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Autonomic dysfunction in PD: A window to early detection?

  • David S. Goldstein
    Correspondence
    Corresponding author at: Clinical Neurocardiology Section, NINDS, NIH, 10 Center Drive, MSC-1620, Building 10, Room 5N220, Bethesda, MD 20892-1620, USA. Tel.: +1 301 496 2103, +1 301 675 1110 (iPhone); fax: +1 301 402 0180.
    Affiliations
    Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1620, USA
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  • LaToya Sewell
    Affiliations
    Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1620, USA
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  • Yehonatan Sharabi
    Affiliations
    Hypertension Unit, Chaim Sheba Medical Center, Tel-HaShomer, Israel
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Published:April 29, 2011DOI:https://doi.org/10.1016/j.jns.2011.04.011

      Abstract

      It has been suggested that autonomic dysfunction constitutes a biomarker for early detection of the disease process in Parkinson disease (PD). Recent findings based on cardiac sympathetic and striatal dopaminergic imaging in the same patients indicate that this view is overly simple. Although evidence of cardiac sympathetic denervation is associated with other non-motor manifestations such as anosmia, REM behavior disorder, dementia, baroreflex failure, and orthostatic hypotension (OH), across individual patients the severities of OH and of the cardiac sympathetic lesion (indicated by thoracic 6-[18F]fluorodopamine PET scanning) are unrelated to the severity of the putamen dopaminergic lesion (indicated by brain 6-[18F]fluorodopa PET scanning). Moreover, whereas cases have been reported with neuroimaging evidence of cardiac sympathetic denervation several years before motor onset of PD, in other cases loss of cardiac sympathetic innervation progresses approximately concurrently with the movement disorder or can even occur as a late finding. Bases for independent sympathetic noradrenergic and striatal dopaminergic lesions in Lewy body diseases remain poorly understood. In elderly patients with unexplained OH or other evidence of autonomic failure, it is reasonable for clinicians to look for subtle signs of parkinsonism, such as masked facies, cogwheel rigidity, and shuffling gate.

      Abbreviations:

      DOPAL (dihydroxyphenylacetaldehyde), OH (orthostatic hypotension), MSA (multiple system atrophy), PAF (pure autonomic failure), PD (Parkinson disease)

      Keywords

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      References

        • Braak H.
        • Rub U.
        • Gai W.P.
        • Del Tredici K.
        Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen.
        J Neural Transm. May 2003; 110: 517-536
        • Goldstein D.S.
        • Holmes C.
        • Cannon III, R.O.
        • Eisenhofer G.
        • Kopin I.J.
        Sympathetic cardioneuropathy in dysautonomias.
        N Engl J Med. Mar 6, 1997; 336: 696-702
        • 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
        • Fujishiro H.
        • Frigerio R.
        • Burnett M.
        • Klos K.J.
        • Josephs K.A.
        • Delledonne A.
        • et al.
        Cardiac sympathetic denervation correlates with clinical and pathologic stages of Parkinson's disease.
        Mov Disord. Jun 15, 2008; 23: 1085-1092
        • 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
        • Goldstein D.S.
        Orthostatic hypotension as an early finding in Parkinson disease.
        Clin Auton Res. 2006; 16: 46-64
        • 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
        • Kaufmann H.
        • Biaggioni I.
        Autonomic failure in neurodegenerative disorders.
        Semin Neurol. Dec 2003; 23: 351-363
        • Goldstein D.S.
        Adrenaline and the inner world: an introduction to scientific integrative medicine.
        The Johns Hopkins University Press, Baltimore, MD2006
        • Sharabi Y.
        • Li S.T.
        • Dendi R.
        • Holmes C.
        • Goldstein D.S.
        Neurotransmitter specificity of sympathetic denervation in Parkinson's disease.
        Neurology. Mar 25, 2003; 60: 1036-1039
        • Orimo S.
        • Oka T.
        • Miura H.
        • Tsuchiya K.
        • Mori F.
        • Wakabayashi K.
        • et al.
        Sympathetic cardiac denervation in Parkinson's disease and pure autonomic failure but not in multiple system atrophy.
        J Neurol Neurosurg Psychiatry. 2002; 73: 776-777
        • Orimo S.
        • Amino T.
        • Takahashi A.
        • Kojo T.
        • Uchihara T.
        • Mori F.
        • et al.
        Cardiac sympathetic denervation in Lewy body disease.
        Parkinsonism Relat Disord. Oct 2006; 12: S99-S105
        • Lee P.H.
        • Yeo S.H.
        • Kim H.J.
        • Youm H.Y.
        Correlation between cardiac 123I-MIBG and odor identification in patients with Parkinson's disease and multiple system atrophy.
        Mov Disord. 2006; 21: 1975-1977
        • Goldstein D.S.
        • Holmes C.
        • Bentho O.
        • Sato T.
        • Moak J.
        • Sharabi Y.
        • et al.
        Biomarkers to detect central dopamine deficiency and distinguish Parkinson disease from multiple system atrophy.
        Parkinsonism Relat Disord. Dec 2008; 14: 600-607
        • Kashihara K.
        • Imamura T.
        • Shinya T.
        Cardiac 123I-MIBG uptake is reduced more markedly in patients with REM sleep behavior disorder than in those with early stage Parkinson's disease.
        Parkinsonism Relat Disord. May 2010; 16: 252-255
        • Miyamoto T.
        • Miyamoto M.
        • Inoue Y.
        • Usui Y.
        • Suzuki K.
        • Hirata K.
        Reduced cardiac 123I-MIBG scintigraphy in idiopathic REM sleep behavior disorder.
        Neurology. Dec 26, 2006; 67: 2236-2238
        • Yoshita M.
        • Taki J.
        • Yokoyama K.
        • Noguchi-Shinohara M.
        • Matsumoto Y.
        • Nakajima K.
        • et al.
        Value of 123I-MIBG radioactivity in the differential diagnosis of DLB from AD.
        Neurology. Jun 27, 2006; 66: 1850-1854
        • Suzuki M.
        • Kurita A.
        • Hashimoto M.
        • Fukumitsu N.
        • Abo M.
        • Ito Y.
        • et al.
        Impaired myocardial 123I-metaiodobenzylguanidine uptake in Lewy body disease: comparison between dementia with Lewy bodies and Parkinson's disease.
        J Neurol Sci. Jan 15, 2006; 240: 15-19
        • Goldstein D.S.
        • Holmes C.S.
        • Dendi R.
        • Bruce S.R.
        • Li S.T.
        Orthostatic hypotension from sympathetic denervation in Parkinson's disease.
        Neurology. Apr 23, 2002; 58: 1247-1255
        • Oka H.
        • Yoshioka M.
        • Onouchi K.
        • Morita M.
        • Mochio S.
        • Suzuki M.
        • et al.
        Characteristics of orthostatic hypotension in Parkinson's disease.
        Brain. Sep 2007; 130: 2425-2432
        • Haensch C.A.
        • Lerch H.
        • Jorg J.
        • Isenmann S.
        Cardiac denervation occurs independent of orthostatic hypotension and impaired heart rate variability in Parkinson's disease.
        Parkinsonism Relat Disord. Feb 2009; 15: 134-137
        • Goldstein D.S.
        • Sewell L.
        • Holmes C.
        Association of anosmia with autonomic failure in Parkinson disease.
        Neurology. 2009; 74: 245-251
        • Creveling C.R.
        The role of catechol quinone species in cellular toxicity.
        FP Graham Publishing Co., Johnson City, TN2000
        • Berman S.B.
        • Hastings T.G.
        Dopamine oxidation alters mitochondrial respiration and induces permeability transition in brain mitochondria: implications for Parkinson's disease.
        J Neurochem. Sep 1999; 73: 1127-1137
        • Vauzour D.
        • Ravaioli G.
        • Vafeiadou K.
        • Rodriguez-Mateos A.
        • Angeloni C.
        • Spencer J.P.
        Peroxynitrite induced formation of the neurotoxins 5-S-cysteinyl-dopamine and DHBT-1: implications for Parkinson's disease and protection by polyphenols.
        Arch Biochem Biophys. Aug 15, 2008; 476: 145-151
        • Burke W.J.
        • Li S.W.
        • Williams E.A.
        • Nonneman R.
        • Zahm D.S.
        3,4-Dihydroxyphenylacetaldehyde is the toxic dopamine metabolite in vivo: implications for Parkinson's disease pathogenesis.
        Brain Res. Nov 7, 2003; 989: 205-213
        • Jinsmaa Y.
        • Florang V.R.
        • Rees J.N.
        • Anderson D.G.
        • Strack S.
        • Doorn J.A.
        Products of oxidative stress inhibit aldehyde oxidation and reduction pathways in dopamine catabolism yielding elevated levels of a reactive intermediate.
        Chem Res Toxicol. May 2009; 22: 835-841
        • Burke W.J.
        • Kumar V.B.
        • Pandey N.
        • Panneton W.M.
        • Gan Q.
        • Franko M.W.
        • et al.
        Aggregation of alpha-synuclein by DOPAL, the monoamine oxidase metabolite of dopamine.
        Acta Neuropathol. Feb 2008; 115: 193-203
        • Ding Y.S.
        • Singhal T.
        • Planeta-Wilson B.
        • Gallezot J.D.
        • Nabulsi N.
        • Labaree D.
        • et al.
        PET imaging of the effects of age and cocaine on the norepinephrine transporter in the human brain using (S, S)-[(11)C]O-methylreboxetine and HRRT.
        Synapse. Jan 2010; 64: 30-38