The Diagnostic Value Of Diffusion Tensor MRI Metrics In Relation To The MND Phenotype Heterogeneity (P7.007)

OBJECTIVE: To investigate diffusion tensor (DT) MRI metrics as predictors of motor neuron disease (MND) diagnosis. BACKGROUND: Reliable markers for upper motor neuron (UMN) and extra-motor white matter (WM) damage may facilitate MND diagnosis. DESIGN/METHODS: Corticospinal tract (CST), corpus callosum (CC) and extra-motor tract DT MRI measures were obtained from 123 MND patients and 35 healthy subjects. DT MRI metric C-indices were estimated using logistic regression analyses. Support vector machine (SVM) classification algorithm assessed DT MRI metric accuracy as predictors of MND diagnosis at individual patient level. RESULTS: MND patients showed damage to CST and motor callosal fibers (C-index range: 0.65-0.74). No DT MRI abnormalities were found in pure lower motor neuron (LMN) and flail arm patients. The most severe and widespread damage was found in pure UMN/pyramidal ALS (C-index up to 0.81 for CST and 0.91 for CC). Classical, respiratory and bulbar ALS showed damage to CST and callosal motor fibers (C-index≍0.70). In bulbar patients, uncinate and cingulum damage was also found. In classical, respiratory and bulbar ALS, patterns of damage were confirmed in cases with disease duration bulbar>classical/respiratory>pure LMN/flail arm. The highest C-index (up to 0.94) was found for CC DT MRI measures distinguishing pure UMN/pyramidal from pure LMN patients. SVM showed the highest diagnostic accuracy (0.93) in the comparison pure UMN/pyramidal vs. pure LMN. Disease severity and UMN involvement correlated with damage to CST, entire CC and motor callosal fibers. CONCLUSIONS: DT MRI provides sensitive objective measures of UMN and extra-motor burden at the individual level in MND patients, including those at the early phase of the disease. This study provides a roadmap for translation of MRI predictors of MND into daily practice. Study Supported by: Italian Ministry of Health (#RF-2010-2313220). Disclosure: Dr. Spinelli has nothing to disclose. Dr. Agosta has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec, Sanofi-Aventis Pharmaceuticals Inc., and Serono Symposia International Foundation. Dr. Agosta has received personal compensation in an editorial capacity for the Journal of Neurology. Dr. Agosta has received research support from the Italian Ministry of Health, and Teva Neuroscience. Dr. Riva has nothing to disclose. Dr. Copetti has nothing to disclose. Dr. Galantucci has nothing to disclose. Dr. Messina has nothing to disclose. Dr. Iannaccone has nothing to disclose. Dr. Calvo has nothing to disclose. Dr. Silani has nothing to disclose. Dr. Falini has nothing to disclose. Dr. Comi has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals Inc., Novartis, Merck Serono, Biogen Idec, Bayer Pharmaceuticals Corp., Teva Neuroscience, and Actellion. Dr. Filippi has received personal compensation for activities with Teva Neuroscience and Genmab AS as a member of scientific advisory boards, and Bayer Pharmaceuticals Corp. as a consultant. Dr. Filippi has received research support from Bayer Schering, Biogen Idec, Genmab AS, Merck Serono, Teva Neuroscience, the Italian Ministry of Health, and the Fondazione Italiana Sclerosi Mult.