Multiple system atrophy is a rare brain disease that gradually takes away a person’s ability to control their movements and body’s automatic functions. This progressive condition affects adults, usually starting in their 50s, and leads to a combination of problems with balance, muscle stiffness, blood pressure control, and other vital functions that most people never think about.
Epidemiology
Multiple system atrophy is considered a rare neurological disease. According to medical research, the estimated number of new cases each year ranges from 0.6 to 0.7 per 100,000 people. When looking at the total number of people living with the condition at any given time, the prevalence is estimated to be between 3.4 and 4.9 cases per 100,000 people. In the United States, this translates to approximately 13,000 to 75,000 people living with MSA, though the exact number is difficult to determine because many patients receive incorrect diagnoses during their lifetime.[1][2][3]
The disease does not show a preference for either men or women, affecting both sexes equally. Multiple system atrophy is an adult-onset condition, meaning it only affects people over the age of 30. The symptoms most commonly begin to appear when people are between 50 and 59 years old, though some cases start in the late 40s or early 70s. The mean age of symptom onset across different studies ranges from 54 to 63 years.[3][8][17]
Despite affecting thousands of people, MSA remains much rarer than more well-known neurological conditions. For comparison, approximately 1 million people in the United States have Parkinson’s disease, and about 7 million have Alzheimer’s disease. This rarity means that many healthcare providers may have limited experience with the condition, which can lead to delays in proper diagnosis.[17]
Causes
The exact cause of multiple system atrophy remains unknown to medical science. What researchers do know is that the disease involves the progressive loss and death of nerve cells in specific areas of the brain and spinal cord. As these nerve cells die, the functions they control begin to fail, leading to the wide range of symptoms seen in people with MSA.[1][2]
At the microscopic level, multiple system atrophy is characterized by the presence of abnormal protein deposits called glial cytoplasmic inclusions, or GCIs. These inclusions are found within special brain cells called oligodendrocytes, which normally help support and protect nerve cells. The main component of these inclusions is a protein called alpha-synuclein, which has become misfolded and clumped together in an insoluble form. Because of this distinctive feature, MSA is classified as an alpha-synucleinopathy, a family of diseases that also includes Parkinson’s disease.[5][8][13]
Recent research has revealed that the disease process involves complex interactions between alpha-synuclein, inflammation within the nervous system, and the relationship between oligodendrocytes and neurons. However, scientists have not yet determined why these abnormal protein deposits form or what triggers the cascade of cell death that follows.[13]
Multiple system atrophy is considered a sporadic disease, meaning it occurs randomly without a clear pattern. There is no evidence that MSA can be inherited or passed down from parents to children. The condition is not contagious and cannot be transmitted from one person to another. Research continues to investigate whether certain individuals might have genetic or environmental factors that make them more susceptible to developing the disease.[5][12]
Risk Factors
Unlike many diseases where clear risk factors have been identified, multiple system atrophy has very few known risk factors. The most significant risk factor is age. The disease primarily affects adults over 30 years old, with the highest risk occurring in people in their 50s. People younger than 30 are not affected by MSA.[3][17]
Gender does not appear to be a risk factor, as the condition affects men and women equally. Unlike some neurological conditions that show clear demographic patterns or associations with lifestyle factors, MSA does not have well-established links to specific behaviors, occupations, or environmental exposures.[3]
Because MSA is sporadic rather than inherited, having a family member with the disease does not significantly increase a person’s risk of developing it. This sets it apart from some other neurodegenerative conditions where family history plays an important role. Researchers continue to study whether subtle genetic variations or environmental factors might influence who develops the disease, but no definitive risk factors beyond age have been established.[12]
Symptoms
Multiple system atrophy causes a wide variety of symptoms that affect many different parts of the body. The specific symptoms each person experiences depend on which areas of their brain are most affected by the disease. Medical professionals have identified two main types of MSA based on the most prominent symptoms a person shows when they are first evaluated: parkinsonian type (MSA-P) and cerebellar type (MSA-C).[1][2]
In the parkinsonian type, the primary symptoms resemble those of Parkinson’s disease. These include stiff muscles that are difficult to bend, slow movement (called bradykinesia), and sometimes tremors that occur either at rest or when moving the arms and legs. People with this type also experience trouble with posture and balance, making them prone to falls. Speech often becomes slurred, slow, or soft, a condition known as dysarthria.[1][2]
The cerebellar type of MSA primarily involves problems with muscle coordination, known as ataxia. People with this type have trouble coordinating their movements, which leads to loss of balance and an unsteady, staggering walk that may appear drunk-like. They may also experience vision changes such as blurred or double vision, along with the same speech difficulties seen in the parkinsonian type.[1][4]
Regardless of type, nearly all people with MSA develop problems with their autonomic nervous system. The autonomic nervous system controls involuntary body functions that normally happen automatically without conscious thought. When this system fails, a condition called dysautonomia develops. One of the earliest and most common autonomic symptoms is orthostatic hypotension, which means blood pressure drops dramatically when standing up from sitting or lying down. This can cause people to feel faint, dizzy, or extremely tired, and may lead to complete loss of consciousness. The danger here is not just the discomfort but the high risk of falls and fall-related injuries.[3][4]
Bladder and bowel problems are also very common in MSA. People may experience increased urinary frequency, a sudden urgent need to urinate, and the feeling that their bladder has not completely emptied. Constipation frequently occurs as the autonomic nervous system loses control over bowel movements. Sexual dysfunction is another early manifestation, with men often experiencing erectile dysfunction or loss of morning erections.[3][4]
Other symptoms that may develop include problems with body temperature regulation, leading to feeling too hot or too cold. Some people experience abnormal sweating patterns or have difficulty chewing and swallowing food. Noisy breathing, unintentional sighing, and snoring can occur as the disease affects respiratory control. Emotional symptoms such as anxiety, depression, or unpredictable laughing and crying may also appear.[1][2][4]
As the disease progresses, additional physical changes may occur. Contractures can develop, which are chronic shortenings of muscles or tendons around joints that prevent joints from moving freely, causing stiffness in the hands and limbs. Some people develop unusual postures, such as Pisa syndrome, where the body leans involuntarily to one side, or anterocollis, where the neck bends forward and the head drops down.[2]
The symptoms of MSA tend to progress rapidly compared to other similar conditions like Parkinson’s disease. Most people will require assistance with walking, such as a cane or walker, within just a few years after symptoms begin. Over time, movement difficulties increase to the point where people eventually become bedridden. Swallowing problems can become severe in later stages, significantly increasing the risk of pneumonia.[1][2]
Prevention
Unfortunately, there are currently no known ways to prevent multiple system atrophy. Because the exact cause of the disease remains unknown and it occurs sporadically without clear risk factors, medical science has not identified any lifestyle changes, dietary modifications, supplements, or other preventive measures that can reduce the risk of developing MSA.[1][12]
The disease is not inherited, so genetic screening or counseling for family members is not applicable. Since MSA is not caused by infection, there are no vaccines or hygiene measures that would offer protection. Unlike some conditions where early screening can detect pre-disease states, there are no screening tests available for MSA in people without symptoms.[12]
While prevention is not possible, early and accurate diagnosis is important. Recognizing symptoms early and getting proper medical evaluation can help people receive appropriate symptom management and support services sooner, potentially improving quality of life even if the disease course cannot be altered. Research continues into understanding what causes MSA, and scientists hope that future discoveries about the disease mechanism might eventually lead to preventive strategies.[13]
Pathophysiology
The pathophysiology of multiple system atrophy involves complex changes in how the brain and nervous system normally function. At the core of the disease process is the death and loss of specific types of nerve cells in certain brain regions. The parts of the brain most commonly affected include the basal ganglia, the brainstem, and the cerebellum.[3][9]
The basal ganglia are structures located near the center of the brain that connect many different brain areas together. They form a critical network that allows various parts of the brain to work cooperatively, particularly for coordinating movement. When nerve cells in the basal ganglia die, as happens in the parkinsonian type of MSA, people develop slowness of movement, stiffness, and other parkinsonian features.[3]
The brainstem sits at the base of the brain and is responsible for managing many of the body’s automatic processes that we never consciously control. These include breathing, heart rate, blood pressure, digestion, and bladder function. When the brainstem deteriorates in MSA, these autonomic processes fail, leading to dangerous blood pressure drops, bladder problems, and difficulties with breathing and swallowing.[3]
The cerebellum is located at the back of the head and plays a crucial role in coordinating movements and maintaining balance. When this structure is primarily affected, as in the cerebellar type of MSA, people develop ataxia with its characteristic unsteady gait and loss of coordination. Research suggests the cerebellum may also contribute to other functions such as emotions and decision-making, though scientists are still learning about all its roles.[3]
What makes MSA unique at the cellular level is the presence of glial cytoplasmic inclusions within oligodendrocytes. Oligodendrocytes are specialized brain cells that normally support and protect nerve cells by producing a fatty coating called myelin that insulates nerve fibers. In MSA, these support cells accumulate abnormal clumps of misfolded alpha-synuclein protein. These protein aggregates are thought to impair the oligodendrocytes’ ability to support neurons, ultimately leading to widespread nerve cell death.[5][13]
Current research indicates that inflammation within the nervous system, called neuroinflammation, plays an important role in the disease process. The abnormal protein deposits trigger inflammatory responses that may further damage brain tissue. Scientists are investigating how alpha-synuclein, oligodendrocytes, neurons, and inflammatory processes interact to cause the progressive degeneration seen in MSA.[13]
The disease gets its name from the multiple systems it affects. It was historically recognized as three separate conditions: striatonigral degeneration (affecting the basal ganglia), olivopontocerebellar atrophy (affecting the cerebellum and related structures), and Shy-Drager syndrome (primarily affecting autonomic functions). Scientists eventually discovered that these conditions shared the same microscopic abnormalities and were actually different manifestations of a single disease, leading to the unified term “multiple system atrophy.”[3][5]
As nerve cells continue to die over time, the affected brain regions progressively lose their ability to function. This explains why symptoms steadily worsen and new symptoms emerge as different areas succumb to the disease process. The rapid progression of MSA compared to conditions like Parkinson’s disease reflects the aggressive nature of the underlying neurodegeneration and the involvement of multiple critical brain systems simultaneously.[1][2]
