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Multiple System Atrophy

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Case-based Approach to Common Neurological Disorders

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Abstract

Informative Abstract: Multiple system atrophy (MSA) is an adult-onset, sporadic, and rapidly progressive neurodegenerative disorder, that currently lacks a cure. It manifests with a combination of symptoms such as parkinsonism, dysfunction of the autonomic system, impairment of the cerebellum, involvement of the pyramidal tract, and a poor response to medications targeting dopamine. The pathological features of MSA include the loss of cells, gliosis, and the presence of abnormal α-synuclein protein aggregates in oligodendroglia in various structures of the central nervous system. Clinically, MSA can be classified into two phenotypes based on the primary motor system affected: the parkinsonian variant (MSA-P) and the cerebellar variant (MSA-C). The diagnosis of MSA primarily relies on a thorough medical history and a meticulous neurological examination. Symptomatic treatment targeting various clinical manifestations and providing palliative care during the advanced stages of MSA form the cornerstone of current treatment strategies.

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References

  1. Wenning GK, Colosimo C, Geser F, Poewe W. Multiple system atrophy. Lancet Neurol. 2004;3(2):93–103.

    Article  PubMed  Google Scholar 

  2. Stefanova N, Bücke P, Duerr S, Wenning GK. Multiple system atrophy: an update. Lancet Neurol. 2009;8(12):1172–8.

    Article  CAS  PubMed  Google Scholar 

  3. Quinn N. Multiple system atrophy – the nature of the beast. J Neurol Neurosurg Psychiatry. 1989;S2(Suppl):78–89.

    Article  Google Scholar 

  4. Wenning GK, Fanciulli A, editors. Multiple system atrophy. Wien: Springer-Verlag; 2014.

    Google Scholar 

  5. 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 

  6. 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 

  7. Wenning GK, Geser F, Krismer F, Seppi K, Duerr S, Boesch S, Kollensperger M, Goebel G, Pfeiffer KP, Barone P, Pellecchia MT, Quinn NP, Koukouni V, Fowler CJ, Schrag A, Mathias CJ, Giladi N, Gurevich T, Dupont E, Ostergaard K, Nilsson CF, Widner H, Oertel W, Eggert KM, Albanese A, del Sorbo F, Tolosa E, Cardozo A, Deuschl G, Hellriegel H, Klockgether T, Dodel R, Sampaio C, Coelho M, Djaldetti R, Melamed E, Gasser T, Kamm C, Meco G, Colosimo C, Rascol O, Meissner WG, Tison F, Poewe W. The natural history of multiple system atrophy: a prospective European cohort study. Lancet Neurol. 2013;12:264–74.

    Article  PubMed  PubMed Central  Google Scholar 

  8. May S, Gilman S, Sowell BB, Thomas RG, Stern MB, Colcher A, Tanner CM, Huang N, Novak P, Reich SG, Jankovic J, Ondo WG, Low PA, Sandroni P, Lipp A, Marshall FJ, Wooten F, Shults CW. Potential outcome measures and trial design issues for multiple system atrophy. Mov Disord. 2007;22:2371–7.

    Article  PubMed  Google Scholar 

  9. Low PA, Reich SG, Jankovic J, Shults CW, Stern MB, Novak P, et al. Natural history of multiple system atrophy in the USA: a prospective cohort study. Lancet Neurol. 2015;14(7):710–9. https://doi.org/10.1016/S1474-4422(15)00058-7.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Kim HJ, Jeon BS, Lee JY, Yun JY. Survival of Korean patients with multiple system atrophy. Mov Disord. 2011;26:909–12.

    Article  PubMed  Google Scholar 

  11. Watanabe H, Saito Y, Terao S, Ando T, Kachi T, Mukai E, Aiba I, Abe Y, Tamakoshi A, Doyu M, Hirayama M, Sobue. Progression and prognosis in multiple system atrophy: an analysis of 230 Japanese patients. Brain. 2002;125:1070–83.

    Article  PubMed  Google Scholar 

  12. Ozawa T, Tada M, Kakita A, Onodera O, Ishihara T, Morita T, Shimohata T, Wakabayashi K, Takahashi H, Nishizawa M. The phenotype spectrum of Japanese multiple system atrophy. J Neurol Neurosurg Psychiatry. 2010;81:1253–5.

    Article  CAS  PubMed  Google Scholar 

  13. Ubhi K, Low P, Masliah E. Multiple system atrophy: a clinical and neuropathological perspective. Trends Neurosci. 2011;34(11):581–90. https://doi.org/10.1016/j.tins.2011.08.003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ahmed Z, Asi YT, Sailer A, Lees AJ, Houlden H, Revesz T, Holton JL. The neuropathology, pathophysiology and genetics of multiple system atrophy. Neuropathol Appl Neurobiol. 2012;38:4–24.

    Article  CAS  PubMed  Google Scholar 

  15. Jellinger KA. Neuropathology and pathophysiology of multiple system atrophy. Neuropathol Appl Neurobiol. 2012;38:379–80. author reply 381

    Article  CAS  PubMed  Google Scholar 

  16. Jellinger KA, Lantos PL. Papp-Lantos inclusions and the pathogenesis of multiple system atrophy: an update. Acta Neuropathol. 2010;119:657–67.

    Article  CAS  PubMed  Google Scholar 

  17. Halliday GM, Holton JL, Revesz T, Dickson DW. Neuropathology underlying clinical variability in patients with synucleinopathies. Acta Neuropathol. 2011;122:187–204.

    Article  CAS  PubMed  Google Scholar 

  18. Jellinger KA. p25alpha immunoreactivity in multiple system atrophy and Parkinson disease. Acta Neuropathol. 2006;112:112.

    Article  PubMed  Google Scholar 

  19. Fellner L, Jellinger KA, Wenning GK, Stefanova N. Glial dysfunction in the pathogenesis of α-synucleinopathies: emerging concepts. Acta Neuropathol. 2011 Jun;121(6):675–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Song YJ, Lundvig DM, Huang Y, Gai WP, Blumbergs PC, Hojrup P, Otzen D, Halliday GM, Jensen PH. p25alpha relocalizes in oligodendroglia from myelin to cytoplasmic inclusions in multiple system atrophy. Am J Pathol. 2007;171:1291–303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. The Multiple-System Atrophy Research Collaboration. Mutations in COQ2 in familial and sporadic multiple-system atrophy. N Engl J Med. 2013;369(3):233–44.

    Article  Google Scholar 

  22. Kollensperger M, Geser F, Ndayisaba JP, Boesch S, Seppi K, Ostergaard K, Dupont E, Cardozo A, Tolosa E, Abele M, Klockgether T, Yekhlef F, Tison F, Daniels C, Deuschl G, Coelho M, Sampaio C, Bozi M, Quinn N, Schrag A, Mathias CJ, Fowler C, Nilsson CF, Widner H, Schimke N, Oertel W, del Sorbo F, Albanese A, Pellecchia MT, Barone P, Djaldetti R, Colosimo C, Meco G, Gonzalez-Mandly A, Berciano J, Gurevich T, Giladi N, Galitzky M, Rascol O, Kamm C, Gasser T, Siebert U, Poewe W, Wenning GK. Presentation, diagnosis, and management of multiple system atrophy in Europe: final analysis of the European multiple system atrophy registry. Mov Disord. 2010;25:2604–12.

    Article  PubMed  Google Scholar 

  23. Sakakibara R, Hattori T, Uchiyama T, Kita K, Asahina M, Suzuki A, Yamanishi T. Urinary dysfunction and orthostatic hypotension in multiple system atrophy: which is the more common and earlier manifestation? J Neurol Neurosurg. Psychiatry. 2000;68:65–9.

    CAS  Google Scholar 

  24. 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 

  25. Schmidt C, Berg D, Prieur S, Junghanns S, Schweitzer K, Globas C, Schols L, Reichmann H, Ziemssen T. Loss of nocturnal blood pressure fall in various extrapyramidal syndromes. Mov Disord. 2009;24:2136–42.

    Article  PubMed  Google Scholar 

  26. Yamaguchi M, Arai K, Asahina M, Hattori T. Laryngeal stridor in multiple system atrophy. Eur Neurol. 2003;49:154–9.

    Article  PubMed  Google Scholar 

  27. Sakakibara R, Odaka T, Uchiyama T, Liu R, Asahina M, Yamaguchi K, Yamaguchi T, Yamanishi T, Hattori T. Colonic transit time, sphincter EMG, and rectoanal videomanometry in multiple system atrophy. Mov Disord. 2004;19:924–9.

    Article  PubMed  Google Scholar 

  28. O’Sullivan SS, Massey LA, Williams DR, Silveira-Moriyama L, Kempster PA, Holton JL, Revesz T, Lees AJ. Clinical outcomes of progressive supranuclear palsy and multiple system atrophy. Brain. 2008;131:1362–72.

    Article  PubMed  Google Scholar 

  29. Iodice V, Lipp A, Ahlskog JE, Sandroni P, Fealey RD, Parisi JE, Matsumoto JY, Benarroch EE, Kimpinski K, Singer W, Gehrking TL, Gehrking JA, Sletten DM, Schmeichel AM, Bower JH, Gilman S, Figueroa J, Low PA. Autopsy confirmed multiple system atrophy cases: Mayo experience and role of autonomic function tests. J Neurol Neurosurg Psychiatry. 2012;83:453–9.

    Article  PubMed  Google Scholar 

  30. Yamashita F, Hirayama M, Nakamura T, Takamori M, Hori N, Uchida K, Hama T, Sobue G. Pupillary autonomic dysfunction in multiple system atrophy and Parkinson’s disease: an assessment by eye-drop tests. Clin Auton Res. 2010;20:191–7.

    Article  PubMed  Google Scholar 

  31. Wenning GK, Tison F, Ben Shlomo Y, Daniel SE, Quinn NP. Multiple system atrophy: a review of 203 pathologically proven cases. Mov Disord. 1997;12:133–47.

    Article  CAS  PubMed  Google Scholar 

  32. Brown RG, Lacomblez L, Landwehrmeyer BG, Bak T, Uttner I, Dubois B, Agid Y, Ludolph A, Bensimon G, Payan C, Leigh NP. Cognitive impairment in patients with multiple system atrophy and progressive supranuclear palsy. Brain. 2010;133:2382–93.

    Article  PubMed  Google Scholar 

  33. Marconi R, Antonini A, Barone P, Colosimo C, Avarello TP, Bottacchi E, Cannas A, Ceravolo MG, Ceravolo R, Cicarelli G, Gaglio RM, Giglia L, Iemolo F, Manfredi M, Meco G, Nicoletti A, Pederzoli M, Petrone A, Pisani A, Pontieri FE, Quatrale R, Ramat S, Scala R, Volpe G, Zappulla S, Bentivoglio AR, Stocchi F, Trianni G, del Dotto P, de Gaspari D, Grasso L, Morgante F, Santangelo G, Fabbrini G, Morgante L. Frontal assessment battery scores and non-motor symptoms in parkinsonian disorders. Neurol Sci. 2012;33:585–93.

    Article  PubMed  Google Scholar 

  34. Colosimo C, Morgante L, Antonini A, Barone P, Avarello TP, Bottacchi E, Cannas A, Ceravolo MG, Ceravolo R, Cicarelli G, Gaglio RM, Giglia L, Iemolo F, Manfredi M, Meco G, Nicoletti A, Pederzoli M, Petrone A, Pisani A, Pontieri FE, Quatrale R, Ramat S, Scala R, Volpe G, Zappulla S, Bentivoglio AR, Stocchi F, Trianni G, del Dotto P, Simoni L, Marconi R. Non-motor symptoms in atypical and secondary parkinsonism: the PRIAMO study. J Neurol. 2010;257:5–14.

    Article  PubMed  Google Scholar 

  35. Boeve BF, Silber MH, Parisi JE, Dickson DW, Ferman TJ, Benarroch EE, Schmeichel AM, Smith GE, Petersen RC, Ahlskog JE, Matsumoto JY, Knopman DS, Schenck CH, Mahowald MW. Synucleinopathy pathology and REM sleep behavior disorder plus dementia or parkinsonism. Neurology. 2003;61:40–5.

    Article  CAS  PubMed  Google Scholar 

  36. Iranzo A, Santamaria J, Tolosa E. The clinical and pathophysiological relevance of REM sleep behavior disorder in neurodegenerative diseases. Sleep Med Rev. 2009;13:385–401.

    Article  PubMed  Google Scholar 

  37. Vetrugno R, Provini F, Cortelli P, Plazzi G, Lotti EM, Pierangeli G, Canali C, Montagna P. Sleep disorders in multiple system atrophy: a correlative video-polysomnographic study. Sleep Med. 2004;5:21–30.

    Article  PubMed  Google Scholar 

  38. Gama RL, Tavora DG, Bomfi m RC, Silva CE, de Bruin VM, de Bruin PF. Sleep disturbances and brain MRI morphometry in Parkinson’s disease, multiple system atrophy and progressive supranuclear palsy – a comparative study. Parkinsonism Relat Disord. 2010;16:275–9.

    Article  PubMed  Google Scholar 

  39. Palma J-A, Norcliffe-Kaufmann L, Kaufmann H. Diagnosis of multiple system atrophy. Auton Neurosci. 2018 May;211:15–25.

    Article  PubMed  Google Scholar 

  40. Burk K, Globas C, Wahl T, Buhring U, Dietz K, Zuhlke C, Luft A, Schulz JB, Voigt K, Dichgans J. MRI-based volumetric differentiation of sporadic cerebellar ataxia. Brain. 2004;127:175–81.

    Article  CAS  PubMed  Google Scholar 

  41. Quattrone A, Nicoletti G, Messina D, Fera F, Condino F, Pugliese P, Lanza P, Barone P, Morgante L, Zappia M, Aguglia U, Gallo O. MR imaging index for differentiation of progressive supranuclear palsy from Parkinson disease and the Parkinson variant of multiple system atrophy. Radiology. 2008;246:214–21.

    Article  PubMed  Google Scholar 

  42. 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;36:166–75.

    Article  CAS  PubMed  Google Scholar 

  43. Eidelberg D, Takikawa S, Moeller JR, Dhawan V, Redington K, Chaly T, Robeson W, Dahl JR, Margouleff D, Fazzini E. Striatal hypometabolism distinguishes striatonigral degeneration from Parkinson’s disease. Ann Neurol. 1993;33:518–52.

    Article  CAS  PubMed  Google Scholar 

  44. Otsuka M, Kuwabara Y, Ichiya Y, Hosokawa S, Sasaki M, Yoshida T, Fukumura T, Kato M, Masuda K. Differentiating between multiple system atrophy and Parkinson’s disease by positron emission tomography with 18F-dopa and 18F-FDG. Ann Nucl Med. 1997;11:251–7.

    Article  CAS  PubMed  Google Scholar 

  45. Tang CC, Poston KL, Eckert T, Feigin A, Frucht S, Gudesblatt M, Dhawan V, Lesser M, Vonsattel JP, Fahn S, Eidelberg D. Differential diagnosis of parkinsonism: a metabolic imaging study using pattern analysis. Lancet Neurol. 2010;9:149–58.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Bosman T, van Laere K, Santens P. Anatomically standardised 99mTc-ECD brain perfusion SPET allows accurate differentiation between healthy volunteers, multiple system atrophy and idiopathic Parkinson’s disease. Eur J Nucl Med Mol Imaging. 2003;30:16–24.

    Article  CAS  PubMed  Google Scholar 

  47. Brooks DJ, Seppi K. Proposed neuroimaging criteria for the diagnosis of multiple system atrophy. Mov Disord. 2009;24:949–64.

    Article  PubMed  Google Scholar 

  48. Fanciulli A, Gobel G, Ndayisaba JP, Granata R, Duerr S, Strano S, Colosimo C, Poewe W, Pontieri FE, Wenning GK. Supine hypertension in Parkinson's disease and multiple system atrophy. Clin Auton Res. 2016;26:97–105.

    Article  PubMed  Google Scholar 

  49. Coon EA, Fealey RD, Sletten DM, Mandrekar JN, Benarroch EE, Sandroni P, Low PA, Singer W. Anhidrosis in multiple system atrophy involves pre- and postganglionic sudomotor dysfunction. Mov Disord. 2017;32:397–404.

    Article  CAS  PubMed  Google Scholar 

  50. Doppler K, Weis J, Karl K, Ebert S, Ebentheuer J, Trenkwalder C, Klebe S, Volkmann J, Sommer C. Distinctive distribution of phospho-alpha-synuclein in dermal nerves in multiple system atrophy. Mov Disord. 2015;30:1688–92.

    Article  CAS  PubMed  Google Scholar 

  51. Lipp A, Sandroni P, Ahlskog JE, Fealey RD, Kimpinski K, Iodice V, Gehrking TL, Weigand SD, Sletten DM, Gehrking JA, Nickander KK, Singer W, Maraganore DM, Gilman S, Wenning GK, Shults CW, Low PA. Prospective differentiation of multiple system atrophy from Parkinson disease, with and without autonomic failure. Arch Neurol. 2009;66:742–50.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Ogawa T, Sakakibara R, Kuno S, Ishizuka O, Kitta T, Yoshimura N. Prevalence and treatment of LUTS in patients with Parkinson disease or multiple system atrophy. Nat Rev Urol. 2017;14:79.

    Article  CAS  PubMed  Google Scholar 

  53. Giladi N, Simon ES, Korczyn AD, Groozman GB, Orlov Y, Shabtai H, Drory VE. Anal sphincter EMG does not distinguish between multiple system atrophy and Parkinson’s disease. Muscle Nerve. 2000;23:731–4.

    Article  CAS  PubMed  Google Scholar 

  54. Garland EM, Raj SR, Peltier AC, Robertson D, Biaggioni I. A cross-sectional study contrasting olfactory function in autonomic disorders. Neurology. 2011;76:456–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Wenning GK, Tison F, Seppi K, Sampaio C, Diem A, Yekhlef F, et al. Multiple system atrophy study group. Development and validation of the unified multiple system atrophy rating scale (UMSARS). Mov Disord. 2004;19(12):1391–402.

    Article  PubMed  Google Scholar 

  56. Kim H-J, Stamelou M, Jeon B. Multiple system atrophy-mimicking conditions: diagnostic challenges. Parkinsonism Relat Disord. 2016;22:S12eS15.

    Article  Google Scholar 

  57. Rohrer G, Hoglinger GU, Levin J. Symptomatic therapy of multiple system atrophy. Auton Neurosci. 2018;211:26–30.

    Article  PubMed  Google Scholar 

  58. Young TM, Mathias CJ. The effects of water ingestion on orthostatic hypotension in two groups of chronic autonomic failure: multiple system atrophy and pure autonomic failure. J Neurol Neurosurg Psychiatry. 2004;75:1737–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Tada M, Onodera O, Ozawa T, Piao YS, Kakita A, Takahashi H, Nishizawa M. Early development of autonomic dysfunction may predict poor prognosis in patients with multiple system atrophy. Arch Neurol. 2007;64:256–60.

    Article  PubMed  Google Scholar 

  60. Ben-Shlomo Y, Wenning GK, Tison F, Quinn NP. Survival of patients with pathologically proven multiple system atrophy: a meta-analysis. Neurology. 1997;48:384–93.

    Article  CAS  PubMed  Google Scholar 

  61. Schulz JB, Klockgether T, Petersen D, Jauch M, Muller-Schauenburg W, Spieker S, Voigt K, Dichgans J. Multiple system atrophy: natural history, MRI morphology, and dopamine receptor imaging with 123IBZM-SPECT. J Neurol Neurosurg Psychiatry. 1994;57:1047–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Petrovic IN, Ling H, Asi Y, Ahmed Z, Kukkle PL, Hazrati LN, Lang AE, Revesz T, Holton JL, Lees AJ. Multiple system atrophy-parkinsonism with slow progression and prolonged survival: a diagnostic catch. Mov Disord. 2012;27:1186–90.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore, India

    Malligurki Raghurama Rukmani & Talakad N. Sathyaprabha

  2. Department of Neurology, National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore, India

    Ravi Yadav

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  1. Malligurki Raghurama Rukmani
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  2. Talakad N. Sathyaprabha
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  3. Ravi Yadav
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Editors and Affiliations

  1. Department of Neurology, Tribhuvan University Teaching Hospital, Kathmandu, Nepal

    Krishna Kumar Oli

  2. Department of Anesthesiology, Tribhuvan University Teaching Hospital, Kathmandu, Nepal

    Gentle Sunder Shrestha

  3. Department of Neurology, Tribhuvan University Teaching Hospital, Kathmandu, Nepal

    Rajeev Ojha

  4. Department of Neurology, NIMHANS, Bangalore, India

    Pramod Kumar Pal

  5. Department of Neurology and Stroke Medicine, Amrita Hospital, Faridabad, Delhi, India

    Sanjay Pandey

  6. Neuroanaesthesia, Neurocritical Care, Institute of Neurosciences, Kolkata, India

    Bibhukalyani Das

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Rukmani, M.R., Sathyaprabha, T.N., Yadav, R. (2024). Multiple System Atrophy. In: Oli, K.K., Shrestha, G.S., Ojha, R., Pal, P.K., Pandey, S., Das, B. (eds) Case-based Approach to Common Neurological Disorders. Springer, Singapore. https://doi.org/10.1007/978-981-99-8676-7_25

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