Multiple system atrophy of the cerebellar type (MSA-C) with concomitant beta-amyloid and tau pathology

Multiple system atrophy (MSA) is a rapidly progressive sporadic alpha-synucleinopathy with adult onset characterized by progressive cerebellar ataxia, basal ganglia symptoms, autonomic dysfunction and pyramidal tract signs. While full-blown dementia is considered an exclusion criterion according to Consensus Guidelines, mild cognitive deficits such as fronto-executive dysfunction have been reported in some MSA individuals. However, the underlying anatomic correlate still has to be elucidated. We here report a 74-year-old patient with a clinical diagnosis of "probable MSA of the cerebellar type (MSA-C)" who developed pronounced clinical symptoms of fronto-executive dysfunction. Neuropathologic investigations revealed (1) numerous glial cytoplasmic inclusions (GCI) in the putamen, mesencephalon and cerebellum, (2) pronounced beta-amyloid-pathology in the frontal lobe and (3) mild hippocampal tau-pathology. In this patient, fronto-executive dysfunction can easily be explained by frontal degeneration typical for AD. These findings challenge the concept of cognitive dysfunction as a core feature of MSA as long as concomitant pathology other than MSA has not been reliably excluded by post mortem analysis.