Spectroscopic Biomarkers of Motor Cortex Developmental Plasticity in Hemiparetic Children After Perinatal Stroke

Overview

Journal Hum Brain Mapp

Publisher Wiley

Specialty Neurology

Date 2016 Nov 19

PMID 27859933

Citations 11

Authors

Helen L Carlson

Frank P MacMaster

Ashley D Harris

Adam Kirton

Affiliations

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Abstract

Perinatal stroke causes hemiparetic cerebral palsy and lifelong motor disability. Bilateral motor cortices are key hubs within the motor network and their neurophysiology determines clinical function. Establishing biomarkers of motor cortex function is imperative for developing and evaluating restorative interventional strategies. Proton magnetic resonance spectroscopy (MRS) quantifies metabolite concentrations indicative of underlying neuronal health and metabolism in vivo. We used functional magnetic resonance imaging (MRI)-guided MRS to investigate motor cortex metabolism in children with perinatal stroke. Children aged 6-18 years with MRI-confirmed perinatal stroke and hemiparetic cerebral palsy were recruited from a population-based cohort. Metabolite concentrations were assessed using a PRESS sequence (3T, TE = 30 ms, voxel = 4 cc). Voxel location was guided by functional MRI activations during finger tapping tasks. Spectra were analysed using LCModel. Metabolites were quantified, cerebral spinal fluid corrected and compared between groups (ANCOVA) controlling for age. Associations with clinical motor performance (Assisting Hand, Melbourne, Box-and-Blocks) were assessed. Fifty-two participants were studied (19 arterial, 14 venous, 19 control). Stroke participants demonstrated differences between lesioned and nonlesioned motor cortex N-acetyl-aspartate [NAA mean concentration = 10.8 ± 1.9 vs. 12.0 ± 1.2, P < 0.01], creatine [Cre 8.0 ± 0.9 vs. 7.4 ± 0.9, P < 0.05] and myo-Inositol [Ins 6.5 ± 0.84 vs. 5.8 ± 1.1, P < 0.01]. Lesioned motor cortex NAA and creatine were strongly correlated with motor performance in children with arterial but not venous strokes. Interrogation of motor cortex by fMRI-guided MRS is feasible in children with perinatal stroke. Metabolite differences between hemispheres, stroke types and correlations with motor performance support functional relevance. MRS may be valuable in understanding the neurophysiology of developmental neuroplasticity in cerebral palsy. Hum Brain Mapp 38:1574-1587, 2017. © 2016 Wiley Periodicals, Inc.

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References

Rae C . A guide to the metabolic pathways and function of metabolites observed in human brain 1H magnetic resonance spectra. Neurochem Res. 2013; 39(1):1-36. DOI: 10.1007/s11064-013-1199-5. View

Craciunas S, Brooks W, Nudo R, Popescu E, Choi I, Lee P . Motor and premotor cortices in subcortical stroke: proton magnetic resonance spectroscopy measures and arm motor impairment. Neurorehabil Neural Repair. 2013; 27(5):411-20. PMC: 3943339. DOI: 10.1177/1545968312469835. View

Shu S, Ashwal S, Holshouser B, NYSTROM G, Hinshaw Jr D . Prognostic value of 1H-MRS in perinatal CNS insults. Pediatr Neurol. 1998; 17(4):309-18. DOI: 10.1016/s0887-8994(97)00140-9. View

Dani K, Warach S . Metabolic imaging of ischemic stroke: the present and future. AJNR Am J Neuroradiol. 2014; 35(6 Suppl):S37-43. DOI: 10.3174/ajnr.A3789. View

Yassi N, Campbell B, Moffat B, Steward C, Churilov L, Parsons M . Association between baseline peri-infarct magnetic resonance spectroscopy and regional white matter atrophy after stroke. Neuroradiology. 2015; 58(1):3-10. DOI: 10.1007/s00234-015-1593-6. View

Raju T, Nelson K, Ferriero D, Lynch J . Ischemic perinatal stroke: summary of a workshop sponsored by the National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke. Pediatrics. 2007; 120(3):609-16. DOI: 10.1542/peds.2007-0336. View

Wyss M, Schulze A . Health implications of creatine: can oral creatine supplementation protect against neurological and atherosclerotic disease?. Neuroscience. 2002; 112(2):243-60. DOI: 10.1016/s0306-4522(02)00088-x. View

Lynch J . Epidemiology and classification of perinatal stroke. Semin Fetal Neonatal Med. 2009; 14(5):245-9. DOI: 10.1016/j.siny.2009.07.001. View

Fonov V, Evans A, Botteron K, Almli C, McKinstry R, Collins D . Unbiased average age-appropriate atlases for pediatric studies. Neuroimage. 2010; 54(1):313-27. PMC: 2962759. DOI: 10.1016/j.neuroimage.2010.07.033. View

10.

Krumlinde-Sundholm L, Holmefur M, Kottorp A, Eliasson A . The Assisting Hand Assessment: current evidence of validity, reliability, and responsiveness to change. Dev Med Child Neurol. 2007; 49(4):259-64. DOI: 10.1111/j.1469-8749.2007.00259.x. View

11.

Albers G, Thijs V, Wechsler L, Kemp S, Schlaug G, Skalabrin E . Magnetic resonance imaging profiles predict clinical response to early reperfusion: the diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study. Ann Neurol. 2006; 60(5):508-517. DOI: 10.1002/ana.20976. View

12.

Jones P, Borich M, Vavsour I, Mackay A, Boyd L . Cortical thickness and metabolite concentration in chronic stroke and the relationship with motor function. Restor Neurol Neurosci. 2016; 34(5):733-46. PMC: 5179035. DOI: 10.3233/RNN-150623. View

13.

Brand A, Richter-Landsberg C, Leibfritz D . Multinuclear NMR studies on the energy metabolism of glial and neuronal cells. Dev Neurosci. 1993; 15(3-5):289-98. DOI: 10.1159/000111347. View

14.

Bourke-Taylor H . Melbourne Assessment of Unilateral Upper Limb Function: construct validity and correlation with the Pediatric Evaluation of Disability Inventory. Dev Med Child Neurol. 2003; 45(2):92-6. View

15.

Eliasson A, Krumlinde-Sundholm L, Rosblad B, Beckung E, Arner M, Ohrvall A . The Manual Ability Classification System (MACS) for children with cerebral palsy: scale development and evidence of validity and reliability. Dev Med Child Neurol. 2006; 48(7):549-54. DOI: 10.1017/S0012162206001162. View

16.

Cirstea C, Brooks W, Craciunas S, Popescu E, Choi I, Lee P . Primary motor cortex in stroke: a functional MRI-guided proton MR spectroscopic study. Stroke. 2011; 42(4):1004-9. PMC: 3266712. DOI: 10.1161/STROKEAHA.110.601047. View

17.

Kirton A, Armstrong-Wells J, Chang T, deVeber G, Rivkin M, Hernandez M . Symptomatic neonatal arterial ischemic stroke: the International Pediatric Stroke Study. Pediatrics. 2011; 128(6):e1402-10. DOI: 10.1542/peds.2011-1148. View

18.

Provencher S . Automatic quantitation of localized in vivo 1H spectra with LCModel. NMR Biomed. 2001; 14(4):260-4. DOI: 10.1002/nbm.698. View

19.

Kobayashi M, Takayama H, Suga S, Mihara B . Longitudinal changes of metabolites in frontal lobes after hemorrhagic stroke of basal ganglia: a proton magnetic resonance spectroscopy study. Stroke. 2001; 32(10):2237-45. DOI: 10.1161/hs1001.096621. View

20.

Eyre J . Corticospinal tract development and its plasticity after perinatal injury. Neurosci Biobehav Rev. 2007; 31(8):1136-49. DOI: 10.1016/j.neubiorev.2007.05.011. View