The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy

Gregor K Wenning¹, Iva Stankovic², Luca Vignatelli³, Alessandra Fanciulli¹, Giovanna Calandra-Buonaura^{3

4}, Klaus Seppi¹, Jose-Alberto Palma⁵, Wassilios G Meissner^{6

7}, Florian Krismer¹, Daniela Berg^{8

9}, Pietro Cortelli^{3

4}, Roy Freeman¹⁰, Glenda Halliday¹¹, Günter Höglinger^{12

13}, Anthony Lang¹⁴, Helen Ling^{15

16}, Irene Litvan¹⁷, Phillip Low¹⁸, Yasuo Miki^{15

19}, Jalesh Panicker^{20

21}, Maria Teresa Pellecchia²², Niall Quinn²⁰, Ryuji Sakakibara²³, Maria Stamelou^{24

25}, Eduardo Tolosa^{26

27}, Shoji Tsuji^{28

29}, Tom Warner¹⁵, Werner Poewe¹, Horacio Kaufmann⁵

Affiliations

¹ Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
² Neurology Clinic, University Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
³ IRCCS, Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
⁴ Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
⁵ Department of Neurology, Dysautonomia Center, Langone Medical Center, New York University School of Medicine, New York, New York, USA.
⁶ French Reference Center for MSA, Department of Neurology for Neurodegenerative Diseases, University Hospital Bordeaux, 33076 Bordeaux and Institute of Neurodegenerative Diseases, University Bordeaux, CNRS, Bordeaux, France.
⁷ Department of Medicine, University of Otago, Christchurch, and New Zealand Brain Research Institute, Christchurch, New Zealand.
⁸ Department of Neurodegeneration and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
⁹ Department of Neurology, Christian-Albrechts-University Kiel, Kiel, Germany.
¹⁰ Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
¹¹ Brain and Mind Centre, Faculty of Medicine and Health, School of Medical Sciences, The University of Sydney, Sydney, New South Wales, Australia.
¹² Department of Neurology, Hanover Medical School, Hanover, Germany.
¹³ German Center for Neurodegenerative Diseases, Munich, Germany.
¹⁴ Edmond J. Safra Program in Parkinson's Disease, University Health Network and the Division of Neurology, University of Toronto, Toronto, Canada.
¹⁵ Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, London, United Kingdom.
¹⁶ Reta Lila Weston Institute of Neurological Studies, UCL Queen Square Institute of Neurology, London, United Kingdom.
¹⁷ Department of Neurosciences, Parkinson and Other Movement Disorders Center, University of California, San Diego, California, USA.
¹⁸ Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
¹⁹ Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
²⁰ UCL Queen Square Institute of Neurology, London, United Kingdom.
²¹ Department of Uro-Neurology, The National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom.
²² Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", Neuroscience Section, University of Salerno, Salerno, Italy.
²³ Neurology, Internal Medicine, Sakura Medical Center, Toho University, Sakura, Japan.
²⁴ Parkinson's Disease and Movement Disorders Department, HYGEIA Hospital, and Aiginiteion Hospital, University of Athens, Athens, Greece.
²⁵ Philipps University Marburg, Germany and European University of Cyprus, Nicosia, Cyprus.
²⁶ Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) Hospital Clínic, IDIBAPS, Universitat de Barcelona, Catalonia, Spain.
²⁷ Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Catalonia, Spain.
²⁸ Department of Molecular Neurology, The University of Tokyo, Graduate School of Medicine, Tokyo, Japan.
²⁹ International University of Health and Welfare, Chiba, Japan.

PMID: 35445419
PMCID: PMC9321158
DOI: 10.1002/mds.29005

The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy

Gregor K Wenning et al. Mov Disord. 2022 Jun.

. 2022 Jun;37(6):1131-1148.

doi: 10.1002/mds.29005. Epub 2022 Apr 21.

Authors

Affiliations

¹ Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
² Neurology Clinic, University Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
³ IRCCS, Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
⁴ Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
⁵ Department of Neurology, Dysautonomia Center, Langone Medical Center, New York University School of Medicine, New York, New York, USA.
⁶ French Reference Center for MSA, Department of Neurology for Neurodegenerative Diseases, University Hospital Bordeaux, 33076 Bordeaux and Institute of Neurodegenerative Diseases, University Bordeaux, CNRS, Bordeaux, France.
⁷ Department of Medicine, University of Otago, Christchurch, and New Zealand Brain Research Institute, Christchurch, New Zealand.
⁸ Department of Neurodegeneration and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
⁹ Department of Neurology, Christian-Albrechts-University Kiel, Kiel, Germany.
¹⁰ Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
¹¹ Brain and Mind Centre, Faculty of Medicine and Health, School of Medical Sciences, The University of Sydney, Sydney, New South Wales, Australia.
¹² Department of Neurology, Hanover Medical School, Hanover, Germany.
¹³ German Center for Neurodegenerative Diseases, Munich, Germany.
¹⁴ Edmond J. Safra Program in Parkinson's Disease, University Health Network and the Division of Neurology, University of Toronto, Toronto, Canada.
¹⁵ Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, London, United Kingdom.
¹⁶ Reta Lila Weston Institute of Neurological Studies, UCL Queen Square Institute of Neurology, London, United Kingdom.
¹⁷ Department of Neurosciences, Parkinson and Other Movement Disorders Center, University of California, San Diego, California, USA.
¹⁸ Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
¹⁹ Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
²⁰ UCL Queen Square Institute of Neurology, London, United Kingdom.
²¹ Department of Uro-Neurology, The National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom.
²² Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", Neuroscience Section, University of Salerno, Salerno, Italy.
²³ Neurology, Internal Medicine, Sakura Medical Center, Toho University, Sakura, Japan.
²⁴ Parkinson's Disease and Movement Disorders Department, HYGEIA Hospital, and Aiginiteion Hospital, University of Athens, Athens, Greece.
²⁵ Philipps University Marburg, Germany and European University of Cyprus, Nicosia, Cyprus.
²⁶ Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) Hospital Clínic, IDIBAPS, Universitat de Barcelona, Catalonia, Spain.
²⁷ Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Catalonia, Spain.
²⁸ Department of Molecular Neurology, The University of Tokyo, Graduate School of Medicine, Tokyo, Japan.
²⁹ International University of Health and Welfare, Chiba, Japan.

PMID: 35445419
PMCID: PMC9321158
DOI: 10.1002/mds.29005

Abstract

Background: The second consensus criteria for the diagnosis of multiple system atrophy (MSA) are widely recognized as the reference standard for clinical research, but lack sensitivity to diagnose the disease at early stages.

Objective: To develop novel Movement Disorder Society (MDS) criteria for MSA diagnosis using an evidence-based and consensus-based methodology.

Methods: We identified shortcomings of the second consensus criteria for MSA diagnosis and conducted a systematic literature review to answer predefined questions on clinical presentation and diagnostic tools relevant for MSA diagnosis. The criteria were developed and later optimized using two Delphi rounds within the MSA Criteria Revision Task Force, a survey for MDS membership, and a virtual Consensus Conference.

Results: The criteria for neuropathologically established MSA remain unchanged. For a clinical MSA diagnosis a new category of clinically established MSA is introduced, aiming for maximum specificity with acceptable sensitivity. A category of clinically probable MSA is defined to enhance sensitivity while maintaining specificity. A research category of possible prodromal MSA is designed to capture patients in the earliest stages when symptoms and signs are present, but do not meet the threshold for clinically established or clinically probable MSA. Brain magnetic resonance imaging markers suggestive of MSA are required for the diagnosis of clinically established MSA. The number of research biomarkers that support all clinical diagnostic categories will likely grow.

Conclusions: This set of MDS MSA diagnostic criteria aims at improving the diagnostic accuracy, particularly in early disease stages. It requires validation in a prospective clinical and a clinicopathological study. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: diagnosis; diagnostic criteria; multiple system atrophy.

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Figures

**FIG. 1**
Brain magnetic resonance imaging (MRI) markers of clinically established multiple system atrophy (MSA) (reprinted from Fancuilli et al © 2019 Elsevier Inc.) Panel 1: midsagittal T1‐weighted images showing infratentorial atrophy including pontine atrophy (solid arrow) and cerebellar atrophy with enlarged fissures and interfolial spaces of the cerebellum (dashed arrow) and consecutive dilated forth ventricle (dotted arrow) in a patient with MSA (a), while there is no relevant infratentorial atrophy in a patient with Parkinson's disease (PD) (c). Panel 2: parasagittal T1‐weighted images showing middle cerebellar peduncles (MCP) atrophy between the peripeduncular cerebrospinal fluid spaces of pontocerebellar cisterns (solid arrow) in a patient with MSA (a), while there is no MCP atrophy (solid arrow) in a patient with PD (b). Moreover, there is cerebellar atrophy with enlarged fissures and interfolial spaces of the cerebellum (dashed arrow) in the patient with MSA (a) compared to the patient with PD (b). Panel 3: “hot cross bun” sign (arrow) in a patient with MSA on T2‐weighted images. Panel 4: putaminal atrophy (solid arrows) (a, b) and signal changes including hyperintense rim (dashed arrows) (a) and putaminal hypointensity in comparison with the globus pallidus (dotted lines) (a, b) at both sides in patients with MSA (a, b) on T2‐weighted images compared to a patient with PD (c) having no putaminal atrophy (arrows). Panel 5: atrophy of MCP (solid arrows) on T2‐weighted images (a, b) with MCP‐sign (hyperintensity in the MCP) (dashed arrows) (a) and “hot cross bun” sign (dotted arrow) (b) in patients with MSA (a, b) compared to a PD patient with normal MCP (solid arrows) (c). Panel 6: note the diffuse hyperintensity (corresponding to increased diffusivity values) in the posterior part of both putamina (solid arrows) in patients with MSA (a, b) compared to a PD patient with no diffusivity changes in the putamen (solid arrows) (c) on diffusion imaging. The changes in the MSA patient (a) were observed only 6 months after onset of levodopa‐responsive parkinsonism with an anticipation of 18 months in relation to the clinical diagnosis of possible MSA and of 24 months for the diagnosis of probable MSA. Panel 7: putaminal atrophy can also be determined with iron‐sensitive sequences as demonstrated in these images. Putaminal atrophy (solid arrows) and putaminal hypointensity (ie, signal decrease) (dashed arrows) on susceptibility weighted imaging in a patient with MSA (a, b) compared to a PD patient with no putaminal atrophy (solid lines) (c). As in these MSA patients, putaminal hypointensity starts typically in the dorsolateral part of the putamen. [Color figure can be viewed at wileyonlinelibrary.com]

See this image and copyright information in PMC

References

1. Fanciulli A, Wenning G. Multiple‐system atrophy. NEJM 2015;372(3):249–263. - PubMed
1. Gilman S, Low PA, Quinn N, et al. Consensus statement on the diagnosis of multiple system atrophy. J Neurol Sci 1999;163(1):94–98. - PubMed
1. Gilman S, Wenning GK, Low PA, et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology 2008;71(9):670–676. - PMC - PubMed
1. Quinn N. Multiple system atrophy ‐ the nature of the beast. J Neurol Neurosurg Psychiatry 1989;78–89. - PMC - PubMed
1. Miki Y, Foti SC, Asi YT, et al. Improving diagnostic accuracy of multiple system atrophy: a clinicopathological study. Brain 2019;142(9):2813–2827. 10.1093/brain/awz214 - DOI - PubMed

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The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy

Affiliations

The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy

Authors

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Research Materials

Miscellaneous