Brain atrophy and CIS

MRI lesion load at baseline predicts brain volume loss in the future. #MSResearch #MSBlog

"The following study in CISers shows a link between focal lesion load at baseline and brain atrophy in the future; CISers with the highest lesion count at baseline had the greatest brain volume loss over the next 4 years. This shows that brain volume changes are primed by past inflammatory lesions and indicates that we will need to adjust how we use brain volume changes in clinical trials. We have to take into account the therapeutic lag associated with brain volume changes; i.e. brain volume loss in this year and possibly next year will be primed by inflammatory lesions in the past few years. Why the lag? I suspect it relates to the delayed biological vacuum cleaner; it takes many months to clear up the debris from inflammatory lesions and hence to feed through into brain volume loss."

"This study is a stark reminder of how much damage may have already occurred prior to the first clinical event (CIS). In the majority of CISers the pathology of MS has been present for many years and explains why so many CISers already have cognitive deficits at presentation. The latter observations are why we have to treat MS early and effectively and if possible suppress all inflammatory activity; zero tolerance with treat-2-target of NEDA (no evident disease activity)."

"On a positive note CISers are lucky in that the disease declares itself early. In comparison PPMSers only get to know about their disease many years later after they have lost their reserve capacity and present with progressive disease. We need to do something about the latter? If only we could get to PPMS in the asymptomatic phase of the disease."

Epub: Varosanec et al. Longitudinal Mixed-Effect Model Analysis of the Association between Global and Tissue-Specific Brain Atrophy and Lesion Accumulation in Patients with Clinically Isolated Syndrome. AJNR Am J Neuroradiol. 2015.

BACKGROUND AND PURPOSE: The relationship between lesion formation and brain atrophy development in the early phase of multiple sclerosis is unclear. We investigated the association between new lesion accumulation and brain atrophy progression in patients with clinically isolated syndrome over 48 months.

MATERIALS AND METHODS: Patients with clinically isolated syndrome (n = 210) were evaluated with 1.5T MR imaging at baseline and at 6, 12, 24, 36, and 48 months as part of a multicenter observational study of early administration of intramuscular interferon β-1a. Mixed-effect model analyses, adjusted for age, sex, and treatment status, investigated the association between accumulation of contrast-enhancing and T2 lesions and brain-volume percent changes in a 48-month period.

RESULTS: In patients with clinically isolated syndrome, the average whole-brain volume decreased 2.5%, the mean lateral ventricle volume increased 16.9%, and a mean of 7.7 new/enlarging T2 lesions accumulated over the follow-up period. Patients with clinically isolated syndrome who showed greater percentages of change in whole-brain, white and gray matter, cortical, and lateral ventricle volumes over the follow-up period had more severe lesion outcomes at baseline (all P < .007). There were significant associations between decreased individual brain-volume measures at baseline and greater percentages of change during follow-up (P < .05). We found a significant association between the total cumulative number of new/enlarging T2 lesions and the evolution of whole-brain (P < .001), lateral ventricle (P = .007), gray matter and thalamic (P = .013), subcortical deep gray matter (P = .015), and cortical (P = .036) volumes over the follow-up period.

CONCLUSIONS: Lesion accumulation and brain-volume changes occur simultaneously in the early phase of clinically isolated syndrome. More severe lesion and brain-volume outcomes at baseline were associated with greater development of brain atrophy over the follow-up period in patients with clinically isolated syndrome.

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