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Multiple System Atrophy - State of the Art

  • Movement Disorders (S Fox, Section Editor)
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Abstract

Multiple system atrophy (MSA) is a rare and fatal neurodegenerative disorder that is characterized by a variable combination of parkinsonism, cerebellar impairment, and autonomic dysfunction. Some symptomatic treatments are available while neuroprotection or disease-modification remain unmet treatment needs. The pathologic hallmark is the accumulation of aggregated alpha-synuclein (α-syn) in oligodendrocytes forming glial cytoplasmic inclusions, which qualifies MSA as synucleinopathy together with Parkinson’s disease and dementia with Lewy bodies. Despite progress in our understanding of the pathogenesis of MSA, the origin of α-syn aggregates in oligodendrocytes is still a matter of an ongoing debate. We critically review here studies published in the field over the past 5 years dealing with pathogenesis, genetics, clinical signs, biomarker for improving diagnostic accuracy, and treatment development.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology. 2008;71(9):670–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Fernagut PO, Dehay B, Maillard A, Bezard E, Perez P, Pavy-Le Traon A, et al. Multiple system atrophy: a prototypical synucleinopathy for disease-modifying therapeutic strategies. Neurobiol Dis. 2014;67:133–9.

    Article  PubMed  Google Scholar 

  3. Papp MI, 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(1/3):79–100.

    Article  CAS  PubMed  Google Scholar 

  4. Papp MI, Lantos PL. The distribution of oligodendroglial inclusions in multiple system atrophy and its relevance to clinical symptomatology. Brain. 1994;117(Pt 2):235–43.

    Article  PubMed  Google Scholar 

  5. 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):205–8.

    Article  CAS  PubMed  Google Scholar 

  6. Salvesen L, Ullerup BH, Sunay FB, Brudek T, Lokkegaard A, Agander TK, et al. Changes in total cell numbers of the basal ganglia in patients with multiple system atrophy—a stereological study. Neurobiol Dis. 2015;74:104–13.

    Article  PubMed  Google Scholar 

  7. Cykowski MD, Coon EA, Powell SZ, Jenkins SM, Benarroch EE, Low PA, et al. Expanding the spectrum of neuronal pathology in multiple system atrophy. Brain. 2015;138(Pt 8):2293–309.

    Article  PubMed  PubMed Central  Google Scholar 

  8. • Asi YT, Simpson JE, Heath PR, Wharton SB, Lees AJ, Revesz T, et al. Alpha-synuclein mRNA expression in oligodendrocytes in MSA. Glia. 2014;62(6):964–70. SNCA gene expression was assessed in several brain regions in patients with MSA, PD and healthy controls. Highest expression was found in the cortex and lowest in the putamen, with no differences observed between groups. SNCA expression was similarly found in neurons and oligodendrocytes.

    Article  PubMed  PubMed Central  Google Scholar 

  9. • May VE, Ettle B, Poehler AM, Nuber S, Ubhi K, Rockenstein E, et al. alpha-Synuclein impairs oligodendrocyte progenitor maturation in multiple system atrophy. Neurobiol Aging. 2014;35(10):2357–68. Post-mortem study describing α-syn deposits in OPCs and an increased number of striatal OPCs in MSA patients.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. • Djelloul M, Holmqvist S, Boza-Serrano A, Azevedo C, Yeung MS, Goldwurm S, et al. Alpha-synuclein expression in the oligodendrocyte lineage: an in vitro and in vivo study using rodent and human models. Stem Cell Reports. 2015;5(2):174–84. Comprehensive in-vitro characterization showing α-syn protein and its transcripts in oligodendrocytes generated from mouse and human embryonic stem cells, in induced pluripotent stem cells derived from fibroblasts of MSA patients and in oligodendrocytes of adult MSA brains.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Reyes JF, Rey NL, Bousset L, Melki R, Brundin P, Angot E. Alpha-synuclein transfers from neurons to oligodendrocytes. Glia. 2014;62(3):387–98.

    Article  PubMed  Google Scholar 

  12. Kisos H, Pukass K, Ben-Hur T, Richter-Landsberg C, Sharon R. Increased neuronal alpha-synuclein pathology associates with its accumulation in oligodendrocytes in mice modeling alpha-synucleinopathies. PLoS One. 2012;7(10), e46817.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Dehay B, Bourdenx M, Gorry P, Przedborski S, Vila M, Hunot S, et al. Targeting alpha-synuclein for treatment of Parkinson's disease: mechanistic and therapeutic considerations. Lancet Neurol. 2015;14(8):855–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Watts JC, Giles K, Oehler A, Middleton L, Dexter DT, Gentleman SM, et al. Transmission of multiple system atrophy prions to transgenic mice. Proc Natl Acad Sci USA. 2013;110(48):19555–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Prusiner SB, Woerman AL, Mordes DA, Watts JC, Rampersaud R, Berry DB, et al. Evidence for alpha-synuclein prions causing multiple system atrophy in humans with parkinsonism. Proc Natl Acad Sci U S A. 2015;112(38):E5308–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Peelaerts W, Bousset L, Van der Perren A, Moskalyuk A, Pulizzi R, Giugliano M, et al. α-Synuclein strains cause distinct synucleinopathies after local and systemic administration. Nature. 2015;522(7556):340–4.

    Article  CAS  PubMed  Google Scholar 

  17. Ahmed Z, Asi YT, Lees AJ, Revesz T, Holton JL. Identification and quantification of oligodendrocyte precursor cells in multiple system atrophy, progressive supranuclear palsy and Parkinson's disease. Brain Pathol. 2013;23(3):263–73.

    Article  PubMed  Google Scholar 

  18. Song YJ, Lundvig DM, Huang Y, Gai WP, Blumbergs PC, Hojrup P, et al. p25alpha relocalizes in oligodendroglia from myelin to cytoplasmic inclusions in multiple system atrophy. Am J Pathol. 2007;171(4):1291–303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ota K, Obayashi M, Ozaki K, Ichinose S, Kakita A, Tada M, et al. Relocation of p25alpha/tubulin polymerization promoting protein from the nucleus to the perinuclear cytoplasm in the oligodendroglia of sporadic and COQ2 mutant multiple system atrophy. Acta Neuropathol Commun. 2014;2:136.

    PubMed  PubMed Central  Google Scholar 

  20. Vieira BD, Radford RA, Chung RS, Guillemin GJ, Pountney DL. Neuroinflammation in multiple system atrophy: response to and cause of alpha-synuclein aggregation. Front Cell Neurosci. 2015;9:437.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Radford R, Rcom-H'cheo-Gauthier A, Wong MB, Eaton ED, Quilty M, Blizzard C, et al. The degree of astrocyte activation in multiple system atrophy is inversely proportional to the distance to alpha-synuclein inclusions. Mol Cell Neurosci. 2015;65:68–81.

    Article  CAS  PubMed  Google Scholar 

  22. Jellinger KA. Interaction between pathogenic proteins in neurodegenerative disorders. J Cell Mol Med. 2012;16(6):1166–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Pukass K, Goldbaum O, Richter-Landsberg C. Mitochondrial impairment and oxidative stress compromise autophagosomal degradation of alpha-synuclein in oligodendroglial cells. J Neurochem. 2015;135(1):194–205.

    Article  CAS  PubMed  Google Scholar 

  24. Bassil F, Canron MH, Vital A, Bezard E, Yazhou L, Greig NH, et al. Insulin resistance and exendin-4 treatment for multiple system atrophy. Brain. 2017; doi:10.1093/brain/awx044.

  25. • Multiple-system atrophy research collaboration. Mutations in COQ2 in familial and sporadic multiple-system atrophy. N Engl J Med. 2013;369(3):233–44. Description of a homozygous mutation and compound heterozygous mutations in the COQ2 gene in two multiplex families with MSA. Additional studies including cohorts from Asia have not confirmed or only partly replicated these findings.

    Article  Google Scholar 

  26. Schottlaender LV, Houlden H, Multiple-System Atrophy Brain Bank C. Mutant COQ2 in multiple-system atrophy. N Engl J Med. 2014;371(1):81.

    CAS  PubMed  Google Scholar 

  27. Jeon BS, Farrer MJ, Bortnick SF, Korean Canadian Alliance on Parkinson's disease, related disease. Mutant COQ2 in multiple-system atrophy. N Engl J Med. 2014;371(1):80.

    Article  CAS  PubMed  Google Scholar 

  28. Sharma M, Wenning G, Kruger R. European multiple-system atrophy study, G. Mutant COQ2 in multiple-system atrophy. N Engl J Med. 2014;371(1):80–1.

    Article  CAS  PubMed  Google Scholar 

  29. Ogaki K, Fujioka S, Heckman MG, Rayaprolu S, Soto-Ortolaza AI, Labbe C, et al. Analysis of COQ2 gene in multiple system atrophy. Mol Neurodegener. 2014;9:44.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Lin CH, Tan EK, Yang CC, Yi Z, Wu RM. COQ2 gene variants associate with cerebellar subtype of multiple system atrophy in Chinese. Mov Disord. 2015;30(3):436–7.

    Article  CAS  PubMed  Google Scholar 

  31. Sun Z, Ohta Y, Yamashita T, Sato K, Takemoto M, Hishikawa N, et al. New susceptible variant of COQ2 gene in Japanese patients with sporadic multiple system atrophy. Neurol Genet. 2016;2(2), e54.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Ronchi D, Di Biase E, Franco G, Melzi V, Del Sorbo F, Elia A, et al. Mutational analysis of COQ2 in patients with MSA in Italy. Neurobiol Aging. 2016;45:213. e1-2.

  33. Barca E, Kleiner G, Tang G, Ziosi M, Tadesse S, Masliah E, et al. Decreased coenzyme Q10 levels in multiple system atrophy cerebellum. J Neuropathol Exp Neurol. 2016;75(7):663–72.

    Article  PubMed  Google Scholar 

  34. Schottlaender LV, Bettencourt C, Kiely AP, Chalasani A, Neergheen V, Holton JL, et al. Coenzyme Q10 levels are decreased in the cerebellum of multiple-system atrophy patients. PLoS One. 2016;11(2), e0149557.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Mitsui J, Matsukawa T, Sasaki H, Yabe I, Matsushima M, Durr A, et al. Variants associated with Gaucher disease in multiple system atrophy. Ann Clin Transl Neurol. 2015;2(4):417–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Sun Z, Jiang H, Jiao B, Hou X, Shen L, Xia K, et al. C9orf72 hexanucleotide expansion analysis in Chinese patients with multiple system atrophy. Parkinsonism Relat Disord. 2015;21(7):811–2.

    Article  PubMed  Google Scholar 

  37. Chelban V, Manole A, Pihlstrom L, Schottlaender L, Efthymiou S, Connor EO, et al. Analysis of the prion protein gene in multiple system atrophy. Neurobiol Aging. 2017;49:216 e15–e18.

    Article  Google Scholar 

  38. Scholz SW, Majounie E, Revesz T, Holton JL, Okun MS, Houlden H, et al. Multiple system atrophy is not caused by C9orf72 hexanucleotide repeat expansions. Neurobiol Aging. 2015;36(2):1223 e1–2.

    Article  Google Scholar 

  39. Chen X, Chen Y, Wei Q, Ou R, Cao B, Zhao B, et al. C9ORF72 repeat expansions in Chinese patients with Parkinson's disease and multiple system atrophy. J Neural Transm (Vienna). 2016.

  40. • Sailer A, Scholz SW, Nalls MA, Schulte C, Federoff M, Price TR, et al. A genome-wide association study in multiple system atrophy. Neurology. 2016;87(15):1591–8. Largest GWAS including 918 MSA patients. No association was found for any of the assessed genes, which may partly be explained by the still relatively low number of assessed cases. Several loci were identified for future follow-up in larger sample series including the genes FBXO47, ELOVL7, EDN1 and MAPT.

  41. Pavy-Le Traon A, Piedvache A, Perez-Lloret S, Calandra-Buonaura G, Cochen-De Cock V, Colosimo C, et al. New insights into orthostatic hypotension in multiple system atrophy: a European multicentre cohort study. J Neurol Neurosurg Psychiatry. 2016;87(5):554–61.

    Article  CAS  PubMed  Google Scholar 

  42. • Giannini G, Calandra-Buonaura G, Mastrolilli F, Righini M, Bacchi-Reggiani ML, Cecere A, et al. Early stridor onset and stridor treatment predict survival in 136 patients with MSA. Neurology. 2016;87(13):1375–83. Large retrospective series of 136 MSA patients among whom 42 presented with stridor. Patients with stridor onset within the first three years showed shorter survival. Thirty-one patients were treated with tracheotomy or continous positive airway pressure (CPAP). Treatment had a positive effect on survival with tracheotomy being more effective than CPAP.

    Article  PubMed  Google Scholar 

  43. Flabeau O, Ghorayeb I, Perez P, Maillard A, Taillard J, Philip P, et al. Impact of sleep apnea syndrome on survival in patients with multiple system atrophy. Parkinsonism Relat Disord. 2017;35:92–95.

  44. Wang Y, Shao WB, Gao L, Lu J, Gu H, Sun LH, et al. Abnormal pulmonary function and respiratory muscle strength findings in Chinese patients with Parkinson's disease and multiple system atrophy—comparison with normal elderly. PLoS One. 2014;9(12), e116123.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Teive HA, Arruda WO, Moro A, Moscovich M, Munhoz RP. Differential diagnosis of sporadic adult-onset ataxia: the role of REM sleep behavior disorder. Parkinsonism Relat Disord. 2015;21(6):640–3.

    Article  PubMed  Google Scholar 

  46. Jecmenica-Lukic M, Poewe W, Tolosa E, Wenning GK. Premotor signs and symptoms of multiple system atrophy. Lancet Neurol. 2012;11(4):361–8.

    Article  PubMed  Google Scholar 

  47. Kass-Iliyya L, Kobylecki C, McDonald KR, Gerhard A, Silverdale MA. Pain in multiple system atrophy and progressive supranuclear palsy compared to Parkinson's disease. Brain Behav. 2015;5(5), e00320.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Stankovic I, Krismer F, Jesic A, Antonini A, Benke T, Brown RG, et al. Cognitive impairment in multiple system atrophy: a position statement by the Neuropsychology Task Force of the MDS Multiple System Atrophy (MODIMSA) study group. Mov Disord. 2014;29(7):857–67.

    Article  PubMed  PubMed Central  Google Scholar 

  49. • Auzou N, Dujardin K, Biundo R, Foubert-Samier A, Barth C, Duval F, et al. Diagnosing dementia in multiple system atrophy by applying Movement Disorder Society diagnostic criteria for Parkinson's disease dementia. Parkinsonism Relat Disord. 2015;21(10):1273–7. This study applied PDD procedures in 111 MSA patients and found that the short screening test may be useful for the diagnosis of MSA dementia, keeping in mind that cognitive impairment is a non-supporting feature of current diagnosis criteria for MSA.

    Article  PubMed  Google Scholar 

  50. Koga S, Aoki N, Uitti RJ, van Gerpen JA, Cheshire WP, Josephs KA, et al. When DLB, PD, and PSP masquerade as MSA: an autopsy study of 134 patients. Neurology. 2015;85(5):404–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Asi YT, Ling H, Ahmed Z, Lees AJ, Revesz T, Holton JL. Neuropathological features of multiple system atrophy with cognitive impairment. Mov Disord. 2014;29(7):884–8.

    Article  CAS  PubMed  Google Scholar 

  52. Lee YC, Liu CS, Wu HM, Wang PS, Chang MH, Soong BW. The “hot cross bun” sign in the patients with spinocerebellar ataxia. Eur J Neurol. 2009;16(4):513–6.

    Article  PubMed  Google Scholar 

  53. Kraft E, Trenkwalder C, Auer DP. T2*-weighted MRI differentiates multiple system atrophy from Parkinson's disease. Neurology. 2002;59(8):1265–7.

    Article  PubMed  Google Scholar 

  54. Deguchi K, Ikeda K, Kume K, Takata T, Kokudo Y, Kamada M, et al. Significance of the hot-cross bun sign on T2*-weighted MRI for the diagnosis of multiple system atrophy. J Neurol. 2015;262(6):1433–9.

    Article  CAS  PubMed  Google Scholar 

  55. • Scherfler C, Gobel G, Muller C, Nocker M, Wenning GK, Schocke M, et al. Diagnostic potential of automated subcortical volume segmentation in atypical parkinsonism. Neurology. 2016;86(13):1242–9. MRI study performing automated volume measures of 22 subcortical regions in patients with MSA, PD and PSP. Midbrain, putamen, and cerebellum were the most useful regions to construct a prediction model. This model was tested in a validation set in which all MSA patients were correctly classified.

    Article  PubMed  Google Scholar 

  56. Barbagallo G, Sierra-Pena M, Nemmi F, Traon AP, Meissner WG, Rascol O, et al. Multimodal MRI assessment of nigro-striatal pathway in multiple system atrophy and Parkinson disease. Mov Disord. 2016;31(3):325–34.

    Article  PubMed  Google Scholar 

  57. Nagayama H, Ueda M, Yamazaki M, Nishiyama Y, Hamamoto M, Katayama Y. Abnormal cardiac [(123)I]-meta-iodobenzylguanidine uptake in multiple system atrophy. Mov Disord. 2010;25(11):1744–7.

    Article  PubMed  Google Scholar 

  58. Laurens B, Constantinescu R, Freeman R, Gerhard A, Jellinger K, Jeromin A, et al. Fluid biomarkers in multiple system atrophy: a review of the MSA Biomarker Initiative. Neurobiol Dis. 2015;80:29–41.

    Article  PubMed  Google Scholar 

  59. Doppler K, Ebert S, Uceyler N, Trenkwalder C, Ebentheuer J, Volkmann J, et al. Cutaneous neuropathy in Parkinson’s disease: a window into brain pathology. Acta Neuropathol. 2014;128(1):99–109.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Donadio V, Incensi A, Leta V, Giannoccaro MP, Scaglione C, Martinelli P, et al. Skin nerve alpha-synuclein deposits: a biomarker for idiopathic Parkinson disease. Neurology. 2014;82(15):1362–9.

    Article  CAS  PubMed  Google Scholar 

  61. • Zange L, Noack C, Hahn K, Stenzel W, Lipp A. Phosphorylated alpha-synuclein in skin nerve fibres differentiates Parkinson's disease from multiple system atrophy. Brain. 2015;138(Pt 8):2310–21. Description of α-syn deposits in skin sympathetic nerve fibers around sweat glands in PD but not in MSA patients. The study also reported decreased density of the fibers innervating autonomic skin structures in PD but not in MSA.

    Article  PubMed  Google Scholar 

  62. • Doppler K, Weis J, Karl K, Ebert S, Ebentheuer J, Trenkwalder C, et al. Distinctive distribution of phospho-alpha-synuclein in dermal nerves in multiple system atrophy. Mov Disord. 2015;30(12):1688–92. Description of distinct patterns of α-syn deposition in the skin of patients with MSA (mainly somatosensory fibers of the subepidermal plexus) and PD (prominent in autonomic fibers).

    Article  CAS  PubMed  Google Scholar 

  63. Haga R, Sugimoto K, Nishijima H, Miki Y, Suzuki C, Wakabayashi K, et al. Clinical utility of skin biopsy in differentiating between parkinson's disease and multiple system atrophy. Parkinsons Dis. 2015;2015:167038.

    PubMed  PubMed Central  Google Scholar 

  64. Provitera V, Nolano M, Caporaso G, Stancanelli A, Manganelli F, Iodice R, et al. Post-ganglionic sudomotor denervation in patients with multiple system atrophy. Neurology. 2014;82(24):2223–9.

    Article  PubMed  Google Scholar 

  65. Corbille AG, Letournel F, Kordower JH, Lee J, Shanes E, Neunlist M, et al. Evaluation of alpha-synuclein immunohistochemical methods for the detection of Lewy-type synucleinopathy in gastrointestinal biopsies. Acta Neuropathol Commun. 2016;4:35.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Pouclet H, Lebouvier T, Coron E, Rouaud T, Flamant M, Toulgoat F, et al. Analysis of colonic alpha-synuclein pathology in multiple system atrophy. Parkinsonism Relat Disord. 2012;18(7):893–5.

    Article  PubMed  Google Scholar 

  67. Chung SJ, Kim J, Lee HJ, Ryu HS, Kim K, Lee JH, et al. Alpha-synuclein in gastric and colonic mucosa in Parkinson's disease: limited role as a biomarker. Mov Disord. 2016;31(2):241–9.

    Article  CAS  PubMed  Google Scholar 

  68. Valera E, Monzio Compagnoni G, Masliah E. Review: novel treatment strategies targeting alpha-synuclein in multiple system atrophy as a model of synucleinopathy. Neuropathol Appl Neurobiol. 2016;42(1):95–106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Dehay B, Decressac M, Bourdenx M, Guadagnino I, Fernagut PO, Tamburrino A, et al. Targeting alpha-synuclein: therapeutic options. Mov Disord. 2016;31(6):882–8.

    Article  CAS  PubMed  Google Scholar 

  70. Sturm E, Fellner L, Krismer F, Poewe W, Wenning GK, Stefanova N. Neuroprotection by epigenetic modulation in a transgenic model of multiple system atrophy. Neurotherapeutics. 2016;13(4):871–879.

  71. • Mandler M, Valera E, Rockenstein E, Mante M, Weninger H, Patrick C, et al. Active immunization against alpha-synuclein ameliorates the degenerative pathology and prevents demyelination in a model of multiple system atrophy. Mol Neurodegener. 2015;10:10. Proof of concept showing beneficial effects of active vaccination with AFF1 (corresponds to Affitope PD01A in human trials) in transgenic MSA mice on accumulation of α-syn, demyelination, and neurodegeneration.

    Article  PubMed  PubMed Central  Google Scholar 

  72. • Bassil F, Fernagut PO, Bezard E, Pruvost A, Leste-Lasserre T, Hoang QQ, et al. Reducing C-terminal truncation mitigates synucleinopathy and neurodegeneration in a transgenic model of multiple system atrophy. Proc Natl Acad Sci USA. 2016;113(34):9593–8. Proof of concept of the ability of the caspase-1 inhibitor prodrug VX-765 to mitigate α-syn pathology and to mediate neuroprotection in transgenic MSA mice. VX-765 prevented motor deficits in PLP-SYN, reduced the levels of truncated α-syn and showed neuroprotective effects by preserving dopamine neurons in the substantia nigra.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Spencer B, Valera E, Rockenstein E, Trejo-Morales M, Adame A, Masliah E. A brain-targeted, modified neurosin (kallikrein-6) reduces alpha-synuclein accumulation in a mouse model of multiple system atrophy. Mol Neurodegener. 2015;10:48.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Stefanova N, Poewe W, Wenning GK. Rasagiline is neuroprotective in a transgenic model of multiple system atrophy. Exp Neurol. 2008;210(2):421–7.

    Article  CAS  PubMed  Google Scholar 

  75. Ubhi K, Inglis C, Mante M, Patrick C, Adame A, Spencer B, et al. Fluoxetine ameliorates behavioral and neuropathological deficits in a transgenic model mouse of alpha-synucleinopathy. Exp Neurol. 2012;234(2):405–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Ubhi K, Rockenstein E, Mante M, Patrick C, Adame A, Thukral M, et al. Rifampicin reduces alpha-synuclein in a transgenic mouse model of multiple system atrophy. Neuroreport. 2008;19(13):1271–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Kaindlstorfer C, Sommer P, Georgievska B, Mather RJ, Kugler AR, Poewe W, et al. Failure of neuroprotection despite microglial suppression by delayed-start myeloperoxidase inhibition in a model of advanced multiple system atrophy: clinical implications. Neurotox Res. 2015;28(3):185–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Stefanova N, Georgievska B, Eriksson H, Poewe W, Wenning GK. Myeloperoxidase inhibition ameliorates multiple system atrophy-like degeneration in a transgenic mouse model. Neurotox Res. 2012;21(4):393–404.

    Article  CAS  PubMed  Google Scholar 

  79. Biaggioni I, Freeman R, Mathias CJ, Low P, Hewitt LA, Kaufmann H, et al. Randomized withdrawal study of patients with symptomatic neurogenic orthostatic hypotension responsive to droxidopa. Hypertension. 2015;65(1):101–7.

    Article  CAS  PubMed  Google Scholar 

  80. Kaufmann H, Freeman R, Biaggioni I, Low P, Pedder S, Hewitt LA, et al. Droxidopa for neurogenic orthostatic hypotension: a randomized, placebo-controlled, Phase 3 trial. Neurology. 2014;83(4):328–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Low PA, Robertson D, Gilman S, Kaufmann H, Singer W, Biaggioni I, et al. Efficacy and safety of rifampicin for multiple system atrophy: a randomized, double-blind, placebo-controlled trial. Lancet Neurol. 2014;13(3):268–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Poewe W, Seppi K, Fitzer-Attas CJ, Wenning GK, Gilman S, Low PA, et al. Efficacy of rasagiline in patients with the parkinsonian variant of multiple system atrophy: a randomized, placebo-controlled trial. Lancet Neurol. 2015;14(2):145–52.

    Article  CAS  PubMed  Google Scholar 

  83. Rascol O. French MSA-Fluoxetine Study Group. Preliminary results of the French MSA-fluoxetine study. Eur J Neurol. 2012;19 Suppl 1:262.

    Google Scholar 

  84. Tada M, Kakita A, Toyoshima Y, Onodera O, Ozawa T, Morita T, et al. Depletion of medullary serotonergic neurons in patients with multiple system atrophy who succumbed to sudden death. Brain. 2009;132(Pt 7):1810–9.

    Article  PubMed  Google Scholar 

  85. Lee PH, Lee JE, Kim HS, Song SK, Lee HS, Nam HS, et al. A randomized trial of mesenchymal stem cells in multiple system atrophy. Ann Neurol. 2012;72(1):32–40.

    Article  PubMed  Google Scholar 

  86. Sacca F, Marsili A, Quarantelli M, Brescia Morra V, Brunetti A, Carbone R, et al. A randomized clinical trial of lithium in multiple system atrophy. J Neurol. 2013;260(2):458–61.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was partly funded by grants to W.G.M. (ANR-14-RARE-0001-01 under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases, and FP7/2007-2013 under grant agreement 602999 from the European Union Seventh Framework Program).

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Authors and Affiliations

  1. Service de Neurologie, Hôpital Pellegrin, CHU de Bordeaux, 33000, Bordeaux, France

    Brice Laurens, Sylvain Vergnet, Alexandra Foubert-Samier, François Tison & Wassilios G. Meissner

  2. Institut des Maladies Neurodégénératives, Univ. de Bordeaux, UMR 5293, 33000, Bordeaux, France

    Miguel Cuina Lopez, François Tison, Pierre-Olivier Fernagut & Wassilios G. Meissner

  3. CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000, Bordeaux, France

    Miguel Cuina Lopez, François Tison, Pierre-Olivier Fernagut & Wassilios G. Meissner

  4. Centre de Référence Maladie Rare AMS, Hôpital Pellegrin, CHU de Bordeaux, F-33076, Bordeaux, France

    Alexandra Foubert-Samier, François Tison & Wassilios G. Meissner

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  1. Brice Laurens
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Correspondence to Wassilios G. Meissner.

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Conflict of Interest

Brice Laurens, Sylvain Vergnet, Miguel Cuina Lopez, Alexandra Foubert-Samier, and Pierre-Olivier Fernagut declare that they have no conflict of interest.

François Tison reports a grant from French Gov (PHRC) and travel grants from Novartis France and ORKYN.

Wassilios G. Meissner reports research grants from University Hospital Bordeaux, PSP France, France Parkinson, MSA Coalition, MJFF, the French Ministry of Health, the French National Research Agency (ANR) and the European Community, payment for lectures from UCB, Novartis, TEVA/Lundbeck, Aguettant, Orkyn and MDS, travel grants from Novartis, TEVA/Lundbeck, and Abbvie, fees for editorial activities from Springer, and consultancy fees from Zambon France and Sanofi.

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This article is part of the Topical Collection on Movement Disorders

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Laurens, B., Vergnet, S., Lopez, M.C. et al. Multiple System Atrophy - State of the Art. Curr Neurol Neurosci Rep 17, 41 (2017). https://doi.org/10.1007/s11910-017-0751-0

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