Changes in spectroscopic biomarkers after transcranial direct current stimulation in children with perinatal stroke.

Helen L Carlson, Patrick Ciechanski, Ashley D Harris, Frank P MacMaster, Adam Kirton

Journal: Brain stimulation 2018;11(1):94-103

PMID: 28958737

Full Text on Elsevier Science View on PubMed

Abstract

BACKGROUND

Perinatal stroke causes lifelong motor disability, affecting independence and quality of life. Non-invasive neuromodulation interventions such as transcranial direct current stimulation (tDCS) combined with intensive therapy may improve motor function in adult stroke hemiparesis but is under-explored in children. Measuring cortical metabolites with proton magnetic resonance spectroscopy (MRS) can inform cortical neurobiology in perinatal stroke but how these change with neuromodulation is yet to be explored.

METHODS

A double-blind, sham-controlled, randomized clinical trial tested whether tDCS could enhance intensive motor learning therapy in hemiparetic children. Ten days of customized, goal-directed therapy was paired with cathodal tDCS over contralesional primary motor cortex (M1, 20 min, 1.0 mA, 0.04 mA/cm) or sham. Motor outcomes were assessed using validated measures. Neuronal metabolites in both M1s were measured before and after intervention using fMRI-guided short-echo 3T MRS.

RESULTS

Fifteen children [age(range) = 12.1(6.6-18.3) years] were studied. Motor performance improved in both groups and tDCS was associated with greater goal achievement. After cathodal tDCS, the non-lesioned M1 showed decreases in glutamate/glutamine and creatine while no metabolite changes occurred with sham tDCS. Lesioned M1 metabolite concentrations did not change post-intervention. Baseline function was highly correlated with lesioned M1 metabolite concentrations (N-acetyl-aspartate, choline, creatine, glutamate/glutamine). These correlations consistently increased in strength following intervention. Metabolite changes were not correlated with motor function change. Baseline lesioned M1 creatine and choline levels were associated with clinical response.

CONCLUSIONS

MRS metabolite levels and changes may reflect mechanisms of tDCS-related M1 plasticity and response biomarkers in hemiparetic children with perinatal stroke undergoing intensive neurorehabilitation.

Address: Calgary Pediatric Stroke Program, Alberta Children's Hospital, Calgary, AB, Canada; Alberta Children's Hospital Research Institute (ACHRI), Calgary, AB, Canada; Neurosciences, Alberta Children's Hospital, Calgary, AB, Canada; Department of Pediatrics, University of Calgary, Calgary, AB, Canada. Electronic address: [email protected].; Calgary Pediatric Stroke Program, Alberta Children's Hospital, Calgary, AB, Canada; Alberta Children's Hospital Research Institute (ACHRI), Calgary, AB, Canada.; Alberta Children's Hospital Research Institute (ACHRI), Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; Child and Adolescent Imaging Research (CAIR) Program, Alberta Children's Hospital, Calgary, AB, Canada; Department of Radiology, University of Calgary, Calgary, AB, Canada.; Alberta Children's Hospital Research Institute (ACHRI), Calgary, AB, Canada; Department of Pediatrics, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; Department of Psychiatry, University of Calgary, AB, Canada; The Mathison Centre for Mental Health Research and Education, University of Calgary, Calgary, AB, Canada; Child and Adolescent Imaging Research (CAIR) Program, Alberta Children's Hospital, Calgary, AB, Canada; Strategic Clinical Network for Addictions and Mental Health, Alberta Health Services, Calgary, AB, Canada.; Calgary Pediatric Stroke Program, Alberta Children's Hospital, Calgary, AB, Canada; Alberta Children's Hospital Research Institute (ACHRI), Calgary, AB, Canada; Neurosciences, Alberta Children's Hospital, Calgary, AB, Canada; Department of Pediatrics, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.

DOI: 10.1016/j.brs.2017.09.007

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MeSH Terms: Adolescent, Aspartic Acid, Biomarkers, Child, Choline, Creatinine, Double-Blind Method, Female, Glutamic Acid, Glutamine, Humans, Male, Motor Cortex, Paresis, Proton Magnetic Resonance Spectroscopy, Stroke, Transcranial Direct Current Stimulation