Pathological Validation of the MDS Criteria for the Diagnosis of Multiple System Atrophy

Abstract Background The recent International Parkinson and Movement Disorder Society diagnostic criteria for multiple system atrophy (MDS‐MSA) have been developed to improve diagnostic accuracy although their diagnostic properties have not been evaluated. Objectives The aims were to validate the MDS‐MSA diagnostic criteria against neuropathological diagnosis and compare their diagnostic performance to previous criteria and diagnosis in clinical practice. Methods Consecutive patients with sporadic, progressive, adult‐onset parkinsonism, or cerebellar ataxia from the Queen Square Brain Bank between 2009 and 2019 were selected and divided based on neuropathological diagnosis into MSA and non‐MSA. Medical records were systematically reviewed, and clinical diagnosis was documented by retrospectively applying the MDS‐MSA criteria, second consensus criteria, and diagnosis according to treating clinicians at early (within 3 years of symptom onset) and final stages. Diagnostic parameters (sensitivity, specificity, positive/negative predictive value, and accuracy) were calculated using neuropathological diagnosis as gold standard and compared between different criteria. Results Three hundred eighteen patients (103 MSA and 215 non‐MSA) were included, comprising 248 patients with parkinsonism and 70 with cerebellar ataxia. Clinically probable MDS‐MSA showed excellent sensitivity (95.1%), specificity (94.0%), and accuracy (94.3%), although their sensitivity at early stages was modest (62.1%). Clinically probable MDS‐MSA outperformed diagnosis by clinicians and by second consensus criteria. Clinically established MDS‐MSA showed perfect specificity (100%) even at early stages although to the detriment of low sensitivity. MDS‐MSA diagnostic accuracy did not differ according to clinical presentation (ataxia vs. parkinsonism). Conclusions MDS‐MSA criteria demonstrated excellent diagnostic performance against neuropathological diagnosis and are useful diagnostic tools for clinical practice and research. © 2023 International Parkinson and Movement Disorder Society.