PET in in ALS Patients with C9ORF72 Mutations (P06.131)

OBJECTIVE: The aim of this study was to evaluate FDG-PET images in a series of ALS patients with C9ORF72 mutation. 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: 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: 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: 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 9systemic9 lesions related to this mutation are already present in the early clinical phases of the disorder. Supported by: In part supported by Compagnia di San Paolo, Programma Neuroscienze 2008–2009 (to C.V. and A. Calvo), Ministero della Salute (Ricerca Sanitaria Finalizzata, 2010, grant RF-2010-2309849) (to A. Chio) European Community9s Health Seventh Framework Programme (FP7/2007-2013 under grants agreement 259867 and 278611) (to A. Chio); The Intramural Research Programmes of the National Institutes of Health (NIH); National Institute on Aging (Z01-AG000949-02) (to B.J.T.). Disclosure: Dr. Calvo has nothing to disclose. Dr. Cistaro has nothing to disclose. Dr. Pagani has nothing to disclose. Dr. Montuschi has nothing to disclose. Dr. Moglia has nothing to disclose. Dr. Canosa has nothing to disclose. Dr. Restagno has nothing to disclose. Dr. Traynor stands to receive future royalty payments for a patent pending on the clinical testing and therapeutic intervention for the hexanucleotide repeat expansion of C9ORF72. Dr. Traynor has received research support from the Myasthenia Gravis Foundation. Dr. Nobili has received personal compensation for activities with Bayer. Dr. Carrara has nothing to disclose. Dr. Lopiano has nothing to disclose. Dr. Valentini has nothing to disclose. Dr. Chio has received personal compensation for activities with Biogen Idec and Cytokinetics.