What is multiple system atrophy (MSA)?

Updated: Oct 17, 2018
  • Author: André Diedrich, MD, PhD; Chief Editor: Selim R Benbadis, MD  more...
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Answer

Multiple system atrophy (MSA) is defined as an adult-onset, sporadic, rapidly progressive, multisystem, neurodegenerative fatal disease of undetermined etiology, characterized clinically by varying severity of parkinsonian features; cerebellar, autonomic, and urogenital dysfunction; and corticospinal disorders. Neuropathological hallmarks of MSA are cell loss in the striatonigral and olivopontocerebellar structures of the brain and spinal cord accompanied by profuse, distinctive glia cytoplasmic inclusions (GCIs) formed by fibrillized alpha-synuclein proteins (defined as primary alpha-synucleinopathy). (See Etiology and Pathophysiology, History and Physical Examination, and Workup.) [1]

A consensus statement by the American Autonomic Society and American Academy of Neurology in 2007 [2] categorized MSA in MSA-P with predominant parkinsonism and MSA-P with dominant cerebellar features (MSA-C). (See Categories of MSA below.)

The concept of MSA as a unitary diagnosis encompassing several clinical syndromes has a long history. The first cases of MSA were presented as olivopontocerebellar atrophy (OPCA) about a century ago. The Shy-Drager syndrome with features of parkinsonism and autonomic failure with OH was described in 1960. The term MSA was introduced to unify different forms of MSA in 1996. The discovery of GCIs and alpha-synuclein immunostaining as a sensitive marker of MSA were major milestones in the definition of MSA as a clinicopathologic entity. (See Table 1, below). [3]

Table 1. Historical Milestones in the Definition of Terms for MSA (Open Table in a new window)

Term

Period

Authors

Comments

Olivopontocerebellar atrophy (OPCA)

1900

Dejerine and Thomas

Introduction of the term olivopontocerebellar atrophy

Orthostatic hypotension (OH)

1925

Bradbury and Eggleston

Introduction of autonomic failure as a clinical syndrome

Shy-Drager syndrome (SDS)

1960

Shy and Drager

Origin of this term as a neuropathologic entity with parkinsonism and autonomic failure with OH

Striatonigral degeneration (SND)

1960

Van der Eecken et al

Description of SND

Multiple system atrophy (MSA)

1969

Graham and Oppenheimer

Introduction of the term MSA, which represents SDS, SND, and OPCA as 1 entity

Glial cytoplasmic inclusions (GCIs)

1989

Papp et al, Matsuo et al

Discovery of GCIs as hallmark of MSA

Alpha-synuclein inclusion

1998

Spillantini et al, Wakabayashi et al

Alpha-synuclein immunostaining as a sensitive marker of MSA

MSA classification

1996-1999

Consensus Committee

Classification of MSA based on clinical domains and features and neuropathology

Unified MSA Rating Scale (UMSARS)

2003

European MSA Study Group

Unified MSA Rating Scale as a standard to define MSA symptoms [4, 5]

Second consensus for MSA

2007

Consensus Committee

New definition of MSA with simplified criteria

A consensus conference in 2007 [6] simplified the older definition of MSA—as determined by the Consensus Committee representing the American Autonomic Society and the American Academy of Neurology in 1996 and 1998 [2] —and incorporated current knowledge for a better assessment of the disease. [7]


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