Myocardial MIBG scintigraphy in genetic Parkinson’s disease as a model for Lewy body disorders
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.
KeywordsParkinson’s disease MIBG cardiac scintigraphy Dysautonomia Genetic Alpha-synuclein
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
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 was obtained from all individual participants included in the study.
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