Spinal cord lesions in sporadic Parkinson's disease

Acta Neuropathologica

Volumn 124, Issue 5, 2012, Pages 643-664

  Del Tredici, Kelly ^a   Braak, Heiko ^a  

^a UNIVERSITY OF ULM   (Germany)

Author keywords

Synuclein; Autonomic nervous system; Central nervous system; Incidental Lewy body disease; Intermediolateral nucleus; Lewy bodies neuritis; Lewy body disease; Locus coeruleus; Lower raphe nuclei; Micturition; Neurodegeneration; Noradrenalin; Nucleus of Onuf; Pain system; Premotor Parkinson's disease; Renshaw cells; Sacral parasympathetic nucleus; Serotonin; Spinal cord; Sporadic Parkinson's disease; Synucleinopathy

Indexed keywords

ALPHA SYNUCLEIN;

ADULT; AGED; ALPHA NERVE FIBER; ARTICLE; BRAIN NERVE CELL; CELLULAR DISTRIBUTION; CLINICAL FEATURE; CONTROLLED STUDY; DIFFUSE LEWY BODY DISEASE; DISEASE ASSOCIATION; FEMALE; GRAY MATTER; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; IMMUNOREACTIVITY; MALE; NERVE CELL NETWORK; NEUROPATHY; PARKINSON DISEASE; PRIORITY JOURNAL; PROTEIN DEFECT; PROTEIN LOCALIZATION; SPINAL CORD DORSAL HORN; SPINAL CORD LESION; SYNUCLEINOPATHY;

AGED; AGED, 80 AND OVER; ALPHA-SYNUCLEIN; BIOPSY; BRAIN; CASE-CONTROL STUDIES; FEMALE; HUMANS; LEWY BODY DISEASE; MALE; MIDDLE AGED; NEURITES; NEURONS; PARKINSON DISEASE; POSTMORTEM CHANGES; SPINAL CORD; SPINAL CORD DISEASES;

EID: 84871004211     PISSN: 00016322     EISSN: 14320533     Source Type: Journal    
DOI: 10.1007/s00401-012-1028-y     Document Type: Article

References (196)

1. Abbott RD, Petrovitch H, White LR et al (2001) Frequency of bowel movements and the risk of Parkinson's disease. Neurology 57:456-462
2. Abbott RD, Ross GW, Petrovitch H et al (2007) Bowel movement frequency in late-life and incidental Lewy bodies. Mov Disord 22:1581-1586
3. Ashraf W, Pfeiffer RF, Quigley EMM (1994) Anorectal manometry in the assessment of anorectal function in Parkinson's disease: a comparison with chronic idiopathic constipation. Mov Disord 9:655-663
4. Aston-Jones G, Cohen JD (2005) Adaptive gain and the role of the locus coeruleus-norepinephrine system in optimal performance. J Comp Neurol 493:99-110
5. Awerbuch GI, Sandyk R (1994) Autonomic functions in the early stages of Parkinson's disease. Int J Neurosci 74:9-16
6. Barson AJ, Sands J (1977) Regional and segmental characteristics of the human spinal cord. J Anat 123:797-803
7. Basbaum AI, Fields HL (1984) Endogeneous pain control systems: brainstem spinal pathways and endorphin circuitry. Ann Rev Neurosci 7:309-338
8. Beach TG, Adler CH, Sue LI et al (2010) Multi-organ distribution of phospohorylated a-synuclein histopathology in subjects with Lewy body disorders. Acta Neuropathol 119:689-702
9. Benarroch EE (1993) The central autonomic network: functional organization, dysfunction, and perspective. Mayo Clin Proc 68:988-1001
10. Benarroch EE (2001) Pain-autonomic interactions: a selective review. Clin Auton Res 11:343-349
11. Benarroch EE (2007) Enteric nervous system: functional organization and neurologic implications. Neurology 69:1953-1957
12. Benarroch EE (2010) Neural control of the bladder: recent advances and neurologic implications. Neurology 75:1839-1846
13. Benarroch EE, Schmeichel AM, Low PA et al (2005) Involvement of medullary regions controlling sympathetic output in Lewy body disease. Brain 128:338-344
14. Blessing WW (2004) Lower brain stem regulation of visceral, cardiovascular, and respiratory function. In: Paxinos G, Mai JK (eds) The human nervous system, 2nd edn. Academic Press, San Diego, pp 464-478
15. Bloch A, Probst A, Bissig H, Adams H, Tolnay M (2006) a-Synuclein pathology of the spinal and peripheral autonomic nervous system in neurologically unimpaired elderly subjects. Neuropathol Appl Neurobiol 12:284-295
16. BohusB, Koolhaas JM, LuitenPGMet al (1996) The neurobiology of the central nucleus of theamygdala in relation to neuroendocrine and autonomic outflow. Progr Brain Res 107:447-460
17. Bowsher D, Abdel-Maguid TE (1984) Superficial dorsal horn of the adult human spinal cord. Neurosurgery 15:893-899
18. Braak E, Sandmann-Keil D, Rüb U et al (2001) Alpha-synuclein immunopositive Parkinson's disease-related inclusion bodies in lower brain stem nuclei. Acta Neuropathol 101:195-201
19. Braak H (1984) Architectonics as seen by lipofuscin stains. In: Jones EG, Peters A (eds) Cerebral cortex. Cellular components of the cerebral cortex, vol I. Plenum Press, New York, pp 59-104
20. Braak H, Braak E (1991) Neuropathological stageing of Alzheimer- related changes. Acta Neuropathol 82:239-259
21. Braak H, Braak E, Yilmazer D et al (1994) Amygdala pathology in Parkinson's disease. Acta Neuropathol 88:493-500
22. Braak H, Sandmann-Keil D, Gai WP, Braak E (1999) Extensive axonal Lewy neurites in Parkinson's disease: a novel pathological feature revealed by a-synuclein. Neurosci Lett 265:67-69
23. Braak H, Rüb U, Sandmann-Keil D et al (2000) Parkinson's disease: affection of brain stem nuclei controlling premotor and motor neurons of the somatomotor system. Acta Neuropathol 99:489-495
24. Braak H, Del Tredici K, Rüb U et al (2003) Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging 24:197-210
25. Braak H, Rüb U, Gai WP, Del Tredici K (2003) 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
26. Braak H, de Vos RAI, Bohl J, Del Tredici K (2006) Gastric asynuclein immunoreactive inclusions in Meissner's and Auerbach's plexuses in cases staged for Parkinson's disease-related brain pathology. Neurosci Lett 396:67-72
27. 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
28. Brown RG, Jahanshahi M, Quinn N, Marsden CD (1990) Sexual function in patients with Parkinson's disease and their partners. J Neurol Neurosurg Psychiatry 53:480-486
29. Buzas B, Max MB (2004) Pain in Parkinson disease. Neurology 62:2156-2157
30. Cersósimo MG, Benarroch EE (2008) Neural control of the gastrointestinal tract: implications for Parkinson disease. Mov Disord 23:1065-1075
31. Cersósimo MG, Perandonas C, Micheli FE et al (2011) Alphasynuclein immunoreactivity in minor salivary gland biopsies of Parkinson's disease patients. Mov Disord 26:188-190
32. Chalmers D, Swash M (1987) Selective vulnerability of urinary Onufmotoneurons in Shy-Drager syndrome. JNeurol 234:259-260
33. Clark FM, Proudfit HK (1991) The projection of locus coeruleus neurons to the spinal cord in the rat determined by anterograde tracing combined with immunocytochemistry. Brain Res 538:231-245
34. Craig AD (1993) Propriospinal input to thoracolumbar sympathetic nuclei from cervical and lumbar lamina I neurons in the cat and monkey. J Comp Neurol 331:517-530
35. Craig AD (2003) Pain mechanisms: labeled lines versus convergence in central processing. Ann Rev Neurosci 26:1-30
36. Dale GE, Probst A, Luthert P et al (1992) Relationships between Lewy bodies and pale bodies in Parkinson's disease. Acta Neuropathol 83:525-529
37. Danzer KM, Krebs SK, Wolff M, Birk G, Hengerer B (2009) Seeding induced by alpha-synuclein oligomers provides evidence for spreading of alpha-synuclein pathology. J Neurochem 111:192-203
38. Defazio G, Beradelli A, Fabrini G et al (2008) Pain as a nonmotor symptom of Parkinson disease: evidence from a casecontrol study. Arch Neurol 65:1191-1194
39. de Jong TR, Veening JG, Waldinger MD, Cools AR, Olivier B (2006) Serotonin and the neurobiology of the ejaculatory threshold. Neurosci Biobehav Rev 30:893-907
40. Delledonne A, Klos KJ, Fujishiro H et al (2008) Incidental Lewy body disease and preclinical Parkinson disease. Arch Neurol 65:1074-1080
41. Del Tredici K, Braak H (2012) Lewy pathology and neurodegeneration in premotor Parkinson's disease. Mov Disord 27:597-607
42. Del Tredici K, Rüb U, de Vos RAI, Bohl JRE, Braak H (2002) Where does Parkinson disease pathology begin in the brain? J Neuropathol Exp Neurol 61:413-426
43. 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
44. 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
45. Desplats P, Lee HJ, Bae EJ et al (2009) Inclusion formation and neuronal cell death through neuron-to-neuron transmission of a-synuclein. Proc Natl Acad Sci USA 106:13010-13015
46. Dickson DW (2001) a-Synuclein and the Lewy body disorders. Curr Opin Neurol 14:423-432
47. Dickson DW, Fujishiro H, DelleDonne A et al (2008) Evidence that incidental Lewy body disease is presymptomatic Parkinson's disease. Acta Neuropathol 115:437-444
48. Dickson DW, Braak H, Duda JE et al (2009) Neuropathological assessment of Parkinson disease: refining the diagnostic criteria. Lancet Neurol 8:1150-1157
49. Dickson DW, Uchikado H, Fujishiro H, Tsuboi Y (2010) Evidence in favor of Braak staging of Parkinson's disease. Mov Disord 25(Suppl 1):S78-S82
50. Djaldetti R, Shifrin A, Rogowski Z et al (2004) Quantitative measurement of pain sensation in patients with Parkinson disease. Neurology 62:2171-2175
51. Duda JE, Lee VMY, Trojanowski JQ (2000) Neuropathology of synuclein aggregates: new insights into mechanism of neurodegenerative diseases. J Neurosi Res 61:121-127
52. Dugger BN, Murray ME, Boeve BR et al (2012) Neuropathological analysis of brainstem cholinergic and catecholaminergic nuclei in relation to rapid eye movement (REM) sleep behaviour disorder. Neuropathol Appl Neurol 38:142-152
53. Dunning CJ, Reyes JF, Steiner JA, Brundin P (2012) Can Parkinson's disease pathology be propagated from one neuron to another? Progr Neurobiol 97:205-219
54. Eadie MJ, Tyrer JH (1965) Alimentary disorder in parkinsonism. Austral Ann Med 14:13-22
55. Edwards LL, Pfeiffer RF, Quigley EMM, Hofman R, Balluff M (1991) Gastrointestinal symptoms in Parkinson's disease. Mov Disord 6:151-156
56. Edwards LL, Quigley EMM, Hofman R, Pfeiffer RF (1993) Gastrointestinal symptoms in Parkinson Disease: 18-month follow-up study. Mov Disord 8:83-86
57. Edwards LL, Quigley EMM, Harned RK et al (1994) Characterization of swallowing and defecation in Parkinson's disease. Am J Gastroenterol 89:15-25
58. Ford B (1998) Pain in Parkinson's disease. Clin Neurosci 5:63-72
59. Foreman RD, Blair RW (1988) Central organization of sympathetic cardiovascular response to pain. Ann Rev Physiol 50:607-622
60. Forger N, Breedlove SM (1986) Sexual dimorphism in human and canine spinal cord: role of early androgen. Proc Natl Acad of Sci USA 83:7527-7531
61. Forno LS (1969) Concentric hyalin intraneuronal inclusions of Lewy type in the brain of elderly persons (50 incidental cases): relationship to parkinsonism. J Am Geriatr Soc 17:557-575
62. Forno LS (1987) The Lewy body in Parkinson's disease. Adv Neurol 45:35-43
63. Fowler CJ (2006) Integrated control of lower urinary tract- clinical perspective. Br J Pharmacol 147:S14-S24
64. Frigerio R, Fujishiro H, Maraganore DM et al (2009) Comparison of risk factor profiles in incidental Lewy body disease and Parkinson disease. Arch Neurol 66:1114-1119
65. Fürst S (1999) Transmitters involved in antinociception in the spinal cord. Brain Res Bull 48:129-141
66. Gallagher DA, Lees AJ, Schrag A (2010) What are the most important nonmotor symptoms in patients with Parkinson's disease and are we missing them? Mov Disord 25:2493-2500
67. Gelb DJ, Oliver E, Gilman S (1999) Diagnostic criteria for Parkinson's disease. Arch Neurol 56:33-39
68. 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
69. Goetz CG, Tanner CM, Levy M, Wilson RS, Garron DC (1986) Pain in Parkinson's disease. Mov Disord 1:45-49
70. Grillner S, Wallén S, Saitoh K, Kozlov A, Robertson B (2008) Neural basis of goal-directed locomotion in vertebrates-an overview. Brain Res Rev 57:2-12
71. Guyenet PG, Koshiya N, Huangfu D et al (1996) Role of medulla oblongata in generation of sympathetic and vagal outflows. Prog Brain Res 107:127-144
72. Hansen C, Li J-Y (2012) Beyond alpha-synuclein transfer: pathology propagation in Parkinson's disease. Trends Mol Med 18:248-255
73. Hansen C, Angot E, Bergström A-L et al (2011) a-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells. J Clin Invest 121:715-725
74. Hilz MJ, Axelrod FB, Braeske K, Stemper B (2002) Cold pressor test demonstrates residual sympathetic cardiovascular activation in familial dysautonomia. J Neurol Sci 196:81-89
75. Holstege G (1992) The emotional motor system. Europ J Morphol 30:67-79
76. Holstege G (1996) The somatic motor system. Progr Brain Res 107:9-26
77. Holstege G (2005) Micturition and the soul. J Comp Neurol 493:15-20
78. Holstege G (2005) Central nervous system control of ejaculation. World J Urol 23:109-114
79. Holstege G, Mouton LJ, Gerrits NM (2004) Emotional motor system. In: Paxinos G, Mai JK (eds) The human nervous system, 2nd edn. Academic Press, San Diego, pp 1306-1325
80. Hopkins DA, Bieger D, de Vente J, Steinbusch HWM (1996) Vagal efferent projections: viscerotopy, neurochemistry and effects of vagotomy. Progr Brain Res 107:79-96
81. Hornung J-P (2003) The human raphe nuclei and the serotonergic system. J Chem Neuroanat 26:331-343
82. Iwanaga K, Wakabayashi K, Yoshimoto M et al (1999) Lewy body-type degeneration in cardiac plexus in Parkinson's and incidental Lewy body diseases. Neurology 52:1269-1271
83. Jacobs BL, Fornal CA (1993) 5-HT and motor control: a hypothesis. Trends Neurosci 16:346-352
84. Jänig W (1996) Spinal cord reflex organization of sympathetic systems. Progr Brain Res 107:43-77
85. Jankovic J (2008) Parkinson's disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry 79:368-376
86. Jellinger KA (1991) Pathology of Parkinson's disease. Changes other than the nigrostriatal pathway. Mol Chem Neuropathol 14:153-197
87. Jost WH, Eckardt VF (2003) Constipation in idiopathic Parkinson's disease. Scand J Gastroenterol 38:681-686
88. Kinder MV, Bastiaanssen EH, Janknegt RA, Marani E (1995) Neuronal circuitry of the lower urinary tract; central and peripheral neuronal control of the micturition cycle. Anat Embryol 192:195-209
89. Klos KJ, Ahlskog JE, Josephs KA et al (2006) a-Synuclein pathology in the spinal cord of neurologically asymptomatic aged individuals. Neurology 66:1100-1102
90. Kojima M, Sano Y (1983) The organization of serotonin fibers in the anterior column of the mammalian spinal cord. Anat Embryol 167:1-11
91. Kojima H, Furuta Y, Fujita M, Fujioka Y, Nagashima K (1989) Onuf's motoneuron is resistant to poliovirus. J Neurol Sci 93:85-92
92. Koller WC (1984) Sensory symptoms in Parkinson's disease. Neurology 34:957-959
93. Korczyn AD (1990) Autonomic nervous system disturbances in Parkinson's disease. Adv Neurol 53:463-468
94. Kordower JH, Chu Y, Hauser RA, Freeman TB, Olanow CW (2008) Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson's disease. Nat Med 14:504-506
95. Kuusisto E, Parkkinen L, Alafuzoff I (2003) Morphogenesis of Lewy bodies: dissimilar incorporation of a-synuclein, ubiquitin, and p62. J Neuropathol Exp Neurol 62:1241-1253
96. Lee SJ (2008) Origins and effects of extracellular alpha synuclein: implications in Parkinson's disease. J Mol Neurosci 34:17-22
97. Lee HJ, Patel S, Lee SJ (2005) Intravesicular localization and exocytosis of a-synuclein and its aggregates. J Neurosci 25:6016-6024
98. Lee SJ, Desplats P, Sigurdson C, Tsigelny I, Masliah E (2010) Cell-to-cell transmission of non-prion protein aggregates. Nat Rev Neurol 26:702-706
99. Light AR (1988) Normal anatomy and physiology of the spinal cord dorsal horn. Appl Neurophysiol 51:78-88
100. Loewy AD (1990) Central autonomic pathways. In: Loewy AD, Spyer KM (eds) Central regulation of autonomic functions. Oxford University Press, New York, pp 88-103
101. Luk KC, Song C, O'Brien P et al (2009) Exogenous alphasynuclein fibrils seed the formation of Lewy body-like intracellular inclusions in cultured cells. Proc Natl Acad Sci USA 106:20051-20056
102. Magerkurth C, Schnitzer R, Braune S (2005) Symptoms of autonomic failure in Parkinson's disease: prevalence and impact on daily life. Clin Auton Res 15:76-82
103. Makaroff L, Gunn A, Gervasoni C, Richy F (2011) Gastrointestinal disorders in Parkinson's disease: prevalence and health outcomes in a US claims database. J Parkinsons Dis 1:65-74
104. Mannen T (2000) Neuropathological findings of Onuf's nucleus and its significance. Neuropathology 20(Suppl):S30-S33
105. Mannen T, Iwata M, Toyokura Y, Nagashima K (1977) Preservation of a certain motoneurone group of the sacral cord in amyotrophic lateral sclerosis: its clinical significance. J Neurol Neurosurg Psychiatry 40:464-469
106. Mannen T, Iwata M, Toyokura Y, Nagashima K (1982) The Onuf's nucleus and the external anal sphincter muscles in amyotrophic lateral sclerosis and Shy-Drager syndrome. Acta Neuropathol 58:255-260
107. Markesbery WR, Jicha GA, Liu H, Schmitt FA (2009) Lewy body pathology in normal elderly subjects. J Neuropathol Exp Neurol 68:816-822
108. Martignoni E, Pacchetti C, Godi L, Miceli G, Nappi G (1995) Autonomic disorders in Parkinson's disease. J Neural Transm 45(Suppl):11-19
109. Martin GF, Holstege G, Mehler WM (1990) Reticular formation of the pons and medulla. In: Paxinos G (ed) The human nervous system, 1st edn. Academic Press, New York, pp 203-220
110. Mathers SE, Kempster PA, Swash M, Lees AJ (1988) Constipation and paradoxical puborectalis contraction in anismus and Parkinson's disease: a dystonic phenomenon? J Neurol Neurosurg Psy-chia-try 51:1503-1507
111. Mathers SE, Kempster PA, Law PJ et al (1989) Anal sphincter dysfunction in Parkinson's disease. Arch Neurol 46:1061-1064
112. McHugh JM, McHugh WB (2000) Pain: neuroanatomy, chemical mediators, and clinical implications. AACN Clin Issues 2:168-178
113. McKeith IG, Dickson DW, Lowe J et al (2005) Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 65:1863-1862
114. Millan MJ (2002) Descending control of pain. Prog Neurbiol 66:355-474
115. Minguez-Castellanos A, Chamorro CE, Escamilla-Sevilla F et al (2007) Do a-synuclein aggregates in autonomic plexuses predate Lewy body disorders? A cohort study. Neurology 68:2012-2018
116. Molony V, Steedman WM, Cervero F, Iggo A (1981) Intracellular marking of identified neurons in the superficial dorsal horn of the cat spinal cord. Quart J Exp Physiol 66:211-223
117. Mylius V, Brebbemann J, Dohmann H et al (2011) Pain sensitivity and clinical progression in Parkinson's disease. Mov Disord 26:2220-2225
118. The National Institute on Aging (1997) Consensus recommendations for the post-mortem diagnosis of Alzheimer's disease. The National Institute on Aging, and Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer's Disease. Neurobiol Aging 18:S1-S2
119. Nieuwenhuys R (1996) The greater limbic system, the emotional motor system and the brain. Progr Brain Res 107:551-580
120. Norris EH, Giasson BI, Lee VM (2004) a-Synuclein: normal function and role in neurodegenerative diseases. Curr Top Dev Biol 60:17-54
121. Nyberg LG, Olson L (1977) A new major projection from locus coeruleus: the main source of noradrenergic nerve terminals in the ventral and dorsal columns of the spinal cord. Brain Res 132:85-93
122. Oinas M, Paetau A, Myillykangas L et al (2010) alpha-Synuclein pathology in the spinal cord autonomic nuclei associates with alpha-synuclein pathology in the brain: a population-based Vantaa 85? study. Acta Neuropathol 119:715-722
123. Onufronwicz B (1899) Notes on the arrangement and function of the cell groups of the sacral regions of the spinal cord. J Nerv Med Dis 26:498-504
124. O'Sullivan SS, Holton JL, Massey LA et al (2008) Parkinson's disease with Onuf's nucleus involvement mimicking multiple system atrophy. J Neurol Neurosurg Psychiatry 79:232-234
125. O'Sullivan SS, Williams DR, Gallagher DW et al (2008) Nonmotor symptoms as presenting complaints in Parkinson's disease: a clinicopathological study. Mov Disord 23:101-106
126. Oyanagi K, Wakabayashi K, Ohama E et al (1990) Lewy bodies in lower sacral parasympathetic neurons of a patient with Parkinson's disease. Acta Neuropathol 80:558-559
127. Pan-Montojo F, Anichtchik O, Dening Y et al (2010) Progression of Parkinson's disease pathology is reproduced by intragastric administration of rotenone in mice. PLoS ONE 5:38762
128. Parkinson JD (1817) An essay on the shaking palsy. Sherwood, Neely and Jones, London
129. Paulus W, Jellinger KA (1991) The neuropathologic basis of different clinical subgroups of Parkinson's disease. J Neuropathol Exp Neurol 50:743-755
130. Paxinos G, Huang X-F, Sengul G, Watson C (2012) Organization of brainstem nuclei: In: Mai JK, Paxinos G (eds) The human nervous system, 3rd edn. Academic Press, San Diego, pp 260-327
131. Perrin FE, Gerber YN, Teigell M et al (2011) Anatomical study of serotonergic innervation and 5-HT1A receptor in the human spinal cord. Cell Death Dis 2:3218
132. Perrotta A, Sandrini G, Serrao M et al (2011) Facilitated temporal summation of pain at spinal level in Parkinson's disease. Mov Disord 26:442-448
133. Pfeiffer RF (2011) Gastrointestinal dysfunction in Parkinson's disease. Parkinsonism Rel Disord 17:10-15
134. Pouclet H, Lebouvier T, Coron E et al (2012) A comparison between rectal and colonic biopsies to detect Lewy pathology in Parkinson's disease. Neurobiol Dis 45:305-309
135. Prasad K, Beach TG, Hedreen J, Richfield EK (2012) Critical role for truncated a-synuclein and aggregates in Parkinson's disease and incidental Lewy body disease. Brain Pathol March 27 [Epub ahead of print] PMID: 22452578
136. Pullen AH, Tucker D, Martin JE (1997) Morphological and morphometric characterization of Onuf's nucleus in the spinal cord in man. J Anat 191:201-213
137. Puskár Z, Polgár E, Todd AJ (2001) A population of large lamina I projections neurons with selective inhibitory input in rat spinal cord. Neuroscience 102:167-176
138. Quinn NP, Koller WC, Lang AE, Marsden CD (1996) Painful Parkinson's disease. Lancet 1:1366-1369
139. Rajaofetra N, Passagia JG, Marlier L et al (1992) Serotoninergic, noradrenergic, and peptidergic innervation of Onuf's nucleus of normal and transacted spinal cords of baboons (Papio papio). J Comp Neurol 318:1-17
140. Ransmayr GN, Holliger S, Schletterer K et al (2008) Lower urinary tract symptoms in dementia with Lewy bodies, Parkinson disease, and Alzheimer disease. Neurology 70:299-303
141. Rexed BA (1954) A cytoarchitectonic atlas of the spinal cord in the cat. J Comp Neurol 100:297-379
142. Ross GW, Abbott RD, Petrovitch H et al (2006) Association of olfactory dysfunction with incidental Lewy bodies. Mov Disord 21:2062-2067
143. Sage JI (2004) Pain in Parkinson's disease. Curr Treat Options Neurol 6:191-200
144. Sakakibara R, Shinotoh H, Uchiyama T et al (2001) Questionnaire- based assessment of pelvic organ dysfunction in Parkinson's disease. Auton Neurosci 92:76-85
145. Sakakibara R, Uchiyama T, Yamanishi T, Kishi M (2010) Genitourinary dysfunction in Parkinson's disease. Mov Disord 25:2-12
146. Sakakibara R, Tateno F, Kishi M et al (2012) Pathophysiology of bladder dysfunction in Parkinson's disease. Neurobiol Dis 46:565-571
147. Samuels ER, Szabadi E (2009) Functional neuroanatomy of the noradrenergic locus coeruleus: its roles in the regulation of arousal and autonomic function part I: principles of functional organization. Curr Neuropharmacol 6:235-253
148. Sandrini G, Serrae M, Rossi P et al (2005) The lower limb flexion reflex in humans. Prog Neurobiol 77:353-395
149. Saper CB, Sorrentino DM, German DC, de Lacalle S (1991) Medullary catecholaminergic neurons in the normal human brain and in Parkinson's disease. Ann Neurol 29:577-584
150. Sasa M, Yoshimura N (1994) Locus coeruleus noradrenergic neurons as a micturition center. Microsc Res Tech 29:226-230
151. Savica R, Cartin JM, Grossardt BR et al (2009) Medical records documentation of constipation preceding Parkinson disease: a case-control study. Neurology 73:1752-1758
152. Scatton B, Dennis T, L'Heureux R et al (1986) Degeneration of noradrenergic and serotonergic but not dopaminergic neurones in the lumbar spinal cord of Parkinson patients. Brain Res 380:181-185
153. Scherder E, Wolters E, Polman C, Serfeant J, Swaab D (2005) Pain in Parkinson's disease and multiple sclerosis: its relation to the medial and lateral pain systems. Neurosci Biobehav Rev 29:1047-1056
154. Schrøder HD (1981) Onuf's nucleus X: a morphological study of a human spinal nucleus. Anat Embryol 162:443-453
155. Sengul G, Watson C (2012) Spinal cord: regional anatomy, cytoarchitecture, and chemoarchitecture. In: Mai JK, Paxinos G (eds) The human nervous system, 3rd edn. Academic Press, Boston, pp 186-232
156. Serrao M, Ranavolo A, Anderson OK et al (2012) Adaptive behaviour of the spinal cord in the transition from quiet stance to walking. BMC Neurosci 16:80
157. Sethi K (2008) Levodopa unresponsive symptoms in Parkinson's disease. Mov Disord 23(Suppl 3):S521-S533
158. Shannon KM, Keshavarzian A, Dodiya HB, Jakate S, Kordower JH (2012) Is alpha-synuclein in the colon a biomarker for premotor Parkinson's disease? Evidence from 3 cases. Mov Disord 27:716-719
159. Siddiqui MF, Rast S, Lynn MJ, Auchus AP, Pfeiffer RF (2002) Autonomic dysfunction in Parkinson's disease: a comprehensive symptom survey. Parkinsonism Rel Disord 8:277-284
160. Sims KS, Williams RS (1990) The human amygdaloid complex: a cytologic and histochemical atlas using Nissl, myelin, acetylcholinesterase and nicotinamide adenine dinucleotide phosphate diaphorase staining. Neuroscience 36:449-472
161. Singer C, Weiner WJ, Sanchez-Ramos JR (1992) Autonomic dysfunction in men with Parkinson's disease. Eur Neurol 32:134-140
162. Snider SR, Fahn S, Isgreen WP, Cote LJ (1976) Primary sensory symptoms in Parkinsonism. Neurology 76:423-429
163. Sofic E, Riederer P, Gsell W et al (1991) Biogenic amines and metabolites in spinal cord of patients with Parkinson's disease and amyotrophic lateral sclerosis. J Neural Transm Park Dis Dement Sect 3:133-142
164. Spillantini MG, Schmidt ML, Lee VMY et al (1997) a-Synuclein in Lewy bodies. Nature 388:839-840
165. Steinbusch HWM (1981) Distribution of serotonin-immunoreactivity in the central nervous system of the rat. Cell bodies and terminals. Neuroscience 6:557-618
166. Strack AM, Sawyer WB, Hughes JH, Platt KB, Loewy AD (1989) A general pattern of CNS innervation of the sympathetic outflow demonstrated by transneuronal pseudorabies viral infections. Brain Res 491:156-162
167. Sun MK (1995) Central neural organization and control of sympathetic nervous system in mammals. Prog Neurobiol 47:157-233
168. 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
169. Thal DR, Rüb U, Orantes M, Braak H (2002) Phases of Abdeposition in the human brain and its relevance for the development of AD. Neurology 58:1791-1800
170. Thor KB (2003) Serotonin and norepinephrine involvement in efferent pathways to the urethral rhabdosphincter: implications for treating stress urinary incontinence. Urology 62(Suppl 1):3-9
171. Thor KB (2004) Targeting serotonin and norepinephrin receptors in stress urinary incontinence. Int J Gynaecol Obstet 86(Suppl 1):38-52
172. Todd AJ (2010) Neuronal circuitry for pain processing in the dorsal horn. Nature Rev Neurosci 11:823-836
173. Tofaris GK, Spillantini MG (2007) Physiological and pathological properties of a-synuclein. Cell Mol Life Sci 64:2194-2201
174. Tracey I (2005) Nociceptive processing in the human brain. Curr Opin Neurobiol 15:478-487
175. Trojanowski JQ, Lee VM (2007) Parkinson's disease and related neurodegenerative synucleinopathies linked to progressive accumulations of synuclein aggregates in the brain. Parkinsonism Relat Disord 7:247-251
176. van de Berg WD, Hepp DH, Dijkstra AA et al (2012) Patterns of alpha-synuclein pathology in incidental cases and clinical subtypes of Parkinson's disease. Parkinsonsim Relat Disord 18(Suppl 1):S28-S30
177. Verbaan D, Marinus J, Visser M et al (2007) Patient-reported autonomic symptoms in Parkinson disease. Neurology 69:333-341
178. Vivacqua G, Casini A, Vaccaro R et al (2011) Spinal cord and parkinsonism: neuromorphological evidences in humans and experimental studies. J Chem Neuroanat 42:327-340
179. Vogt BA, Sikes RW (2000) The medial pain system, cingulate cortex, and parallel processing of nociceptive information. Progr Brain Res 122:223-235
180. Wakabayashi K, Takahashi H (1997) Neuropathology of autonomic nervous system in Parkinson's disease. Eur Neurol 38(Suppl 2):2-7
181. Wakabayashi K, Takahashi H (1997) The intermediolateral nucleus and Clarke's column in Parkinson's disease. Acta Neuropathol 94:287-289
182. 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
183. Wakabayashi K, Takahashi H, Ohama E, Ikuta F (1990) Parkinson's disease: an immunohistochemical study of Lewy bodycontaining neurons in the enteric nervous system. Acta Neuropathol 79:581-583
184. Wakabayashi K, Takahashi H, Ohama E, Takeda S, Ikuta F (1993) Lewy bodies in the visceral autonomic nervous system in Parkinson's disease. Adv Neurol 60:609-612
185. Waseem S, Gwinn-Hardy K (2001) Pain in Parkinson's disease. Postgrad Med 110:1-5
186. Watson C, Paxinos G, Kayalioglu G (eds) (2009) The spinal cord: a Christopher and Dana Reeve Foundation Text and Atlas. Academic Press, Boston
187. Waxman EA, Giasson BI (2009) Molecular mechanisms of alphasynuclein neurodegeneration. Biochim Biophys Acta 1792: 616-624
188. Westlund KN, Coulter JD (1980) Descending projections of the locus coeruleus and subcoeruleus/medial parabrachial nuclei in the monkey: axonal transport studies and dopamine-b-hydroxylase immunocytochemistry. Brain Res Rev 2:235-264
189. Westlund KN, Craig (1996) LC receives ascending input from nociceptive fibers located in lamina I of the spinal cord
190. Willis WD, Westlund KN (1997) Neuroanatomy of the pain system and of the pathways that modulate pain. J Clin Neurophysiol 14:2-31
191. Winge K, Fowler CJ (2006) Bladder dysfunction in parkinsonism: mechanisms, prevalence, symptoms, and management. Mov Disord 21:737-745
192. Yamamoto T, Satomi H, Ise H, Takatama H, Takahashi K (1978) Sacral spinal innervations of the rectal and vesical smooth muscles and the sphincteric striated muscles as demonstrated by the horseradish peroxidase method. Neurosci Lett 7:41-47
193. Yeo L, Singh R, Gundeti M, Barua JM, Masood J (2012) Urinary tract dysfunction in Parkinson's disease: a review. Int Urol Nephrol 44:415-424
194. Zarow C, Lyness SA, Mortimer JA, Chui HC (2003) Neuronal loss is greater in the locus coeruleus than nucleus basalis and substantia nigra in Alzheimer and Parkinson diseases. Arch Neurol 60:337-341
195. Zhang ET, Craig AD (1997) Morphology and distribution of spinothalamic lamina I neurons in the monkey. J Neurosci 17:3274-3284
196. Zesiewicz TA, Sullivan KL, Arnulf I et al (2010) Practice parameter: treatment of nonmotor symptoms of Parkinson disease: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 74:924-931