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Sudden vision loss or weakness in your arms and legs can be alarming. Finding out what’s wrong as soon as possible is key for getting the care you need.
Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) can cause similar symptoms, which can make diagnosis difficult. In the past, NMOSD was thought to be a subtype of MS. As a result, some people may have been misdiagnosed and received the wrong treatment. Today, we know that NMOSD and MS are two distinct conditions with different causes and treatment plans.
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To tell the difference between MS and NMOSD, healthcare providers use many tests, including one called the aquaporin-4-immunoglobulin G (AQP4-IgG) test. This test checks for a specific protein in the blood that’s often found in people with NMOSD. A positive result can help confirm an NMOSD diagnosis.
It’s important to know that this test is helpful only when NMOSD is suspected. If MS is clearly diagnosed, the AQP4-IgG test isn’t needed and could add confusion.
Understanding how this test works and what the results mean will help you feel prepared and confident when you talk with your doctor about your diagnosis.
Your immune system helps protect you from getting sick. It uses special proteins called antibodies to fight off viruses and bacteria.
Sometimes, however, the immune system makes a mistake. Instead of targeting germs, the immune system creates autoantibodies that attack healthy parts of the body. That’s what happens in an autoimmune disease like NMOSD.
IgG proteins are the most common type of antibody in your blood. In NMOSD, some of these IgG antibodies turn into AQP4-IgG autoantibodies. These autoantibodies attack the nerves that control vision and muscles, causing NMOSD symptoms. The NMOSD IgG antibody test checks blood for AQP4-IgG antibodies and helps doctors confirm a diagnosis of NMOSD.
AQP4-IgG antibodies target AQP4 proteins that help manage water balance in the nervous system. These proteins sit on the surface of astrocytes — support cells in the brain and spinal cord.
When AQP4-IgG antibodies attach to AQP4 proteins, they trigger the immune system to attack the astrocytes. This causes inflammation that damages nearby nerve cells, leading to NMOSD symptoms, including:
If AQP4-IgG attacks the optic nerve, it can cause optic neuritis. If it attacks the spinal cord, it can cause myelitis.
The AQP4-IgG test is a simple way to confirm an NMOSD diagnosis. Whichever test you get, the goal is the same: to see if you have AQP4-IgG antibodies in your body.
For this AQP4-IgG test, a healthcare provider draws blood from a vein and sends it to a lab for analysis. A lab technician will check the blood sample for AQP4-IgG antibodies.
If your blood test is negative but you have NMOSD symptoms, your doctor may still suspect the condition based on clinical guidelines. In rare cases, a doctor might recommend testing cerebrospinal fluid (CSF) — the fluid around the brain and spinal cord — to look for AQP4-IgG antibodies. This is done through a procedure called a lumbar puncture (spinal tap). A thin needle is inserted into the lower back to draw out a small sample of CSF.
A positive result can support a diagnosis of NMOSD, even if the blood test was negative. However, a lumbar puncture isn’t required to make the diagnosis.
A positive result from an AQP4-IgG test means that these antibodies were found in your body. This helps confirm that you have NMOSD because these antibodies are very specific for the condition. If testing shows AQP4-IgG antibodies, it’s very likely you have NMOSD, not MS — more than 70 percent of people with NMOSD test positive for AQP4-IgG antibodies.
Getting the right diagnosis means your doctor can start you on an effective treatment plan as soon as possible, which is essential for protecting your long-term health.
A negative result from an AQP4-IgG test means no AQP4-IgG antibodies were found in your blood or spinal fluid. However, you could still have NMOSD. Some people with NMOSD test negative for these antibodies.
If you test negative but still have NMOSD symptoms, your doctor will consider other possible explanations and may use additional tests or imaging to guide the diagnosis.
Sometimes, AQP4-IgG antibodies don’t show up on tests because levels go up and down depending on treatment or whether someone is having a flare. When AQP4-IgG antibodies aren’t found but NMOSD is still suspected, it’s known as seronegative NMOSD. About 20 percent of people with NMOSD fall into this group.
If your symptoms and MRI findings strongly match NMOSD — even with a negative test — your doctor may still diagnose you with NMOSD.
Another condition that can look a lot like NMOSD is myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). In MOGAD, the immune system mistakenly makes antibodies against the MOG protein — a key part of the myelin sheath (the protective layer around nerves in the brain, spine, and eyes).
MOGAD symptoms can be similar to those of NMOSD and MS, making it hard for doctors to tell these conditions apart.
If your AQP4-IgG test is negative, your doctor may recommend testing for MOG-IgG antibodies. In one study, 70 percent of people with NMOSD symptoms who tested negative for AQP4-IgG were positive for MOG-IgG. A positive MOG-IgG test — along with matching symptoms — can help confirm a diagnosis of MOGAD.
If someone has symptoms that suggest a condition such as NMOSD, MOGAD or MS — and both the AQP4-IgG and MOG-IgG tests come back negative — then MS may be more likely, especially if other tests support that diagnosis.
Before the AQP4-IgG test was available, NMOSD and MS were often mistaken for each other. Many people with NMOSD were diagnosed with MS — a serious problem, because some older medications actually make NMOSD worse. Thanks to research, we now better understand the differences between NMOSD, MS, and MOGAD, making these mix-ups less common.
In most cases, doctors already have a strong idea of which condition is most likely based on symptoms and test results. Antibody testing — whether positive or negative — is a key tool that helps confirm the final diagnosis. Getting the right diagnosis means that you can get safe and effective treatment as soon as possible.
On MyMSTeam, people share their experiences with multiple sclerosis, get advice, and find support from others who understand.
What steps did you take after getting a negative AQP4-IgG test? Let others know in the comments below.
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