The metabolic signature of C9ORF72-related ALS: FDG PET comparison with nonmutated patients.
OBJECTIVE
Recently, a GGGGCC hexanucleotide repeat expansion in the C9ORF72 gene, located on chromosome 9p21 has been demonstrated to be the commonest cause of familial amyotrophic lateral sclerosis (ALS) and to account for 5 to 10 % of apparently sporadic ALS. Relatively little is known about the brain metabolism profile of patients carrying the expansion. Our aim was to identify the [(18)F]FDG PET profile in ALS patients with the C9ORF72 expansion (C9ORF72-ALS).


METHODS
Fifteen C9ORF72-ALS patients were compared with 12 patients with ALS and comorbid frontotemporal dementia (FTD) without the C9ORF72 expansion (ALS-FTD) and 30 cognitively normal patients with ALS without mutations of ALS-related genes (sALS). The three groups were then cross-matched to 40 neurologically normal controls. All patients underwent FDG PET within 4 months of diagnosis.


RESULTS
The C9ORF72-ALS patients compared with the sALS patients showed significant hypometabolism in the anterior and posterior cingulate cortex, insula, caudate and thalamus, the left frontal and superior temporal cortex, and hypermetabolism in the midbrain, bilateral occipital cortex, globus pallidus and left inferior temporal cortex. The ALS-FTD patients compared with the sALS patients showed more limited hypometabolic areas, including the orbitofrontal, prefrontal, anterior cingulate and insular cortex, and hypermetabolic areas, including the bilateral occipital cortex, the left precentral and postcentral cortex and superior temporal gyrus. The C9ORF72-ALS patients compared with the ALS-FTD patients showed hypometabolism in the left temporal cortex.


CONCLUSIONS
ALS patients with the C9ORF72 hexanucleotide repeat expansion had a more widespread central nervous system involvement than ALS patients without genetic mutations, with or without comorbid FTD, consistent with their more severe clinical picture.
Positron Emission Tomography Center IRMET S.p.A, Torino, Italy.
Angelina
A
Cistaro
Marco
M
Pagani
Anna
A
Montuschi
Andrea
A
Calvo
Cristina
C
Moglia
Antonio
A
Canosa
Gabriella
G
Restagno
Maura
M
Brunetti
Bryan J
BJ
Traynor
Flavio
F
Nobili
Giovanna
G
Carrara
Piercarlo
P
Fania
Leonardo
L
Lopiano
M Consuelo
MC
Valentini
Adriano
A
Chiò
D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism; D000073885:C9orf72 Protein; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D049268:Positron-Emission Tomography; D011506:Proteins / Q000235:genetics*; D019275:Radiopharmaceuticals
D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18