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Abnormalities of white and grey matter in early multiple system atrophy: comparison of parkinsonian and cerebellar variants

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Multiple system atrophy (MSA) is a neurodegenerative disorder with progressive motor and autonomic dysfunction. There is a paucity of information on the early neurostructural changes in MSA, especially its subtypes, MSA-P (patients with predominant parkinsonism) and MSA-C (patients with predominant cerebellar signs). This study investigates the abnormalities of grey matter (GM) and white matter (WM) in early MSA and its subtypes using multi-modal voxel-based analysis.

Materials and methods

Twenty-six patients with MSA with duration of symptoms ≤ 2.5 years (mean duration: 1.6 ±0.9 years) were assessed clinically and with 3T MRI. Voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) were performed to identify the structural changes in MSA and its subtypes. The GM changes and diffusion parameters of WM tracts were correlated with the clinical scores. The results were compared with MRI of 25 age- and gender-matched healthy controls.


The early structural changes in MSA included GM loss of the cerebellum and subcallosal gyrus with widespread involvement of supratentorial and infratentorial WM fibres. In MSA-C, GM loss was limited to the cerebellum with WM changes predominantly affecting the infratentorial WM and association tracts. In contrast, MSA-P did not demonstrate any GM loss and the WM involvement was mainly supratentorial. There was no significant correlation between structural changes and clinical severity score.


In early MSA, WM microstructure was more affected than GM. These changes were greater in MSA-C than in MSA-P, suggesting variable deterioration in the subtypes of MSA.

Key Points

• Structural changes in early multiple system atrophy were evaluated using multi-modal neuroimaging.

• White matter was more affected than grey matter in early MSA.

• Clinical variables did not correlate with early structural changes.

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Fig. 1
Fig. 2



Corpus callosum


Diffusion tensor imaging


European multiple system atrophy study group


Fractional anisotropy


Grey matter


Internal capsule


Inferior cerebellar peduncle


Inferior fronto-occipital fasciculus


Middle cerebellar peduncle


Mean diffusivity


Magnetic resonance imaging


Cerebellar ataxia predominant multiple system atrophy


Parkinsonism predominant multiple system atrophy


Multiple system atrophy


North American multiple system atrophy study group


Superior longitudinal fasciculus


Unified multiple system atrophy rating scale


Voxel-based morphometry


White matter


  1. Fanciulli A, Wenning GK (2015) Multiple-System Atrophy. N Engl J Med 372:249–263.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  3. Wenning GK, Ben-Shlomo Y, Hughes A et al (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  CAS  PubMed  PubMed Central  Google Scholar 

  4. Gilman S, Wenning GK, Low PA et al (2008) Second consensus statement on the diagnosis of multiple system atrophy. Neurology 71:670–676.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ubhi K, Low P, Masliah E (2011) Multiple system atrophy: A clinical and neuropathological perspective. Trends Neurosci 34:581–590.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  Google Scholar 

  7. Kim H-J, Jeon BS, Kim YE et al (2013) Clinical and imaging characteristics of dementia in multiple system atrophy. Parkinsonism Relat Disord 19:617–21. doi:

  8. Brenneis C, Boesch SM, Egger KE et al (2006) Cortical atrophy in the cerebellar variant of multiple system atrophy: A voxel-based morphometry study. Mov Disord 21:159–165.

    Article  PubMed  Google Scholar 

  9. Chang CC, Chang YY, Chang WN et al (2009) Cognitive deficits in multiple system atrophy correlate with frontal atrophy and disease duration. Eur J Neurol 16:1144–1150.

    Article  CAS  PubMed  Google Scholar 

  10. Tzarouchi LC, Astrakas LG, Konitsiotis S et al (2010) Voxel-based morphometry and voxel-based relaxometry in parkinsonian variant of multiple system atrophy. J Neuroimaging 20:260–266.

    Article  PubMed  Google Scholar 

  11. Hauser T-K, Luft A, Skalej M et al (2006) Visualization and quantification of disease progression in multiple system atrophy. Mov Disord 21:1674–1681.

    Article  PubMed  Google Scholar 

  12. Lee MJ, Shin J-H, Seoung J-K et al (2016) Cognitive impairments associated with morphological changes in cortical and subcortical structures in multiple system atrophy of the cerebellar type. Eur J Neurol 23:92–100.

    Article  CAS  PubMed  Google Scholar 

  13. Oishi K, Konishi J, Mori S et al (2009) Reduced fractional anisotropy in early-stage cerebellar variant of multiple system atrophy. J Neuroimaging 19:127–131.

    Article  PubMed  Google Scholar 

  14. Zanigni S, Evangelisti S, Testa C et al (2017) White matter and cortical changes in atypical parkinsonisms: A multimodal quantitative MR study. Parkinsonism Relat Disord 39:44–51.

    Article  PubMed  Google Scholar 

  15. Wang J, Wai Y, Lin W-Y et al (2010) Microstructural changes in patients with progressive supranuclear palsy: a diffusion tensor imaging study. J Magn Reson Imaging 32:69–75.

    Article  CAS  PubMed  Google Scholar 

  16. Blain CRV, Barker GJ, Jarosz JM et al (2006) Measuring brain stem and cerebellar damage in parkinsonian syndromes using diffusion tensor MRI. Neurology 67:2199–2205.

    Article  CAS  PubMed  Google Scholar 

  17. Wang PS, Wu HM, Lin CP, Soong BW (2011) Use of diffusion tensor imaging to identify similarities and differences between cerebellar and Parkinsonism forms of multiple system atrophy. Neuroradiology 53:471–481.

    Article  PubMed  Google Scholar 

  18. Wang P-S, Yeh C-L, Lu C-F et al (2016) The involvement of supratentorial white matter in multiple system atrophy: a diffusion tensor imaging tractography study. Acta Neurol Belg 117:213–220.

    Article  PubMed  Google Scholar 

  19. Ji L, Zhu D, Xiao C, Shi J (2014) Tract based spatial statistics in multiple system atrophy: A comparison between clinical subtypes. Parkinsonism Relat Disord 20:1050–1055.

    Article  PubMed  Google Scholar 

  20. Ito S, Makino T, Shirai W, Hattori T (2008) Diffusion tensor analysis of corpus callosum in progressive supranuclear palsy. Neuroradiology 50:981–985.

    Article  PubMed  Google Scholar 

  21. Rulseh AM, Keller J, Rusz J et al (2016) Diffusion tensor imaging in the characterization of multiple system atrophy. Neuropsychiatr Dis Treat 12:2181–2187.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Wenning GK, Geser F, Krismer F et al (2013) The natural history of multiple system atrophy: A prospective European cohort study. Lancet Neurol. 12:264–274.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Low PA, Reich SG, Jankovic J et al (2015) Natural history of multiple system atrophy in the USA: a prospective cohort study. Lancet Neurol. 14:710–719.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Popescu V, Battaglini M, Hoogstrate WS et al (2012) Optimizing parameter choice for FSL-Brain Extraction Tool (BET) on 3D T1 images in multiple sclerosis. Neuroimage 61:1484–1494.

    Article  CAS  PubMed  Google Scholar 

  25. Tristán-Vega A, Aja-Fernández S (2010) DWI filtering using joint information for DTI and HARDI. Med Image Anal. 14:205–218.

    Article  PubMed  Google Scholar 

  26. Mestre TA, Gupta A, Lang A E (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. 87 443–4.

  27. Laurens B, Vergnet S, Lopez MC et al (2017) Multiple System Atrophy - State of the Art. Curr Neurol Neurosci Rep 17.

  28. Roncevic D, Palma JA, Martinez J et al (2014) Cerebellar and parkinsonian phenotypes in multiple system atrophy: similarities, differences and survival. J Neural Transm (Vienna). 121:507–512

    Article  PubMed  Google Scholar 

  29. Worker A, Blain C, Jarosz J et al (2014) Diffusion Tensor Imaging of Parkinson’s Disease, Multiple System Atrophy and Progressive Supranuclear Palsy: A Tract-Based Spatial Statistics Study. PLoS One. 9:e112638.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Tha KK, Terae S, Yabe I et al (2010) Microstructural white matter abnormalities of multiple system atrophy: in vivo topographic illustration by using diffusion-tensor MR imaging. Radiology. 255:563–569.

    Article  PubMed  Google Scholar 

  31. Tir M, Delmaire C, Le Thuc V et al (2009) Motor-related circuit dysfunction in MSA-P: Usefulness of combined whole-brain imaging analysis. Mov Disord 24:863–870

    Article  PubMed  Google Scholar 

  32. Kim JS, Yang JJ, Lee DK et al (2015) Cognitive impairment and its structural correlates in the parkinsonian subtype of multiple system atrophy. Neurodegener Dis 15:294–300.

    Article  CAS  PubMed  Google Scholar 

  33. Shigemoto Y, Matsuda H, Kamiya K et al (2013) In vivo evaluation of gray and white matter volume loss in the parkinsonian variant of multiple system atrophy using SPM8 plus DARTEL for VBM. NeuroImage Clin 2:491–496.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Minnerop M, Specht K, Ruhlmann J et al (2007) Voxel-based morphometry and voxel-based relaxometry in multiple system atrophy-A comparison between clinical subtypes and correlations with clinical parameters. Neuroimage. 36:1086–1095.

    Article  CAS  PubMed  Google Scholar 

  35. Minnerop M, Lüders E, Specht K et al (2010) Callosal tissue loss in multiple system atrophy-A one-year follow-up study. Mov Disord 25:2613–2620.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Specht K, Minnerop M, Müller-Hübenthal J et al (2005) Complementary results by combining voxel-based morphometry and voxel-based relaxometry. Neuroimage. 25:287–293.

    Article  PubMed  Google Scholar 

  37. Brenneis C, Egger K, Scherfler C et al (2007) Progression of brain atrophy in multiple system atrophy: A longitudinal VBM study. J Neurol 254:191–196.

    Article  PubMed  Google Scholar 

  38. Yang H, Wang X, Liao W et al (2015) Application of diffusion tensor imaging in multiple system atrophy: the involvement of pontine transverse and longitudinal fibers. Int J Neurosci 125: 18–24.

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Correspondence to Pramod Kumar Pal.

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The scientific guarantor of this publication is Dr. Pramod Kumar Pal.

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The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

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The authors report no financial interests or conflicts of interest.

Statistics and biometry

No complex statistical methods were necessary for this paper.

Informed consent

Written informed consent was obtained from all subjects in this study.

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Institutional review board approval was obtained.


• prospective

• case-control study

• performed at one institution

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Dash, S.K., Stezin, A., Takalkar, T. et al. Abnormalities of white and grey matter in early multiple system atrophy: comparison of parkinsonian and cerebellar variants. Eur Radiol 29, 716–724 (2019).

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