Magnetic resonance imaging correlates of physical disability in relapse onset multiple sclerosis of long disease duration

Institute of Neurology, University College London, UK.
Multiple Sclerosis (Impact Factor: 4.82). 06/2013; 20(1). DOI: 10.1177/1352458513492245
Source: PubMed


Understanding long-term disability in multiple sclerosis (MS) is a key goal of research; it is relevant to how we monitor and treat the disease.
The Magnetic Imaging in MS (MAGNIMS) collaborative group sought to determine the relationship of brain lesion load, and brain and spinal cord atrophy, with physical disability in patients with long-established MS.
Patients had a magnetic resonance imaging (MRI) scan of their brain and spinal cord, from which we determined brain grey (GMF) and white matter (WMF) fractional volumes, upper cervical spinal cord cross-sectional area (UCCA) and brain T2-lesion volume (T2LV). We assessed patient disability using the Expanded Disability Status Scale (EDSS). We analysed associations between EDSS and MRI measures, using two regression models (dividing cohort by EDSS into two and four sub-groups).
In the binary model, UCCA (p < 0.01) and T2LV (p = 0.02) were independently associated with the requirement of a walking aid. In the four-category model UCCA (p < 0.01), T2LV (p = 0.02) and GMF (p = 0.04) were independently associated with disability.
Long-term physical disability was independently linked with atrophy of the spinal cord and brain T2 lesion load, and less consistently, with brain grey matter atrophy. Combinations of spinal cord and brain MRI measures may be required to capture clinically-relevant information in people with MS of long disease duration.

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Available from: Alex Rovira, Sep 28, 2014
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    • "The existence of a correlation between hyperintense lesion load in T2-weighted images and disability level (EDSS) remains controversial (Barkhof 2002; Charil et al. 2003; Popescu et al. 2013; Kearney et al. 2014). Here, we found a higher disease severity (MSSS) in MS ? "
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    ABSTRACT: Typical multiple sclerosis (MS) lesions occur in the brain as well as in the spinal cord. However, two extreme magnetic resonance imaging phenotypes appear occasionally: those with predominantly spinal cord lesions (MS + SL) and those with cerebral lesions and no detectable spinal lesions (MS + CL). We assessed whether morphological differences can be found between these two extreme phenotypes. We examined 19 patients with MS + SL, 18 with MS + CL and 20 controls. All subjects were examined using magnetic resonance imaging, including anatomical and diffusion tensor imaging sequences. Voxel-based morphologic and regions of interest-based analyses and tract-based spatial statistics were performed. Patients also underwent neuropsychological testing. Demographic, clinical and neuropsychological characteristics did not differ between MS + SL and MS + CL patients. Patients with MS + SL showed significantly larger putamen volumes than those with MS + CL which correlated negatively with disability. Compared to controls, only MS + CL revealed clear cortical and deep gray matter atrophy, which correlated with cerebral lesion volume. Additionally, extensive white matter microstructural damage was found only in MS + CL compared to MS + SL and controls in the tract-based spatial statistics. Higher putamen volumes in MS + SL could suggest compensatory mechanisms in this area responsible for motor control. Widely reduced fractional anisotropy values in MS + CL were caused by higher cerebral lesion volume and thus presumably stronger demyelination, which subsequently leads to higher global gray matter atrophy.
    Journal of Neural Transmission 05/2015; DOI:10.1007/s00702-015-1406-4 · 2.40 Impact Factor
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    • "Magnetic resonance imaging (MRI) permits to assess tissue abnormalities in vivo and approximate histopathological changes of the multiple sclerosis (MS) disease (Ganiler et al., 2014; Kearney et al., 2014). "
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    ABSTRACT: Multiple sclerosis white matter (WM) lesions can affect brain tissue volume measurements of voxel-wise segmentation methods if these lesions are included in the segmentation process. Several authors have presented different techniques to improve brain tissue volume estimations by filling WM lesions before segmentation with intensities similar to WM. Here, we propose a new method to refill WM lesions, where contrary to similar approaches, lesion voxels intensities are replaced by random values of a normal distribution generated from the mean WM signal intensity of each two-dimensional slice. We test the performance of our method by estimating the deviation in tissue volume between a set of 30 T1-w 1.5 T and 30 T1-w 3T images of healthy subjects and the same images where: WM lesions have been previously registered, and afterwards replaced their voxel intensities to those between gray matter (GM) and WM tissue. Tissue volume is computed independently using FAST and SPM8. When compared with the state-of-the-art, on 1.5 T data our method yields the lowest deviation in WM between original and filled images, independently of the segmentation method used. It also performs the lowest differences in GM when FAST is used, and equals to the best method, when SPM8 is employed. On 3T data, our method also outperforms the state-of-the-art when FAST is used, while performs similar to the best method when SPM8 is used. The proposed technique is currently available to researchers as standalone program and as an SPM extension.
    Clinical neuroimaging 12/2014; 6. DOI:10.1016/j.nicl.2014.08.016 · 2.53 Impact Factor
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    • "T2 lesion volume is positively correlated with disability measured by EDSS at 2 [47] and 10 years of follow-up [48] and number of relapses after 2 years of follow up [34, 47]. A recent study evaluated MRI correlates of disability in a cohort of 159 patients with relapsing-remitting MS (median EDSS = 4) followed for mean of 26 years from first attack and found that T2 lesion volume was associated with long-term disability and independent of cervical spinal cord atrophy and grey matter atrophy [49]. Similarly, a study of 107 MS patients followed for mean of 20 years from first attack showed that T2 lesion volume correlated with 20-year EDSS (rs = 0.48–0.67) "
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    ABSTRACT: Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease that manifests as acute relapses and progressive disability. As a primary endpoint for clinical trials in MS, disability is difficult to both characterize and measure. Furthermore, the recovery from relapses and the rate of disability vary considerably among patients. Given these challenges, investigators have developed and studied the performance of various outcome measures and surrogate endpoints in MS clinical trials. This review defines the outcome measures and surrogate endpoints used to date in MS clinical trials and presents challenges in the design of both adult and pediatric trials.
    05/2014; 2014:262350. DOI:10.1155/2014/262350
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