Advertisement

Mechanisms of orthostatic hypotension and supine hypertension in Parkinson disease

  • Yehonatan Sharabi
    Correspondence
    Corresponding author at: Hypertension Unit, Chaim Sheba Medical Center, Tel-HaShomer 52621, Israel. Tel.: +972 35302624; fax: +972 35355428.
    Affiliations
    Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892–1620, USA

    Hypertension Unit, Chaim Sheba Medical Center, Tel-HaShomer, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Israel
    Search for articles by this author
  • David S. Goldstein
    Affiliations
    Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892–1620, USA
    Search for articles by this author

      Abstract

      Non-motor aspects of Parkinson disease (PD) are now recognized to be important both clinically and scientifically. Among these facets are abnormalities in blood pressure regulation. As much as 40% of PD patients have orthostatic hypotension (OH), which is usually associated with supine hypertension (SH). Symptoms of OH range from light-headedness to falls with serious trauma. SH, while typically asymptomatic, poses a significant increased risk for cardiovascular morbidity and mortality. Neuroimaging, neurochemical, and neuropharmacological studies indicate cardiac and extra-cardiac sympathetic noradrenergic denervation and baroreflex failure in virtually all PD patients with OH, and cardiac sympathetic denervation has been confirmed histopathologically. Mechanisms of SH in PD+OH remain poorly understood. The diurnal blood pressure profile shows increased variability that is correlated with decreased baroreflex gain and with increased morbidity and mortality. Treatment should be individually tailored according to the timing of OH or SH, using primarily short-acting sympathomimetic medications in the daytime for OH and short-acting antihypertensive in the nighttime for SH. Future research is needed to understand better and attenuate blood pressure fluctuations through manipulations that improve baroreflex function.

      Abbreviations:

      PD (Parkinson disease), OH (orthostatic hypotension), SH (supine hypertension, SNS, sympathetic nervous system, MSA, multiple system atrophy), PAF (pure autonomic failure), NE (norepinephrine)

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of the Neurological Sciences
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Dickson D.W.
        • Fujishiro H.
        • Orr C.
        • DelleDonne A.
        • Josephs K.A.
        • Frigerio R.
        • et al.
        Neuropathology of non-motor features of Parkinson disease.
        Parkinsonism Relat Disord. Dec 2009; 15: S1-S5
        • Truong D.D.
        • Bhidayasiri R.
        • Wolters E.
        Management of non-motor symptoms in advanced Parkinson disease.
        J Neurol Sci. Mar 15 2008; 266: 216-228
        • Park A.
        • Stacy M.
        Non-motor symptoms in Parkinson's disease.
        J Neurol. Aug 2009; 256: 293-298
        • Poewe W.
        Non-motor symptoms in Parkinson's disease.
        Eur J Neurol. Apr 2008; 15: 14-20
        • Goldstein D.S.
        • Sharabi Y.
        • Karp B.I.
        • Bentho O.
        • Saleem A.
        • Pacak K.
        • et al.
        Cardiac sympathetic denervation preceding motor signs in Parkinson disease.
        Clin Auton Res. Apr 2007; 17: 118-121
        • Oka H.
        • Toyoda C.
        • Yogo M.
        • Mochio S.
        Cardiovascular dysautonomia in de novo Parkinson's disease without orthostatic hypotension.
        Eur J Neurol. Feb 2011; 18: 286-292
        • Kaufmann H.
        Consensus statement on the definition of orthostatic hypotension, pure autonomic failure and multiple system atrophy.
        Clin Auton Res. Apr 1996; 6: 125-126
        • Allcock L.M.
        • Ullyart K.
        • Kenny R.A.
        • Burn D.J.
        Frequency of orthostatic hypotension in a community based cohort of patients with Parkinson's disease.
        J Neurol Neurosurg Psychiatry. Oct 2004; 75: 1470-1471
        • Druschky A.
        • Hilz M.J.
        • Platsch G.
        • Radespiel-Troger M.
        • Druschky K.
        • Kuwert T.
        • et al.
        Differentiation of Parkinson's disease and multiple system atrophy in early disease stages by means of I-123-MIBG-SPECT.
        J Neurol Sci. 2000; 175: 3-12
        • Jost W.H.
        • Del Tredici K.
        • Landvogt C.
        • Braune S.
        Importance of 123I-metaiodobenzylguanidine scintigraphy/single photon emission computed tomography for diagnosis and differential diagnostics of Parkinson syndromes.
        Neurodegener Dis. 2010; 7: 341-347
        • Goldstein D.S.
        • Holmes C.
        • Li S.T.
        • Bruce S.
        • Metman L.V.
        • Cannon III, R.O.
        Cardiac sympathetic denervation in Parkinson disease.
        Ann Intern Med. Sep 5 2000; 133: 338-347
        • Orimo S.
        • Uchihara T.
        • Nakamura A.
        • Mori F.
        • Kakita A.
        • Wakabayashi K.
        • et al.
        Axonal alpha-synuclein aggregates herald centripetal degeneration of cardiac sympathetic nerve in Parkinson's disease.
        Brain. Mar 2008; 131: 642-650
        • Senard J.M.
        • Brefel-Courbon C.
        • Rascol O.
        • Montastruc J.L.
        Orthostatic hypotension in patients with Parkinson's disease: pathophysiology and management.
        Drugs Aging. 2001; 18: 495-505
        • Shy G.M.
        • Drager G.A.
        A neurological syndrome associated with orthostatic hypotension.
        Arch Neurol. 1960; 3: 511-527
        • Goldstein D.S.
        Orthostatic hypotension as an early finding in Parkinson disease.
        Clin Auton Res. 2006; 16: 46-64
        • Kaufmann H.
        • Nahm K.
        • Purohit D.
        • Wolfe D.
        Autonomic failure as the initial presentation of Parkinson disease and dementia with Lewy bodies.
        Neurology. 2004; 63: 1093-1095
        • Senard J.M.
        • Rai S.
        • Lapeyre-Mestre M.
        • Brefel C.
        • Rascol O.
        • Rascol A.
        • et al.
        Prevalence of orthostatic hypotension in Parkinson's disease.
        J Neurol Neurosurg Psychiatry. 1997; 63: 584-589
        • Bonuccelli U.
        • Lucetti C.
        • Del Dotto P.
        • Ceravolo R.
        • Gambaccini G.
        • Bernardini S.
        • et al.
        Orthostatic hypotension in de novo Parkinson disease.
        Arch Neurol. 2003; 60: 1400-1404
        • Micieli G.
        • Martignoni E.
        • Cavallini A.
        • Sandrini G.
        • Nappi G.
        Postprandial and orthostatic hypotension in Parkinson's disease.
        Neurology. Mar 1987; 37: 386-393
        • Goldstein D.S.
        • Sharabi Y.
        Neurogenic orthostatic hypotension: a pathophysiological approach.
        Circulation. Jan 6 2009; 119: 139-146
        • Goldstein D.S.
        • Pechnik S.
        • Holmes C.
        • Eldadah B.
        • Sharabi Y.
        Association between supine hypertension and orthostatic hypotension in autonomic failure.
        Hypertension. Aug 2003; 42: 136-142
        • Goldstein D.S.
        Dysautonomia in Parkinson's disease: neurocardiological abnormalities.
        Lancet Neurol. Nov 2003; 2: 669-676
        • Goldstein D.S.
        • Eldadah B.A.
        • Holmes C.
        • Pechnik S.
        • Moak J.
        • Saleem A.
        • et al.
        Neurocirculatory abnormalities in Parkinson disease with orthostatic hypotension: independence from levodopa treatment.
        Hypertension. Dec 2005; 46: 1333-1339
        • Kato S.
        • Oda M.
        • Hayashi H.
        • Shimizu T.
        • Hayashi M.
        • Kawata A.
        • et al.
        Decrease of medullary catecholaminergic neurons in multiple system atrophy and Parkinson's disease and their preservation in amyotrophic lateral sclerosis.
        J Neurol Sci. 1995; 132: 216-221
        • Goldstein D.S.
        Cardiac denervation in patients with Parkinson disease.
        Cleve Clin J Med. 2007; 74: S91-S94
        • Tipre D.N.
        • Goldstein D.S.
        Cardiac and extra-cardiac sympathetic denervation in Parkinson disease with orthostatic hypotension and in pure autonomic failure.
        J Nucl Med. 2005; 46: 1775-1781
        • Sharabi Y.
        • Imrich R.
        • Holmes C.
        • Pechnik S.
        • Goldstein D.S.
        Generalized and neurotransmitter-selective noradrenergic denervation in Parkinson's disease with orthostatic hypotension.
        Mov Disord. Sep 15 2008; 23: 1725-1732
        • Sharabi Y.
        • Eldadah B.
        • Li S.T.
        • Dendi R.
        • Pechnik S.
        • Holmes C.
        • et al.
        Neuropharmacologic distinction of neurogenic orthostatic hypotension syndromes.
        Clin Neuropharmacol. May-Jun 2006; 29: 97-105
        • Biaggioni I.
        • Robertson R.M.
        Hypertension in orthostatic hypotension and autonomic dysfunction.
        Cardiol Clin. May 2002; 20 (vii): 291-301
        • Schmidt C.
        • Berg D.
        • Prieur S.
        • Junghanns S.
        • Schweitzer K.
        • Globas C.
        • et al.
        Loss of nocturnal blood pressure fall in various extrapyramidal syndromes.
        Mov Disord. Oct 30 2009; 24: 2136-2142
        • Frattola A.
        • Parati G.
        • Cuspidi C.
        • Albini F.
        • Mancia G.
        Prognostic value of 24-hour blood pressure variability.
        J Hypertens. Oct 1993; 11: 1133-1137
        • Sander D.
        • Kukla C.
        • Klingelhofer J.
        • Winbeck K.
        • Conrad B.
        Relationship between circadian blood pressure patterns and progression of early carotid atherosclerosis: A 3-year follow-up study.
        Circulation. Sep 26 2000; 102: 1536-1541
        • Pringle E.
        • Phillips C.
        • Thijs L.
        • Davidson C.
        • Staessen J.A.
        • de Leeuw P.W.
        • et al.
        Systolic blood pressure variability as a risk factor for stroke and cardiovascular mortality in the elderly hypertensive population.
        J Hypertens. Dec 2003; 21: 2251-2257
        • Driver J.A.
        • Kurth T.
        • Buring J.E.
        • Gaziano J.M.
        • Logroscino G.
        Parkinson disease and risk of mortality: a prospective comorbidity-matched cohort study.
        Neurology. Apr 15 2008; 70: 1423-1430
        • Osborn J.W.
        • Jacob F.
        • Guzman P.
        A neural set point for the long-term control of arterial pressure: beyond the arterial baroreceptor reflex.
        Am J Physiol Regul Integr Comp Physiol. Apr 2005; 288: R846-R855
        • Cai G.J.
        • Miao C.Y.
        • Xie H.H.
        • Lu L.H.
        • Su D.F.
        Arterial baroreflex dysfunction promotes atherosclerosis in rats.
        Atherosclerosis. Nov 2005; 183: 41-47
        • Freeman R.
        Clinical practice. Neurogenic orthostatic hypotension.
        N Engl J Med. Feb 7 2008; 358: 615-624
        • Krediet C.T.
        • van Dijk N.
        • Linzer M.
        • van Lieshout J.J.
        • Wieling W.
        Management of vasovagal syncope: controlling or aborting faints by leg crossing and muscle tensing.
        Circulation. Sep 24 2002; 106: 1684-1689
        • Goldstein D.S.
        • Holmes C.
        • Kaufmann H.
        • Freeman R.
        Clinical pharmacokinetics of the norepinephrine precursor L-threo-DOPS in primary chronic autonomic failure.
        Clin Auton Res. Dec 2004; 14: 363-368
        • Kaufmann H.
        • Saadia D.
        • Voustianiouk A.
        • Goldstein D.S.
        • Holmes C.
        • Yahr M.D.
        • et al.
        Norepinephrine precursor therapy in neurogenic orthostatic hypotension.
        Circulation. Aug 12 2003; 108: 724-728
        • Shibao C.
        • Gamboa A.
        • Abraham R.
        • Raj S.R.
        • Diedrich A.
        • Black B.
        • et al.
        Clonidine for the treatment of supine hypertension and pressure natriuresis in autonomic failure.
        Hypertension. Mar 2006; 47: 522-526
        • Shibao C.
        • Gamboa A.
        • Diedrich A.
        • Biaggioni I.
        Management of hypertension in the setting of autonomic dysfunction.
        Curr Treat Options Cardiovasc Med. Apr 2006; 8: 105-109
        • Gamboa A.
        • Shibao C.
        • Diedrich A.
        • Paranjape S.Y.
        • Farley G.
        • Christman B.
        • et al.
        Excessive nitric oxide function and blood pressure regulation in patients with autonomic failure.
        Hypertension. Jun 2008; 51: 1531-1536