Multiple system atrophy (MSA) is a progressive, neurodegenerative disorder that affects adults, causing a combination of movement problems and difficulty with the automatic functions of the body, known as the autonomic nervous system. Movement problems can include stiffness, slow movement, poor coordination, and balance difficulties. Dysfunction of the autonomic nervous system can cause severe symptoms related to blood pressure (such as fainting or dizziness when standing), urinary urgency or incontinence, constipation, difficulty swallowing or speaking, erectile dysfunction in men, and sleep disturbances.

While these symptoms can also happen in people who have Parkinson’s disease, MSA symptoms are more severe and appear earlier. Many people with MSA develop significant disability, with movement and autonomic symptoms typically worsening over time. Unlike Parkinson’s disease, MSA lowers a person’s life expectancy, typically ranging from six to 10 years after diagnosis.

According to the NIH, an estimated 15,000 to 50,000 people are affected by the condition. Symptoms typically begin in people in their 50s, with the risk for MSA increasing with age.

While there is currently no cure for MSA, symptoms may be managed with a combination of medications, physical and occupational therapy, and supportive care.

Multiple system atrophy (MSA) is a rare, progressive neurodegenerative disorder that causes a wide range of symptoms involving both movement and autonomic functions. In MSA, nerve cells in the brain and spinal cord are gradually lost, in particular in areas involved in regulating movement, balance, and involuntary processes.

There are two types of MSA. They are categorized based on the most prominent symptoms:

• Parkinsonian type MSA (MSA-P), which mainly causes symptoms similar to Parkinson’s disease, such as slow movement and stiff muscles, among others.
• Cerebellar type MSA (MSA-C), which mainly causes problems with coordination and balance.

The symptoms of the two types of MSA may overlap. As the disease progresses, people diagnosed with one type of MSA typically develop symptoms of the other type. Both types of MSA present early with autonomic dysfunction.

In a healthy nervous system, the brain communicates with the body through networks of nerve cells. These cells help coordinate voluntary movements (such as walking), maintain balance, and regulate involuntary processes such as heart rate and blood pressure.

In people with MSA, however, nerve cells in important regions of the brain—such as the basal ganglia (which helps control coordinated movements), the cerebellum (which coordinates both movement and balance), and areas that regulate the autonomic nervous system—degenerate over time. As these cells are lost, people develop symptoms such as muscle stiffness, slow movement, tremor, loss of coordination, and urinary problems, among others.

MSA symptoms most commonly begin in people in their 50s, though they can occur as early as a person’s 30s or as late as a person’s 70s.

The exact cause of multiple system atrophy (MSA) is unknown. However, research has shown that people with MSA have a buildup of a protein called alpha-synuclein in specialized cells in the brain known as oligodendrocytes. These cells support the neurons of our brain, and this abnormal accumulation is thought to disrupt the normal function of these cells. This can lead to the loss of nerve cells in areas of the brain that control movement, balance, and involuntary body functions.

Although the reason for this protein buildup is not fully understood, scientists have explored several theories. Some research suggests that changes in the production, folding, or clearance of alpha-synuclein from the brain may play a role. Other factors, such as problems with cell energy production (mitochondrial dysfunction), inflammation in the brain, and issues with how support cells mature, may also contribute to the development of MSA. Rare genetic changes have been found in some families, but most cases of MSA are not inherited and occur randomly.

Currently, there is no single known cause of MSA, and it is likely that a combination of genetic, molecular, and possibly environmental factors contribute to the condition in ways that are not yet fully understood.

Advancing age is the only known risk factor for MSA.

Symptoms of multiple system atrophy may include:

• Muscle stiffness or rigidity
• Slowness of movement
• Poor balance or frequent falls
• Tremor
• Loss of coordination
• Difficulty walking or wide, irregular steps
• Speech problems or slurred or soft voice
• Difficulty swallowing
• Abnormal eye movements
• Difficulty getting the eyes to focus properly
• Fainting or dizziness when standing
• Urinary urgency, frequency, incontinence, or retention
• Constipation
• Erectile dysfunction in men and sexual dysfunction in women
• Reduced sweating, dry mouth
• Difficulty breathing, including noisy or high-pitched breathing (stridor)
• Sleep disturbances, including REM sleep behavior disorder (acting out dreams)
• Contractures (chronic shortening of muscles or tendons around joints)
• Pisa syndrome (involuntary leaning of the body to one side)
• Anterocollis (forward bending of the neck)
• Depression or anxiety

Symptoms may start gradually and get worse over time. As the disease progresses, people may become unable to walk, require help with daily activities, and experience increasing problems with swallowing, speech, and breathing.

To diagnose multiple system atrophy, your doctor will review your medical history, conduct a physical exam, and order one or more diagnostic tests. Diagnosis can be challenging because the symptoms of MSA overlap with other neurological conditions, especially Parkinson’s disease and other movement disorders. However, a movement disorders specialist can diagnose this condition through clinical evaluation.

Your doctor will ask about symptoms such as urination issues, dizziness or fainting when you stand up, slow movement, stiff muscles, and slurred speech, among others. They may ask you when the symptoms began and if they have worsened over time. During the physical exam, your doctor will check your blood pressure while lying down and standing up, use a stethoscope to listen to your breathing, check your posture and eye movement, look for signs of tremor, and assess your gait. Your doctor will also perform a neurological exam to evaluate movement, coordination, balance, reflexes, and autonomic functions to identify patterns consistent with MSA.

Your doctor may order additional tests to confirm the diagnosis and rule out other conditions. These tests may include:

• Imaging studies that are sometimes used:
• MRI, to assess specific brain regions affected by MSA, such as shrinkage (atrophy) of the cerebellum, putamen (part of the basal ganglia, a group of structures in the brain) , pons (a part of the brainstem), or middle cerebellar peduncle (connections between the cerebellum to the pons). MRI is also used to rule out other possible causes of the symptoms.
• Dopamine transporter (DaT) scan, to assess dopamine transporter (DaT), a protein, activity in the brain. Dopamine is a chemical messenger in the brain that sends signals between nerve cells. In MSA, brain cells that produce and release dopamine are lost. Dopamine transporter (DaT) is embedded in the membrane of these brain cells. In a DaT scan, a radioactive tracer is injected into the bloodstream. It travels to the brain, where it attaches to DaTs. A single-photon emission computed tomography (SPECT) scanner generates an image, highlighting the radioactive tracer and allowing doctors to assess DaT activity. Abnormal results may indicate MSA, however, scans can also be normal in MSA and the scan cannot differentiate MSA from Parkinson’s disease.
• Autonomic function tests to measure involuntary body functions such as how well the body regulates blood pressure, heart rate, sweating, and other involuntary functions which are often impaired in MSA.
• Skin punch biopsies can be evaluated from three sites on the body to look for the abnormal protein that builds up in the brain (alpha synuclein) which can also be found in the skin.
• Urodynamic studies to evaluate bladder function.
• MIBG cardiac scintigraphy, an imaging test that can help differentiate MSA from Parkinson’s disease.
• Sleep studies (polysomnography): Identify sleep disturbances such as REM sleep behavior disorder (a sleep disorder in which people move or speak during REM sleep, often involving acting out dreams, which can result in injury) or breathing problems that can occur with MSA.

Doctors often diagnose MSA by recognizing a combination of symptoms and test results while ruling out other conditions that can cause similar symptoms.

Treatment focuses on managing symptoms. Treatment is tailored to each person’s symptoms and may involve regular follow-up to adjust therapies as the disease progresses. Multidisciplinary care approach is often preferred.

Main treatments for multiple system atrophy include:

• Medications for movement symptoms: Drugs that increase dopamine in the brain, such as levodopa, may help with stiffness, slowness, and other movement problems. However, their effectiveness is often limited in MSA compared to Parkinson’s disease, and the benefit may decrease over time.
• Medications for blood pressure control: Medicines, such as fludrocortisone, midodrine, or droxidopa, may be used to help manage low blood pressure, especially when standing, to reduce dizziness and the risk of fainting. Non-drug strategies, such as increasing salt and fluid intake, wearing compression stockings or an abdominal binder (to help prevent low blood pressure by compressing the calves and abdomen, thereby reducing blood pooling and improving blood return to the heart), and elevating the head of the bed, can also help.
• Botulinum toxin injections: Botulinum toxin, commonly known by the trade name Botox, may be used to treat involuntary contractions in specific muscles (known as focal dystonia), including neck muscle spasms and eyelid blinking.
• Bladder management: Medications, bladder training, or intermittent catheterization may help with urinary urgency, frequency, or retention. Anticholinergic drugs or beta-3 agonists may be used for overactive bladder symptoms, while intermittent self-catheterization is often needed for incomplete bladder emptying.
• Physical therapy: Exercises and training help maintain mobility, improve balance, and reduce the risk of falls. Physical therapists can also recommend walking aids, such as canes or walkers, and strategies to prevent falls.
• Occupational therapy: Occupational therapists help individuals adapt daily activities and recommend assistive devices to promote independence, making it easier to dress, eat, and perform household tasks.
• Speech and swallowing therapy: Speech-language pathologists provide strategies to address speech difficulties and swallowing problems. Swallowing therapy and dietary modifications (such as thickened liquids or softer foods) can help prevent choking.
• Nutritional support: Dietary adjustments and, in some cases, feeding tubes may be recommended to maintain adequate nutrition and prevent weight loss—especially if swallowing becomes severely impaired.
• Sleep management: Treatment of sleep disturbances may include medications, devices (such as continuous positive airway pressure, or CPAP for sleep apnea or stridor), or behavioral changes to improve sleep quality and breathing.
• Management of constipation: Increased dietary fiber, adequate fluid intake, stool softeners, or laxatives may be recommended to relieve constipation.
• Management of sexual dysfunction: Medications or devices may be used to treat erectile dysfunction in men, though some of these medications can worsen orthostatic hypotension (a drop in blood pressure when standing from a seated or prone position).
• Psychological support: Counseling or support groups may help individuals and families cope with emotional and psychological challenges related to MSA. Treating depression or anxiety with medications or therapy may also be recommended.
• Palliative care: As the condition progresses, palliative care specialists can help manage symptoms, increase comfort, and provide support for end-of-life decisions.

People with multiple system atrophy may be at increased risk for certain complications, including:

• Frequent falls and injuries
• Difficulty swallowing, which can lead to choking or aspiration pneumonia (a lung infection caused by inhaling food or liquids into the lungs)
• Severe low blood pressure, especially when standing, which can cause fainting
• Bladder dysfunction, including urinary retention or incontinence
• Breathing problems, including sleep-related breathing difficulties or airway obstruction
• Malnutrition and weight loss
• Pressure sores from immobility
• Severe constipation or bowel obstruction
• Speech loss or severe communication difficulties
• Increased risk of infections, such as urinary tract infections or pneumonia

Other complications can include contractures (tightening of muscles or tendons), loss of independence, and social isolation. Some people may require feeding tubes or breathing support in advanced stages of the disease.

The outlook for people with MSA can vary depending on several factors, including the specific symptoms, how quickly the disease progresses, and the person’s overall health. The average duration from symptom onset to death is typically six to 10 years, though some people may live longer, especially with attentive care and support.

MSA is a progressive condition, and most people develop increasing difficulties with movement, balance, and autonomic functions such as blood pressure and bladder control, significantly affecting daily life and independence.

Although there is no cure for MSA, treatments and therapies may help manage symptoms and improve quality of life. With supportive care, people may maintain some level of independence for a few years after diagnosis. Over time, however, complications such as difficulty swallowing, frequent infections, and severe blood pressure problems may arise. The condition often leads to severe disability within five to 10 years after symptoms begin, and most people require assistance with daily activities or require the use of a wheelchair as it advances.

Planning ahead, including discussions about advance directives and preferences for end-of-life care, is recommended soon after diagnosis, so individuals and their families can make informed decisions about care as the disease progresses.

At Yale Medicine, our Comprehensive Parkinson’s Disease and Movement Disorders Care Center delivers holistic, patient-centered care that improves lives and empowers patients to take ownership of their condition, rather than allowing it to define them. As a Mission MSA Center of Excellence, we are setting a nationwide standard in clinical excellence, outreach, and world-class education to train the next generation of specialists. Our team includes subspecialty-trained movement disorder neurologists, neuropsychologists, physician assistants, MSA-trained nurses, a social worker, neurorehabilitation specialists, and movement disorder pharmacists.

"We help patients participate in their health care through comprehensive self-reporting and personalized coaching, education and tailored resource referrals, participation in research opportunities, and follow-up care that encourages understanding of and compliance with treatment plans," says Veronica Santini, MD, associate professor of neurology, clinical chief of Yale's Movement Disorders Division, and chief of the Comprehensive Parkinson Disease Care Program. "With a calendar of events to meet all the therapeutic needs of our patients, patient can be empowered in healthy living when they are not in the clinic receiving the knowledge they and their caregivers need to best support their journey."