Veronica Castelnovo1,2, Silvia Paola Caminiti1,3, Nilo Riva4, Giuseppe Magnani4, Vincenzo Silani5,6, Daniela Perani7,8,9. 1. Vita-Salute San Raffaele University, Milan, Italy. 2. Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy. 3. In vivo Structural and Molecular Neuroimaging Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy. 4. Department of Neurology, San Raffaele Hospital, Milan, Italy. 5. Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy. 6. Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, Università degli Studi di Milano, Milan, Italy. 7. Vita-Salute San Raffaele University, Milan, Italy. perani.daniela@hsr.it. 8. In vivo Structural and Molecular Neuroimaging Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy. perani.daniela@hsr.it. 9. Nuclear Medicine Unit, San Raffaele Hospital, Milan, Italy. perani.daniela@hsr.it.
Abstract
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVE: 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. METHODS: 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/ALSpatients carrying the C9orf72 mutation. RESULTS: 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. CONCLUSIONS: 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.
Authors: Stacey Li Hi Shing; Mary Clare McKenna; We Fong Siah; Rangariroyashe H Chipika; Orla Hardiman; Peter Bede Journal: Brain Imaging Behav Date: 2021-01-05 Impact factor: 3.978
Authors: Joke De Vocht; Jeroen Blommaert; Martijn Devrome; Ahmed Radwan; Donatienne Van Weehaeghe; Maxim De Schaepdryver; Jenny Ceccarini; Ahmadreza Rezaei; Georg Schramm; June van Aalst; Adriano Chiò; Marco Pagani; Daphne Stam; Hilde Van Esch; Nikita Lamaire; Marianne Verhaegen; Nathalie Mertens; Koen Poesen; Leonard H van den Berg; Michael A van Es; Rik Vandenberghe; Mathieu Vandenbulcke; Jan Van den Stock; Michel Koole; Patrick Dupont; Koen Van Laere; Philip Van Damme Journal: JAMA Neurol Date: 2020-08-01 Impact factor: 18.302