Sections

Overview

Practice Essentials

Signs and symptoms

Usually autonomic and/or urinary dysfunction develops first. The earliest symptom that brings patients to medical attention typically is orthostatic hypotension.

Other symptoms of MSA are based on mixed dysfunction. When the disorder results in nonautonomic features, imbalance caused by cerebellar or extrapyramidal abnormalities is the most common feature.

Diagnosis

MSA is a difficult diagnosis, especially early in the clinical course, and the initial physician often misdiagnoses the condition. The most common initial diagnosis is idiopathic Parkinson disease.^[1]

The diagnosis of MSA is based mainly on clinical features.

Management

The cause of MSA remains unknown, and no current therapy can reverse or halt progression of the disease. The extrapyramidal and cerebellar aspects of the disease are debilitating and difficult to treat.

Drug therapy is directed mainly toward alleviation of symptoms of the movement disorder and orthostatic hypotension. Urinary incontinence, constipation, erectile dysfunction, and supine hypertension can also be addressed through pharmacologic therapy.

Next: Background

Background

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.)^[2]

A consensus statement by the American Autonomic Society and American Academy of Neurology in 2007^[3]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).^[4]

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^{[5, 6]}
Second consensus for MSA	2007	Consensus Committee	New definition of MSA with simplified criteria

A consensus conference in 2007^[7]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^[3]—and incorporated current knowledge for a better assessment of the disease.^[8]

Categories of MSA

The 2 categories of MSA are as follows:

MSA with predominant parkinsonism (MSA-P) - Extrapyramidal features predominate; the term striatonigral degeneration, parkinsonian variant is sometimes used
MSA with cerebellar features (MSA-C) - Cerebellar ataxia predominates; it is sometimes termed sporadic olivopontocerebellar atrophy

The designation of MSA-P or MSA-C depends on the dominant feature at the time of evaluation, which can change with time.

Shy-Drager syndrome

When autonomic failure predominates, MSA was sometimes termed Shy-Drager syndrome (not defined in the present consensus anymore).

Characteristics of MSA

Features indicating the presence of MSA (tables 2a and 2b) or of another disorder (Table 3) are described below. (Corticospinal tract dysfunction with extensor plantar response with hyperreflexia [pyramidal sign] is not used to categorize MSA.) (See DDx.)

Table 2a. Main Features for the Diagnosis of MSA (Open Table in a new window)

Clinical Domain	Feature	Comment
Autonomic dysfunction	Severe orthostatic hypotension (OH) Asymptomatic Symptomatic	OH is defined as blood pressure fall by at least 30mm Hg systolic and 15mm Hg diastolic within 3 minutes of standing from a previous 3-minute interval in the recumbent position.**
Urogenital dysfunction	Urinary incontinence (UI) or incomplete bladder emptying	UI is defined as persistent, involuntary, partial or total bladder emptying. ED usually occurs before symptomatic OH.***
Urogenital dysfunction	Erectile dysfunction (ED) in men
Parkinsonian features (87% incidence *)	Bradykinesia (BK)	BK is slowness of voluntary movement with progressive reduction in speed and amplitude during repetitive actions. PI not caused by primary visual, vestibular, cerebellar, or proprioceptive dysfunction.
	Rigidity
	Postural instability (PI)
	Tremor - Postural, resting, or both
Cerebellar dysfunction (54% incidence *)	Gait ataxia (GA)	GA is a wide-based stance with steps of irregular length and direction. Sustained gaze-evoked nystagmus
	Ataxic dysarthria
	Limb ataxia
	Oculomotor dysfunction
Coritcospinal tract dysfunction	Extensor plantar response with hyperreflexia	Babinsky sign, Pyramidal sign
Incidence of clinical features recorded during the lifetimes of 203 patients (Gilman et al^[3]). OH caused by drugs, food, temperature, deconditioning, or diabetes are excluded. **ED does not count in the definition of onset of disease, because it is a general feature in older people.

Table 2b. Additional Features for the Diagnosis of Possible MSA* (Open Table in a new window)

Category	Additional Features
Possible MSA-P Possible MSA-C	Babinski sign with hyperreflexia Stridor
Possible MSA-P	Rapidly progressive parkinsonism Poor response to levodopa Postural instability within 3 years of motor onset Gait ataxia, cerebellar dysarthria, limb ataxia, or cerebellar oculomotor dysfunction Dysphagia within 5 years of motor onset Atrophy on magnetic resonance imaging (MRI) of putamen, middle cerebellar peduncle, pons, or cerebellum Hypometabolism on 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) scanning in putamen, brainstem, or cerebellum
Possible MSA-C	Parkinsonism (bradykinesia and rigidity) Atrophy on MRI of the putamen, middle cerebellar peduncle, or pons Hypometabolism on FDG-PET in the putamen Presynaptic striatonigral dopaminergic denervation on single-photon emission computed tomography (SPECT) or PET scanning
*Modified from second consensus^[7]

Table 3. Characteristics That Do Not Support the Diagnosis of MSA (Open Table in a new window)

Procedure	Nonsupporting Features
History taking	Symptomatic onset at < 30 years Onset after age 75 years Family history of ataxia or parkinsonism Systemic diseases or other identifiable causes for features listed in Table 2a Hallucinations unrelated to medication Dementia
Physical examination	Classic parkinsonian pill-rolling rest tremor Clinically significant neuropathy Prominent slowing of vertical saccades or vertical supranuclear gaze palsy Evidence of focal cortical dysfunction, such as aphasia, alien limb syndrome, and parietal dysfunction
Laboratory study	Metabolic, molecular genetic, and imaging evidence of alternative cause of features listed in Table 2a White matter lesions suggesting multiple sclerosis

Levels of certainty of MSA

MSA can be ascertained as possible, probable, or definite MSA (see Table 4, below), based on autonomic and urogenital features, on the presence of parkinsonism, and on cerebellar dysfunction, as well as on additional features (see tables 2a and 2b, above).

Only pathologic findings of high density of alpha-synuclein-positive glial cytoplasmic inclusions (GCIs) and degenerative changes in the striatonigral or olivopontocerebellar pathways can definitively confirm the diagnosis of MSA. (See Workup.)

Table 4. Diagnostic Categories of MSA (Open Table in a new window)

Category	Definition
Possible MSA	A sporadic, progressive, adult (>30y) with onset disease* characterized by the following: Parkinsonism or cerebellar syndrome At least 1 feature of autonomic or urogenital dysfunction At least 1 of the additional features from Table 2b
Probable MSA	A sporadic, progressive, adult (>30y) with onset disease* characterized by the following: Autonomic failure involving urinary dysfunction Poorly levodopa-responsive parkinsonism or cerebellar dysfunction
Definitive MSA	A sporadic, progressive, adult (>30y) with onset disease pathologically confirmed by presence of high density GCIs in association with degenerative changes in striatonigral and olivopontocerebellar pathways
*Disease onset is defined as the initial presentation of any parkinsonian or cerebellar motor problems or autonomic features (except erectile dysfunction).

Red flags supporting the diagnosis of MSA include the following:

Orofacial dystonia
Disproportionate antecollis
Severe anterior flexion of the spine (camptocormia)
Severe lateral flexion of the spine (Pisa syndrome)
Contractures of hands and feet
Inspiratory sighs
Severe dysphonia
Severe dysarthria
New or increased snoring
Cold hands and feet
Pathologic laughter or crying
Jerky myoclonic postural/action tremor

Patient education

A variety of resources are available for patient education. These include the Web sites of the Multiple System Atrophy Coalitions, Autonomic Disorder Consortium of the Clinical Rare Diseases Research Network, and Vanderbilt Autonomic Dysfunction Center.

Next: Background

Etiology and Pathophysiology

MSA is characterized by progressive loss of neuronal and oligodendroglial cells in numerous sites in the central nervous system (CNS). The cause of MSA remains unclear, although a history of trauma has been suggested. Pesticide exposure as a causative factor in MSA has been suggested but has not been confirmed statistically.^[9]Autoimmune mechanisms have also been suggested as potential causes of MSA, but evidence for these is weak.

There is some evidence of genetic predispositions in Japanese cohorts. Autosomal recessive inheritance^[10]and genetic alterations with abnormal expansion of 1 allele of the SCA type 3 gene has been reported.^[11]Single nucleotide polymorphisms (SNPs) at the SNCA locus coding for alpha-synuclide have been identified. G51D mutation in the SNCA locus has been described, but a connection between SCNA locus and MSA disease could not be confirmed. Associations with COQ2 and C9orf72 have been reported.^{[12, 13]}

Researchers initially assumed that gray-matter damage caused MSA. However, the discovery of oligodendroglial glial cytoplasmic inclusions (GCIs) (see Table 8) indicated that damage primarily affects the white matter.^[14]The chronic alterations in glial cells may impair trophic function between oligodendrocytes and axons and cause secondary neuronal damage. Whether the inclusions represent primary lesions or nonspecific secondary markers of cellular injury remains unknown. In addition to the GCIs, extensive myelin degeneration occurs in the brain. Changes in myelin may play an important role in the pathogenesis of MSA. The clinical symptoms of MSA correlate with cell loss in different CNS sites. (See Table 5, below.)

Table 5. Clinicopathologic Correlations (Open Table in a new window)

Clinical Symptom	Pathologic Findings and Location of Damage or Cell Loss
Orthostatic hypotension	Primary preganglionic damage of intermediolateral cell columns
Urinary incontinence (not retention)	Preganglionic cell loss in spinal cord (intermediolateral cell columns), related to detrusor hyperreflexia caused mainly by loss of inhibitory input to pontine micturition center (rather than to external urethral sphincter denervation alone)
Urinary retention caused by detrusor atonia	Sacral intermediolateral cell columns
Cerebellar ataxia	Cell loss in inferior olives, pontine nuclei, and cerebellar cortex
Pyramidal signs	Pyramidal tract demyelination
Extensor plantar response	Pyramidal tract lesion
Hyperreflexia	Pyramidal tract lesion
Motor abnormalities	GCIs in cortical motor areas or basal ganglia
Akinesia	Putamen, globus pallidus
Rigidity	Putaminal (not nigral) damage
Limb and gait ataxia	Inferior olives, basis pontis
Decreased or absent levodopa responsiveness	Striatal cell loss, loss of D1 and D2 receptors in striatum or impaired functional coupling of D1 and D2 receptors
Nystagmus	Inferior olives, pontine nuclei
Dysarthria	Pontine nuclei
Laryngeal stridor	Severe cell loss in nucleus ambiguus or biochemical defect causing atrophy of posterior cricoarytenoid muscles
Excessive daytime sleepiness	Loss of putative wake-active ventral periaqueductal gray matter dopaminergic neurons^[15]
Adapted from Wenning et al and other sources.

Next: Background

Epidemiology

Occurrence in the United States

The prevalence of MSA is reported to be between 3.4-4.9 cases per 100,000 population. The estimated mean incidence is 0.6-0.7 cases per 100,000 person-years. MSA meets orphan disease status.^{[16, 17]}

Many patients do not receive the correct diagnosis during their lifetime because of the difficulty in differentiating MSA from other disorders (eg, Parkinson disease, pure autonomic failure [PAF], other rare movement disorders). About 29-33% of patients with isolated late-onset cerebellar ataxia and 8-10% of patients with parkinsonism will develop MSA. Therefore, a higher prevalence than that estimated can be assumed.

International occurrence

In the European Union (EU), the prevalence rates show 4-5 cases per 100,000 persons. The incidence rate is about 0.6 cases per 100,000 persons per year.^[18]

In the United Kingdom, the crude prevalence of MSA, including all probable and possible cases, is 3.3 per 100,000 population.^[19]

In Iceland, the incidence is 0.6 per 100,000 and prevalence is 3.1 per 100,000.^[20]

In Japan, the prevalence is 13.1 per 100,000 individuals. The mean annual incidence is 0.68.^[21]

Race-, sex-, and age-related demographics

MSA has been encountered in Caucasian, African, and Asian populations. In Western countries, MSA-P predominates, occurring in 66-82% of patients. In Eastern countries (e.g., Japan), MSA-C is common, occurring in 67% of patients.

The disease more often affects men than women. The female-to-male ratio is around 1:2. (A ratio of 1:3-9 has also been reported.) However, the early and easy diagnosis of impotence may have led to the male statistical predominance of MSA. The mean age at onset in MSA is 52.5-55 years. The disease progresses over intervals of 1-18 years.

Next: Background

Prognosis

Patients with MSA have a poor prognosis. The disease progresses rapidly. Median survivals of 6.2-9.5 years from the onset of first symptoms have been reported since the late 20th century. No current therapeutic modality reverses or halts the progress of this disease. MSA-P and MSA-C have the same survival times, but MSA-P shows more rapid dysfunctional progression.

An older age at onset has been associated with shorter duration of survival in MSA. The overall striatonigral cell loss is correlated with the severity of disease at the time of death.

Bronchopneumonia (48%) and sudden death (21%) are common terminal conditions in MSA. Urinary dysfunction in MSA often leads to lower urinary tract infections (UTIs); more than 50% of patients with MSA suffer from recurrent lower UTIs and a significant number die of related complications.^[22]

Clinical Presentation

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Author

André Diedrich, MD, PhD Research Professor of Medicine and Biomedical Engineering, Autonomic Dysfunction Center, Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center

André Diedrich, MD, PhD is a member of the following medical societies: American Autonomic Society

Disclosure: Nothing to disclose.

Coauthor(s)

David Robertson, MD Director, Clinical and Translational Research Center, Vanderbilt Institute for Clinical and Translational Research, Principal Investigator, Autonomic Rare Disease Clinical Research Consortium, Elton Yates Professor of Medicine, Pharmacology, and Neurology, Vanderbilt University School of Medicine

David Robertson, MD is a member of the following medical societies: American Heart Association, Association of American Physicians

Disclosure: Nothing to disclose.

Chief Editor

Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida Morsani College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, American Medical Association

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Bioserenity, Catalyst, Ceribell, Eisai, Jazz, LivaNova, Neurelis, Neuropace, SK Life Science Science, Sunovion, Takeda, UCB<br/>Serve(d) as a speaker or a member of a speakers bureau for: Catalyst, Jazz, LivaNova, Neurelis, SK Life Science, Stratus, UCB<br/>Received research grant from: Cerevel Therapeutics; Ovid Therapeutics; Neuropace; Jazz; SK Life Science, Xenon Pharmaceuticals, UCB, Marinus, Longboard.

Acknowledgements

Nestor Galvez-Jimenez, MD, MSc, MHA Chairman, Department of Neurology, Program Director, Movement Disorders, Department of Neurology, Division of Medicine, Cleveland Clinic Florida

Nestor Galvez-Jimenez, MD, MSc, MHA is a member of the following medical societies: American Academy of Neurology, American College of Physicians, and Movement Disorders Society

Disclosure: Nothing to disclose.

Christopher Luzzio, MD Clinical Assistant Professor, Department of Neurology, University of Wisconsin at Madison School of Medicine and Public Health

Christopher Luzzio, MD is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Characteristic	MSA	Parkinson Disease
Response to chronic levodopa therapy*	Poor or unsustained motor response because of loss of postsynaptic dopamine receptors Initial improvement in 30% of patients with MSA, but 90% were unresponsive over a longer time; 50% develop levodopa-induced dyskinesia of orofacial and neck muscles	Good response
Effects on striatonigral transmission	Presynaptic and postsynaptic; dopaminergic cell bodies in substantia nigra and their terminals in striatum, as well as their striatal target cells, have reduced dopamine receptors	Presynaptic
Symmetry of movement disorder	Possibly asymmetrical	No data
Progression of symptoms	Rapid	Slow
Postural instability and falling**	Early Fast progression Worsen >20% of UPDRS scale**	Late Less progression (< 10%)
Progress of disability	Relatively fast disability; 30% decrease of activities of daily living in 1 year; 40% of patients in a wheelchair within 5 years (wheel chair sign)	Relatively slow disability
Abnormal speech	Severely affected speech in 30% of patients with MSA Dysarthrophonia and severe dysarthria are common	Less affected
Abnormal Respiration	Abnormal aspiration, inspiratory gasps, and stridor in 60% of patients with MSA Stridor caused by paralysis of vocal cord occurs especially at night but is also present during day	Less common
Lewy bodies (hyaline eosinophilic cytoplasmic neuronal inclusions)	Not present***	Primarily in substantia nigra
Cytoplasmic inclusions (immunocytochemical reaction with antibodies to alpha synuclein)	Glial inclusions; argyrophilic cellular inclusions in oligodendrocytes	Absent
Thermoregulation, skin perfusion	Cold hands and decrease of warm-up after cold-pack stimulus	Normal
Caudate-putamen index of dopamine uptake (on positron emission tomography [PET] scanning)	Decreased in putamen and caudate	Decreased in putamen with smaller decrease in caudate
Growth hormone release with intravenous (IV) injection of clonidine	No release; dysfunction of hypothalamic-pituitary pathway (alpha2-adrenoceptor-hypothalamic deficit)	Increase of growth hormone, intact function
^* A positive response to levodopa is defined as a significant improvement of motor features during 3 months’ application of escalating doses of levodopa with a peripheral decarboxylase inhibitor.^[7] ^ Postural instability as defined by item 30 of the Unified Parkinson's Disease Rating Scale (UPDRS) part III (motor examination).^[7] ^* Pakiam et al reported that patients with diffuse Lewy-body disease may present with parkinsonism and prominent autonomic dysfunction, fulfilling some proposed criteria for the striatonigral form of MSA.^[29]

Characteristic	MSA	Pure Autonomic Failure
CNS involvement	Multiple involvement	Unaffected
Site of lesion	Mainly preganglionic, central; degeneration of intermediolateral cell columns; ganglionic neurons relatively intact	Mainly postganglionic; loss of ganglionic neurons
Progression	Fast; median survival 6.5-9.5 years	Slow; some patients survive >10-30 years
Prognosis	Poor	Good
Extrapyramidal involvement	Common	Not present
Cerebellar involvement	Common	Not present
Gastrointestinal symptoms	Uncommon	Absent, except constipation
Plasma supine norepinephrine level	Normal	Reduced
Antidiuretic hormone (ADH) response to tilt	Impaired because of catecholaminergic denervation of hypothalamus (but normal ADH response to osmotic stimuli)	Maintained
Adrenocorticotropic hormone and beta-endorphin response to hypoglycemia	Impaired because of central cholinergic dysfunction or dysfunction of adrenergic input to paraventricular nucleus	Normal
Growth hormone release with clonidine IV injection	No release, dysfunction of hypothalamic-pituitary pathway (alpha2-adrenoceptor-hypothalamic deficit)	Increase of growth hormone; intact function
Substance P, catecholamine, 5-HT, and acetylcholine markers in cerebrospinal fluid	Decreased levels	No data
Lewy bodies	Mostly absent	Present in autonomic neurons
BP response to oral water intake	Increased	Increased but variable
BP response to ganglionic blockade	Profound decrease	Modest decrease

	GCIs in MSA	Lewy Bodies in Parkinson Disease	Neurofibrillary Pathology in Alzheimer Disease	Glial Lesions in Corticobasal and Progressive Supranuclear Palsy
Shape	Sickle shaped to flame shaped to ovoid, various neurofibrillary tangles	Target-shaped inclusions	Tangles	Tufted astrocytes, coiled bodies
Membrane	No limiting membrane; tubular profiles and electrodense granules	Present	Present	Present
Ultrastructure	Loosely aggregated filaments	No data	No data	Astrocytic plaques
Immunocytochemistry	Ubiquitin positive, alpha-B-crystallin (synuclein) positive, alpha- and beta-tubulin positive, tau-protein positive	Hyaline eosinophilic cytoplasmic neuronal inclusions, ubiquitin	No data	Absence of phosphorylated tau
Localization	In oligodendroglial cells and neurons	In neuronal cells and oligodendroglial cells	No data	No data

Class	Drug	Description or Mechanism
Corticosteroids	Fludrocortisone (Florinef)	Mineralocorticoid; sodium retention, primarily in extravascular compartment, causes tissue edema to venous capacitance bed in lower extremity. With this edema, venous bed accommodates decreased volume of blood in an upright posture (high doses, late effect); increases sensitivity to norepinephrine (even with small doses)
Sympathomimetic amines	Midodrine	Alpha1-adrenoreceptor agonist acts directly on vasculature, causes venous and arteriolar vasoconstriction
Sympathomimetic amines	Droxidopa	Droxidopa is a synthetic precursor of norepinephrine. It acts by conversion to norepinephrine in the body.
Recombinant erythropoietin (EPO)	Epoetin alfa	Increases sensitivity to pressor effects of angiotensin II; increases plasma endothelin level; increases cytosolic free calcium in vascular smooth muscle; increases intravascular volume
NSAIDs	Indomethacin, ibuprofen	Inhibition of vasodilator prostaglandins proposed but not proven
Antihistamines	Diphenhydramine, cimetidine	Reduce vasodilatation caused by histamine release
Somatostatin analogs	Octreotide	Reduce splanchnic capacitance
Vasopressin agonists	Desmopressin (DDAVP)	Vasopressin analogs; no effect on V1 receptors, which are responsible for vasopressin-induced vasoconstriction; acts on V2 receptors on renal tubuli, which are responsible for antidiuretic effect; prevents nocturnal diuresis, raises BP in morning
Other sympathomimetics	Yohimbine	Alpha2-adrenoreceptor antagonist
Other sympathomimetics	Caffeine	Adenosine receptor antagonist

Multiple System Atrophy

Practice Essentials

Signs and symptoms

Diagnosis

Management

Background

Categories of MSA

Characteristics of MSA

Levels of certainty of MSA

Patient education

Etiology and Pathophysiology

Epidemiology

Occurrence in the United States

International occurrence

Race-, sex-, and age-related demographics

Prognosis

References

Tables

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