To determine whether cross-sectional multimodal brain imaging of patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) reveals divergent structural gray matter (GM) and white matter (WM) degeneration in regions with hypo- and hypermetabolism.

Approximately 50% of patients with ALS develop some degree of cognitive dysfunction, with a fraction of these developing FTD. Such patients with ALS-FTD have greater morbidity and shorter survival times than ALS patients without FTD. While electromyography can clinically evaluate peripheral nervous system dysfunction, advanced noninvasive neuroimaging techniques are being used more often to assess and quantify central nervous system abnormalities. Initial [¹⁸F]-fluoro-2-deoxy-D-glucose positron emission tomography (¹⁸F-FDG PET) studies in ALS and ALS-FTD showed only hypometabolism in motor and extramotor brain regions while subsequent studies also demonstrated regional hypermetabolic changes. We were intrigued by the co-occurrence of these contrasting metabolic changes in ALS-FTD and wished to study their underlying structural correlates.

Analyses of cerebral glucose metabolic rate (CMR_glc), cortical thickness (CT), fractal dimension (FD), and graph theory WM network were performed on clinically-obtained MRI and ¹⁸F-FDG PET images from eight ALS-FTD patients and 14 control individuals to assess differences of structural GM and WM degeneration in hypo- and hypermetabolic brain regions.

CMR_glc revealed significant hypometabolism in frontal and precentral brain regions but hypermetabolism in temporal, occipital and cerebellar areas of patients with ALS-FTD. Decreased CT was observed in both hypo- and hypermetabolic regions while FD showed no abnormalities in areas with either type of CMR_glc abnormality. Graph theory analysis demonstrated differential WM degeneration between hypo- and hypermetabolic regions in ALS-FTD patients, most severe in hypometabolic areas and predominantly in the right hemisphere.