Spinal Cord MRI for Early Detection of Presymptomatic Pathology in c9orf72 Mutation Carriers: A Longitudinal Neuroimaging Study

Objective: The objective of this study was to investigate whether cervical spinal cord (SC) degeneration can be detected in asymptomatic c9orf72 hexanucleotide carriers using multimodal quantitative imaging. Background: Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal dementia (FTD) are neurodegenerative conditions with a large portion of familial cases due to c9orf72gene mutations. Brain imaging studies in asymptomatic c9orf72 carriers have demonstrated white (WM) and grey matter (GM) degeneration before the age of 40. Design/Methods: 72 asymptomatic individuals were enrolled in a prospective study of first-degree relatives of ALS and FTD patients carrying the c9orf72 mutation. 40 (C9+) were carriers. Each subject underwent a 3T cervical SC MRI. Quantitative measures of GM and WM atrophy and DTI parameters were evaluated at baseline, after 18 and after 36 months. Results: No significant difference was observed between C9+ and C9- subjects younger than 40 years of age regarding morphometric and DTI parameters at each time point. At baseline, significant WM atrophy was detected in C9+ subjects older than 40 years of age (p-value Conclusions: Cervical SC imaging of c9orf72 hexanucleotide carriers does not detect degeneration in subjects younger than 40 years, but WM atrophy is observed in C9+ subjects older than 40. While WM atrophy remains stable, progressive pyramidal tract FA reduction can be detected on follow-up acquisitions. SC MRI in c9orf72 related conditions is a powerful tool to characterise presymptomatic pathological changes and to predict phenotypic conversion to ALS versus FTD. Disclosure: Dr. Querin has nothing to disclose. Dr. Bede has nothing to disclose. Dr. El Mendili has nothing to disclose. Dr. Pellegrini-Issac has nothing to disclose. Dr. Rinaldi has nothing to disclose. Dr. Catala has nothing to disclose. Dr. Saracino has nothing to disclose. Dr. Salachas has nothing to disclose. Dr. Camuzat has nothing to disclose. Dr. Marchand-Pauvert has nothing to disclose. Dr. Cohen-Adad has nothing to disclose. Dr. Colliot has nothing to disclose. Dr. Le Ber has nothing to disclose. Dr. Pradat has nothing to disclose.