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Peripheral and central autonomic nervous system: does the sympathetic or parasympathetic nervous system bear the brunt of the pathology during the course of sporadic PD?

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Abstract

It is a well-established fact that the sympathetic, parasympathetic and enteric nervous systems are affected at early stages in Parkinson’s disease (PD). However, it is not yet clarified whether the earliest pathological events preferentially occur in any of these three divisions of the autonomic nervous system (ANS). Significant involvement of the peripheral autonomic nervous system of the heart and gastrointestinal tract has been documented in PD. Accumulating evidence suggests that the PD pathology spreads centripetally from the peripheral to central nervous system through autonomic nerve fibers, implicating the ANS as a major culprit in PD pathogenesis and a potential target for therapy. This study begins with a brief overview of the structures of the central and peripheral autonomic nervous system and then outlines the major clinicopathological manifestations of cardiovascular and gastrointestinal disturbances in PD.

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References

  • Adler CH, Connor DJ, Hentz JG, Sabbagh MN, Caviness JN, Shill HA, Noble B, Beach TG (2010) Incidental Lewy body disease: clinical comparison to a control cohort. Mov Disord 25:642–646

    Article  PubMed  PubMed Central  Google Scholar 

  • Adler CH, Dugger BN, Hinni ML, Lott DG, Driver-Dunckley E, Hidalgo J, Henry-Watson J, Serrano G, Sue LI, Nagel T, Duffy A, Shill HA, Akiyama H, Walker DG, Beach TG (2014) Submandibular gland needle biopsy for the diagnosis of Parkinson disease. Neurology 82:858–864

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Adler CH, Dugger BN, Hentz JG, Hinni ML, Lott DG, Driver-Dunckley E, Mehta S, Serrano G, Sue LI, Duffy A, Intorcia A, Filon J, Pullen J, Walker DG, Beach TG (2016) Peripheral synucleinopathy in early Parkinson’s disease: submandibular gland needle biopsy findings. Mov Disord 31:250–256

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Alafuzoff I, Parkkinen L, Al-Sarraj S, Arzberger T, Bell J, Bodi I, Bogdanovic N, Budka H, Ferrer I, Gelpi E, Gentleman S, Giaccone G, Kamphorst W, King A, Korkolopoulou P, Kovács GG, Larionov S, Meyronet D, Monoranu C, Morris J, Parchi P, Patsouris E, Roggendorf W, Seilhean D, Streichenberger N, Thal DR, Kretzschmar H, BrainNet Europe Consortium (2008) Assessment of α-synuclein pathology: a study of the BrainNet Europe Consortium. J Neuropathol Exp Neurol 67:125–143

    Article  PubMed  Google Scholar 

  • Aldecoa I, Navarro-Otano J, Stefanova N, Sprenger FS, Seppi K, Poewe W, Cuatrecasas M, Valldeoriola F, Gelpi E, Tolosa E (2015) Alpha-synuclein immunoreactivity patterns in the enteric nervous system. Neurosci Lett 602:145–149

    Article  PubMed  CAS  Google Scholar 

  • Amino T, Orimo S, Ihoh Y, Takahashi A, Uchihara T, Mizusawa H (2005) Profound cardiac sympathetic denervation occurs in Parkinson disease. Brain Pathol 15:29–34

    Article  PubMed  Google Scholar 

  • Anderson JP, Walker DE, Goldstein JM, de Laat R, Banducci K, Caccavello RJ, Barbour R, Huang J, Kling K, Lee M, Diep L, Keim PS, Shen X, Chataway T, Schlossmacher MG, Seubert P, Schenk D, Sinha S, Gai WP, Chilcote TJ (2006) Phosphorylation of Ser-129 is the dominant pathological modification of alpha-synuclein in familial and sporadic Lewy body disease. J Biol Chem 281:29739–29752

    Article  PubMed  CAS  Google Scholar 

  • 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 124:665–680

    Article  PubMed  PubMed Central  Google Scholar 

  • Arai K, Kato N, Kawashima K, Hattori T (2000) Pure autonomic failure in association with human a-synucleinopathy. Neurosci Lett 296:171–173

    Article  PubMed  CAS  Google Scholar 

  • Bacon SJ, Smith AD (1993) A monosynaptic pathway from an identified vasomotor centre in the medial prefrontal cortex to an autonomic area in the thoracic spinal cord. Neuroscience 54:719–728

    Article  PubMed  CAS  Google Scholar 

  • Barrenschee M, Zorenkov D, Böttner M, Lange C, Cossais F, Bernadette Scharf A, Deuschl G, Schneider SA, Ellrichmann M, Fritscher-Ravens A, Wedel T (2017) Distinct pattern of enteric phospho-alpha-synuclein aggregates and gene expression profiles in patients with Parkinson’s disease. Acta Neuropathol Commun 5:1

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Beach TG, Adler CH, Sue LI, Vedders L, Lue L, White CL III, 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 119:689–702

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Beach TG, Adler CH, Dugger BN, Serrano G, Hidalgo J, Henry-Watson J, Shill HA, Sue LI, Sabbagh MN, Akiyama H, Arizona Parkinson’s Disease Consortium (2013) Submandibular gland biopsy for the diagnosis of Parkinson disease. J Neuropathol Exp Neurol 72:130–136

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Beach TG, Corbillé A-G, Letournel F, Kordower JH, Kremer T, Munoz DG, Intorcia A, Hentz J, Adler CH, Sue LI, Walker J, Serrano G, Derkinderen P (2016) Multicenter assessment of immunohistochemical methods for pathological alpha-synuclein in sigmoid colon of autopsied Parkinson’s disease and control subjects. J Parkinsons Dis 6:761–770

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Benarroch EE, Schmeichel AM, Sandroni P, Low PA, Parisi JE (2006) Involvement of vagal autonomic nuclei in multiple system atrophy and Lewy body diseases. Neurology 66:378–383

    Article  PubMed  CAS  Google Scholar 

  • Bloch A, Probst A, Bissig H, Adams H, Tolnay M (2006) Alpha-synuclein pathology of the spinal cord and peripheral autonomic nervous system in neurologically unimpaired elderly subjects. Neuropathol Appl Neurobiol 32:284–295

    Article  PubMed  CAS  Google Scholar 

  • Borghammer P (2018) How does Parkinson’s disease begin? Perspectives on neuroanatomical pathways, prions, and histology. Mov Disord 33:48–57

    Article  PubMed  Google Scholar 

  • Böttner M, Zorenkov D, Hellwig I, Barrenschee M, Harde J, Fricke T, Deuschl G, Egberts J-H, Becker T, Fritscher-Ravens A, Arlt A, Wedel T (2012) Expression pattern and localization of alpha-synuclein in the human enteric nervous system. Neurobiol Dis 48:474–480

    Article  PubMed  CAS  Google Scholar 

  • Braak H, Del Tredici K (2009) Neuroanatomy and pathology of sporadic Parkinson’s disease. Adv Anat Embryol Cell Biol 201:1–119.

  • Braak H, Rueb U, Gai WP, Del Tredici K (2003a) Idiopathic Parkinson’s disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm 110:517–536

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Braak H, Ghebremedhin E, Udo Rueb U, Bratzke HJ, Del Tredici K (2004) Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res 318:121–134

    Article  PubMed  Google Scholar 

  • Braak H, de Vos RA, Bohl J, Del Tredici K (2006) Gastric alpha-synuclein immunoreactive inclusions in Meissner’s and Auerbach’s plexuses in cases staged for Parkinson’s disease-related brain pathology. Neurosci Lett 396:67–72

    Article  PubMed  CAS  Google Scholar 

  • Braak H, Sastre M, Bohl JR, de Vos RA, Del Tredici K (2007) Parkinson’s disease: lesions in dorsal horn layer I, involvement of parasympathetic and sympathetic pre-and postganglionic neurons. Acta Neuropathol 113:421–429

    Article  PubMed  Google Scholar 

  • 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 PD. Clin Res Cardiol 99:701–706

    Article  PubMed  Google Scholar 

  • Bussolati G, Leonardo E (2008) Technical pitfalls potentially affecting diagnoses in immunohistochemistry. J Clin Pathol 61:1184–1192

    Article  PubMed  CAS  Google Scholar 

  • Cersosimo MG, Benarroch EE (2012a) Pathological correlates of gastrointestinal dysfunction in Parkinson’s disease. Neurobiol Dis 46:559–564

    Article  PubMed  Google Scholar 

  • Cersosimo MG, Benarroch EE (2012b) Autonomic involvement in Parkinson’s disease: pathology, pathophysiology, clinical features and possible peripheral biomarkers. J Neurol Sci 313:57–63

    Article  PubMed  CAS  Google Scholar 

  • Cersosimo MG, Raina GB, Calandra CR, Pellene A, Gutiérrez C, Micheli FE, Benarroch EE (2011) Dry mouth: an overlooked autonomic symptom of Parkinson’s disease. J Parkinsons Dis 1:169–173

    PubMed  Google Scholar 

  • Cersosimo MG, Raina GB, Pecci C, Pellene A, Calandra CR, Gutiérrez C, Micheli FE, Benarroch EE (2013) Gastrointestinal manifestations in Parkinson’s disease: prevalence and occurrence before motor symptoms. J Neurol 260:1332–1338

    Article  PubMed  CAS  Google Scholar 

  • Chaudhuri KR, Healy DG, Schapira AH (2006) Non-motor symptoms of Parkinson’s disease: diagnosis and management. Lancet Neurol 5:235–245

    Article  PubMed  Google Scholar 

  • Corbillé AG, Coron E, Neunlist M, Derkinderen P, Lebouvier T (2014) Appraisal of the dopaminergic and noradrenergic innervation of the submucosal plexus in PD. J Parkinsons Dis 4:571–576

    PubMed  Google Scholar 

  • Courbon F, Brefel-Courbon C, Thalamas C, Alibelli MJ, Berry I, Montastruc JL, Rascol O, Senard JM (2003) Cardiac MIBG scintigraphy is a sensitive tool for detecting cardiac sympathetic denervation in Parkinson’s disease. Mov Disord 18:890–897

    Article  PubMed  Google Scholar 

  • Croisier E, MRes DE, Deprez M, Goldring K, Dexter DT, Pearce RK, Graeber MB, Roncaroli F (2006) Comparative study of commercially available anti-alpha-synuclein antibodies. Neuropathol Appl Neurobiol 32:351–356

    Article  PubMed  CAS  Google Scholar 

  • Del Tredici K, Braak H (2012) Spinal cord lesions in sporadic Parkinson’s disease. Acta Neuropathol 124:643–664

    Article  PubMed  CAS  Google Scholar 

  • Del Tredici K, Duda JE (2011) Peripheral Lewy body pathology in Parkinson’s disease and incidental Lewy body disease: four cases. J Neurol Sci 310:100–106

    Article  PubMed  Google Scholar 

  • Del Tredici K, Rueb U, de Vos RAI, Bohl JRE, Braak H (2002) Where does Parkinson pathology begin in the brain? J Neuropathol Exp Neurol 61:413–426

    Article  PubMed  Google Scholar 

  • Del Tredici K, Hawkes CH, Ghebremedhin E, Braak H (2010) Lewy pathology in the submandibular gland of individuals with incidental Lewy body disease and sporadic Parkinson’s disease. Acta Neuropathol 119:703–713

    Article  PubMed  Google Scholar 

  • Den Hartog Jager WA, Bethlem J (1960) The distribution of Lewy bodies in the central and autonomic nervous systems in idiopathic paralysis agitans. J Neurol Neurosurg Psychiatry 23:283–290

    Article  Google Scholar 

  • Deuchars SA (2007) Multi-tasking in the spinal cord—do “sympathetic” interneurons work harder than we give them credit for? J Physiol 580:723–729

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Eadie MJ (1963) The pathology of certain medullary nuclei in parkinsonism. Brain 86:781–792

    Article  PubMed  CAS  Google Scholar 

  • Ebbesson SOE (1965) Quantitative studies of superior cervical sympathetic ganglia in a variety of primates including man. 1. The ratio of preganglionic fibers to ganglionic neurons. J Morph 124:117–132

    Article  Google Scholar 

  • Fedorova TD, Seidelin LB, Knudsen K, Schacht AC, Geday J, Pavese N, Brooks DJ, Borghammer P (2017) Decreased intestinal acetylcholinesterase in early Parkinson disease: an 11C-donepezil PET study. Neurology 88:775–781

    Article  PubMed  CAS  Google Scholar 

  • Folgoas E, Lebouvier T, Leclair-Visonneau L, Cersosimo MG, Barthelaix A, Derkinderen P, Letournel F (2013) Diagnostic value of minor salivary glands for the detection of Lewy pathology. Neurosci Lett 551:62–64

    Article  PubMed  CAS  Google Scholar 

  • Forno LS (1996) Neuropathology of Parkinson’s disease. J Neuropathol Exp Neurol 55:259–272

    Article  PubMed  CAS  Google Scholar 

  • Gai WP, Blessing WW (1996) Human brainstem preganglionic parasympathetic neurons localized by markers for nitric oxide synthesis. Brain 119:1145–1152

    Article  PubMed  Google Scholar 

  • Gai WP, Geffen LB, Denoroy L, Blessing WW (1992) Age-related loss of dorsal vagal neurons in Parkinson’s disease. Neurology 42:2106–2111

    Article  PubMed  CAS  Google Scholar 

  • Gai WP, Blessing WW, Blumbergs PC (1995) Ubiquitin-positive degenerating neurites in the brainstem in Parkinson’s disease. Brain 118:1447–1459

    Article  PubMed  Google Scholar 

  • Gao L, Chen H, Li X, Li F, Ou-Yang Q, Feng T (2015) The diagnostic value of minor salivary gland biopsy in clinically diagnosed patients with Parkinson’s disease: comparison with DAT PET scans. Neurol Sci 36:1575–1580

    Article  PubMed  Google Scholar 

  • Gelpi E, Navarro-Otano J, Tolosa E, Gaig C, Compta Y, Rey MJ, Marti MJ, Hernandez I, Valldeoriola F, Rene R, Ribalta T (2014) Multiple organ involvement by alpha-synuclein pathology in Lewy body disorders. Mov Disord 29:1010–1018

    Article  PubMed  Google Scholar 

  • Ghebremedhin E, Del Tredici K, Langston JW, Braak H (2009) Diminished tyrosine hydroxylase immunoreactivity in the cardiac conduction system and myocardium in Parkinson’s disease: an anatomical study. Acta Neuropathol 118:777–784

    Article  PubMed  CAS  Google Scholar 

  • Giancola F, Torresan F, Repossi R, Bianco F, Latorre R, Ioannou A, Guarino M, Volta U, Clavenzani P, Mazzoni M, Chiocchetti R, Bazzoli F, Travagli RA, Sternini C, De Giorgio R (2017) Downregulation of neuronal vasoactive intestinal polypeptide in Parkinson’s disease and chronic constipation. Neurogastroenterol Motil 29(5). https://doi.org/10.1111/nmo.12995

  • Gjerløff 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 138:653–663

    Article  PubMed  Google Scholar 

  • Goedert M, Spillantini MG, Del Tredici K, Braak H (2013) 100 years of Lewy pathology. Nat Rev Neurol 9:13–24

    Article  PubMed  CAS  Google Scholar 

  • Goedert M, Masuda-Suzukake M, Falcon B (2017) Like prions: the propagation of aggregated tau and α-synuclein in neurodegeneration. Brain 140:266–278

    Article  PubMed  Google Scholar 

  • Gold A, Turkalp ZT, Munoz DG (2013) Enteric alpha-synuclein expression is increased in Parkinson’s disease but not Alzheimer’s disease. Mov Disord 28:237–240

    Article  PubMed  CAS  Google Scholar 

  • Goldstein DS, Holmes C, Cannon RO III, Eisenhofer G, Kopin IJ (1997) Sympathetic cardioneuropathy in dysautonomias. N Engl J Med 336:696–702

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Gray MT, Munoz DG, Gray DA, Schlossmacher MG, Woulfe JM (2014) Alpha-synuclein in the appendiceal mucosa of neurologically intact subjects. Mov Disord 29:991–998

    Article  PubMed  CAS  Google Scholar 

  • Grube D (1980) Immunoreactivities of gastrin (G-) cells. II. Non-specific binding of immunoglobulins to G-cells by ionic interactions. Histochemistry 66:149–167

    Article  PubMed  CAS  Google Scholar 

  • Grundy G (2006) Signalling the state of the digestive tract. Auton Neurosci 125:76–80

    Article  PubMed  Google Scholar 

  • Halliday GM, Blumbergs PC, Cotton RG, Blessing WW, Geffen LB (1990) Loss of brainstem serotonin- and substance P-containing neurons in Parkinson’s disease. Brain Res 510:104–107

    Article  PubMed  CAS  Google Scholar 

  • Hardoff R, Sula M, Tamir A, Soil A, Front A, Badarna S, Honigman S, Giladi N (2001) Gastric emptying time and gastric motility in patients with Parkinson’s disease. Mov Disord 16:1041–1047

    Article  PubMed  CAS  Google Scholar 

  • Hilton D, Stephens M, Kirk L, Edwards P, Potter R, Zajicek J, Broughton E, Hagan H, Carroll C (2014) Accumulation of α-synuclein in the bowel of patients in the preclinical phase of Parkinson’s disease. Acta Neuropathol 127:235–241

    Article  PubMed  CAS  Google Scholar 

  • Holmqvist S, Chutna O, Bousset L, Aldrin-Kirk P, Li W, Björklund T, Wang ZY, Roybon L, Melki R, Li JY (2014) Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats. Acta Neuropathol 128:805–820

    Article  PubMed  Google Scholar 

  • Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55:181–184

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hunter S (1985) The rostral mesencephalon in Parkinson’s disease and Alzheimer’s disease. Acta Neuropathol 68:53–58

    Article  PubMed  CAS  Google Scholar 

  • Iranzo A, Tolosa E, Gelpi E (2013) Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behavior disorder: an observational cohort study. Lancet Neurol 12:443–453

    Article  PubMed  Google Scholar 

  • Iranzo A, Gelpi E, Tolosa E, Molinuevo JL, Serradell M, Gaig C, Santamaria J (2014) Neuropathology of prodromal Lewy body disease. Mov Disord 29:410–415

    Article  PubMed  Google Scholar 

  • Iwanaga K, Wakabayashi K, Yoshimoto M, Tomita I, Satoh H, Takashima H, Satoh A, Seto M, Tsujihata M, Takahashi H (1999) Lewy body-type degeneration in cardiac plexus in Parkinson's and incidental Lewy body diseases. Neurology 52:1269–1271

    Article  PubMed  CAS  Google Scholar 

  • Jain S, Goldstein DS (2012) Cardiovascular dysautonomia in Parkinson disease: from pathophysiology to pathogenesis. Neurobiol Dis 46:572–580

    Article  PubMed  CAS  Google Scholar 

  • Janes RD, Brandys JC, Hopkins DA, Johnstone DE, Murphy DA, Armour JA (1986) Anatomy of human extrinsic cardiac nerves and ganglia. Am J Cardiol 57:299–309

    Article  PubMed  CAS  Google Scholar 

  • Jellinger K (2003) a-Synuclein pathology in Parkinson’s and Alzheimer’s disease brain: incidence and topographic distribution—a pilot study. Acta Neuropathol 106:191–202

    Article  PubMed  Google Scholar 

  • Jellinger KA (2008) A critical reappraisal of current staging of Lewy-related pathology in human brain. Acta Neuropathol 116:1–16

    Article  PubMed  CAS  Google Scholar 

  • Junqueira and Carneiro (1971) Histologie 3rd Ed. Verdauungsorgane, chapter 20. Springer Verlag, Berlin, pp 465–514

    Google Scholar 

  • Kalaitzakis ME, Graeber MB, Gentleman SM, Pearce RK (2008) The dorsal motor nucleus of the vagus is not an obligatory trigger site of Parkinson’s disease: a critical analysis of alpha-synuclein staging. Neuropathol Appl Neurobiol 34:284–295

    Article  PubMed  CAS  Google Scholar 

  • Kaufmann H, Goldstein DS (2013) Autonomic dysfunction in Parkinson’s disease. In: Buijs RM, Swaab DF (eds) Handbook of clinical neurology, 3rd edn. Elsevier, Amsterdam, pp 259–278

    Google Scholar 

  • Klos KJ, Ahlskog JE, Josephs KA, Apaydin H, Parisi JE, Boeve BF, DeLucia MW, Dickson DW (2006) Alpha-synuclein pathology in the spinal cords of neurologically asymptomatic aged individuals. Neurology 66:1100–1102

    Article  PubMed  CAS  Google Scholar 

  • Kozicz T, Bittencourt JC, May PJ, Reiner A, Gamlin PDR, Palkovits M, Horn AKE, Toledo CAB, Ryabinin AE (2011) The Edinger-Westphal nucleus: a historical, structural, and functional perspective on a dichotomous terminology. J Comp Neurol 519:1413–1434

    Article  PubMed  PubMed Central  Google Scholar 

  • Krassioukov AV, Bygrave MA, Puckett WR, Bunge RP, Rogers KA (1998) Human sympathetic preganglionic neurons and motoneurons retrogradely labelled with DiI. J Auton Nerv Syst 70:123–128

    Article  PubMed  CAS  Google Scholar 

  • Kuusisto E, Parkkinen L, Alafuzoff I (2003) Morphogenesis of Lewy bodies: dissimilar incorporation of alpha-synuclein, ubiquitin, and p62. J Neuropathol Exp Neurol 62:1241–1253

    Article  PubMed  CAS  Google Scholar 

  • Langley JN (1898) On the union of cranial autonomic (visceral) fibers with nerve cells of the superior cervical ganglion. J Physiol 23:240–270

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Langley JN (1921) The autonomic nervous system. Part I. W. Heffer & Sons, Cambridge

    Google Scholar 

  • Langston JW (2006) The Parkinson’s complex: parkinsonism is just the tip of the iceberg. Ann Neurol 59:591–596

    Article  PubMed  Google Scholar 

  • Langston JW, Forno LS (1978) The hypothalamus in Parkinson’s disease. Ann Neurol 3:129–133

    Article  PubMed  CAS  Google Scholar 

  • Lebouvier T, Chaumette T, Damier P, Coron E, Touchefeu Y, Vrignaud S, Naveilhan P, Galmiche JP, Bruley d, Varannes S, Derkinderen P, Neunlist M (2008) Pathological lesions in colonic biopsies during Parkinson’s disease. Gut 57:1741–1743

    Article  PubMed  CAS  Google Scholar 

  • Lebouvier T, Coron E, Chaumette T, Paillusson S, Bruley des Varannes S, Neunlist M, Derkinderen P (2010a) Routine colonic biopsies as a new tool to study the enteric nervous system in living patients. Neurogastroenterol Motil 22:e11–e14

    PubMed  CAS  Google Scholar 

  • Lebouvier T, Neunlist M, Bruley des Varannes S, Coron E, Drouard A, N’Guyen JM, Chaumette T, Tasselli M, Paillusson S, Flamand M, Galmiche JP, Damier P, Derkinderen P (2010b) Colonic biopsies to assess the neuropathology of Parkinson’s disease and its relationship with symptoms. PLoS One 5:e12728

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lee PH, Kim JS, Shin DH, Yoon SN, Huh K (2006) Cardiac 123I-MIBG scintigraphy in patients with drug induced parkinsonism. J Neurol Neurosurg Psychiatry 77:372–374

    Article  PubMed  CAS  Google Scholar 

  • Lionnet A, Leclair-Visonneau L, Neunlist M, Murayama S, Takao M, Adler CH, Derkinderen P, Beach TG (2018) Does Parkinson’s disease start in the gut? Acta Neuropathol 135:1–12

    Article  PubMed  Google Scholar 

  • Loewy AD, Spyer KM (1990) Central regulation of autonomic functions. New York, Oxford

    Google Scholar 

  • Loewy AD, Saper CB, Yamodis ND (1978) Re-evaluation of the efferent projections of the Edinger-Westphal nucleus in the cat. Brain Res 141:153–159

    Article  PubMed  CAS  Google Scholar 

  • Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC (2006) Functional bowel disorders. Gastroenterology 130:1480–1491

    Article  PubMed  Google Scholar 

  • Miki Y, Mori F, Wakabayashi K, Kuroda N, Orimo S (2009) Incidental Lewy body disease restricted to the heart and stellate ganglia. Mov Disord 24:2299–2301

    Article  PubMed  Google Scholar 

  • Minguez-Castellanos A, Chamorro CE, Escamilla-Sevilla F, Ortega-Moreno A, Rebollo AC, Gomez-Rio M, Concha A, Munoz DG (2007) Do alpha-synuclein aggregates in autonomic plexuses predate Lewy body disorders?: a cohort study. Neurology 68:2012–2018

    Article  PubMed  CAS  Google Scholar 

  • Molander C, Xu Q, Grant G (1984) The cytoarchitectonic organisation of the spinal cord in the rat. I. The lower thoracic and lumbosacral cord. J Comp Neurol 230:133–141

    Article  PubMed  CAS  Google Scholar 

  • Nakamura K, Mori F, Tanji K, Miki Y, Toyoshima Y, Kakita A, Takahashi H, Yamada M, Wakabayashi K (2016) α-Synuclein pathology in cranial and spinal nerves in Lewy body disease. Neuropathology 36:262–269

    Article  PubMed  CAS  Google Scholar 

  • Notari S, Moleres FJ, Hunter SB, Belay ED, Schonberger LB, Cali I, Parchi P, Shieh WJ, Brown P, Zaki S, Zou W-Q, Gambetti P (2010) Multiorgan detection and characterization of protease-resistant prion protein in a case of variant CJD examined in the United States. PLoS One 5:e8765

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Oinas M, Paetau A, Myllykangas L, Notkola IL, Kalimo H, Polvikoski T (2010) a-Synuclein pathology in the spinal cord autonomic nuclei associates with a-synuclein pathology in the brain: a population-based Vantaa 85+ study. Acta Neuropathol 119:715–722

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Okada Y, Ito Y, Aida J, Yasuhara M, Ohkawa S, Hirokawa K (2004) Lewy bodies in the sinoatrial nodal ganglion: clinicopathological studies. Pathol Int 54:682–687

    Article  PubMed  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Orimo S, Oka T, Miura H, Tsuchiya K, Mori F, Wakabayashi K, Nagao T, Yokochi M (2002) Sympathetic cardiac denervation in Parkinson’s disease and pure autonomic failure but not in multiple system atrophy. J Neurol Neurosurg Psychiatry 73:776–777

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Orimo S, Amino T, Ito Y, Takahashi A, Kojo T, Uchihara T, Tsuchiya K, Mori F, Wakabayashi K, Takahashi H (2005) Cardiac sympathetic denervation precedes neuronal loss in the sympathetic ganglia in Lewy body disease. Acta Neuropathol 109:583–588

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Orimo S, Uchihara T, Nakamura A, Mori F, Kakita A, Wakabayashi K, Takahashi H (2008) Axonal alpha-synuclein aggregates herald centripetal degeneration of cardiac sympathetic nerve in Parkinson’s disease. Brain 131:642–650

    Article  PubMed  Google Scholar 

  • Orimo S, Suzuki M, Inaba A, Mizusawa H (2012) 123I-MIBG myocardial scintigraphy for differentiating Parkinson’s disease from other neurodegenerative parkinsonism: a systematic review and meta-analysis. Parkinsonism Relat Disord 18:49–500

    Article  Google Scholar 

  • Orimo S, Yogo M, Nakamura T, Suzuki M, Watanabe H (2016) Brain imaging in Aging Special Issue of Ageing Research Reviews. 123I-Meta-iodobenzylguanidine (MIBG) cardiac scintigraphy in α-synucleinopathies. Aging Res Rev 30:122–133

    Article  CAS  Google Scholar 

  • Oyanagi K, Wakabayashi K, Ohama E, Takeda S, Horikawa Y, Morita T, Ikuta F (1990) Lewy bodies in the lower sacral parasympathetic neurons of a patient with Parkinson’s disease. Acta Neuropathol 80:558–559

    Article  PubMed  CAS  Google Scholar 

  • Petras JM, Cummings JF (1972) Autonomic neurons in the spinal cord of the rhesus monkey: a correlation of the findings of cytoarchitectonics and sympathectomy with fiber degeneration following dorsal rhizotomy. J Comp Neurol 146:189–218

    Article  PubMed  CAS  Google Scholar 

  • Pfeiffer RF (2011) Gastrointestinal dysfunction in Parkinson’s disease. Parkinsonism Relat Disord 17:10–15

    Article  PubMed  Google Scholar 

  • 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 153:733–750

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Postuma RB, Gagnon JF, Bertrand JA, Génier Marchand D, Montplaisir JY (2015) Parkinson risk in idiopathic REM sleep behavior disorder: preparing for neuroprotective trials. Neurology 84:1104–1113

    Article  PubMed  PubMed Central  Google Scholar 

  • Pouclet H, Lebouvier T, Coron E, des Varannes SB, Rouaud T, Roy M, Neunlist M, Derkinderen P (2011) A comparison between rectal and colonic biopsies to detect Lewy pathology in Parkinson’ disease. Neurobiol Dis 45:305–309

    Article  PubMed  Google Scholar 

  • Pouclet H, Lebouvier T, Coron E, Des Varannes SB, Neunlist M, Derkinderen P (2012) A comparison between colonic submucosa and mucosa to detect Lewy pathology in Parkinson’s disease. Neurogastroenterol Motil 24:e202–e205

    Article  PubMed  CAS  Google Scholar 

  • Probst A, Bloch A, Tolnay M (2008) New insights into the pathology of Parkinson’s disease: does the peripheral autonomic system become central? Eur J Neurol 15(Suppl 1):1–4

    Article  PubMed  Google Scholar 

  • Qualman SJ, Haupt HM, Yang P, Hamilton SR (1984) Esophageal Lewy bodies associated with ganglion cell loss in achalasia. Similarity to Parkinson’s disease. Gastroenterology 87:848–856

    PubMed  CAS  Google Scholar 

  • Rajput AH, Rozdilsky B (1976) Dysautonomia in Parkinsonism: a clinicopathological study. J Neurol Neurosurg Psychiatry 39(1092–1):100

    Google Scholar 

  • Recasens A, Dehay B (2014) Alpha-synuclein spreading in Parkinson’s disease. Front Neuroanat 8:1–9

    Article  Google Scholar 

  • Rexed B (1952) The cytoarchitectonic organization of the spinal cord in the cat. J Comp Neurol 96:415–466

    Article  Google Scholar 

  • Ryabinin AE, Tsivkovskaia NO, Ryabinin SA (2005) Urocortin 1-containing neurons in the human Edinger-Westphal nucleus. Neuroscience 134:1317–1323

    Article  PubMed  CAS  Google Scholar 

  • Sánchez-Ferro Á, Rábano A, Catalán MJ, Rodríguez-Valcárcel FC, Fernández Díez S, Herreros-Rodríguez J, García-Cobos E, Álvarez-Santullano MM, López-Manzanares L, Mosqueira AJ, Vela Desojo L, López-Lozano JJ, López-Valdés E, Sánchez-Sánchez R, Molina-Arjona JA (2015) In vivo gastric detection of α-synuclein inclusions in Parkinson’s disease. Mov Disord 30:517–524

    Article  PubMed  CAS  Google Scholar 

  • Sandroni P (2012) Clinical evaluation of autonomic disorders. In: Robertson D, Bioggioni I, Burnstock G, Low PA, Paton JFR (eds) Primer on the autonomic nervous system, 3rd edn. Academic Press, London, pp 377–382

    Chapter  Google Scholar 

  • Seidel K, Mahlke J, Siswanto S, Krüger R, Heinsen H, Auburger G, Bouzrou M, Grinberg LT, Wicht H, Korf HW, den Dunnen W, Rüb U (2015) The brainstem pathologies of Parkinson’s disease and dementia with Lewy bodies. Brain Pathol 25:121–135

    Article  PubMed  Google Scholar 

  • Shannon KM, Keshavarzian A, Mutlu E, Dodiya HB, Daian D, Jaglin JA, Kordower JH (2012a) Alpha-synuclein in colonic submucosa in early untreated Parkinson’s disease. Mov Disord 27:709–715

    Article  PubMed  Google Scholar 

  • Shannon KM, Keshavarzian A, Dodiya HB, Jakate S, Kordower JH (2012b) Is alpha-synuclein in the colon a biomarker for premotor Parkinson’s disease? Evidence from 3 cases. Mov Disord 27:716–719

    Article  PubMed  Google Scholar 

  • Singaram C, Ashraf W, Gaumnitz EA, Torbey C, Sengupta A, Pfeiffer R, Quigley EM (1995) Dopaminergic defect of enteric nervous system in Parkinson’s disease patients with chronic constipation. Lancet 346(8979):861–864

    Article  PubMed  CAS  Google Scholar 

  • Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (1997) Alpha-synuclein in Lewy bodies. Nature 388(6645):839–840

    Article  PubMed  CAS  Google Scholar 

  • Sprenger FS, Stefanova N, Gelpi E, Seppi K, Navarro-Otano J, Offner F, Vilas D, Valldeoriola F, Pont-Sunyer C, Aldecoa I, Gaig C, Gines A, Cuatrecasas M, Högl B, Frauscher B, Iranzo A, Wenning GK, Vogel W, Tolosa E, Poewe W (2015) Enteric nervous system α-synuclein immunoreactivity in idiopathic REM sleep behavior disorder. Neurology 85:1761–1768

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Stokholm MG, Danielsen EH, Hamilton-Dutoit SJ, Borghammer P (2016) Pathological α-synuclein in gastrointestinal tissues from prodromal Parkinson disease patients. Ann Neurol 79:940–949

    Article  PubMed  CAS  Google Scholar 

  • Su A, Gandhy R, Barlow C, Triadafilopoulos G (2017) Clinical and manometric characteristics of patients with Parkinson’s disease and esophageal symptoms. Dis Esophagus 30:1–6

    Article  CAS  PubMed  Google Scholar 

  • Sumikura H, Takao M, Hatsuta H, Ito S, Uchino A, Nogami A, Saito Y, Mochizuki H, Murayama S (2015) Distribution of α-synuclein in the spinal cord and dorsal root ganglia in an autopsy cohort of elderly persons. Acta Neuropathol Commun 3:57

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Takahashi M, Ikemura M, Oka T, Uchihara T, Wakabayashi K, Kakita A, Takahashi H, Yoshida M, Toru S, Kobayashi T, Orimo S (2015) Quantitative correlation between cardiac MIBG uptake and remaining axons in the cardiac sympathetic nerve in Lewy body disease. J Neurol Neurosurg Psychiatry 86:939–944

    Article  PubMed  Google Scholar 

  • Takeda S, Yamazaki K, Miyakawa T, Arai H (1993) Parkinson’s disease with involvement of the parasympathetic ganglia. Acta Neuropathol 86:397–398

    Article  PubMed  CAS  Google Scholar 

  • Taki J, Nakajima K, Hwang E-H, Matsunari I, Komai K, Yoshita M, Sakajiri K, Tonami N (2000) Peripheral sympathetic dysfunction in patients with Parkinson’s disease without autonomic failure is heart selective and disease specific. Eur J Nucl Med 27:566–573

    Article  PubMed  CAS  Google Scholar 

  • Tamura T, Yoshida M, Hashizume Y, Sobue G (2012) Lewy body-related a-synucleinopathy in the spinal cord of cases with incidental Lewy body disease. Neuropathology 32:13–22

    Article  PubMed  Google Scholar 

  • Tolosa E, Wenning G, Poewe W (2006) The diagnosis of Parkinson’s disease. Lancet Neurol 5:75–86

    Article  PubMed  Google Scholar 

  • Treglia G, Cason E, Stefanelli A, Cocciolillo F, Di Giuda D, Fagioli G, Giordano A (2012) MIBG scintigraphy in differential diagnosis of Parkinsonism: a meta-analysis. Clin Auton Res 22:43–55

    Article  PubMed  Google Scholar 

  • Uchiyama M, Isse K, Tanaka K, Yokota N, Hamamoto M, Aida S, Ito Y, Yoshimura M, Okawa M (1995) Incidental Lewy body disease in a patient with REM sleep behaviour disorder. Neurology 45:709–712

    Article  PubMed  CAS  Google Scholar 

  • Ulusoy A, Phillips RJ, Helwig M, Klinkenberg M, Powley TL, Di Monte DA (2017) Brain-to-stomach transfer of α-synuclein via vagal preganglionic projections. Acta Neuropathol 133:381–383

    Article  PubMed  CAS  Google Scholar 

  • VanderHorst VG, Samardzic T, Saper CB, Anderson MP, Nag S, Schneider JA, Bennett DA, Buchman AS (2015) Alpha-synuclein pathology accumulates in sacral spinal visceral sensory pathways. Ann Neurol 78:142–149

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vilas D, Iranzo A, Tolosa E, Aldecoa I, Berenguer J, Vilaseca I, Martí C, Serradell M, Lomeña F, Alós L, Gaig C, Santamaria J, Gelpi E (2016) Assessment of α-synuclein in submandibular glands of patients with idiopathic rapid-eye-movement sleep behaviour disorder: a case-control study. Lancet Neurol 15:708–718

    Article  PubMed  CAS  Google Scholar 

  • Visanji NP, Marras C, Kern DS, Al Dakheel A, Gao A, Liu LW, Lang AE, Hazrati LN (2015) Colonic mucosal α-synuclein lacks specificity as a biomarker for Parkinson disease. Neurology 84:609–616

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wakabayashi K, Takahashi H (1997a) The intermediolateral nucleus and Clarke’s column in Parkinson’s disease. Acta Neuropathol 94:287–289

    Article  PubMed  CAS  Google Scholar 

  • Wakabayashi K, Takahashi H (1997b) Neuropathology of autonomic nervous system in Parkinson’s disease. Eur Neurol 38(Suppl 2):2–7

    Article  PubMed  Google Scholar 

  • Wakabayashi K, Takahashi H, Takeda S, Ohama E, Ikuta F (1988) Parkinson’s disease: the presence of Lewy bodies in Auerbach’s and Meissner’s plexuses. Acta Neuropathol 76:217–221

    Article  PubMed  CAS  Google Scholar 

  • Wakabayashi K, Takahashi H, Ohama E, Ikuta F (1990) Parkinson’s disease: an immunohistochemical study of Lewy body-containing neurons in the enteric nervous system. Acta Neuropathol 79:581–583

    Article  PubMed  CAS  Google Scholar 

  • Watanabe H, Ieda T, Katayama T, Takeda A, Aiba I, Doyu M, Hirayama M, Sobue G (2001) Cardiac 123I-meta-iodobenzylguanidine (MIBG) uptake in dementia with Lewy bodies: comparison with Alzheimer’s disease. J Neurol Neurosurg Psychiatry 70:781–783

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgements

Part of these studies has been possible thanks to the SINBAR Innsbruck-Barcelona collaboration, the IDIBAPS Barcelona Brain Bank, the Fondo De Investigación Sanitaria (FIS)-Instituto de Salud Carlos III and the Spanish Ministry of Economy and Competitiveness PI13/01455.

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Authors and Affiliations

  1. Department of Neurology, Kanto Central Hospital, 6-25-1 Kami-Yoga, Setagaya-ku, Tokyo, 158-8531, Japan

    Satoshi Orimo

  2. Institute of Clinical Neuroanatomy, J. W. Goethe-University, Theodor-Stern-Kai 7, 60590, Frankfurt/Main, Germany

    Estifanos Ghebremedhin

  3. Neurological Tissue Bank of the Biobank-Hospital Clinic-IDIBAPS, Barcelona, Spain

    Ellen Gelpi

  4. Institute of Neurology, Medical University of Vienna, Vienna, Austria

    Ellen Gelpi

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  1. Satoshi Orimo
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  2. Estifanos Ghebremedhin
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  3. Ellen Gelpi
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Correspondence to Satoshi Orimo.

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Satoshi Orimo and Estifanos Ghebremedhin contributed equally to this work

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Orimo, S., Ghebremedhin, E. & Gelpi, E. Peripheral and central autonomic nervous system: does the sympathetic or parasympathetic nervous system bear the brunt of the pathology during the course of sporadic PD?. Cell Tissue Res 373, 267–286 (2018). https://doi.org/10.1007/s00441-018-2851-9

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