Current Landscape of Clinical Diagnosis in Multiple System Atrophy: A 15-Year Analysis From 2008 to 2022

Clinical diagnosis of multiple system atrophy (MSA) is challenging. In 2022, new diagnostic criteria for MSA were proposed. We hypothesized that the positive predictive value (PPV) of clinical diagnosis of MSA improved because of advanced diagnostic tools, including brain MRI. This study aimed to understand temporal changes in PPV of MSA.

We conducted a retrospective analysis of patients clinically diagnosed with MSA whose brains were examined in the Mayo Clinic brain bank from 2008 to 2022. PPV was compared between 2 periods (2008-2017 and 2018-2022) and successively with a 4-year moving average. PPV for each clinical subtype (parkinsonism type [MSA-P] and cerebellar type [MSA-C]) was assessed.

This study included 321 patients (136 women, age at death 68 ± 9 years) with a clinical diagnosis of MSA. Among them, 225 were pathologically confirmed as MSA, resulting in an overall PPV of 70%. The remaining 30% had alternative pathologic diagnoses including Lewy body disease (18%), progressive supranuclear palsy (4%), cerebrovascular disease (1%), corticobasal degeneration (1%), and others (6%). PPV improved from 63% in 2008-2017 to 78% in 2018-2022 (odds ratio [OR] 2.0 [1.2-3.5], p = 0.005). Linear analysis also demonstrated increased PPV over time (r = 0.66 [0.14-0.89], p = 0.02). Brain MRI scans were more frequently performed in 2018-2022 compared with 2008-2017 (91% vs 80%; OR 2.4 [1.2-5.0], p = 0.012). PPV was higher in patients with brain MRI compared with those without (73% vs 52%; OR 2.5 [1.3-4.9], p = 0.0057). PPV for MSA-C was similar in both groups (87% in 2008-2017 and 93% in 2018-2022), while that for MSA-P improved from 59% in 2008-2017 to 72% in 2018-2022 (OR 1.8 [1.0-3.2], p = 0.04).

This study demonstrates an improvement in the PPV of MSA in recent years, potentially attributed to the increased use of brain MRI. Nevertheless, it also highlights that it remains difficult to make a correct diagnosis for some patients based on their clinical presentation. These findings provide a baseline for future clinicopathologic research on MSA.