Testing the diagnostic accuracy of [18F]FDG-PET in discriminating spinal- and bulbar-onset amyotrophic lateral sclerosis

Purpose: The role for [18F]FDG-PET in supporting amyotrophic lateral sclerosis (ALS) diagnosis is not fully established. In this study, we aim at evaluating [18F]FDG-PET hypo- and hyper-metabolism patterns in spinal- and bulbar-onset ALS cases, at the single-subject level, testing the diagnostic value in discriminating the two conditions, and the correlations with core clinical symptoms severity. Methods: We included 95 probable-ALS patients with [18F]FDG-PET scan and clinical follow-up. [18F]FDG-PET images were analyzed with an optimized voxel-based-SPM method. The resulting single-subject SPM-t maps were used to: a) assess brain regional hypo- and hyper-metabolism; b) evaluate the accuracy of regional hypo- and hyper metabolism in discriminating spinal vs. bulbar-onset ALS; c) perform correlation analysis with motor symptoms severity, as measured by ALS-FRS-R. Results: a) Primary motor cortex showed the most frequent hypo-metabolism in both spinal-onset (~57%) and bulbar-onset (~64%) ALS; hyper-metabolism was prevalent in the cerebellum in both spinal-onset (~56.5%) and bulbar-onset (~55.7%) ALS, and in the occipital cortex in bulbar-onset (~62.5%) ALS. b) Regional hypo-and hyper-metabolism at single-subject SPM-t-maps yielded a very low accuracy (AUC<0.63) in discriminating spinal- vs. bulbar-onset ALS; c) Severity of motor symptoms correlated with hypo-metabolism in sensorimotor cortex in spinal-onset ALS, and with cerebellar hyper-metabolism in bulbar-onset ALS. Conclusions: The high variability in regional hypo- and hyper-metabolism patterns, likely reflecting the heterogeneous pathology and clinical phenotypes, limits the diagnostic potential of [18F]FDG-PET in discriminating spinal and bulbar onset patients.