Heterogeneous brain FDG-PET metabolic patterns in patients with C9orf72 mutation

  • Veronica Castelnovo
  • Silvia Paola Caminiti
  • Nilo Riva
  • Giuseppe Magnani
  • Vincenzo Silani
  • Daniela Perani
Original Article



The hexanucleotide repeat expansion in C9orf72 is an associated genetic cause in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In the “ALS/FTD” spectrum prevails clinical heterogeneity and an in vivo knowledge of the underling brain dysfunction in patients carrying C9orf72 mutation remain limited and only described at group level. The study aimed to assess the brain metabolic alterations characterizing patients with C9orf72 mutation using FDG-PET in single individuals.


We applied a validated statistical parametric mapping (SPM) voxel-based procedure for FDG-PET data to obtain maps of brain relative hypometabolism and hypermetabolism at single-subject level in six FTD/ALS patients carrying the C9orf72 mutation.


Clinical diagnoses classified the patients as right semantic variant of frontotemporal dementia (one case, C9svFTD), behavioral variant of frontotemporal dementia (two cases, C9bvFTD), and bulbar amyotrophic lateral sclerosis (three cases, C9bALS). The FDG-PET SPM revealed a prevalent frontal hypometabolism in C9bvFTD cases, and right temporal polar and lateral involvement in C9svFTD, consistent with the clinical diagnosis. There was a quite comparable occipital and cerebellar hypermetabolism in these cases. The three C9bALS patients showed variable patterns of hypo- and hypermetabolism.


The present work is the first in vivo FDG-PET study showing the heterogeneous patterns of brain regional hypo- and hypermetabolism in single patients sharing C9orf72 mutation. Brain hypometabolism was consistent with the clinical phenotypes, supporting the diagnostic importance of neuroimaging functional biomarkers to capture at single-subject level specific brain dysfunction.


ALS-FTD spectrum C9orf72 Heterogeneity Positron emission tomography Statistical parametric mapping 



This work was supported by the Italian Ministry of Health (Ricerca Finalizzata Progetto Reti Nazionale AD NET-2011-02346784) and a grant from IVASCOMAR Project (grant agreement no. CTN01_00177_165430).

Supplementary material

10072_2018_3685_MOESM1_ESM.docx (38 kb)
ESM 1 (DOCX 37 kb)


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Copyright information

© Fondazione Società Italiana di Neurologia 2018

Authors and Affiliations

  1. 1.Vita-Salute San Raffaele UniversityMilanItaly
  2. 2.Neuroimaging Research Unit, Institute of Experimental Neurology, Division of NeuroscienceSan Raffaele Scientific InstituteMilanItaly
  3. 3.In vivo Structural and Molecular Neuroimaging Unit, Division of NeuroscienceSan Raffaele Scientific InstituteMilanItaly
  4. 4.Department of NeurologySan Raffaele HospitalMilanItaly
  5. 5.Department of Neurology and Laboratory of NeuroscienceIRCCS Istituto Auxologico ItalianoMilanItaly
  6. 6.Department of Pathophysiology and Transplantation, “Dino Ferrari” CenterUniversità degli Studi di MilanoMilanItaly
  7. 7.Nuclear Medicine UnitSan Raffaele HospitalMilanItaly

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