Brain atrophy helps predict the development of disability

#MSBlog: Brain atrophy is more important than you realise.

Epub: Popescu et al. Brain atrophy and lesion load predict long term disability in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2013 Mar 23.

OBJECTIVE: To determine whether brain atrophy and lesion volumes predict subsequent 10 year clinical evolution in multiple sclerosis (MS).

DESIGN: From eight MAGNIMS (MAGNetic resonance Imaging in MS) centres, we retrospectively included 261 MSers with MR imaging at baseline and after 1-2 years, and Expanded Disability Status Scale (EDSS) scoring at baseline and after 10 years. Annualised whole brain atrophy, central brain atrophy rates and T2 lesion volumes were calculated. MSers were categorised by baseline diagnosis as primary progressive MS (n=77), clinically isolated syndromes (n=18), relapsing-remitting MS (n=97) and secondary progressive MS (n=69). Relapse onset MSers were classified as minimally impaired (EDSS=0-3.5, n=111) or moderately impaired (EDSS=4-6, n=55) according to their baseline disability (and regardless of disease type). Linear regression models tested whether whole brain and central atrophy, lesion volumes at baseline, follow-up and lesion volume change predicted 10 year EDSS and MS Severity Scale scores.

RESULTS: In the whole MSer group, whole brain and central atrophy predicted EDSS at 10 years, corrected for imaging protocol, baseline EDSS and disease modifying treatment. The combined model with central atrophy and lesion volume change as MRI predictors predicted 10 year EDSS with R2=0.74 in the whole group and R2=0.72 in the relapse onset group. In subgroups, central atrophy was predictive in the minimally impaired relapse onset patients (R2=0.68), lesion volumes in moderately impaired relapse onset patients (R2=0.21) and whole brain atrophy in primary progressive MS (R2=0.34).

CONCLUSIONS: This large multicentre study points to the complementary predictive value of atrophy and lesion volumes for predicting long term disability in MS.

“Are you surprised? If your brain has already shrunk, or is shrinking, you have a worse prognosis than someone who has no brain shrinkage or atrophy. What is remarkable about this study is the so called R2 or R-squared values; these range from 0.68 to 0.74. In other words the model that includes both atrophy and lesions explains 74% of the variance in relation to disability progression at 10 years. The implications of  this are very profound; if these factors are linked causally then preventing lesion formation and brain atrophy should prevent most MS-related disability.”

“It is becoming increasingly important to include a brain atrophy metric into our definition of NEDA (no evidence of disease activity).” 

“Clearly these results will need to be replicated by others before we get too excited!”

“It is interesting that the survey results below from a few months ago tell us how important the issue of brain atrophy is to you. You therefore need to raise this issue with your consultant.”

Other posts on brain atrophy:

31 Jan 2013
The first problem is that our neuroradiologists don’t routinely report brain atrophy, unless it is gross atrophy, i.e. easy to see with the naked eye. Although we know that brain atrophy occurs early in the disease course it is often 
15 Feb 2013
“This study confirms what we already know from several other studies that MS is associated with progressive brain atrophy that begins early in the disease and is associated with disability progression. This is why it is important 
26 Nov 2012
Poll results: outcome measures and brain atrophy. “The headline result is that MSers rate a delay in disease progression the most important outcome measures in relation to DMTs.” “The problem with disability progression in 
17 Nov 2012
“Data from several emerging DMTs now supports the natural history studies and the observation that there is a disconnect between relapses and disease progression and importantly an impact on brain atrophy. We have 
01 Feb 2013
Atrophy: a picture tells a 1000 words. “As a follow-up to yesterday’s post on brain atrophy; please study the MRIs above. These MRIs are from two MSers I met when I did my PhD from 1993 to 1996; they were participating in a 
20 Oct 2012
Natalizumab may reduce cognitive changes and brain atrophy rate in relapsing-remitting multiple sclerosis: a prospective, non-randomized pilot study. Eur J Neurol. 2012 Oct 11. doi: 10.1111/j.1468-1331.2012.03882.x.
31 May 2012
METHODOLOGY/PRINCIPAL FINDINGS: Based on MRI scans of 60 MS cases and 37 healthy volunteers, we measured the volumes of white matter (WM) lesions, cortical gray matter (GM), cerebral WM, caudate nucleus, 
29 Nov 2011
RESULTS: The mean (SD) annualized brain atrophy rate in MS’ers with benign MS (-0.16% [0.51%]) was lower than that in patients with early MS (-0.46% [0.72%]) (P = .02). The difference remained significant after controlling 
20 Mar 2012
Research: Brain Shrinkage. Riccitelli et al. Mapping regional grey and white matter atrophy in relapsing-remitting multiple sclerosis.Mult Scler. 2012 Mar 15. [Epub ahead of print] Objective: We aimed to investigate the regional 
06 Feb 2013
Measures of retinal atrophy are associated with the brain parenchymal fraction (BPF) assessed by magnetic resonance imaging (MRI). However, in MS, data on the relation of OCT measures and grey and white matter 
21 Nov 2012
More relapses were associated with poorer recovery of neurological function and accelerated brain atrophy. CONCLUSIONS: Neurological impairment is more permanent, brain atrophy is accelerated and focal inflammatory 
23 Nov 2012
BACKGROUND: Brain size, white matter hyperintensity, and the development of brain atrophy are known to be highly heritable. The decrease of brain volume starts from the very onset of MS and is 10-fold compared with 

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