8 Important Ways NMOSD Is Different From MS

Sure, on paper NMOSD sounds super similar to MS. But, in the body, the two conditions look and feel very different.

by Jeanine Barone Health Writer

It’s no wonder neuromyelitis optica spectrum disorder (NMOSD) is frequently mistaken for multiple sclerosis (MS). “Both NMOSD and MS are autoimmune disorders that damage the nervous system,” says Eric Lowell Singman, M.D., associate professor of ophthalmology at the Johns Hopkins Wilmer Eye Institute in Baltimore. With both conditions, your immune system, which normally defends you against bacteria and viruses, decides to attack your own tissues. And people with either neurological condition may experience blurred vision, numbness or tingling in their legs.

With such similar symptoms, it took more than a century (really!) for scientists and physicians to realize that NMOSD wasn’t just a spoke of the MS umbrella. Turns out, NMOSD is distinctly different.

1. NMOSD Targets a Specific Protein

Though both MS and NMOSD involve the body attacking itself and both result in inflammation, what’s doing the attacking and what’s being primarily attacked differs between the two conditions. In MS, T-cells (a.k.a. T-lymphocytes) attack myelin, the sheaths that wrap around long nerve fibers (normally these immune cells destroy invading bacteria and viruses). However, with NMOSD, it’s not T-cells that have gone awry. Instead, specialized proteins called antibodies attack AQP4, a key protein that regulates how water moves in and out of cells. And they don't attack all the AQP4 proteins in your body, only the ones present in nerve cells called astrocytes.

Astrocytes are nerve-cell caretakers that live in the brain and spinal cord. One of their most important functions is to deliver energy to neurons and to kickstart the release of neurotransmitters, chemicals that allow the neurons to communicate with each other. If something were to damage the astrocytes, depending on the location and the extent of the damage, it can result in anything from difficulty walking to blindness.

2. Gastrointestinal Symptoms May Be Severe

“The first symptom of NMOSD may be uncontrollable nausea and vomiting for weeks,” says Sean Pittock, M.D., director of Mayo Clinic's Center for Multiple Sclerosis and Autoimmune Neurology and the Neuroimmunology Research Laboratory in Rochester, MN. (Or you may have hiccups that don’t abate for weeks on end.) These gastrointestinal (GI) symptoms are not your run-of-the-mill indigestion, reflux or nausea that can readily be resolved with an OTC drug. Rather, they are extremely severe and constant, and affect your ability to go about your daily activities. With MS, having nausea, vomiting or hiccups that won't go away is rare.

3. The Optic Nerve Is Hit Hard

Vision loss can occur with NMOSD because of severe inflammation of the optic nerve (optic neuritis), which impairs the proper transmission of nerve impulses from the back of the eye (retina) to the visual center of the brain. Often NMOSD affects the part of the brain where the two optic nerves—one from each eye—connect, referred to as the optic chiasma. That’s why the damage to vision can be bilateral.

Your vision may be blurry, colors may appear washed out, you may lose vision in the upper or lower half of your visual field, or you may temporarily or permanently go blind in one or both eyes. You can also develop severe pain when you move your eyes, or a stabbing pain in the back of your eye. With MS, vision difficulties usually occur in just one eye, and they often improve once inflammation abates. Visual field defects, like spots, are rare with MS.

4. Damage Tends to Cluster in Certain Parts of the CNS

“MS damages the entire central nervous system,” says, Dr. Singman. This includes the optic nerves, spinal cord, and all parts of the brain: the cerebellum (which manages balance and coordination); the brainstem (the lower part of the brain that regulates numerous vital functions, including swallowing and breathing); and the cerebrum (which controls everything from memory, problem solving, and learning to walk), continues Dr. Singman.

Meanwhile, the damage associated with NMOSD is focused on the optic nerve, brainstem, and spinal cord. The reason people with NMOSD have uncontrolled nausea, vomiting or hiccups, for instance, is because there's damage to the area postrema on the brainstem, explains Dr. Singman.

5. Lesions on the Spinal Cord Are Much Larger

People with NMOSD have lesions on their spinal cord that are longer than those found in MS, often extending along several segments of the spinal cord, says Dr. Pittock. In MS, the areas of damage are generally short. These larger lesions contribute to more severe symptoms.

6. Diagnosis Techniques Vary

Doctors diagnose NMOSD by taking a blood sample, looking for the antibody to AQP4 as well as one called myelin oligodendrocyte glycoprotein (MOG). “If you have this antibody, you have the disease; it is not found in the blood of patients with MS, which has no biomarker substance that tells you that you have the disease,” says Dr. Pittock. Testing for this antibody is now standard.

Typically the diagnosis for MS is made based on symptoms, an MRI, and sometimes the results of a spinal tap to look for various immune cells and antibodies in the cerebrospinal fluid. Though your doctor might also do an MRI and spinal fluid test if they suspect NMOSD, the blood test is the definitive one.

7. Standard MS Treatments Make NMOSD Worse

MS is typically treated with disease-modifying therapies (DMTs), which operate by suppressing the immune system. However, some of the DMTs are either ineffective in treating NMOSD or can actually make the condition worse. Among the DMTs that can worsen NMOSD are the new generation drugs that successfully treat MS, including Gilenya (fingolimod) and Tysabri (natalizumab).

Unlike with MS, NMOSD has fewer treatment options. Up until 2019, doctors treated the condition with off-label drugs that had been approved for other autoimmune disorders like lupus. The FDA recently approved two immunosuppressants, Soliris (eculizumab) and Uplizna (inebilizumab), that suppress your immune system to prevent future attacks. Physicians believe a third immunosuppressant drug called Enspryng (satralizumab) will also be approved by the FDA.

8. Disease Progression Looks Very Different

With MS, most people do not experience permanent disability from the relapses; they, in fact, make a good recovery. When disability does occur, it’s usually with the more advanced progressive form of the disease: SPMS (secondary progressive multiple sclerosis). With SPMS, symptoms come on, but they either don’t improve or worsen without a relapse.

“It’s different with NMOSD; the progression is related to the attacks,” says Dr. Pittock. “Between the attacks there’s not much progression.” But with each attack there is accumulated nerve damage, resulting in sensory losses (including worsening vision difficulties), problems with bladder and bowel control as well as the ability to move your muscles properly.

For example, with MS, 90% of people recover from optic neuritis, but not so with NMOSD, which has a high likelihood of vision loss. That’s why it’s so important to stop the attacks. “If you stop the attacks, you stop the disability,” adds Pittock.

Jeanine Barone
Meet Our Writer
Jeanine Barone

Jeanine Barone is a scientist and journalist with an eclectic background. She’s a nutritionist and exercise physiologist who regularly writes about travel, health, fitness, and food for numerous top-tier publications. Jeanine enjoys active travel, especially long-distance cycling and cross-country skiing.