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Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
Evidence of early cortical atrophy in MS: relevance to white matter changes and disability
N De Stefano1, P M Matthews, M Filippi
1Institute of Neurological Sciences, University of Siena, Italy. destefano@unisi.it
Objective:
To assess cortical gray matter (GM) changes in MS and establish their relevance to clinical disability and to inflammatory changes of white matter (WM) in patients with the relapsing-remitting (RR) and primary progressive (PP) forms of the disease.
Methods:
Conventional MRI examinations were obtained in patients with definite MS who had either the RR or the PP form of the disease. An automated analysis tool was used with conventional T1-weighted MR images to obtain total and cortical brain volumes normalized for head size. Total brain lesion load was estimated on conventional proton density and T2-weighted MR images. The relationship between volumetric MR measures and scores of clinical disability was assessed.
Results:
Normalized cortical volumes (NCV) were lower for both RR and PP MS patients than for normal control subjects (p < 0.001) but were similar between the two patient groups (p > 0.5). NCV decreases in both patients groups were detected even in those patients with short disease duration (<5 years; p < 0.001 in RR MS and p < 0.05 in PP MS) and minimal brain lesion volume (<5 mL; p < 0.0001 in RR MS and p < 0.005 in PP MS). Measures of NCV in individual patients were negatively correlated with T2-weighted lesion volume (r = -0.47, p < 0.001) and disease duration (r = -0.25, p < 0.05) only in the patients with RR MS. NCV correlated with Expanded Disability Status Scale scores across all of the patients, but the strength of the correlation was stronger (p < 0.05) for PP (r = -0.64, p < 0.0001) than for RR (r = -0.27, p = 0.04) MS patients.
Conclusions:
These data confirm substantial neocortical volume loss in MS patients and suggest that neocortical GM pathology may occur early in the course of the disease in both RR and PP MS patients and contribute significantly to neurologic impairment. Although a proportion of this neocortical pathology may be secondary to WM inflammation, the extent of the changes suggests that, especially in patients with PP MS, an independent neurodegenerative process also is active.
Insights
Multiple sclerosis (MS) patients show significant gray matter volume loss, even early in the disease. This cortical gray matter reduction contributes to disability in both relapsing-remitting (RR) and primary progressive (PP) MS.
Area of Science:
- Neurology
- Neuroimaging
- Neurodegeneration
Background:
- Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system.
- Gray matter (GM) pathology, including cortical GM, is increasingly recognized in MS.
- Understanding GM changes is crucial for assessing disease progression and disability.
Purpose of the Study:
- To quantify cortical GM volume changes in patients with relapsing-remitting (RR) and primary progressive (PP) MS.
- To determine the association between cortical GM volume and clinical disability.
- To investigate the relationship between cortical GM changes and white matter (WM) inflammatory lesions.
Main Methods:
- Conventional MRI scans were acquired from definite MS patients (RR and PP forms).
- Automated analysis of T1-weighted MR images was used to calculate normalized cortical volumes (NCV).
- Proton density and T2-weighted images assessed total brain lesion load; correlations with disability scores were analyzed.
Main Results:
- Both RR and PP MS patients exhibited significantly lower NCV compared to controls.
- NCV reduction was evident even in early disease stages (<5 years) and with minimal lesion load.
- NCV correlated negatively with T2 lesion load and disease duration in RR MS, and strongly with disability scores in PP MS.
Conclusions:
- Substantial neocortical volume loss occurs in MS, indicating early GM pathology in both RR and PP forms.
- Cortical GM changes contribute significantly to neurologic impairment.
- While partly secondary to WM inflammation, an independent neurodegenerative process is suggested, particularly in PP MS.
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