P.217 Cervical spinal cord MRI parameters as predictors of early degeneration in asymptomatic C9Orf72 carriers: a longitudinal study.

Abstract

Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal dementia (FTD) share genetic susceptibility and a large portion of familial cases are due to <i>C9orf72</i> gene mutations. Brain and spinal cord (SC) imaging studies in asymptomatic <i>C9orf72</i> carriers have demonstrated white (WM) and grey matter (GM) degeneration up to 20 years before the expected symptom onset. The objective of this study is to longitudinally describe, using quantitative MRI, the evolution of SC degeneration over 36 months' observation in a cohort of asymptomatic <i>C9orf72</i> mutation carriers. 40 asymptomatic <i>C9orf72</i> carriers (C9+) and 32 non-mutated healthy controls were enrolled in the study. Each subject underwent a 3T cervical SC MRI at baseline, after 18 and 36 months. Quantitative measures of GM and WM atrophy and DTI parameters (FA, AD, MD, RD) in the cortico-spinal tracts (CSTs) were computed. We used linear mixed-effects models to test for significant differences in MRI parameters between time points. Time point, baseline age, gender, genetic status and interaction terms between time point and age, and between time point and genetic status were considered as fixed effects. Multivariate linear regression was used to test if MRI parameters are capable of predict genetic status of the subjects. Sex and family phenotype (ALS or FTD) were used as covariates. Mean age at inclusion was 41.18 years +/- 11.46. No significant difference in GM and WM cross-sectional area was observed over the three time points in C9+ subjects. A significant progressive reduction of fractional anisotropy (FA) in the CSTs was observed over time with a significant difference between the baseline and the 36-months evaluation (p = 0.04). No other significant modifications in DTI parameters were detected. FA in the CSTs was also the only significant parameter in a multivariate model predicting mutation status of the study subjects (p = 0.03). Cervical SC imaging of <i>C9orf72</i> hexanucleotide carriers detect a progressive pyramidal tract FA reduction which seems to be continuous but not linear. CSTs degeneration as described by FA decrease also allows to identify C9+ carriers, suggesting that it could be a useful parameter for early diagnosis of the disease.