Common Misdiagnoses: MS and NMO

Neuromyelitis optica spectrum disorder (NMO) and multiple sclerosis (MS) are diseases that share similar symptoms. NMO was once thought to be a type of MS. After years of research and advancing medicine, NMO is now considered to be a distinct disease. But many with NMO may still be misdiagnosed with MS or first diagnosed with MS. This can be devastating, since some treatments for MS may not be right for NMO.1

Knowing the differences and similarities between NMO and MS may help to decrease the risk of misdiagnosis and lead to quicker treatment.

What is NMO?

NMO is a rare inflammatory disease of the central nervous system. Also called the CNS, this includes the eye nerves, spinal cord, and brain. NMO may also be called neuromyelitis optica or NMO.1

NMO is an autoimmune disease. This means that the immune system cannot tell the difference between healthy cells and invaders like viruses, fungi, or bacteria. Because it cannot tell the difference, the body begins to attack and damage healthy cells. In NMO, the body damages the nerve fibers’ outer coating in the brain and spinal cord (myelin).1

What is MS?

MS is also an autoimmune disease affecting the CNS. Damage to different areas of the CNS may cause a variety of brain and nerve symptoms in people with MS. These symptoms vary in type and severity.2

What do NMO and MS share?

Figure 1. A chart breaking down the differences between NMO and MS side by side

A chart breaking down the differences between NMO and MS side by side

Demyelination

Nerve fibers in your brain, spinal cord, and eye have a protective coating (myelin). Damage to this layer is called demyelination. Some conditions, including NMO and MS, are demyelinating because they damage this protective layer.1,2

When this layer is damaged, nerve signals can slow or stop. This leads to brain and nerve problems. Muscle movement problems may also occur in both MS and NMO.1,2

Lesions

Because both NMO and MS can damage the myelin, both diseases show lesions (damage) to nerve fibers on magnetic resonance imaging (MRI).1,2

What are the differences?

Understanding and recognizing the differences between NMO and MS is important to getting the right treatment as quickly as possible. This could improve the overall outcome for either disease.3

Location of lesions

While both NMO and MS have lesions from nerve damage, the typical locations of the lesions are in different areas of the brain and spinal cord. NMO often affects only the optic nerve and spinal cord at the beginning of the disease. However, lesions may also occur in other areas of the brain. MS lesions occur in the brain as well as the spinal cord and optic nerve.4

AQP4 antibodies and MOG antibodies

Antibodies are chemicals the immune system makes to kill germs. In autoimmune diseases, antibodies can also be harmful. One antibody that is harmful in NMO attacks a protein called aquaporin-4 (AQP4).5,6

AQP4 is found on a type of brain cells called astrocytes and helps control water balance in the brain. The brain, spinal cord, and eye nerve (optic nerve) have AQP4. AQP4 antibodies (AQP4-IgG) damage the myelin of the brain cells and make more proteins that lead to inflammation.5,6

Antibodies targeting another protein called myelin oligodendrocyte glycoprotein (MOG) can also be present in NMO. They are believed to cause similar optic nerve or spinal cord attacks in MOG antibody (MOG-IgG) NMO. However, symptoms of this condition develop differently and need to be treated differently from those of AQP4 antibody (AQP4-IgG) NMO. Men and women are equally likely to get MOG antibody (MOG-IgG) NMO. Children have this disease more often than they have AQP4 antibody (AQP4-IgG) NMO.7-9

While many with NMO test positive for AQP4 antibodies (AQP4-IgG), about 1 in 4 do not. Some have no antibodies at all. This adds to the mystery behind the cause of the disease.7

Blood tests for AQP4 antibodies (AQP4-IgG) and MOG antibodies (MOG-IgG) help doctors rule out MS.7-9

Onset and severity of symptoms

In MS, relapses may be mild. Over time, MS relapses may or may not cause progressive symptoms and loss of function. In NMO, attacks are often severe, making early and correct diagnosis critical. NMO attacks can have devastating, irreversible effects on how a person can function.4,6

Vision loss

NMO may cause sudden vision loss in both eyes at the same time. Vision loss from MS usually affects only 1 eye at a time.4

Who gets NMO and MS?

NMO occurs across the world and affects non-white people more often than white people. Multiple sclerosis affects more white people than others and more of those who live in temperate climates (areas that have 4 seasons a year).4

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Written by: Katie Murphy | Last reviewed: September 2021