Does the extent of axonal loss and demyelination from chronic lesions in multiple sclerosis correlate with the clinical subgroup?
OBJECTIVE
To determine non-invasively the relation between the degree of axonal loss and the extent of demyelination in chronic lesions visible on MRI in patients with different subgroups of clinically definite multiple sclerosis using (1)H magnetic resonance spectroscopy ((1)H MRS) and magnetisation transfer imaging (MT). Conventional MRI is unable to differentiate between the various pathological processes occurring in the multiple sclerosis lesion. There are, however, newer MR techniques which show promise in this respect.


METHODS
(1)H MRS and MT were performed in 18 patients with clinically definite multiple sclerosis who had a wide range of disability and disease duration.


RESULTS
A significant correlation was found between a reduction in the concentration of N-acetyl aspartate (NAA; an in vivo marker of axonal loss or dysfunction) and a reduction in MT ratio (a probable marker of demyelination) in patients who had entered the secondary progressive stage of the disease. Patients with minimal disability after a disease duration of greater than 10 years-so called benign multiple sclerosis-showed a relative preservation of NAA and MT.


CONCLUSIONS
Because a reduction in MT seems to be a relative marker for demyelination and a reduction of NAA from chronic lesions is indicative of axonal loss, this study supports the hypothesis that demyelination and axonal loss occur in the same chronic multiple sclerosis lesions. In addition, the degree of axonal loss and demyelination correlates with clinical heterogeneity.
Davie
C A
CA
NMR Research Unit. Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Silver
N C
NC
Barker
G J
GJ
Tofts
P S
PS
Thompson
A J
AJ
McDonald
W I
WI
Miller
D H
DH
D001224:Aspartic Acid / Q000032:analysis; D001369:Axons / Q000737:chemistry / Q000473:pathology*; D002540:Cerebral Cortex / Q000737:chemistry; D002908:Chronic Disease; D003711:Demyelinating Diseases / Q000150:complications / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D008279:Magnetic Resonance Imaging; D009103:Multiple Sclerosis / Q000150:complications / Q000473:pathology*; D017590:Myelinolysis, Central Pontine / Q000473:pathology; D014867:Water / Q000032:analysis
D014867:Water; D001224:Aspartic Acid