Abstract: Promising Imaging Markers of Disability Progression in Early Multiple Sclerosis (The 27th Annual Meeting of the CMSC and the 5th Cooperative Meeting of the CMSC-ACTRIMS)

Saturday, June 1, 2013

Amir-Hadi Maghzi, MD , Neurology, University of California, San Francisco, San Francisco, CA

Nisha Revirajan, MD , Neurology, University of California, San Francisco, San Francisco, CA

Rebecca I Spain, MD , Neurology, Oregon Health & Science University, Portland, OR

Laura Julian, PhD , University of California, San Francisco, San Francisco, CA

Shuang Liu, PhD , Neurology, Yale University, New Haven, CT

Chengshi Jin, PhD , Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA

Ari J Green, MD , Neurology, University of California, San Francisco, San Francisco, CA

Charles E McCulloch, PhD , Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA

Daniel Pelletier, MD , Neurology, Yale University, New Haven, CT

Emmanuelle Waubant, MD, PhD , Neurology, University of California, San Francisco, San Francisco, CA

Background: Currently approved drugs for multiple sclerosis (MS) have unclear benefit in reducing the rate of neurodegeneration associated with the disease. One of the challenges in the design of neuroprotective trials is the lack of surrogates for clinical progression.

Objectives: We aimed to find imaging markers that may be associated with clinical progression in early MS patients.

Methods: Patients with relapsing-remitting MS or clinically isolated syndromes seen within 12 months of onset and naïve to disease-modifying therapies were enrolled in a trial of neuroprotection with riluzole vs. placebo in combination with intramuscular interferon-beta 1a. Baseline and month 12 clinical, time domain optical coherence tomography (OCT), magnetic resonance imaging (MRI), clinical data were obtained. Clinical measures included cognitive function (symbol digit modality test -SDMT), and different domains of MS functional composite (MSFC) including timed 25-foot walk (T25FW), 9-hole peg test (9HPT), three seconds paced auditory serial addition test (PASAT). Possible biomarkers of neuroprotection included, brain volume [Structural Image Evaluation, using Normalization, of Atrophy, (SIENA and SIENAX)], peripapillary retinal nerve fiber layer (RNFL), and radial macular volume (MV)]. Spearman’s rank correlation was used to assess the association between the measures. Adjustment for treatment with riluzole or placebo was not made as treatment assignment is still blinded.

Results: Data for these measures at baseline and month 12 evaluations were available for 41 patients (73% females; mean age 35.8±9.1; median baseline EDSS 2.0; mean disease duration of 7.3±5.3 months). Brain volume change was not significantly correlated with any of T25FW, 9HPT, PASAT, SDMT changes over one year (all r values were < 0.25). RNFL change was correlated with T25FW change over one year (n=26, r= -0.46, 95% CI: -0.72 to -0.08, p=0.019) but not with any other clinical measures. MV change was correlated with PASAT change (n=24, r=0.41, 95%CI: 0.01 to 0.7, p=0.046) but not with changes in any other clinical measures. RNFL and MV changes were not correlated with brain volume changes. Analyses for SIENAX data and year two and three data are ongoing.

Conclusions: That RNFL correlates with T25FW while MV correlates with PASAT suggests that these measures may represent promising markers of distinct clinical dimension of MS. These results should be confirmed in a larger study.

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