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23.04.2024 | Research Article

Sympathetic dysfunction as an early indicator of autonomic involvement in Parkinson’s disease

verfasst von: Jin-Woo Park, Luis E. Okamoto, Sung-Hwan Kim, Chan-Nyoung Lee, Kun Woo Park, Seol-Hee Baek, Joo Hye Sung, Namjoon Jeon, Seong-Beom Koh, Alfredo Gamboa, Cyndya A. Shibao, André Diedrich, Byung-Jo Kim, Italo Biaggioni

Erschienen in: Clinical Autonomic Research | Ausgabe 2/2024

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Abstract

Purpose

The specific characteristics of autonomic involvement in patients with early Parkinson’s disease (PD) are unclear. This study aimed to evaluate the characteristics of autonomic dysfunction in drug-naïve patients with early-stage PD without orthostatic hypotension (OH) by analyzing Valsalva maneuver (VM) parameters.

Methods

We retrospectively analyzed drug-naïve patients without orthostatic hypotension (n = 61) and controls (n = 20). The patients were subcategorized into early PD (n = 35) and mid-PD (n = 26) groups on the basis of the Hoehn and Yahr staging. VM parameters, including changes in systolic blood pressure at late phase 2 (∆SBP_VM2), ∆HR_VM3, Valsalva ratio (VR), pressure recovery time, adrenergic baroreflex sensitivity, and vagal baroreflex sensitivity, were assessed.

Results

In the early PD group, ∆SBP_VM2, a marker of sympathetic function, was significantly lower compared with that in controls (risk ratio = 0.95, P = 0.027). Receiver operating characteristic (ROC) curve analysis showed an optimal cut-off value of −10 mmHg for ∆SBP_VM2 [P = 0.002, area under the curve (AUC): 0.737]. VR exhibited an inverse relationship with Unified Parkinson’s Disease Rating Scale Part 3 scores in the multivariable regression analysis (VR: P = 0.038, β = −28.61), whereas age showed a positive relationship (age: P = 0.027, β = 0.35).

Conclusion

The ∆BP_VM2 parameter of the VM may help detect autonomic nervous system involvement in early-PD without OH. Our results suggest that sympathetic dysfunction is an early manifestation of autonomic dysfunction in patients with PD.

Park JW, Kwon DY, Choi JH, Park MH, Yoon HK (2018) Olfactory dysfunctions in drug-naïve Parkinson’s disease with mild cognitive impairment. Parkinsonism Relat Disord 46:69–73. https://doi.org/10.1016/j.parkreldis.2017.11.334CrossRefPubMed

Tolosa E, Garrido A, Scholz SW, Poewe W (2021) Challenges in the diagnosis of Parkinson’s disease. Lancet Neurol 20:385–397. https://doi.org/10.1016/s1474-4422(21)00030-2CrossRefPubMedPubMedCentral

Postuma RB, Berg D (2019) Prodromal Parkinson’s disease: the decade past, the decade to come. Mov Disord 34:665–675. https://doi.org/10.1002/mds.27670CrossRefPubMed

You S, Jeon SM, Do SY, Cho YW (2019) Restless legs syndrome in parkinson’s disease patients: clinical features including motor and nonmotor symptoms. J Clin Neurol 15:321–327. https://doi.org/10.3988/jcn.2019.15.3.321CrossRefPubMedPubMedCentral

Tomic S, Kuric I, Kuric TG, Popovic Z, Kragujevic J, Zubonja TM, Rajkovaca I, Matosa S (2022) Seborrheic dermatitis is related to motor symptoms in Parkinson’s Disease. J Clin Neurol 18:628–634. https://doi.org/10.3988/jcn.2022.18.6.628CrossRefPubMedPubMedCentral

Schapira AHV, Chaudhuri KR, Jenner P (2017) Non-motor features of Parkinson disease. Nat Rev Neurosci 18:435–450. https://doi.org/10.1038/nrn.2017.62CrossRefPubMed

Heinzel S, Berg D, Gasser T, Chen H, Yao C, Postuma RB (2019) Update of the MDS research criteria for prodromal Parkinson’s disease. Mov Disord 34:1464–1470. https://doi.org/10.1002/mds.27802CrossRefPubMed

Postuma RB, Aarsland D, Barone P, Burn DJ, Hawkes CH, Oertel W, Ziemssen T (2012) Identifying prodromal Parkinson’s disease: pre-motor disorders in Parkinson’s disease. Mov Disord 27:617–626. https://doi.org/10.1002/mds.24996CrossRefPubMed

Kaufmann H, Biaggioni I (2003) Autonomic failure in neurodegenerative disorders. Semin Neurol 23:351–363. https://doi.org/10.1055/s-2004-817719CrossRefPubMed

10.

Kim JB, Phillips Z, Paik SH, Kang SY, Jeon NJ, Kim BJ, Kim BM (2020) Cerebral hemodynamic monitoring of Parkinson’s disease patients with orthostatic intolerance during head-up tilt test. Neurophotonics 7:025002. https://doi.org/10.1117/1.NPh.7.2.025002CrossRefPubMedPubMedCentral

11.

Kim JB, Kim H, Lee CN, Park KW, Kim BJ (2021) Regional gray matter volume changes in parkinson’s disease with orthostatic hypotension. Brain Sci. https://doi.org/10.3390/brainsci11030294CrossRefPubMedPubMedCentral

12.

Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, Obeso J, Marek K, Litvan I, Lang AE, Halliday G, Goetz CG, Gasser T, Dubois B, Chan P, Bloem BR, Adler CH, Deuschl G (2015) MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord 30:1591–1601. https://doi.org/10.1002/mds.26424CrossRefPubMed

13.

Berg D, Postuma RB, Adler CH, Bloem BR, Chan P, Dubois B, Gasser T, Goetz CG, Halliday G, Joseph L, Lang AE, Liepelt-Scarfone I, Litvan I, Marek K, Obeso J, Oertel W, Olanow CW, Poewe W, Stern M, Deuschl G (2015) MDS research criteria for prodromal Parkinson’s disease. Mov Disord 30:1600–1611. https://doi.org/10.1002/mds.26431CrossRefPubMed

14.

Merola A, Romagnolo A, Rosso M, Suri R, Berndt Z, Maule S, Lopiano L, Espay AJ (2018) Autonomic dysfunction in Parkinson’s disease: a prospective cohort study. Mov Disord 33:391–397. https://doi.org/10.1002/mds.27268CrossRefPubMed

15.

Merola A, Sawyer RP, Artusi CA, Suri R, Berndt Z, Lopez-Castellanos JR, Vaughan J, Vizcarra JA, Romagnolo A, Espay AJ (2018) Orthostatic hypotension in Parkinson disease: impact on health care utilization. Parkinsonism Relat Disord 47:45–49. https://doi.org/10.1016/j.parkreldis.2017.11.344CrossRefPubMed

16.

Horsager J, Knudsen K, Sommerauer M (2022) Clinical and imaging evidence of brain-first and body-first Parkinson’s disease. Neurobiol Dis 164:105626. https://doi.org/10.1016/j.nbd.2022.105626CrossRefPubMed

17.

Low PA, Tomalia VA (2015) Orthostatic hypotension: mechanisms, causes, management. J Clin Neurol 11:220–226. https://doi.org/10.3988/jcn.2015.11.3.220CrossRefPubMedPubMedCentral

18.

Goldstein DS, Sewell L, Sharabi Y (2011) Autonomic dysfunction in PD: a window to early detection? J Neurol Sci 310:118–122. https://doi.org/10.1016/j.jns.2011.04.011CrossRefPubMed

19.

Park JW, Okamoto LE, Kim SH, Baek SH, Sung JH, Jeon N, Gamboa A, Shibao CA, Diedrich A, Kim BJ, Biaggioni I (2023) Use of valsalva maneuver to detect late-onset delayed orthostatic hypotension. Hypertension 80:792–801. https://doi.org/10.1161/hypertensionaha.122.20098CrossRefPubMed

20.

Gibbons CH, Freeman R (2020) Delayed orthostatic hypotension. Auton Neurosci 229:102724. https://doi.org/10.1016/j.autneu.2020.102724CrossRefPubMed

21.

Palma JA, Gomez-Esteban JC, Norcliffe-Kaufmann L, Martinez J, Tijero B, Berganzo K, Kaufmann H (2015) Orthostatic hypotension in Parkinson disease: how much you fall or how low you go? Mov Disord 30:639–645. https://doi.org/10.1002/mds.26079CrossRefPubMedPubMedCentral

22.

Kim JB, Kim BJ, Koh SB, Park KW (2014) Autonomic dysfunction according to disease progression in Parkinson’s disease. Parkinsonism Relat Disord 20:303–307. https://doi.org/10.1016/j.parkreldis.2013.12.001CrossRefPubMed

23.

Goldstein DS (2014) Dysautonomia Parkinson disease Compr Physiol 4:805–826. https://doi.org/10.1002/cphy.c130026CrossRefPubMed

24.

Goldstein DS, Sewell L, Holmes C (2010) Association of anosmia with autonomic failure in parkinson disease. Neurology 74:245–251. https://doi.org/10.1212/WNL.0b013e3181ca014cCrossRefPubMedPubMedCentral

25.

Rocchi C, Pierantozzi M, Galati S, Chiaravalloti A, Pisani V, Prosperetti C, Lauretti B, Stampanoni Bassi M, Olivola E, Schillaci O, Stefani A (2015) Autonomic function tests and mibg in parkinson’s disease: correlation to disease duration and motor symptoms. CNS Neurosci Ther 21:727–732. https://doi.org/10.1111/cns.12437CrossRefPubMedPubMedCentral

26.

Oka H, Toyoda C, Yogo M, Mochio S (2011) Cardiovascular dysautonomia in de novo Parkinson’s disease without orthostatic hypotension. Eur J Neurol 18:286–292. https://doi.org/10.1111/j.1468-1331.2010.03135.xCrossRefPubMed

27.

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

28.

Low PA, Tomalia VA, Park KJ (2013) Autonomic function tests: some clinical applications. J Clin Neurol 9:1–8. https://doi.org/10.3988/jcn.2013.9.1.1CrossRefPubMedPubMedCentral

29.

Kim JB, Kim H, Sung JH, Baek SH, Kim BJ (2020) Heart-rate-based machine-learning algorithms for screening orthostatic hypotension. J Clin Neurol 16:448–454. https://doi.org/10.3988/jcn.2020.16.3.448CrossRefPubMedPubMedCentral

30.

Gibb WR, Lees AJ (1988) The relevance of the lewy body to the pathogenesis of idiopathic Parkinson’s disease. J Neurol Neurosurg Psychiatry 51:745–752. https://doi.org/10.1136/jnnp.51.6.745CrossRefPubMedPubMedCentral

31.

Pagano G, Boess FG, Taylor KI, Ricci B, Mollenhauer B, Poewe W, Boulay A, Anzures-Cabrera J, Vogt A, Marchesi M, Post A, Nikolcheva T, Kinney GG, Zago WM, Ness DK, Svoboda H, Britschgi M, Ostrowitzki S, Simuni T, Marek K, Koller M, Sevigny J, Doody R, Fontoura P, Umbricht D, Bonni A (2021) A phase II study to evaluate the safety and efficacy of prasinezumab in early parkinson’s disease (PASADENA): rationale, design, and baseline data. Front Neurol 12:705407. https://doi.org/10.3389/fneur.2021.705407CrossRefPubMedPubMedCentral

32.

Hou Y, Zhang L, Ou R, Wei Q, Liu K, Lin J, Yang T, Xiao Y, Gong Q, Shang H (2022) Resting-state fMRI study on drug-naïve early-stage patients with Parkinson’s disease and with fatigue. Parkinsonism Relat Disord 105:75–82. https://doi.org/10.1016/j.parkreldis.2022.11.009CrossRefPubMed

33.

Hacker ML, Turchan M, Heusinkveld LE, Currie AD, Millan SH, Molinari AL, Konrad PE, Davis TL, Phibbs FT, Hedera P, Cannard KR, Wang L, Charles D (2020) Deep brain stimulation in early-stage Parkinson disease: five-year outcomes. Neurology 95:e393–e401. https://doi.org/10.1212/wnl.0000000000009946CrossRefPubMedPubMedCentral

34.

Fanciulli A, Jordan J, Biaggioni I, Calandra-Buonaura G, Cheshire WP, Cortelli P, Eschlboeck S, Grassi G, Hilz MJ, Kaufmann H, Lahrmann H, Mancia G, Mayer G, Norcliffe-Kaufmann L, Pavy-Le Traon A, Raj SR, Robertson D, Rocha I, Struhal W, Thijs R, Tsioufis KP, van Dijk JG, Wenning GK (2018) Consensus statement on the definition of neurogenic supine hypertension in cardiovascular autonomic failure by the American Autonomic Society (AAS) and the European Federation of Autonomic Societies (EFAS): Endorsed by the European Academy of Neurology (EAN) and the European Society of Hypertension (ESH). Clin Auton Res 28:355–362. https://doi.org/10.1007/s10286-018-0529-8CrossRefPubMedPubMedCentral

35.

Mar PL, Nwazue V, Black BK, Biaggioni I, Diedrich A, Paranjape SY, Loyd JE, Hemnes AR, Robbins IM, Robertson D, Raj SR, Austin ED (2016) Valsalva maneuver in pulmonary arterial hypertension: susceptibility to syncope and autonomic dysfunction. Chest 149:1252–1260. https://doi.org/10.1016/j.chest.2015.11.015CrossRefPubMedPubMedCentral

36.

Schroeder C, Heusser K, Tank J, Diedrich A, Luft FC, Jordan J (2009) The valsalva maneuver: screening for drug-induced baroreflex dysfunction. Clin Auton Res 19:32–38. https://doi.org/10.1007/s10286-008-0508-6CrossRefPubMed

37.

Raj SR, Robertson D, Biaggioni I, Diedrich A (2007) Abnormal valsalva maneuver is not always a sign of congestive heart failure. Am J Med 120:e15-16. https://doi.org/10.1016/j.amjmed.2006.03.022CrossRefPubMed

38.

Seok HY, Kim YH, Kim H, Kim BJ (2018) Patterns of orthostatic blood pressure changes in patients with orthostatic hypotension. J Clin Neurol 14:283–290. https://doi.org/10.3988/jcn.2018.14.3.283CrossRefPubMedPubMedCentral

39.

Kallio M, Haapaniemi T, Turkka J, Suominen K, Tolonen U, Sotaniemi K, Heikkilä VP, Myllylä V (2000) Heart rate variability in patients with untreated Parkinson’s disease. Eur J Neurol 7:667–672. https://doi.org/10.1046/j.1468-1331.2000.00127.xCrossRefPubMed

40.

Buob A, Winter H, Kindermann M, Becker G, Möller JC, Oertel WH, Böhm M (2010) Parasympathetic but not sympathetic cardiac dysfunction at early stages of Parkinson’s disease. Clin Res Cardiol 99:701–706. https://doi.org/10.1007/s00392-010-0170-6CrossRefPubMed

41.

Goldstein DS, Holmes CS, Dendi R, Bruce SR, Li ST (2002) Orthostatic hypotension from sympathetic denervation in Parkinson’s disease. Neurology 58:1247–1255. https://doi.org/10.1212/wnl.58.8.1247CrossRefPubMed

42.

Goldstein DS, Sharabi Y (2023) Baroreflex-sympathoneural dysfunction characterizes at-risk individuals with preclinical central Lewy body diseases. Clin Auton Res 33:41–49. https://doi.org/10.1007/s10286-022-00912-yCrossRefPubMed

43.

Asahina M, Vichayanrat E, Low DA, Iodice V, Mathias CJ (2013) Autonomic dysfunction in parkinsonian disorders: assessment and pathophysiology. J Neurol Neurosurg Psychiatry 84:674–680. https://doi.org/10.1136/jnnp-2012-303135CrossRefPubMed

44.

Orimo S, Takahashi A, Uchihara T, Mori F, Kakita A, Wakabayashi K, Takahashi H (2007) Degeneration of cardiac sympathetic nerve begins in the early disease process of Parkinson’s disease. Brain Pathol 17:24–30. https://doi.org/10.1111/j.1750-3639.2006.00032.xCrossRefPubMedPubMedCentral

45.

Braak H, Del Tredici K, Rüb U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24:197–211. https://doi.org/10.1016/s0197-4580(02)00065-9CrossRefPubMed

46.

Umehara T, Toyoda C, Oka H (2014) Postprandial hypotension in de novo Parkinson’s disease: a comparison with orthostatic hypotension. Parkinsonism Relat Disord 20:573–577. https://doi.org/10.1016/j.parkreldis.2014.02.007CrossRefPubMed

47.

Shibao CA, Biaggioni I (2020) Management of orthostatic hypotension, postprandial hypotension, and supine hypertension. Semin Neurol 40:515–522. https://doi.org/10.1055/s-0040-1713886CrossRefPubMed

48.

Goldstein DS, Holmes C, Li ST, Bruce S, Metman LV, Cannon RO 3rd (2000) Cardiac sympathetic denervation in Parkinson disease. Ann Intern Med 133:338–347. https://doi.org/10.7326/0003-4819-133-5-200009050-00009CrossRefPubMed

49.

Berg A, Bech S, Aasly J, Farrer MJ, Skaalum Petersen M (2022) Autonomic dysfunction in Parkinson’s disease: results from the faroese parkinson’s disease cohort. Neurosci Lett 785:136789. https://doi.org/10.1016/j.neulet.2022.136789CrossRefPubMed

50.

De Pablo-Fernandez E, Tur C, Revesz T, Lees AJ, Holton JL, Warner TT (2017) Association of autonomic dysfunction with disease progression and survival in parkinson disease. JAMA Neurol 74:970–976. https://doi.org/10.1001/jamaneurol.2017.1125CrossRefPubMedPubMedCentral

51.

Fanciulli A, Campese N, Goebel G, Ndayisaba JP, Eschlboeck S, Kaindlstorfer C, Raccagni C, Granata R, Bonuccelli U, Ceravolo R, Seppi K, Poewe W, Wenning GK (2020) Association of transient orthostatic hypotension with falls and syncope in patients with Parkinson disease. Neurology 95:e2854–e2865. https://doi.org/10.1212/wnl.0000000000010749CrossRefPubMedPubMedCentral

Titel: Sympathetic dysfunction as an early indicator of autonomic involvement in Parkinson’s disease
verfasst von: Jin-Woo Park
Luis E. Okamoto
Sung-Hwan Kim
Chan-Nyoung Lee
Kun Woo Park
Seol-Hee Baek
Joo Hye Sung
Namjoon Jeon
Seong-Beom Koh
Alfredo Gamboa
Cyndya A. Shibao
André Diedrich
Byung-Jo Kim
Italo Biaggioni
Publikationsdatum: 23.04.2024
Verlag: Springer Berlin Heidelberg
Erschienen in: Clinical Autonomic Research / Ausgabe 2/2024
Print ISSN: 0959-9851
Elektronische ISSN: 1619-1560
DOI: https://doi.org/10.1007/s10286-024-01031-6

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Sympathetic dysfunction as an early indicator of autonomic involvement in Parkinson’s disease