Multiple system atrophy

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by a combination of symptoms that affect both the central nervous system (which controls how a person moves), and the autonomic nervous system, which controls involuntary functions such as blood pressure or digestion. MSA was formerly known as Shy-Drager syndrome, olivopontocerebellar atrophy (OCPA), or striatonigral degeneration.

The symptoms of MSA reflect the progressive loss of function and death of different types of nerve cells in the brain and spinal cord. MSA is one of a family of neurological disorders known as an atypical parkinsonian disorder. The initial symptoms can be difficult to distinguish from those of Parkinson's disease, and can include:

• Slowness of movement, tremor, or stiffness
• Clumsiness or lack of coordination
• Croaky, quivering voice
• Fainting or lightheadedness
• Bladder control problems

Symptoms tend to appear in a person's 50s and advance rapidly over the course of five to 10 years. A person with MSA will have increased difficulty with movement and eventually become bedridden. People with MSA often develop swallowing problems that can lead to pneumonia in the later stages of the disease.

There are two different types of MSA, which are categorized by the person’s most prominent symptoms when they’re evaluated by a doctor:

1. Parkinsonian type MSA (MSA-P) has primary symptoms similar to Parkinson's disease (such as slowness of movement, stiffness, and tremor) along with problems with balance, coordination, and autonomic nervous system dysfunction (such as urinary problems, sweating abnormalities, and digestion difficulties).
   
2. Cerebellar type MSA (MSA-C) is associated with balance and coordination problems (ataxia), difficulty swallowing, speech problems or a quivering voice, and abnormal eye movements.

MSA tends to progress more rapidly than Parkinson's disease, and most people with MSA will require an aid for walking, such as a cane or walker, within a few years after symptoms begin.

Other symptoms of MSA include:

• Stiffness in the hands or limbs caused by contractures (chronic shortening of muscles or tendons around joints, which prevents the joints from moving freely)
• A posture in which the body leans involuntarily to one side (known as Pisa syndrome)
• Anterocollis, in which the neck bends forward and the head drops down
• Anxiety or depression
• REM (Rapid Eye Movement) sleep behavior disorder (RBD) - a tendency to act out dreams
• Other sleep disorders, including sleep apnea

Who is more likely to get multiple system atrophy?

MSA is a rare disease, affecting potentially 15,000 to 50,000 Americans, including people of all racial groups. The cause of MSA is unknown. The vast majority of cases are sporadic, meaning they occur at random.

One distinguishing feature of MSA is the buildup of a protein called alpha-synuclein in glia, specialized cells that support nerve cells in the brain. The deposits of alpha-synuclein particularly occur in a type of glia cell that that makes myelin, a coating that helps nerve cells send electrical signals. In Parkinson’s, alpha-synuclein accumulates in the nerve cells, rather than in the glia, as seen in MSA. Because both conditions have a buildup of the same protein, MSA and Parkinson's disease are sometimes referred to as “synucleinopathies.”

Certain genetic variants have been reported to influence MSA risk, including genes related to oxidative stress, inflammation, and other genes related to Parkinson’s disease. However, a specific gene responsible for causing MSA has not yet been identified, and the genetic basis of MSA is not well understood. There is currently no definitive evidence about the effect of environmental factors (such as chemicals in food, air, or water) on a person’s risk for MSA. It is believed that a combination of genetic and environmental factors likely contributes to the development and progression of the disease.

How is multiple system atrophy diagnosed and treated?

Diagnosing MSA. Diagnosing MSA can be difficult, particularly in the early stages because many of the features are similar to those observed in Parkinson's disease. In addition to taking a person’s medical and family history and performing a neurological examination, a doctor may order tests to support the diagnosis. These tests might include:

• Autonomic testing (such as blood pressure and heart rate control)
• Assessment of bladder function
• Brain scans (Neuroimaging):
  • Magnetic resonance imaging (MRI) may identify changes that suggest MSA or rule out other causes of the symptoms.
  • Positron emission tomography (PET) scans can be used to monitor metabolic function in specific parts of the brain.
  • Dopamine transporter (DaT) scans can assess the distribution and activity of dopamine in the brain.

People with MSA typically do not see their systems improve long-term when taking medicines commonly prescribed for treating Parkinson’s disease. If Parkinson’s drugs are not effective for the treating the disease, that finding can help support the diagnosis of MSA.

Treating MSA. Currently, there are no treatments to stop or slow the progression of MSA, and there is no cure. However, there are treatments to help people cope with the symptoms.

• For some individuals, levodopa (a drug used to treat Parkinson’s symptoms) may help improve motor function, but the benefits are often short-lived.
  
• The fainting and lightheadedness caused by a decrease in blood pressure upon standing (orthostatic hypotension) may be helped by wearing compression stockings or an abdominal binder, adding extra salt to the diet, increasing water intake, and avoiding heavy meals. Doctors may prescribe medicines to keep blood pressure from dropping.
  
• Doctors may prescribe Botulinum toxin (commonly known as botox) injections to ease abnormal muscle postures (dystonia).
  
• Medicines are also available to help with the bladder control and certain sleep problems seen in MSA such as RBD.
  
• Speech therapy may help identify strategies to address swallowing difficulties. Some people with MSA experiencing significant swallowing problems may need a feeding tube or nutritional support.
  
• Physical therapy helps maintain mobility, reduce contractures, and decrease muscle spasms and abnormal posture.
  
• Walkers and wheelchairs can help as mobility declines in the person with MSA. Occupational therapists can help with home safety and learning new ways to address activities of daily living, such as dressing and eating.

What are the latest updates on multiple system atrophy?

NINDS, part of the National Institutes of Health, and other NIH institutes support research on MSA and related disorders. NINDS supports research to develop and test better clinical measures for MSA and validate biological markers for accurate diagnosis and improved treatment, which can help ensure that clinical trials of any therapies developed for MSA are able to enroll the individuals most likely to benefit.

Other efforts include the NINDS Biospecimen Exchange for Neurological Disorders (BioSEND), which houses biological samples such as blood or spinal fluid collected through NINDS-supported studies focused on biomarkers, and the NINDS Data Management Resource (DMR), which provides researchers with tools that allow for the collection and quality assurance of clinical data in a standardized format. NINDS also participates in Accelerating Medicines Partnership® Parkinson's Disease (AMP PD)—a public-private collaboration focused on biomarker discovery to advance therapies for Parkinson’s disease and other synucleinopathies, including MSA.

Understanding Alpha-Synuclein Accumulation. Research findings indicate that abnormal alpha-synuclein accumulation in nerve cells and their supporting cells, including glia, leads to cellular dysfunction and progressive loss of nerve cell function (known as neurodegeneration). Studies suggest that the diverse forms and structures of alpha-synuclein might explain why the protein accumulates in glial cells in MSA and nerve cells in Parkinson's disease.

Studies have demonstrated that MSA-specific alpha-synuclein leads to protein clumping in animal models of MSA. Ongoing research is currently focused on finding ways to prevent and treat alpha-synuclein from building up and spreading throughout the brain.

Improving Diagnostics. MSA and other debilitating movement disorders are often hard to distinguish from one another. NINDS-funded scientists are using special brain imaging tools to develop biomarkers (signs that may indicate risk of a disease and improve diagnosis) that can distinguish MSA from other movement disorders and track disease-specific neurodegeneration over time.

NINDS-supported scientists also are studying whether identifying specific types of abnormal protein alpha-synuclein can help differentially diagnose MSA and other neurodegenerative diseases.

The NIH-supported North American Prodromal Synucleinopathy (NAPS) Consortium is collecting clinical information, biofluids, and neuroimaging data to develop biomarkers of synucleinopathies such as MSA and to create a clinical trial-ready registry of potential participants.

Additional research on MSA can be found using NIH RePORTER, a searchable database of current and past research projects supported by NIH and some other federal agencies.

How can I or my loved one help improve care for people with multiple system atrophy?

Consider participating in a clinical trial so clinicians and scientists can learn more about MSA and related disorders. Clinical research uses human volunteers to help researchers learn more about a disorder and perhaps find better ways to safely detect, treat, or prevent disease.

All types of volunteers are needed—those who are healthy or may have an illness or disease—of all different ages, sexes, races, and ethnicities to ensure that study results apply to as many people as possible, and that treatments will be safe and effective for everyone who will use them.

For information about participating in clinical research visit NIH Clinical Research Trials and You. Learn about clinical trials currently looking for people with MSA at Clinicaltrials.gov. For information on studies at NIH, contact the Clinical Center Office of Patient Recruitment.

Where can I find more information about multiple system atrophy?

Information may be available from the following organizations and resources:

Cure PSP
Phone: 800-457-4777 or 410-785-7004

Defeat MSA Alliance
Phone: 855-542-5672

National Library of Medicine
Phone: 301-496-6308 or 888-346-3656

National Organization for Rare Disorders (NORD)
Phone: 203-744-0100

The Multiple System Atrophy Coalition
Phone: 866-737-5999

Content source: https://www.ninds.nih.gov/health-information/disorders/multiple-system-atrophy Accessed July 13, 2023.

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