Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare inflammatory condition where the immune system mistakenly attacks the protective covering of nerves in the brain, spinal cord, and eyes, causing symptoms that can range from vision loss to paralysis.

Table of contents

• What is MOGAD?
• How common is MOGAD?
• Symptoms and clinical patterns
• What causes MOGAD?
• How is MOGAD diagnosed?
• Treatment options
• Disease course and outlook
• Possible complications

What is MOGAD?

Myelin oligodendrocyte glycoprotein antibody-associated disease, known as MOGAD, is a rare inflammatory disease that affects the central nervous system (the brain, spinal cord, and eyes)^[1]. In MOGAD, the immune system produces antibodies that attack a protein called myelin oligodendrocyte glycoprotein, or MOG^[2].

MOG is a protein found on the outer surface of myelin, which is the fatty protective covering that surrounds nerve fibers in the brain, spinal cord, and optic nerves^[5]. Myelin acts like insulation around electrical wires, allowing nerve signals to travel quickly and efficiently throughout the body^[3]. When antibodies damage myelin, they affect the messages that pass from your brain and spinal cord to the rest of your body^[2].

The damage to myelin is known as demyelination. While the precise function of MOG is not fully understood, it likely plays a role in myelin maturation, myelin integrity, and cell surface interactions^[5].

How common is MOGAD?

MOGAD is a relatively rare condition. It affects an estimated 1 to 3 people per million each year^[2]. The disease can affect people at any age, but the median age at onset is around 20 to 30 years^[6]. MOGAD occurs more commonly in children than in adults and affects males and females equally^[3].

Symptoms and clinical patterns

MOGAD causes inflammation in different parts of the central nervous system, leading to various symptoms. The symptoms depend on which part of the nervous system is affected^[1].

Eye symptoms (optic neuritis): When MOGAD affects the optic nerves, which connect the eyes to the brain, it causes a condition called optic neuritis. This is the most common presenting symptom in adults^[6]. Optic neuritis can affect one or both eyes and may cause blurry vision, double vision, vision loss, eye pain that gets worse with eye movement, and loss of color vision^[2]. In children, optic neuritis may be mistaken for a headache^[1].

Spinal cord symptoms (transverse myelitis): Inflammation of the spinal cord can lead to muscle weakness, numbness, stiff muscles, bowel or bladder control issues, difficulty emptying the bladder, and sharp, shooting pain or tingling sensations in the neck, back, or abdominal region^[2]. It may also cause arm or leg weakness, muscle stiffness, paralysis, and changes in sensory function^[1].

Brain symptoms (acute disseminated encephalomyelitis or ADEM): This is the most common presenting symptom in children, especially those under ten years of age^[3]. ADEM may cause confusion, loss of balance and coordination, headaches, behavioral changes, loss of consciousness, seizures, vision loss, weakness, unsteady walk, and changes in mental function^[1][2].

Other symptoms of MOGAD may include seizures, headaches, and fever^[1]. In children, MOGAD most often targets the brain, causing symptoms like confusion and loss of coordination, often accompanied by optic neuritis. In adults, MOGAD typically targets the spinal cord and eyes, causing weakness, numbness, and blurry vision^[2].

What causes MOGAD?

The exact cause of MOGAD is unknown^[2][5]. MOGAD is an autoimmune disorder, meaning the body’s immune system, which normally protects against illness from viruses and bacteria, mistakenly attacks healthy parts of the body^[1]. The immune system forms antibodies against MOG, a component of the myelin sheath in the brain and spinal cord^[3].

It is not known why some people develop MOGAD. It frequently happens after an illness^[3]. MOGAD is not inherited and does not have a known genetic cause^[2]. However, a recent infection or vaccination may increase the risk of developing MOGAD^[1].

How is MOGAD diagnosed?

MOGAD is usually diagnosed after healthcare professionals confirm two things: that symptoms were caused by a typical attack type, and that MOG antibodies are present in the blood or spinal fluid^[9].

A healthcare professional will first review your symptoms and may perform a physical exam to look for signs of MOGAD^[9]. Several procedures help confirm the diagnosis:

MOG antibody testing: This is a blood test that uses a cell-based assay to look at cells with MOG on their surface to see if MOG antibodies are present^[9]. This test is considered the gold standard for testing for MOGAD. A critical element of reliable diagnosis is detection of pathogenic MOG antibodies with accurate, specific, and sensitive methods^[4].

Spinal tap (lumbar puncture): This procedure collects a small sample of cerebrospinal fluid for testing. The sample can show if there is an elevated white blood cell count, which causes inflammation and is common in MOGAD^[9]. A spinal tap can also look for a type of protein called oligoclonal bands, which are more common in multiple sclerosis and may help distinguish between the two diseases^[9].

Imaging tests (MRI): An MRI of the brain, spine, and optic nerve can show irregular spots called lesions and inflammation of the optic nerve^[9]. MRI imaging can help differentiate MOGAD from other neuroinflammatory disorders^[4]. The lesions in the brain typically involve both sides and usually involve the white matter of the cortex. They may look “fluffy” or “cloudy” on MRI, meaning the edges of the lesions are not crisp and clearly defined^[3].

Eye exam (optical coherence tomography): This test can help diagnose MOGAD by examining the optic nerves^[9].

• Brain
• Spinal cord
• Optic nerves
• Central nervous system

Treatment options

There is no cure for MOGAD. However, treatments are available to help speed recovery from attacks, manage symptoms, and reduce the likelihood of symptoms returning^[1].

Treatment for acute attacks: High-dose steroids given through a vein in the arm (infusion) are the main treatment for MOGAD attacks^[9]. After infusion, patients continue taking a smaller dose of steroids by mouth. Acute immunotherapy is very effective, and severe disability is less frequent than in similar conditions^[4]. If steroids are not effective, treatments may include plasma exchange or intravenous immune globulin^[4].

Long-term management: For people who experience relapses, ongoing treatment with medications that suppress the immune system may be considered^[13]. Since about 40 to 50 percent of people with MOGAD only experience one attack, immunosuppression is generally reserved for those who have relapsing disease^[13].

There are no FDA-approved medications specifically for maintenance treatment in MOGAD, so anything prescribed is done off-label. The primary therapies used in the United States include mycophenolate mofetil (CellCept), rituximab (Rituxan), azathioprine (Imuran), and repeated intravenous or subcutaneous immunoglobulin infusions^[13][8].

Disease course and outlook

MOGAD can follow different patterns. Some people experience only one attack of symptoms, called monophasic MOGAD, which is slightly more common. Others experience multiple attacks, called relapsing MOGAD, where symptoms go away for a period (remission) before coming back (relapse)^[2][1].

About 40 to 50 percent of people with MOGAD only experience one attack^[13]. Young children or children who present with ADEM are more likely to have only one MOGAD attack. Older children or those with optic neuritis appear to have a higher risk of relapse^[3].

MOG antibodies may decrease over time and may not be detectable early in the disease process or during remission, especially for MOGAD associated with ADEM^[13]. Individuals who continue to test positive for MOG antibodies seem to have a higher chance of relapse^[13].

The level of disability after MOGAD attacks is usually less severe than in similar conditions, and recovery is typically better with therapies^[13][4]. Most children have very good recovery with treatment^[3]. In individuals who relapse, later attacks tend to be less severe^[13].

Attacks usually develop over days and can be severe. Disability may worsen with each attack, but recovery can take weeks to months^[1].

Possible complications

Damage to myelin can permanently affect how the body functions. People with MOGAD may experience the following complications^[2]:

• Blindness or permanent vision problems
• Bladder or bowel dysfunction
• Paralysis of arms and legs
• Chronic pain
• Chronic fatigue
• Cognitive impairment, including difficulty learning, remembering, and thinking

People with spinal cord inflammation (transverse myelitis) as their first MOGAD attack may have a higher chance of long-term disability^[13].

It can be difficult to live with and manage MOGAD. When symptoms happen, they can prevent you from participating in activities you enjoy and may leave you feeling helpless^[2]. Support from medical specialists, therapists, and family members can help with physical and mental wellness and recovery^[18].