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Brain atrophy and physical disability in primary progressive multiple sclerosis: A volumetric study.

ABSTRACT: Grey matter atrophy has been shown in primary progressive multiple sclerosis (PPMS), but its association with physical incapacity is unclear. We submitted 19 patients with PPMS to a neurological evaluation and brain magnetic resonance imaging (MRI) with volumetric analysis using FreeSurfer. We found no relation between the Expanded Disability Status Scale or disease duration and the grey matter or white matter structures analysed. Lesion load was negatively correlated with cortical and subcortical grey matter volumes, but not with total white matter volume. We concluded that physical disability in PPMS is not directly related to brain atrophy and that focal inflammatory white matter lesions may contribute to progressive neuronal degeneration.Primary progressive multiple sclerosis (PPMS) is characterized by chronic progression since onset, with predominant involvement of the spinal cord and prominent neurodegeneration. Grey matter atrophy has been shown in patients with PPMS, but its association with clinical incapacity is uncertain. We investigated the relationship between regional brain atrophy and physical disability in patients with PPMS.Patients with an established diagnosis of PPMS underwent a neurological evaluation followed by brain MRI at 1.5 T. Volumetric analysis was performed with FreeSurfer software, and evaluated the neocortex, total white matter, total subcortical grey matter, putamen, caudate, globus pallidus, thalamus, hippocampus, brainstem, corpus callosum and pre-central gyrus volumes. Clinical data obtained included physical disability as measured by the Expanded Disability Status Scale (EDSS).Nineteen patients were included, 14 female (73.7%), mean age of 55.7 (SD 7.6) and mean disease duration of 13.0 years (SD 8.8). Median EDSS score was 6.0 (3.5-8.0). The average T1 lesion load (4.9 cm³, SD 3.4) and T2 load (10.5 cm³, SD 9.9) did not relate to disease duration. There was no significant correlation between EDSS score or disease duration and the cortical grey matter, deep grey matter or white matter structures analysed. Lesion load was negatively correlated with cortical and subcortical grey matter volumes (p < 0.05), but not with total white matter volume.Physical disability in PPMS is not directly related to brain volume loss. Grey matter atrophy correlates with lesion load in patients with PPMS, indicating that focal inflammatory white matter lesions may contribute to progressive neuronal degeneration.

SUBMITTER: Galego O

PROVIDER: S-EPMC4757290 | biostudies-other | 2015 Jun

REPOSITORIES: biostudies-other

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Project description:Grey matter (GM) atrophy occurs early in primary progressive MS (PPMS), but it is unknown whether its progression involves different brain regions at different rates, as is seen in other neurodegenerative diseases. We aimed to investigate the temporal and regional evolution of GM volume loss over 5years and its relationship with disability progression in early PPMS. We studied 36 patients with PPMS within five years from onset and 19 age and gender-matched healthy controls with clinical and imaging assessments at study entry and yearly for 3years and then at 5years. Patients were scored on the expanded disability status scale (EDSS) and MS Functional Composite (MSFC) at each time-point. An unbiased longitudinal voxel-based morphometry approach, based on high-dimensional spatial alignment within-subject, was applied to the serial imaging data. The rate of local (voxel-wise) volume change per year was compared between groups and its relationship with clinical outcomes was assessed. Patients deteriorated significantly during the five years follow-up. Patients showed a greater decline of GM volume (p<0.05, FWE-corrected) bilaterally in the cingulate cortex, thalamus, putamen, precentral gyrus, insula and cerebellum when compared to healthy controls over five years, although the rate of volume loss varied across the brain, and was the fastest in the cingulate cortex. Significant (p<0.05, FWE-corrected) volume loss was detected in the left insula, left precuneus, and right cingulate cortex in patients at three years, as compared to baseline, whilst the bilateral putamen and the left superior temporal gyrus showed volume loss at five years. In patients, there was a relationship between a higher rate of volume loss in the bilateral cingulate cortex and greater clinical disability, as measured by the MSFC, at five years (Pearson's r=0.49, p=0.003). Longitudinal VBM demonstrated that the progression of GM atrophy in PPMS occurs at different rates in different regions across the brain. The involvement of the cingulate cortex occurs early in the disease course, continues at a steady rate throughout the follow-up period and is associated with patient outcome. These findings provide new insights into the characteristics of GM atrophy across the brain in MS, and have potential consequences for the selection of brain atrophy as an outcome measure in neuroprotective clinical trials.

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Brain atrophy and physical disability in primary progressive multiple sclerosis: A volumetric study.

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