Progressive-relapsing multiple sclerosis is the rarest form of MS, affecting only about 5% of all people living with the disease. Understanding when and how to get tested is crucial for proper management, as this condition steadily worsens from the start while also bringing occasional sudden flare-ups of symptoms.

Introduction: Who Should Undergo Diagnostics

Getting tested for progressive-relapsing multiple sclerosis should happen when someone experiences symptoms that suggest problems with their central nervous system, which includes the brain, spinal cord, and optic nerve. The central nervous system acts like the body’s command center, sending signals throughout the body to control movement, sensation, and many other functions.^[1]

People who notice a gradual worsening of their abilities over time should seek medical evaluation. This might show up as increasing difficulty with walking, growing muscle weakness, vision changes that don’t improve, or worsening problems with balance and coordination. What makes progressive-relapsing MS different from other forms is that these symptoms get steadily worse from the very beginning, similar to primary progressive MS. However, people with this condition also experience occasional episodes where symptoms suddenly intensify or new symptoms appear, similar to what happens in relapsing-remitting MS.^[1]

The pattern that should prompt someone to seek diagnostic testing includes both steady decline and periodic flare-ups. When symptoms have been gradually worsening, and then suddenly become much worse or new symptoms appear out of nowhere, this combination suggests progressive-relapsing MS might be present. These sudden worsening episodes, called relapses or attacks, happen because of inflammation in the nervous system, while the ongoing decline occurs because nerves are being damaged or lost.^[1]

Most people receive a diagnosis of progressive-relapsing MS in their mid-to-late 30s, though the condition can affect people at any age. Interestingly, this form of MS affects men and women equally, which is different from other types where women are more commonly affected.^[1]

Anyone experiencing persistent numbness or tingling, vision problems like double vision, unexplained fatigue that interferes with daily activities, muscle stiffness, difficulty controlling bladder or bowel functions, or problems with memory and information processing should consult a doctor for evaluation. These symptoms don’t automatically mean someone has progressive-relapsing MS, as many conditions can cause similar problems, but they warrant medical investigation.^[1]

Diagnostic Methods

Diagnosing progressive-relapsing multiple sclerosis is not straightforward because no single test can confirm or rule out the condition. Instead, doctors gather information from multiple sources to piece together the full picture. The diagnostic process requires careful detective work to distinguish progressive-relapsing MS from other nervous system disorders that might cause similar symptoms.^[1]

The journey to diagnosis begins with a detailed medical history. Your doctor will ask about when symptoms first appeared, how they have changed over time, whether there have been periods when symptoms suddenly worsened, and whether symptoms have improved at all or only gotten worse. This conversation helps establish whether the pattern matches progressive-relapsing MS, where disability progresses from the beginning with occasional relapses on top of the steady decline.^[1]

After taking your medical history, your doctor will perform a neurological examination. This physical examination tests how well your nervous system is working. The doctor checks your reflexes, muscle strength, coordination, balance, sensation, vision, and other functions controlled by the brain and spinal cord. The neurological exam can reveal problems that might not be obvious from symptoms alone and helps doctors understand which parts of the nervous system are affected.^[1]

One of the most important diagnostic tools is magnetic resonance imaging, commonly called an MRI scan. This test uses magnets and radio waves to create detailed pictures of the brain and spinal cord without using radiation. An MRI can show areas where myelin, the protective coating around nerve fibers, has been damaged. These damaged areas appear as bright spots or lesions on the scan. The pattern, location, and number of these lesions help doctors determine whether MS is present and what type it might be.^[1]

A lumbar puncture, also known as a spinal tap, may be ordered as part of the diagnostic workup. During this procedure, a doctor inserts a thin needle between the bones of the lower spine to collect a small sample of cerebrospinal fluid, the liquid that surrounds and protects the brain and spinal cord. Laboratory analysis of this fluid can reveal patterns that are characteristic of MS, such as the presence of certain proteins or immune system cells that shouldn’t be there in large numbers. The findings from cerebrospinal fluid analysis help support or rule out an MS diagnosis.^[1]

Blood tests play an important role in the diagnostic process, but not to directly diagnose progressive-relapsing MS. Instead, blood tests help doctors rule out other conditions that can mimic MS symptoms. Many other diseases affecting the nervous system can cause symptoms similar to MS, including certain infections, vitamin deficiencies, and other autoimmune conditions. By testing for these other possibilities and finding them absent, doctors can be more confident that MS is the correct diagnosis.^[1]

Nerve function tests, also called evoked potential studies, measure how quickly and accurately your nerves transmit electrical signals. During these tests, sensors are placed on your scalp or skin, and you might be asked to look at a pattern on a screen, listen to clicking sounds, or feel gentle electrical stimulation. The tests measure how long it takes for signals to travel through your nerves. Slowed or delayed responses can indicate nerve damage caused by MS, even in areas where you haven’t noticed symptoms yet.^[1]

The diagnostic challenge with progressive-relapsing MS lies in recognizing both the progressive nature of the disease and the presence of relapses. Because symptoms worsen continuously from the start, doctors must carefully distinguish whether sudden symptom changes represent true relapses caused by new inflammation, or simply fluctuations in existing symptoms due to other factors like heat, stress, or infection. A true relapse must involve new symptoms or significant worsening of old symptoms that persist for at least 24 to 48 hours without another explanation.^[1][2]

Diagnostics for Clinical Trial Qualification

When people with progressive-relapsing MS are considered for participation in clinical trials, they undergo additional testing beyond standard diagnostic procedures. Clinical trials are research studies that test whether new treatments are safe and effective, and they have strict requirements about who can participate to ensure the study results are reliable and meaningful.^[3]

While specific clinical trial requirements vary depending on the study’s goals, certain diagnostic tests serve as standard criteria for qualifying patients with progressive-relapsing MS. The medical history and neurological examination remain fundamental, but researchers conducting trials need very detailed and precise information about each participant’s condition at the start of the study. This baseline information helps researchers measure whether the treatment being tested makes any difference.^[3]

MRI scans are typically required for clinical trial enrollment. Researchers need to document the extent of disease in the brain and spinal cord before treatment begins. These baseline scans are then compared to scans taken during and after the trial to see if the treatment slows down the formation of new lesions or prevents existing lesions from getting larger. The number, size, and location of lesions visible on MRI help researchers track disease activity objectively, beyond just asking patients about their symptoms.

Clinical trials often require cerebrospinal fluid analysis through lumbar puncture to confirm the diagnosis and establish baseline measurements of various proteins and immune cells in the fluid. Some trials specifically look for changes in these fluid markers as evidence that a treatment is working to reduce inflammation or protect nerves from damage.

Blood tests become more extensive in clinical trial settings. Beyond ruling out other conditions, researchers collect blood samples to measure various markers of inflammation, immune system activity, and nerve damage. These biological markers, called biomarkers, help researchers understand how the disease is affecting the body at a molecular level and whether a treatment is having its intended effect. Some trials specifically measure levels of proteins called neurofilament light chains in blood, which leak out of damaged nerve cells and can indicate how much nerve destruction is occurring.

Nerve function tests or evoked potential studies may be required at the beginning of a clinical trial and then repeated at regular intervals. These tests provide objective measurements of how well the nervous system is functioning, which helps researchers determine if a treatment is preventing further nerve damage or even helping the nervous system work better.

Many clinical trials use standardized tests to measure disability levels. While not strictly diagnostic tests, these assessment tools are essential for determining whether someone’s level of disability meets the trial’s entry criteria and for tracking whether disability worsens, stays the same, or improves during the study. These might include timed walking tests to measure mobility, tests that assess hand coordination and speed, and cognitive tests that evaluate memory and thinking abilities.

The diagnostic requirements for clinical trial qualification serve multiple purposes. They ensure that participants truly have the condition being studied, establish baseline measurements against which changes can be measured, and sometimes help researchers understand why some people respond to treatment while others don’t. While these extensive testing requirements might seem burdensome, they are necessary to develop safe and effective new treatments for progressive-relapsing MS.