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.

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."