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Cardiac parasympathetic dysfunction in the early phase of Parkinson’s disease

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Abstract

Cardiac parasympathetic function is strongly affected by aging. Although sympathetic dysfunction has been well documented in Parkinson’s disease (PD), cardiac parasympathetic dysfunction has not been well studied. The objective of this study was to clarify the development of cardiac parasympathetic dysfunction in the early phase of PD and to explore the age-corrected correlation between cardiac parasympathetic dysfunction and cardiac sympathetic dysfunction. We reviewed 25 healthy controls and 56 patients with idiopathic PD of Hoehn and Yahr stages I–III. We evaluated cardiac parasympathetic function using the Valsalva ratio, the baroreflex sensitivity (BRS) and the coefficient of variation of RR intervals in the resting state (resting-CVRR) and during deep breathing (DB-CVRR). In addition, we measured cardiac 123I-metaiodobenzylguanidine (MIBG) uptake to investigate the relationship between cardiac sympathetic and parasympathetic dysfunction in PD. Compared with healthy controls, patients with PD showed significantly decreased cardiac parasympathetic parameters (resting-CVRR 2.8 ± 1.3 vs. 1.7 ± 0.6%, p < 0.001; DB-CVRR 5.8 ± 2.3 vs. 3.8 ± 1.7%, p < 0.001; Valsalva ratio 1.52 ± 0.26 vs. 1.34 ± 0.17, p < 0.01; BRS 10.6 ± 9.5 vs. 5.0 ± 5.4 ms/mmHg, p < 0.01). In particular, resting-CVRR and DB-CVRR were significantly decreased in the early phase of PD. In age-corrected analyses, none of the parasympathetic indices correlated with the delayed cardiac 123I-MIBG uptake. These observations indicate that cardiac parasympathetic dysfunction occurs in the early phase of PD, but not necessarily in parallel with cardiac sympathetic dysfunction.

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References

  1. Chaudhuri KR, Schapira AH (2009) Non-motor symptoms of Parkinson’s disease: dopaminergic pathophysiology and treatment. Lancet Neurol 8(5):464–474. doi:10.1016/s1474-4422(09)70068-7

    Article  CAS  PubMed  Google Scholar 

  2. Goldman JG, Postuma R (2014) Premotor and non-motor features of Parkinson’s disease. Curr Opin Neurol 27(4):434–441. doi:10.1097/wco.0000000000000112

    Article  PubMed  PubMed Central  Google Scholar 

  3. Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24(2):197–211

    Article  PubMed  Google Scholar 

  4. Hamada K, Hirayama M, Watanabe H, Kobayashi R, Ito H, Ieda T, Koike Y, Sobue G (2003) Onset age and severity of motor impairment are associated with reduction of myocardial 123I-MIBG uptake in Parkinson’s disease. J Neurol Neurosurg Psychiatry 74(4):423–426

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Hirayama M, Hakusui S, Koike Y, Ito K, Kato T, Ikeda M, Hasegawa Y, Takahashi A (1995) A scintigraphical qualitative analysis of peripheral vascular sympathetic function with meta-[123I]iodobenzylguanidine in neurological patients with autonomic failure. J Auton Nerv Syst 53(2–3):230–234

    Article  CAS  PubMed  Google Scholar 

  6. Nakamura T, Hirayama M, Ito H, Takamori M, Hamada K, Takeuchi S, Watanabe H, Koike Y, Sobue G (2007) Dobutamine stress test unmasks cardiac sympathetic denervation in Parkinson’s disease. J Neurol Sci 263(1–2):133–138. doi:10.1016/j.jns.2007.07.005

    Article  PubMed  Google Scholar 

  7. Haensch CA, Lerch H, Jorg J, Isenmann S (2009) Cardiac denervation occurs independent of orthostatic hypotension and impaired heart rate variability in Parkinson’s disease. Parkinsonism Relat Dis 15(2):134–137. doi:10.1016/j.parkreldis.2008.04.031

    Article  Google Scholar 

  8. Oka H, Toyoda C, Yogo M, Mochio S (2011) Reduced cardiac 123I-MIBG uptake reflects cardiac sympathetic dysfunction in de novo Parkinson’s disease. J Neural Trans (Vienna, Austria : 1996) 118(9):1323–1327. doi:10.1007/s00702-011-0598-5

    Article  Google Scholar 

  9. Oka H, Yoshioka M, Morita M, Mochio S, Inoue K (2003) Cardiac sympathetic dysfunction in Parkinson’s disease–relationship between results of 123I-MIBG scintigraphy and autonomic nervous function evaluated by the Valsalva maneuver. Rinsho Shinkeigaku Clin Neurol 43(8):465–469

    Google Scholar 

  10. Orimo S, Ozawa E, Oka T, Nakade S, Tsuchiya K, Yoshimoto M, Wakabayashi K, Takahashi H (2001) Different histopathology accounting for a decrease in myocardial MIBG uptake in PD and MSA. Neurology 57(6):1140–1141

    Article  CAS  PubMed  Google Scholar 

  11. Shibata M, Morita Y, Shimizu T, Takahashi K, Suzuki N (2009) Cardiac parasympathetic dysfunction concurrent with cardiac sympathetic denervation in Parkinson’s disease. J Neurol Sci 276(1–2):79–83. doi:10.1016/j.jns.2008.09.005

    Article  PubMed  Google Scholar 

  12. Korkushko OV, Shatilo VB, Plachinda YuI, Shatilo TV (1991) Autonomic control of cardiac chronotropic function in man as a function of age: assessment by power spectral analysis of heart rate variability. J Auton Nerv Syst 32(3):191–198

    Article  CAS  PubMed  Google Scholar 

  13. Gibb WR, Lees AJ (1988) The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson’s disease. J Neurol Neurosurg Psychiatry 51(6):745–752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology (1996) Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Euro Heart J 17(3):354–381

  15. Ewing DJ, Martyn CN, Young RJ, Clarke BF (1985) The value of cardiovascular autonomic function tests: 10 years experience in diabetes. Diabetes Care 8(5):491–498

    Article  CAS  PubMed  Google Scholar 

  16. Schmidt C, Herting B, Prieur S, Junghanns S, Schweitzer K, Globas C, Schols L, Reichmann H, Berg D, Ziemssen T (2009) Valsalva manoeuvre in patients with different Parkinsonian disorders. J Neural Transm (Vienna) 116(7):875–880. doi:10.1007/s00702-009-0239-4

    Article  CAS  Google Scholar 

  17. Wada N, Singer W, Gehrking TL, Sletten DM, Schmelzer JD, Low PA (2014) Comparison of baroreflex sensitivity with a fall and rise in blood pressure induced by the Valsalva manoeuvre. Clinical Sci (London, England: 1979) 127(5):307–313. doi:10.1042/cs20130802

    Article  Google Scholar 

  18. Nakamura T, Hirayama M, Hara T, Hama T, Watanabe H, Sobue G (2011) Does cardiovascular autonomic dysfunction contribute to fatigue in Parkinson’s disease? Mov Dis Off J Mov Dis Soc 26(10):1869–1874. doi:10.1002/mds.23744

    Article  Google Scholar 

  19. Solanki KK, Bomanji J, Moyes J, Mather SJ, Trainer PJ, Britton KE (1992) A pharmacological guide to medicines which interfere with the biodistribution of radiolabelled meta-iodobenzylguanidine (MIBG). Nucl Med Commun 13(7):513–521

    Article  CAS  PubMed  Google Scholar 

  20. Robert GDS (1959) A multiple comparison rank sum test: treatments versus control. Biometrics 15(4):560–572. doi:10.2307/2527654

    Article  Google Scholar 

  21. Freeman R, Wieling W, Axelrod FB, Benditt DG, Benarroch E, Biaggioni I, Cheshire WP, Chelimsky T, Cortelli P, Gibbons CH, Goldstein DS, Hainsworth R, Hilz MJ, Jacob G, Kaufmann H, Jordan J, Lipsitz LA, Levine BD, Low PA, Mathias C, Raj SR, Robertson D, Sandroni P, Schatz I, Schondorff R, Stewart JM, van Dijk JG (2011) Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res Off J Clin Auton Res Soc 21(2):69–72. doi:10.1007/s10286-011-0119-5

    Article  Google Scholar 

  22. Orimo S, Ozawa E, Nakade S, Sugimoto T, Mizusawa H (1999) (123)I-metaiodobenzylguanidine myocardial scintigraphy in Parkinson’s disease. J Neurol Neurosurg Psychiatry 67(2):189–194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kallio M, Haapaniemi T, Turkka J, Suominen K, Tolonen U, Sotaniemi K, Heikkila VP, Myllyla V (2000) Heart rate variability in patients with untreated Parkinson’s disease. Euro J Neurol Off J Euro Fed Neurol Soc 7(6):667–672

    CAS  Google Scholar 

  24. Sorensen GL, Mehlsen J, Jennum P (2013) Reduced sympathetic activity in idiopathic rapid-eye-movement sleep behavior disorder and Parkinson’s disease. Auton Neurosci Basic Clin 179(1–2):138–141. doi:10.1016/j.autneu.2013.08.067

    Article  Google Scholar 

  25. Gjerloff T, Fedorova T, Knudsen K, Munk OL, Nahimi A, Jacobsen S, Danielsen EH, Terkelsen AJ, Hansen J, Pavese N, Brooks DJ, Borghammer P (2015) Imaging acetylcholinesterase density in peripheral organs in Parkinson’s disease with 11C-donepezil PET. Brain J Neurol 138(Pt 3):653–663. doi:10.1093/brain/awu369

    Article  Google Scholar 

  26. Pursiainen V, Haapaniemi TH, Korpelainen JT, Huikuri HV, Sotaniemi KA, Myllyla VV (2002) Circadian heart rate variability in Parkinson’s disease. J Neurol 249(11):1535–1540. doi:10.1007/s00415-002-0884-0

    Article  PubMed  Google Scholar 

  27. Alonso A, Huang X, Mosley TH, Heiss G, Chen H (2015) Heart rate variability and the risk of Parkinson disease: the Atherosclerosis Risk in Communities study. Annals Neurol 77(5):877–883. doi:10.1002/ana.24393

    Article  Google Scholar 

  28. Thenganatt MA, Jankovic J (2014) Parkinson disease subtypes. JAMA Neurol 71(4):499–504. doi:10.1001/jamaneurol.2013.6233

    Article  PubMed  Google Scholar 

  29. Beach TG, Adler CH, Sue LI, Vedders L, Lue L, White Iii CL, Akiyama H, Caviness JN, Shill HA, Sabbagh MN, Walker DG (2010) Multi-organ distribution of phosphorylated alpha-synuclein histopathology in subjects with Lewy body disorders. Acta Neuropathol 119(6):689–702. doi:10.1007/s00401-010-0664-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Annerino DM, Arshad S, Taylor GM, Adler CH, Beach TG, Greene JG (2012) Parkinson’s disease is not associated with gastrointestinal myenteric ganglion neuron loss. Acta Neuropathol 124(5):665–680. doi:10.1007/s00401-012-1040-2

    Article  PubMed  PubMed Central  Google Scholar 

  31. Phillips RJ, Walter GC, Wilder SL, Baronowsky EA, Powley TL (2008) Alpha-synuclein-immunopositive myenteric neurons and vagal preganglionic terminals: autonomic pathway implicated in Parkinson’s disease? Neuroscience 153(3):733–750. doi:10.1016/j.neuroscience.2008.02.074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Greene JG (2014) Causes and consequences of degeneration of the dorsal motor nucleus of the vagus nerve in Parkinson’s disease. Antioxid Redox Signal 21(4):649–667. doi:10.1089/ars.2014.5859

    Article  CAS  PubMed  Google Scholar 

  33. Eadie MJ (1963) The Pathology of Certain Medullary Nuclei in Parkinsonism. Brain J Neurol 86:781–792

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho Showa-ku, Nagoya, 466-8550, Japan

    Masashi Suzuki, Tomohiko Nakamura, Miki Ueda, Masahisa Katsuno & Gen Sobue

  2. Department of Pathophysiological Laboratory Science, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Masaaki Hirayama

  3. Research Division of Dementia and Neurodegeneration Disease, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Gen Sobue

Authors
  1. Masashi Suzuki
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  2. Tomohiko Nakamura
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  3. Masaaki Hirayama
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  4. Miki Ueda
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  5. Masahisa Katsuno
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  6. Gen Sobue
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Correspondence to Tomohiko Nakamura or Gen Sobue.

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This work was supported by JSPS KAKENHI Grant Nos. JP24590691, JP16K09713; and Grants from the Ministry of Health, Labor and Welfare of Japan.

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None of the authors reports any financial interests or potential conflicts of interest.

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Suzuki, M., Nakamura, T., Hirayama, M. et al. Cardiac parasympathetic dysfunction in the early phase of Parkinson’s disease. J Neurol 264, 333–340 (2017). https://doi.org/10.1007/s00415-016-8348-0

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  • DOI: https://doi.org/10.1007/s00415-016-8348-0

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