Brain, Vol. 122, No. 10, 1933-1939,
October 1999
© 1999 Oxford University Press
In vivo evidence for axonal dysfunction remote from focal cerebral demyelination of the type seen in multiple sclerosis
1 Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, Quebec, Canada, 2 Institute of Neurological Sciences, Neurometabolic Unit, University of Siena, Italy and 3 Centre for Functional Magnetic Resonance Imaging of the Brain, Department of Clinical Neurology, University of Oxford, UK
Correspondence to:
Dr Douglas L. Arnold, Montreal Neurological Institute, 3801 University Street, Montreal, Quebec, Canada H3A 2B4
To test for axonal damage or dysfunction in white matter tracts remote from acute demyelinating lesions, we used brain proton magnetic resonance spectroscopic imaging to measure changes in N-acetyl aspartate (NAA), an index of neuronal integrity, in the white matter of the normal-appearing hemisphere of three patients with large, solitary brain demyelinating lesions of the type seen early in multiple sclerosis. During the acute phase of their disease, all patients showed normal ratios of NAA to creatine (Cr) resonance intensity throughout the hemisphere contralateral to the lesion. However, on examination 1 month later, all of the patients showed abnormally low NAA/Cr resonance intensity ratios (reduction of NAA/Cr by 22–35%) in voxels of the contralateral hemisphere which were homologous to the demyelinating lesion. Other voxels in the normal-appearing hemisphere showed normal NAA relative resonance intensities. The decrease in NAA/Cr in voxels of the normal-appearing hemispheres resolved in all patients after 6 months, with a time course similar to that observed for NAA from voxels within the lesions. We conclude that effects of damage or dysfunction to axons traversing inflammatory lesions can be transmitted over long distances in the normal-appearing white matter. Such remote, secondary effects may be an expression of dysfunction of axons in projection pathways or of the reorganization of functional pathways seen in brains recovering from an acute injury.
demyelination; axon; magnetic resonance spectroscopy; multiple sclerosis; N-acetyl aspartate
Cho = choline; Cr = creatine; NAA = N-acetyl aspartate; MR = magnetic resonance; MRSI = magnetic resonance spectroscopic imaging
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