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Progression of dopamine transporter decline in patients with the Parkinson variant of multiple system atrophy: a voxel-based analysis of [123I]β-CIT SPECT

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Abstract

Purpose

We characterized the progression of dopamine transporter (DAT) decline in the striatum and extrastriatal regions including the midbrain and pons of patients with the Parkinson variant of multiple system atrophy (MSA-P) and compared longitudinally collected SPECT results with those in a cohort of patients with Parkinson's disease (PD).

Methods

Eight patients with MSA-P (age 60.4 ± 7.7 years, disease duration 2.4 ± 1 years, UPDRS-III motor score 39.7 ± 4.7), and 11 patients with PD (age 61.2 ± 6.4 years, disease duration 2.4 ± 1.1 years, UPDRS-III motor score 18.9 ± 7.6) underwent a baseline and follow-up [123I]β-CIT SPECT investigation within a time period of 1.3 years. Statistical parametric mapping (SPM) and a repetitive ANOVA design were used to objectively localize the decline in DAT availability without having to make an a priori hypothesis as to its location.

Results

SPM localized significant reductions in [123I]β-CIT uptake in the dorsal brainstem of MSA-P patients compared to PD patients (p < 0.001) at baseline. Additional reductions in the DAT signal were localized in the caudate and anterior putamen of patients with MSA-P patients compared to PD patients at the follow-up examination (p < 0.001). Relative decline in tracer binding was evident in the caudate and anterior putamen of MSA-P patients compared to PD patients in the longitudinal analysis (p < 0.05), whereas no significant relative signal alteration was observed in the brainstem.

Conclusion

In contrast to PD, the relatively higher rate of signal reduction in the caudate and anterior putamen is consistent with the faster disease progression reported in MSA-P. At baseline, the tracer uptake in the brainstem was already at very low levels in the MSA-P patients compared to that in healthy control subjects and did not progress any further, suggesting that the degeneration of monoaminergic neurons is almost complete early in the disease course.

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References

  1. Lantos PL. The definition of multiple system atrophy: a review of recent developments. J Neuropathol Exp Neurol. 1998;57:1099–111.

    Article  PubMed  CAS  Google Scholar 

  2. Wenning GK, Tison F, Ben Shlomo Y, Daniel SE, Quinn NP. Multiple system atrophy: a review of 203 pathologically proven cases. Mov Disord. 1997;12:133–47.

    Article  PubMed  CAS  Google Scholar 

  3. Wenning GK, Ben Shlomo Y, Magalhães M, Daniel SE, Quinn NP. Clinical features and natural history of multiple system atrophy. An analysis of 100 cases. Brain 1994;117(Pt 4):835–45.

    Article  PubMed  Google Scholar 

  4. Watanabe H, Saito Y, Terao S, Ando T, Kachi T, Mukai E, et al. Progression and prognosis in multiple system atrophy: an analysis of 230 Japanese patients. Brain. 2002;125:1070–83.

    Article  PubMed  Google Scholar 

  5. Ben-Shlomo Y, Wenning GK, Tison F, Quinn NP. Survival of patients with pathologically proven multiple system atrophy: a meta-analysis. Neurology. 1997;48:384–93.

    PubMed  CAS  Google Scholar 

  6. Seibyl JP, Marek KL, Quinlan D, Sheff K, Zoghbi S, Zea-Ponce Y, et al. Decreased single-photon emission computed tomographic [123I]beta-CIT striatal uptake correlates with symptom severity in Parkinson's disease. Ann Neurol. 1995;38:589–98.

    Article  PubMed  CAS  Google Scholar 

  7. Brucke T, Asenbaum S, Pirker W, Djamshidian S, Wenger S, Wober C, et al. Measurement of the dopaminergic degeneration in Parkinson's disease with [123I]beta-CIT and SPECT. Correlation with clinical findings and comparison with multiple system atrophy and progressive supranuclear palsy. J Neural Transm Suppl. 1997;50:9–24.

    PubMed  CAS  Google Scholar 

  8. Marek K, Innis R, van Dyck C, Fussell B, Early M, Eberly S, et al. [123I]beta-CIT SPECT imaging assessment of the rate of Parkinson's disease progression. Neurology. 2001;57:2089–94.

    PubMed  CAS  Google Scholar 

  9. Varrone A, Marek KL, Jennings D, Innis RB, Seibyl JP. [(123)I]beta-CIT SPECT imaging demonstrates reduced density of striatal dopamine transporters in Parkinson's disease and multiple system atrophy. Mov Disord. 2001;16:1023–32.

    Article  PubMed  CAS  Google Scholar 

  10. Knudsen GM, Karlsborg M, Thomsen G, Krabbe K, Regeur L, Nygaard T, et al. Imaging of dopamine transporters and D2 receptors in patients with Parkinson's disease and multiple system atrophy. Eur J Nucl Med Mol Imaging. 2004;31:1631–8.

    Article  PubMed  CAS  Google Scholar 

  11. Scherfler C, Seppi K, Donnemiller E, Goebel G, Brenneis C, Virgolini I, et al. Voxel-wise analysis of [123I]beta-CIT SPECT differentiates the Parkinson variant of multiple system atrophy from idiopathic Parkinson's disease. Brain. 2005;128:1605–12.

    Article  PubMed  Google Scholar 

  12. Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology. 1967;17:427–42.

    PubMed  CAS  Google Scholar 

  13. Fahn S, Elton R. Unified Parkinson's disease rating scale. In: Fahn S, Marsden CD, Calne DB, Goldstein M, editors. Recent developments in Parkinson's disease. Vol. 2. Florham Park (NJ): Macmillan Health Care Information; 1987. p. 153–164.

  14. Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry. 1992;55:181–4.

    Article  PubMed  CAS  Google Scholar 

  15. Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology. 2008;71(9):670–6.

    Article  PubMed  CAS  Google Scholar 

  16. Kuikka JT, Bergstrom KA, Ahonen A, Lansimies E. The dosimetry of iodine-123 labelled 2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane. Eur J Nucl Med. 1994;21:53–6.

    PubMed  CAS  Google Scholar 

  17. Laruelle M, Wallace E, Seibyl JP, Baldwin RM, Zea-Ponce Y, Zoghbi SS, et al. Graphical, kinetic, and equilibrium analyses of in vivo [123I]beta-CIT binding to dopamine transporters in healthy human subjects. J Cereb Blood Flow Metab. 1994;14:982–94.

    Article  PubMed  CAS  Google Scholar 

  18. Innis RB, Cunningham VJ, Delforge J, Fujita M, Gjedde A, Gunn RN, et al. Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab. 2007;27:1533–9.

    Article  PubMed  CAS  Google Scholar 

  19. De Keyser J, De Backer JP, Ebinger G, Vauquelin G. [3H]GBR 12935 binding to dopamine uptake sites in the human brain. J Neurochem. 1989;53:1400–4.

    Article  PubMed  Google Scholar 

  20. Rorden C, Brett M. Stereotaxic display of brain lesions. Behav Neurol. 2000;12:191–200.

    PubMed  Google Scholar 

  21. Friston KJ, Ashburner J, Frith CD, Poline JB, Heather JD, Frackowiak RS. Spatial registration and normalization of images. Hum Brain Mapp. 1995;2:165–189.

    Article  Google Scholar 

  22. Rakshi JS, Uema T, Ito K, Bailey DL, Morrish PK, Ashburner J, et al. Frontal, midbrain and striatal dopaminergic function in early and advanced Parkinson's disease. A 3D [(18)F]dopa-PET study. Brain. 1999;122(Pt 9):1637–50.

    Article  PubMed  Google Scholar 

  23. Worsley KJ, Marrett S, Neelin P, Vandal AC, Friston KJ, Evans AC. A unified statistical approach for determining significant signals in images of cerebral activation. Hum Brain Mapp. 1996;4:58–73.

    Article  PubMed  CAS  Google Scholar 

  24. Antonini A, Benti R, De Notaris R, Tesei S, Zecchinelli A, Sacilotto G, et al. 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. 2003;24:149–50.

    Article  PubMed  CAS  Google Scholar 

  25. Pirker W, Djamshidian S, Asenbaum S, Gerschlager W, Tribl G, Hoffmann M, et al. Progression of dopaminergic degeneration in Parkinson's disease and atypical parkinsonism: a longitudinal beta-CIT SPECT study. Mov Disord. 2002;17:45–53.

    Article  PubMed  Google Scholar 

  26. Scherfler C, Nocker M. Dopamine transporter SPECT: how to remove subjectivity? Mov Disord. 2009;24 Suppl 2:S721–4.

    Article  PubMed  Google Scholar 

  27. Kim YJ, Ichise M, Ballinger JR, Vines D, Erami SS, Tatschida T, et al. Combination of dopamine transporter and D2 receptor SPECT in the diagnostic evaluation of PD, MSA, and PSP. Mov Disord. 2002;17:303–12.

    Article  PubMed  Google Scholar 

  28. Brooks DJ, Salmon EP, Mathias CJ, Quinn N, Leenders KL, Bannister R, et al. The relationship between locomotor disability, autonomic dysfunction, and the integrity of the striatal dopaminergic system in patients with multiple system atrophy, pure autonomic failure, and Parkinson's disease, studied with PET. Brain. 1990;1990:1539–52.

    Article  Google Scholar 

  29. Kume A, Takahashi A, Hashizume Y. Neuronal cell loss of the striatonigral system in multiple system atrophy. J Neurol Sci. 1993;117:33–40.

    Article  PubMed  CAS  Google Scholar 

  30. Morrish PK, Sawle GV, Brooks DJ. The rate of progression of Parkinson's disease. A longitudinal [18F]DOPA PET study. Adv Neurol. 1996;69:427–31.

    PubMed  CAS  Google Scholar 

  31. Parkinson Study Group. Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression. JAMA. 2002;287(13):1653–61.

    Article  Google Scholar 

  32. Seibyl JP, Marek K, Sheff K, Baldwin RM, Zoghbi S, Zea-Ponce Y, et al. Test/retest reproducibility of iodine-123-betaCIT SPECT brain measurement of dopamine transporters in Parkinson's patients. J Nucl Med. 1997;38:1453–9.

    PubMed  CAS  Google Scholar 

  33. Booij J, Habraken JB, Bergmans P, Tissingh G, Winogrodzka A, Wolters EC, et al. Imaging of dopamine transporters with iodine-123-FP-CIT SPECT in healthy controls and patients with Parkinson's disease. J Nucl Med. 1998;39:1879–84.

    PubMed  CAS  Google Scholar 

  34. Morrish PK. How valid is dopamine transporter imaging as a surrogate marker in research trials in Parkinson’s disease. Mov Disord. 2003;18: Suppl 7:S63–70.

    Article  PubMed  Google Scholar 

  35. Seppi K, Scherfler C, Donnemiller E, Virgolini I, Schocke MF, Goebel G, et al. Topography of dopamine transporter availability in progressive supranuclear palsy: a voxelwise [123I]beta-CIT SPECT analysis. Arch Neurol. 2006;63:1154–60.

    Article  PubMed  Google Scholar 

  36. Innis R, Baldwin R, Sybirska E, Zea Y, Laruelle M, al-Tikriti M, et al. Single photon emission computed tomography imaging of monoamine reuptake sites in primate brain with [123I]CIT. Eur J Pharmacol. 1991;200:369–70.

    Article  PubMed  CAS  Google Scholar 

  37. Staley JK, Basile M, Flynn DD, Mash DC. Visualizing dopamine and serotonin transporters in the human brain with the potent cocaine analogue [125I]RTI-55: in vitro binding and autoradiographic characterization. J Neurochem. 1994;62:549–56.

    Article  PubMed  CAS  Google Scholar 

  38. Pirker W, Asenbaum S, Kasper S, Walter H, Angelberger P, Koch G, et al. beta-CIT SPECT demonstrates blockade of 5HT-uptake sites by citalopram in the human brain in vivo. J Neural Transm Gen Sect. 1995;100:247–56.

    Article  PubMed  CAS  Google Scholar 

  39. Uhl GR. Neurotransmitter transporters (plus): a promising new gene family. Trends Neurosci. 1992;15:265–8.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  41. Papp MI, Lantos PL. The distribution of oligodendroglial inclusions in multiple system atrophy and its relevance to clinical symptomatology. Brain. 1994;117(Pt 2):235–43.

    Article  PubMed  Google Scholar 

  42. Benarroch EE, Schmeichel AM, Low PA, Parisi JE. Involvement of medullary serotonergic groups in multiple system atrophy. Ann Neurol. 2004;55:418–22.

    Article  PubMed  Google Scholar 

  43. Glover G, Pelc N. The nonlinear partial volume artefact. J Comput Assist Tomogr. 1979;25:79–86.

    Google Scholar 

  44. Hoffman EJ, Huang SC, Phelps ME. Quantification in positron emission tomography. 1. Effect of object size. J Comput Assist Tomogr. 1979;22:324–33.

    Google Scholar 

  45. Kojima A, Matsumoto M, Takahashi M, Hirota Y, Yoshida H. Effect of spatial resolution on SPECT quantification values. J Nucl Med. 1989;30:508–14.

    PubMed  CAS  Google Scholar 

  46. Pirker W, Holler I, Gerschlager W, Asenbaum S, Zettinig G, Brucke T. Measuring the rate of progression of Parkinson's disease over a 5-year period with beta-CIT SPECT. Mov Disord. 2003;18:1266–72.

    Article  PubMed  Google Scholar 

  47. Muller J, Wenning GK, Jellinger K, McKee A, Poewe W, Litvan I. Progression of Hoehn and Yahr stages in Parkinsonian disorders: a clinicopathologic study. Neurology. 2000;55:888–91.

    PubMed  CAS  Google Scholar 

  48. Jankovic J, McDermott M, Carter J, Gauthier S, Goetz C, Golbe L, et al. Variable expression of Parkinson's disease: a base-line analysis of the DATATOP cohort. The Parkinson Study Group Neurology. 1990;40:1529–34.

    PubMed  CAS  Google Scholar 

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Acknowledgment

This study was supported by grant GZ 70038/2 PR 4/98 from the Austrian Federal Ministry of Science and Transport.

Ethics approval

The study was approved by the Ethics Committee of the Innsbruck Medical University. Subjects’ consent was obtained in accordance with the Declaration of Helsinki.

Conflicts of interest

None.

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Authors and Affiliations

  1. Department of Neurology, Innsbruck Medical University, Anichstrasse 35, 6020, Innsbruck, Austria

    Michael Nocker, Klaus Seppi, Gregor K. Wenning, Werner Poewe & Christoph Scherfler

  2. Department of Nuclear Medicine, Innsbruck Medical University, Innsbruck, Austria

    Eveline Donnemiller & Irene Virgolini

Authors
  1. Michael Nocker
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  2. Klaus Seppi
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  3. Eveline Donnemiller
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  4. Irene Virgolini
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  5. Gregor K. Wenning
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  6. Werner Poewe
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  7. Christoph Scherfler
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Corresponding author

Correspondence to Michael Nocker.

Additional information

Michael Nocker and Klaus Seppi contributed equally to this research project.

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Nocker, M., Seppi, K., Donnemiller, E. et al. Progression of dopamine transporter decline in patients with the Parkinson variant of multiple system atrophy: a voxel-based analysis of [123I]β-CIT SPECT. Eur J Nucl Med Mol Imaging 39, 1012–1020 (2012). https://doi.org/10.1007/s00259-012-2100-5

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  • DOI: https://doi.org/10.1007/s00259-012-2100-5

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