Your immune system is designed to protect you from harmful invaders such as bacteria and viruses, but sometimes it mistakenly attacks your own body instead. Neuromyelitis optica spectrum disorder (NMOSD) is a condition that happens when the immune system becomes overactive and attacks certain nerves in the central nervous system (CNS). This can lead to serious damage and symptoms like muscle weakness, difficulty moving, and vision problems.

Doctors and researchers don’t entirely understand why NMOSD develops, but they’ve identified some factors that may play a role. These risk factors include genetics (traits passed down from family members) and environmental triggers.

NMOSD is sometimes called neuromyelitis optica (NMO) or Devic’s disease. In this article, we’ll explore what researchers have learned about the causes of NMOSD, ways this condition affects the body, and factors that may increase the risk of developing it. To learn more about your own risk of NMOSD, talk with your neurologist (a doctor who specializes in conditions affecting the brain and nerves).

What Is Neuromyelitis Optica?

Neuromyelitis optica spectrum disease is a rare autoimmune disease that affects the CNS, which includes the brain, spinal cord, and optic nerves (which connect the eyes to the brain). In NMOSD, the immune system mistakenly attacks the CNS, leading to inflammation and nerve damage. When inflammation affects the spinal cord, it’s called transverse myelitis. When the optic nerve becomes inflamed, it’s known as optic neuritis.

Neuromyelitis optica spectrum disorder develops when abnormal immune proteins attack the brain, spinal cord, and optic nerves.

Neurological symptoms of NMOSD include:

• Eye pain
• Vision loss (in one or both eyes)
• Muscle weakness
• Spasticity (muscle stiffness or tightening)
• Uncontrollable hiccups

Causes of Neuromyelitis Optica

The exact cause of NMOSD isn’t fully understood, but researchers know it’s an autoimmune disease, meaning the immune system mistakenly attacks healthy cells, causing inflammation and tissue damage. In many autoimmune diseases, the immune system produces abnormal proteins called autoantibodies. Normally, antibodies (also known as immunoglobulins) help the body fight infection by marking harmful invaders for destruction. But in autoimmune diseases, autoantibodies see healthy cells as threats, leading the immune system to attack them instead.

How NMOSD Develops

Neuromyelitis optica spectrum disorder develops when autoantibodies attack the CNS, specifically targeting proteins that help nerve cells function. Researchers have found two types of autoantibodies that attack different proteins.

About 70 percent of people with NMOSD have antibodies against aquaporin-4 (AQP4), a protein found on astrocytes — support cells that help protect and maintain CNS nerves. When AQP4 antibodies flag these proteins as threats, this activates the complement system — a complex part of the immune system that normally destroys bacteria and viruses. However, in NMOSD, this response damages myelin, the protective layer around nerves, leading to nerve dysfunction and inflammation. This is why NMOSD is known as a demyelinating disease.

People with a history of other autoimmune conditions have a higher risk of developing NMOSD, which is also most common in females.

Some people with NMOSD have antibodies against myelin oligodendrocyte glycoprotein (MOG), another protein involved in protecting nerves. People with MOG antibodies tend to have less severe attacks and better recovery compared to those with AQP4 antibodies. Their optic neuritis is more likely to cause swelling at the optic nerve head and affect the front part of the optic nerve, and their transverse myelitis tends to affect the lower spinal cord. These differences suggest that NMOSD may involve multiple immune system pathways rather than a single cause.

Risk Factors for Neuromyelitis Optica

Researchers have identified several factors that may raise the risk of neuromyelitis optica spectrum disorder. Some, such as genetics and medical history, are beyond your control. However, you may be able to reduce your risk by addressing certain environmental factors.

Sex, Race, and Ethnicity

According to Cleveland Clinic, 80 percent to 90 percent of NMOSD cases occur in females. Study findings show that females are also more likely to have autoantibodies that attack aquaporin proteins, and researchers believe that the sex hormone estrogen may play a role. Males with aquaporin antibodies tend to develop NMOSD when they’re older and are more likely to have spinal cord inflammation.

Although the condition can affect anyone, certain racial and ethnic groups also have a higher risk. NMOSD is most common in Asians and Africans, according to a 2023 study in the journal Autoimmunity Reviews.

Family and Medical History

NMOSD isn’t usually inherited, but some genetic factors may increase susceptibility. Only 3 percent of people with NMOSD have a close relative with the condition. However, up to half of people with NMOSD have a personal or family history of other autoimmune diseases.

For example, studies suggest a genetic link between NMOSD and systemic lupus erythematosus (SLE), an autoimmune disease that causes inflammation in the joints, heart, brain, and skin. Research shows that people with NMOSD and SLE may share certain gene variants.

Other autoimmune diseases linked with neuromyelitis optica include:

• Sjögren’s disease — Damages glands that produce tears and saliva, leading to dry eyes and mouth
• Celiac disease — Triggers an immune response to gluten, a protein found in wheat and other grains
• Sarcoidosis — Causes tiny clumps of inflammatory cells to form in organs throughout the body

Other risk factors related to medical history or the immune system include a personal history of cancer, certain cancer treatments that affect the immune system (such as checkpoint inhibitors), and allergic reactions.

Environmental Risk Factors

Certain environmental factors are more likely to raise your risk of neuromyelitis optica. For example, infections may play a role — studies show that up to a third of new NMOSD episodes follow an infection such as chickenpox or shingles.

In addition, some research suggests that people who smoke have more severe NMOSD symptoms. Nicotine in tobacco may affect the immune system and contribute to autoimmunity.

Gut Bacteria

A few studies point to a possible link between the microbiome (gut bacteria) and NMOSD. Some bacteria have proteins that look very similar to aquaporins, so they may share patterns recognized by antibodies. In one small study, researchers found that compared with others, people with NMOSD have higher levels of certain gut bacteria. However, more studies are needed to confirm an association, such as whether gut bacteria directly contribute to NMOSD or if changes in the microbiome are a result of the disease.

Talk With Others Who Understand

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Do you have any risk factors associated with NMOSD? What other questions do you have about the causes of this disease? Share your experience and questions in the comments below, or start a conversation by posting on your Activities page.