What is Multiple System Atrophy?
Multiple System Atrophy
Multiple system atrophy (MSA) is a rare, progressive neurodegenerative disease in which nerve cells in the brain and spinal cord break down and die. It especially affects the autonomic nervous system, the part of the nervous system that controls automatic body functions like heart rate, blood pressure, breathing and digestion. As these systems break down, people with MSA develop a wide range of symptoms.
How Common Is MSA?
MSA affects an estimated 15,000 to 50,000 people in the United States. It affects men and women of all racial and ethnic groups (1).
What Causes MSA?
The cause of MSA is not well understood, but researchers have found buildup of a misfolded protein called alpha-synuclein in oligodendrocytes (2). Oligodendrocytes are support cells that make myelin, the protective coating around nerve fibers that helps signals travel quickly and efficiently. When alpha-synuclein builds up in these cells, they can no longer properly support and protect nerve cells, which leaves the nerve cells more vulnerable to damage and early death.
The same protein builds up in Parkinson’s disease, but there it collects mainly in dopamine-producing nerve cells. Because both diseases involve alpha-synuclein, they are called synucleinopathies (1). Variations in the SNCA gene, which provides the instructions for making alpha-synuclein, may raise the risk of these diseases (3).
What Are the Early Symptoms of MSA?
Early symptoms of MSA can look a lot like Parkinson’s disease. They can include loss of coordination; slow movement, tremor or stiffness; slow or slurred speech or a quiet, shaky voice; fainting or lightheadedness when standing, caused by a drop in blood pressure called orthostatic hypotension; difficulty chewing or swallowing; and loss of bladder and bowel control.
MSA is divided into two types, depending on which symptoms are most prominent (1). The parkinsonian type (MSA-P) mainly looks like Parkinson’s disease, with slow movement, tremor, shuffling walk, balance problems and autonomic problems. The cerebellar type (MSA-C) mainly involves the cerebellum, with ataxia (problems with balance and coordination), difficulty swallowing, voice changes and abnormal eye movements.
What Are the Later Symptoms of MSA?
MSA usually progresses faster than Parkinson’s disease. Later symptoms can include contractures, where muscles or tendons around the joints shorten and limit movement; Pisa syndrome, where the body leans to one side like the Leaning Tower of Pisa; antecollis, where the head drops forward; involuntary sighing or gasping as breathing control changes; sleep disorders; anxiety or depression; and worsening dysautonomia, which makes it hard to control heart rate, blood pressure, sweating, sexual function, and bladder and bowel function (4).
Some people with MSA develop noisy, high-pitched breathing during sleep, called stridor. Because this can be a sign of a serious breathing problem, tell your doctor right away if you or a bed partner notice it.
How Does MSA Affect the Brain?
Alpha-synuclein buildup makes nerve cells in affected areas more likely to die. When the oligodendrocytes can no longer maintain myelin and support nearby nerve cells, those nerve cells lose the support they need to survive (2).
MSA also appears to affect how cells make energy. Nerve cells make energy in tiny structures called mitochondria. Coenzyme Q10 (CoQ10) plays an important role in this process, and genetic studies have linked problems with CoQ10 production to MSA. Problems with other energy-producing enzymes have also been found. These mitochondrial problems may not cause MSA, but they may speed up nerve cell loss (5).
Research is also exploring a connection between the gut and MSA. Studies have found that people with MSA have different gut bacteria than healthy people, along with signs of increased intestinal permeability and inflammation (6). One theory is that an overactive immune response to gut bacteria, together with a leakier intestinal lining, may trigger inflammation that contributes to alpha-synuclein buildup (7).
Another line of research suggests that misfolded alpha-synuclein may spread from cell to cell through the nervous system in both Parkinson’s disease and MSA, somewhat like a prion. Prions are misfolded proteins that can cause other proteins to misfold. There is no evidence that MSA or Parkinson’s disease can be passed from person to person, but research supports the idea that, once they begin, they may spread through the nervous system in a prion-like way (8). Research has also found biochemical differences between the alpha-synuclein in MSA and in Parkinson’s, with the MSA form spreading more readily between cells. In the future, these differences may help with diagnosis (9).
How Is MSA Diagnosed?
MSA is diagnosed by a physician, usually a neurologist. A careful medical history and thorough neurological exam are essential. Other tests can help support the diagnosis, rule out similar conditions and guide treatment. These may include brain imaging, heart and blood pressure testing, smell testing, a sleep study, bladder evaluation, swallowing studies and cognitive testing. Researchers are also developing new tools, such as skin biopsies, eye scans, blood and spinal fluid tests, and genetic testing, which may allow earlier and more accurate diagnosis.
How Is MSA Usually Treated?
There is no known cure for MSA, and treatment focuses on managing symptoms. Medications are often used for specific symptoms. Blood pressure drops and lightheadedness may be helped by increasing salt and fluid intake, wearing compression stockings and avoiding large meals. Botulinum toxin (Botox) injections may help with tight or contracted muscles. Physical therapy can help maintain mobility, muscle length and posture, and assistive devices may be needed for stability (10).
How the NeuroRescue Program Can Help
We cannot cure MSA or stop its progression. Our goal is to help you make the most of the function you have, with a focus on balance, walking, safety, eye movements, thinking and quality of life. Our care works alongside your neurologist and other providers, never in place of them. Please don’t change any medication without talking with your prescriber. Because blood pressure drops are common in MSA, we take them into account when planning and pacing your therapy.
Eye movements and balance. Much of the difficulty in MSA involves knowing where you are in space. Your brain combines signals from your muscles and joints, your inner ear and your eyes to build a picture of where you are. Your eyes constantly scan your surroundings using saccades, quick jumps from one point to another.
To move safely through the world, saccades need to be fast, accurate and quick to start. Because the brainstem and cerebellum help control saccades, they often become less accurate and quick to tire in MSA (11).
Smooth pursuit, the ability to follow a moving target, is also affected in both MSA and Parkinson’s disease, but in different ways (12). These differences can even help tell the two conditions apart (13).
Research has linked saccade problems in MSA and related conditions to poor balance, difficulty turning and freezing while walking (14). We use targeted saccade exercises with the goal of supporting balance, walking and stability.
Anti-saccades are a more complex type of eye movement, in which a person must hold back the urge to look at a new target and look the other way instead. Anti-saccades draw on the brain’s planning and self-control systems. Research shows that anti-saccades are affected in MSA, and these changes have been linked to problems with planning, reasoning and emotional control (15). We use anti-saccade exercises with the goal of supporting flexible thinking and emotional regulation.
Other therapies. Much of the research on these therapies has been done in Parkinson’s disease and related conditions rather than in MSA specifically. Depending on your needs, your program may include vestibular rehabilitation, which has been studied for balance, walking and thinking (16); optokinetic visual stimulation, which has been studied for movement control and posture (17, 18); various forms of electrical stimulation, applied through the skin, which have been studied for balance, walking, eye movements, tremor, blood pressure regulation and swallowing (19, 20, 21); and virtual reality exercises, which have been studied for improving daily function and reducing fall risk (22).
Transcranial magnetic stimulation. TMS has been studied for improving movement, balance and mood in parkinsonian conditions (23). At our clinic, TMS is provided by our psychiatric mental health nurse practitioner, who will evaluate whether it’s appropriate for you.
Every person with MSA is different, and so is every NeuroRescue Program. Your plan is based on your test results and the specific factors of your case.
How the NeuroRescue Program Works
Your NeuroRescue Program begins with your Discovery Day. We start with a detailed history of your condition and your life on a timeline. This helps us understand the factors that may have contributed to where you are now, and identify related conditions that may be making it harder to move forward. When appropriate, we may also look at metabolic factors such as gut health, oxidative stress and mitochondrial function.
We measure how your visual, vestibular and balance systems are working through computerized analysis of your eye movements, inner ear reflexes and balance under different conditions. Our testing includes videonystagmography and saccadometry to measure several types of eye movements, the video head impulse test to measure inner ear reflexes, and CAPS computerized posturography to assess your balance under different sensory conditions. We also use NeuroSensoryMotor Integration testing to evaluate hand-eye coordination and cognition, and Virtualis testing to assess dynamic eye tracking and your perception of vertical in a virtual reality environment.
We combine this with a thorough physical and neurological exam of your sensory, motor, autonomic and cognitive systems. We also review any relevant lab work, imaging and prior testing, and integrate it with our findings.
Together, this helps us understand which parts of your nervous system are working well, which are struggling, and how quickly they tire. We use that information to design your personal NeuroRescue Program, aimed at supporting function and endurance in the systems that need it. Our testing also helps us decide when to push and when to let you rest.
We can’t bring back nerve cells that have been lost. What we can do is work with the pathways that remain, helping them work as efficiently as possible and work better together. Our goal is to help you stay as active, safe and independent as possible, for as long as possible.
Your Next Step
Living with MSA is challenging. While we cannot cure it, many symptoms can be managed, and function and quality of life can often be supported. To find out if the NeuroRescue Program is right for you, contact one of our patient care coordinators to schedule your Discovery Day.
It’s never too late to take the next step.
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