Does the extent of axonal loss and demyelination from chronic lesions in multiple sclerosis correlate with the clinical subgroup?

Abstract

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 diVerent 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 diVerentiate 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. (J Neurol Neurosurg Psychiatry 1999;67:710-715)

Structural and functional MRI correlates of Stroop control in benign MS

“…To have a comprehensive picture of the patients studied, we also investigated the possible structural correlates of fMRI abnormalities in these patients, by assessing global brain damage, in terms of T 2 -visible lesions, brain volume, NAWM and GM involvement, and regional damage of WM fiber bundles variously related with the cognitive tasks investigated. In agreement with previous studies [Brass et al, 2004;Davie et al, 1999;De Stefano et al, 2006;Droogan et al, 1999;Falini et al, 1998;Filippi et al, 1996;Horsfield et al, 1996;Traboulsee et al, 2003], we found a relatively high proportion of T 2 -visible lesions in these patients and widespread abnormalities in the NABTs. Consistent with previous studies reporting the Stroop effect on fMRI activations in healthy people [Bench et al, 1993;Carter et al, 1995;Mitchell, 2005;Pardo et al, 1990], both groups of subjects showed the activation of several areas located in the frontal (PFC, ACC, and IFG) and parietal lobes (IPL and postcentral gyrus), and the cerebellum during the interference and facilitation conditions.…”

“…Since, as the majority of the quantitative MRI studies in BMS provided conflicting results [Brass et al, 2004;Davie et al, 1999;De Stefano et al, 2006;Droogan et al, 1999;Falini et al, 1998;Filippi et al, 1996Filippi et al, , 1999Filippi et al, , 2000Horsfield et al, 1996;Traboulsee et al, 2003], we expanded the widely used approach of quantification of NAWM and GM damage by assessing the extent of damage of several WM fiber bundles, by means of MR tractography. In addition, to test whether brain plasticity in these patients is elicited by damage of tracts specifically related to the performance of the task investigated or, conversely, represent a non specific response to a widespread central nervous system damage, we included in this analysis also measures of damage of fiber bundles not directly associated to the performance of the task investigated, including the CST.…”

“…On the contrary, magnetic resonance imaging (MRI) has provided combersome and controversial results. In detail, the majority of the studies showed that the load of T 2 -visible lesions is similar between patients with BMS and those with other disease phenotypes, whereas the extent of normal-appearing brain tissue (NABT) damage was found to be less pronounced in patients with BMS than in other forms of the disease in some studies [Davie et al, 1999;De Stefano et al, 2006;Falini et al, 1998;Filippi et al, 1996Filippi et al, , 1999Filippi et al, , 2000, but not in others [Brass et al, 2004;Droogan et al, 1999;Horsfield et al, 1996;Traboulsee et al, 2003].…”

“…Such an approach was driven by two considerations: (a) to investigate cortical functional changes in patients with a ''real'' benign course (i.e., with no locomotor and cognitive impairment), and (b) to study the underlying functional cortical correlates of brain-mediated clinical aspects (contrary to cognition, locomotor ability is indeed likely to be associated to both brain and spinal cord integrity). Differently from previous studies based on an ''overall'' assessment of brain damage [Brass et al, 2004;Davie et al, 1999;De Stefano et al, 2006;Droogan et al, 1999;Falini et al, 1998;Filippi et al, 1996Filippi et al, , 1999Filippi et al, , 2000Horsfield et al, 1996;Traboulsee et al, 2003], we investigated the structural correlates of fMRI abnormalities, by using diffusion tensor (DT) tractography, since it is likely that damage of ''strategic'' white matter (WM) fiber bundles of the brain might be more strictly linked to functional cortical changes than ''overall'' NABT damage. DT MRI provides quantitative data on water molecular motion, a marker of tissue structure and organization.…”

Biology: The Significance of MR Parameters in Multiple Sclerosis

“…This may be because MTR decrease is more influenced by myelin loss than axonal loss. However, Davie et al (1999) found a good correlation between a reduction in NAA concentration and a reduction in MTR within MS lesions of patients who had entered the secondary progressive phase of the disease, while patients with a more benign disease course showed a relative preservation of MTR and NAA.…”