Neuromyelitis optica spectrum disorder (NMOSD), also known as neuromyelitis optica (NMO) or Devic disease, is a rare autoimmune disease that causes inflammation and damage in the central nervous system, mainly affecting the optic nerves and spinal cord. The most common symptoms include sudden vision loss or eye pain, limb weakness or paralysis, numbness, sensory changes, bladder and bowel dysfunction, and, in some cases, persistent hiccups, nausea, or vomiting. Some people may also experience muscle spasms, difficulty walking, vertigo, or confusion. Children with NMOSD may experience seizures.

In the United States, NMOSD is estimated to affect approximately 0.4 to 10 people per 100,000, with higher rates among Black Americans (about 13 per 100,000) compared to White Americans (about 4 per 100,000). The condition is much more common in women than men, especially among those who test positive for aquaporin-4 antibodies, and the median age of onset is around 40 years, though it can occur at any age. NMOSD can affect people of all racial and ethnic backgrounds and may begin in childhood, adulthood, or later in life.

NMOSD can affect individuals in diverse ways, and people can have a variety of outcomes. Although NMOSD can cause serious symptoms and disability, effective treatments are available that can reduce the frequency of episodes of eye pain and vision problems, manage symptoms, and help many people maintain their quality of life.

In a healthy person, the optic nerves carry visual information from the eyes to the brain, and the spinal cord transmits signals between the brain and the rest of the body, allowing for movement, sensation, and control of bladder and bowel function.

In NMOSD, the immune system mistakenly attacks important proteins in the optic nerves, spinal cord, and sometimes the brain, resulting in inflammation that can damage the protective covering of nerve fibers (myelin) and the nerve fibers themselves. People with NMOSD may experience sudden attacks of symptoms, which can vary depending on which nerves are affected. Inflammation of the optic nerve, known as optic neuritis, can cause vision loss or eye pain. Inflammation of the spinal cord, known as transverse myelitis, can lead to weakness or paralysis in the arms or legs, sensory changes (such as numbness or tingling), and problems with bladder or bowel control. Symptoms related to brain involvement, such as persistent hiccups, nausea, and vomiting, among other symptoms may also occur. Attacks affecting the optic nerve, spinal cord, and brain can occur separately or together, and the severity can range from mild to disabling. Most people with NMOSD experience repeated attacks separated by periods of remission. Each attack can cause lasting damage.

Over time, repeated attacks can lead to permanent vision loss, difficulty walking, or other long-term disabilities if not managed appropriately.

In NMOSD, the immune system attacks proteins in the central nervous system. The protein that is attacked most often is called aquaporin-4. It is found on support cells called astrocytes in the optic nerves, spinal cord, and certain areas of the brain. This immune attack leads to inflammation, loss of the protective myelin covering on nerves, and damage to nerve fibers.

Most people with NMOSD have antibodies (proteins made by the immune system that detect specific substances) in their blood called aquaporin-4 immunoglobulin G (AQP4-IgG), which specifically target the aquaporin-4 protein. In some individuals with NMOSD, especially those who do not have AQP4-IgG, the immune system may instead produce antibodies against another protein called myelin oligodendrocyte glycoprotein (MOG).

The underlying reason why the immune system begins to attack these proteins is unknown, though some theories have been proposed. Genetic factors may play a role, as certain genetic variants have been linked to a higher risk of NMOSD. The condition is also more common in people who have other autoimmune diseases, such as systemic lupus erythematosus or Sjögren’s syndrome. In some cases, NMOSD attacks have occurred after infections or, rarely, after vaccination, but no specific infection or environmental trigger has been proven to cause the disease.

Risk factors for NMOSD include:

• Female sex, especially for those who are aquaporin-4 antibody positive
• Black, Asian, or Afro-Caribbean ancestry
• Age between 30 and 50 years at onset
• Presence of other autoimmune diseases, such as systemic lupus erythematosus or Sjögren’s syndrome
• Family history of NMOSD or other autoimmune conditions
• Certain genetic variants
• Previous infections or, rarely, recent vaccination

Symptoms of NMOSD may include:

• Sudden vision loss or eye pain, which may affect one or both eyes
• Limb weakness or paralysis
• Numbness or sensory changes in the arms, legs, or trunk
• Bladder or bowel dysfunction, such as urinary retention, incontinence, or difficulty controlling urination or bowel movements
• Persistent or intractable hiccups
• Nausea and vomiting
• Painful muscle spasms
• Sexual dysfunction
• Cognitive changes, such as confusion or sleepiness
• Seizures (more common in children)
• Episodes of excessive daytime sleepiness or narcolepsy
• Depression or anxiety
• In rare cases, difficulty breathing (which can be life-threatening)

To diagnose NMOSD, your doctor will review your medical history, conduct a physical exam, and order one or more diagnostic tests.

Your doctor may ask you about your symptoms, such as vision loss, limb weakness, numbness, bladder or bowel problems, and any history of other autoimmune diseases. During the physical exam, your doctor checks your vision, muscle strength, sensation, reflexes, coordination, and other neurological functions.

Additional tests are necessary to make a diagnosis, including:

• Magnetic resonance imaging (MRI) of the brain, optic nerves, and spinal cord: This imaging test helps identify areas of inflammation or damage, such as lesions in the optic nerves or spinal cord, and can help distinguish NMOSD from other conditions like multiple sclerosis.
• Blood tests for AQP4-IgG antibodies: This test detects antibodies that are highly specific for NMOSD and helps confirm the diagnosis.
• Blood tests for MOG antibodies: This test may be used if AQP4-IgG is not detected, as some people with NMOSD have MOG antibodies instead.
• Lumbar puncture (spinal tap): This test analyzes cerebrospinal fluid for signs of inflammation and helps rule out other conditions. In NMOSD, certain findings can help distinguish it from multiple sclerosis.
• Optical coherence tomography: This eye test measures the thickness of the retinal nerve fiber layer and can show damage from optic neuritis.
• Additional blood tests: Your doctor may order tests to check for other autoimmune diseases or infections that can cause similar symptoms.
  

There is no cure for NMOSD, but effective treatments are available to manage symptoms, stop attacks, and reduce the risk of future relapses. Treatment usually involves managing attacks and the use of long-term therapies to prevent new episodes.

There are two goals to treating NMOSD. Acute treatments are used to help people recover from attacks as quickly as possible. Separately, long-term treatments are necessary to prevent future episodes and protect the tissue in the central nervous system from additional injury. There are several monoclonal antibody treatments approved by the U.S. Food and Drug Administration (FDA) to treat cases of NMOSD that are associated with AQP4-IgG.

Acute treatments include:

• High-dose intravenous corticosteroids: Used to treat attacks by reducing inflammation in the central nervous system, often with methylprednisolone given for several days.
• Plasma exchange (plasmapheresis): This procedure removes harmful antibodies from the blood and is used during severe attacks or when symptoms do not improve with corticosteroids.

Long-term treatments include:

• Oral medications: These include azathioprine, mycophenolate mofetil, and methotrexate; any of these may be used to suppress the immune system and reduce the risk of relapses.
• Monoclonal antibody therapies: These include medications that target specific parts of the immune system, such as those that block complement proteins (eculizumab, ravulizumab), deplete B cells (rituximab, inebilizumab), or block interleukin-6 signaling (satralizumab, tocilizumab). These treatments are especially effective for people who test positive for aquaporin-4 antibodies.

In addition to treatments targeting the immune system, people who have NMOSD may need additional symptomatic therapies. These treatments do not change the underlying disease, but help minimize symptoms caused by nerve damage that took place in the past.

• Medical symptom management: Additional medications and therapies may be used to relieve muscle spasms, pain, bladder or bowel problems, and other symptoms that result from nerve damage.
• Physical and occupational therapy: Rehabilitation can help improve strength, mobility, and daily functioning for people who have lasting symptoms after attacks.

Early and ongoing treatment is important to reduce the risk of permanent disability and maintain or improve quality of life for people with NMOSD.

People with NMOSD may be at increased risk for certain complications, including:

• Permanent vision loss or blindness, often due to repeated or severe attacks of optic neuritis
• Weakness or paralysis in the arms or legs, which can be long-lasting or permanent after spinal cord involvement
• Loss of sensation or abnormal sensations, such as numbness, tingling, or pain
• Bladder and bowel dysfunction, including incontinence or difficulty controlling urination or bowel movements
• Muscle spasms and stiffness, which can interfere with movement and daily activities
• Difficulty walking or the need for assistance with mobility
• Fatigue, which can be persistent
• Sexual dysfunction, due to nerve damage
• Cognitive changes, such as problems with memory or thinking, especially if the brain is affected
• Depression or anxiety, which may result from living with a chronic and disabling condition
• Neurogenic respiratory failure, which can be life-threatening if spinal cord inflammation affects the nerves that control breathing
• Increased risk of infections, especially for those receiving long-term immunosuppressive therapy
• Death may occur in severe cases, often due to respiratory failure or complications from immobility

The outlook for people with NMOSD can vary widely depending on several factors, including the frequency and severity of attacks, how quickly treatment is started, and whether there is lasting nerve damage after each episode. Some people may experience only a few attacks with mild symptoms, while others may have frequent or severe relapses that lead to significant disability, such as vision loss or difficulty walking.

With early diagnosis and ongoing treatment, people with NMOSD may be able to reduce the number of attacks, limit permanent damage, and maintain their quality of life. Regular follow-up with a health care provider can help manage symptoms and prevent complications.

“Yale Medicine’s Interventional Immunology Center is a site of comprehensive care for people with all kinds of neuroimmune diseases, including NMOSD,” says Yale Medicine neurologist Erin Longbrake, MD, PhD. “To make a diagnosis, most people need medical testing, including MRIs, lumbar punctures, blood testing, and optical coherence tomography can be done on-site. We offer a team-based approach, incorporating physicians, nurse practitioners, nurses, social workers, nutritionists, and pharmacists. We specialize in early diagnosis and early use of cutting-edge, highly efficient medications to bring NMOSD into remission.”