Abstract Details

Title PET in in ALS Patients with C9ORF72 Mutations

Topic Anterior Horn

Presentation(s) P06 - (-)

Poster/Presentation
Number 131

Objective

Background BACKGROUND: Recently, a GGGGCC hexanucleotide repeat expansion in the C9ORF72 gene has been demonstrated to be the commonest cause of familial ALS and to account also for 5 to 10% of apparently sporadic ALS. Relatively little is known about the imaging profile of patients carrying the expansion.

Design/Methods DESIGN/METHODS: FDG-PET scans of 12 ALS patients carryng C9ORF72 mutation were compared with those of 40 controls and 30 ALS patients without mutations of ALS-related genes, matched to cases by age, gender, disease duration and clinical phenotype. ALS patients and controls underwent neuropsychological testing and classified as FTD, isolate executive impairment, and cognitively normal; these groups of subjects were fully comparable, with the exception of FTD, which was more common in ALS patients with C9ORF72 mutation.

Results RESULTS: ALS cases with C9ORF72 mutation compared to controls had a relative hypometabolism in bilateral frontal and anterior cingulate cortex, and in bilateral caudate head, thalamus and midbrain and a relative hypermetabolism in the pons and cerebellum. ALS cases with C9ORF72 mutation compared to ALS cases without genetic mutations showed a relative hypometabolism in the thalamus, posterior and anterior cingulate cortex, the medial frontal cortex bilaterally, and in the right prefrontal cortex, insula and caudate head, and relative hypermetabolism in bilateral cerebellum, midbrain and pons and in the left claustrum, lateral globus pallidus and putamen.

Conclusions CONCLUSIONS: We conclude that ALS patients with C9ORF72 hexanucleotide repeat expansion have a more widespread CNS involvement compared to ALS patients without genetic mutations consistent with their more severe clinical picture, involving FTD, psychotic-like and extrapyramidal symptoms, and more rarely cerebellar signs. Our data also suggest that the 'systemic' lesions related to this mutation are already present in the early clinical phases of the disorder.

Authors/Disclosures
Andrea Calvo, MD, PhD, FAAN (Dept. of Neuroscience, University of Turin) PRESENTER	Dr. Calvo has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Cristina Moglia (University of Torino)	Cristina Moglia has nothing to disclose.
	No disclosure on file
	No disclosure on file
Bryan Traynor, MD (National Institute on Aging)	The institution of Dr. Traynor has received research support from ALS Association. The institution of Dr. Traynor has received research support from Merck. The institution of Dr. Traynor has received research support from Myasthenia Gravis Foundation. The institution of Dr. Traynor has received research support from Cerevel Therapeutics. Dr. Traynor has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
	No disclosure on file
Leonardo Lopiano, MD	No disclosure on file
	No disclosure on file
Adriano Chio, MD, FAAN (Dept. of Neuroscience, University of Turin)	Dr. Chio has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cytokinetics. Dr. Chio has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi. Dr. Chio has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Chio has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Corcept.

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