Diagnosing Multiple System Atrophy (MSA) presents unique challenges because there is no single test that confirms the condition. Instead, doctors rely on a combination of clinical observations, symptom tracking, and specialized examinations to piece together a diagnosis that can sometimes take months or even years to confirm.
Introduction: When to Seek Diagnostic Testing for MSA
People who should consider seeking diagnostic evaluation for Multiple System Atrophy are those experiencing a combination of troubling symptoms that affect movement, balance, and automatic body functions. If you or a loved one notice symptoms such as difficulty with coordination, unexplained falls, problems controlling blood pressure when standing up, or bladder control issues alongside movement problems similar to Parkinson’s disease, it’s time to see a doctor. These symptoms typically appear in adults over age 30, most commonly between ages 50 and 59, though they can develop earlier or later in life.[1][3]
The decision to seek diagnostics should not be delayed when symptoms interfere with daily activities or quality of life. Many people with MSA initially see their primary care doctor for individual symptoms—perhaps dizziness when standing, urinary urgency, or stiffness—before being referred to a specialist. Because MSA is rare, affecting only about 3 to 5 people per 100,000, many general practitioners may not immediately recognize the pattern of symptoms.[3][8]
It’s particularly important to seek evaluation when symptoms progress quickly or when multiple body systems seem affected at once. For instance, if movement problems are accompanied by fainting spells, difficulty swallowing, or sleep disturbances where you act out vivid dreams, these combinations warrant thorough investigation. Early evaluation allows for better symptom management and helps rule out other conditions that might be treatable.[4]
Diagnostic Methods for Identifying Multiple System Atrophy
Diagnosing Multiple System Atrophy can be challenging because there is no single definitive test that confirms the condition. Instead, doctors must rely on a careful evaluation of symptoms, their progression over time, and how quickly they worsen. The diagnosis is primarily clinical, meaning it’s based on what doctors observe and what patients report about their experiences.[7][5]
Clinical Evaluation and Medical History
The diagnostic process typically begins with a thorough medical history and physical examination. Your healthcare provider, usually a neurologist (a doctor who specializes in brain and nerve disorders), will ask detailed questions about when symptoms started, how they’ve changed, and which parts of your body they affect. The neurologist will perform a physical examination that tests your muscle strength, coordination, balance, reflexes, and ability to sense touch and temperature. They’ll also evaluate how your body manages automatic functions like blood pressure regulation.[7]
During the examination, doctors look for specific patterns of symptoms. MSA is classified into two types based on which symptoms are most prominent when diagnosed. The parkinsonian type (MSA-P) shows symptoms similar to Parkinson’s disease, such as stiff muscles, slow movement, tremors, and difficulty with balance. The cerebellar type (MSA-C) primarily involves poor muscle coordination, problems with balance and walking steadily, and slurred speech. Both types also include problems with automatic body functions, which helps distinguish MSA from Parkinson’s disease.[1][3]
Testing Autonomic Functions
One of the key features that helps identify MSA is autonomic dysfunction, which means problems with the body’s automatic processes. Several specialized tests can evaluate how well these systems are working. The tilt table test is particularly useful for diagnosing issues with blood pressure control. In this test, you lie on a motorized table that’s tilted upward to about 70 degrees while healthcare professionals monitor your blood pressure and heart rate. People with MSA often experience a significant drop in blood pressure when moving from lying down to an upright position, a condition called orthostatic hypotension. This happens because the autonomic nervous system fails to make the necessary adjustments to keep blood pressure stable.[7][19]
Other autonomic function tests may include measuring blood pressure while lying down and standing without using a tilt table, conducting a sweat test to evaluate which areas of the body produce sweat normally, examining bladder and bowel function, and performing an electrocardiogram (ECG or EKG) to track the electrical signals of your heart. If you’ve reported sleep problems, your doctor might recommend a sleep study to look for conditions like REM sleep behavior disorder, where people physically act out their dreams. This sleep disorder is common in MSA and often appears before other symptoms.[4][7]
Brain Imaging Studies
While brain imaging cannot definitively diagnose MSA, it plays an important supportive role by showing changes in specific brain regions and helping rule out other conditions. Magnetic Resonance Imaging (MRI) is the most commonly used imaging technique. An MRI uses powerful magnets and radio waves to create detailed pictures of the brain’s soft tissues. In people with MSA, the MRI may show changes in areas like the cerebellum, brainstem, or basal ganglia—the parts of the brain most affected by the disease.[5][7]
However, it’s important to understand that MRI results can be normal, especially in the early stages of MSA. Changes in the brain may not be visible on imaging until the disease has progressed. This is why MRI is used alongside clinical evaluation rather than as a standalone diagnostic tool. The imaging helps doctors feel more confident in their diagnosis when characteristic changes are present, but the absence of these changes doesn’t rule out MSA.[7]
Some medical centers may use additional imaging techniques such as PET scanning (Positron Emission Tomography), which can show how different parts of the brain are functioning, or a DaTscan, which looks at dopamine transporters in the brain. These specialized scans can help distinguish MSA from Parkinson’s disease or support the diagnosis, but like MRI, they are not sensitive or specific enough to diagnose MSA on their own.[7]
Distinguishing MSA from Other Conditions
One of the biggest diagnostic challenges is distinguishing MSA from other conditions with similar symptoms, particularly Parkinson’s disease. The most common initial misdiagnosis is Parkinson’s disease because both conditions can cause slow movement, stiff muscles, and tremors.[5][17]
Several features help differentiate MSA from Parkinson’s disease. People with MSA tend to progress more rapidly and often require a walking aid within just a few years of symptom onset, whereas Parkinson’s disease typically progresses more slowly. Additionally, the characteristic medications used for Parkinson’s disease (such as levodopa) either don’t work well in MSA or provide only minimal, temporary improvement. The presence of significant autonomic problems—particularly orthostatic hypotension and urinary difficulties—early in the disease course is much more common in MSA than in Parkinson’s disease.[2][4]
Blood tests and other laboratory work are typically performed, not to diagnose MSA directly, but to rule out other conditions that could cause similar symptoms. For example, certain vitamin deficiencies, thyroid problems, or other metabolic disorders can affect movement and coordination. By excluding these treatable conditions, doctors can be more confident in an MSA diagnosis.[7]
The Diagnostic Journey
Because of these diagnostic complexities, many people go through a lengthy process before receiving a definitive diagnosis. You may see multiple specialists, undergo various tests, and possibly receive different diagnoses before MSA is identified. This uncertainty can be frustrating and emotionally draining for patients and families. The diagnosis of MSA is classified as either “clinically probable MSA” or “clinically established MSA” depending on the combination and severity of symptoms present. A definitive diagnosis can only be made by examining brain tissue under a microscope after death, where doctors look for characteristic abnormal protein deposits in cells called glial cytoplasmic inclusions.[7][5]
Given the rarity of MSA, seeking evaluation at a medical center with experience in movement disorders can be beneficial. Specialists at these centers have more familiarity with atypical parkinsonian syndromes and may recognize the pattern of symptoms more quickly. They also have access to specialized testing equipment and stay current with the latest diagnostic criteria.[13]
Diagnostics for Clinical Trial Qualification
For individuals interested in participating in clinical trials studying potential treatments for MSA, additional diagnostic criteria and testing may be required beyond standard clinical practice. Clinical trials are research studies that test new approaches to treating or understanding diseases, and they require careful patient selection to ensure the safety of participants and the accuracy of study results.
Clinical trial eligibility typically requires a diagnosis that meets specific consensus criteria. In 2008, a widely adopted set of diagnostic criteria was established, and in 2022, the Movement Disorder Society proposed updated criteria specifically designed to facilitate research and clinical trial enrollment. These criteria define MSA based on the presence of specific combinations of symptoms and signs, including autonomic failure, parkinsonism, and cerebellar problems.[5][13]
Trials may require documentation of symptom progression over time, often asking patients to have been symptomatic for a certain period but not so advanced that they wouldn’t benefit from or safely tolerate the experimental treatment. Some trials specify that participants must have MSA-P or MSA-C type specifically, while others may accept both. The requirement to document how rapidly symptoms have worsened helps researchers understand whether an experimental treatment is slowing disease progression.[8]
Brain imaging studies, particularly MRI scans, are commonly required for trial participation. Researchers may want to see specific changes in the brain that support the MSA diagnosis or to establish a baseline against which future scans can be compared to measure disease progression. Some trials may use advanced imaging techniques not typically available in routine clinical care, such as specialized MRI sequences that can detect subtle changes in brain structure.[13]
Autonomic function testing is often mandatory for trial enrollment, particularly measurements of blood pressure response to standing and formal assessment of orthostatic hypotension. Trials may require that patients have documented autonomic failure meeting specific severity thresholds. This standardization helps ensure that all participants in the trial truly have MSA and not another condition.[8]
Additional laboratory tests may be required to ensure participant safety. These can include comprehensive blood work to check kidney and liver function, blood cell counts, and screening for conditions that might make participation unsafe. Some trials studying specific types of therapies may require specialized biomarker testing—measurements of certain proteins or other substances in blood or spinal fluid that might predict how well someone will respond to the experimental treatment.[8]
For trials testing treatments aimed at slowing or stopping disease progression, researchers may want to collect cerebrospinal fluid (the liquid that surrounds the brain and spinal cord) through a procedure called a lumbar puncture or spinal tap. This fluid can be analyzed for proteins associated with MSA, particularly alpha-synuclein, which forms abnormal deposits in the brains of people with the condition. While this procedure isn’t part of routine diagnostic practice, it’s becoming more common in research settings as scientists work to develop biomarkers that could help with earlier diagnosis or treatment monitoring.[13]
Cognitive and psychological assessments may also be part of trial screening. While severe dementia is unusual in MSA, researchers may want to document baseline cognitive function to track any changes during the study or to ensure participants can provide informed consent and follow trial procedures. Similarly, assessments of mood, particularly for depression and anxiety, help researchers understand the full impact of the disease and any effects of the experimental treatment on quality of life.[17]
Physical function assessments using standardized scales and questionnaires are standard in clinical trials. These might include timed walking tests, questionnaires about daily activities, and measurements of balance and coordination. These baseline measurements provide objective ways to track whether an experimental treatment affects disease progression. Quality of life questionnaires help capture the patient’s perspective on how symptoms affect their daily experiences.[8]
It’s worth noting that the field of MSA research is actively working to develop better diagnostic methods that could identify the disease earlier and more reliably. Studies are investigating various biomarkers in blood, spinal fluid, and imaging that might one day allow diagnosis before symptoms become severe. Some of these investigational techniques may be incorporated into clinical trials, giving participants access to cutting-edge diagnostic approaches while contributing to validating these methods for future clinical use.[13]
