Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)

Myelin oligodendrocyte glycoprotein antibody-associated disease, also known as MOGAD, is a rare inflammatory disease that affects the central nervous system. In MOGAD, the immune system attacks the fatty substance that protects nerve fibers in the optic nerves, brain and spinal cord.

Symptoms of MOGAD may include vision loss, muscle weakness, stiffness or paralysis, confusion, seizures, and headaches. These symptoms can be sometimes confused with other diseases such as multiple sclerosis.

There's no cure for MOGAD. However, there are treatments to help speed the recovery from attacks, manage symptoms and reduce the likelihood of symptoms returning.

MOGAD causes painful swelling, known as inflammation. Symptoms are caused by attacks from:

• Inflammation of the optic nerve. Called optic neuritis, this condition may lead to vision loss in one or both eyes and eye pain that gets worse with eye movement. Optic neuritis in children may be mistaken for a headache.
• Inflammation of the spinal cord. Called transverse myelitis, this condition may lead to arm or leg weakness, muscle stiffness, or paralysis. It also may cause sensory loss and changes in bowel, bladder or sexual function.
• Inflammation of the brain and spinal cord. Called acute disseminated encephalomyelitis, also known as ADEM, this condition may lead to vision loss, weakness, unsteady walk and confusion. ADEM is more common in children with MOGAD.

Other symptoms of MOGAD may include:

• Seizures.
• Headaches.
• Fever.

Disease course

Some people who have MOGAD only experience one attack of symptoms. This is called monophasic MOGAD and is slightly more common. However, some people experience multiple attacks, called relapsing MOGAD. Attacks usually develop over days and can be severe and debilitating. Disability usually gets worse with each attack. Attack recovery can take weeks to months.

When to see a doctor

See a doctor or other healthcare professional if you experience any of the above symptoms for unknown reasons.

The cause of MOGAD is not known. It's an autoimmune disorder in which the body's immune system attacks its own tissues. In people with MOGAD, the immune system destroys the fatty substance called myelin. Myelin coats and protects nerve fibers in the optic nerve, brain and spinal cord.

The brain sends messages down nerve fibers that help tell parts of the body what to do. When the myelin is damaged and nerve fibers are exposed, those messages may be slowed or blocked. This means those parts of the body won't work properly.

MOGAD is often misdiagnosed as another disease that attacks myelin and causes similar symptoms. It may be mistaken for multiple sclerosis, known as MS. Or it may be confused with a condition called neuromyelitis optica spectrum disorder, also known as NMOSD.

MOGAD is different from MS and NMOSD because the first attack of MOGAD is usually the most severe, but people with the disease can have a complete recovery. MOGAD also is diagnosed differently, using results from MRI and blood tests. People with MS and NMOSD typically have multiple attacks, while about half of people with MOGAD have only one attack.

These factors may increase your risk of developing MOGAD:

• Age. Children and young adults are slightly more likely to develop MOGAD.
• Recent infection or vaccination. MOGAD may develop after an infectious illness or vaccination, such as SARS-CoV-2.

MOGAD complications are caused by the attacks on the fatty substance that protects nerve fibers in the optic nerves, brain and spinal cord. The first attack is usually the worst, but each attack can cause more damage. Some possible complications may include:

• Permanent paralysis in the arms and legs.
• Long-term bowel and bladder difficulties.
• Blindness in one or both eyes.
• Trouble with language, memory and thinking.

Some MOGAD treatments also may cause complications. Long-term use of certain medicines may result in:

• Infection.
• Lymphoma or skin cancers.
• Slowed growth in children.
• Headaches.
• Kidney failure.

Your healthcare team will work with you to decide which treatment options are the best and how long to continue them.

A healthcare professional reviews any symptoms you're having and may do a physical exam to look for any signs of MOGAD.

MOGAD is usually diagnosed after two things have been confirmed. Healthcare professionals confirm that symptoms were caused by a typical attack type, such as optic neuritis, transverse myelitis or acute disseminated encephalomyelitis (ADEM). MOGAD also is diagnosed after the MOG-antibody is found in the blood or spinal fluid.

These two things can be confirmed by a few procedures, including:

• MOG antibody testing with a cell-based assay. This test looks at cells with MOG on their surface to see if the MOG-antibody is present in the blood. This test is considered the gold standard for testing for MOGAD, but there is potential for false positives. Caution is needed if the symptoms aren't typical or are similar to those of another disease, such as multiple sclerosis.
• Spinal tap. Also called a lumbar puncture, this procedure collects a small sample of cerebrospinal fluid for testing. This sample can show if there is an elevated white blood cell count. This causes inflammation and is common in MOGAD. A spinal tap also can look for a type of protein in the spinal fluid called oligoclonal bands. These bands are more common in multiple sclerosis and may help make a distinction between the two diseases.
• Imaging tests. You may need an MRI of the brain, spine and optic nerve. These images can show irregular spots on the brain and spinal cord, called lesions, and inflammation of the optic nerve.
• Eye exam. An eye exam, called an optical coherence tomography, can help diagnose MOGAD. This test shows the layers of the part of the eye called the retina. During episodes of optic neuritis, the retina is often thicker than usual. After these episodes, damage to the nerve cells in the retina causes the retina to get thinner.

The MOG antibody test isn't always accurate. Sometimes healthy people or people with other diseases can have MOG antibodies at lower levels. Your healthcare team uses your test results to make sure there isn't something else causing your symptoms.

There is no cure for MOGAD. Treatment typically focuses on speeding recovery from attacks, managing symptoms and reducing relapses. You meet with your healthcare team to come up with a treatment plan that fits your needs.

Treatments for attacks

Attacks for MOGAD are usually severe and should be treated right away for the most complete recovery. Treatment options may include:

• Corticosteroids. Corticosteroids are medicines used to reduce nerve inflammation and quickly reverse MOGAD symptoms. They are given at high doses and may be taken by mouth or given through an IV. Side effects may include trouble sleeping, increased blood pressure and blood glucose levels, mood swings, and fluid retention.
• Plasma exchange. This procedure involves removing the liquid portion of your blood, called plasma, and separating it from your blood cells. This process removes the MOG antibodies from your blood. The blood cells are then mixed with a protein solution and put back into your body. Plasma exchange may be used if your symptoms are new, severe or haven't responded to the corticosteroids.
• IV immune globulin. Also known as IVIG, this treatment uses antibodies from plasma of a donor to treat MOGAD. IVIG helps neutralize the MOG antibodies and reduce inflammation. IVIG also can suppress the immune system to prevent future attacks. It is more commonly used in children.

Treatments for symptoms

Treating symptoms of MOGAD can help reduce pain and side effects after attacks. Treatment options may include:

• Antiseizure medicines. Seizures may happen in some people with MOGAD. Antiseizure medicines help reduce the number of seizures and can stop them from coming back.
• Therapies. MOGAD attacks can lead to muscle weakness, stiffness and paralysis. Physical therapy and occupational therapy can be used to help rehabilitate the body parts that were damaged during attacks.
• Other medicines. Additional medicines may be used to help with symptoms of MOGAD. Pain, fatigue, bowel and bladder symptoms, and erectile dysfunction can be treated with medicines.

Treatments to prevent attacks

Since MOGAD is a recently discovered disease, there are no proven treatments to prevent attacks. However, clinical trials are underway to find treatments.

Treatment to prevent attacks of MOGAD is typically only used if you experience multiple attacks, known as relapsing MOGAD. Attacks can be prevented by suppressing the immune system. However, this type of treatment can lead to other illnesses and is only used if necessary. Attack-prevention treatments are usually started after the second attack to try to prevent more from happening. But it may be used if your first attack was so severe that it caused permanent damage.

Treatment options may include:

• Oral immunosuppressants. Medicines such as azathioprine, mycophenolate mofetil and prednisone can be taken orally. These medicines suppress the immune system so it stops attacking the myelin and causing damage. However, they can take up to a few months to work, so a relapse still may happen. Oral immunosuppressants can have negative effects on the body. They may include infection, rash and risk of cancer if used long term.
• IV medicines. IV immune globulin can be used to prevent attacks because it suppresses the immune system. Other medicines such as rituximab and tocilizumab also may be given through an IV to help suppress the immune system. Side effects may include headaches and increased risk of infection.

The type of prevention treatment you have affects how long you need the treatment. Some treatments may have negative effects if used long term. Your healthcare team can help decide what the best treatment is for you.

Living with any illness can be difficult. To manage the stress of living with MOGAD, consider these suggestions:

• Maintain normal daily activities as best you can.
• Stay connected to friends and family.
• Continue to pursue hobbies that you enjoy and are able to do.
• Contact a support group, for yourself or for family members.
• Discuss your feelings and concerns about living with MOGAD with your healthcare team or a counselor.

You may be referred to a doctor who specializes in disorders of the brain and nervous system, called a neurologist.

What you can do

• Write down your symptoms, including any that may not seem related to the reason for your appointment.
• Make a list of all your medicines, vitamins and supplements.
• Bring any clinical notes, scans, lab test results or other information from your other healthcare professionals to your neurologist.
• Write down your key medical information, including other conditions.
• Write down key personal information, including any recent changes or stressors in your life.
• Write down questions to ask your healthcare team.
• Take a family member or friend along. Sometimes it can be difficult to remember all the information provided during an appointment. Someone who accompanies you may remember something that you missed or forgot.

Your time with your healthcare team is limited, so preparing a list of questions can help you make the most of your time together. List your questions from most important to least important in case time runs out. For MOGAD, some basic questions to ask include:

• What's the most likely cause of my symptoms?
• What kinds of tests do I need? Do they require any special preparation?
• Is my condition likely temporary or ongoing?
• Will my condition progress?
• What treatments are available?
• I have these other health conditions. How can I best manage them together?

Don't hesitate to ask other questions during your appointment.

What to expect from your doctor

Be prepared to answer questions, such as:

• When did your symptoms begin?
• Have your symptoms been continuous or occasional?
• How severe are your symptoms?
• What, if anything, seems to improve your symptoms?
• What, if anything, appears to worsen your symptoms?