We aimed to establish the diagnostic performance of the 2008 consensus criteria for multiple system atrophy (MSA) in a neuropathologically defined cohort.

The 2008 diagnostic criteria for MSA are accepted in research and clinical practice, however, validation of these criteria using neuropathology as a gold standard has not been performed.

From a database of 251 pathological cases of neurodegenerative parkinsonism or cerebellar disorders referred to the Mayo Clinic between 1995 and 2020, 83 patients with a definite pathological diagnosis of MSA were identified by one of the authors (EAC) and 130 cases were excluded due to insufficient data. A neurologist (GL), blinded to the neuropathologic diagnoses, performed a retrospective chart review of symptoms, examination findings, laboratory, and imaging of 121 cases (quality check performed by FA). Variables were recorded for the first 6 months after initial evaluation (T1) and the last 6 months prior to the final evaluation (T2).

Patients had a pathological diagnosis of MSA (N=83), PD (N=4), DLB (N=20), PSP (N=10), vascular parkinsonism (N=3), and Alzheimer disease (N=1). Follow-up data was available for 63 patients (49.2%). Median times from symptom onset to T1, T1 to T2, and T2 to death were 35.6, 34.6, and 52.2 months respectively. At T1, 72/83 (86.7%) patients with MSA met the MSA clinical criteria (probable N=52, possible N=20) compared to 11/38 (28.9%) patients with other disorders (possible N=5, probable N=6). At T2, 40/41 (97.6%) patients with MSA met the clinical criteria for MSA (probable N=36, possible N=4) compared to 7/22 (31.8%) patients with other disorders (probable N=1, possible N=6).

For patients evaluated by a specialist, the sensitivity and specificity of the 2008 criteria for the diagnosis of MSA are 86.7% and 71.1%, respectively. The sensitivity increases to 97.6% with follow-up while the specificity remains low at 68.2%.