Neuromyelitis Optica Spectrum Disorder

Neuromyelitis optica spectrum disorder is a rare autoimmune condition that attacks the nervous system, primarily affecting the eyes and spinal cord, and can lead to severe disability including blindness and paralysis if left untreated.

NMO, NMOSD, Devic disease, Devic’s disease, neuromyelitis optica

Table of contents

• What is neuromyelitis optica spectrum disorder?
• Who gets NMOSD?
• What causes NMOSD?
• Symptoms of NMOSD
• How is NMOSD diagnosed?
• Treatment for attacks
• Long-term prevention treatment
• Outlook and prognosis
• Living with NMOSD

What is neuromyelitis optica spectrum disorder?

Neuromyelitis optica spectrum disorder, commonly called NMOSD or NMO, is a rare and serious condition that affects the central nervous system (the brain, spinal cord, and optic nerves that connect the eyes to the brain). This condition was first described in 1894 by Dr. Eugene Devic, which is why it’s sometimes called Devic disease or Devic’s disease^[3].

• Optic nerves
• Spinal cord
• Brainstem
• Brain

NMOSD is an autoimmune disease, meaning the body’s immune system mistakenly attacks its own healthy cells and tissues. In this condition, the immune system produces harmful proteins called antibodies that attack a protein called aquaporin-4, which is found on cells in the nervous system^[2]. This attack causes inflammation and damage, particularly to the protective coating around nerve fibers called myelin, which is why NMOSD is described as a demyelinating disease^[2].

For many years, doctors thought NMO was a rare type of multiple sclerosis (MS), but researchers now know it is a completely separate condition^[2][3]. This distinction is important because the two conditions require different treatments, and some MS treatments can actually make NMOSD symptoms worse^[4].

Who gets NMOSD?

NMOSD is a rare condition. Approximately 15,000 to 22,000 people in the United States have NMOSD, with worldwide estimates ranging from 24,000 to 350,600 cases^[2][21]. The number of diagnosed cases is increasing as doctors become better at recognizing and diagnosing the condition^[5].

NMOSD affects women much more frequently than men. Women make up about 80% to 90% of all cases^[2]. The condition typically appears in middle age, with the average age of onset around 40 years old, though it can occur at any age^[2][4]. Cases in children are very uncommon, making up only about 5% of all diagnoses^[2].

While people of all racial and ethnic backgrounds can develop NMOSD, it does not affect all populations equally. The condition is two to three times more common in people of Asian and African descent, particularly those of African Caribbean heritage^[2][4]. The Caribbean island of Martinique has the highest number of cases relative to its population, with about 10 cases per 100,000 people^[2].

Most people with NMOSD do not have a family history of the condition. Only about 3 in every 100 people with NMOSD have a relative with the disease^[6][13]. However, about half of patients have a personal or family history of another autoimmune disorder^[5].

What causes NMOSD?

The exact cause of NMOSD is not fully understood. The condition is classified as an autoimmune disorder, which means it occurs when the body’s immune system attacks its own tissues^[1][2]. Sometimes NMOSD appears after an infection, such as the flu, or it can be linked with another autoimmune condition^[1][6].

Scientists do understand what happens in the body when NMOSD develops. The immune system produces an antibody called AQP4-IgG (aquaporin-4 immunoglobulin G) that attacks a specific protein called aquaporin-4^[5][8]. This protein is found abundantly on special cells called astrocytes, which support and protect nerve cells in the brain and spinal cord. Aquaporin-4 helps carry water across cell membranes^[5].

When the AQP4-IgG antibody binds to aquaporin-4, it triggers a damaging inflammatory response. This process, called astrocytopathy, leads to injury and loss of astrocytes, damage to the protective myelin coating around nerves, activation of immune cells, and ultimately injury to nerve cells themselves^[12]. About 80% of people with NMOSD test positive for AQP4 antibodies in their blood, which confirms the diagnosis^[4].

Symptoms of NMOSD

The symptoms of NMOSD vary from person to person and can range from mild to severe. Symptoms typically start over a period of hours or days, last for days or weeks, and then gradually improve^[6]. However, recovery can be incomplete, and symptoms often return in episodes called relapses or attacks^[1].

For about 90% of patients, NMOSD follows a relapsing-remitting pattern, meaning they experience attacks followed by periods of recovery that can last weeks, months, or years^[5]. Each attack can cause new damage and lead to increasing disability over time^[5][7].

The symptoms depend on which parts of the nervous system are affected. NMOSD most frequently affects the optic nerves and spinal cord, but can also affect the brainstem and brain^[1][2].

Vision problems occur when the optic nerves are inflamed, a condition called optic neuritis. These symptoms may include^[1][6]:

• Blurred vision or loss of vision in one or both eyes
• Eye pain
• Difficulty seeing colors
• Problems seeing in dark or bright light

Spinal cord problems occur when inflammation affects the spinal cord, called transverse myelitis. These symptoms may include^[1][6]:

• Weakness, numbness, or paralysis in the legs and sometimes the arms
• Stiffness in the legs or arms
• Loss of feeling or sensation throughout the body
• Painful muscle spasms
• Inability to empty the bladder completely
• Bladder or bowel dysfunction, including incontinence or constipation
• Sexual problems, such as difficulty getting an erection or reaching orgasm

Brainstem symptoms can include^[1][6]:

• Persistent nausea and vomiting
• Persistent or uncontrollable hiccups
• Sleep problems

Other common symptoms reported by people with NMOSD include^[15]:

• Fatigue (extreme tiredness)
• Sharp, burning, or shooting nerve pain
• Difficulty walking

If you experience a sudden onset of these symptoms, you should see a doctor immediately, as this could signal an acute attack that requires urgent medical attention^[1][6].

How is NMOSD diagnosed?

Diagnosing NMOSD can be challenging because the symptoms are similar to other conditions, particularly multiple sclerosis. Many people spend weeks, months, or even years going from doctor to doctor before receiving the correct diagnosis^[4].

If your doctor thinks you might have NMOSD, they will refer you to a specialist called a neurologist, who specializes in conditions affecting the nervous system^[6]. The diagnosis process involves several steps.

The doctor will start with a physical and neurological exam to check your movement, muscle strength, coordination, sensation, memory, thinking, vision, and speech. An eye doctor may also be involved^[8].

The most important diagnostic test is a blood test to look for AQP4-IgG antibodies. The presence of these antibodies in your blood confirms you have NMOSD and not MS^[4][8]. It’s essential to request this specific blood test, as it aids in accurate diagnosis and helps determine treatment options^[4]. Another antibody test called MOG-IgG may also be performed to check for a different inflammatory disorder that can look like NMOSD^[8].

MRI scans (magnetic resonance imaging) create detailed pictures of the brain, optic nerves, and spinal cord. These images can show areas of inflammation or damage called lesions^[8].

A lumbar puncture, also called a spinal tap, involves inserting a needle into the lower back to remove a small sample of spinal fluid for testing^[8].

Additional tests may include eye examinations and vision tests to check for optic nerve damage^[8].

Early and accurate diagnosis is extremely important. Without proper treatment, NMOSD can cause severe, permanent disability. Within one year without treatment, 60% of people with NMOSD will have repeat attacks^[4]. After five years, four out of 10 people with NMOSD may be legally blind in at least one eye, and two out of 10 may require a walker^[4].

Treatment for attacks

The treatment of NMOSD has two main goals: treating acute attacks when they happen and preventing future attacks from occurring^[7][9]. Prompt treatment of an acute attack is important to prevent permanent disability^[9].

When symptoms first start or during a relapse, the main treatments include^[6][9]:

High-dose steroid injections, usually given intravenously (through a vein), help reduce inflammation quickly and are typically the first treatment used^[9].

Plasma exchange, also called plasmapheresis, is a procedure where some of your blood is removed, treated to remove harmful antibodies, and then returned to your body. This treatment may be used if steroids alone are not effective^[6][9].

Immunoglobulins, which are antibodies collected from donated blood, may be given through a drip into a vein to help regulate the immune system^[6].

Long-term prevention treatment

Because NMOSD is a relapsing condition with a high risk of repeat attacks, most people need to take medicines long-term to prevent future relapses. The goal is to reduce or eliminate attacks and prevent the accumulation of permanent disability^[7][11].

Preventive treatments work by reducing the activity of the immune system. Several types of medicines are used^[6][7]:

Immunosuppressants are medicines that suppress the immune system. Common ones include azathioprine (Imuran) and mycophenolate mofetil (CellCept)^[6][11].

Steroid tablets, such as prednisolone, may be used at lower doses for long-term prevention^[6].

Biological medicines, also called targeted therapies, are newer treatments. Rituximab (Rituxan) has been used off-label for years and works by targeting specific immune cells^[11].

Four preventive treatments have been specifically approved for AQP4-IgG-positive NMOSD in many countries^[7]:

• Eculizumab
• Ravulizumab
• Inebilizumab
• Satralizumab

Studies have shown that more AQP4-positive adult patients were relapse-free with these approved treatments compared to placebo at 96 weeks^[18].

All immunosuppressive medicines carry some risks, particularly an increased risk of infections such as upper respiratory infections and urinary tract infections. Good hand washing and hygiene are important when taking these medications^[11]. Your doctor will discuss the potential benefits and risks of each treatment option with you.

You may also be offered medicines to help manage ongoing symptoms^[6]:

• Painkillers for general pain
• Antidepressant or anticonvulsant medicines (such as amitriptyline or gabapentin) for nerve pain
• Muscle relaxant medicines (such as baclofen or carbamazepine) for muscle spasms
• Medicines for bladder problems (such as oxybutynin)
• Laxatives for bowel problems

Physical therapy, occupational therapy, and other rehabilitation services can help with muscle weakness, mobility problems, and performing daily activities^[6][15].

Outlook and prognosis

Without treatment, NMOSD can lead to serious disability over time. The likelihood of disease activity recurring is greater than 90%^[11]. Before effective preventive treatments became available, about 50% of people diagnosed with NMOSD were dependent on a wheelchair and/or functionally blind within five years^[11].

However, with early diagnosis and proper treatment, the outlook has improved significantly. Preventive medications can reduce the risk of relapses and help prevent the accumulation of permanent disability^[7][11].

Recovery from individual attacks varies. Some people recover well with treatment, while others have longer-lasting problems. Among those who experience optic neuritis affecting vision, 67% had only partial recovery or no recovery following an NMOSD attack^[4].

Each relapse can cause new damage, and over time, relapses can lead to permanent problems such as vision loss or difficulty walking^[5][6]. This is why starting preventive treatment as soon as possible after diagnosis is so important.

Living with NMOSD

Living with NMOSD presents many challenges, but there are strategies and resources that can help you manage the condition and maintain the best possible quality of life.

Understanding your condition is an important first step. Learning about NMOSD and how it affects your body can help you better understand your treatment and make informed decisions about your care^[20]. Don’t be afraid to ask your doctor questions.

Managing vision problems may require various adaptations. If you experience vision loss, consider using contrasting colors in your home decor and on electronic devices, purchasing items with large text displays, staying organized by keeping things in consistent locations, and asking for help when needed^[13][14]. Low vision rehabilitation specialists and occupational therapists can teach you skills to make the best use of your remaining vision^[15].

Addressing mobility challenges may involve physical therapy to strengthen muscles and improve movement, using assistive devices such as canes, walkers, or braces to help with balance, and making home modifications like installing railings or ramps for safety^[13][15].

Regular exercise can help boost energy, strengthen muscles, improve bladder and bowel function, reduce fatigue and depression, and promote better sleep. Always check with your doctor before starting an exercise program^[15].

Managing fatigue is important, as extreme tiredness is a common symptom. Listen to your body and rest when needed. Plan activities for times when you typically have more energy^[15].

Mental health support is crucial. Surveys show that 92% of patients with NMOSD report that the disease has impacted their mental health and well-being^[13]. It’s normal to experience feelings of sadness, frustration, and loss. Your healthcare provider can connect you with mental health professionals who can help^[13].

Talking with family and friends about your condition can help them understand what you’re experiencing and how they can support you. You don’t have to tell them everything at once—share what feels comfortable. Start with basic facts about NMOSD, give examples of how it affects you, and be clear about what kind of support you need^[13].

Building a support network is valuable for managing the emotional challenges of living with a rare disease. Consider joining support groups, connecting with advocacy organizations, participating in social media groups for people with NMOSD, and attending educational events^[13][17]. Connecting with others who understand what you’re going through can help you feel less isolated.

Financial considerations are important, as NMOSD can lead to significant medical expenses. Look into financial assistance programs offered by pharmaceutical companies, nonprofit organizations, and patient advocacy groups^[17].

Planning for the future includes considering issues like family planning. If you’re thinking about having a baby, talk with your doctor to develop a care plan. NMOSD is not usually inherited, and with proper planning and medical support, many women with NMOSD can have children^[13].

Many people with NMOSD find that focusing on what they can control, celebrating small victories, and maintaining hope for the future helps them cope with the uncertainties of the condition^[16][21]. With proper treatment and support, it’s possible to continue doing the things that matter most to you.