Handbook of the Cerebellum and Cerebellar Disorders pp 2119-2141 | Cite as
Multiple System Atrophy (MSA)
Abstract
Multiple system atrophy (MSA) is a sporadic, rapidly progressive neurodegenerative disorder characterized clinically by a combination of cerebellar dysfunction or parkinsonism and autonomic failure. The histopathological hallmark of MSA is the presence of glial cytoplasmic inclusions composed predominantly of α-synuclein within multiple systems of the brain and the spinal cord accompanied by gliosis and neuronal loss. In the past few years there has been substantial progress in the understanding of the pathogenesis of this fatal neurodegenerative disease. The most recent studies indicate that this is a primary oligodendroglial disorder with synucleinopathy leading to subsequent neurodegeneration.
The authors review the epidemiology, clinical features, diagnostic criteria, neuropathology, pathogenesis, management and therapeutic approaches to this disease.
Keywords
Multiple System Atrophy Progressive Supranuclear Palsy Cerebellar Ataxia Autonomic Failure Multiple System Atrophy PatientReferences
- Adams MR, Van Bogaert L, van der Eecken H (1961) Nigro-striate and cerebello-nigro-striate degeneration (Clinical uniqueness and pathological variability of presenile degeneration of the extrapyramidal rigidity type). Psychiatr Neurol 142:219–259CrossRefGoogle Scholar
- Alam M, Smith G, Bleasdale-Barr K et al (1995) Effects of the peptide release inhibitor, octreotide, on daytime hypotension and on nocturnal hypertension in primary autonomic failure. J Hypertens 13:1664–1669PubMedGoogle Scholar
- Al-Chalabi A, Durr A, Wood NW et al (2009) Genetic variants of the alpha-synuclein gene SNCA are associated with multiple system atrophy. PLoS ONE 4:e7114PubMedCrossRefGoogle Scholar
- Angot E, Steiner JA, Hansen C et al (2010) Are synucleinopathies prion-like disorders? Lancet Neurol 9:1128–1138PubMedCrossRefGoogle Scholar
- Apostolidis A, Dasgupta P, Denys P et al (2009) Recommendations on the use of botulinum toxin in the treatment of lower urinary tract disorders and pelvic floor dysfunctions: a European consensus report. Eur Urol 55:100–119PubMedCrossRefGoogle Scholar
- Armstrong RA, Cairns NJ, Lantos PL (2007) A quantitative study of the pathological changes in white matter in multiple system atrophy. Neuropathology 27:221–227PubMedCrossRefGoogle Scholar
- Beck RO, Betts CD, Fowler CJ (1994) Genitourinary dysfunction in multiple system atrophy: clinical features and treatment in 62 cases. J Urol 151:1336–1341PubMedGoogle Scholar
- Ben Shlomo Y, Wenning GK, Tison F et al (1997) Survival of patients with pathologically proven multiple system atrophy: a meta-analysis. Neurology 48:384–393PubMedCrossRefGoogle Scholar
- Bensimon G, Ludolph A, Agid Y et al (2009) Riluzole treatment, survival and diagnostic criteria in Parkinson plus disorders: the NNIPPS study. Brain 132:156–171PubMedCrossRefGoogle Scholar
- Berg D, Godau J, Walter U (2008) Transcranial sonography in movement disorders. Lancet Neurol 7:1044–1055PubMedCrossRefGoogle Scholar
- Boesch SM, Wenning GK, Ransmayr G et al (2002) Dystonia in multiple system atrophy. J Neurol Neurosurg Psychiatry 72:300–303PubMedCrossRefGoogle Scholar
- Bower JH, Maraganore DM, McDonnell SK et al (1997) Incidence of progressive supranuclear palsy and multiple system atrophy in Olmsted County, Minnesota, 1976 to 1990. Neurology 49:1284–1288PubMedCrossRefGoogle Scholar
- Brooks DJ, Seppi K (2009) Proposed neuroimaging criteria for the diagnosis of multiple system atrophy. Mov Disord 24:949–964PubMedCrossRefGoogle Scholar
- Casarejos MJ, Menendez J, Solano RM et al (2006) Susceptibility to rotenone is increased in neurons from parkin null mice and is reduced by minocycline. J Neurochem 97:934–946PubMedCrossRefGoogle Scholar
- Chrysostome V, Tison F, Yekhlef F et al (2004) Epidemiology of multiple system atrophy: a prevalence and pilot risk factor study in Aquitaine, France. Neuroepidemiology 23:201–208PubMedCrossRefGoogle Scholar
- Cilia R, Marotta G, Benti R et al (2005) Brain SPECT imaging in multiple system atrophy. J Neural Transm 112:1635–1645PubMedCrossRefGoogle Scholar
- Colosimo C, Merello M, Pontieri FE (1996) Amantadine in parkinsonian patients unresponsive to levodopa: a pilot study. J Neurol 243:422–425PubMedCrossRefGoogle Scholar
- Daniel S (1999) The neuropathology and neurochemistry of multiple system atrophy. In: Mathias CJ, Bannister R (eds) Autonomic failure: a textbook of clinical disorders of the autonomic nervous system. Oxford University Press, OxfordGoogle Scholar
- Danzer KM, Haasen D, Karow AR et al (2007) Different species of alpha-synuclein oligomers induce calcium influx and seeding. J Neurosci 27:9220–9232PubMedCrossRefGoogle Scholar
- Danzer KM, Krebs SK, Wolff M et al (2009) Seeding induced by alpha-synuclein oligomers provides evidence for spreading of alpha-synuclein pathology. J Neurochem 111:192–203PubMedCrossRefGoogle Scholar
- Deguchi K, Ikeda K, Shimamura M et al (2007) Assessment of autonomic dysfunction of multiple system atrophy with laryngeal abductor paralysis as an early manifestation. Clin Neurol Neurosurg 109:892–895PubMedCrossRefGoogle Scholar
- Dejerine J, Thomas A (1900) L'atrophie olivo-ponto-cérébelleuse. Nouvelle iconographie de la Salpétrière: Clinique des maladies du système nerveux 13:330–370Google Scholar
- Dodel R, Spottke A, Gerhard A et al (2010) Minocycline 1-year therapy in multiple-system-atrophy: effect on clinical symptoms and [(11)C] (R)-PK11195 PET (MEMSA-trial). Mov Disord 25:97–107PubMedGoogle Scholar
- Eckert T, Barnes A, Dhawan V et al (2005) FDG PET in the differential diagnosis of parkinsonian disorders. Neuroimage 26:912–921PubMedCrossRefGoogle Scholar
- Eichhorn TE, Oertel WH (2001) Macrogol 3350/electrolyte improves constipation in Parkinson‘s disease and multiple system atrophy. Mov Disord 16:1176–1177PubMedCrossRefGoogle Scholar
- Fowler CJ, O’Malley KJ (2003) Investigation and management of neurogenic bladder dysfunction. J Neurol Neurosurg Psychiatry 74(Suppl 4):iv27–iv31PubMedGoogle Scholar
- Freeman R (2008) Current pharmacologic treatment for orthostatic hypotension. Clin Auton Res 18(Suppl 1):14–18PubMedCrossRefGoogle Scholar
- Frey KA, Koeppe RA, Kilbourn MR et al (1996) Presynaptic monoaminergic vesicles in Parkinson‘s disease and normal aging. Ann Neurol 40:873–884PubMedCrossRefGoogle Scholar
- Friess E, Kuempfel T, Modell S et al (2006) Paroxetine treatment improves motor symptoms in patients with multiple system atrophy. Parkinsonism Relat Disord 12:432–437PubMedCrossRefGoogle Scholar
- Geser F, Wenning GK, Seppi K et al (2006) Progression of multiple system atrophy (MSA): a prospective natural history study by the European MSA Study Group (EMSA SG). Mov Disord 21:179–186PubMedCrossRefGoogle Scholar
- Giannantoni A, Rossi A, Mearini E et al (2009) Botulinum toxin A for overactive bladder and detrusor muscle overactivity in patients with Parkinson‘s disease and multiple system atrophy. J Urol 182:1453–1457PubMedCrossRefGoogle Scholar
- Gilman S, Markel DS, Koeppe RA et al (1988) Cerebellar and brainstem hypometabolism in olivopontocerebellar atrophy detected with positron emission tomography. Ann Neurol 23:223–230PubMedCrossRefGoogle Scholar
- Gilman S, Koeppe RA, Junck L et al (1994) Patterns of cerebral glucose metabolism detected with positron emission tomography differ in multiple system atrophy and olivopontocerebellar atrophy. Ann Neurol 36:166–175PubMedCrossRefGoogle Scholar
- Gilman S, Frey KA, Koeppe RA et al (1996) Decreased striatal monoaminergic terminals in olivopontocerebellar atrophy and multiple system atrophy demonstrated with positron emission tomography. Ann Neurol 40:885–892PubMedCrossRefGoogle Scholar
- Gilman S, Low P, Quinn N et al (1998) Consensus statement on the diagnosis of multiple system atrophy. American Autonomic Society and American Academy of Neurology. Clin Auton Res 8:359–362PubMedCrossRefGoogle Scholar
- Gilman S, Koeppe RA, Junck L et al (1999) Decreased striatal monoaminergic terminals in multiple system atrophy detected with positron emission tomography. Ann Neurol 45:769–777PubMedCrossRefGoogle Scholar
- Gilman S, Little R, Johanns J et al (2000) Evolution of sporadic olivopontocerebellar atrophy into multiple system atrophy. Neurology 55:527–532PubMedCrossRefGoogle Scholar
- Gilman S, Wenning GK, Low PA et al (2008) Second consensus statement on the diagnosis of multiple system atrophy. Neurology 71:670–676PubMedCrossRefGoogle Scholar
- Goetz CG, Tanner CM, Klawans HL (1984) The pharmacology of olivopontocerebellar atrophy. Adv Neurol 41:143–148PubMedGoogle Scholar
- Graham JG, Oppenheimer DR (1969) Orthostatic hypotension and nicotine sensitivity in a case of multiple system atrophy. J Neurol Neurosurg Psychiatry 32:28–34PubMedCrossRefGoogle Scholar
- Halaska M, Ralph G, Wiedemann A et al (2003) Controlled, double-blind, multicentre clinical trial to investigate long-term tolerability and efficacy of trospium chloride in patients with detrusor instability. World J Urol 20:392–399PubMedGoogle Scholar
- Hanna PA, Jankovic J, Kirkpatrick JB (1999) Multiple system atrophy: the putative causative role of environmental toxins. Arch Neurol 56:90–94PubMedCrossRefGoogle Scholar
- Hara K, Momose Y, Tokiguchi S et al (2007) Multiplex families with multiple system atrophy. Arch Neurol 64:545–551PubMedCrossRefGoogle Scholar
- Hlavanda E, Kovacs J, Olah J et al (2002) Brain-specific p25 protein binds to tubulin and microtubules and induces aberrant microtubule assemblies at substoichiometric concentrations. Biochemistry 41:8657–8664PubMedCrossRefGoogle Scholar
- Holmberg B, Johansson JO, Poewe W et al (2007) Safety and tolerability of growth hormone therapy in multiple system atrophy: A double-blind, placebo-controlled study. Mov Disord 22:1138–1144PubMedCrossRefGoogle Scholar
- Horimoto Y, Aiba I, Yasuda T et al (2002) Longitudinal MRI study of multiple system atrophy - when do the findings appear, and what is the course? J Neurol 249:847–854PubMedCrossRefGoogle Scholar
- Hsu LJ, Sagara Y, Arroyo A et al (2000) Alpha-synuclein promotes mitochondrial deficit and oxidative stress. Am J Pathol 157:401–410PubMedCrossRefGoogle Scholar
- Hughes AJ, Colosimo C, Kleedorfer B et al (1992) The dopaminergic response in multiple system atrophy. J Neurol Neurosurg Psychiatry 55:1009–1013PubMedCrossRefGoogle Scholar
- Hussain IF, Brady CM, Swinn MJ et al (2001) 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 71:371–374PubMedCrossRefGoogle Scholar
- Iranzo A, Santamaria J, Tolosa E et al (2004) Long-term effect of CPAP in the treatment of nocturnal stridor in multiple system atrophy. Neurology 63:930–932PubMedCrossRefGoogle Scholar
- Ito T, Sakakibara R, Yasuda K et al (2006) Incomplete emptying and urinary retention in multiple-system atrophy: when does it occur and how do we manage it? Mov Disord 21:816–823PubMedCrossRefGoogle Scholar
- Jain S, Dawson J, Quinn NP et al (2004) Occupational therapy in multiple system atrophy: a pilot randomized controlled trial. Mov Disord 19:1360–1364PubMedCrossRefGoogle Scholar
- Jankovic J, Gilden JL, Hiner BC et al (1993) Neurogenic orthostatic hypotension: a double-blind, placebo-controlled study with midodrine. Am J Med 95:38–48PubMedCrossRefGoogle Scholar
- Jellinger KA (2006) P25alpha immunoreactivity in multiple system atrophy and Parkinson disease. Acta Neuropathol 112:112PubMedCrossRefGoogle Scholar
- Jellinger KA, Seppi K, Wenning GK (2005) Grading of neuropathology in multiple system atrophy: proposal for a novel scale. Mov Disord 20(Suppl 12):S29–S36PubMedCrossRefGoogle Scholar
- Kahle PJ, Neumann M, Ozmen L et al (2002) Hyperphosphorylation and insolubility of alpha-synuclein in transgenic mouse oligodendrocytes. EMBO Rep 3:583–588PubMedCrossRefGoogle Scholar
- Kato S, Nakamura H (1990) Cytoplasmic argyrophilic inclusions in neurons of pontine nuclei in patients with olivopontocerebellar atrophy: immunohistochemical and ultrastructural studies. Acta Neuropathol 79:584–594PubMedCrossRefGoogle Scholar
- Kaufmann H (2008) L-dihydroxyphenylserine (Droxidopa): a new therapy for neurogenic orthostatic hypotension: the US experience. Clin Auton Res 18(Suppl 1):19–24PubMedCrossRefGoogle Scholar
- Kaufmann H, Saadia D, Voustianiouk A et al (2003) Norepinephrine precursor therapy in neurogenic orthostatic hypotension. Circulation 108:724–728PubMedCrossRefGoogle Scholar
- Klos KJ, Bower JH, Josephs KA et al (2005) Pathological hypersexuality predominantly linked to adjuvant dopamine agonist therapy in Parkinson‘s disease and multiple system atrophy. Parkinsonism Relat Disord 11:381–386PubMedCrossRefGoogle Scholar
- Kluin KJ, Gilman S, Markel DS et al (1988) Speech disorders in olivopontocerebellar atrophy correlate with positron emission tomography findings. Ann Neurol 23:547–554PubMedCrossRefGoogle Scholar
- Kollensperger M, Stampfer-Kountchev M, Seppi K et al (2007) Progression of dysautonomia in multiple system atrophy: a prospective study of self-perceived impairment. Eur J Neurol 14:66–72PubMedCrossRefGoogle Scholar
- Kollensperger M, Geser F, Ndayisaba JP et al (2010) Presentation, diagnosis, and management of multiple system atrophy in Europe: final analysis of the European multiple system atrophy registry. Mov Disord 25(15):2604–2612PubMedCrossRefGoogle Scholar
- Kovacs GG, Gelpi E, Lehotzky A et al (2007) The brain-specific protein TPPP/p25 in pathological protein deposits of neurodegenerative diseases. Acta Neuropathol 113:153–161PubMedCrossRefGoogle Scholar
- Lahrmann H, Cortelli P, Hilz M et al (2006) EFNS guidelines on the diagnosis and management of orthostatic hypotension. Eur J Neurol 13:930–936PubMedCrossRefGoogle Scholar
- Lee PH, Kim JW, Bang OY et al (2008) Autologous mesenchymal stem cell therapy delays the progression of neurological deficits in patients with multiple system atrophy. Clin Pharmacol Ther 83:723–730PubMedCrossRefGoogle Scholar
- Lees AJ, Bannister R (1981) The use of lisuride in the treatment of multiple system atrophy with autonomic failure (Shy-Drager syndrome). J Neurol Neurosurg Psychiatry 44:347–351PubMedCrossRefGoogle Scholar
- Lindersson E, Lundvig D, Petersen C et al (2005) p25alpha Stimulates alpha-synuclein aggregation and is co-localized with aggregated alpha-synuclein in alpha-synucleinopathies. J Biol Chem 280:5703–5715PubMedCrossRefGoogle Scholar
- Liu Z, Sakakibara R, Odaka T et al (2005) Mosapride citrate, a novel 5-HT4 agonist and partial 5-HT3 antagonist, ameliorates constipation in parkinsonian patients. Mov Disord 20:680–686PubMedCrossRefGoogle Scholar
- Low PA, Gilden JL, Freeman R et al (1997) Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension. A randomized, double-blind multicenter study. Midodrine Study Group. J Am Med Assoc 277:1046–1051CrossRefGoogle Scholar
- Luk KC, Song C, O'Brien P et al (2009) Exogenous alpha-synuclein fibrils seed the formation of Lewy body-like intracellular inclusions in cultured cells. Proc Natl Acad Sci USA 106:20051–20056PubMedGoogle Scholar
- Mancini F, Zangaglia R, Cristina S et al (2003) Double-blind, placebo-controlled study to evaluate the efficacy and safety of botulinum toxin type A in the treatment of drooling in parkinsonism. Mov Disord 18:685–688PubMedCrossRefGoogle Scholar
- Mathias CJ (2008) L-dihydroxyphenylserine (Droxidopa) in the treatment of orthostatic hypotension: the European experience. Clin Auton Res 18(Suppl 1):25–29PubMedCrossRefGoogle Scholar
- Mathias CJ, Fosbraey P, da Costa DF et al (1986) The effect of desmopressin on nocturnal polyuria, overnight weight loss, and morning postural hypotension in patients with autonomic failure. Brit Med J 293:353–354, Clin Res.EdCrossRefGoogle Scholar
- Mathias CJ, Senard JM, Braune S et al (2001) L-threo-dihydroxyphenylserine (L-threo-DOPS; droxidopa) in the management of neurogenic orthostatic hypotension: a multi-national, multi-center, dose-ranging study in multiple system atrophy and pure autonomic failure. Clin Auton Res 11:235–242PubMedCrossRefGoogle Scholar
- Matsuo A, Akiguchi I, Lee GC et al (1998) Myelin degeneration in multiple system atrophy detected by unique antibodies. Am J Pathol 153:735–744PubMedCrossRefGoogle Scholar
- Miller DW, Johnson JM, Solano SM et al (2005) Absence of alpha-synuclein mRNA expression in normal and multiple system atrophy oligodendroglia. J Neural Transm 112:1613–1624PubMedCrossRefGoogle Scholar
- Muller J, Wenning GK, Wissel J et al (2002) Botulinum toxin treatment in atypical parkinsonian disorders associated with disabling focal dystonia. J Neurol 249:300–304PubMedCrossRefGoogle Scholar
- Nicoletti G, Lodi R, Condino F et al (2006) Apparent diffusion coefficient measurements of the middle cerebellar peduncle differentiate the Parkinson variant of MSA from Parkinson‘s disease and progressive supranuclear palsy. Brain 129:2679–2687PubMedCrossRefGoogle Scholar
- Nishie M, Mori F, Fujiwara H et al (2004) Accumulation of phosphorylated alpha-synuclein in the brain and peripheral ganglia of patients with multiple system atrophy. Acta Neuropathol 107:292–298PubMedCrossRefGoogle Scholar
- Orimo S, Kanazawa T, Nakamura A et al (2007) Degeneration of cardiac sympathetic nerve can occur in multiple system atrophy. Acta Neuropathol 113:81–86PubMedCrossRefGoogle Scholar
- O'Sullivan JD (2002) Apomorphine as an alternative to sildenafil in Parkinson‘s disease. J Neurol Neurosurg Psychiatry 72:681PubMedCrossRefGoogle Scholar
- O'Sullivan JD, Hughes AJ (1998) Apomorphine-induced penile erections in Parkinson‘s disease. Mov Disord 13:536–539PubMedCrossRefGoogle Scholar
- Ozawa T (2007) Morphological substrate of autonomic failure and neurohormonal dysfunction in multiple system atrophy: impact on determining phenotype spectrum. Acta Neuropathol 114:201–211PubMedCrossRefGoogle Scholar
- Ozawa T, Paviour D, Quinn NP et al (2004) The spectrum of pathological involvement of the striatonigral and olivopontocerebellar systems in multiple system atrophy: clinicopathological correlations. Brain 127:2657–2671PubMedCrossRefGoogle Scholar
- Papatsoris AG, Papapetropoulos S, Singer C et al (2008) Urinary and erectile dysfunction in multiple system atrophy (MSA). Neurourol Urodyn 27:22–27PubMedCrossRefGoogle Scholar
- Papp MI, Lantos PL (1992) Accumulation of tubular structures in oligodendroglial and neuronal cells as the basic alteration in multiple system atrophy. J Neurol Sci 107:172–182PubMedCrossRefGoogle Scholar
- Papp MI, Lantos PL (1994) The distribution of oligodendroglial inclusions in multiple system atrophy and its relevance to clinical symptomatology. Brain 117(Pt 2):235–243PubMedCrossRefGoogle Scholar
- Papp MI, Kahn JE, Lantos PL (1989) Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome). J Neurol Sci 94:79–100PubMedCrossRefGoogle Scholar
- Park HJ, Bang G, Lee BR et al. (2010) Neuroprotective effect of human mesenchymal stem cells in an animal model of double toxin-induced multiple system atrophy-parkinsonism. Cell Transplant. http://www.ingentaconnect.com/content/cog/ct/pre-prints/ct0169park. Epub ahead of print
- Paviour DC, Williams D, Fowler CJ et al (2005) Is sphincter electromyography a helpful investigation in the diagnosis of multiple system atrophy? A retrospective study with pathological diagnosis. Mov Disord 20:1425–1430PubMedCrossRefGoogle Scholar
- Quinn N (1989) Multiple system atrophy – the nature of the beast. J Neurol Neurosurg Psychiatry 52:78–89CrossRefGoogle Scholar
- Raffel DM, Koeppe RA, Little R et al (2006) PET measurement of cardiac and nigrostriatal denervation in Parkinsonian syndromes. J Nucl Med 47:1769–1777PubMedGoogle Scholar
- Rascol O, Schelosky L (2009) 123I-metaiodobenzylguanidine scintigraphy in Parkinson‘s disease and related disorders. Mov Disord 24(Suppl 2):S732–S741PubMedCrossRefGoogle Scholar
- Riley DE (2000) Orthostatic hypotension in multiple system atrophy. Curr Treat Options Neurol 2:225–230PubMedCrossRefGoogle Scholar
- Rosenthal G, Gilman S, Koeppe RA et al (1988) Motor dysfunction in olivopontocerebellar atrophy is related to cerebral metabolic rate studied with positron emission tomography. Ann Neurol 24:414–419PubMedCrossRefGoogle Scholar
- Saha AR, Ninkina NN, Hanger DP et al (2000) Induction of neuronal death by alpha-synuclein. Eur J Neurosci 12:3073–3077PubMedCrossRefGoogle Scholar
- Sakakibara R, Hattori T, Uchiyama T et al (2000) Urinary dysfunction and orthostatic hypotension in multiple system atrophy: which is the more common and earlier manifestation? J Neurol Neurosurg Psychiatry 68:65–69PubMedCrossRefGoogle Scholar
- Sakakibara R, Yamaguchi T, Uchiyama T et al (2007) Calcium polycarbophil improves constipation in primary autonomic failure and multiple system atrophy subjects. Mov Disord 22:1672–1673PubMedCrossRefGoogle Scholar
- Schocke MF, Seppi K, Esterhammer R et al (2002) Diffusion-weighted MRI differentiates the Parkinson variant of multiple system atrophy from PD. Neurology 58:575–580PubMedCrossRefGoogle Scholar
- Scholz SW, Houlden H, Schulte C et al (2009) SNCA variants are associated with increased risk for multiple system atrophy. Ann Neurol 65:610–614PubMedCrossRefGoogle Scholar
- Schrag A, Good CD, Miszkiel K et al (2000) Differentiation of atypical parkinsonian syndromes with routine MRI. Neurology 54:697–702PubMedCrossRefGoogle Scholar
- Schrag A, Geser F, Stampfer-Kountchev M et al (2006) Health-related quality of life in multiple system atrophy. Mov Disord 21(6):809–815PubMedCrossRefGoogle Scholar
- Seppi K, Poewe W (2010) Brain magnetic resonance imaging techniques in the diagnosis of parkinsonian syndromes. Neuroimaging Clin N Am 20:29–55PubMedCrossRefGoogle Scholar
- Seppi K, Schocke MF, Esterhammer R et al (2003) Diffusion-weighted imaging discriminates progressive supranuclear palsy from PD, but not from the parkinson variant of multiple system atrophy. Neurology 60:922–927PubMedCrossRefGoogle Scholar
- Seppi K, Peralta C, Diem-Zangerl A et al (2006) Placebo-controlled trial of riluzole in multiple system atrophy. Eur J Neurol 13:1146–1148PubMedCrossRefGoogle Scholar
- Shannon JR, Diedrich A, Biaggioni I et al (2002) Water drinking as a treatment for orthostatic syndromes. Am J Med 112:355–360PubMedCrossRefGoogle Scholar
- Shults CW, Rockenstein E, Crews L et al (2005) Neurological and neurodegenerative alterations in a transgenic mouse model expressing human alpha-synuclein under oligodendrocyte promoter: implications for multiple system atrophy. J Neurosci 25:10689–10699PubMedCrossRefGoogle Scholar
- Shy GM, Drager GA (1960) A neurological syndrome associated with orthostatic hypotension: a clinical-pathologic study. Arch Neurol 2:511–527PubMedCrossRefGoogle Scholar
- Singer W, Sandroni P, Opfer-Gehrking TL et al (2006) Pyridostigmine treatment trial in neurogenic orthostatic hypotension. Arch Neurol 63:513–518PubMedCrossRefGoogle Scholar
- Sone M, Yoshida M, Hashizume Y et al (2005) Alpha-Synuclein-immunoreactive structure formation is enhanced in sympathetic ganglia of patients with multiple system atrophy. Acta Neuropathol 110:19–26PubMedCrossRefGoogle Scholar
- Song YJ, Lundvig DM, Huang Y et al (2007) p25alpha relocalizes in oligodendroglia from myelin to cytoplasmic inclusions in multiple system atrophy. Am J Pathol 171:1291–1303PubMedCrossRefGoogle Scholar
- Spillantini MG, Crowther RA, Jakes R et al (1998) Filamentous alpha-synuclein inclusions link multiple system atrophy with Parkinson‘s disease and dementia with Lewy bodies. Neurosci Lett 251:205–208PubMedCrossRefGoogle Scholar
- Stefanova N, Tison F, Reindl M et al (2005a) Animal models of multiple system atrophy. Trends Neurosci 28:501–506PubMedCrossRefGoogle Scholar
- Stefanova N, Reindl M, Poewe W et al (2005b) In vitro models of multiple system atrophy. Mov Disord 20(Suppl 12):S53–S56PubMedCrossRefGoogle Scholar
- Stefanova N, Reindl M, Neumann M et al (2007) Microglial activation mediates neurodegeneration related to oligodendroglial alpha-synucleinopathy: implications for multiple system atrophy. Mov Disord 22:2196–2203PubMedCrossRefGoogle Scholar
- Stefanova N, Poewe W, Wenning GK (2008) Rasagiline is neuroprotective in a transgenic model of multiple system atrophy. Exp Neurol 210:421–427PubMedCrossRefGoogle Scholar
- Stefanova N, Bucke P, Duerr S et al (2009a) Multiple system atrophy: an update. Lancet Neurol 8:1172–1178PubMedCrossRefGoogle Scholar
- Stefanova N, Hainzer M, Stemberger S et al (2009b) Striatal transplantation for multiple system atrophy–are grafts affected by alpha-synucleinopathy? Exp Neurol 219:368–371PubMedCrossRefGoogle Scholar
- Stemberger S, Poewe W, Wenning GK, Stefanova N (2010) Targeted overexpression of human alpha-synuclein in oligodendroglia induces lesions linked to MSA-like progressive autonomic failure. Exp Neurol 224(2):459–464PubMedCrossRefGoogle Scholar
- Tada M, Kakita A, Toyoshima Y et al (2009) Depletion of medullary serotonergic neurons in patients with multiple system atrophy who succumbed to sudden death. Brain 132:1810–1819PubMedCrossRefGoogle Scholar
- Testa D, Filippini G, Farinotti M et al (1996) Survival in multiple system atrophy: a study of prognostic factors in 59 cases. J Neurol 243:401–404PubMedCrossRefGoogle Scholar
- Thobois S, Broussolle E, Toureille L et al (2001) Severe dysphagia after botulinum toxin injection for cervical dystonia in multiple system atrophy. Mov Disord 16:764–765PubMedCrossRefGoogle Scholar
- Trojanowski JQ, Revesz T (2007) Proposed neuropathological criteria for the post mortem diagnosis of multiple system atrophy. Neuropathol Appl Neurobiol 33:615–620PubMedCrossRefGoogle Scholar
- Ubhi K, Rockenstein E, Mante M et al (2008) Rifampicin reduces alpha-synuclein in a transgenic mouse model of multiple system atrophy. Neuroreport 19:1271–1276PubMedCrossRefGoogle Scholar
- Vodusek DB (2001) Sphincter EMG and differential diagnosis of multiple system atrophy. Mov Disord 16:600–607PubMedCrossRefGoogle Scholar
- Walter U, Behnke S, Eyding J (2007) Transcranial brain parenchyma sonography in movement disorders: state of the art. Ultrasound Med Biol 33:15–25PubMedCrossRefGoogle Scholar
- Watanabe H, Saito Y, Terao S et al (2002) Progression and prognosis in multiple system atrophy: an analysis of 230 Japanese patients. Brain 125:1070–1083PubMedCrossRefGoogle Scholar
- Wenning GK (2005) Placebo-controlled trial of amantadine in multiple-system atrophy. Clin Neuropharmacol 28:225–227PubMedCrossRefGoogle Scholar
- Wenning GK, Ben Shlomo Y, Magalhaes M et al (1994) Clinical features and natural history of multiple system atrophy. An analysis of 100 cases. Brain 117(Pt 4):835–845PubMedCrossRefGoogle Scholar
- Wenning GK, Tison F, Elliott L et al (1996) Olivopontocerebellar pathology in multiple system atrophy. Mov Disord 11:157–162PubMedCrossRefGoogle Scholar
- Wenning GK, Seppi K, Tison F et al (2002) A novel grading scale for striatonigral degeneration (multiple system atrophy). J Neural Transm 109:307–320PubMedCrossRefGoogle Scholar
- Wenning GK, Geser F, Stampfer-Kountchev M et al (2003) Multiple system atrophy: an update. Mov Disord 18(Suppl 6):S34–S42PubMedCrossRefGoogle Scholar
- Wenning GK, Colosimo C, Geser F et al (2004) Multiple system atrophy. Lancet Neurol 3:93–103PubMedCrossRefGoogle Scholar
- Wenning GK, Stefanova N, Jellinger KA et al (2008) Multiple system atrophy: a primary oligodendrogliopathy. Ann Neurol 64:239–246PubMedCrossRefGoogle Scholar
- Wullner U, Abele M, Schmitz-Huebsch T et al (2004) Probable multiple system atrophy in a German family. J Neurol Neurosurg Psychiatry 75:924–925PubMedCrossRefGoogle Scholar
- Yamamoto T, Sakakibara R, Uchiyama T et al (2005) When is Onuf's nucleus involved in multiple system atrophy? A sphincter electromyography study. J Neurol Neurosurg Psychiatry 76:1645–1648PubMedCrossRefGoogle Scholar
- Yoshida M (2007) Multiple system atrophy: alpha-synuclein and neuronal degeneration. Neuropathology 27:484–493PubMedCrossRefGoogle Scholar
- Young TM, Mathias CJ (2004) 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 75:1737–1741PubMedCrossRefGoogle Scholar
- Zhu S, Stavrovskaya IG, Drozda M et al (2002) Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice. Nature 417:74–78PubMedCrossRefGoogle Scholar