Brain volume dynamics in multiple sclerosis. A case-control study (original) (raw)
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Association between brain volume and disability over time in multiple sclerosis
Multiple Sclerosis Journal - Experimental, Translational and Clinical
Background Most previous multiple sclerosis (MS) brain atrophy studies using MS impact scale 29 (MSIS-29) or symbol digit modalities test (SDMT) have been cross-sectional with limited sets of clinical outcomes. Objectives To investigate which brain and lesion volume metrics show the strongest long-term associations with the expanded disability status scale (EDSS), SDMT, and MSIS-29, and whether MRI-clinical associations vary with age. Methods We acquired MRI and clinical data from a real-world Swedish MS cohort. FreeSurfer and SPM Lesion Segmentation Tool were used to obtain brain parenchymal, cortical and subcortical grey matter, thalamic and white matter fractions as well as T1- and T2-lesion volumes. Mixed-effects and rolling regression models were used in the statistical analyses. Results We included 989 persons with MS followed for a median of 9.3 (EDSS), 10.1 (SDMT), and 9.3 (MSIS-29) years, respectively. In a cross-sectional analysis, the strength of the associations of the M...
Correlation of clinical findings and brain volume data in multiple sclerosis
, on behalf of theBrazilian Brain Volume Studies (B-BRAVOS) group a b s t r a c t Brain volume measurements are becoming an important tool for assessing success in controlling multiple sclerosis (MS) activity. MSmetrix (icometrix) is an easy-to-use platform, specific for MS magnetic resonance imaging (MRI) of the brain. It provides data on total brain volume, grey matter volume and lesion load volume. The objective of the present study was to assess whether disability and the number of relapses during the previous year correlated with brain volume measurements from MSmetrix. Data on 185 icometrix reports from patients with MS were used to evaluate the potential correlation between brain volume measurements and clinical parameters. There was a significant correlation between higher disability and decreased brain volume (total and grey matter). Increased lesion load in the brain and higher number of relapses in the previous year were also independently correlated with decreased brain tissue volume and with increased disability. This is the first study with real-world data to show that icometrix is a relevant tool for the study of brain volume loss in MS.
Clinical Relevance of Brain Volume Measures in Multiple Sclerosis
CNS Drugs, 2014
Multiple sclerosis (MS) is a chronic disease with an inflammatory and neurodegenerative pathology. Axonal loss and neurodegeneration occurs early in the disease course and may lead to irreversible neurological impairment. Changes in brain volume, observed from the earliest stage of MS and proceeding throughout the disease course, may be an accurate measure of neurodegeneration and tissue damage. There are a number of magnetic resonance imaging-based methods for determining global or regional brain volume, including cross-sectional (e.g. brain parenchymal fraction) and longitudinal techniques (e.g. SIENA [Structural Image Evaluation using Normalization of Atrophy]). Although these methods are sensitive and reproducible, caution must be exercised when interpreting brain volume data, as numerous factors (e.g. pseudoatrophy) may have a confounding effect on measurements, especially in a disease with complex pathological substrates such as MS. Brain volume loss has been correlated with disability progression and cognitive impairment in MS, with the loss of grey matter volume more closely correlated with clinical measures than loss of white matter volume. Preventing brain volume loss may therefore have important clinical implications affecting treatment decisions, with several clinical trials now demonstrating an effect of disease-modifying treatments (DMTs) on reducing brain volume loss. In clinical practice, it may therefore
Assessing Biological and Methodological Aspects of Brain Volume Loss in Multiple Sclerosis
JAMA neurology, 2018
Before using brain volume loss (BVL) as a marker of therapeutic response in multiple sclerosis (MS), certain biological and methodological issues must be clarified. To assess the dynamics of BVL as MS progresses and to evaluate the repeatability and exchangeability of BVL estimates with Jacobian Integration (JI) and Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library (FSL) (specifically, the Structural Image Evaluation, Using Normalisation, of Atrophy-Cross-Sectional [SIENA-X] tool or FMRIB's Integrated Registration and Segmentation Tool [FIRST]). A cohort of patients who had either clinically isolated syndrome or MS was enrolled from February 2011 through October 2015. All underwent a series of annual magnetic resonance imaging (MRI) scans. Images from 2 cohorts of healthy volunteers were used to evaluate short-term repeatability of the MRI measurements (n = 34) and annual BVL (n = 20). Data analysis occurred from January to May 2017. The goodness of fit...
Journal of the Neurological Sciences, 2009
Objective: To perform voxel-wise assessments of regional brain atrophy state and rate in subjects with relapsing-remitting (RR) multiple sclerosis (MS). Background: Recently, attention has focused on defining the tissue compartments and regions within which brain atrophy occurs. These regional measures of brain volume changes may help to better define the nature of the pathology underlying MS. In this context, specific regional measures of grey matter (GM) volume changes can be obtained by using the voxel-based morphometry (VBM) approach. Methods: Fifty-nine subjects with RR MS underwent conventional MRI at baseline and after a mean follow-up period of 3 years. Cross-sectionally, two VBM analyses (SPM-VBM, based on the Statistical Parametric Mapping software package, and FSL-VBM, based on the FMRIB Software Library tools) were performed to assess cortical GM volumes in RR MS patients compared to 25 age-and sex-matched normal controls (NC). Longitudinally, FSL-VBM and the regional extension of the SIENA method (SIENAr) were both used to assess regional brain atrophy rate in the RR MS patients and its relationship with increases in T 2 -weighted white matter (WM) lesion volume over the follow-up period. Results: Widespread decrease in cortical GM volume was found in the RR MS patients compared to NC. Both SPM-VBM and FSL-VBM showed similar involvement of cortical regions (frontal, temporal, parietal, occipital lobes and insula), with a close correlation between the numbers of significant voxels obtained with the two different procedures (r = 0.73, p b 0.001). After 3-year follow-up, both FSL-VBM and SIENAr showed a further significant reduction in GM volume in the lateral frontal and parietal cortices, bilaterally. Regional volume changes also appeared significantly pronounced in correspondence to the increase in T 2 -weighted WM lesion volume over the follow-up period. Conclusions: By using different methodologies, we showed similar widespread tissue loss in the cerebral cortex of patients with RR MS. This brain tissue loss further progresses over time, particularly in the frontoparietal cortex and seems to be partially dependent upon the increase of lesion load.
Brain and Lesion Volumes Correlate with Edss in Relapsing-Remitting Multiple Sclerosis
Journal of IMAB - Annual Proceeding (Scientific Papers), 2015
Background: Demyelination and neurodegeneration are hallmarks of multiple sclerosis (MS). Axonal damage is considered to be the leading factor for persisting disability in the course of the disease. In different studies, expanded disability status scale (EDSS) scores have been found to correlate with brain atrophy, lesion load, or both. Objective: To assess the possible correlations between EDSS scores and volumes of brain, grey and white matter, and subcortical structures in patients with relapsingremitting multiple sclerosis. Subjects and Methods: 46 patients with RRMS were included in the study. Total brain volume, grey and white matter volumes were calculated using SIENAX, and subcortical structure volumes were obtained using FIRST, parts of FSL. EDSS was scored by a qualified rater. Statistical analysis was performed. Results: Moderate negative correlation of EDSS was demonstrated with total brain volume, grey and white matter volume, volumes of left and right pallidum, putamen, caudate nucleus, n. accumbens (p<0.01), and with the volumes of left and right thalamus (p<0.05). Moderate positive correlation was found between EDSS and T2 lesion volume (p<0.01). Correlation between EDSS and hippocampal volumes was weak. Conclusions: Our results demonstrate that in patients with relapsing-remitting multiple sclerosis, higher disability correlates with lower volumes of brain, grey and white matter, and some subcortical structures, but also with higher T2 lesion load. We support the hypothesis about a possible causal relationship between white matter damage and brain atrophy, as well as the role of both demyelination and neurodegeneration for disability in MS.
Journal of the Neurological Sciences, 1998
We compared the volumes of the brain as a whole and of different cerebral structures from patients with multiple sclerosis (MS) and normal subjects. In the patients, we also correlated brain volumes with T2 and T1 lesion loads and disability. A magnetization-prepared rapid acquisition gradient echo (MP RAGE) sequence with subsequent reconstruction of axial 1-mm thick slices and a dual-echo sequence were obtained in 15 patients with relapsing-remitting or secondary progressive MS and 15 sex-, age-, height-and weight-matched normal subjects. The brains and the different cerebral structures studied (cerebral hemispheres, cerebellum and brainstem) were segmented manually by a single observer on the 1-mm MP RAGE scans. The hyperintense lesion volumes seen on dual-echo scans and the hypointense lesion volumes seen on the 1-mm MP RAGE scans were measured using a semi-automated segmentation technique based on local thresholding. Compared to the normal volunteers, patients had significantly lower cerebral (P50.008), hemispheric (P50.01) and brainstem (P50.03) volumes. Cerebral atrophy was detected in seven (47%) MS patients. Patients with brainstem signs had significantly lower mean brainstem volume than the others (P50.04). No significant correlations were found between the cerebral volumes and the EDSS scores, the hyperintense lesion volumes and the hypointense lesion volumes. We conclude that cerebral atrophy is a relatively frequent finding in MS, but its relationship with physical disability is modest.
Pathological cut-offs of global and regional brain volume loss in multiple sclerosis
Multiple sclerosis (Houndmills, Basingstoke, England), 2017
Volumetric MRI surrogate markers of disease progression are lacking. To establish cut-off values of brain volume loss able to discriminate between healthy controls and MS patients. In total, 386 patients after first demyelinating event suggestive of MS (CIS), 964 relapsing-remitting MS (RRMS) patients, 63 secondary-progressive MS (SPMS) patients and 58 healthy controls were included in this longitudinal study. A total of 11,438 MRI scans performed on the same MRI scanner with the same protocol were analysed. Annualised percentage changes of whole brain, grey matter, thalamus and corpus callosum volumes were estimated. We investigated cut-offs able to discriminate between healthy controls and MS patients. At a predefined specificity of 90%, the annualised percentage change cut-off of corpus callosum volume (-0.57%) was able to distinguish between healthy controls and patients with the highest sensitivity (51% in CIS, 48% in RRMS and 42% in SPMS patients). Lower sensitivities (22%-49%...
Journal of Clinical Medicine
Multiple sclerosis (MS) is a chronic inflammatory demyelinating and degenerative disorder of the central nervous system. Accelerated brain volume loss (BVL) has emerged as a promising magnetic resonance imaging marker (MRI) of neurodegeneration, correlating with present and future clinical disability. We have systematically selected MS patients fulfilling ‘no evidence of disease activity-3′ (NEDA-3) criteria under high-efficacy disease-modifying treatment (DMT) from the database of two Belgian MS centers. BVL between both MRI scans demarcating the NEDA-3 period was assessed and compared with a group of prospectively recruited healthy volunteers who were matched for age and gender. Annualized whole brain volume percentage change was similar between 29 MS patients achieving NEDA-3 and 24 healthy controls (−0.25 ± 0.49 versus −0.24 ± 0.20, p = 0.9992; median follow-up 21 versus 33 months; respectively). In contrast, we found a mean BVL increase of 72%, as compared with the former, in a...