Multiple System Atrophy

 

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ABSTRACT

Multiple system atrophy (MSA) is an adult-onset sporadic progressive neurodegenerative disorder of unknown etiology. It is clinically characterized by the variable combination of autonomic failure, parkinsonism, cerebellar ataxia, and pyramidal signs. The present review summarizes up-to-date knowledge on the clinical diagnosis and molecular pathology of MSA. We also review the role of additional investigations that may support a clinical diagnosis of MSA. Finally, we briefly discuss the management of MSA, focusing on possible future therapeutic strategies.

REFERENCES

• 1 Bower J H, Maraganore D M, McDonnell S K, Rocca W A. Incidence of progressive supranuclear palsy and multiple system atrophy in Olmsted County, Minnesota, 1976 to 1990.  Neurology . 1997;  49 1284-1288
  CrossrefPubMedGoogle Scholar
• 2 Schrag A, Ben-Shlomo Y, Quinn N P. Prevalence of progressive supranuclear palsy and multiple system atrophy: a cross-sectional study.  Lancet . 1999;  354 1771-1775
  CrossrefPubMedGoogle Scholar
• 3 Gilman S, Low P A, Quinn N. Consensus statement on the diagnosis of multiple system atrophy.  J Auton Nerv Syst . 1998;  74 189-192
  PubMedGoogle Scholar
• 4 Wenning G K, Ben Shlomo Y, Magalhaes M, Daniel S E, Quinn N P. Clinical features and natural history of multiple system atrophy: an analysis of 100 cases.  Brain . 1994;  117 835-845
  CrossrefPubMedGoogle Scholar
• 5 Wenning G K, Tison F, Ben Shlomo Y, Daniel S E, Quinn N P. Multiple system atrophy: a review of 203 pathologically proven cases.  Mov Disord . 1997;  12 133-147
  CrossrefPubMedGoogle Scholar
• 6 Quinn N. Multiple system atrophy: the nature of the beast.  J Neurol Neurosurg Psychiatry . 1989;  78-89 (78-89)
  PubMedGoogle Scholar
• 7 Quinn N. Multiple system atrophy. In: Marsden CD, Fahn S, eds. Movement Disorders 3 London: Butterworth-Heinemann 1994: 262-281
  Google Scholar
• 8 Litvan I, Booth V, Wenning G K. Retrospective application of a set of clinical diagnostic criteria for the diagnosis of multiple system atrophy.  J Neural Transm . 1998;  105 217-227
  CrossrefPubMedGoogle Scholar
• 9 Poewe W H, Wenning G K. The natural history of Parkinson's disease.  Ann Neurol . 1998;  S1-S9 (S1-S9)
  PubMedGoogle Scholar
• 10 Wenning G K, Scherfler C, Granata R. Time course of symptomatic orthostatic hypotension and urinary incontinence in patients with postmortem confirmed parkinsonian syndromes: a clinicopathological study.  J Neurol Neurosurg Psychiatry . 1999;  67 620-623
  CrossrefPubMedGoogle Scholar
• 11 Litvan I, Mangone C A, McKee A. Natural history of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) and clinical predictors of survival: a clinicopathological study.  J Neurol Neurosurg Psychiatry . 1996;  60 615-620
  PubMedGoogle Scholar
• 12 Kompoliti K, Goetz C G, Boeve B F. Clinical presentation and pharmacological therapy in corticobasal degeneration.  Arch Neurol . 1998;  55 957-961
  CrossrefPubMedGoogle Scholar
• 13 Wenning G K, Litvan I, Jankovic J. Natural history and survival of 14 patients with corticobasal degeneration confirmed at postmortem examination.  J Neurol Neurosurg Psychiatry . 1998;  64 184-189
  CrossrefPubMedGoogle Scholar
• 14 Gilman S, Koeppe R A, Junck L. Benzodiazepine receptor binding in the cerebellum in multiple system atrophy and olivopontocerebellar atrophy studied with positron emission tomography.  Adv Neurol . 1996;  69 459-466
  PubMedGoogle Scholar
• 15 Mathias C, Bannister R. Investigation of autonomic disorders. In: Bannister R, Mathias C, eds. Autonomic Failure London: Oxford University Press 1992: 255-290
  Google Scholar
• 16 Wenning G K, Litvan I, Verny M. Is EEG useful in the differential diagnosis of parkinsonism?.  Parkinsonism Relat Disord . 1998;  4 79-80
  CrossrefPubMedGoogle Scholar
• 17 Beck R O, Betts C D, Fowler C J. Genitourinary dysfunction in multiple system atrophy: clinical features and treatment in 62 cases.  J Urol . 1994;  151 1336-1341
  PubMedGoogle Scholar
• 18 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
  CrossrefPubMedGoogle Scholar
• 19 Schrag A, Kingsley D, Phatouros C. Clinical usefulness of magnetic resonance imaging in multiple system atrophy.  J Neurol Neurosurg Psychiatry . 1998;  65 65-71
  CrossrefPubMedGoogle Scholar
• 20 Schulz J B, Skalej M, Wedekind D. Magnetic resonance imaging-based volumetry differentiates idiopathic Parkinson's syndrome from multiple system atrophy and progressive supranuclear palsy.  Ann Neurol . 1999;  45 65-74
  CrossrefPubMedGoogle Scholar
• 21 Davie C A, Wenning G K, Barker G J. Differentiation of multiple system atrophy from idiopathic Parkinson's disease using proton magnetic resonance spectroscopy.  Ann Neurol . 1995;  37 204-210
  CrossrefPubMedGoogle Scholar
• 22 Schwarz J, Tatsch K, Gasser T. 123I-IBZM binding compared with long-term clinical follow up in patients with de novo parkinsonism.  Mov Disord . 1998;  13 16-19
  CrossrefPubMedGoogle Scholar
• 23 Brucke T, Asenbaum S, Pirker W. Measurement of the dopaminergic degeneration in Parkinson's disease with [¹²³I] beta-CIT and SPECT: correlation with clinical findings and comparison with multiple system atrophy and progressive supranuclear palsy.  J Neural Transm Suppl . 1997;  50 9-24
  PubMedGoogle Scholar
• 24 Terao S, Sobue G, Hashizume Y, Mitsuma T, Takahashi A. Disease-specific patterns of neuronal loss in the spinal ventral horn in amyotrophic lateral sclerosis, multiple system atrophy and X-linked recessive bulbospinal neuronopathy, with special reference to the loss of small neurons in the intermediate zone.  J Neurol . 1994;  241 196-203
  PubMedGoogle Scholar
• 25 Daniel S E. The neuropathology and neurochemistry of multiple system atrophy. In: Bannister R, Mathias C, eds. A Textbook of Clinical Disorders of Autonomic Nervous System 3rd ed. Oxford: Oxford University Press 1992: 564-585
  Google Scholar
• 26 Wenning G K, Ebersbach G, Verny M. Progression of falls in postmortem-confirmed parkinsonian disorders.  Mov Disord . 1999;  14 947-950
  CrossrefPubMedGoogle Scholar
• 27 Papp M I, Lantos P L. Accumulation of tubular structures in oligodendroglial and neuronal cells as the basic alteration in multiple system atrophy.  J Neurol Sci . 1992;  107 172-182
  CrossrefPubMedGoogle Scholar
• 28 Lantos P L. The definition of multiple system atrophy: a review of recent developments.  J Neuropathol Exp Neurol . 1998;  57 1099-1111
  PubMedGoogle Scholar
• 29 Papp M I, Lantos P L. The distribution of oligodendroglial inclusions in multiple system atrophy and its relevance to clinical symptomatology.  Brain . 1994;  117 235-243
  CrossrefPubMedGoogle Scholar
• 30 Papp M I, Kahn J E, 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
  CrossrefPubMedGoogle Scholar
• 31 Cairns N J, Atkinson P F, Hanger D P, Anderton B H, Daniel S E, Lantos P L. 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 49-52
  CrossrefPubMedGoogle Scholar
• 32 Spillantini M G, Crowther R A, Jakes R, Cairns N J, Lantos P L, Goedert M. Filamentous alpha-synuclein inclusions link multiple system atrophy with Parkinson's disease and dementia with Lewy bodies.  Neurosci Lett . 1998;  251 205-208
  CrossrefPubMedGoogle Scholar
• 33 Takeda A, Arai N, Komori T, Iseki E, Kato S, Oda M. Tau immunoreactivity in glial cytoplasmic inclusions in multiple system atrophy.  Neurosci Lett . 1997;  234 63-66
  CrossrefPubMedGoogle Scholar
• 34 Goedert M, Spillantini M G. Lewy body diseases and multiple system atrophy as alpha-synucleinopathies.  Mol Psychiatry . 1998;  3 462-465
  CrossrefPubMedGoogle Scholar
• 35 Spillantini M G, Schmidt M L, Lee V M, Trojanowski J Q, Jakes R, Goedert M. Alpha-synuclein in Lewy bodies.  Nature . 1997;  388 839-840
  CrossrefPubMedGoogle Scholar
• 36 Wakabayashi K, Yoshimoto M, Tsuji S, Takahashi H. α-Synuclein immunoreactivity in glial cytoplasmic inclusions in multiple system atrophy.  Neurosci Lett . 1998;  249 180-182
  CrossrefPubMedGoogle Scholar
• 37 Arima K, Ueda K, Sunohara N. 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
  CrossrefPubMedGoogle Scholar
• 38 Tu P, Galvin J E, Baba M. Glial cytoplasmic inclusions in white matter oligodendrocytes of multiple system atrophy brains contain insoluble α-synuclein.  Ann Neurol . 1998;  44 415-422
  CrossrefPubMedGoogle Scholar
• 39 Clayton D F, George J M. Synucleins in synaptic plasticity and neurodegenerative disorders.  J Neurosci Res . 1999;  58 120-129
  CrossrefPubMedGoogle Scholar
• 40 Dickson D W, Liu W, Hardy J. Widespread alterations of alpha-synuclein in multiple system atrophy.  Am J Pathol . 1999;  155 1241-1251
  CrossrefPubMedGoogle Scholar
• 41 Abeliovich A, Schmitz, Farinas I. Mice lacking α-synclein display functional deficits in the nigrostriatal dopamine system.  Neuron . 2000;  25 239-252
  CrossrefPubMedGoogle Scholar
• 42 Farrer M, Wavrant-De Vrieze F. Low frequency of alpha-synuclein mutations in familial Parkinson's disease.  Ann Neurol . 1998;  43 394-397
  CrossrefPubMedGoogle Scholar
• 43 Kruger R, Kuhn W, Muller T. Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease.  Nat Genet . 1998;  18 106-108
  PubMedGoogle Scholar
• 44 Ozawa T, Takano H, Onodera O. No mutation in the entire coding region of the alpha-synuclein gene in pathologically confirmed cases of multiple system atrophy.  Neurosci Lett . 1999;  270 110-112
  CrossrefPubMedGoogle Scholar
• 45 Colosimo C, Merello M, Pontieri F E. Amantadine in parkinsonian patients unresponsive to levodopa: a pilot study [letter].  J Neurol . 1996;  243 422-425
  PubMedGoogle Scholar
• 46 Lang A E, Lozano A M. Parkinson's disease: second of two parts.  N Engl J Med . 1998;  339 1130-1143
  CrossrefPubMedGoogle Scholar
• 47 Wenning G K, Granata R, Laboyrie P M, Quinn N P, Jenner P, Marsden C D. Reversal of behavioural abnormalities by fetal allografts in a novel rat model of striatonigral degeneration.  Mov Disord . 1996;  11 522-532
  CrossrefPubMedGoogle Scholar
• 48 Puschban Z, Scherfler C, Granata R. Autoradiographic study of striatal dopamine reuptake 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 co-grafts.  Neuroscience . 2000;  95 377-388
  PubMedGoogle Scholar
• 49 Wenning G K, Tison F, Scherfler C. Towards neurotransplantation in multiple system atrophy: clinical rationale, pathophysiological basis, and preliminary experimental evidence.  Cell Transplant . 2000;  9 279-288
  PubMedGoogle Scholar
• 50 Wenning G K, Ben-Shlomo Y, Magalhaes M, Daniel S E, Quinn N P. Clinicopathological study of 35 cases of multiple system atrophy.  J Neurol Neurosurg Psychiatry . 1995;  58 160-166
  PubMedGoogle Scholar
• 51 Wenning G K, Ben-Shlomo Y, Hughes A, Daniel S E, Lees A, Quinn N P. What clinical features are most useful to distinguish definite multiple system atrophy from Parkinson's disease?.  J Neurol Neurosurg Psychiatry . 2000;  68 434-440
  CrossrefPubMedGoogle Scholar
• 52 Litvan I, Campbell G, Mangone C A. Which clinical features differentiate progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) from related disorders?.  <~>A clinicopathological study. Brain . 1997;  120 65-74
  PubMedGoogle Scholar
• 53 Schulz J B, Klockgether T, Petersen D. Multiple system atrophy: natural history, MRI morphology, and dopamine receptor imaging with 123IBZM-SPECT.  J Neurol Neurosurg Psychiatry . 1994;  57 1047-1056
  PubMedGoogle Scholar
• 54 Herrlinger K, Waldner R, Ceballos-Baumann A, Weindl A. 123-I-iodobenzamide-SPECT dopamine D2 receptor imaging in normals, patients with Parkinson's disease and other akinetic-rigid syndromes.  Mov Disord . 1992;  7 146
  CrossrefPubMedGoogle Scholar
• 55 van Royen E, Verhoeff N F, Speelman J D, Wolters E C, Kuiper M A, Janssen A G. Multiple system atrophy and progressive supranuclear palsy: diminished striatal D2 dopamine receptor activity demonstrated by 123I-IBZM single photon emission computed tomography.  Arch Neurol . 1993;  50 513-516
  CrossrefPubMedGoogle Scholar
• 56 Pirker W, Asenbaum S, Wenger S. Iodine-123-epidepride-SPECT: studies in Parkinson's disease, multiple system atrophy and Huntington's disease.  J Nucl Med . 1997;  38 1711-1717
  PubMedGoogle Scholar
• 57 De Volder G A, Francart J, Laterre C. Decreased glucose utilization in the striatum and frontal lobe in probable striatonigral degeneration.  Ann Neurol . 1989;  26 239-247
  CrossrefPubMedGoogle Scholar
• 58 Eidelberg D, Takikawa S, Moeller J R. Striatal hypometabolism distinguishes striatonigral degeneration from Parkinson's disease.  Ann Neurol . 1993;  33 518-527
  CrossrefPubMedGoogle Scholar
• 59 Otsuka M, Kuwabara Y, Ichiya Y. Differentiating between multiple system atrophy and Parkinson's disease by positron emission tomography with ¹⁸F-dopa and ¹⁸F-FDG.  Ann Nucl Med . 1997;  11 251-257
  CrossrefPubMedGoogle Scholar
• 60 Gilman S, Koeppe R A, Junck L, Kluin K J, Lohman M, St. Laurent T R. Benzodiazepine receptor binding in the cerebellum in multiple system atrophy and olivopontocerebellar atrophy studied with positron emission tomography.  Adv Neurol . 1996;  69 459-466
  PubMedGoogle Scholar
• 61 Antonini A, Leenders K L, Vontobel P. Complementary PET studies of striatal neuronal function in the differential diagnosis between multiple system atrophy and Parkinson's disease.  Brain . 1997;  120 2187-2195
  CrossrefPubMedGoogle Scholar
• 62 Brooks D J, Ibanez V, Sawle G V. Differing patterns of striatal ¹⁸F-dopa uptake in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy.  Ann Neurol . 1990;  28 547-555
  CrossrefPubMedGoogle Scholar
• 63 Eidelberg D. Positron emission tomography studies in parkinsonism.  Neurol Clin . 1992;  10 421-433
  PubMedGoogle Scholar
• 64 Gilman S, Koeppe R A, Junck L. Decreased striatal monoaminergic terminals in multiple system atrophy detected with positron emission tomography.  Ann Neurol . 1999;  45 769-777
  CrossrefPubMedGoogle Scholar
• 65 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
  PubMedGoogle Scholar
• 66 Brooks D J, Ibanez V, Sawle G V. 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;  31 184-192
  CrossrefPubMedGoogle Scholar
• 67 Momose T, Sasaki Y. Striatal dopamine D2 receptor in Parkinson disease and its related disorders assessed by C-11 NMSP and PET.  Nippon Rinsho . 1997;  55 227-232
  PubMedGoogle Scholar
• 68 Burn D J, Rinne J O, Quinn N P, Lees A J, Marsden C D, Brooks D J. Striatal opioid receptor binding in Parkinson's disease, striatonigral degeneration and Steele-Richardson-Olszewski syndrome, a [¹¹C]diprenorphine PET study.  Brain . 1995;  118 951-958
  PubMedGoogle Scholar
• 69 Schrag A, Rinne J O, Burn D J. Olivopontocerebellar atrophy and multiple system atrophy: clinical follow-up of 10 patients studied with PET [letter; comment].  Ann Neurol . 1998;  44 151-152
  PubMedGoogle Scholar