Myocardial MIBG scintigraphy in genetic Parkinson’s disease as a model for Lewy body disorders

  • Iñigo GabilondoEmail author
  • Verónica Llorens
  • Trinidad Rodriguez
  • Manuel Fernández
  • Tomas Pérez Concha
  • Marian Acera
  • Beatriz Tijero
  • Ane Murueta-Goyena
  • Rocío del Pino
  • Jesús Cortés
  • Juan Carlos Gómez-Esteban
Original Article



To identify myocardial sympathetic denervation patterns suggestive of Lewy body (LB) pathology in patients with genetic and idiopathic parkinsonisms by 123I-metaiodobenzylguanidine (MIBG) scintigraphy.


We retrospectively analysed myocardial MIBG images acquired with a dual-head gamma camera and low-energy high-resolution collimator (LEHR) in 194 patients with suspected synucleinopathy or atypical parkinsonism, including 34 with genetic Parkinson’s disease (PD; 4 PARK1, 8 PARK2 and 22 PARK8), 85 with idiopathic PD (iPD), 6 with idiopathic REM sleep behaviour disorder (iRBD), 17 with dementia with LB (DLB), 40 with multiple system atrophy (MSA) and 12 with progressive supranuclear palsy (PSP), and in 45 healthy controls. We calculated heart-to-mediastinum MIBG uptake ratios (HMR) at 15 min and 4 h (HMR4H) for the LEHR and standardized medium-energy collimators, to obtain classification accuracies and optimal cut-off values for HMR using supervised classification and ROC analyses.


While patients with LB disorders had markedly lower HMR4HLEHR than controls (controls 1.86 ± 0.26, iPD 1.38 ± 0.29, iRBD 1.23 ± 0.09, PARK1 1.20 ± 0.09, DLB 1.17 ± 0.11; p < 0.05), for the remaining patient categories differences were smaller (PARK8 1.51 ± 0.32; p < 0.05) or not significant (MSA 1.82 ± 0.37, PSP 1.59 ± 0.23, PARK2 1.51 ± 0.30; p > 0.05). The diagnostic accuracy of HMR4HLEHR was highest in patients with LB disorders (PARK1, iPD, DLB, iRBD; 89% to 97%) and lowest in those with PARK2, PARK8, PSP and MSA (65% to 76%), with an optimal HMR4HLEHR cut-off value of 1.72 for discriminating most patients with LB disorders including iPD and 1.40 for discriminating those with aggressive LB spectrum phenotypes (DLB, PARK1 and iRBD).


Our study including patients with a wide spectrum of genetic and idiopathic parkinsonisms with different degrees of LB pathology further supports myocardial MIBG scintigraphy as an accurate tool for discriminating patients with LB spectrum disorders.


Parkinson’s disease MIBG cardiac scintigraphy Dysautonomia Genetic Alpha-synuclein 


Authors’ contributions

I.G., V.L. and J.C.G.-E. designed the study, and I.G., V.L., T.R., J.C.G.-E., A.M.-G. and BT collected the data. I.G., V.L. and J.C.G.-E. supervised the study. I.G., J.C. and J.C.G.-E. did the statistical analysis, and I.G. and V.L. created the figures and tables. I.G., V.L. and J.C.G.-E. interpreted the results of the analysis with subsequent substantial contributions from all the coauthors. I.G., V.L. and J.C.G.-E. drafted the manuscript, to which all the authors contributed with revisions, and all the authors approved the final version.


This study was funded by Michael J. Fox Foundation via the RRIA (Rapid Response Innovation Awards) 2014 Program (grant ID 10189) and the Instituto de Salud Carlos III through the project PI14/00679 and Juan Rodes grant JR15/00008 (I.G.; cofunded by the European Regional Development Fund/European Social Fund ‘Investing in Your Future’).

Compliance with ethical standards

Conflicts of interest


Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

259_2018_4183_Fig3_ESM.png (7.1 mb)
Supplementary figure 1

(PNG 7219 kb)

259_2018_4183_MOESM1_ESM.tif (4.5 mb)
High resolution image (TIF 4569 kb)
259_2018_4183_Fig4_ESM.png (1.1 mb)
Supplementary figure 2

(PNG 1097 kb)

259_2018_4183_MOESM2_ESM.tif (208 kb)
High resolution image (TIF 207 kb)
259_2018_4183_MOESM3_ESM.pdf (139 kb)
ESM 1 (PDF 138 kb)
259_2018_4183_MOESM4_ESM.pdf (140 kb)
ESM 2 (PDF 139 kb)


  1. 1.
    Goldstein DS. Sympathetic neuroimaging. Handb Clin Neurol. 2013;117:365–70. Scholar
  2. 2.
    Orimo S, Ozawa E, Nakade S, Sugimoto T, Mizusawa H. (123)I-metaiodobenzylguanidine myocardial scintigraphy in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 1999;67:189–94.CrossRefGoogle Scholar
  3. 3.
    Miyamoto T, Miyamoto M, Inoue Y, Usui Y, Suzuki K, Hirata K. Reduced cardiac 123I-MIBG scintigraphy in idiopathic REM sleep behavior disorder. Neurology. 2006;67:2236–8. Scholar
  4. 4.
    Berganzo K, Tijero B, Somme JH, Llorens V, Sanchez-Manso JC, Low D, et al. SCOPA-AUT scale in different parkinsonisms and its correlation with (123)I-MIBG cardiac scintigraphy. Parkinsonism Relat Disord. 2012;18:45–8. Scholar
  5. 5.
    Taki J, Yoshita M, Yamada M, Tonami N. Significance of 123I-MIBG scintigraphy as a pathophysiological indicator in the assessment of Parkinson’s disease and related disorders: it can be a specific marker for Lewy body disease. Ann Nucl Med. 2004;18:453–61.CrossRefGoogle Scholar
  6. 6.
    Suzuki M, Kurita A, Hashimoto M, Fukumitsu N, Abo M, Ito Y, et al. Impaired myocardial 123I-metaiodobenzylguanidine uptake in Lewy body disease: comparison between dementia with Lewy bodies and Parkinson's disease. J Neurol Sci. 2006;240:15–9. Scholar
  7. 7.
    Kashihara K, Imamura T, Shinya T. Cardiac 123I-MIBG uptake is reduced more markedly in patients with REM sleep behavior disorder than in those with early stage Parkinson's disease. Parkinsonism Relat Disord. 2010;16:252–5. Scholar
  8. 8.
    Oda H, Ishii K, Terashima A, Shimada K, Yamane Y, Kawasaki R, et al. Myocardial scintigraphy may predict the conversion to probable dementia with Lewy bodies. Neurology. 2013;81:1741–5. Scholar
  9. 9.
    Zarranz JJ, Alegre J, Gomez-Esteban JC, Lezcano E, Ros R, Ampuero I, et al. The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann Neurol. 2004;55:164–73. Scholar
  10. 10.
    Tijero B, Gomez-Esteban JC, Lezcano E, Fernandez-Gonzalez C, Somme J, Llorens V, et al. Cardiac sympathetic denervation in symptomatic and asymptomatic carriers of the E46K mutation in the alpha synuclein gene. Parkinsonism Relat Disord. 2013;19:95–100. Scholar
  11. 11.
    Singleton A, Gwinn-Hardy K, Sharabi Y, Li ST, Holmes C, Dendi R, et al. Association between cardiac denervation and parkinsonism caused by alpha-synuclein gene triplication. Brain. 2004;127:768–72. Scholar
  12. 12.
    Tijero B, Gabilondo I, Lezcano E, Teran-Villagra N, Llorens V, Ruiz-Martinez J, et al. Autonomic involvement in parkinsonian carriers of PARK2 gene mutations. Parkinsonism Relat Disord. 2015;21:717–22. Scholar
  13. 13.
    Valldeoriola F, Gaig C, Muxi A, Navales I, Paredes P, Lomena F, et al. 123I-MIBG cardiac uptake and smell identification in parkinsonian patients with LRRK2 mutations. J Neurol. 2011;258:1126–32. Scholar
  14. 14.
    Nonnekes J, Timmer MH, de Vries NM, Rascol O, Helmich RC, Bloem BR. Unmasking levodopa resistance in Parkinson’s disease. Mov Disord. 2016;31:1602–9. Scholar
  15. 15.
    Stefanelli A, Treglia G, Bruno I, Rufini V, Giordano A. Pharmacological interference with 123I-metaiodobenzylguanidine: a limitation to developing cardiac innervation imaging in clinical practice? Eur Rev Med Pharmacol Sci. 2013;17:1326–33.PubMedGoogle Scholar
  16. 16.
    Flotats A, Carrio I, Agostini D, Le Guludec D, Marcassa C, Schafers M, et al. Proposal for standardization of 123I-metaiodobenzylguanidine (MIBG) cardiac sympathetic imaging by the EANM Cardiovascular Committee and the European Council of Nuclear Cardiology. Eur J Nucl Med Mol Imaging. 2010;37:1802–12. Scholar
  17. 17.
    Verschure DO, Poel E, Nakajima K, Okuda K, van Eck-Smit BL, Somsen GA, et al. A European myocardial (123)I-mIBG cross-calibration phantom study. J Nucl Cardiol. 2018;25:1191–7.
  18. 18.
    Inoue Y, Suzuki A, Shirouzu I, Machida T, Yoshizawa Y, Akita F, et al. Effect of collimator choice on quantitative assessment of cardiac iodine 123 MIBG uptake. J Nucl Cardiol. 2003;10:623–32.CrossRefGoogle Scholar
  19. 19.
    Perkins NJ, Schisterman EF. The inconsistency of "optimal" cutpoints obtained using two criteria based on the receiver operating characteristic curve. Am J Epidemiol. 2006;163:670–5. Scholar
  20. 20.
    Hall M, Frank E, Holmes G, Pfahringer B, Reutemann P, Witten IH. The WEKA data mining software: an update. J SIGKDD Explor Newsl. 2009;11:10–8. Scholar
  21. 21.
    Schisterman EF, Perkins NJ, Liu A, Bondell H. Optimal cut-point and its corresponding Youden index to discriminate individuals using pooled blood samples. Epidemiology. 2005;16:73–81.CrossRefGoogle Scholar
  22. 22.
    Tijero B, Gomez Esteban JC, Somme J, Llorens V, Lezcano E, Martinez A, et al. Autonomic dysfunction in parkinsonian LRRK2 mutation carriers. Parkinsonism Relat Disord. 2013;19:906–9. Scholar
  23. 23.
    Lamotte G, Morello R, Lebasnier A, Agostini D, Defer GL. Accuracy and cutoff values of delayed heart to mediastinum ratio with (123)I-metaiodobenzylguanidine cardiac scintigraphy for Lewy body disease diagnoses. BMC Neurol. 2015;15:83. Scholar
  24. 24.
    Miyamoto T, Miyamoto M, Suzuki K, Nishibayashi M, Iwanami M, Hirata K. 123I-MIBG cardiac scintigraphy provides clues to the underlying neurodegenerative disorder in idiopathic REM sleep behavior disorder. Sleep. 2008;31:717–23.CrossRefGoogle Scholar
  25. 25.
    Braune S, Reinhardt M, Schnitzer R, Riedel A, Lucking CH. Cardiac uptake of [123I]MIBG separates Parkinson's disease from multiple system atrophy. Neurology. 1999;53:1020–5.CrossRefGoogle Scholar
  26. 26.
    Berg D, Postuma RB, Bloem B, Chan P, Dubois B, Gasser T, et al. Time to redefine PD? Introductory statement of the MDS Task Force on the definition of Parkinson's disease. Mov Disord. 2014;29:454–62. Scholar
  27. 27.
    Nagayama H, Ueda M, Yamazaki M, Nishiyama Y, Hamamoto M, Katayama Y. Abnormal cardiac [(123)I]-meta-iodobenzylguanidine uptake in multiple system atrophy. Mov Disord. 2010;25:1744–7. Scholar
  28. 28.
    Sone M, Yoshida M, Hashizume Y, Hishikawa N, Sobue G. α-Synuclein-immunoreactive structure formation is enhanced in sympathetic ganglia of patients with multiple system atrophy. Acta Neuropathol. 2005;110:19–26. Scholar
  29. 29.
    Orimo S, Kanazawa T, Nakamura A, Uchihara T, Mori F, Kakita A, et al. Degeneration of cardiac sympathetic nerve can occur in multiple system atrophy. Acta Neuropathol. 2007;113:81–6. Scholar
  30. 30.
    King AE, Mintz J, Royall DR. Meta-analysis of 123I-MIBG cardiac scintigraphy for the diagnosis of Lewy body-related disorders. Mov Disord. 2011;26:1218–24. Scholar
  31. 31.
    Nagamachi S, Fujita S, Nishii R, Futami S, Tamura S, Mizuta M, et al. Prognostic value of cardiac I-123 metaiodobenzylguanidine imaging in patients with non-insulin-dependent diabetes mellitus. J Nucl Cardiol. 2006;13:34–42. Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Iñigo Gabilondo
    • 1
    • 2
    Email author
  • Verónica Llorens
    • 1
    • 3
  • Trinidad Rodriguez
    • 3
  • Manuel Fernández
    • 1
    • 2
    • 4
  • Tomas Pérez Concha
    • 2
  • Marian Acera
    • 1
  • Beatriz Tijero
    • 1
    • 2
  • Ane Murueta-Goyena
    • 1
  • Rocío del Pino
    • 1
  • Jesús Cortés
    • 5
    • 6
    • 7
  • Juan Carlos Gómez-Esteban
    • 1
    • 2
    • 4
  1. 1.Neurodegenerative Diseases GroupBiocruces-Bizkaia Health Research InstituteBarakaldoSpain
  2. 2.Neurology DepartmentCruces University HospitalBarakaldoSpain
  3. 3.Nuclear Medicine DepartmentCruces University HospitalBarakaldoSpain
  4. 4.Department of NeurosciencesUniversity of the Basque Country (UPV/EHU)LeioaSpain
  5. 5.Computational Neuroimaging GroupBiocruces-Bizkaia Health Research InstituteBarakaldoSpain
  6. 6.Ikerbasque: The Basque Foundation for ScienceBilbaoSpain
  7. 7.Department of Cell Biology and HistologyUniversity of the Basque Country (UPV/EHU)LeioaSpain

Personalised recommendations