Skip to main content

Advertisement

SpringerLink
Log in

Diagnosis and differential diagnosis of MSA: boundary issues

  • Review
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Because the progression of multiple system atrophy (MSA) is usually rapid and there still is no effective cause-related therapy, early and accurate diagnosis is important for the proper management of patients as well as the development of neuroprotective agents. However, despite the progression in the field of MSA research in the past few years, the diagnosis of MSA in clinical practice still relies largely on clinical features and there are limitations in terms of sensitivity and specificity, especially in the early course of the disease. Furthermore, recent pathological, clinical, and neuroimaging studies have shown that (1) MSA can present with a wider range of clinical and pathological features than previously thought, including features considered atypical for MSA; thus, MSA can be misdiagnosed as other diseases, and conversely, disorders with other etiologies and pathologies can be clinically misdiagnosed as MSA; and (2) several investigations may help to improve the diagnosis of MSA in clinical practice. These aspects should be taken into consideration when revising the current diagnostic criteria. This is especially true given that disease-modifying treatments for MSA are under investigation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Stefanova N, Bücke P, Duerr S, Wenning GK (2009) Multiple system atrophy: an update. Lancet Neurol 8:1172–1178

    Article  CAS  PubMed  Google Scholar 

  2. Kim HJ, Jeon BS, Lee JY, Yun JY (2011) Survival of Korean patients with multiple system atrophy. Mov Disord 26:909–912

    Article  PubMed  Google Scholar 

  3. Wenning GK, Geser F, Krismer F, Seppi K, Duerr S, Boesch S, Köllensperger M, Goebel G, Pfeiffer KP, Barone P (2013) The natural history of multiple system atrophy: a prospective European cohort study. Lancet Neurol 12:264–274

    Article  PubMed Central  PubMed  Google Scholar 

  4. Jellinger KA (2014) Neuropathology of multiple system atrophy: New thoughts about pathogenesis. Mov Disord 29:1720–1741

    Article  CAS  PubMed  Google Scholar 

  5. Kim H-J, Jeon BS, Shin J, Lee W-W, Park H, Jung YJ, Ehm G (2014) Should genetic testing for SCAs be included in the diagnostic workup for MSA? Neurology 83:1733–1738

    Article  PubMed  Google Scholar 

  6. Kimpinski K, Iodice V, Burton DD, Camilleri M, Mullan BP, Lipp A, Sandroni P, Gehrking TL, Sletten DM, Ahlskog J (2012) The role of autonomic testing in the differentiation of Parkinson’s disease from multiple system atrophy. J Neurol Sci 317:92–96

    Article  PubMed Central  PubMed  Google Scholar 

  7. Lee J-Y, Yun JY, Shin C-W, Kim H-J, Jeon BS (2010) Putaminal abnormality on 3-T magnetic resonance imaging in early parkinsonism-predominant multiple system atrophy. J Neurol 257:2065–2070

    Article  PubMed  Google Scholar 

  8. Linder J, Libelius R, Nordh E, Holmberg B, Stenlund H, Forsgren L (2012) Anal sphincter electromyography in patients with newly diagnosed idiopathic parkinsonism. Acta Neurol Scand 126:248–255

    Article  CAS  PubMed  Google Scholar 

  9. Petrovic IN, Ling H, Asi Y, Ahmed Z, Kukkle PL, Hazrati LN, Lang AE, Revesz T, Holton JL, Lees AJ (2012) Multiple system atrophy–parkinsonism with slow progression and prolonged survival: a diagnostic catch. Mov Disord 27:1186–1190

    Article  PubMed  Google Scholar 

  10. Stankovic I, Krismer F, Jesic A, Antonini A, Benke T, Brown RG, Burn DJ, Holton JL, Kaufmann H, Kostic VS (2014) 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 29:857–867

    Article  PubMed Central  PubMed  Google Scholar 

  11. Wüllner U, Schmitt I, Kammal M, Kretzschmar HA, Neumann M (2009) Definite multiple system atrophy in a German family. J Neurol Neurosurg Psychiatry 80:449–450

    Article  PubMed  Google Scholar 

  12. Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, Wood NW, Colosimo C, Durr A, Fowler CJ (2008) Second consensus statement on the diagnosis of multiple system atrophy. Neurology 71:670–676

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Colosimo C (2011) Nonmotor presentations of multiple system atrophy. Nat Rev Neurol 7:295–298

    Article  CAS  PubMed  Google Scholar 

  14. Klockgether T (2010) Sporadic ataxia with adult onset: classification and diagnostic criteria. Lancet Neurol 9:94–104

    Article  CAS  PubMed  Google Scholar 

  15. Stamelou M, Hoeglinger GU (2013) Atypical parkinsonism: an update. Curr Opin Neurol 26:401–405

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Kamm C, Healy DG, Quinn NP, Wüllner U, Moller JC, Schols L, Geser F, Burk K, Børglum AD, Pellecchia MT (2005) The fragile X tremor ataxia syndrome in the differential diagnosis of multiple system atrophy: data from the EMSA Study Group. Brain 128:1855–1860

    Article  CAS  PubMed  Google Scholar 

  17. Gatto E, Rodríguez-Violante M, Consentino C, Chana-Cuevas P, Miranda M, Gallin E, Etcheverry JL, Nuñez Y, Parisi V, Persi G (2014) Pan-American Consortium of Multiple System Atrophy (PANMSA). A Pan-American multicentre cohort study of multiple system Atrophy. J Parkinsons Dis. doi:10.3233/JPD-140434

    PubMed  Google Scholar 

  18. Köllensperger M, Geser F, Ndayisaba JP, Boesch S, Seppi K, Ostergaard K, Dupont E, Cardozo A, Tolosa E, Abele M (2010) Presentation, diagnosis, and management of multiple system atrophy in Europe: final analysis of the European multiple system atrophy registry. Mov Disord 25:2604–2612

    Article  PubMed  Google Scholar 

  19. Goode PS, Burgio KL, Redden DT, Markland A, Richter HE, Sawyer P, Allman RM (2008) Population based study of incidence and predictors of urinary incontinence in black and white older adults. J Urol 179:1449–1454

    Article  PubMed Central  PubMed  Google Scholar 

  20. Hannestad YS, Rortveit G, Sandvik H, Hunskaar S (2000) A community-based epidemiological survey of female urinary incontinence: the Norwegian EPINCONT Study. J Clin Epidemiol 53:1150–1157

    Article  CAS  PubMed  Google Scholar 

  21. Smart C (2014) Male urinary incontinence and the urinary sheath. Br J Nurs 23:S20–S25

    Article  PubMed  Google Scholar 

  22. Norton P, Brubaker L (2006) Urinary incontinence in women. Lancet 367:57–67

    Article  PubMed  Google Scholar 

  23. Oertel WH, Wächter T, Quinn NP, Ulm G, Brandstädter D (2003) Reduced genital sensitivity in female patients with multiple system atrophy of parkinsonian type. Mov Disord 18:430–432

    Article  PubMed  Google Scholar 

  24. Senard J, Rai S, Lapeyre-Mestre M, Brefel C, Rascol O, Rascol A, Montastruc J (1997) Prevalence of orthostatic hypotension in Parkinson’s disease. J Neurol Neurosurg Psychiatry 63:584–589

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Mader SL, Josephson KR, Rubenstein LZ (1987) Low prevalence of postural hypotension among community-dwelling elderly. JAMA 258:1511–1514

    Article  CAS  PubMed  Google Scholar 

  26. Kim HJ, Jeon BS (2012) Multiple system atrophy with prolonged survival. Mov Disord 27:1837–1840

    Article  Google Scholar 

  27. Jellinger KA, Lantos PL (2010) Papp-Lantos inclusions and the pathogenesis of multiple system atrophy: an update. Acta Neuropathol 119:657–667

    Article  CAS  PubMed  Google Scholar 

  28. Jellinger KA (2014) Neuropathology. In: Wenning GK, Fanciulli A (eds) Multiple System Atrophy. Springer-Verlag, Vienna, pp 17–55

    Chapter  Google Scholar 

  29. Trojanowski J, Revesz T (2007) Proposed neuropathological criteria for the post mortem diagnosis of multiple system atrophy. Neuropathol Appl Neurobiol 33:615–620

    Article  CAS  PubMed  Google Scholar 

  30. Dickson DW, Liu W, Hardy J, Farrer M, Mehta N, Uitti R, Mark M, Zimmerman T, Golbe L, Sage J, Sima A, D’Amato C, Albin R, Gilman S, Yen SH (1999) Widespread alterations of alpha-synuclein in multiple system atrophy. Am J Pathol 155(4):1241–1251

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Jellinger KA (2014) Aetiopathogenesis. In: Wenning GK, Fanciulli A (eds) Multiple System Atrophy. Springer-Verlag, Vienna, pp 57–81

    Chapter  Google Scholar 

  32. Houlden H, Singleton AB (2012) The genetics and neuropathology of Parkinson’s disease. Acta Neuropathol 124:325–338

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Osaki Y, Ben-Shlomo Y, Lees AJ, Wenning GK, Quinn NP (2009) A validation exercise on the new consensus criteria for multiple system atrophy. Mov Disord 24:2272–2276

    Article  PubMed  Google Scholar 

  34. Halliday GM, Holton JL, Revesz T, Dickson DW (2011) Neuropathology underlying clinical variability in patients with synucleinopathies. Acta Neuropathol 122:187–204

    Article  CAS  PubMed  Google Scholar 

  35. Campbell BC, McLean CA, Culvenor JG, Gai WP, Blumbergs PC, Jakala P, Beyreuther K, Masters CL, Li QX (2001) The solubility of alpha-synuclein in multiple system atrophy differs from that of dementia with Lewy bodies and Parkinson’s disease. J Neurochem 76(1):87–96

    Article  CAS  PubMed  Google Scholar 

  36. Armstrong RA, Lantos PL, Cairns NJ (2007) Spatial topography of the neurofibrillary tangles in cortical and subcortical regions in progressive supranuclear palsy. Parkinsonism Relat Disord 13:50–54

    Article  PubMed  Google Scholar 

  37. Ozawa T (2007) Morphological substrate of autonomic failure and neurohormonal dysfunction in multiple system atrophy: impact on determining phenotype spectrum. Acta Neuropathol 114:201–211

    Article  PubMed  Google Scholar 

  38. Pouclet H, Lebouvier T, Coron E, Rouaud T, Flamant M, Toulgoat F, Roy M, Vavasseur F, Bruley des Varannes S, Neunlist M (2012) Analysis of colonic alpha-synuclein pathology in multiple system atrophy. Parkinsonism Relat Disord 18:893–895

    Article  PubMed  Google Scholar 

  39. Jellinger KA (2007) More frequent Lewy bodies but less frequent Alzheimer-type lesions in multiple system atrophy as compared to age-matched control brains. Acta Neuropathol 114:299–303

    Article  PubMed  Google Scholar 

  40. Wenning G, Ben-Shlomo Y, Magalhaes M, Daniel S, Quinn N (1995) Clinicopathological study of 35 cases of multiple system atrophy. J Neurol Neurosurg Psychiatry 58:160–166

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Fuchs J, Nilsson C, Kachergus J, Munz M, Larsson EM, Schüle B, Langston JW, Middleton FA, Ross O, Hulihan M (2007) Phenotypic variation in a large Swedish pedigree due to SNCA duplication and triplication. Neurology 68:916–922

    Article  CAS  PubMed  Google Scholar 

  42. Ozawa T, Tada M, Kakita A, Onodera O, Ishihara T, Morita T, Shimohata T, Wakabayashi K, Takahashi H, Nishizawa M (2010) The phenotype spectrum of Japanese multiple system atrophy. J Neurol Neurosurg Psychiatry 81:1253–1255

    Article  CAS  PubMed  Google Scholar 

  43. Mochizuki A, Komatsuzaki Y, Shoji S (2002) Association of Lewy bodies and glial cytoplasmic inclusions in the brain of Parkinson’s disease. Acta Neuropathol 104:534–537

    CAS  PubMed  Google Scholar 

  44. Tison F, Wenning GK, Danie S, Quinn NP (1995) Multiple system atrophy with Lewy bodies. Rev Neurol (Paris) 151:398–403

    CAS  Google Scholar 

  45. Wenning GK, Jellinger KA (2005) The role of α-synuclein in the pathogenesis of multiple system atrophy. Acta Neuropathol 109:129–140

    Article  CAS  PubMed  Google Scholar 

  46. Kiely AP, Asi YT, Kara E, Limousin P, Ling H, Lewis P, Proukakis C, Quinn N, Lees AJ, Hardy J (2013) α-Synucleinopathy associated with G51D SNCA mutation: a link between Parkinson’s disease and multiple system atrophy? Acta Neuropathol 125:753–769

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  47. Pasanen P, Myllykangas L, Siitonen M, Raunio A, Kaakkola S, Lyytinen J, Tienari PJ, Pöyhönen M, Paetau A (2014) A novel α-synuclein mutation A53E associated with atypical multiple system atrophy and Parkinson’s disease-type pathology. Neurobiol Aging 35:2180 (e2181–2185)

    Article  PubMed  CAS  Google Scholar 

  48. Hughes AJ, Daniel SE, Ben-Shlomo Y, Lees AJ (2002) The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service. Brain 125:861–870

    Article  PubMed  Google Scholar 

  49. Joutsa J, Gardberg M, Röyttä M, Kaasinen V (2014) Diagnostic accuracy of parkinsonism syndromes by general neurologists. Parkinsonism Relat Disord 20:840–844

    Article  PubMed  Google Scholar 

  50. Fanciulli A, Wenning GK (2015) Multiple-system atrophy. N Engl J Med 372:249–263

    Article  PubMed  CAS  Google Scholar 

  51. Arabia G, Morelli M, Paglionico S, Novellino F, Salsone M, Giofrè L, Torchia G, Nicoletti G, Messina D, Condino F (2010) An magnetic resonance imaging T2*-weighted sequence at short echo time to detect putaminal hypointensity in Parkinsonisms. Mov Disord 25:2728–2734

    Article  PubMed  Google Scholar 

  52. Brooks DJ, Seppi K (2009) Proposed neuroimaging criteria for the diagnosis of multiple system atrophy. Mov Disord 24:949–964

    Article  PubMed  Google Scholar 

  53. Ito S, Shirai W, Hattori T (2007) Evaluating posterolateral linearization of the putaminal margin with magnetic resonance imaging to diagnose the Parkinson variant of multiple system atrophy. Mov Disord 22:578–581

    Article  PubMed  Google Scholar 

  54. Meijer FJ, Aerts MB, Abdo WF, Prokop M, Borm GF, Esselink RA, Goraj B, Bloem BR (2012) Contribution of routine brain MRI to the differential diagnosis of parkinsonism: a 3-year prospective follow-up study. J Neurol 259:929–935

    Article  PubMed Central  PubMed  Google Scholar 

  55. Wang Y, Butros SR, Shuai X, Dai Y, Chen C, Liu M, Haacke E, Hu J, Xu H (2012) Different iron-deposition patterns of multiple system atrophy with predominant parkinsonism and idiopathetic Parkinson diseases demonstrated by phase-corrected susceptibility-weighted imaging. AJNR 33:266–273

    Article  CAS  PubMed  Google Scholar 

  56. Konagaya M, Matsuoka Y, Goto Y, Yoshida M, Hashizume Y (1999) Pathological correlate of the slitlike changes on MRI at the putaminal margin in multiple system atrophy. J Neurol 246:142–143

    Article  CAS  PubMed  Google Scholar 

  57. Matsusue E, Fujii S, Kanasaki Y, Sugihara S, Miyata H, Ohama E, Ogawa T (2008) Putaminal lesion in multiple system atrophy: postmortem MR-pathological correlations. Neuroradiology 50:559–567

    Article  PubMed  Google Scholar 

  58. Feng J-y, Huang B, Yang W-Q, Zhang Y-h, Wang L-m, Wang L-j, Zhong X-l (2014) The putaminal abnormalities on 3.0 T magnetic resonance imaging: can they separate parkinsonism-predominant multiple system atrophy from Parkinson’s disease? Acta Radiol. doi:10.1177/0284185114524090

    Google Scholar 

  59. Fujii S, Matsusue E, Kinoshita T, Sugihara S, Ohama E, Ogawa T (2007) Hyperintense putaminal rim at 3T reflects fewer ferritin deposits in the lateral marginal area of the putamen. AJNR 28:777–781

    CAS  PubMed  Google Scholar 

  60. Lee W-H, Lee C-C, Shyu W-C, Chong P-N, Lin S-Z (2005) Hyperintense putaminal rim sign is not a hallmark of multiple system atrophy at 3T. AJNR 26:2238–2242

    PubMed  Google Scholar 

  61. Tha KK, Terae S, Tsukahara A, Soma H, Morita R, Yabe I, Ito YM, Sasaki H, Shirato H (2012) Hyperintense putaminal rim at 1.5 T: prevalence in normal subjects and distinguishing features from multiple system atrophy. BMC Neurol 12:39

    Article  PubMed Central  PubMed  Google Scholar 

  62. Horimoto Y, Aiba I, Yasuda T, Ohkawa Y, Katayama T, Yokokawa Y, Goto A, Ito Y (2002) Longitudinal MRI study of multiple system atrophy—when do the findings appear, and what is the course? J Neurol 249:847–854

    Article  PubMed  Google Scholar 

  63. Watanabe H, Saito Y, Terao S, Ando T, Kachi T, Mukai E, Aiba I, Abe Y, Tamakoshi A, Doyu M (2002) Progression and prognosis in multiple system atrophy an analysis of 230 Japanese patients. Brain 125:1070–1083

    Article  PubMed  Google Scholar 

  64. Jain RS, Sannegowda RB, Agrawal A, Hemrajani D, Jain R, Mathur T (2013) ‘Hot cross bun’sign in a case of cerebrotendinous xanthomatosis: a rare neuroimaging observation. BMJ Case Rep. doi:10.1136/bcr-2012-006641

    Google Scholar 

  65. Lee YC, Liu CS, Wu HM, Wang PS, Chang MH, Soong BW (2009) The ‘hot cross bun’sign in the patients with spinocerebellar ataxia. Eur J Neurol 16:513–516

    Article  PubMed  Google Scholar 

  66. Muqit M, D Mort KM, Shakir R (2001) “Hot cross bun” sign in a patient with parkinsonism secondary to presumed vasculitis. J Neurol Neurosurg Psychiatry 71:565

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  67. Rho SY, H-s Jang, Kim YH (2013) Hot Cross Bun Sign Following Bilateral Pontine Infarction: a Case Report. J Mov Disord 6:37–39

    Article  Google Scholar 

  68. Kim YJ, Ichise M, Ballinger JR, Vines D, Erami SS, Tatschida T, Lang AE (2002) Combination of dopamine transporter and D2 receptor SPECT in the diagnostic evaluation of PD, MSA, and PSP. Mov Disord 17:303–312

    Article  PubMed  Google Scholar 

  69. Perju-Dumbrava LD, Kovacs GG, Pirker S, Jellinger K, Hoffmann M, Asenbaum S, Pirker W (2012) Dopamine transporter imaging in autopsy-confirmed Parkinson’s disease and multiple system atrophy. Mov Disord 27:65–71

    Article  PubMed  Google Scholar 

  70. Muñoz E, Iranzo A, Rauek S, Lomeña F, Gallego J, Ros D, Santamaría J, Tolosa E (2011) Subclinical nigrostriatal dopaminergic denervation in the cerebellar subtype of multiple system atrophy (MSA-C). J Neurol 258:2248–2253

    Article  PubMed  Google Scholar 

  71. King AE, Mintz J, Royall DR (2011) Meta-analysis of 123I-MIBG cardiac scintigraphy for the diagnosis of Lewy body–related disorders. Mov Disord 26:1218–1224

    Article  PubMed  Google Scholar 

  72. Orimo S, Suzuki M, Inaba A, Mizusawa H (2012) 123I-MIBG myocardial scintigraphy for differentiating Parkinson’s disease from other neurodegenerative parkinsonism: a systematic review and meta-analysis. Parkinsonism Relat Disord 18:494–500

    Article  PubMed  Google Scholar 

  73. Chung EJ, Lee WY, Yoon WT, Kim BJ, Lee GH (2009) MIBG scintigraphy for differentiating Parkinson’s disease with autonomic dysfunction from Parkinsonism-predominant multiple system atrophy. Mov Disord 24:1650–1655

    Article  PubMed  Google Scholar 

  74. Nagayama H, Ueda M, Yamazaki M, Nishiyama Y, Hamamoto M, Katayama Y (2010) Abnormal cardiac [123I]-meta-iodobenzylguanidine uptake in multiple system atrophy. Mov Disord 25:1744–1747

    Article  PubMed  Google Scholar 

  75. Behnke S, Berg D, Naumann M, Becker G (2005) Differentiation of Parkinson’s disease and atypical parkinsonian syndromes by transcranial ultrasound. J Neurol Neurosurg Psychiatry 76:423–425

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  76. Walter U, Niehaus L, Probst T, Benecke R, Meyer B, Dressler D (2003) Brain parenchyma sonography discriminates Parkinson’s disease and atypical parkinsonian syndromes. Neurology 60:74–77

    Article  CAS  PubMed  Google Scholar 

  77. Vlaar AM, Bouwmans A, Mess WH, Tromp SC, Weber WE (2009) Transcranial duplex in the differential diagnosis of parkinsonian syndromes. J Neurol 256:530–538

    Article  PubMed  Google Scholar 

  78. Walter U, Školoudík D (2014) Transcranial sonography (TCS) of brain parenchyma in movement disorders: quality standards, diagnostic applications and novel technologies. Ultraschall Med 35:322–331

    Article  CAS  PubMed  Google Scholar 

  79. Hellwig S, Reinhard M, Amtage F, Guschlbauer B, Buchert R, Tüscher O, Weiller C, Niesen W, Meyer P (2014) Transcranial sonography and [18F] fluorodeoxyglucose positron emission tomography for the differential diagnosis of parkinsonism: a head-to-head comparison. Eur J Neurol 21:860–866

    Article  CAS  PubMed  Google Scholar 

  80. Vodušek DB (2001) Sphincter EMG and differential diagnosis of multiple system atrophy. Mov Disord 16:600–607

    Article  PubMed  Google Scholar 

  81. Gilman S, Low P, Quinn N, Albanese A, Ben-Shlomo Y, Fowler C, Kaufmann H, Klockgether T, Lang A, Lantos P (1998) Consensus statement on the diagnosis of multiple system atrophy. Clin Auton Res 8:359–362

    Article  CAS  PubMed  Google Scholar 

  82. Yamamoto T, Sakakibara R, Uchiyama T, Liu Z, Ito T, Awa Y, Yamamoto K, Kinou M, Yamanishi T, Hattori T (2005) When is Onuf’s nucleus involved in multiple system atrophy? A sphincter electromyography study. J Neurol Neurosurg Psychiatry 76:1645–1648

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  83. Reimann M, Schmidt C, Herting B, Prieur S, Junghanns S, Schweitzer K, Globas C, Schoels L, Reichmann H, Berg D (2010) Comprehensive autonomic assessment does not differentiate between Parkinson’s disease, multiple system atrophy and progressive supranuclear palsy. J Neural Transm 117:69–76

    Article  PubMed  Google Scholar 

  84. Schmidt C, Herting B, Prieur S, Junghanns S, Schweitzer K, Globas C, Schöls L, Reichmann H, Berg D, Ziemssen T (2009) Valsalva manoeuvre in patients with different Parkinsonian disorders. J Neural Transm 116:875–880

    Article  CAS  PubMed  Google Scholar 

  85. Iodice V, Lipp A, Ahlskog JE, Sandroni P, Fealey RD, Parisi JE, Matsumoto JY, Benarroch EE, Kimpinski K, Singer W (2012) Autopsy confirmed multiple system atrophy cases: mayo experience and role of autonomic function tests. J Neurol Neurosurg Psychiatry 83:453–459

    Article  PubMed Central  PubMed  Google Scholar 

  86. Anderson T, Luxon L, Quinn N, Daniel S, David Marsden C, Bronstein A (2008) Oculomotor function in multiple system atrophy: clinical and laboratory features in 30 patients. Mov Disord 23:977–984

    Article  PubMed  Google Scholar 

  87. Lee JY, Lee WW, Kim JS, Kim HJ, Kim JK, Jeon BS (2009) Perverted head-shaking and positional downbeat nystagmus in patients with multiple system atrophy. Mov Disord 24:1290–1295

    Article  PubMed  Google Scholar 

  88. Dickson DW, Hauw J, Agid Y, Litvan I (2011) Progressive supranuclear palsy and corticobasal degeneration. In: Dickson DW, Weller RO (eds) Neurodegeneration: The Molecular Pathology of Dementia and Movement Disorders, 2nd edn. Blackwell Publishing Ltd, Oxford, pp 135–155

    Chapter  Google Scholar 

  89. Silveira-Moriyama L, González AM, O’Sullivan SS, Williams DR, Massey L, Parkkinen L, Ahmed Z, de Silva R, Chacón JR, Revesz T (2009) Concomitant progressive supranuclear palsy and multiple system atrophy: more than a simple twist of fate? Neurosci Lett 467:208–211

    Article  CAS  PubMed  Google Scholar 

  90. Silveira-Moriyama L, Holton JL, Kingsbury A, Ayling H, Petrie A, Sterlacci W, Poewe W, Maier H, Lees AJ, Revesz T (2009) Regional differences in the severity of Lewy body pathology across the olfactory cortex. Neurosci Lett 453:77–80

    Article  CAS  PubMed  Google Scholar 

  91. Uchikado H, DelleDonne A, Uitti R, Dickson DW (2006) Coexistence of PSP and MSA: a case report and review of the literature. Acta Neuropathol 111:186–192

    Article  PubMed  Google Scholar 

  92. Iwasaki Y, Mori K, Ito M, Tatsumi S, Mimuro M, Yoshida M (2013) An autopsied case of progressive supranuclear palsy presenting with cerebellar ataxia and severe cerebellar involvement. Neuropathology 33:561–567

    CAS  PubMed  Google Scholar 

  93. Williams DR, de Silva R, Paviour DC, Pittman A, Watt HC, Kilford L, Holton JL, Revesz T, Lees AJ (2005) Characteristics of two distinct clinical phenotypes in pathologically proven progressive supranuclear palsy: Richardson’s syndrome and PSP-parkinsonism. Brain 128:1247–1258

    Article  PubMed  Google Scholar 

  94. Wenning GK, Colosimo C, Geser F, Poewe W (2004) Multiple system atrophy. Lancet Neurol 3:93–103

    Article  PubMed  Google Scholar 

  95. Bujan B, Hofer MJ, Oertel WH, Pagenstecher A, Bürk K (2012) Multiple system atrophy of the cerebellar type (MSA-C) with concomitant beta-amyloid and tau pathology. Clin Neuropathol 32:286–290

    Article  Google Scholar 

  96. Terni B, Rey MJ, Boluda S, Torrejón-Escribano B, Sabate MP, Calopa M, van Leeuwen FW, Ferrer I (2007) Mutant ubiquitin and p62 immunoreactivity in cases of combined multiple system atrophy and Alzheimer’s disease. Acta Neuropathol 113:403–416

    Article  PubMed  Google Scholar 

  97. Klockgether T, Schroth G, Diener H, Dichgans J (1990) Idiopathic cerebellar ataxia of late onset: natural history and MRI morphology. J Neurol Neurosurg Psychiatry 53:297–305

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  98. Tsuji S, Onodera O, Goto J, Nishizawa M (2008) Sporadic ataxias in Japan–a population-based epidemiological study. Cerebellum 7:189–197

    Article  CAS  PubMed  Google Scholar 

  99. Gilman S, Little R, Johanns J, Heumann M, Kluin K, Junck L, Koeppe R, An H (2000) Evolution of sporadic olivopontocerebellar atrophy into multiple system atrophy. Neurology 55:527–532

    Article  CAS  PubMed  Google Scholar 

  100. Abele M, Bürk K, Schöls L, Schwartz S, Besenthal I, Dichgans J, Zühlke C, Riess O, Klockgether T (2002) The aetiology of sporadic adult-onset ataxia. Brain 125:961–968

    Article  CAS  PubMed  Google Scholar 

  101. Futamura N, Matsumura R, Fujimoto Y, Horikawa H, Suzumura A, Takayanagi T (1998) CAG repeat expansions in patients with sporadic cerebellar ataxia. Acta Neurol Scand 98:55–59

    Article  CAS  PubMed  Google Scholar 

  102. Schöls L, Szymanski S, Peters S, Przuntek H, Epplen JT, Hardt C, Riess O (2000) Genetic background of apparently idiopathic sporadic cerebellar ataxia. Hum Genet 107:132–137

    Article  PubMed  Google Scholar 

  103. Kim JM, Hong S, Kim GP, Choi YJ, Kim YK, Park SS, Kim SE, Jeon BS (2007) Importance of low-range CAG expansion and CAA interruption in SCA2 Parkinsonism. Arch Neurol 64:1510–1518

    Article  PubMed  Google Scholar 

  104. Kim JY, Kim SY, Kim JM, Kim YK, Yoon KY, Lee BC, Kim JS, Paek SH, Park SS, Kim SE (2009) Spinocerebellar ataxia type 17 mutation as a causative and susceptibility gene in parkinsonism. Neurology 72:1385–1389

    Article  CAS  PubMed  Google Scholar 

  105. Factor SA, Qian J, Lava NS, Hubbard JD, Payami H (2005) False-positive SCA8 gene test in a patient with pathologically proven multiple system atrophy. Ann Neurol 57:462–463

    Article  PubMed  Google Scholar 

  106. Nirenberg MJ, Libien J, Vonsattel JP, Fahn S (2007) Multiple system atrophy in a patient with the spinocerebellar ataxia 3 gene mutation. Mov Disord 22:251–253

    Article  PubMed  Google Scholar 

  107. Takao M, Aoyama M, Ishikawa K, Sakiyama Y, Yomono H, Saito Y, Kurisaki H, Mihara B, Murayama S (2011) Spinocerebellar ataxia type 2 is associated with Parkinsonism and Lewy body pathology. BMJ Case Rep. doi:10.1136/bcr.1101.2011.3685

    Google Scholar 

  108. Mehta AR, Fox SH, Tarnopolsky M, Yoon G (2011) Mitochondrial mimicry of multiple system atrophy of the cerebellar subtype. Mov Disord 26:753–755

    Article  PubMed  Google Scholar 

  109. Stamelou M, Quinn NP, Bhatia KP (2013) “Atypical” atypical parkinsonism: new genetic conditions presenting with features of progressive supranuclear palsy, corticobasal degeneration, or multiple system atrophy—A diagnostic guide. Mov Disord 28:1184–1199

    Article  CAS  PubMed  Google Scholar 

  110. Fujioka S, Ogaki K, Tacik PM, Uitti RJ, Ross OA, Wszolek ZK (2014) Update on novel familial forms of Parkinson’s disease and multiple system atrophy. Parkinsonism Relat Disord 20:S29–S34

    Article  PubMed Central  PubMed  Google Scholar 

  111. Vidal J-S, Vidailhet M, Derkinderen P, Tzourio C, Alpérovitch A (2010) Familial aggregation in atypical Parkinson’s disease: a case control study in multiple system atrophy and progressive supranuclear palsy. J Neurol 257:1388–1393

    Article  PubMed  Google Scholar 

  112. MSA Research Collaboration (2013) Mutations in COQ2 in familial and sporadic multiple-system atrophy. N Engl J Med 369:233–244

    Article  CAS  Google Scholar 

  113. Hara K, Momose Y, Tokiguchi S, Shimohata M, Terajima K, Onodera O, Kakita A, Yamada M, Takahashi H, Hirasawa M (2007) Multiplex families with multiple system atrophy. Arch Neurol 64:545–551

    Article  PubMed  Google Scholar 

  114. Jeon BS, Farrer MJ, Bortnick SF (2014) Mutant COQ2 in multiple-system atrophy. N Engl J Med 371:80

    Article  CAS  PubMed  Google Scholar 

  115. Schottlaender L, Houlden H (2014) Mutant COQ2 in multiple-system atrophy. N Engl J Med 371:81

    CAS  PubMed  Google Scholar 

  116. Sharma M, Wenning GK, Kruger R (2014) Mutant COQ2 in multiple-system atrophy. N Engl J Med 371:80–81

    Article  CAS  PubMed  Google Scholar 

  117. Bak T, Caine D, Hearn V, Hodges J (2006) Visuospatial functions in atypical parkinsonian syndromes. J Neurol Neurosurg Psychiatry 77:454–456

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  118. Bürk K, Daum I, Rüb U (2006) Cognitive function in multiple system atrophy of the cerebellar type. Mov Disord 21:772–776

    Article  PubMed  Google Scholar 

  119. Wenning G, Tison F, Ben Shlomo Y, Daniel S, Quinn N (1997) Multiple system atrophy: a review of 203 pathologically proven cases. Mov Disord 12:133–147

    Article  CAS  PubMed  Google Scholar 

  120. Wenning G, Ben-Shlomo Y, Hughes A, Daniel S, Lees A, Quinn N (2000) What clinical features are most useful to distinguish definite multiple system atrophy from Parkinson’s disease? J Neurol Neurosurg Psychiatry 68:434–440

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  121. Asi YT, Ling H, Ahmed Z, Lees AJ, Revesz T, Holton JL (2014) Neuropathological features of multiple system atrophy with cognitive impairment. Mov Disord 29:884–888

    Article  CAS  PubMed  Google Scholar 

  122. Kawai Y, Suenaga M, Takeda A, Ito M, Watanabe H, Tanaka F, Kato K, Fukatsu H, Naganawa S, Kato T (2008) Cognitive impairments in multiple system atrophy MSA-C vs MSA-P. Neurology 70:1390–1396

    Article  CAS  PubMed  Google Scholar 

  123. McKeith I, Dickson D, Lowe J, Emre M, O’brien J, Feldman H, Cummings J, Duda J, Lippa C, Perry E (2005) Diagnosis and management of dementia with Lewy bodies third report of the DLB consortium. Neurology 65:1863–1872

    Article  CAS  PubMed  Google Scholar 

  124. Kao AW, Racine CA, Quitania LC, Kramer JH, Christine CW, Miller BL (2009) Cognitive and neuropsychiatric profile of the synucleinopathies: Parkinson’s disease, dementia with Lewy bodies and multiple system atrophy. Alzheimer Dis Assoc Disord 23:365–370

    Article  PubMed Central  PubMed  Google Scholar 

  125. Williams DR, Lees AJ (2005) Visual hallucinations in the diagnosis of idiopathic Parkinson’s disease: a retrospective autopsy study. Lancet Neurol 4:605–610

    Article  PubMed  Google Scholar 

  126. Kolenc M, Popović M, Grmek M, Pirtošek Z, Trošt M (2012) A case of multiple system atrophy with normal dopamine transporter imaging. J Neurol 259:2729–2731

    Article  PubMed  Google Scholar 

  127. McKinley J, O’Connell M, Farrell M, Lynch T (2014) Normal dopamine transporter imaging does not exclude multiple system atrophy. Parkinsonism Relat Disord 20:933–934

    Article  PubMed  Google Scholar 

  128. Kim H-J, Jeon BS, Lee J-Y, Yun JY, Kim YE, Paek SH (2012) Young-onset multiple system atrophy. J Neurol Sci 319:168–170

    Article  PubMed  Google Scholar 

  129. Masui K, Nakata Y, Fujii N, Iwaki T (2012) Extensive distribution of glial cytoplasmic inclusions in an autopsied case of multiple system atrophy with a prolonged 18-year clinical course. Neuropathology 32:69–76

    Article  PubMed  Google Scholar 

  130. Gaig C, Iranzo A, Tolosa E, Vilaseca I, Rey M, Santamaria J (2008) Pathological description of a non-motor variant of multiple system atrophy. J Neurol Neurosurg Psychiatry 79:1399–1400

    Article  CAS  PubMed  Google Scholar 

  131. Berciano J, Valldeoriola F, Ferrer I, Rumià J, Pascual J, Marín C, Rey MJ, Tolosa E (2002) Presynaptic parkinsonism in multiple system atrophy mimicking Parkinson’s disease: a clinicopathological case study. Mov Disord 17:812–816

    Article  PubMed  Google Scholar 

  132. Fujishiro H, Ahn T-B, Frigerio R, DelleDonne A, Josephs KA, Parisi JE, Ahlskog JE, Dickson DW (2008) Glial cytoplasmic inclusions in neurologically normal elderly: prodromal multiple system atrophy? Acta Neuropathol 116:269–275

    Article  PubMed Central  PubMed  Google Scholar 

  133. Kon T, Mori F, Tanji K, Miki Y, Wakabayashi K (2013) An autopsy case of preclinical multiple system atrophy (MSA-C). Neuropathology 33:667–672

    Article  CAS  PubMed  Google Scholar 

  134. Parkkinen L, Hartikainen P, Alafuzoff I (2006) Abundant glial alpha-synuclein pathology in a case without overt clinical symptoms. Clin Neuropathol 26:276–283

    Article  Google Scholar 

  135. Wenning G, Shlomo YB, Magalhaes M, Danie S, Quinn N (1994) Clinical features and natural history of multiple system atrophy An analysis of 100 cases. Brain 117:835–845

    Article  PubMed  Google Scholar 

  136. Wakabayashi K, Mori F, Nishie M, Oyama Y, Kurihara A, Yoshimoto M, Kuroda N (2005) An autopsy case of early (“minimal change”) olivopontocerebellar atrophy (multiple system atrophy-cerebellar). Acta Neuropathol 110:185–190

    Article  PubMed  Google Scholar 

  137. Ahmed Z, Asi Y, Sailer A, Lees A, Houlden H, Revesz T, Holton J (2012) The neuropathology, pathophysiology and genetics of multiple system atrophy. Neuropathol Appl Neurobiol 38:4–24

    Article  CAS  PubMed  Google Scholar 

  138. Rodriguez-Diehl R, Rey MJ, Gironell A, Martinez-Saez E, Ferrer I, Sánchez-Valle R, Jagüe J, Nos C, Gelpi E (2012) “Preclinical” MSA in definite Creutzfeldt-Jakob disease. Neuropathology 32:158–163

    Article  PubMed  Google Scholar 

  139. DelleDonne A, Klos KJ, Fujishiro H, Ahmed Z, Parisi JE, Josephs KA, Frigerio R, Burnett M, Wszolek ZK, Uitti RJ (2008) Incidental Lewy body disease and preclinical Parkinson disease. Arch Neurol 65:1074–1080

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by a grant of the Korea Health technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A101273).

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Department of Neurology and Movement Disorder Center, Parkinson study group, and Neuroscience Research Institute, College of Medicine, Seoul National University, Seoul, Korea

    Han-Joon Kim & Beom S. Jeon

  2. Institute of Clinical Neurobiology, Vienna, Austria

    Kurt A. Jellinger

Authors
  1. Han-Joon Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Beom S. Jeon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kurt A. Jellinger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Beom S. Jeon.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, HJ., Jeon, B.S. & Jellinger, K.A. Diagnosis and differential diagnosis of MSA: boundary issues. J Neurol 262, 1801–1813 (2015). https://doi.org/10.1007/s00415-015-7654-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-015-7654-2

Keywords

Search

Navigation