Validation Study of the MDS Criteria for the Diagnosis of Multiple System Atrophy in the Mayo Clinic Brain Bank

Abstract

Background and Objective: The second consensus criteria in 2008 have been used in diagnosing multiple system atrophy (MSA). The International Parkinson and Movement Disorder Society (MDS) proposed new diagnostic criteria for MSA in 2022. This study aimed to compare the diagnostic accuracy between these two criteria and validate the clinical utility of the newly proposed criteria for MSA. Methods: We conducted a retrospective autopsy cohort study of consecutive patients with a clinical or pathological diagnosis of MSA from the Mayo Clinic brain bank between 1998 and 2021. We studied 352 patients (250 pathologically-diagnosed MSA and 102 non-MSA); MDS criteria and the second consensus criteria were applied. The sensitivity, specificity, and area under the curve (AUC) of receiver operating characteristic curves were compared between these criteria. Comparison was conducted between clinical subtypes and among clinically challenging cases (those with different clinical diagnoses or those with suspected but undiagnosed MSA before death). We also employed machine learning algorithm, eXtreme Gradient Boosting, to identify clinical features contributing diagnostic performance. Results: The sensitivity and specificity of clinically established and probable MSA by the MDS criteria were 16% and 99% and 64% and 74%, respectively. The sensitivity and specificity of probable MSA and possible MSA by the second consensus criteria were 72% and 52% and 93% and 21%, respectively. The AUC of MDS clinically probable MSA was the highest (0.69). The diagnostic performance did not differ between clinical subtypes. In clinically challenging cases, MDS clinically established MSA maintained high specificity and MDS clinically probable MSA demonstrated the highest AUC (0.62). MRI findings contributed to high specificity. In addition, combining core clinical features with two or more from any of the 13 supporting features and the absence of exclusion criteria also yielded high specificity. Among supporting features, rapid progression was most important for predicting MSA pathology. Discussion: The MDS criteria showed high specificity with clinically established MSA and moderate sensitivity and specificity with clinically probable MSA. The observation that high specificity could be achieved with clinical features alone suggests that MSA diagnosis with high specificity is possible even in areas where MRI is not readily available.

The Movement Disorder Society Criteria: Its Clinical Usefulness in Multiple System Atrophy

“…However, Virameteekul et al ( 13) and Sekiya et al ( 14) performed a patho-logical evaluation of the usefulness of MDS criteria. In these studies, the sensitivity of the clinically established and clinically probable classifications was 20.4% and 62.1% (13), respectively, and 16% and 64% (14). The specificity of the clinically established and clinically probable classifications was 100% and 95.3% (13), respectively, and 99% and 74% (14).…”

“…In these studies, the sensitivity of the clinically established and clinically probable classifications was 20.4% and 62.1% (13), respectively, and 16% and 64% (14). The specificity of the clinically established and clinically probable classifications was 100% and 95.3% (13), respectively, and 99% and 74% (14). Therefore, the patients enrolled in this study generally met the diagnostic criteria from the early stages of disease onset, and a high rate of positive diagnoses was expected.…”