Abstract Details

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

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) S33 - Aging and Dementia: Non-Alzheimer Dementia (4:42 PM-4:54 PM)

Poster/Presentation
Number 007

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 < 0.05) without associated changes in GM and DTI parameters. At 18 and 36-month follow-up, WM atrophy in C9+ subjects older than 40 years was accompanied by significant progressive corticospinal tract fractional anisotropy (FA) reduction (p-value = 0.031). Intriguingly, asymptomatic C9+ subjects older than 40 years with a family history of ALS exhibited significant global CSA and CST FA reduction on their baseline scans.

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.

Authors/Disclosures
Giorgia Querin, MD (Universita Degli Studi Di Padova) PRESENTER	No disclosure on file
Peter Bede, MD, PhD (Academic Unit of Neurology)	Dr. Bede has nothing to disclose.
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Dario Saracino (Paris Brain Institute / Sorbonne Université / Hôpital Pitié-Salpêtrière)	Dario Saracino has nothing to disclose.
Francois Salachas (Hopital De La Pitie Salpetriere Fed Maladies)	No disclosure on file
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