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

Gregor K Wenning, Iva Stankovic, Luca Vignatelli, Alessandra Fanciulli, Giovanna Calandra-Buonaura, Klaus Seppi, Jose-Alberto Palma, Wassilios G Meissner, Florian Krismer, Daniela Berg, Pietro Cortelli, Roy Freeman, Glenda Halliday, Günter Höglinger, Anthony Lang, Helen Ling, Irene Litvan, Phillip Low, Yasuo Miki, Jalesh Panicker, Maria Teresa Pellecchia, Niall Quinn, Ryuji Sakakibara, Maria Stamelou, Eduardo Tolosa, Shoji Tsuji, Tom Warner, Werner Poewe, Horacio Kaufmann, Gregor K Wenning, Iva Stankovic, Luca Vignatelli, Alessandra Fanciulli, Giovanna Calandra-Buonaura, Klaus Seppi, Jose-Alberto Palma, Wassilios G Meissner, Florian Krismer, Daniela Berg, Pietro Cortelli, Roy Freeman, Glenda Halliday, Günter Höglinger, Anthony Lang, Helen Ling, Irene Litvan, Phillip Low, Yasuo Miki, Jalesh Panicker, Maria Teresa Pellecchia, Niall Quinn, Ryuji Sakakibara, Maria Stamelou, Eduardo Tolosa, Shoji Tsuji, Tom Warner, Werner Poewe, Horacio Kaufmann

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.

© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Figures

FIG. 1
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]

References

    1. Fanciulli A, Wenning G. Multiple‐system atrophy. NEJM 2015;372(3):249–263.
    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.
    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.
    1. Quinn N. Multiple system atrophy ‐ the nature of the beast. J Neurol Neurosurg Psychiatry 1989;78–89.
    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
    1. Koga S, Aoki N, Uitti R, et al. When DLB, PD, and PSP masquerade as MSA. Neurology 2015;85(5):404–412.
    1. Osaki Y, Ben‐Shlomo Y, Lees A, Wenning G, Quinn N. A validation exercise on the new consensus criteria for multiple system atrophy. Mov Disord 2009;24(15):2272–2276.
    1. Stankovic I, Quinn N, Vignatelli L, et al. A critique of the second consensus criteria for multiple system atrophy. Mov Disord 2019;34(7):975–984.
    1. Keeney S, Hasson F, McKenna H. The Delphi Technique in Nursing and Health Research. Oxford, UK: Wiley‐Blackwell; 2010;1–208.
    1. Eriksen MB, Frandsen TF. The impact of patient, intervention, comparison, outcome (PICO) as a search strategy tool on literature search quality: a systematic review. J Med Libr Assoc 2018;106(4):420–431.
    1. Gronseth GS, Cox J, Gloss D, et al. Clinical Practice Guideline Process Manual. 7th ed. Minneapolis: AAN (American Academy of Neurology); 2017.
    1. Burns KEA, Duffett M, Kho ME, et al. A guide for the design and conduct of self‐administered surveys of clinicians. CMAJ 2008;179(3):245–252.
    1. Nair R, Aggarwal R, Khanna D. Methods of formal consensus in classification/diagnostic criteria and guideline development. Semin Arthritis Rheum 2011;41(2):95–105.
    1. Trojanowski JQ, Revesz T. Neuropathology Working Group on MSA. Proposed neuropathological criteria for the post mortem diagnosis of multiple system atrophy. Neuropathol Appl Neurobiol 2007;33(6):615–620.
    1. Sakakibara R, Panicker J, Simeoni S, et al. Bladder dysfunction as the initial presentation of multiple system atrophy: a prospective cohort study. Clin Aut Res 2019;29(6):627–631. 10.1007/s10286-018-0550-y
    1. Ozawa T, Tanaka H, Nakano R, et al. Nocturnal decrease in vasopressin secretion into plasma in patients with multiple system atrophy. J Neurol Neurosurg Psychiatry 1999;67(4):542–545.
    1. Hahn K, Ebersbach G. Sonographic assessment of urinary retention in multiple system atrophy and idiopathic Parkinson's disease. Mov Disord 2005;20(11):1499–1502.
    1. Kim M, Hyun J, Park J, Son H, Jin S. Impaired detrusor contractility is the pathognomonic urodynamic finding of multiple system atrophy compared to idiopathic Parkinson's disease. Parkinson's Relat Disord. 2015;21(3):205–210.
    1. Kim KJ, Jeong SJ, Kim J‐M. Neurogenic bladder in progressive supranuclear palsy: a comparison with Parkinson's disease and multiple system atrophy. NeurourolUrodyn 2018;37(5):1724–1730.
    1. Fanciulli A, Lazzeri G, Granata R, et al. Urinary retention discriminates multiple system atrophy from Parkinson's disease. Mov Disord 2019;34(12):1926–1928.
    1. Kirchhof K, Apostolidis AN, Mathias CJ, Fowler CJ. Erectile and urinary dysfunction may be the presenting features in patients with multiple system atrophy: a retrospective study. Int J Impot Res 2003;15(4):293–298.
    1. Norcliffe‐Kaufmann L, Kaufmann H, Palma J, et al. Orthostatic heart rate changes in patients with autonomic failure caused by neurodegenerative synucleinopathies. Ann Neurol 2018;83(3):522–531.
    1. Fanciulli A, Kerer K, Leys F, et al. Validation of the neurogenic orthostatic hypotension ratio with active standing. Ann Neurol 2020;88(3):643–645.
    1. Fedorowski A, Hamrefors V, Sutton R, et al. Do we need to evaluate diastolic blood pressure in patients with suspected orthostatic hypotension? Clin Aut Res 2017;27(3):167–173.
    1. Sun Z, Jia D, Shi Y, et al. Prediction of orthostatic hypotension in multiple system atrophy and Parkinson disease. Sci Rep 2016;6:21649
    1. Wenning G, Scherfler C, Granata R, et al. Time course of symptomatic orthostatic hypotension and urinary incontinence in patients with postmortem confirmed parkinsonian syndromes: a clinicopathological study. J Neurol Neurosurg Psychiatry 1999;67:620–623.
    1. Fanciulli A, Goebel G, Lazzeri G, et al. Early distinction of Parkinson‐variant multiple system atrophy from Parkinson's disease. Mov Disord 2019;34(3):440–441.
    1. Lin D, Hermann K, Schmahmann J. The diagnosis and natural history of multiple system atrophy, cerebellar type. Cerebellum 2017;15(6):663–679.
    1. Lloyd‐Smith A, Jacova P, Schulzer M, Spacey SD. Early clinical features differentiate cerebellar variant MSA and sporadic ataxia. Can J Neurol Sci 2013;40(2):252–254.
    1. Pavy‐Le Traon A, Piedvache A, Perez‐Lloret S, et al. New insights into orthostatic hypotension in multiple system atrophy: a European multicentre cohort study. J Neurol Neurosurg Psychiatry 2016;87(5):554–561.
    1. Thijs RD, Brignole M, Falup‐pecurariu C, et al. Recommendations for tilt table testing and other provocative cardiovascular autonomic tests in conditions that may cause transient loss of consciousness: consensus statement of the European Federation of Autonomic Societies (EFAS) endorsed by the American Autonomic Society (AAS) and the European Academy of Neurology (EAN). Aut Neurosci 2021;233:102792
    1. Vogel ER, Sandroni P, Low PA. Blood pressure recovery from Valsalva maneuver in patients with autonomic failure. Neurology 2005;65(10):1533–1537.
    1. Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord 2015;30(12):1591–1601.
    1. Low PA, Reich SG, Jankovic J, et al. Natural history of multiple system atrophy in the USA: a prospective cohort study. Lancet Neurol 2015;14(7):710–719.
    1. Wenning GK, Geser F, Krismer F, et al. The natural history of multiple system atrophy: a prospective European cohort study. Lancet Neurol 2013;12(3):264–274.
    1. Stankovic I, Fanciulli A, Kostic VS, et al. Laboratory supported multiple system atrophy beyond autonomic function testing and imaging: a systematic review by the MoDiMSA study group. Mov Disord Clin Pr 2021;8(3):322–340.
    1. Köllensperger M, Geser F, Seppi K, et al. Red flags for multiple system atrophy. Mov Disord 2008;23(8):1093–1099.
    1. Respondek G, Kurz C, Azberger T, et al. Which ante mortem clinical features predict progressive supranuclear palsy pathology? Mov Disord 2017;37(7):995–1005.
    1. Wenning GK, Ebersbach G, Verny M, et al. Progression of falls in postmortem‐confirmed parkinsonian disorders. Mov Disord 1999;14(6):947–950.
    1. Wenning G, Tison F, Ben‐Shlomo Y, Daniel S, Quinn N. Multiple system atrophy: a review of 203 pathologically proven cases. Mov Disord 1997;12(2):133–147.
    1. Teive H, Arruda W, Moro A, Moscovich M, Munhoz R. Differential diagnosis of sporadic adult‐onset ataxia: the role of REM sleep behavior disorder. Parkinson's Relat Disord. 2015;21(6):640–643.
    1. Giannini G, Calandra‐Buonaura G, Mastrolilli F, et al. Early stridor onset and stridor treatment predict survival in 136 patients with MSA. Neurology 2016;87(13):1375–1383.
    1. Iranzo A, Munoz E, Santamaria J, Vilaseca I, Mila M, Tolosa E. REM sleep behavior disorder and vocal cord paralysis in Machado‐Joseph disease. Mov Disord 2003;18(10):1179–1183.
    1. Cortelli P, Calandra‐Buonaura G, Benarroch EE, et al. Stridor in multiple system atrophy consensus statement on diagnosis, prognosis, and treatment. Neurology 2019;93(14):630–639.
    1. Massey L, Micallef C, Paviour D, et al. Conventional magnetic resonance imaging in confirmed progressive supranuclear palsy and multiple system atrophy. Mov Disord 2012;27(14):1754–1762.
    1. Pellecchia MT, Stankovic I, Fanciulli A, et al. Can autonomic testing and imaging contribute to the early diagnosis of multiple system atrophy? A systematic review and recommendations by the Movement Disorder Society Multiple System Atrophy Study Group. Mov Disord Clin Pract 2020;7(7):750–762. 10.1002/mdc3.13052
    1. Mahlknecht P, Hotter A, Hussl A, Esterhammer R, Schocke M, Seppi K. Significance of MRI in diagnosis and differential diagnosis of Parkinson's disease. Neurodegener Dis 2010;7(5):300–318.
    1. Muqit M, Mort D, Miskiel K, Shakir R. “Hot cross bun” sign in a patient with parkinsonism secondary to presumed vasculitis. J Neurol Neurosurg Psychiatry 2001;71(4):565–566.
    1. Burk K, Skalej M, Dichgans J. Pontine MRI hyperintensities (“the cross sign”) are not pathognomonic for multiple system atrophy (MSA). Mov Disord 2001;16(3):535–536.
    1. Bajaj S, Krismer F, Palma J, et al. Diffusion‐weighted MRI distinguishes Parkinson disease from the parkinsonian variant of multiple system atrophy: a systematic review and meta‐analysis. PLoS One 2017;12(12):e0189897
    1. Scherfler C, Göbel G, Müller C, et al. Diagnostic potential of automated subcortical volume segmentation in atypical parkinsonism. Neurology 2016;86:1242–1249.
    1. Krismer F, Beliveau V, Seppi K, et al. Automated analysis of diffusion‐weighted magnetic resonance imaging for the differential diagnosis of multiple system atrophy from Parkinson's disease. Mov Disord 2020;36(1):241–245.
    1. Péran P, Barbagallo G, Nemmi F, et al. MRI supervised and unsupervised classification of Parkinson's disease and multiple system atrophy. Mov Disord 2018;33(4):600–608.
    1. Krismer F, Pinter B, Mueller C, et al. Sniffing the diagnosis: olfactory testing in neurodegenerative parkinsonism. Parkinson's Relat Disord. 2017;35:36–41.
    1. Stankovic I, Krismer F, Jesic A, et al. Cognitive impairment in multiple system atrophy: a position statement by the Neuropsychology Task Force of the MDS Multiple System Atrophy (MODIMSA) study group. Mov Disord 2014;29(7):857–867.
    1. Stamelou M, Quinn NP, Bhatia KP. “Atypical” atypical parkinsonism: new genetic conditions presenting with features of progressive supranuclear palsy, corticobasal degeneration, or multiple system atrophy ‐ a diagnostic guide. Mov Disord 2013;28(9):1184–1199.
    1. Kim H‐J, Jeon BS, Shin J, et al. Should genetic testing for SCAs be included in the diagnostic workup for MSA? Neurology 2014;83(19):1733–1738.
    1. Postuma RB, Iranzo A, Hogl B, et al. Risk factors for neurodegeneration in idiopathic rapid eye movement sleep behavior disorder: a multicenter study. Ann Neurol 2015;77(5):830–839.
    1. Kaufmann H, Norcliffe‐Kaufmann L, Palma J‐A, et al. Natural history of pure autonomic failure: a United States prospective cohort. Ann Neurol 2017;81(2):287–297.
    1. Singer W, Berini SE, Sandroni P, et al. Pure autonomic failure predictors of conversion to clinical CNS involvement. Neurology 2017;88(12):1129–1136.
    1. Giannini G, Calandra‐Buonaura G, Asioli GM, et al. The natural history of idiopathic autonomic failure: the IAF‐BO cohort study. Neurology 2018;91(13):e1245–e1254.
    1. Gandor F, Vogel A, Claus I, et al. Laryngeal movement disorders in multiple system atrophy: a diagnostic biomarker? Mov Disord 2020;35(12):2174–2183. 10.1002/mds.28220
    1. Hines P, Hiu YL, Guy RH, Brand A, Papaluca‐Amati M. Scanning the horizon: a systematic literature review of methodologies. BMJ Open 2019;9(5):1–9.
    1. Meyer P, Frings L, Rucker G, Hellwig S. F‐FDG PET in Parkinsonism: differential diagnosis and cognitive impairment in Parkinson's disease. J Nucl Med 2017;58(12):1888–1898.
    1. Fulham M, Dubinsky R, Polinsky R, et al. Computed tomography, magnetic resonance imaging and positron emission tomography with [18F] fluorodeoxyglucose in multiple system atrophy and pure autonomic failure. Clin Aut Res 1991;1(1):27–36.
    1. Eidelberg D, Takikawa S, Moeller JR, et al. Striatal hypometabolism distinguishes striatonigral degeneration from Parkinson's disease. Ann Neurol 1993;33(5):518–527.
    1. Eckert T, Barnes A, Dhawan V, et al. FDG PET in the differential diagnosis of parkinsonian disorders. Neuroimage 2005;26(3):912–921.
    1. Orimo S, Suzuki M, Inaba A, Mizusawa H. 123I‐MIBG myocardial scintigraphy for differentiating Parkinson's disease from other neurodegenerative parkinsonism: a systematic review and meta‐analysis. Parkinson's Relat Disord 2012;18(5):494–500.
    1. Treglia G, Stefanelli A, Cason E, Cocciolillo F, Di Giuda D, Giordano A. Diagnostic performance of iodine‐123‐metaiodobenzylguanidine scintigraphy in differential diagnosis between Parkinson's disease and multiple‐system atrophy: a systematic review and a meta‐analysis. Clin Neurol Neurosurg 2011;113(10):823–829.
    1. King A, Mintz J, Royall D. Meta‐analysis of 123I‐MIBG cardiac scintigraphy for the diagnosis of Lewy body‐related disorders. Mov Disord 2011;26(7):1218–1224.
    1. Satoh A, Serita T, Seto M, et al. Loss of 123I‐MIBG uptake by the heart in Parkinson's disease: assessment of cardiac sympathetic denervation and diagnostic value. J Nucl Med 1999;40(3):371–375.
    1. Druschky K, Kuwert T, Druschky A, Hilz MJ, Platsch G, Neundorfer B. Differentiation of Parkinson's disease and multiple system atrophy in early disease stages by means of I‐123‐MIBG–SPECT. J Neurol Sci 2000;175(1):3–12.
    1. Yoshita M. Differentiation of idiopathic Parkinson's disease from striatonigral degeneration and progressive supranuclear palsy using iodine‐123 meta‐iodobenzylguanidine myocardial scintigraphy. J Neurol Sci 1998;155(1):60–67.
    1. Hirayama M, Hakusui S, Koike Y, et al. A scintigraphical qualitative analysis of peripheral vascular sympathetic function with meta‐[123I] iodobenzylguanidine in neurological patients with autonomic failure. J Aut Nerv Syst 1995;53(2–3):230–234.
    1. Boeve B, Silber M, Ferman T, et al. Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder. Sleep Med 2013;14(8):754–762.
    1. American Academy of Sleep Medicine . International Classification of Sleep Disorders. 3rd ed. Darien: American Academy of Sleep Medicine; 2014.
    1. Paviour DC, Williams D, Fowler CJ, Quinn NP, Lees AJ. Is sphincter electromyography a helpful investigation in the diagnosis of multiple system atrophy? A retrospective study with pathological diagnosis. Mov Disord 2005;20(11):1425–1430.
    1. Singer W, Schmeichel AM, Shahnawaz M, et al. Alpha‐synuclein oligomers and neurofilament light chain in spinal fluid differentiate multiple system atrophy from Lewy body synucleinopathies. Ann Neurol 2020;88(3):503–512. 10.1002/ana.25824
    1. Rossi M, Candelise N, Baiardi S, et al. Ultrasensitive RT‐QuIC assay with high sensitivity and specificity for Lewy body‐associated synucleinopathies. Acta Neuropathol 2020;140(1):49–62.
    1. Singer W, Schmeichel AM, Shahnawaz M, et al. Alpha‐synuclein oligomers and neurofilament light chain predict phenoconversion of pure autonomic failure. Ann Neurol 2021;89(6):1212–1220.
    1. Fanciulli A, Stankovic I, Krismer F, Seppi K, Levin J, Wenning GK. Multiple system atrophy. Int Rev Neurobiol 2019;149:137–192.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe