Brain 18Fluorodeoxyglucose-Positron Emission Tomography changes in Amyotrophic Lateral Sclerosis with TARDBP mutations

Amyotrophic Lateral Sclerosis (ALS) is a motor neuron degenerative disorder, causing death within 2-5 years from onset. In 2008, mutations of TARDBP gene, encoding for TDP-43, were identified as cause of familial (fALS) and sporadic ALS (sALS).1 The cytoplasmic inclusions of hyperphosphorylated TDP-43 (pTDP-43) within neurons and glia in the motor cortex is the neuropathological hallmark in ~95% of ALS cases, with the exception of those with SOD1 and FUS mutations.2 In a population-based study the presence of TARDBP mutations was associated with an increased frequency of a predominantly upper motor neuron phenotype (Chiò A, Moglia C, Canosa A, et al. ALS phenotype is influenced by age, sex, and genetics: A population-based study. Neurology. 2020;94(8):e802-e810. doi:10.1212/WNL.0000000000008869). Currently, neuroimaging studies evaluating in vivo the extent of the neurodegenerative process in patients with TARDBP mutations (TARDBP-ALS) are limited, highlighting frontotemporal changes in cases with cognitive-behavioural impairment (Häkkinen S, Chu SA, Lee SE. Neuroimaging in genetic frontotemporal dementia and amyotrophic lateral sclerosis. Neurobiol Dis. 2020;145:105063. doi:10.1016/j.nbd.2020.105063). We aimed to assess the brain metabolic changes associated with TARDBP-ALS, performing brain 18-F-2-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG-PET).