Multiple system atrophy (MSA) may be difficult to distinguish clinically from other disorders, particularly in the early stages of the disease. An autonomic-only presentation can be indistinguishable from
pure autonomic failure. Patients presenting with
parkinsonism may be misdiagnosed as having
Parkinson disease. Patients presenting with the cerebellar phenotype of MSA can mimic other adult-onset
ataxias due to alcohol, chemotherapeutic agents, lead,
lithium, and
toluene, or
vitamin E deficiency, as well as paraneoplastic, autoimmune, or genetic
ataxias. A careful medical history and meticulous neurological examination remain the cornerstone for the accurate diagnosis of MSA. Ancillary investigations are helpful to support the diagnosis, rule out potential mimics, and define therapeutic strategies. This review summarizes diagnostic investigations useful in the differential diagnosis of patients with suspected MSA. Currently used techniques include structural and functional brain imaging, cardiac sympathetic imaging, cardiovascular autonomic testing, olfactory testing, sleep study, urological evaluation, and
dysphagia and cognitive assessments. Despite advances in the diagnostic tools for MSA in recent years and the availability of consensus criteria for clinical diagnosis, the diagnostic accuracy of MSA remains sub-optimal. As other diagnostic tools emerge, including skin biopsy,
retinal biomarkers, blood and cerebrospinal fluid
biomarkers, and advanced genetic testing, a more accurate and earlier recognition of MSA should be possible, even in the
prodromal stages. This has important implications as misdiagnosis can result in inappropriate treatment, patient and family distress, and erroneous eligibility for clinical trials of disease-modifying drugs.