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

ABSTRACT: BACKGROUND AND PURPOSE: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. MATERIALS AND METHODS: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. RESULTS: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 (P < .001), percentage normalized brain volume change (P = .002), and percentage lateral ventricle volume change (P = .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 (P < .001) and normalized brain volume (P = .002) and a 33% increase in lateral ventricle volume (P = .004). CONCLUSIONS: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.

SUBMITTER: Ghione E

PROVIDER: S-EPMC6295216 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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

Ghione E E Bergsland N N Dwyer M G MG Hagemeier J J Jakimovski D D Paunkoski I I Ramasamy D P DP Silva D D Carl E E Hojnacki D D Kolb C C Weinstock-Guttman B B Zivadinov R R

AJNR. American journal of neuroradiology 20181122 12

<h4>Background and purpose</h4>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.<h4>Materials and methods</h4>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 ...[more]

PMID: 30467212

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Project description:BackgroundMultiple sclerosis (MS) is a chronic, immune-mediated neurodegenerative disorder of the central nervous system (CNS). While current MS therapies target the inflammatory processes, no treatment explicitly targets mitochondrial dysfunction and resulting axonal loss. Therefore, the aim of this study was to determine whether idebenone inhibits mitochondrial dysfunction and accumulation of disability in primary progressive MS (PPMS) and to enhance understanding of pathogenic mechanisms of PPMS progression using cerebrospinal fluid (CSF) biomarkers.MethodsThe double-blind, placebo-controlled Phase I/II clinical trial of Idebenone in patients with Primary Progressive MS (IPPoMS; NCT00950248) was an adaptively designed, baseline-versus-treatment, placebo-controlled, CSF-biomarker-supported trial. Based on interim analysis of the 1-year pre-treatment data, change in the area under the curve of Combinatorial Weight-Adjusted Disability Score (CombiWISE) became the primary outcome, with >80% power to detect ≥40% efficacy with 28 patients/arm treated for 2 years in baseline versus treatment paradigm. Changes in traditional disability scales and in brain ventricular volume were secondary outcomes. Exploratory outcomes included CSF biomarkers of mitochondrial dysfunction (Growth/differentiation factor 15 [GDF15] and lactate), axonal damage (neurofilament light chain [NFL]), innate immunity (sCD14), blood brain barrier leakage (albumin quotient) and retinal nerve fiber layer thinning.ResultsIdebenone was well tolerated but did not inhibit disability progression or CNS tissue destruction. Concentrations of GDF15, secreted predominantly by astrocytes and choroid plexus epithelium in vitro, increased after exposure to mitochondrial toxin rotenone, validating the ability of this biomarker to measure intrathecal mitochondrial damage. CSF GDF15 levels correlated strongly with age and MS patients had CSF levels of GDF15 significantly above age-adjusted healthy volunteers, with highest levels measured in PPMS. Idebenone did not change CSF GDF15 levels.ConclusionMitochondrial dysfunction exceeding normal aging reflected by age-adjusted CSF GDF15 is present in the majority of PPMS patients, but it is not inhibited by idebenone.

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

Publications

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

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