Thalamic Atrophy in RIS: MRI Evidence of Early CNS Neurodegeneration (S13.002)

OBJECTIVE: To identify the presence of thalamic atrophy in Radiologically Isolated Syndrome (RIS). BACKGROUND: There is increasing evidence that the thalamus may be a location of early neurodegeneration in MS. Thalamic atrophy has been seen in early relapsing remitting MS, clinically isolated syndrome at presentation, and pediatric MS. A relationship has been observed between thalamic volume and white matter lesions within thalamocortical projections. We hypothesized that thalamic atrophy would be present in RIS. DESIGN/METHODS: Each RIS subject was carefully age- and gender-matched to two healthy controls. All subjects (n=63) underwent brain MRIs on a single 3T, including a 1mm³-resolution 3D T1-weighted sequence. After manual lesion segmentation and inpainting, images were submitted to FreeSurfer(v5.2) for fully automated and unbiased segmentation. FreeSurfer’s output was manually edited to ensure accurate segmentation. Normalized thalamic volumes in RIS were compared to controls using t-tests, and were correlated with white matter lesion volumes using Pearson’s correlation. Exploratory cortical thickness maps were created using QDEC, a tool within FreeSurfer that performs vertex-wise comparisons. RESULTS: Normalized left (0.0046±0.0005 vs. 0.0049±0.0004 units, p=0.006), right (0.0045±0.0005 vs. 0.0048±0.0004 units, p=0.008) and mean (0.0045±0.0005 vs. 0.0049 ± 0.0004 units, p=0.004) thalamic volumes were significantly lower in RIS (n=21, mean age=41.9±12.7 years) compared with controls (n=42, mean age=41.4±11.2 years). Traditional normalized whole grey matter (0.45±0.03 vs. 0.46±0.02 units, p=0.06) and white matter (0.33±0.02 vs. 0.33±0.02 units, p=0.6) volumes were not statistically different. As seen in other stages of MS, thalamic volumes correlated with white matter lesions (range: rho=-0.34 to -0.47). QDEC analysis demonstrated a ~3cm region in the right superior and inferior parietal gyri significantly thinner in RIS after multiple comparison correction (MonteCarlo threshold of p<0.005). CONCLUSIONS: Our data provide the first evidence of thalamic atrophy in RIS subjects and are consistent with previous reports in early MS stages. Thalamic volume loss is an early event and should be further investigated as a metric associated with neurodegeneration. Study supported by:NINDS/R01-NS062885(PI:D.Pelletier) Disclosure: Dr. Azevedo has received personal compensation for activities with Genzyme Corporation. Dr. Overton has nothing to disclose. Dr. Khadka has nothing to disclose. Dr. Buckley has nothing to disclose. Dr. Liu has nothing to disclose. Dr. Sampat has nothing to disclose. Dr. Kantarci has nothing to disclose. Dr. Lebrun has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec, Merck Serono, Genzyme Corp., Almirall, Allergan Inc., Novartis, and Sanofi-Aventis Pharmaceuticals Inc. as a speaker. Dr. Lebrun has received personal compensation in an editorial capacity from Elsevier. Dr. Okuda has received personal compensation for activities with Acorda Therapeutics, Biogen Idec, Genzyme Corporation, Ipsen, and Teva Neuroscience. Dr. Pelletier has received personal compensation for activities with Teva Neuroscience, Genentech Inc., Biogen Idec as a speaker and advisory board member, and activities with Bayer Pharmaceuticals Corp. and Synarc as a consultant. Dr. Pelletier has received research support from Biogen Idec.