Multiple System Atrophy

  • Felix Geser
  • Gregor K. Wenning
Part of the Current Clinical Neurology book series (CCNEU)


Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder characterized clinically by various combinations of parkinsonian, autonomic, cerebellar, or pyramidal symptoms and signs and pathologically by cell loss, gliosis, and glial cytoplasmic inclusions in several brain and spinal cord structures. The term MSA was introduced in 1969, however cases of MSA were previously reported under the rubrics of striatonigral degeneration, olivopontocerebellar atrophy, Shy-Drager syndrome and idiopathic orthostatic hypotension. In the late 1990s, α-synuclein immunostaining was recognized as most sensitive marker of inclusion pathology in MSA: because of these advances in molecular pathogenesis, MSA has been firmly established as α-synucleinopathy along with Parkinson’s disease (PD) and dementia with Lewy bodies. Recent epidemiological surveys have shown that MSA is not a rare disorder (∼5 cases per 100,000 population), and that misdiagnosis, especially with PD, is still common due to variable clinical presentations of MSA. However, the clinical picture of MSA in its full-blown form is distinctive. The patient is hypomimic with orofacial and anterior neck dystonia resulting in a grinning smile akin to “risus sardonicus” and sometimes disproportionate antecollis. The voice is often markedly impaired with a characteristic quivering high-pitched dysarthria. The motor disorder of MSA is often mixed with parkinsonism, cerebellar ataxia, limb dystonia, myoclonus, and pyramidal features occurring at the same time. However, akinesia and rigidity are the predominating features in 80% of patients, and cerebellar ataxia within the remaining 20%. According to the predominant motor presentation, MSA patients may be labeled as parkinsonian or cerebellar variant (MSA-P, MSA-C). The diagnosis of MSA is largely based on clinical expertise, and this is well illustrated by the consensus diagnostic criteria, which comprise clinical features only (divided into four domains including autonomic dysfunction, parkinsonism, cerebellar dysfunction, and corticospinal tract dysfunction). Nevertheless, several autonomic function, imaging, neurophysiological, and biochemical studies have been proposed in the last decade to help in the differential diagnosis of MSA. No drug treatment consistently benefits patients with this disease. Indeed, parkinsonism often shows a poor or unsustained response to chronic levodopa therapy, however, one-third of the patients may show a moderate-to-good dopaminergic response initially. There is no effective drug treatment for cerebellar ataxia. On the other hand, features of autonomic failure such as orthostatic hypotension, urinary retention or incontinence, constipation, and impotence, may often be relieved if recognized by the treating physician. Novel symptomatic and neuroprotective therapies are urgently required.


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  1. 1.
    Bower J, Maraganore D, McDonnell S, Rocca W. Incidence of progressive supranuclear palsy and multiple system atrophy in Olmsted County, Minnesota, 1976 to 1990. Neurology 1997;49:1284–1288.PubMedGoogle Scholar
  2. 2.
    Tison F, Yekhlef F, Chrysostome V, Sourgen C. Prevalence of multiple system atrophy. Lancet 2000; 355(9202):495–496.PubMedCrossRefGoogle Scholar
  3. 3.
    Schrag A, Ben-Shlomo Y, Quinn NP. Prevalence of progressive supranuclear palsy and multiple system atrophy: a cross-sectional study. Lancet 1999;354:1771–1775.PubMedCrossRefGoogle Scholar
  4. 4.
    Wermuth L, Joensen P, Bunger N, Jeune B. High prevalence of Parkinson’s disease in the Faroe Islands. Neurology 1997;49(2):426–432.PubMedGoogle Scholar
  5. 5.
    Chio A, Magnani C, Schiffer D. Prevalence of Parkinson’s disease in Northwestern Italy: comparison of tracer methodology and clinical ascertainment of cases. Mov Disord 1998;13(3):400–405.PubMedCrossRefGoogle Scholar
  6. 6.
    Trenkwalder C, Schwarz J, Gebhard J, Ruland D, Trenkwalder P, Hense HW, et al. Starnberg trial on epidemiology of Parkinsonism and hypertension in the elderly. Prevalence of Parkinson’s disease and related disorders assessed by a door-to-door survey of inhabitants older than 65 years. Arch Neurol 1995;52(10): 1017–1022.PubMedGoogle Scholar
  7. 7.
    Nee LE, Gomez MR, Dambrosia J, Bale S, Eldridge R, Polinsky RJ. Environmental-occupational risk factors and familial associations in multiple system atrophy: a preliminary investigation. Clin Auton Res 1991;1: 9–13.PubMedCrossRefGoogle Scholar
  8. 8.
    Gilman S, Low P, Quinn N, Albanese A, Ben-Shlomo Y, Fowler CJ, et al. Consensus statement on the diagnosis of multiple system atrophy. Clin Auton Res 1998;8:359–362.PubMedCrossRefGoogle Scholar
  9. 9.
    Hanna P, Jankovic J, Kirkpatrick JB. Multiple system atrophy: the putative causative role of environmental toxins. Arch Neurol 1999;56:90–94.PubMedCrossRefGoogle Scholar
  10. 10.
    Vanacore N, Bonifati V, Fabbrini G, Colosimo C, Marconi R, Nicholl D, et al. Smoking habits in multiple system atrophy and progressive supranuclear palsy. Neurology 2000;54:114–119.PubMedGoogle Scholar
  11. 11.
    Quinn N. Multiple system atrophy—the nature of the beast. J Neurol Neurosurg Psychiatry 1989; 52(Suppl):78–89.CrossRefGoogle Scholar
  12. 12.
    Quinn N. Multiple system atrophy. In: Marsden CD, Fahn S, eds. Movement Disorders 3. London: Butterworth-Heinemann, 1994:262–281.Google Scholar
  13. 13.
    Wenning GK, Ben Shlomo Y, Magalhaes M, Daniel SE, Quinn NP. Clinical features and natural history of multiple system atrophy. An analysis of 100 cases. Brain 1994;117(Pt 4):835–845.PubMedCrossRefGoogle Scholar
  14. 14.
    Magalhaes M, Wenning GK, Daniel SE, Quinn NP. Autonomic dysfunction in pathologically confirmed multiple system atrophy and idiopathic Parkinson’s disease—a retrospective comparison. Acta Neurol Scand 1995; 91(2):98–102.PubMedCrossRefGoogle Scholar
  15. 15.
    Quinn NP, Wenning G, Marsden CD. The Shy Drager syndrome. What did Shy and Drager really describe? Arch Neurol 1995;52(7):656–657.PubMedGoogle Scholar
  16. 16.
    Litvan I, Booth V, Wenning GK, Bartko JJ, Goetz CG, McKee A, et al. Retrospective application of a set of clinical diagnostic criteria for the diagnosis of multiple system atrophy. J Neural Transm 1998; 105(2–3):217–227.PubMedCrossRefGoogle Scholar
  17. 17.
    Colosimo C, Vanacore N, Bonifati V, Fabbrini G, Rum A, De Michele G, et al. Clinical diagnosis of multiple system atrophy: level of agreement between Quinn’s criteria and the consensus conference guidelines. Acta Neurol Scand 2001;103:261–264.PubMedCrossRefGoogle Scholar
  18. 18.
    Osaki Y, Wenning GK, Daniel SE, Hughes A, Lees AJ, Mathias CJ, et al. Do published criteria improve clinical diagnostic accuracy in multiple system atrophy? Neurology 2002;59(10):1486–1491.PubMedGoogle Scholar
  19. 19.
    Ben Shlomo Y, Wenning GK, Tison F, Quinn NP. Survival of patients with pathologically proven multiple system atrophy: a meta-analysis. Neurology 1997;48(2):384–393.PubMedGoogle Scholar
  20. 20.
    Wenning G, Tison F, Ben-Shlomo Y, Daniel SE, Quinn NP. Multiple system atrophy: a review of 203 pathologically proven cases. Mov Disord 1997;12(2):133–147.PubMedCrossRefGoogle Scholar
  21. 21.
    Schwarz J, Tatsch K, Arnold G, Gasser T, Trenkwalder C, Kirsch C. 123I-iodobenzamide-SPECT predicts dopaminergic responsiveness in patients with de novo parkinsonism. Neurology 1992;42:556–561.PubMedGoogle Scholar
  22. 22.
    Schelosky L, Hierholzer J, Wissel J, Cordes M, Poewe W. Correlation of clinical response in apomorphine test with D2-receptor status as demonstrated by 123I IBZM-SPECT. Mov Disord 1993;8(4):453–458.PubMedCrossRefGoogle Scholar
  23. 23.
    Wenning GK, Ben Shlomo Y, Hughes A, Daniel SE, Lees A, Quinn NP. What clinical features are most useful to distinguish definite multiple system atrophy from Parkinson’s disease? J Neurol Neurosurg Psychiatry 2000; 68(4):434–440.PubMedCrossRefGoogle Scholar
  24. 24.
    Boesch SM, Wenning GK, Ransmayr G, Poewe W. Dystonia in multiple system atrophy. J Neurol Neurosurg Psychiatry 2002;72(3):300–303.PubMedCrossRefGoogle Scholar
  25. 25.
    Hughes A, Colosimo C, Kleedorfer B, Daniel SE, Lees AJ. The dopaminergic response in multiple system atrophy. J Neurol Neurosurg Psychiatry 1992;55:1009–1013.PubMedGoogle Scholar
  26. 26.
    Parati E, Fetoni V, Geminiani C, Soliveri P, Giovannini P, Testa D, et al. Response to L-Dopa in multiple system atrophy. Clin Neuropharmacol 1993;16(2):139–144.PubMedCrossRefGoogle Scholar
  27. 27.
    Schulz J, Klockgether T, Petersen D, Jauch M, Müller-Schauenburg W, Spieker S, et al. Multiple system atrophy: natural history, MRI morphology, and dopamine receptor imaging with 123IBZM-SPECT. J Neurol Neurosurg Psychiatry 1994;57:1047–1056.PubMedCrossRefGoogle Scholar
  28. 28.
    Wenning GK, Kraft E, Beck R, Fowler CJ, Mathias CJ, Quinn NP, et al. Cerebellar presentation of multiple system atrophy. Mov Disord 1997;12(1):115–117.PubMedCrossRefGoogle Scholar
  29. 29.
    Watanabe H, Saito Y, Terao S, Ando T, Kachi T, Mukai E. Progression and prognosis in multiple system atrophy: an analysis of 230 Japanese patients. Brain 2002;125:1070–1083.PubMedCrossRefGoogle Scholar
  30. 30.
    Gouider-Khouja N, Vidailhet M, Bonnet AM, Pichon J, Agid Y. “Pure” striatonigral degeneration and Parkinson’s disease: a comparative clinical study. Mov Disord 1995;10(3):288–294.PubMedCrossRefGoogle Scholar
  31. 31.
    Holmberg B, Rosengren L, Karlsson JE, Johnels B. Increased cerebrospinal fluid levels of neurofilament protein in progressive supranuclear palsy and multiple-system atrophy compared with Parkinson’s disease. Mov Disord 1998;13(1):70–77.PubMedCrossRefGoogle Scholar
  32. 32.
    Holmberg B, Johnels B, Ingvarsson P, Eriksson B, Rosengren L. CSF-neurofilament and levodopa tests combined with discriminant analysis may contribute to the differential diagnosis of Parkinsonian syndromes. Parkinsonism Relat Disord 2001;8(1):23–31.PubMedCrossRefGoogle Scholar
  33. 33.
    Polinsky RJ, Brown RT, Lee GK, Timmers K, Culman J, Foldes O, et al. Beta-endorphin, ACTH, and catecholamine responses in chronic autonomic failure. Ann Neurol 1987;21(6):573–577.PubMedCrossRefGoogle Scholar
  34. 34.
    Kimber JR, Watson L, Mathias CJ. Distinction of idiopathic Parkinson’s disease from multiple-system atrophy by stimulation of growth-hormone release with clonidine. Lancet 1997;349(9069):1877–1881.PubMedCrossRefGoogle Scholar
  35. 35.
    Kaufmann H, Oribe E, Miller M, Knott P, Wiltshire-Clement M, Yahr MD. Hypotension-induced vasopressin release distinguishes between pure autonomic failure and multiple system atrophy with autonomic failure. Neurology 1992; 42(3 Pt 1):590–593.PubMedGoogle Scholar
  36. 36.
    Zoukos Y, Thomaides T, Pavitt DV, Cuzner ML, Mathias CJ. Beta-adrenoceptor expression on circulating mononuclear cells of idiopathic Parkinson’s disease and autonomic failure patients before and after reduction of central sympathetic outflow by clonidine. Neurology 1993;43(6):1181–1187.PubMedGoogle Scholar
  37. 37.
    Clarke CE, Ray PS, Speller JM. Failure of the clonidine growth hormone stimulation test to differentiate multiple system atrophy from early or advanced idiopathic Parkinson’s disease. Lancet 1999; 353(9161): 1329–1330.PubMedCrossRefGoogle Scholar
  38. 38.
    Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. J Neurol Sci 1996;144(1-2):218–219.Google Scholar
  39. 39.
    Bannister R, Mathias C. Investigation of autonomic disorders. In: Mathias C, Bannister R, eds. Autonomic Failure: A Textbook of Clinical Disorders of the Autonomic Nervous System. Oxford: Oxford University Press, 1999:169–195.Google Scholar
  40. 40.
    Braune S, Auer A, Schulte-Mönting J, Schwerbrock S, Lücking C. Cardiovascular parameters: sensitivity to detect autonomic dysfunction and influence of age and sex in normal subjects. Clin Auton Res 1996; 6:3–15.PubMedCrossRefGoogle Scholar
  41. 41.
    Braune S, Schulte-Mönting J, Schwerbrock S, Lücking CH. Retest variation of cardiovascular parameters in autonomic testing. J Auton Nerv Syst 1996;60(3):103–107.PubMedCrossRefGoogle Scholar
  42. 42.
    Riley D, Chemlinsky T. Autonomic nervous system testing may not distinguish multiple system atrophy from Parkinson’s disease. J Neurol Neurosurg Psychiatry 2003;74(1):56–60.PubMedCrossRefGoogle Scholar
  43. 43.
    Ziegler M, Lake C, Kopin I. The sympathetic-nervous-system defect in primary orthostatic hypotension. N Engl J Med 1977;296:293–297.PubMedCrossRefGoogle Scholar
  44. 44.
    Polinsky R, Kopin I, Ebert M, Weise V. Pharmacologic distinction of different orthostatic hypotension syndromes. Neurology 1981;31:1–7.PubMedGoogle Scholar
  45. 45.
    Braune S, Reinhardt M, Schnitzer R, Riedel A, Lücking CH. Cardiac uptake of (123I)MIBG separates Parkinson’s disease from multiple system atrophy. Neurology 1999;53(5):1020–1025.PubMedGoogle Scholar
  46. 46.
    Orimo S, Ozawa E, Nakade S, Sugimoto T, Mizusawa H. (123)I-metaiodobenzylguanidine myocardial scintigraphy in Parkinson’s disease. J Neurol Neurosurg Psychiatry 1999;67(2):189–194.PubMedGoogle Scholar
  47. 47.
    Takatsu H, Nagashima K, Murase M, Fujiwara H, Nishida H, Matsuo H, et al. Differentiating Parkinson disease from multiple-system atrophy by measuring cardiac iodine-123 metaiodobenzylguanidine accumulation. JAMA 2000; 284(1):44–45.PubMedCrossRefGoogle Scholar
  48. 48.
    Taki J, Nakajima K, Hwang EH, Matsunari I, Komai K, Yoshita M, et al. Peripheral sympathetic dysfunction in patients with Parkinson’s disease without autonomic failure is heart selective and disease specific. Eur J Nucl Med 2000;27(5):566–573.PubMedCrossRefGoogle Scholar
  49. 49.
    Kirby R, Fowler CJ, Gosling J, Bannister R. Urethro-vesical dysfunction in progressive autonomic failure with multiple system atrophy. J Neurol Neurosurg Psychiatry 1986;49:554–562.PubMedGoogle Scholar
  50. 50.
    Beck R, Betts C, Fowler C. Genitourinary dysfunction in multiple system atrophy: clinical features and treatment in 62 cases. J Urol 1994;151(5):1336–1341.PubMedGoogle Scholar
  51. 51.
    Wenning GK, Tison F, Elliott L, Quinn NP, Daniel SE. Olivopontocerebellar pathology in multiple system atrophy. Mov Disord 1996;11(2):157–162.PubMedCrossRefGoogle Scholar
  52. 52.
    Schrag A, Good CD, Miszkiel K, Morris HR, Mathias CJ, Lees AJ, et al. Differentiation of atypical parkinsonian syndromes with routine MRI. Neurology 2000;54(3):697–702.PubMedGoogle Scholar
  53. 53.
    Klockgether T, Schroth G, Diener HC, Dichgans J. Idiopathic cerebellar ataxia of late onset: natural history and MRI morphology. J Neurol Neurosurg Psychiatry 1990;53:297–305.PubMedGoogle Scholar
  54. 54.
    Wüllner U, Klockgether T, Petersen D, Naegele T, Dichgans J. Magnetic resonance imaging in hereditary and idiopathic ataxia. Neurology 1993;43:318–325.PubMedGoogle Scholar
  55. 55.
    Wakai M, Kume A, Takahashi A, Ando T, Hashizume Y. A study of parkinsonism in multiple system atrophy: clinical and MRI correlation. Acta Neurol Scand 1994;90(4):225–231.PubMedCrossRefGoogle Scholar
  56. 56.
    Albanese A, Colosimo C, Bentivoglio A, Fenici R, Melillo G, Colosimo C, et al. Multiple system atrophy presenting as parkinsonism: clinical features and diagnostic criteria. J Neurol Neurosurg Psychiatry 1995; 59: 144–151.PubMedGoogle Scholar
  57. 57.
    Konagaya M, Konagaya Y, Sakai M, Matsuoka Y, Hashizume Y. Progressive cerebral atrophy in multiple system atrophy. J Neurol Sci 2002;195(2):123–127.PubMedCrossRefGoogle Scholar
  58. 58.
    Savoiardo M, Strada L Girotti F. Olivopontocerebellar atrophy: MR diagnosis and relationship to multisystem atrophy. Radiology 1990;174:693–696.PubMedGoogle Scholar
  59. 59.
    Drayer B, Olanow W, Burger P, Johnson GA, Herfkens R, Riederer S. Parkinson Plus syndrome: diagnosis using high field MR imaging of brain iron. Radiology 1986;159:493–498.PubMedGoogle Scholar
  60. 60.
    Pastakia B, Polinsky R, Di Chiro G, Simmon JT, Brown R, Wener L. Multiple system atrophy (Shy-Drager syndrome): MR imaging. Radiology 1986;159:499–502.PubMedGoogle Scholar
  61. 61.
    Olanow C. Magnetic resonance imaging in parkinsonism. Neurol Clin 1992;10:405–420.PubMedGoogle Scholar
  62. 62.
    Lang A, Curran T, Provias J, Bergeron C. Striatonigral degeneration: iron deposition in putamen correlated with the slit-like void signal of magnetic resonance imaging. Can J Neurol Sci 1994;21:311–318.PubMedGoogle Scholar
  63. 63.
    O’Brien C, Sung JH, McGeachie RE, Lee MC. Striatonigral degeneration: Clinical, MRI, and pathologic correlation. Neurology 1990;40:710–711.PubMedGoogle Scholar
  64. 64.
    Schwarz J, Weis S, Kraft E. Signal changes on MRI and increases in reactive microgliosis, astrogliosis, and iron in the putamen of two patients with multiple system atrophy. J Neurol Neurosurg Psychiatry 1996;60: 98–101.PubMedGoogle Scholar
  65. 65.
    Stern M, Braffman BH, Skolnick BE, Hurtig HI, Grossman RI. Magnetic resonance imaging in Parkinson’s disease and parkinsonian syndromes. Neurology 1989;39:1524–1526.PubMedGoogle Scholar
  66. 66.
    Schrag A, Kingsley D, Phatouros C, Mathias CJ, Lees AJ, Daniel SE, et al. Clinical usefulness of magnetic resonance imaging in multiple system atrophy. J Neurol Neurosurg Psychiatry 1998;65(1):65–71.PubMedCrossRefGoogle Scholar
  67. 67.
    Brooks D, Luthert P, Gadian D, Marsden C. Does signal-attentuation on high-field T2-weighted MRI of the brain reflect regional cerebral iron deposition? Observations on the relationship between regional cerebral water proton T2-values and iron levels. J Neurol Neurosurg Psychiatry 1989;52:108–111.PubMedGoogle Scholar
  68. 68.
    Kraft E, Trenkwalder C, Auer DP. T2*-weighted MRI differentiates multiple system atrophy from Parkinson’s disease. Neurology 2002;59(8):1265–1267.PubMedGoogle Scholar
  69. 69.
    Konagaya M, Konagaya Y, Iida M. Clinical and magnetic resonance imaging study of extrapyramidal symptoms in multiple system atrophy. J Neurol Neurosurg Psychiatry 1994;57:1528–1531.PubMedCrossRefGoogle Scholar
  70. 70.
    Konagaya M, Konagaya Y, Honda H, Iida M. A clinico-MRI study of extrapyramidal symptoms in multiple system atrophy—linear hyperintensity in the outer margin of the putamen. No To Shinkei 1993;45(6): 509–513.PubMedGoogle Scholar
  71. 71.
    Yekhlef F, Ballan G, Macia F, Delmer O, Sourgen C, Tison F. Routine MRI for the differential diagnosis of Parkinson’s disease, MSA, PSP, and CBD. J Neural Transm 2003;110(2):151–169.PubMedCrossRefGoogle Scholar
  72. 72.
    Kraft E, Schwarz J, Trenkwalder C, Vogl T, Pfluger T, Oertel WH. The combination of hypointense and hyperintense signal changes on T2-weighted magnetic resonance imaging sequences: a specific marker of multiple system atrophy? Arch Neurol 1999;56(2):225–228.PubMedCrossRefGoogle Scholar
  73. 73.
    Konagaya M, Sakai M, Matsuoka Y, Goto Y, Yoshida M, Hashizume Y. Patho-MR imaging study in the putaminal margin in multiple system atrophy. No To Shinkei 1998;50(4):383–385.PubMedGoogle Scholar
  74. 74.
    Schocke M, Seppi K, Esterhammer R, Kremser C, Jaschke W, Poewe W. Diffusion-weighted MRI differentiates the Parinson variant of multiple system atrophy from PD. Neurology 2002;58:575–580.PubMedGoogle Scholar
  75. 75.
    Seppi K, Schocke MF, Esterhammer R, Kremser C, Brenneis C, Mueller J, et al. Diffusion-weighted imaging discriminates progressive supranuclear palsy from PD, but not from the parkinson variant of multiple system atrophy. Neurology 2003;60(6):922–927.PubMedGoogle Scholar
  76. 76.
    Schulz J, Skalej M, Wedekind D, Luft AR, Abele M, Voigt K, et al. Magnetic resonance imaging-based volumetry differentiates idiopathic Parkinson’s syndrome from multiple system atrophy and progressive supranuclear palsy. Ann Neurol 1999;45:65–74.PubMedCrossRefGoogle Scholar
  77. 77.
    Brenneis C, Seppi K, Schocke M, Müller J, Luginger E, Bösch S, et al. Voxel-based morphometry detects cortical atrophy in the parkinson variant of multiple system atrophy. Mov Disord 2003;18(10): 1132–1138.PubMedCrossRefGoogle Scholar
  78. 78.
    Robbins TW, James M, Lange KW, Owen AM, Quinn NP, Marsden CD. Cognitive performance in multiple system atrophy. Brain 1992;115(Pt 1):271–291.PubMedCrossRefGoogle Scholar
  79. 79.
    Davie CA, Wenning GK, Barker GJ, Tofts PS, Kendall BE, Quinn N, et al. Differentiation of multiple system atrophy from idiopathic Parkinson’s disease using proton magnetic resonance spectroscopy. Ann Neurol 1995; 37(2):204–210.PubMedCrossRefGoogle Scholar
  80. 80.
    Federico F, Simone IL, Lucivero V, Mezzapesa DM, de Mari M, Lamberti P, et al. Usefulness of proton magnetic resonance spectroscopy in differentiating parkinsonian syndromes. Ital J Neurol Sci 1999;20(4): 223–229.PubMedCrossRefGoogle Scholar
  81. 81.
    Ellis C, Lemmens G, Williams S, Simmons A, Leigh PN, Chaudhuri K. Striatal changes in striatonigral degeneration and Parkinson’s disease: a proton magnetic resonance spectroscopy study. Mov Disord 1996; 11:104.CrossRefGoogle Scholar
  82. 82.
    Hu M, Simmons A, Glover A. Proton magnetic resonance spectroscopy of the putamen in Parkinson’s disease and multiple system atrophy. Mov Disord 1998;13:182.CrossRefGoogle Scholar
  83. 83.
    Brooks D, Ibanez V, Sawle GV, Quinn N, Lees AJ, Mathias CJ, et al. Differing patterns of striatal 18F-dopa uptake in Parkinson’s disease, multiple system atrophy, and progressive supranuclear palsy. Ann Neurol 1990;28:547–555.PubMedCrossRefGoogle Scholar
  84. 84.
    Brooks D, Salmon E, Mathias C, Quinn N, Leenders K, Bannister R, et al. The relationship between locomotor disability, autonomic dysfunction, and the integrity of the striatal dopaminergic system in patients with multiple system atrophy, pure autonomic failure, and Parkinson’s disease, studied with PET. Brain 1990;113: 1539–1552.PubMedCrossRefGoogle Scholar
  85. 85.
    Burn D, Sawle G, Brooks D. Differential diagnosis of Parkinson’s disease, multiple system atrophy, and Steele-Richardson-Olszewski syndrome: discriminant analysis of striatal 18F-dopa PET data. J Neurol Neurosurg Psychiatry 1994;57(3):278–284.PubMedGoogle Scholar
  86. 86.
    Brooks D, Ibanez V, Sawle G, Playford E, Quinn N, Mathias C, et al. Striatal D2 receptor status in patients with Parkinson’s disease, striatonigral degeneration, and progressive supranuclear palsy, measured with 11C-raclopride and positron emission tomography. Ann Neurol 1992;31(2):184–192.PubMedCrossRefGoogle Scholar
  87. 87.
    Burn D, Rinne J, Quinn N, Lees A, Marsden C, Brooks D. Striatal opioid receptor binding in Parkinson’s disease, striatonigral degeneration and Steele-Richardson-Olsewski syndrome A (11C)diprenorphine PET study. Brain 1995;118:951–958.PubMedCrossRefGoogle Scholar
  88. 88.
    De Volder A, Francart J, Laterre C, Dooms G, Bol A, Michel C, et al. Decreased glucose utilization in the striatum and frontal lobe in probable striatonigral degeneration. Ann Neurol 1989;26:239–247.PubMedCrossRefGoogle Scholar
  89. 89.
    Eidelberg D, Takikawa S, Moeller JR, Dhawan V, Redington K, Chaly T, et al. Striatal hypometabolism distinguishes striatonigral degeneration from Parkinson’s disease. Ann Neurol 1993;33:518–527.PubMedCrossRefGoogle Scholar
  90. 90.
    Perani D, Bressi S, Testa D, Grassi F, Cortelli P, Gentrini S, et al. Clinical/metabolic correlations in multiple system atrophy. A fludeoxyglucose F18 positron emission tomography study. Arch Neurol 1995;52: 179–185.PubMedGoogle Scholar
  91. 91.
    Antonini A, Kazamuta k, Feigin A, Mandel F, Dhawan V, Margouleff C, et al. Differential diagnosis of parkinsonism with 18F-fluorodeoxyglucose and PET. Mov Disord 1998;13(2):268–274.PubMedCrossRefGoogle Scholar
  92. 92.
    Ghaemi M, Hilker R, Rudolf J, Sobesky J, Heiss WD. Differentiating multiple system atrophy from Parkinson’s disease: contribution of striatal and midbrain MRI volumetry and multi-tracer PET imaging. J Neurol Neurosurg Psychiatry 2002;73(5):517–523.PubMedCrossRefGoogle Scholar
  93. 93.
    Gilman S, Koeppe RA, Junck L, Kluin KJ, Lohman M, St. Laurent RT. Patterns of cerebral glucose metabolism detected with positron emission tomography differ in multiple system atrophy and olivopontocerebellar atrophy. Ann Neurol 1994;36:166–175.PubMedCrossRefGoogle Scholar
  94. 94.
    Rinne J, Burn DJ, Mathias CJ, Quinn NP, Marsden CD, Brooks DJ. Positron emission tomography studies on the dopaminergic system and striatal opioid binding in the olivopontocerebellar atrophy variant of multiple system atrophy. Ann Neurol 1995;37:568–573.PubMedCrossRefGoogle Scholar
  95. 95.
    Gilman S, Koeppe RA, Junck L, Kluin KJ, Lohman M, St. Laurent RT. Benzodiazepine receptor binding in cerebellar degenerations studied with positron emission tomography. Ann Neurol 1995;38:176–185.PubMedCrossRefGoogle Scholar
  96. 96.
    Shinotoh H, Inoue O, Hirayama K. Dopamine D1 receptors in Parkinson’s disease and striatonigral degeneration: a positron emission tomography study. J Neurol Neurosurg Psychiatry 1993;56:467–472.PubMedCrossRefGoogle Scholar
  97. 97.
    Schwarz J, Tatsch K, Arnold G, Ott M, Trenkwalder C, Kirsch CM, et al. 123I-iodobenzamide-SPECT in 83 patients with de novo parkinsonism. Neurology 1993;43(6):17–20.Google Scholar
  98. 98.
    Brücke T, Wenger S, Asenbaum S. Dopamine D2 receptor imaging and measurement with SPECT. Adv Neurol 1993;60:494–500.PubMedGoogle Scholar
  99. 99.
    Pirker W, Djamshidian S, Asenbaum S, Gerschlager W, Tribl G, Hoffmann M, et al. Progression of dopaminergic degeneration in Parkinson’s disease and atypical parkinsonism: a longitudinal beta-CIT SPECT study. Mov Disord 2002;17:45–53.PubMedCrossRefGoogle Scholar
  100. 100.
    Yoshita M. Differentiation of idiopathic Parkinson’s disease from striatonigral degeneration and progressive supranuclear palsy using iodine-123 meta-iodobenzylguanidine myocardial scintigraphy. J Neurol Sci 1998;155:60–67.PubMedCrossRefGoogle Scholar
  101. 101.
    Martinelli P, Coccagna G. Etude electromyographique du sphincter strie de l’anus dans trois cas de syndrome de Shy-Drager. In: Arbus L, Cadilhac J, eds. Electromyographie. Toulouse: Premieres Journees Languedociennes d’Electromyographie, 1978:321–326.Google Scholar
  102. 102.
    Eardley I, Quinn NP, Fowler CJ, Kirby RS, Parkhouse HF, Marsden CD, et al. The value of urethral sphincter electromyography in the differential diagnosis of parkinsonism. Br J Urol 1989;64:360–362.PubMedCrossRefGoogle Scholar
  103. 103.
    Pramstaller PP, Wenning GK, Smith SJ, Beck RO, Quinn NP, Fowler CJ. Nerve conduction studies, skeletal muscle EMG, and sphincter EMG in multiple system atrophy. J Neurol Neurosurg Psychiatry 1995;58(5): 618–621.PubMedGoogle Scholar
  104. 104.
    Palace J, Chandiramani VA, Fowler CJ. Value of sphincter electromyography in the diagnosis of multiple system atrophy. Muscle Nerve 1997;20(11):1396–1403.PubMedCrossRefGoogle Scholar
  105. 105.
    Tison F, Arne P, Sourgen C, Chrysostome V, Yeklef F. The value of external anal sphincter electromyography for the diagnosis of multiple system atrophy. Mov Disord 2000;15(6):1148–1157.PubMedCrossRefGoogle Scholar
  106. 106.
    Valldeoriola F, Valls-Sole J, Tolosa ES, Marti MJ. Striated anal sphincter denervation in patients with progressive supranuclear palsy. Mov Disord 1995;10(5):550–555.PubMedCrossRefGoogle Scholar
  107. 107.
    Giladi N, Simon ES, Korczyn AD, Groozman GB, Orlov Y, Shabtai H, et al. Anal sphincter EMG does not distinguish between multiple system atrophy and Parkinson’s disease. Muscle Nerve 2000;23: 731–734.PubMedCrossRefGoogle Scholar
  108. 108.
    Libelius R, Johannson F. Quantitative electromyography of the external anal sphincter in Parkinson’s disease and multiple system atrophy. Muscle Nerve 2000;23:1250–1256.PubMedCrossRefGoogle Scholar
  109. 109.
    Colosimo C, Inghilleri M, Chaudhuri KR. Parkinson’s disease misdiagnosed as multiple system atrophy by sphincter electromyography. J Neurol 2000;247:559–561.PubMedCrossRefGoogle Scholar
  110. 110.
    Vodusek B. Sphincter EMG and differential diagnosis of multiple system atrophy. Mov Disord 2001; 16(4):600–607.PubMedCrossRefGoogle Scholar
  111. 111.
    Wenning G, Smith SJM. Magnetic brain stimulation in multiple system atrophy. Mov Disord 1997; 12(3):452–453.PubMedCrossRefGoogle Scholar
  112. 112.
    Abbruzzese G, Marchese R, Trompetto C. Sensory and motor evoked potentials in multiple system atrophy: comparative study with Parkinson’s disease. Mov Disord 1997;12(3):315–321.PubMedCrossRefGoogle Scholar
  113. 113.
    Abele M, Schulz JB, Burk K, Topka H, Dichgans J, Klockgether T. Evoked potentials in multiple system atrophy (MSA). Acta Neurol Scand 2000;101(2):111–115.PubMedCrossRefGoogle Scholar
  114. 114.
    Delalande I, Hache JC, Forzy G, Bughin M, Benhadjali J, Destee A. Do visual-evoked potentials and spatiotemporal contrast sensitivity help to distinguish idiopathic Parkinson’s disease and multiple system atrophy? Mov Disord 1998;13(3):446–452.PubMedCrossRefGoogle Scholar
  115. 115.
    Montagna P, Martinelli P, Rizzuto N, Salviati A, Rasi F, Lugaresi E. Amyotrophy in Shy-Drager syndrome. Acta Neurol Belg 1983;83:142–157.PubMedGoogle Scholar
  116. 116.
    Cohen J, Low P, Fealey R, Sheps S, Jiang NS. Somatic and autonomic function in progressive autonomic failure and multiple system atrophy. Ann Neurol 1987;22:692–699.PubMedCrossRefGoogle Scholar
  117. 117.
    Abele M, Schulz J, Burk K, Topka H, Dichgans J, Klockgether T. Nerve conduction studies in multiple system atrophy. Eur Neurol 2000;43(4):221–223.PubMedCrossRefGoogle Scholar
  118. 118.
    Kofler M, Muller J, Wenning GK, Reggiani L, Hollosi P, Bosch S, et al. The auditory startle reaction in parkinsonian disorders. Mov Disord 2001;16(1):62–71.PubMedCrossRefGoogle Scholar
  119. 119.
    Kofler M, Muller J, Seppi K, Wenning GK. Exaggerated auditory startle responses in multiple system atrophy: a comparative study of parkinson and cerebellar subtypes. Clin Neurophysiol 2003;114(3):541–547.PubMedCrossRefGoogle Scholar
  120. 120.
    Kume A, Takahashi A, Hashizume Y. Neuronal cell loss of the striatonigral system in multiple system atrophy. J Neurol Sci 1993;117:33–40.PubMedCrossRefGoogle Scholar
  121. 121.
    Sung J, Mastri A, Segal E. Pathology of Shy-Drager syndrome. J Neuropathol Exp Neurol 1979;38: 353–368.PubMedGoogle Scholar
  122. 122.
    Benarroch EE, Smithson IL, Low PA, Parisi JE. Depletion of catecholaminergic neurons of the rostral ventrolateral medulla in multiple systems atrophy with autonomic failure. Ann Neurol 1998;43(2): 156–163.PubMedCrossRefGoogle Scholar
  123. 123.
    Shy G, Drager GA. A neurological syndrome associated with orthostatic hypotension. A clinicopathological study. Arch Neurol 1960;2:511–527.PubMedGoogle Scholar
  124. 124.
    Nakamura S, Ohnishi K, Nishimura M, Suenaga T, Akiguchi I, Kimura J, et al. Large neurons in the tuberomammillary nucleus in patients with Parkinson’s disease and multiple system atrophy. Neurology 1996; 46(6):1693–1696.PubMedGoogle Scholar
  125. 125.
    Papp M, Lantos PL. The distribution of oligodendroglial inclusions in multiple system atrophy and its relevance to clinical symptomatology. Brain 1994;117:235–243.PubMedCrossRefGoogle Scholar
  126. 126.
    Konno H, Yamamoto T, Iwasaki Y, Iizuka H. Shy-Drager syndrome and amyotrophic lateral sclerosis. Cytoarchitectonic and morphometric studies of sacral autonomic neurons. J Neurol Sci 1986;73(2): 193–204.PubMedCrossRefGoogle Scholar
  127. 127.
    Daniel S. The neuropathology and neurochemistry of multiple system atrophy. In: Mathias C, Bannister R, eds. Autonomic Failure: A Textbook of Clinical Disorders of the Autonomic Nervous System. Oxford: Oxford University Press, 1999:321–328.Google Scholar
  128. 128.
    Oppenheimer DR. Lateral horn cells in progressive autonomic failure. J Neurol Sci 1980;46(3): 393–404.PubMedCrossRefGoogle Scholar
  129. 129.
    Bannister R, Oppenheimer D. Degenerative diseases of the nervous system associated with autonomic failure. Brain 1972;95:457–474.PubMedCrossRefGoogle Scholar
  130. 130.
    Tsuchiya K, Ozawa E, Haga C, Watabiki S, Ikeda M, Sano M, et al. Constant involvement of the Betz cells and pyramidal tract in multiple system atrophy: a clinicopathological study of seven autopsy cases. Acta Neuropathol (Berl) 2000;99:628–636.CrossRefGoogle Scholar
  131. 131.
    Wakabayashi K, Ikeuchi T, Ishikawa A, Takahashi H. Multiple system atrophy with severe involvement of the motor cortical areas and cerebral white matter. J Neurol Sci 1998; 156(1): 114–117.PubMedCrossRefGoogle Scholar
  132. 132.
    Konagaya M, Sakai M, Matsuoka Y, Konagaya Y, Hashizume Y. Multiple system atrophy with remarkable frontal lobe atrophy. Acta Neuropathol (Berl) 1999;97(4):423–428.CrossRefGoogle Scholar
  133. 133.
    Sima A, Caplan M, D’Amato CJ, Pevzner M, Furlong JW. Fulminant multiple system atrophy in a young adult presenting as motor neuron disease. Neurology 1993;43:2031–2035.PubMedGoogle Scholar
  134. 134.
    Hayashi M, Isozaki E, Oda M, Tanabe H, Kimura J. Loss of large myelinated nerve fibres of the recurrent laryngeal nerve in patients with multiple system atrophy and vocal cord palsy. J Neurol Neurosurg Psychiatry 1997; 62:234–238.PubMedGoogle Scholar
  135. 135.
    Braak H, Braak E. Cortical and subcortical argyrophilic grains characterize a disease associated with adult onset dementia. Neuropathol Appl Neurobiol 1989;15(1):13–26.PubMedGoogle Scholar
  136. 136.
    Yamada T, McGeer PL. Oligodendroglial microtubular masses: an abnormality observed in some human neurodegenerative diseases. Neurosci Lett 1990;120:163–166.PubMedCrossRefGoogle Scholar
  137. 137.
    Arima K, Nakamura M, Sunohara N, Ogawa M, Anno M, Izumiyama Y, et al. Ultrastructural characterization of the tau-immunoreactive tubules in the oligodendroglial perikarya and their inner loop processes in progressive supranuclear palsy. Acta Neuropathol (Berl) 1997;93(6):558–566.CrossRefGoogle Scholar
  138. 138.
    Chin SS, Goldman JE. Glial inclusions in CNS degenerative diseases. J Neuropathol Exp Neurol 1996; 55(5):499–508.PubMedGoogle Scholar
  139. 139.
    Wenning G, Quinn N. Are Lewy bodies non-specific epiphenomena of nigral damage? Mov Disord 1994; 9(3):378–379.PubMedCrossRefGoogle Scholar
  140. 140.
    Papp M, Kahn JE, Lantos PL. Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome). J Neurol Sci 1989;94: 79–100.PubMedCrossRefGoogle Scholar
  141. 141.
    Lantos PL. The definition of multiple system atrophy: a review of recent developments. J Neuropathol Exp Neurol 1998;57(12):1099–1111.PubMedCrossRefGoogle Scholar
  142. 142.
    Gai WP, Pountney DL, Power JH, Li QX, Culvenor JG, McLean CA, et al. alpha-Synuclein fibrils constitute the central core of oligodendroglial inclusion filaments in multiple system atrophy. Exp Neurol 2003;181(1): 68–78.PubMedCrossRefGoogle Scholar
  143. 143.
    Papp M, Lantos PI. Accumulation of tubular structures in oligodendroglial and neuronal cells as the basic alteration in multiple system atrophy. J Neurol Sci 1992;107:172–182.PubMedCrossRefGoogle Scholar
  144. 144.
    Cairns NJ, Atkinson PF, Hanger DP, Anderton BH, Daniel SE, Lantos PL. Tau protein in the glial cytoplasmic inclusions of multiple system atrophy can be distinguished from abnormal tau in Alzheimer’s disease. Neurosci Lett 1997;230(1):49–52.PubMedCrossRefGoogle Scholar
  145. 145.
    Dickson DW, Lin W, Liu WK, Yen SH. Multiple system atrophy: a sporadic synucleinopathy. Brain Pathol 1999;9(4):721–732.PubMedCrossRefGoogle Scholar
  146. 146.
    Goedert M, Spillantini MG. Lewy body diseases and multiple system atrophy as alpha-synucleinopathies. Mol Psychiatry 1998;3(6):462–465.PubMedCrossRefGoogle Scholar
  147. 147.
    Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M. Alpha-synuclein in Lewy bodies. Nature 1997;388(6645):839–840.PubMedCrossRefGoogle Scholar
  148. 148.
    Wakabayashi K, Yoshimoto M, Tsuji S, Takahashi H. Alpha-synuclein immunoreactivity in glial cytoplasmic inclusions in multiple system atrophy. Neurosci Lett 1998;249(2-3):180–182.PubMedCrossRefGoogle Scholar
  149. 149.
    Wakabayashi K, Hayashi S, Kakita A, Yamada M, Toyoshima Y, Yoshimoto M, et al. Accumulation of alpha-synuclein/NACP is a cytopathological feature common to Lewy body disease and multiple system atrophy. Acta Neuropathol (Berl) 1998;96:445–452.CrossRefGoogle Scholar
  150. 150.
    Arima K, Ueda K, Sunohara N, Arakawa K, Hirai S, Nakamura M, et al. NACP/alpha-synuclein immunoreactivity in fibrillary components of neuronal and oligodendroglial cytoplasmic inclusions in the pontine nuclei in multiple system atrophy. Acta Neuropathol (Berl) 1998;96:439–444.CrossRefGoogle Scholar
  151. 151.
    Tu P, Galvin JE, Baba M, Giasson B, Tomita T, Leight S, et al. Glial cytoplasmic inclusions in white matter oligodendrocytes of multiple system atrophy brains contain insoluble alpha-synuclein. Ann Neurol 1998; 44(3): 415–422.PubMedCrossRefGoogle Scholar
  152. 152.
    Spillantini MG, Crowther RA, Jakes R, Cairns NJ, Lantos PL, Goedert M. Filamentous alpha-synuclein inclusions link multiple system atrophy with Parkinson’s disease and dementia with Lewy bodies. Neurosci Lett 1998;251(3):205–208.PubMedCrossRefGoogle Scholar
  153. 153.
    Trojanowski JQ. Tauists, Baptists, Syners, Apostates, and new data. Ann Neurol 2002;52(3): 263–265.PubMedCrossRefGoogle Scholar
  154. 154.
    Gai WP, Power JH, Blumbergs PC, Blessing WW. Multiple-system atrophy: a new alpha-synuclein disease? Lancet 1998;352(9127):547–548.PubMedCrossRefGoogle Scholar
  155. 155.
    Hirsch EC, Hunot S, Damier P, Faucheux B. Glial cells and inflammation in Parkinson’s disease: a role in neurodegeneration? Ann Neurol 1998;44(3 Suppl 1): S115–S120.PubMedGoogle Scholar
  156. 156.
    Togo T, Iseki E, Marui W, Akiyama H, Ueda K, Kosaka K. Glial involvement in the degeneration process of Lewy body-bearing neurons and the degradation process of Lewy bodies in brains of dementia with Lewy bodies. J Neurol Sci 2001;184(1):71–75.PubMedCrossRefGoogle Scholar
  157. 157.
    Vila M, Jackson-Lewis V, Guegan C, Wu DC, Teismann P, Choi DK, et al. The role of glial cells in Parkinson’s disease. Curr Opin Neurol 2001;14(4):483–489.PubMedCrossRefGoogle Scholar
  158. 158.
    Allan SM, Rothwell NJ. Cytokines and acute neurodegeneration. Nat Rev Neurosci 2001;2(10): 734–744.PubMedCrossRefGoogle Scholar
  159. 159.
    Boka G, Anglade P, Wallach D, Javoy-Agid F, Agid Y, Hirsch EC. Immunocytochemical analysis of tumor necrosis factor and its receptors in Parkinson’s disease. Neurosci Lett 1994;172(1-2):151–154.PubMedCrossRefGoogle Scholar
  160. 160.
    Hunot S, Dugas N, Faucheux B, Hartmann A, Tardieu M, Debre P, et al. FcepsilonRII/CD23 is expressed in Parkinson’s disease and induces, in vitro, production of nitric oxide and tumor necrosis factor-alpha in glial cells. J Neurosci 1999;19(9):3440–3447.PubMedGoogle Scholar
  161. 161.
    Mogi M, Harada M, Riederer P, Narabayashi H, Fujita K, Nagatsu T. Tumor necrosis factor-alpha (TNF-alpha) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients. Neurosci Lett 1994; 165(1-2):208–210.PubMedCrossRefGoogle Scholar
  162. 162.
    McGuire SO, Ling ZD, Lipton JW, Sortwell CE, Collier TJ, Carvey PM. Tumor necrosis factor alpha is toxic to embryonic mesencephalic dopamine neurons. Exp Neurol 2001;169(2):219–230.PubMedCrossRefGoogle Scholar
  163. 163.
    Aloe L, Fiore M. TNF-alpha expressed in the brain of transgenic mice lowers central tyroxine hydroxylase immunore-activity and alters grooming behavior. Neurosci Lett 1997;238(1-2):65–68.PubMedCrossRefGoogle Scholar
  164. 164.
    Gerhard A, Banati RB, Goerres GB, Cagnin A, Myers R, Gunn RN, et al. [(11)C](R)-PK11195 PET imaging of microglial activation in multiple system atrophy. Neurology 2003;61(5):686–689.PubMedGoogle Scholar
  165. 165.
    Wenning G, Granata R, Laboyrie PM, Quinn NP, Jenner P, Marsden CD. Reversal of behavioural abnormalities by fetal allografts in a novel rat model of striatonigral degeneration. Mov Disord 1996;11(5):522–532.PubMedCrossRefGoogle Scholar
  166. 166.
    Wenning G, Granata R, Puschban Z, Scherfler C, Poewe W. Neural transplantation in animal models of multiple system atrophy: a review. J Neural Transm 1999;55:103–113.Google Scholar
  167. 167.
    Scherfler C, Puschban Z, Ghorayeb I, Goebel GP, Tison F, Jellinger K, et al. Complex motor disturbances in a sequential double lesion rat model of striatonigral degeneration (multiple system atrophy). Neuroscience 2000; 99(1):43–54.PubMedCrossRefGoogle Scholar
  168. 168.
    Ghorayeb I, Puschban Z, Fernagut PO, Scherfler C, Rouland R, Wenning GK, et al. Simultaneous intrastriatal 6-hydroxydopamine and quinolinic acid injection: a model of early-stage striatonigral degeneration. Exp Neurol 2001;167(1):133–147.PubMedCrossRefGoogle Scholar
  169. 169.
    Waldner R, Puschban Z, Scherfler C, Seppi K, Jellinger K, Poewe W, et al. No functional effects of embryonic neuronal grafts on motor deficits in a 3-nitropropionic acid rat model of advanced striatonigral degeneration (multiple system atrophy). Neuroscience 2001;102(3):581–592.PubMedCrossRefGoogle Scholar
  170. 170.
    Ghorayeb I, Fernagut PO, Hervier L, Labattu B, Bioulac B, Tison F. A “single toxin-double lesion” rat model of striatonigral degeneration by intrastriatal 1-methyl-4-phenylpyridinium ion injection: a motor behavioural analysis. Neuroscience 2002;115(2):533–546.PubMedCrossRefGoogle Scholar
  171. 171.
    Stefanova N, Puschban Z, Fernagut PO, Brouillet E, Tison F, Reindl M, et al. Neuropathological and behavioral changes induced by various treatment paradigms with MPTP and 3-nitropropionic acid in mice: towards a model of striatonigral degeneration (multiple system atrophy). Acta Neuropathol (Berl) 2003;106(2):157–166.CrossRefGoogle Scholar
  172. 172.
    Fernagut PO, Diguet E, Bioulac B, Tison F. MPTP potentiates 3-nitropronionic acid-induced striatal damage in mice: reference to striatonigral degeneration. Exp Neurol. 2004;185(1):47–62.PubMedCrossRefGoogle Scholar
  173. 173.
    Ghorayeb I, Fernagut PO, Aubert I, Bezard E, Poewe W, Wenning GK, et al. Toward a primate model of L-dopaunresponsive parkinsonism mimicking striatonigral degeneration. Mov Disord 2000;15(3):531–536.PubMedCrossRefGoogle Scholar
  174. 174.
    Ghorayeb I, Fernagut PO, Stefanova N, Wenning GK, Bioulac B, Tison F. Dystonia is predictive of subsequent altered dopaminergic responsiveness in a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine+3-nitropropionic acid model of striatonigral degeneration in monkeys. Neurosci Lett 2002;335(1):34–38.PubMedCrossRefGoogle Scholar
  175. 175.
    Kahle PJ, Neumann M, Ozmen L, Muller V, Jacobsen H, Spooren W, et al. Hyperphosphorylation and insolubility of alpha-synuclein in transgenic mouse oligodendrocytes. EMBO Rep 2002;3(6):583–588.PubMedCrossRefGoogle Scholar
  176. 176.
    Zuscik M, Sands S, Ross SA, Waugh DJJ, Gaivin RJ, Morilak D, et al. Overexpression of the alpha1B-adrenergic receptor causes apoptotic neurodegeneration: multiple system atrophy. Nat Med 2000;6(12):1388–1394.PubMedCrossRefGoogle Scholar
  177. 177.
    Puschban Z, Scherfler C, Granata R, Laboyrie P, Quinn NP, Jenner P, et al. Autoradiographic study of striatal dopamine re-uptake sites and dopamine D1 and D2 receptors in a 6-hydroxydopamine and quinolinic acid double-lesion rat model of striatonigral degeneration (multiple system atrophy) and effects of embryonic ventral mesencephalic, striatal or cografts. Neuroscience 2000;95(2):377–388.PubMedCrossRefGoogle Scholar
  178. 178.
    Jankovic J, Gilden JL, Hiner BC, Kaufmann H, Brown DC, Coghlan CH, et al. Neurogenic orthostatic hypotension: a double-blind, placebo-controlled study with midodrine. Am J Med 1993;95(1):38–48.PubMedCrossRefGoogle Scholar
  179. 179.
    Low PA, Gilden JL, Freeman R, Sheng KN, McElligott MA. Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension. A randomized, double-blind multicenter study. Midodrine Study Group. JAMA 1997; 277(13):1046–1051.PubMedCrossRefGoogle Scholar
  180. 180.
    Wright RA, Kaufmann HC, Perera R, Opfer-Gehrking TL, McElligott MA, Sheng KN et al. A double-blind, doseresponse study of midodrine in neurogenic orthostatic hypotension. Neurology 1998;51(1):120–124.PubMedGoogle Scholar
  181. 181.
    Mathias CJ, Senard JM, Braune S, Watson L, Aragishi A, Keeling JE, et al. L-threo-dihydroxyphenylserine (L-threo-DOPS; droxidopa) in the management of neurogenic orthostatic hypotension: a multi-national, multi-center, doseranging study in multiple system atrophy and pure autonomic failure. Clin Auton Res 2001;11(4): 235–242.PubMedCrossRefGoogle Scholar
  182. 182.
    Alam M, Smith G, Bleasdale-Barr K, Pavitt DV, Mathias CJ. Effects of the peptide release inhibitor, octreotide, on daytime hypotension and on nocturnal hypertension in primary autonomic failure. J Hypertens 1995; 13(12 Pt 2):1664–1669.PubMedGoogle Scholar
  183. 183.
    Raimbach SJ, Cortelli P, Kooner JS, Bannister R, Bloom SR, Mathias CJ. Prevention of glucose-induced hypotension by the somatostatin analogue octreotide (SMS 201-995) in chronic autonomic failure: haemodynamic and hormonal changes. Clin Sci (Lond) 1989;77(6):623–628.Google Scholar
  184. 184.
    Mathias CJ, Fosbraey P, da Costa DF, Thornley A, Bannister R. The effect of desmopressin on nocturnal polyuria, overnight weight loss, and morning postural hypotension in patients with autonomic failure. Br Med J (Clin Res Ed) 1986;293(6543):353–354.Google Scholar
  185. 185.
    Perera R, Isola L, Kaufmann H. Effect of recombinant erythropoietin on anemia and orthostatic hypotension in primary autonomic failure. Clin Auton Res 1995;5(4):211–213.PubMedCrossRefGoogle Scholar
  186. 186.
    Winkler A, Marsden J, Parton M, Watkins P, Chaudhuri K. Erythropoietin deficiency and anaemia in multiple system atrophy. Mov Disord 2001;16:233–239.PubMedCrossRefGoogle Scholar
  187. 187.
    Mathias C, Kimber JR. Postural hypotension: causes, clinical features, investigation, and management. Annu Rev Med 1999;50:317–326.PubMedCrossRefGoogle Scholar
  188. 188.
    Sakakibara R, Hattori T, Uchiyama T, Suenaga T, Takahashi H, Yamanishi T, et al. Are alpha-blockers involved in lower urinary tract dysfunction in multiple system atrophy? A comparison of prazosin and moxisylyte. J Auton Nerv Syst 2000;79:191–195.PubMedCrossRefGoogle Scholar
  189. 189.
    Colosimo C, Pezzella FR. The symptomatic treatment of multiple system atrophy. Eur J Neurol 2002; 9(3):195–199.PubMedCrossRefGoogle Scholar
  190. 190.
    Zesiewicz T, Helal M, Hauser RA. Sildenafil Citrate (Viagra) for the treatment of erectile dysfunction in men with Parkinson’s disease. Mov Disord 2000;15(2):305–308.PubMedCrossRefGoogle Scholar
  191. 191.
    Hussain IF, Brady CM, Swinn MJ, Mathias CJ, Fowler CJ. Treatment of erectile dysfunction with sildenafil citrate (Viagra) in parkinsonism due to Parkinson’s disease or multiple system atrophy with observations on orthostatic hypotension. J Neurol Neurosurg Psychiatry 2001;71(3):371–374.PubMedCrossRefGoogle Scholar
  192. 192.
    Eichhorn TE, Oertel WH. Macrogol 3350/electrolyte improves constipation in Parkinson’s disease and multiple system atrophy. Mov Disord 2001;16(6):1176–1177.PubMedCrossRefGoogle Scholar
  193. 193.
    Iranzo A, Santamaria J, Tolosa E, Barcelona Multiple System Atrophy Study Group. Continuous positive air pressure eliminates nocturnal stridor in multiple system atrophy. Lancet 2000;356:1329–1330.PubMedCrossRefGoogle Scholar
  194. 194.
    Lees A. The treatment of the motor disorder of multiple system atrophy. In: Mathias C, Bannister R, eds. Autonomic Failure. Oxford: Oxford University Press, 1999:357–363.Google Scholar
  195. 195.
    Lees A, Bannister R. The use of lisuride in the treatment of multiple system atrophy with autonomic failure (Shy-Drager syndrome). J Neurol Neurosurg Psychiatry 1981;44:347–351.PubMedGoogle Scholar
  196. 196.
    Colosimo C, Merello M, Pontieri FE. Amantadine in parkinsonian patients unresponsive to levodopa: a pilot study. J Neurol 1996;243(5):422–425.PubMedCrossRefGoogle Scholar
  197. 197.
    Lang AE, Lozano A, Duff J, Tasker R, Miyasaki J, Galvez-Jimenez N, et al. Medial pallidotomy in late-stage Parkinson’s disease and striatonigral degeneration. Adv Neurol 1997;74:199–211.PubMedGoogle Scholar
  198. 198.
    Visser-Vandewalle V, Temel Y, Colle H, van der LC. Bilateral high-frequency stimulation of the subthalamic nucleus in patients with multiple system atrophy—parkinsonism. Report of four cases. J Neurosurg 2003; 98(4):882–887.PubMedGoogle Scholar
  199. 199.
    Graham J, Oppenheimer DR. Orthostatic-hypotension and nicotine sensitivity in a case of multiple system atrophy. J Neurol Neurosurg Psychiatry 1969;32:28–34.PubMedGoogle Scholar
  200. 200.
    Johnsen J, Miller VT. Tobacco intolerance in multiple system atrophy. Neurology 1986;36: 986–988.PubMedGoogle Scholar
  201. 201.
    Wenning GK, Seppi K, Sampaio C, Quinn NP, Poewe W, Tison F. European Multiple System Atrophy Study Group (EMSA-SG): Validation of the Unified MSA Rating Scale (UMSARS). Mov Disord 2002;17(Suppl 5):252.Google Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2005

Authors and Affiliations

  • Felix Geser
    • 1
  • Gregor K. Wenning
    • 1
  1. 1.Department of NeurologyUniversity HospitalInnsbruckAustria

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