites in vivo
MRS can directly assess the neurometabolic correlates of changes in cortical structure or function, which stands to increase our understanding of the neurobiological consequences of injury to the corticospinal tract (CST) and processes underpinning stroke recovery

Summary

| INTRODUCTION

Upper-extremity motor impairments are a significant source of chronic disability after stroke (Veerbeek, Kwakkel, van Wegen, Ket, & Heymans, 2011). Previous MRS studies in individuals with chronic stroke (>6 months poststroke) measured cerebral metabolite concentrations from primary and secondary sensorimotor cortices, which contribute to upper-extremity sensorimotor function (Carlson, MacMaster, Harris, & Kirton, 2017; Cirstea et al, 2011; Craciunas et al, 2013; Jones, Borich, Vavasour, Mackay, & Boyd, 2016) Findings from these studies have generally been congruent with hypothesized patterns of cortical neurochemical changes in chronic stroke, based on inference from other neuroimaging and noninvasive brain stimulation modalities (Auriat et al, 2015). We explored changes to four other cerebral metabolites (GLX, myo-inositol, creatine, and choline) without specific hypotheses about the direction of stroke-related effects

| Participants

| RESULTS

Findings

| DISCUSSION