Multiple system atrophy is a relentlessly progressive neurodegenerative disorder causing pyramidal, cerebellar, and autonomic dysfunction. It includes 3 disorders previously thought to be distinct: olivopontocerebellar atrophy, striatonigral degeneration, and Shy-Drager syndrome. Symptoms include hypotension, urinary retention, constipation, ataxia, parkinsonism, and postural instability. Diagnosis is clinical. Treatment is symptomatic, with volume expansion, compression garments, and vasoconstrictor medications.
(See also Overview of the Autonomic Nervous System.)
Multiple system atrophy affects men and women equally. Mean age at onset is about 53 years; after symptoms appear, patients live about 9 to 10 years.
There are 2 types of multiple system atrophy (MSA); types are based on the initial symptoms that predominate:
MSA-C: Characterized by ataxia and postural instability (cerebellar dysfunction)
Both types involve autonomic nervous system dysfunction. Although multiple system atrophy begins as one type, symptoms of the other type eventually develop. After about 5 years, symptoms tend to be similar regardless of which disorder developed first.
Etiology of Multiple System Atrophy
Etiology of multiple system atrophy is unknown, but neuronal degeneration occurs in several areas of the brain; the area and amount damaged determine initial symptoms. A characteristic finding is cytoplasmic inclusion bodies containing alpha-synuclein within oligodendroglial cells.
Multiple system atrophy is a synucleinopathy (due to synuclein deposition); synuclein can also accumulate in patients with Parkinson disease, pure autonomic failure, or dementia with Lewy bodies. Synuclein is a neuronal and glial cell protein that can aggregate into insoluble fibrils and form Lewy bodies.
Symptoms and Signs of Multiple System Atrophy
Initial symptoms of multiple system atrophy vary but include a combination of
Cerebellar abnormalities
Symptoms due to autonomic insufficiency
Parkinsonian symptoms
Parkinsonian symptoms predominate in striatonigral degeneration. They include rigidity, bradykinesia, postural instability, and jerky postural tremor. High-pitched, quavering dysarthria is common.
Cerebellar abnormalities
Cerebellar abnormalities predominate in olivopontocerebellar atrophy. They include ataxia, dysmetria, dysdiadochokinesia (difficulty performing rapidly alternating movements), poor coordination, and abnormal eye movements.
Autonomic symptoms
Typically, autonomic insufficiency causes orthostatic hypotension (symptomatic fall in blood pressure (BP) when a person stands, often with syncope), urinary retention, urinary incontinence, constipation, and erectile dysfunction.
Other autonomic symptoms, which may occur early or late, include decreased sweating, difficulty breathing and swallowing, fecal incontinence, and decreased tearing and salivation.
Rapid eye movement (REM) sleep behavior disorder (eg, speech or skeletal muscle movement during REM sleep), respiratory stridor, and sleep apnea are common. Patients are often unaware of REM sleep behavior disorder.
Diagnosis of Multiple System Atrophy
MRI
Autonomic tests
Diagnosis of multiple system atrophy is suspected clinically, based on the combination of autonomic insufficiency and parkinsonism or cerebellar symptoms. Similar symptoms may result from Parkinson disease, dementia with Lewy bodies, pure autonomic failure, autonomic neuropathies, progressive supranuclear palsy, multiple cerebral infarcts, or medication-induced parkinsonism.
No diagnostic test is definitive, but some (eg, MRI, nuclear imaging with 123I-metaiodobenzylguanidine [MIBG], autonomic tests) help confirm clinical suspicion of multiple system atrophy—for example, if
MRI shows characteristic changes in the midbrain, pons, or cerebellum.
MIBG scans show intact innervation of the heart (because the lesion is preganglionic in multiple system atrophy)
Autonomic tests indicate generalized autonomic failure.
Treatment of Multiple System Atrophy
Supportive care
There is no specific treatment for multiple system atrophy, but symptoms are managed as follows:
Orthostatic hypotension:midodrine
Parkinsonism: may be tried to relieve rigidity and other parkinsonian symptoms, but this combination may be ineffective or provide only modest benefit.
Urinary incontinence:tamsulosin, mirabegron does not worsen orthostatic hypotension.
Decreased sweating, tearing, and salivation:
Constipation: A high-fiber diet and stool softeners can be used; for refractory cases, enemas may be necessary.
Patients require supportive therapy because the disorder is progressive and fatal. Thus, clinicians should advise patients to prepare advance directives soon after multiples system atrophy is diagnosed.
Key Points
Multiple system atrophy can include parkinsonian symptoms, cerebellar abnormalities, and autonomic insufficiency in various degrees of severity.
Diagnose this disorder based on clinical, autonomic, and MRI findings, but consider Parkinson disease, dementia with Lewy bodies, pure autonomic failure, autonomic neuropathies, progressive supranuclear palsy, multiple cerebral infarcts, and medication-induced parkinsonism, which can all cause similar symptoms.
Use treatments specific for the symptoms present.
