(See also Overview of the Autonomic Nervous System Overview of the Autonomic Nervous System The autonomic nervous system regulates physiologic processes. Regulation occurs without conscious control, ie, autonomously. The 2 major divisions are the Sympathetic system Parasympathetic... read more 
.)
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 Cerebellar Disorders Cerebellar disorders have numerous causes, including congenital malformations, hereditary ataxias, and acquired conditions. Symptoms vary with the cause but typically include ataxia (impaired... read more )
MSA-P: Similar to Parkinson disease but often without tremor and often unresponsive to levodopa (parkinsonian symptoms Symptoms and Signs Secondary parkinsonism refers to a group of disorders that have features similar to those of Parkinson disease but have a different etiology. Atypical parkinsonism refers to a group of neurodegenerative... read more )
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 Pathophysiology (due to synuclein deposition); synuclein can also accumulate in patients with Parkinson disease Parkinson Disease Parkinson disease is a slowly progressive, degenerative disorder characterized by resting tremor, stiffness (rigidity), slow and decreased movement (bradykinesia), and eventually gait and/or... read more , pure autonomic failure Pure Autonomic Failure Pure autonomic failure results from neuronal loss in autonomic ganglia, causing orthostatic hypotension and other autonomic symptoms. (See also Overview of the Autonomic Nervous System.) Pure... read more , or dementia with Lewy bodies Dementia with Lewy Bodies and Parkinson Disease Dementia Lewy body dementia includes clinically diagnosed dementia with Lewy bodies and Parkinson disease dementia. Dementia with Lewy bodies is chronic cognitive deterioration characterized by cellular... read more . 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
Parkinsonism unresponsive to levodopa
Cerebellar abnormalities
Symptoms due to autonomic insufficiency
Parkinsonian symptoms
Parkinsonian symptoms Symptoms and Signs Secondary parkinsonism refers to a group of disorders that have features similar to those of Parkinson disease but have a different etiology. Atypical parkinsonism refers to a group of neurodegenerative... read more predominate in striatonigral degeneration. They include rigidity, bradykinesia, postural instability, and jerky postural tremor. High-pitched, quavering dysarthria is common.
In contrast to Parkinson disease, multiple system atrophy usually does not usually cause resting tremor and dyskinesia, and symptoms respond poorly and transiently to levodopa.
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 Orthostatic Hypotension Orthostatic (postural) hypotension is an excessive fall in blood pressure (BP) when an upright position is assumed. The consensus definition is a drop of > 20 mm Hg systolic, > 10 mm Hg... read more (symptomatic fall in blood pressure (BP) when a person stands, often with syncope), urinary retention Urinary Retention Urinary retention is incomplete emptying of the bladder or cessation of urination. Urinary retention may be Acute Chronic Causes include impaired bladder contractility, bladder outlet obstruction... read more , urinary incontinence Urinary Incontinence in Adults Urinary incontinence is involuntary loss of urine; some experts consider it present only when a patient thinks it is a problem. The disorder is greatly underrecognized and underreported. Many... read more , constipation Constipation Constipation is difficult or infrequent passage of stool, hardness of stool, or a feeling of incomplete evacuation. (See also Constipation in Children.) No bodily function is more variable and... read more , and erectile dysfunction Erectile Dysfunction Erectile dysfunction is the inability to attain or sustain an erection satisfactory for sexual intercourse. Most erectile dysfunction is related to vascular, neurologic, psychologic, and hormonal... read more .
Other autonomic symptoms, which may occur early or late, include decreased sweating, difficulty breathing and swallowing, fecal incontinence Fecal Incontinence Fecal incontinence is involuntary defecation. Diagnosis is clinical. Treatment is a bowel management program and perineal exercises, but sometimes colostomy is needed. (See also Evaluation of... read more , and decreased tearing and salivation.
Rapid eye movement (REM) sleep behavior disorder Rapid eye movement (REM) sleep behavior disorder Parasomnias are undesirable behaviors that occur during entry into sleep, during sleep, or during arousal from sleep. Diagnosis is clinical. Treatment may include drugs and psychotherapy. (See... read more (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.
Patients may have nocturnal polyuria; contributing factors may include a circadian decrease in arginine vasopressin and treatments used to increase blood volume.
Diagnosis of Multiple System Atrophy
Clinical evaluation (autonomic insufficiency plus parkinsonism or cerebellar symptoms that respond poorly to levodopa)
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 Parkinson Disease Parkinson disease is a slowly progressive, degenerative disorder characterized by resting tremor, stiffness (rigidity), slow and decreased movement (bradykinesia), and eventually gait and/or... read more , dementia with Lewy bodies Dementia with Lewy Bodies and Parkinson Disease Dementia Lewy body dementia includes clinically diagnosed dementia with Lewy bodies and Parkinson disease dementia. Dementia with Lewy bodies is chronic cognitive deterioration characterized by cellular... read more , pure autonomic failure Pure Autonomic Failure Pure autonomic failure results from neuronal loss in autonomic ganglia, causing orthostatic hypotension and other autonomic symptoms. (See also Overview of the Autonomic Nervous System.) Pure... read more , autonomic neuropathies Autonomic Neuropathies Autonomic neuropathies are peripheral nerve disorders with disproportionate involvement of autonomic fibers. (See also Overview of the Autonomic Nervous System.) The best known autonomic neuropathies... read more , progressive supranuclear palsy Progressive Supranuclear Palsy (PSP) Progressive supranuclear palsy is a rare, degenerative central nervous system disorder that progressively impairs voluntary eye movements and causes bradykinesia, muscular rigidity with progressive... read more , 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 Treatment Orthostatic (postural) hypotension is an excessive fall in blood pressure (BP) when an upright position is assumed. The consensus definition is a drop of > 20 mm Hg systolic, > 10 mm Hg... read more : Treatment includes intravascular volume expansion with salt and water supplementation and sometimes fludrocortisone. Use of compression garments for the lower body (eg, abdominal binder, compression stockings) and alpha-adrenoreceptor stimulation with midodrine may help. However, midodrine also increases peripheral vascular resistance and supine blood pressure (BP), which may be problematic. Raising the head of the bed about 10 cm reduces nocturnal polyuria and supine hypertension and may reduce morning orthostatic hypotension. Alternatively, droxidopa may be used; its action is similar to that of midodrine, but duration of action is longer.
Parkinsonism Treatment Secondary parkinsonism refers to a group of disorders that have features similar to those of Parkinson disease but have a different etiology. Atypical parkinsonism refers to a group of neurodegenerative... read more : Levodopa/carbidopa Levodopa Parkinson disease is a slowly progressive, degenerative disorder characterized by resting tremor, stiffness (rigidity), slow and decreased movement (bradykinesia), and eventually gait and/or... read more may be tried to relieve rigidity and other parkinsonian symptoms, but this combination may be ineffective or provide only modest benefit.
Urinary incontinence Treatment Urinary incontinence is involuntary loss of urine; some experts consider it present only when a patient thinks it is a problem. The disorder is greatly underrecognized and underreported. Many... read more : If the cause is detrusor hyperreflexia, oxybutynin chloride or tolterodine may be used. Tamsulosin may be effective for urinary urgency. Alternatively, the beta-3 adrenergic agonist mirabegron can be used; unlike tamsulosin, mirabegron does not worsen orthostatic hypotension.
Decreased sweating, tearing, and salivation: If sweating is reduced or absent, patients are advised to avoid warm environments and overheating the body. Patients with dry mouth are advised to use good dental care and to have regular dental check-ups. Artificial tears may help patients with dry eyes.
Urinary retention Treatment Urinary retention is incomplete emptying of the bladder or cessation of urination. Urinary retention may be Acute Chronic Causes include impaired bladder contractility, bladder outlet obstruction... read more : Many patients must self-catheterize their bladder. Sometimes medications that induce bladder contraction (eg, bethanechol) are used.
Constipation Treatment Constipation is difficult or infrequent passage of stool, hardness of stool, or a feeling of incomplete evacuation. (See also Constipation in Children.) No bodily function is more variable and... read more : A high-fiber diet and stool softeners can be used; for refractory cases, enemas may be necessary.
Erectile dysfunction Treatment Erectile dysfunction is the inability to attain or sustain an erection satisfactory for sexual intercourse. Most erectile dysfunction is related to vascular, neurologic, psychologic, and hormonal... read more : Medications such as sildenafil or tadalafil can be used, but these medications may worsen orthostatic hypotension.
Patients require supportive therapy because the disorder is progressive and fatal. Thus, clinicians should advise patients to prepare advance directives Advance Directives Advance directives are legal documents that extend a person's control over health care decisions in the event that the person becomes incapacitated. They are called advance directives because... read more 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.
Drugs Mentioned In This Article
| Drug Name | Select Trade |
|---|---|
levodopa |
INBRIJA, Larodopa |
arginine |
Arginine, Nutricia SHS L-Arginine, R-Gene |
vasopressin |
Pitressin, Vasostrict |
fludrocortisone |
Florinef |
midodrine |
Orvaten, ProAmatine |
droxidopa |
NORTHERA |
carbidopa |
Lodosyn |
oxybutynin |
Ditropan, Ditropan XL, Gelnique , Oxytrol, Oxytrol for Women |
tolterodine |
Detrol, Detrol LA |
tamsulosin |
Flomax |
mirabegron |
Myrbetriq |
artificial tears |
Advanced Eye Relief, Akwa Tears, Akwa Tears Renewed, Alcon Tears, Artificial Tears, Bion Tears, Blink Tears, Clear eyes, Clear eyes Advance Dry and Itchy Relief, Clear eyes Outdoor Dry Eye Protection, Eye Lubricant , FreshKote, Gen Teal Moderate to Severe, GenTeal , GenTeal Mild, GenTeal Moderate, GenTeal PF, GenTeal Severe, GenTeal Tears Mild, GenTeal Tears Severe Dry Eye, Gonak, Goniosoft, Hypo Tears , Isopto Tears, LiquiTears, LubriFresh P.M., Moisture Eyes, Moisture Eyes Preservative Free, Murine, Natural Balance Tears, Nature's Tears, Opti-Free, Puralube Tears, Refresh, Refresh Celluvisc, Refresh Endura, Refresh Lacri-Lube, Refresh Liquigel, Soothe Lubricant Dry Eye Therapy, Systane, Systane Balance, Systane Complete, Systane Ultra, Teargen, Tears Naturale Forte, Tears Naturale Free, Tears Naturale II, Tears Renewed , TheraTears, Visine Dry Eye Relief, Visine Maximum Redness Relief, Visine Pure Tears, Visine Tears, Visine Tired Eye Relief, Viva |
bethanechol |
Duvoid , Urecholine, Urecholine Solution |
sildenafil |
LiQrev, Revatio, Viagra |
tadalafil |
Adcirca, ALYQ, Cialis, Tadliq |
