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      Brain Atrophy Is Associated with Disability Progression in Patients with MS followed in a Clinical Routine

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          Abstract

          <div class="section"> <a class="named-anchor" id="d983130e254"> <!-- named anchor --> </a> <h5 class="section-title" id="d983130e255">BACKGROUND AND PURPOSE:</h5> <p id="d983130e257">The assessment of brain atrophy in a clinical routine is not performed routinely in multiple sclerosis. Our aim was to determine the feasibility of brain atrophy measurement and its association with disability progression in patients with MS followed in a clinical routine for 5 years. </p> </div><div class="section"> <a class="named-anchor" id="d983130e259"> <!-- named anchor --> </a> <h5 class="section-title" id="d983130e260">MATERIALS AND METHODS:</h5> <p id="d983130e262">A total of 1815 subjects, 1514 with MS and 137 with clinically isolated syndrome and 164 healthy individuals, were collected retrospectively. Of 11,794 MR imaging brain scans included in the analysis, 8423 MRIs were performed on a 3T, and 3371 MRIs, on a 1.5T scanner. All patients underwent 3D T1WI and T2-FLAIR examinations at all time points of the study. Whole-brain volume changes were measured by percentage brain volume change/normalized brain volume change using SIENA/SIENAX on 3D T1WI and percentage lateral ventricle volume change using NeuroSTREAM on T2-FLAIR. </p> </div><div class="section"> <a class="named-anchor" id="d983130e264"> <!-- named anchor --> </a> <h5 class="section-title" id="d983130e265">RESULTS:</h5> <p id="d983130e267">Percentage brain volume change failed in 36.7% of the subjects; percentage normalized brain volume change, in 19.2%; and percentage lateral ventricle volume change, in 3.3% because of protocol changes, poor scan quality, artifacts, and anatomic variations. Annualized brain volume changes were significantly different between those with MS and healthy individuals for percentage brain volume change ( <i>P</i> &lt; .001), percentage normalized brain volume change ( <i>P</i> = .002), and percentage lateral ventricle volume change ( <i>P</i> = .01). In patients with MS, mixed-effects model analysis showed that disability progression was associated with a 21.9% annualized decrease in percentage brain volume change ( <i>P</i> &lt; .001) and normalized brain volume ( <i>P</i> = .002) and a 33% increase in lateral ventricle volume ( <i>P</i> = .004). </p> </div><div class="section"> <a class="named-anchor" id="d983130e288"> <!-- named anchor --> </a> <h5 class="section-title" id="d983130e289">CONCLUSIONS:</h5> <p id="d983130e291">All brain volume measures differentiated MS and healthy individuals and were associated with disability progression, but the lateral ventricle volume assessment was the most feasible. </p> </div>

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          Most cited references23

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          The measurement and clinical relevance of brain atrophy in multiple sclerosis.

          Brain atrophy has emerged as a clinically relevant component of disease progression in multiple sclerosis. Progressive loss of brain tissue bulk can be detected in vivo in a sensitive and reproducible manner by MRI. Clinical studies have shown that brain atrophy begins early in the disease course. The increasing amount of data linking brain atrophy to clinical impairments suggest that irreversible tissue destruction is an important determinant of disease progression to a greater extent than can be explained by conventional lesion assessments. In this review, we will summarise the proposed mechanisms contributing to brain atrophy in patients with multiple sclerosis. We will critically discuss the wide range of MRI-based methods used to quantify regional and whole-brain-volume loss. Based on a review of current information, we will summarise the rate of atrophy among phenotypes for multiple sclerosis, the clinical relevance of brain atrophy, and the effect of disease-modifying treatments on its progression.
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            Clinical relevance of brain volume measures in multiple sclerosis.

            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 be important to consider the potential impact of a therapy on reducing the rate of brain volume loss. This article reviews the measurement of brain volume in clinical trials and practice, the effect of DMTs on brain volume change across trials and the clinical relevance of brain volume loss in MS.
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              Assessing brain atrophy rates in a large population of untreated multiple sclerosis subtypes.

              To assess the time course of brain atrophy and the difference across clinical subtypes in multiple sclerosis (MS). The percent brain volume change (PBVC) was computed on existing longitudinal (2 time points) T1-weighted MRI from untreated (trial and nontrial) patients with MS. Patients (n = 963) were classified as clinically isolated syndromes suggestive of MS (CIS, 16%), relapsing-remitting (RR, 60%), secondary progressive (SP, 15%), and primary progressive (9%) MS. The median length of follow-up was 14 months (range 12-68). There was marked heterogeneity of the annualized PBVC (PBVC/y) across MS subtypes (p = 0.003), with higher PBVC/y in SP than in CIS (p = 0.003). However, this heterogeneity disappeared when data were corrected for the baseline normalized brain volume. When the MS population was divided into trial and nontrial subjects, the heterogeneity of PBVC/y across MS subtypes was present only in the second group, due to the higher PBVC/y values found in trial data in CIS (p = 0.01) and RR (p < 0.001). The estimation of the sample sizes required for demonstrating a reduction of brain atrophy in patients in a placebo-controlled trial showed that this was larger in patients with early MS than in those with the progressive forms of the disease. This first large study in untreated patients with multiple sclerosis (MS) with different disease subtypes shows that brain atrophy proceeds relentlessly throughout the course of MS, with a rate that seems largely independent of the MS subtype, when adjusting for baseline brain volume.
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                Author and article information

                Journal
                American Journal of Neuroradiology
                AJNR Am J Neuroradiol
                American Society of Neuroradiology (ASNR)
                0195-6108
                1936-959X
                December 14 2018
                December 2018
                December 2018
                November 22 2018
                : 39
                : 12
                : 2237-2242
                Article
                10.3174/ajnr.A5876
                6295216
                30467212
                69f40954-8c67-47dd-accd-386609865f3a
                © 2018
                History

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