Neuromyelitis Optica Spectrum Disorder (NMOSD)

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease that affects the central nervous system. This consists of the optic nerves, brain and spinal cord. It is also known as neuromyelitis optica (NMO) or Devic’s disease. Some of its symptoms are similar to the symptoms of multiple sclerosis, so it may be misdiagnosed as such.

NMOSD is a relapsing disease. This means that new inflammation in the nervous system produces relapses (flare-ups, attacks or exacerbations). The relapses can be weeks, months or years apart. Relapses usually last for days. Also, we know that demyelination and inflammation trigger relapses, but we do not know the root cause of the demyelination and inflammation. Between relapses, people may experience some recovery. It is unclear what triggers relapses, and their timing is unpredictable. 

Relapses, which usually affect the optic nerves or spinal cord, can happen over hours or days. Some people have pain behind their eyes or notice that colors look faint or gray. They may also lose some strength and sensation in the arms, trunk and legs and have bladder or bowel control problems. Attacks require immediate medical attention to prevent worsening and minimize permanent disability.

With effective treatments, the risk of relapses is now lower, but attacks can still be devastating. Doctors recommend early and ongoing treatment to prevent relapses and long-term disability.

NMOSD is an autoimmune disorder, in which the immune system thinks healthy tissues are a threat and attacks them.

While we do not know the root cause of the demyelination and inflammation that occurs in NMOSD, scientists do understand what happens in the body.

In most people with NMOSD, blood tests detect antibodies (anti-AQP4) that attack Aquaporin-4 (AQP4) in the central nervous system. AQP4 is a protein on astrocytes, a type of cell that helps the nerves in the central nervous system work properly.

This attack leads to inflammation and damage to the astrocytes, as well as to the nerve cells and their myelin insulation. This damage disrupts the messages from the brain and spinal cord to the rest of the body, causing weakness, worsened vision or other symptoms.

Changes in vision (optic neuritis) and symptoms caused by spinal cord inflammation (transverse myelitis) are common in NMOSD.

Symptoms caused by optic neuritis include:

• Loss or blurring of vision in one or both eyes
• Loss of color vision
• Eye pain

Symptoms caused by transverse myelitis include:

• Weakness, numbness or loss of sensation
• Loss of muscle function
• Loss of bowel or bladder control or difficulty emptying the bladder
• Spasticity (increased muscle tone or stiffness in the arms or legs)
• Shooting pain or tingling in the neck, back or abdomen

Other symptoms that commonly occur with an NMOSD attack include uncontrollable hiccups, nausea and vomiting.

How quickly does NMOSD progress?

NMOSD progresses at variable rates and, as with MS, it is unpredictable. Each relapse causes new damage, and, over time, relapses can lead to serious disability.

Healthcare providers consider several things when diagnosing NMOSD, including symptoms, medical history and tests results. The diagnosis process may include:

• Medical history to identify any past or present symptoms that might be caused by NMOSD, MS or another disorder
• Neurologic exam of your thinking, vision, hearing, sensations, strength, swallowing, reflexes, coordination, walking and balance
• MRI of your brain, optic nerves and spinal cord
• Spinal tap (lumbar puncture) to examine cerebrospinal fluid
• Eye scans and vision tests
• Blood tests, including anti-AQP4 antibody testing

Some people who test negative for anti-AQP4 may have a related condition called myelin oligodendrocyte glycoprotein antibody disorders (MOGAD).

There are an estimated 4,000 to 8,000 people with NMOSD in the United States and a quarter-million people worldwide.

• NMOSD is more common in women (> 80 percent) than men.
• NMOSD occurs in all parts of the world. It is more common among people of African and Eastern Asian descent than in people who are white. NMOSD may be the most common demyelinating disease within the African and Eastern Asian communities.
• NMOSD can occur at any age — in children as young as 3 and adults as old as 90 — but appears most often between ages 30 and 50.

NMOSD and MS share some symptoms, and in fact experts used to think it was a form of MS. But there are key differences between the two of them:

• NMOSD attacks may affect both eyes at the same time. MS usually affects one at a time.
• NMOSD usually affects only the optic nerve and spinal cord although there may be lesions in specific areas of the brain (such as the brainstem). MS typically affects multiple areas of the brain as well as the spinal cord and optic nerve.
• Cognitive changes are not typically a symptom of NMOSD. Due to the effects on the brain, people with MS experience cognitive changes over time, such as changes in memory, reasoning and problem-solving.
• Disability from NMOSD results from relapses and is rarely progressive. MS can start off as or develop into a progressive disease.
• NMOSD attacks are generally more severe than MS attacks.
• In addition to the procedures doctors use to diagnose MS, they also have a blood test for NMOSD. It looks for the AQP4-IgG antibody, which is present in about 70% of people with NMOSD.

Read about other diseases with symptoms similar to NMOSD and MS.

There is no cure for NMOSD at this time, but there are effective treatments. The standard of care for an attack of NMOSD includes the following:

• Intravenous (into the vein) high-dose corticosteroids (methylprednisolone) to reduce the inflammation of the nervous system.
• Plasma exchange (PLEX) for severe attacks or if no improvement occurs with corticosteroids.
  • The goal of PLEX is to lower the level of anti-AQP4 antibodies in the blood.
  • PLEX involves removing blood from the body through a needle and tubing. Through a series of steps, the plasma (the liquid part of the blood) is separated from blood cells and replaced with an artificial plasma substitute. The plasma substitute and blood cells are combined and then returned to the body intravenously.
  • The procedure lasts several hours and may be repeated multiple times over a number of days.

Because the likelihood of recurrence is very high and attacks are generally severe and often result in permanent disability, ongoing treatment to suppress the immune system is necessary. The U.S. Food and Drug Administration (FDA) has approved 3 drugs specifically for treatment of anti-AQP4 positive NMOSD:

• Eculizumab (Soliris®)
  • View the medication guide.
• Inebilizumab-cdon (Uplizna®)
  • View the medication guide.
• Satralizumab-mwge (Enspryng®)
  • View the medication guide.

Other drugs that are used off-label to prevent attacks include:

• Azathioprine (Azasan® and Imuran®)
  • View the Azasan medication guide.
  • View the Imuran medication guide.
• Mycophenolate mofetil (Cellcept®)
  • View the medication guide.
• Prednisone
• Rituximab (Rituxan®) and biosimilars
  • View the medication guide.

The resources below offer information and support for people living with NMOSD and their families.

• The Siegel Rare Neuroimmune Association (SRNA) is a nonprofit organization dedicated to the support of people with Acute Disseminated Encephalomyelitis (ADEM), MOGAD, NMOSD, optic neuritis and transverse myelitis. They support individuals living with these diseases and their families, maintain a clinical care network and fund research.
• The Sumaira Foundation is dedicated to generating global awareness of NMOSD and MOGAD, supporting research to find cures and creating a community of support for those affected by these diseases.
• The Guthy-Jackson Charitable Foundation funds research to accelerate solutions for NMOSD, spreads awareness and runs support groups for those living with NMOSD and their loved ones.
• Ask an MS Navigator — While the organizations above are the best resources for information and research on NMOSD, our MS Navigator team can provide help in understanding health insurance, resources for facing financial challenges and assessments for personalized case management.

Reviewed by Shuvro Roy, MD, and Elias Sotirchos, MD, August 2022.