Regional reduction of high-energy phosphorus metabolites characterizes the cerebellar subtype of multiple system atrophy

Abstract Multiple system atrophy (MSA) is a severe neurodegenerative disorder with various underlying pathophysiological features. Mitochondrial dysfunction has been implied as a viable treatment target in patients with MSA. Yet, there is a lack of in-vivo studies examining regional metabolic differences between the Parkinsonian (MSAp) and the cerebellar (MSAc) subtype of MSA. Twenty-four patients with MSA (12 patients with MSAp and 12 patients with MSAc), 24 patients with Parkinson’s disease (PD), and 24 age- and sex-matched healthy controls (HCs) underwent clinical evaluations and multimodal neuroimaging, including 31 P-MRSI targeting the basal ganglia and the cerebellum. Ratios of high-energy phosphorus-containing metabolites (HEPs) were compared between groups. Only patients with MSAc showed decreased HEP levels in the cerebellum. Conversely, no differences in basal ganglia HEP levels appeared between both MSA subtypes, patients with PD, or HCs. Our findings provide preliminary in-vivo evidence for regionally detectable bioenergetic alterations in the cerebellum of patients with MSAc, while basal ganglia results, particularly in MSAp, require cautious interpretation because of the spatial-resolution limits of the present 31 P-MRSI approach.