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Cited by 129Amyotrophic Lateral Sclerosis ResearchDementia and Cognitive Impairment ResearchGenetic Neurodegenerative Diseases

The metabolic signature of C9ORF72-related ALS: FDG PET comparison with nonmutated patients

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Cistaro, Angelina, Pagani, Marco, Montuschi, Anna, Calvo, Andrea, Moglia, Cristina, Canosa, Antonio, Restagno, Gabriella, Brunetti, Maura +7 more·2014·European Journal of Nuclear Medicine and Molecular Imaging
DOI 10.1007/s00259-013-2667-5PMC PMC8957062
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Abstract

PURPOSE: 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. CONCLUSION: 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.

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  • Higher severity of symptoms in genetic FTD correlates with more widespread areas of hypometabolism on FDG-PET.

    “and the higher severity of symptoms in these forms correlates with more widespread areas of hypometabolism on FDG-PET [134].”

    From The use of neuroimaging techniques in the early and differential diagnosis of dementia (2023) · cites this paper as [134]

    The Results (PET findings; page not available) report more extensive FDG-PET hypometabolism in C9ORF72-related ALS than in ALS-FTD without the expansion. The Discussion links the metabolic pattern to symptoms, but does not report a correlation between symptom severity and the extent of hypometabolism in genetic FTD; the studied genetic group had ALS. (LLM, conf=0.84)

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Authors
Cistaro, A., Pagani, M., Montuschi, A., Calvo, A., Moglia, C., Canosa, A., Restagno, G., Brunetti, M., Traynor, B. J., Nobili, F., Carrara, G., Fania, P., Lopiano, L., Valentini, M. C., & Chiò, A.
Affiliations
  • Karolinska University Hospital (SE)
  • University of Turin (IT)
  • Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT)
  • National Institutes of Health (US)
  • University of Genoa (IT)
Corresponding author
Chiò, Adriano
ORCID
Venue
European Journal of Nuclear Medicine and Molecular Imaging
Publisher
Springer Science and Business Media LLC
Published
2014-01-21
Volume
41
Issue
5
Pages
844-852
ISSN
  • 1619-7070 (ISSN-L)
  • 1619-7089
DOI
10.1007/s00259-013-2667-5
PMC
PMC8957062
OpenAlex
W2069443367
Cited by
129
References
5
Citations by year
2026: 5 · 2025: 13 · 2024: 7 · 2023: 17 · 2022: 7 · 2021: 16 · 2020: 7 · 2019: 10 · 2018: 9 · 2017: 7 · 2016: 12 · 2015: 10 · 2014: 9
FWCI
8.26
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • European Journal of Nuclear Medicine and Molecular Imaging (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
  • CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion)
Funders
  • Biogen
  • Compagnia di San Paolo
  • Cytokinetics
  • Ministero della Salute (RF-2010-2309849, 259867, RF 2010)
  • National Institutes of Health (Z01‐AG000949‐02, Z01-AG000949)
  • National Institute on Aging (Z01AG000949, ZIAAG000933)
Topics
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
Keywords
C9orf72, amyotrophic lateral sclerosis, hexanucleotide repeat expansion, FDG-PET, brain metabolism, frontotemporal dementia, sporadic ALS, hypometabolism, hypermetabolism, cingulate cortex, insula, thalamus, disease severity
MeSH terms
C9orf72 Protein, Aged, Amyotrophic Lateral Sclerosis, Cerebral Cortex, Female, Humans, Male, Middle Aged, Mutation, Proteins, Case-Control Studies, Radiopharmaceuticals, Fluorodeoxyglucose F18, Positron-Emission Tomography

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