Atrophy of spinal cord gray matter is detectable at an early stage of multiple sclerosis (S2.003)

Objective: To estimate spinal cord (SC) gray matter (GM) area’s potential as a biomarker of disease progression in multiple sclerosis (MS), we must understand how early in the MS course SC GM atrophy can be detected, which parts of the cord are affected, and the relationship to SC-relapses and T2-lesions. Background: SC GM atrophy was recently described in vivo in patients with long-standing MS and was shown to correlate with disability and disease type. Design/Methods: As part of an observational cohort study, one hundred seventeen subjects were scanned with axial 2D-phase sensitive inversion recovery (PSIR) MRI at 3T: Sixty-four MS patients (mean disease duration from first symptom onset 1.2 years (0–4 years), mean age 36.9 years, median Expanded Disability Status Scale (EDSS) Score 2.0, 44 women) and 53 healthy controls (mean age 37.4 years, 38 women). PSIR images were acquired at the intervertebral disc levels C2/C3 and T9/10. EDSS scores were determined in patients. Results: In cervical and thoracic SC, patients had significantly smaller GM areas than controls (C2/C3: p=0.005; T9/T10: p=0.041), but had no significant difference in either the SC white matter or total cord areas. Cervical and thoracic GM areas were not correlated with the number of SC T2-lesions. In the subgroup of patients without prior SC relapses (N=32), a multivariable model based on cervical SC GM area as the predictor variable with age and sex as covariates explained 48% of EDSS variance. While in the patients with prior SC relapses there was no significant association between SC GM area and EDSS, the number of SC T2-lesions did predict 26% of EDSS variance in this subgroup in a linear model (with age and sex as covariates). Conclusions: SC GM atrophy is already detectable at an early stage of MS, in absence of detectable WM atrophy, and affects both the cervical and thoracic cord. Disclosure: Dr. Schlaeger has nothing to disclose. Dr. Papinutto has nothing to disclose. Dr. Zhu has nothing to disclose. Dr. Datta has nothing to disclose. Dr. Bevan has nothing to disclose. Dr. Caverzasi has nothing to disclose. Dr. Jordan has nothing to disclose. Dr. Lobach has nothing to disclose. Dr. Keshavan has nothing to disclose. Dr. Kirkish has nothing to disclose. Dr. Stern has nothing to disclose. Dr. Devereux has nothing to disclose. Dr. Baker has nothing to disclose. Dr. Bove has nothing to disclose. Dr. Gelfand has received compensation for consulting on a scientific advisory board for Genentech. He also also received compensation for medical-legal consulting. Dr. Gelfand9s wife received compensation for consulting on a scientific advisory board for Eli Lilly, Zosano and travel expense reimbursement from Teva. . Research support to UCSF from Genentech for a clinical trial and Quest Diagnostics for development of a dementia care pathway. Dr. Gelfand9s wife received research support to UCSF from Allergan and eNeura.. Dr. Graves has received research support from Genentech, Biogen and S3 Group. Dr. Green has received personal compensation for activities with Inception Sciences, Mylan Pharma, Medimmune, and Bionure. Dr. Green has received personal compensation for serving on the board of Inception Sciences. Dr. Green holds stock and/or stock options in Inception Sciences. Dr. Green has received research support from Inception Sciences, Biogen, and Novartis. Dr. Waubant has received research support from Roche, Biogen Idec and Novartis. Dr. Wilson has nothing to disclose. Dr. Goodin has received personal compensation for scholarly activities from pharmaceutical companies that develop products for multiple sclerosis, including Bayer-Schering Pharma Dr. Cree has received personal compensation for activities with AbbVie, Biogen, EMD Serono, Novartis and Shire as a consultant. Dr. Hauser has received personal compensation for activities with Annexon, Symbiotix, Bionure as a scientific advisory board member and from F. Hoffmann-La Roche Ltd. Dr. Henry has nothing to disclose.