A Guide for the Differential Diagnosis of Multiple System Atrophy in Clinical Practice

Multiple system atrophy (MSA) is a sporadic and progressive neurodegenerative disorder with a complex differential diagnosis. A range of disorders- also of nondegenerative etiology- can mimic MSA, expanding its differential diagnosis. Both misdiagnosis and diagnostic delays are relatively common in clinical practice. A correct diagnosis is vital for daily clinical practice, in order to facilitate proper counselling and to timely install therapies in treatable disorders that mimic MSA. A correct diagnosis is also essential for including properly classified individuals into research studies that aim to better understand the pathophysiology of MSA, to develop specific biomarkers or to evaluate novel symptomatic or disease-modifying therapies. Here, we offer some practical guidance to support the diagnostic process, by highlighting conditions that may be considered as MSA lookalikes, by emphasizing some key clinical aspects of these mimics, and by discussing several useful ancillary diagnostic tests.