Brain MRI of multiple system atrophy of cerebellar type: a prospective study with implications for diagnosis criteria

  • G. Carré
  • J. L. Dietemann
  • O. Gebus
  • S. Montaut
  • O. Lagha-Boukbiza
  • T. Wirth
  • S. Kremer
  • I. J. Namer
  • M. Anheim
  • C. TranchantEmail author
Original Communication



The second consensus statement for the diagnosis of multiple system atrophy type cerebellar (MSA-C) includes pons and middle cerebellar peduncle (MCP) atrophy as MRI features. However, other MRI abnormalities such as MCP hyperintensity, hot cross bun sign (HCB), putaminal hypointensity and hyperintense putaminal rim have been described.


To evaluate, in patients with sporadic late-onset cerebellar ataxia (SLOCA), the discriminative value of several MRI features for the diagnosis of MSA-C, to follow their evolution during the course of MSA-C, and to search for correlations between these MRI features and clinical signs.


Consecutive patients referred for SLOCA underwent comprehensive clinical evaluation and laboratory investigations, brain MRI, DaTscan and a 1-year follow-up.


Among 80 patients, 26 had MSA-C, 22 another diagnosis, and 32 no diagnosis at the end of the follow-up. At baseline, MCP hyperintensity and HCB were more frequent in patients finally diagnosed with MSA-C than in other patients with SLOCA (p < 0.0001), and had the highest specificity (98.5%) and positive predictive value (91.7%) for the diagnosis of MSA-C, compared to all other MRI signs. The most relevant MRI sequence regarding HCB sign was the T2-proton density (DP) weighted. All MRI features were more frequent with disease duration. No correlation was found between any MRI feature and neither clinical data, nor dopaminergic neuronal loss (p = 0.5008), except between vermis atrophy and UPDRSIII score.


MCP hyperintensity and HCB sign should be added into the list of additional features of possible MSA-C. MRI signal abnormalities suggestive of MSA-C should be searched for in suitable sequence.


Multiple system atrophy Late-onset cerebellar ataxia Magnetic resonance imaging Hot cross bun sign DaTscan 



This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study has been approved by the local ethical committee.

Supplementary material

415_2020_9702_MOESM1_ESM.pdf (10 kb)
Figure 1: Scale for the Assessment and Rating of Ataxia (SARA) with disease duration in group 1. Each point is the average value obtained when considering all the data obtained for MSA-C patients (PDF 10 kb)
415_2020_9702_MOESM2_ESM.pdf (10 kb)
Figure 2: Spinocerebellar Degeneration Functional Score (SDFS) with disease duration in group 1. Each point is the average value obtained when considering all the data obtained for MSA-C patients. (PDF 9 kb)
415_2020_9702_MOESM3_ESM.pdf (11 kb)
Figure 3: Unified Parkinson’s Disease Rating Scale III (UPDRS III) with disease duration in group 1. Each point is the average value obtained when considering all the data obtained for MSA-C patients. (PDF 10 kb)


  1. 1.
    Gebus O, Montaut S, Monga B, Wirth T, Cheraud C, Rego AC, Zinchenko I, Carré G, Hamdaoui M, Hautecloque G, Nguyen-Them L, Lannes B, Chanson JB, Lagha-Boukbiza O, Fleury MC, Devys D, Nicolas G, Rudolf G, Bereau M, Mallaret M, Renaud M, Acquaviva M, Koenig M, Koob M, Kremer S, Namer IJ, Cazeneuve C, -Laguna A, Tranchant C, Anheim M (2017) Deciphering the causes of sporadic late-onset cerebellar ataxias: a prospective study with implications for diagnostic work. J Neurol 264(6):1118–1126PubMedCrossRefGoogle Scholar
  2. 2.
    Hadjivassiliou M, Martindale J, Shanmugarajah P, Grünewald RA, Sarrigiannis PG, Beauchamp N, Garrard K, Warburton R, Sanders DS, Friend D, Duty S, Taylor J, Hoggard N (2017) Causes of progressive cerebellar ataxia: prospective evaluation of 1500 patients. J Neurol Neurosurg Psychiatry 88(4):301–309PubMedCrossRefGoogle Scholar
  3. 3.
    Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, Wood NW, Colosimo C, Dürr A, Fowler CJ, Kaufmann H, Klockgether T, Lees A, Poewe W, Quinn N, Revesz T, Robertson D, Sandroni P, Seppi K, Vidailhet M (2008) Second consensus statement on the diagnosis of multiple system atrophy. Neurology 71(9):670–676PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Lewinski F, Werner C, Jörn T, Mohr A, Sixel-Döring F, Trenkwalder C (2007) T2*-weighted MRI in diagnosis of multiple system atrophy: a practical approach for clinicians. J Neurol 254(9):1184–1188CrossRefGoogle Scholar
  5. 5.
    Righini A, Antonini A, Ferrarini M, de Notaris R, Canesi M, Triulzi F, Pezzoli G (2002) Thin section MR study of the basal ganglia in the differential diagnosis between striatonigral degeneration and Parkinson disease. J Comput Assist Tomogr 26(2):266–271PubMedCrossRefGoogle Scholar
  6. 6.
    Lee EA, Cho HI, Kim SS, Lee WY (2004) Comparison of magnetic resonance imaging in subtypes of multiple system atrophy. Parkinsonism Relat Disord 10(6):363–368PubMedCrossRefGoogle Scholar
  7. 7.
    Bhattacharya K, Saadia D, Eisenkraft B, Yahr M, Olanow W, Drayer B, Kaufmann H (2002) Brain magnetic resonance imaging in multiple-system atrophy and Parkinson disease: a diagnostic algorithm. Arch Neurol 59(5):835–842PubMedCrossRefGoogle Scholar
  8. 8.
    Nicoletti G, Fera F, Condino F, Auteri W, Gallo O, Pugliese P, Arabia G, Morgante L, Barone P, Zappia M, Quattrone A (2006) MR imaging of middle cerebellar peduncle width: differentiation of multiple system atrophy from Parkinson disease. Radiology 239(3):825–830PubMedCrossRefGoogle Scholar
  9. 9.
    Seppi K, Schocke MFH, Prennschuetz-Schuetzenau K, Mair KJ, Esterhammer R, Kremser C, Muigg A, Scherfler C, Jaschke W, Wenning GK, Poewe W (2006) Topography of putaminal degeneration in multiple system atrophy: a diffusion magnetic resonance study. Mov Disord Off J Mov Disord Soc 21(6):847–852CrossRefGoogle Scholar
  10. 10.
    Bürk K, Bühring U, Schulz JB, Zühlke C, Hellenbroich Y, Dichgans J (2005) Clinical and magnetic resonance imaging characteristics of sporadic cerebellar ataxia. Arch Neurol 62(6):981–985PubMedCrossRefGoogle Scholar
  11. 11.
    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 Am J Neuroradiol 26(9):2238–2242PubMedGoogle Scholar
  12. 12.
    -Metz M, Naumann M, Csoti I, Solymosi L (2001) Measurement of the midbrain diameter on routine magnetic resonance imaging: a simple and accurate method of differentiating between Parkinson disease and progressive supranuclear palsy. Arch Neurol 58(7):1076–1079PubMedCrossRefGoogle Scholar
  13. 13.
    Anheim M, Lagier-Tourenne C, Stevanin G, Fleury M, Durr A, Namer IJ, Denora P, Brice A, Mandel JL, Koenig M, Tranchant C (2009) SPG11 spastic paraplegia. A new cause of juvenile parkinsonism. J Neurol 256(1):104–108PubMedCrossRefGoogle Scholar
  14. 14.
    Murata Y, Yamaguchi S, Kawakami H, Imon Y, Maruyama H, Sakai T, Kazuta T, Ohtake T, Nishimura M, Saida T, Chiba S, Oh-I T, Nakamura S (1998) Characteristic magnetic resonance imaging findings in Machado-Joseph disease. Arch Neurol 55(1):33–37PubMedCrossRefGoogle Scholar
  15. 15.
    Namekawa M, Honda J, Shimazaki H (2015) “Hot Cross Bun” sign associated with SCA1. Intern Med 54(7):859–860PubMedCrossRefGoogle Scholar
  16. 16.
    Bürk K, Skalej M, Dichgans J (2001) Pontine MRI hyperintensities (“the cross sign”) are not pathognomonic for multiple system atrophy (MSA). Mov Disord Off J Mov Disord Soc 16(3):535CrossRefGoogle Scholar
  17. 17.
    Sugiyama A, Ito S, Suichi T, Sakurai T, Mukai H, Yokota H, Yonezu T, Kuwabara S (2015) Putaminal hypointensity on T2*-weighted MR imaging is the most practically useful sign in diagnosing multiple system atrophy: a preliminary study. J Neurol Sci 349(1–2):174–178PubMedCrossRefGoogle Scholar
  18. 18.
    Deguchi K, Ikeda K, Kume K, Takata T, Kokudo Y, Kamada M, Touge T, Honjo N, Masaki T (2015) Significance of the hot-cross bun sign on T2*-weighted MRI for the diagnosis of multiple system atrophy. J Neurol 262(6):1433–1439PubMedCrossRefGoogle Scholar
  19. 19.
    Kasahara S, Miki Y, Kanagaki M, Kondo T, Yamamoto A, Morimoto E, Okadaa T, Itoc H, Takahashic H, Togashi K (2012) “Hot cross bun” sign in multiple system atrophy with predominant cerebellar ataxia: A comparison between proton density-weighted imaging and T2-weighted imaging. Eur J Radiol 81(10):2848–2852PubMedCrossRefGoogle Scholar
  20. 20.
    Schrag A, Good CD, Miszkiel K, Morris HR, Mathias CJ, Lees AJ, Quinn NP (2000) Differentiation of atypical parkinsonian syndromes with routine MRI. Neurology 54(3):697–702PubMedCrossRefGoogle Scholar
  21. 21.
    Schrag A, Kingsley D, Phatouros C, Mathias CJ, Lees AJ, Daniel SE, Quinn NP (1998) Clinical usefulness of magnetic resonance imaging in multiple system atrophy. J Neurol Neurosurg Psychiatry 65(1):65–71PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Lin DJ, Hermann KL, Schmahmann JD (2016) The diagnosis and natural history of multiple system atrophy, cerebellar type. Cerebellum 15(6):663–679PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Pradhan S, Tandon R (2017) Relevance of non-specific MRI features in multiple system atrophy. Clin Neurol Neurosurg 159:29–33PubMedCrossRefGoogle Scholar
  24. 24.
    Burk K (2004) MRI-based volumetric differentiation of sporadic cerebellar ataxia. Brain 127(1):175–181PubMedCrossRefGoogle Scholar
  25. 25.
    Abe K, Hikita T, Yokoe M, Mihara M, Sakoda S (2006) The “cross” signs in patients with multiple system atrophy: a quantitative study. J Neuroimaging 16(1):73–77PubMedCrossRefGoogle Scholar
  26. 26.
    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(7):847–854PubMedCrossRefGoogle Scholar
  27. 27.
    Konagaya M, Konagaya Y, Iida M (1994) Clinical and magnetic resonance imaging study of extrapyramidal symptoms in multiple system atrophy. J Neurol Neurosurg Psychiatry 57(12):1528–1531PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Wakai M, Kume A, Takahashi A, Ando T, Hashizume Y (1994) A study of parkinsonism in multiple system atrophy: clinical and MRI correlation. Acta Neurol Scand 90(4):225–231PubMedCrossRefGoogle Scholar
  29. 29.
    Wenning GK, Tison F, Shlomo Y, Daniel SE, Quinn NP (1997) Multiple system atrophy: a review of 203 pathologically proven cases. Mov Disord 12(2):133–147PubMedCrossRefGoogle Scholar
  30. 30.
    Mestre TA, Gupta A, Lang AE (2016) MRI signs of multiple system atrophy preceding the clinical diagnosis: the case for an imaging-supported probable MSA diagnostic category. J Neurol Neurosurg Psychiatry 87(4):443–444PubMedCrossRefGoogle Scholar
  31. 31.
    Antonini A, Benti R, De Notaris R, Tesei S, Zecchinelli A, Sacilotto G, Meucci N, Canesi M, Mariani C, Pezzoli G, Gerundini P (2003) 123I-Ioflupane/SPECT binding to striatal dopamine transporter (DAT) uptake in patients with Parkinson’s disease, multiple system atrophy, and progressive supranuclear palsy. Neurol Sci 24(3):149–150PubMedCrossRefGoogle Scholar
  32. 32.
    Pirker W, Asenbaum S, Bencsits G, Prayer D, Gerschlager W, Deecke L, Brücke T (2000) [123I]beta-CIT SPECT in multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration. Mov Disord Off J Mov Disord Soc 15(6):1158–1167CrossRefGoogle Scholar
  33. 33.
    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(12):2248–2253PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2020

Authors and Affiliations

  • G. Carré
    • 1
    • 2
  • J. L. Dietemann
    • 3
  • O. Gebus
    • 1
  • S. Montaut
    • 1
  • O. Lagha-Boukbiza
    • 1
  • T. Wirth
    • 1
  • S. Kremer
    • 3
  • I. J. Namer
    • 4
  • M. Anheim
    • 1
    • 5
    • 6
  • C. Tranchant
    • 1
    • 5
    • 6
    Email author
  1. 1.Service de NeurologieHôpitaux Universitaires de Strasbourg, Hôpital de HautepierreStrasbourgFrance
  2. 2.Service de NeurologieHôpitaux Civils de Colmar, Hôpital Louis PasteurColmarFrance
  3. 3.Service d’imagerie 2, Hôpitaux Universitaires de Strasbourg, Hôpital de HautepierreStrasbourg CedexFrance
  4. 4.Service de Médecine NucléaireHôpitaux Universitaires de Strasbourg, Hôpital de HautepierreStrasbourgFrance
  5. 5.Fédération de Médecine Translationnelle de Strasbourg (FMTS)Université de StrasbourgStrasbourgFrance
  6. 6.Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC)INSERM-U964/CNRS-UMR7104/Université de StrasbourgIllkirchFrance

Personalised recommendations