How Certain Are You When Making The Diagnosis of Multiple System Atrophy?

EDITORIAL
How Certain Are You When Making the Diagnosis of

Multiple System Atrophy?
Kinya Ishikawa, MD, PhD Correspondence
Dr. Ishikawa
®
Neurology 2023;101:1081-1082. doi:10.1212/WNL.0000000000208066 [email protected]
Multiple system atrophy (MSA) is a multisystem neurodegenerative disorder affecting adults RELATED ARTICLE
older than 30 years and presenting with a constellation of symptoms, including parkinsonian
Research Article
features, ataxia, and autonomic disturbances. The pathophysiology of MSA has gradually been
Validation Study of the
unveiled. It is characterized by α-synuclein protein aggregates in neurons and glial cells that are
MDS Criteria for the
different from those seen in Parkinson disease (PD).1 MSA is the most common condition,
Diagnosis of Multiple
after PD, that has parkinsonism as a cardinal feature, and it is also one of the most common
System Atrophy in the
causes of sporadic cerebellar ataxias. Because the clinical presentation is heterogeneous, we as Mayo Clinic Brain Bank
clinicians must always be certain of the probability of an MSA diagnosis for each patient we are
Page 1092
facing.
The new Movement Disorder Society (MDS) criteria include 4 categories: neuropathologically
established MSA, clinically established MSA, clinically probable MSA, and possible prodromal
MSA (as a research category).2 Clinically established MSA was designed to have maximum
specificity with acceptable specificity. In this issue of Neurology®, Sekiya et al.3 publish the
results of a study in which they validated recently proposed Movement Society Criteria for the
diagnosis of MSA using data from patients in the Mayo Clinic brain bank; they compared these
criteria with the second Consensus Statement on the diagnosis of MSA.4 Sekiya et al. completed
a detailed retrospective review of clinical charts and neuropathology data on 352 cases in the
Mayo Clinic brain bank that had clinical and pathologic diagnosis of MSA. These 352 cases
were divided into 3 groups by their clinical and pathologic diagnoses: (1) clinically and
pathologically diagnosed MSA (213 cases); (2) clinically diagnosed but pathologically excluded
(102 cases); and (3) clinically diagnosed as non-MSA, but pathologically confirmed as MSA
(37 cases). The authors applied the new MDS criteria (clinically established MSA and clinically
probable MSA) and the second Consensus Statement to the diagnosis of MSA (probable MSA
and possible MSA) to the 3 groups. The specificity of each diagnostic criterion was evaluated in
102 patients who were clinically diagnosed with MSA but whose MSA was not pathologically
confirmed. The sensitivity of each criterion was assessed in combined 2 groups of cases where
pathologic diagnosis was MSA (213 and 37 cases). In addition to comparing the sensitivity and
specificity of 4 criteria, the area under the curve (AUC) of receiver operating characteristics
between criteria was analyzed.
The highest specificity was seen with the clinically established MSA of the MDS criteria (99%),
followed by clinically probable MSA of the MDS criteria (74%), probable MSA of the second
Consensus Statement (52%), and possible MSA of the second Consensus Statement (21%).
The AUC was the highest in clinically probable MSA of the MDS criteria (0.69). High reliability
of the MDS criteria was consistently seen not only in cases with MSA-P or MSA-C but also in
clinically challenging cases because the specificity was the highest when conforming to the
clinically established MSA and the AUC was the highest (0.62) with the clinically probable
MSA. Different levels of specificity and AUC are important for clinicians seeing patients with
MSA. Sekiya et al. carefully discuss advantages of the second Consensus Statement when
considering the sensitivity, which was the highest in possible MSA (93%), followed by probable
MSA (72%), compared with the sensitivities in the MDS criteria (64% for probable MSA, 16%
for clinically established MSA). This means fewer cases fulfill MDS criteria than second
From the Department for Personalized Genomic Medicine for Health and the Center for Personalized Medicine for Healthy Aging; and Department of Neurology and Neurological
Sciences, Tokyo Medical and Dental University, Japan.
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Copyright © 2023 American Academy of Neurology 1081

Copyright © 2023 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
Consensus Statement criteria. Therefore, the authors state Study Funding
that failure to meet possible MSA by the second Consensus The author reports no targeted funding.
Statement might be useful when exclusion of MSA is considered.
They also addressed contributions of MR imaging, supporting Disclosure
features, and exclusion criteria to making accurate diagnosis of The author reports no relevant disclosures. Go to Neurology.
MSA. As such, this article is highly relevant for all neurologists in org/N for full disclosures.
clinical practice seeing patients with possible MSA.
Publication History
As noted by the authors, there are still many issues to be Received by Neurology August 16, 2023. Accepted in final form
addressed by future research. One such issue would be the October 5, 2023.
development of a machine learning algorithm for unbiased
diagnosis of MSA; this would also be useful for earlier de- References
1. Stefanova N, Wenning GK. Multiple system atrophy: at the crossroads of cellular,
tection of this disease. Furthermore, this tool would be im- molecular and genetic mechanisms. Nat Rev Neurosci. 2023;24(6):334-346. doi:
portant for both developing disease-modifying therapy and 10.1038/s41583-023-00697-7
2. Wenning GK, Stankovic I, Vignatelli L, et al. The movement disorder society criteria
providing MSA prognosis disease for affected patients, their for the diagnosis of multiple system atrophy. Mov Disord. 2022;37(6):1131-1148. doi:
families, and clinical professionals. The time line for when the 10.1002/mds.29005.
3. Sekiya H, Koga S, Murakami A, et al. Validation study of the MDS criteria for the
criteria may be met is also unclear. Appropriate prospective diagnosis of multiple system atrophy in the Mayo Clinic brain bank. Neurology. 2023;
study may be needed. Overall, the article by Sekiya et al. is a 101(24):e2460-e2471.
4. Gilman S, Wenning GK, Low PA, et al. Second consensus statement on the di-
strong reference both for clinical neurologists and for re- agnosis of multiple system atrophy. Neurology. 2008;71(9):670-676. doi:10.1212/
searchers regarding this complex disease. 01.wnl.0000324625.00404.15
1082 Neurology | Volume 101, Number 24 | December 12, 2023 Neurology.org/N

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EDITORIAL

How Certain Are You When Making the Diagnosis of

Copyright © 2023 American Academy of Neurology 1081

1082 Neurology | Volume 101, Number 24 | December 12, 2023 Neurology.org/N

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