Abstract
Background
PARK2 is an autosomal recessive parkinsonism caused by parkin gene mutations. Several Parkinson’s Disease (PD) cases harbor single parkin mutations, raising a debate about the pathogenic meaning of heterozygous mutations. Here, we evaluate cardiac autonomic innervation in patients with either two or one parkin mutations compared to patients with idiopathic PD (IPD).
Patients and Methods
Myocardial 123I-metaiodobenzylguanidine (MIBG) scintigraphy was performed in six PD patients with single parkin mutations (HET), four with two mutations (PARK2), and eight with IPD.
Results
In comparison to control group, IPD patients showed lower early and late heart-to-mediastinum (H/M) ratios and higher washout rates, whereas HET patients had only lower early H/M ratio, and PARK2 patients were not different for any parameter. At individual level, MIBG findings were abnormal in 7/8 IPD, in 4/6 HET and in 1/4 PARK2 patients.
Conclusions
Preserved cardiac 123I-MIBG uptake confirms that PARK2 pathogenic mechanism, at least partially, differs from that responsible for IPD. HET subjects show intermediate findings, suggesting possible heterogeneity.
References
Lücking CB, Dürr A, Bonifati V, De Michele G, Gasser T, Harhangi BS, et al. Association between early-onset Parkinson’s disease and mutations in the parkin gene. N Engl J Med 2000;342:1560-7.
Khan NL, Graham E, Critchley P, Schrag AE, Wood NW, Lees AJ, et al. Parkin disease: A phenotypic study of a large case series. Brain 2003;126:1279-92.
Bonifati V, De Michele G, Lücking CB, Fabrizio E, Ambrosio G, Vanacore N, et al. The parkin gene and its phenotype. Italian PD Genetics Study Group, French PD Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson’s Disease. Neurol Sci 2001;22:51-2.
Khan NL, Katzenschlager R, Watt H, Bathia KB, Wood NW, Quinn N, et al. Olfaction differentiates parkin disease from early-onset parkinsonism and Parkinson disease. Neurology 2004;62:1224-6.
Alcalay RN, Siderowf A, Ottman R, Caccappolo E, Mejia-Santana H, Tang M-X, et al. Olfaction in Parkin heterozygotes and compound heterozygotes: The CORE-PD study. Neurology 2011;76:319-26.
Poulopoulos M, Levy OA, Alcalay RN. The neuropathology of genetic Parkinson’s disease. Mov Disord 2012;27:831-42.
Miyakawa S, Ogino M, Funabe S, Uchino A, Shimo Y, Hattori N, et al. Lewy body pathology in a patient with a homozygous parkin deletion. Mov Disord 2013;28:388-91.
Kashihara K, Ohno M, Kawada S, Okumura Y. Reduced cardiac uptake and enhanced washout of 123I-MIBG in pure autonomic failure occurs conjointly with Parkinson’s disease and dementia with Lewy bodies. J Nucl Med 2006;47:1099-101.
Quattrone A, Bagnato A, Annesi G, Novellino F, Morgante L, Savettieri G, et al. Myocardial 123metaiodobenzylguanidine uptake in genetic Parkinson’s disease. Mov Disord 2008;23:21-7.
Orimo S, Amino T, Yokochi M, Kojo T, Uchihara T, Takahashi A, et al. Preserved cardiac sympathetic nerve accounts for normal cardiac uptake of MIBG in PARK2. Mov Disord 2005;20:1350-3.
Suzuki M, Hattori N, Orimo S, Fukumitsu N, Abo M, Kono Y, et al. Preserved myocardial [123I]metaiodobenzylguanidine uptake in autosomal recessive juvenile parkinsonism: First case report. Mov Disord 2005;20:634-6.
West A, Periquet M, Lincoln S. Complex relationship between parkin mutations and parkinson disease. Am J of Med Genet 2002;114:584-91.
Morales B, Martínez A, Gonzalo I, Vidal L, Ros R, Gomez-Tortosa E, et al. Steele-Richardson-Olszewski syndrome in a patient with a single C212Y mutation in the parkin protein. Mov Disord 2002;17:1374-80.
Sharp ME, Marder KS, Côté L, Clark LN, Nichols WC, Vonsattel JP, et al. Parkinson’s disease with Lewy bodies associated with a heterozygous PARKIN dosage mutation. Mov Disord 2014;29:566-8.
De Rosa A, Volpe G, Marcantonio L, Santoro L, Brice A, Filla A, et al. Neurophysiological evidence of corticospinal tract abnormality in patients with Parkin mutations. J Neurol 2006;253:275-9.
Criscuolo C, De Rosa A, Guacci A, Simons EJ, Breedveld GJ, Peluso S, et al. The LRRK2 R1441C mutation is more frequent than G2019S in Parkinson’s disease patients from southern Italy. Mov Disord 2011;26:1733-6.
Flotats A, Carrió I, Agostini D, Le Guludec D, Marcassa C, Schäfers M, et al. Proposal for standardization of 123Imetaiodobenzylguanidine (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.
Pellegrino T, Petretta M, De Luca S, Paolillo S, Boemio A, Carotenuto R, et al. Observer reproducibility of results from a low-dose 123I-metaiodobenzylguanidine cardiac imaging protocol in patients with heart failure. Eur J Nucl Med Mol Imaging 2013;40:1549-57.
Disclosure
The authors have neither financial disclosures nor conflict of interest related to current manuscript.
Author information
Authors and Affiliations
Corresponding author
Additional information
See related editorial, doi:10.1007/s12350-015-0353-7.
Rights and permissions
About this article
Cite this article
De Rosa, A., Pellegrino, T., Pappatà, S. et al. Myocardial 123I-metaiodobenzylguanidine scintigraphy in patients with homozygous and heterozygous parkin mutations. J. Nucl. Cardiol. 24, 103–107 (2017). https://doi.org/10.1007/s12350-015-0332-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12350-015-0332-z