title: Evidence for adaptive functional changes in the cerebral cortex with axonal injury from multiple sclerosis.
abstract: Axonal injury occurs even in the earliest stages of multiple sclerosis. Magnetic resonance spectroscopic imaging (MRSI) measurements of brain N:-acetylaspartate (NAA), a marker of axonal integrity, show that this axonal injury can occur even in the absence of clinically evident functional impairments. To test whether cortical adaptive responses contribute to the maintenance of normal motor function in patients with multiple sclerosis, we performed MRSI and functional MRI (fMRI) examinations of nine multiple sclerosis patients who had unimpaired hand function. We found that activation of the ipsilateral sensorimotor cortex with simple hand movements was increased by a mean of fivefold relative to normal controls (n = 8) and that the extent of this increase was strongly correlated (sigma = -0.93, P = 0.001) with decreases in brain NAA. These results suggest that compensatory cortical adaptive responses may help to account for the limited relationship between conventional MRI measures of lesion burden and clinical measures of disability, and that therapies directed towards promoting cortical reorganization in response to brain injury could enhance recovery from relapses of multiple sclerosis.
authors.affiliation: Centre for Functional Magnetic Resonance Imaging of the Brain, Department of Clinical Neurology, University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: H
authors.initials: H
authors.lastname: Reddy
authors.forename: S
authors.initials: S
authors.lastname: Narayanan
authors.forename: R
authors.initials: R
authors.lastname: Arnoutelis
authors.forename: M
authors.initials: M
authors.lastname: Jenkinson
authors.forename: J
authors.initials: J
authors.lastname: Antel
authors.forename: P M
authors.initials: PM
authors.lastname: Matthews
authors.forename: D L
authors.initials: DL
authors.lastname: Arnold
mesh_terms: D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism*; D001369:Axons / Q000378:metabolism / Q000473:pathology*; D005385:Fingers / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D009044:Motor Cortex / Q000473:pathology / Q000503:physiopathology*; D009068:Movement / Q000502:physiology; D009103:Multiple Sclerosis / Q000473:pathology / Q000503:physiopathology*; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology*; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology; D009473:Neuronal Plasticity / Q000502:physiology*; D020127:Recovery of Function / Q000502:physiology*
chemical_list: D001224:Aspartic Acid; C000179:N-acetylaspartate