Neuromyelitis optica: Symptoms, causes, diagnosis and treatment

What is neuromyelitis optica (Devic's disease)?

Neuromyelitis optica (NMO) is a rare condition in which the immune system attacks the optic nerves and spinal cord, and sometimes the brain. Approximately 80% of people with NMO test positive for aquaporin-4 (AQP4) antibodies. Symptoms include vision loss, eye pain, limb weakness and fatigue.

In general, NMO affects:

• About 22,000 people in the U.S
• A higher proportion of people with Asian or African (specifically African Caribbean) heritage
• Women more than men (four to 10 times more)
• Middle-aged people more frequently
• A higher proportion of people with a family history or personal history of another autoimmune disorder

Many people with NMO improve with steroid treatment. They often regain some or most of their sight and movement. However, if the condition keeps returning, they can have chronic issues. Each time an NMO attack occurs, additional injury to the optic nerve, spinal cord or brain can occur. This can result in permanent vision loss, trouble walking and/or other long-term problems. 

Early diagnosis and using medications to prevent attacks are key to managing this condition. Lab tests can help confirm most cases of NMO, so doctors can recognize and start treatment as soon as possible.

What is neuromyelitis optica spectrum disorder (NMOSD)?

Neuromyelitis optica spectrum disorder, or NMOSD, is the newer, official name for neuromyelitis optica. NMOSD was chosen because it includes more disorders and diagnoses details than NMO did.

However, many doctors and patients use the two terms interchangeably, so you may still hear it called neuromyelitis optica or NMO.

NMOSD is also now recognized as separate from a related condition called myelin oligodendrocyte glycoprotein antibody-associated disease, or MOGAD. The two can look very similar early on, but doctors classify them differently because they involve different antibodies, follow different courses and respond to different treatments. 

What causes neuromyelitis optica?

Neuromyelitis optica is an autoimmune disease. Normally, your immune system protects you by producing antibodies against bacteria and viruses. In NMO, the immune system mistakenly produces antibodies against your body's own proteins.  

Most people with NMO have antibodies in their blood to the protein aquaporin-4 (AQP4). Doctors can order a blood test that confirms the presence of these antibodies when diagnosing the condition. The immune system attack typically affects the optic nerve and spinal cord the most, causing: 

• Inflammation
• Nerve fiber damage
• Damage to the myelin sheath, the protective layer that surrounds and insulates nerves

When the immune response damages the myelin sheath, it is referred to as demyelination. NMO is a demyelinating disease. Myelin is critical for the normal flow of signals through nerve pathways. Demyelination contributes to many of the symptoms in this condition, such as vision changes and mobility issues.  

Why does the immune system target the proteins?

The specific reason why the immune system targets these proteins remains unclear. It is possible that genetics may factor into the risk for NMO. It is more often seen in people who also have another autoimmune disorder, such as Sjögren’s disease, celiac disease, myasthenia gravis or systemic lupus erythematosus. In some cases, there may be a family history of autoimmune conditions.

What are the symptoms of neuromyelitis optica?

Inflammation and demyelination can cause mild to severe symptoms. These symptoms can also vary from person to person.

Attacks

People with NMO have episodes during which symptoms flare up. The episodes, or attacks, can last from several days to months. People may experience issues impacting their eyes, spinal cord and/or brain. In some cases, these episodes can cause permanent damage.

During an attack, symptoms typically begin within hours to days and can last for a few days to weeks before improving. A relapse can occur after a few weeks, months or even years. Without treatment, people with NMO might have repeated episodes.

Vision symptoms of NMO include: 

• Vision loss
• Eye pain
• Faded appearance of colors

Systemic symptoms (which affect the whole body) of NMO include:

• Early onset of fever, muscle pain and headache
• Weakness, spasms, numbness or paralysis of legs and arms
• Bowel or bladder issues
• Vomiting and hiccups that cannot be controlled
• Fatigue
• Anxiety or depression
• Memory or thinking difficulties (when the brain is affected)
• Breathing difficulties in severe cases

Symptoms are typically caused by specific complications that are commonly seen in NMO, such as:

Optic neuritis

The optic nerve carries light signals from the retina, which is the light-sensitive tissue at the back of the eye. These signals then go to the brain, where they are processed as visual images. 

During an attack, the optic nerve can become inflamed, which is a condition called optic neuritis. This results in pain within the eye, as well as decreased vision. In NMO, one or both eyes can be affected. Symptoms of optic neuritis may include: 

• Eye discomfort – Typically occurs or worsens during eye movement
• Blurred sight – May worsen during physical activity or after a hot shower
• Vision loss – Complete or partial vision loss (one or both eyes in NMO)
• Color vision difficulties – Colors appear dim or hard to distinguish
• Abnormal pupil reaction – Exposure to light does not cause a normal pupil response

Myelitis

Myelitis is when the spinal cord becomes inflamed. This swelling can compress the spinal cord and nearby nerves, blocking nerve signals to the part of the body the nerves supply.

The part of the spinal cord that is damaged determines which body regions are affected. Symptoms are usually felt from the level of injury and extend downward, impacting everything below the site of damage. 

Generally, transverse myelitis occurs when myelin damage is in the upper back nerves. The word “transverse” describes the distribution of symptoms. People with transverse myelitis often feel a tight band around their torso. They may feel weakness and other symptoms in the areas below that region.

Impact on the brain

NMO can affect the brainstem (which connects the brain and spinal cord) and the hypothalamus (a region deep within the brain that regulates automatic functions like sleep, temperature and hormone release). They also control automatic processes like breathing and blood pressure. 

When NMO affects the hypothalamus, it can disrupt other body systems. For example, it can cause symptoms such as severe daytime drowsiness. 

When the condition impacts the brainstem, symptoms can include:

• Experiencing double vision, uncontrolled eye movements or difficulty controlling your eye movements
• Weakness or paralysis on one side of the face
• Facial pain related to nerve issues
• Feeling dizzy or like you’re spinning
• Having trouble with your balance or coordination
• Persistent hiccups
• Severe itching
• Feeling nauseated or vomiting
• Experiencing problems with your hearing

Are there different types of NMO?

There are different types of NMO. This condition is usually categorized into two types, based on the duration and frequency of attacks:

Monophasic form

Approximately 10% of individuals with NMO experience only one episode and never have another. This is the monophasic form. It is less common than was once thought. Earlier estimates included patients who are now recognized as having MOGAD — a separate condition that more often runs a one-time course. True monophasic NMO is now believed to account for a smaller share of cases, most often in people who test negative for AQP4 antibodies. 

Relapsing form

The relapsing form is more common, occurring in 80% to 90% of people with NMO. People with this severe form have relapses after the first attack. These episodes can occur months or years apart with periods of partial recovery. Some people will have chronic issues that continue after each episode. 

How is NMO different from multiple sclerosis?

Neuromyelitis optica and multiple sclerosis (MS) are both autoimmune diseases. They cause inflammation and damage in the central nervous system, affecting the brain, spinal cord and optic nerve. They have important similarities as well as critical differences.

What are the similarities between neuromyelitis optica and multiple sclerosis?

Early on, the symptoms of MS and NMO may look very much alike, which can make it hard for doctors to tell them apart. In fact, neuromyelitis optica was thought to be a subtype of multiple sclerosis in the past. For example:

• Both are characterized by an abnormal immune system response.
• The demyelination that occurs in both conditions is due to inflammation.
• Both affect the central nervous system.
• Both are more common in women.
• Both can cause sudden vision problems (optic neuritis).
• Both may result in inflammation of the spinal cord (myelitis), leading to weakness or numbness.

What are the differences between neuromyelitis optica and multiple sclerosis?

There are many distinctions that help doctors tell MS and NMO apart so they can provide the most appropriate treatment. These include:

• Many patients with neuromyelitis optica test positive for anti-AQP4 antibodies.
• People with NMO don’t usually have changes in memory or thinking.
• Vision issues caused by MS typically only affect one eye. In NMO, both eyes may be affected at the same time.
• NMO usually starts around age 40, while MS often begins near age 30.
• Optic neuritis and myelitis in NMO are generally more severe.
• Magnetic resonance imaging (MRI) scans of the brain are more often normal in NMO, while people with MS usually have visible changes on MRI scans.
• Spinal fluid tests usually show different results between NMO and MS.

READ MORE: How multiple sclerosis impacts eyes and vision

Diagnosis and tests

To find out if you have NMO, your doctor will look at your health history, examine you and run some tests. Your doctor will check for other autoimmune diseases or infections that could cause similar symptoms.

History

The first step is for your doctor to learn about your symptoms and medical history.

This includes any vision changes, weakness in your arms or legs, numbness, and issues with bladder or bowel control. They’ll also want to know if you’ve had other autoimmune conditions in the past.

Physical examination

Next, your doctor will do a physical exam to check how your nervous system is working. During your visit, your doctor might:  

• Check your eyesight.
• Assess your muscle strength.
• Test your sense of touch.
• Evaluate your reflexes.
• Check your coordination.
• Assess other nervous system functions.

Imaging

Imaging studies allow doctors to visualize internal structures and identify any abnormalities.

Magnetic resonance imaging (MRI)

An MRI can provide highly detailed 3D images of soft tissue and organs including your brain, optic nerves and spinal cord. These pictures help doctors see areas of swelling and damage. They also help doctors distinguish NMO from other conditions, such as multiple sclerosis.

Optical coherence tomography

Optical coherence tomography (OCT) provides detailed cross sections and thickness measurements of the nerve layer, optic nerve and retina. OCT can help eye doctors detect damage from optic neuritis.

Antibody testing

Blood tests check for specific antibodies that can help confirm an NMO diagnosis:

Aquaporin-4 antibodies

About 80% of people with NMO have antibodies in their blood to the protein aquaporin-4 (AQP4). The AQP4 protein is found in cells called astrocytes, which support the optic nerve, spinal cord and certain areas of the brain. 

Myelin oligodendrocyte glycoprotein antibodies

If the AQP4-IgG test is negative, doctors may also test for the myelin oligodendrocyte glycoprotein (MOG) antibody. MOG is a protein that helps build and protect the myelin layer surrounding nerve cells. 

A positive MOG antibody result usually points to a different diagnosis called MOG antibody-associated disease, or MOGAD. In 2023, an international panel of experts published a report that recognized MOGAD as a separate condition from NMO, which has its own set of symptoms and signs along with management and treatment approach. 

Testing for both antibodies (AQP4 and MOG) helps doctors to make an accurate diagnosis and choose appropriate treatment options. 

Lumbar puncture

A lumbar puncture, or spinal tap, lets doctors check the fluid around the brain and spinal cord. This helps detect inflammation and rule out other conditions. The results can aid doctors in telling NMO apart from multiple sclerosis.

If your antibody test is positive

When doctors find NMO antibodies in your blood, they will check for these signs and symptoms to determine a diagnosis:

• Swelling of the optic nerve (optic neuritis)
• Spinal cord inflammation (myelitis)
• Nausea/vomiting episodes
• Unexplained persistent hiccups
• Brain abnormalities with MRI-visible lesions characteristic of NMO patterns

If your antibody test is negative

If both the AQP4 and MOG antibodies come back negative, doctors will look for specific signs and imaging clues before diagnosing NMO. This usually requires the presence of optic neuritis or myelitis along with at least one other significant finding on an exam or MRI. If MOG antibodies are positive, doctors will evaluate for MOGAD rather than NMO.

Treatment options

NMO affects many different parts of the body, so treatment needs to address various areas to help manage symptoms. Your doctor will create a treatment plan that's specifically designed for you and your needs. 

The main treatments focus on two goals: 

1. First, they will treat sudden attacks when they happen. Quick treatment during an attack is very important to prevent lasting damage.
2. They will also try to keep your immune system calm. This helps prevent future attacks or makes them less severe and shorter. 

Additional medications may be needed to help manage symptoms caused by nerve damage.

Treatments for sudden attacks

Getting treatments within five days may help you recover better. These treatments may include:

IV corticosteroids

During a sudden NMO attack, doctors may give strong steroids through an IV. Methylprednisolone is often given to help reduce inflammation.

Plasma exchange

Plasma exchange (PLEX) may also be administered to remove antibodies circulating in the blood. 

Preventing future attacks

Long-term treatment involves medications that calm your immune system. This can prevent future attacks and prevent lasting damage. This treatment may include:

Oral medications

Oral medications can take at least four to six months to work fully, so doctors may give oral steroids along with these drugs during the first few months. Oral medications may include:

• Azathioprine
• Mycophenolate
• Methotrexate

Monoclonal antibody therapies 

Monoclonal antibody therapies target specific parts of the immune system. They are particularly useful for people who are AQP4-positive. Therapies approved by the U.S. Food and Drug Administration (FDA) include:

• Inebilizumab – Reduce immune cells called B cells
• Eculizumab, ravulizumab – Block specific proteins
• Satralizumab – Block certain signals from a type of cytokine (interleukin-6)

Two additional therapies might be chosen for NMO patients which are commonly used, but considered off-label:

• Rituximab – Reduces B cells
• Tocilizumab – Blocks interleukin-6 signals

Emerging therapies

Researchers continue to work on developing better treatments for NMO. These new treatments undergo testing through clinical trials. Information on these trials can be found at:

• ClinicalTrials.gov
• National Organization for Rare Disorders (NORD)
• CenterWatch
• EU Clinical Trials Register

Is there a cure for neuromyelitis optica?

Unfortunately, there is currently no cure for neuromyelitis optica. But NMO is treatable. Ongoing research has greatly improved treatment options, making management more effective. 

Living with neuromyelitis optica

Living with NMO involves ongoing management and support to maintain quality of life. For individuals with AQP4 or MOG antibodies, NMO often becomes a chronic condition. Long-term medications will be needed to help prevent future attacks. 

Daily management tips

Following some simple steps can make a big difference. Daily tips to manage your condition include:

• Follow your medication schedule and never discontinue medications without consulting your health care provider first.
• Go to your doctor's appointments. This helps your doctor check your health and adjust your medications if needed.
• Get routine blood work as advised by your doctor so they can track your immune system activity levels.
• Consider physical and occupational therapy. They are important for boosting strength and movement in daily activities.
• Take steps to stay healthy, especially when taking immune-suppressing medications. 

Support resources

Support for emotional health is also crucial, as living with NMO can sometimes lead to depression or anxiety. Your health care team can help connect you with support resources, such as:

• National Institute of Neurological Disorders and Stroke
• The Sumaira Foundation
• The Guthy-Jackson Charitable Foundation

A team of trusted specialists can help you manage your NMOSD, including eye doctors, neuro-ophthalmologists (an ophthalmologist who specializes in diagnosing and treating complex vision problems linked to the brain, nerves and nervous system), neurologists and radiologists. Support from family, friends and other health care providers is also key to staying healthy and managing your symptoms.