Evidence for adaptive functional changes in the cerebral cortex with axonal injury from multiple sclerosis

Axonal injury occurs even in the earliest stages of multiple sclerosis, Mag netic resonance spectroscopic imaging (MRSI) measurements of brain N-acetyl aspartate (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 pat ients who had unimpaired hand function. We found that activation of the ips ilateral sensorimotor cortex with simple hand movements was increased by a mean of fivefold relative to normal controls (n = 8) and that the extent. o f this increase was strongly correlated (sigma = -0.93, P = 0.001) with dec reases in brain NAA, These results suggest that compensatory cortical adapt ive responses may help to account for the limited relationship between conv entional MRI measures of lesion burden and clinical measures of disability, and that therapies directed towards promoting cortical reorganization in r esponse to brain injury could enhance recovery from relapses of multiple sc lerosis.