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)
MSA-P: Similar to Parkinson disease but often without tremor and often unresponsive to levodopa (parkinsonian symptoms)
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
Parkinsonism unresponsive to levodopa
Cerebellar abnormalities
Symptoms due to autonomic insufficiency
Симптоми паркінсонізму
Parkinsonian symptoms 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.
Аномалії мозочка
Cerebellar abnormalities predominate in olivopontocerebellar atrophy. They include ataxia, dysmetria, dysdiadochokinesia (difficulty performing rapidly alternating movements), poor coordination, and abnormal eye movements.
Вегетативні симптоми
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.
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, 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: 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: Levodopa/carbidopa may be tried to relieve rigidity and other parkinsonian symptoms, but this combination may be ineffective or provide only modest benefit.
Urinary incontinence: 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: Many patients must self-catheterize their bladder. Sometimes medications that induce bladder contraction (eg, bethanechol) are used.
Constipation: A high-fiber diet and stool softeners can be used; for refractory cases, enemas may be necessary.
Erectile dysfunction: 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 soon after multiples system atrophy is diagnosed.
Ключові моменти
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.