Causes and Risk Factors of Neuromyelitis Optica Spectrum Disorder

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Neuromyelitis optica spectrum disorder (NMOSD) is a rare, chronic (long-term), demyelinating, autoimmune disease of the central nervous system (CNS). It is also commonly referred to as Devic’s disease. The disorder primarily affects the optic nerve and spinal cord. It can also affect the brain in some instances. When the brain is involved, it usually occurs in the later phases of the disease, causing intractable (uncontrollable) vomiting and hiccoughing from inflammation in part of the brainstem.

For people with NMOSD, the body’s immune system begins to attack the healthy cells and tissues (specifically, the covering of the nerves called the myelin sheath) instead of only attacking foreign invaders such as viruses. This results in inflammation and injury to the nerves in the eyes (causing visual problems or blindness) and the spinal cord (causing muscle weakness, paralysis and more).

With each episode or relapse, a person has a higher risk of becoming visually impaired, blind, or disabled (this often occurs within five years of diagnosis).

Two Forms of NMOSD

There are two types of NMOSD, including:

  • The relapsing form of NMOSD is the most common type of the disorder, involving recurrent relapses/episodes and periods of recovery, lasting months or sometimes even years apart.
  • The monophasic form of NMOSD involves one single episode that may last from 30 to 60 days. Once this initial episode is over, there are no subsequent flare-ups.

Common Causes

The cause of autoimmune diseases is not well understood. Some experts think that there may be a genetic predisposition, combined with some sort of environmental trigger (such as contracting a specific infectious viral disease). A 2018 study reports that NMOSD’s immune dysfunction is likely to be linked with a genetic predisposition, combined with environmental triggers, including various infection-causing organisms such as:

  • Mycoplasma pneumoniae
  • Mycobacterium tuberculosis
  • Treponema pallidum
  • Helicobacter pylori
  • Chlamydia pneumoniae

Researchers are also exploring a possible hormonal link to autoimmune disorders. This may explain why women are more likely to be diagnosed with some types of autoimmune diseases, such as the relapsing form of NMOSD. But there is not enough solid clinical research data yet to back these claims.

Autoimmune Disorders

Under normal circumstances, the body can discern between a foreign invader (non-self) and the body’s own cells and tissues (self). Antibodies are normally only produced when the body perceives an attack from a foreign invader or non-self (such as a virus or bacteria).

When the immune system fails to recognize one or more of the body’s own elements (such as specific proteins) as self, it sometimes produces what is called “autoantibodies” that attack its own cells, tissues or organs. In NMOSD, there have been two autoantibodies discovered. These autoantibodies are formed in response to specific proteins, including:

  1. Aquaporin-4 (AQP4-Ab or NMO-IgG) Note, IgG stands for immune globulins which are a type of antibody, and Ab is an acronym for antibody.
  2. Myelin oligodendrocyte glycoprotein (MOG-IgG)

The type of autoimmune disorder that a person develops depends on the systems that are targeted for attack by the autoantibodies. In NMOSD, the system involved is the central nervous system (including the brain and spinal column).

Research

Although the exact cause of most autoimmune disorders (including NMOSD) is unknown, medical studies have shown that an autoimmunity is linked with harmful autoantibodies. What causes these antibodies to attack one’s own cells and tissues is not fully understood. But the Mayo Clinic has become a recognized institution of excellence in diagnosing and treating NMOSD. In 2002, Mayo Clinic researchers proposed that NMOSD is a disease that is caused by one or more harmful antibodies. The researchers went on to identify two such, specific antibodies linked with NMOSD, these include:

  1. The aquaporin-4 IgG (AQP4 IgG/NMO-IgG antibody) was discovered in 2004, by Vanda Lennon, M.D., Ph.D., Brian Weinshenker, M.D., and other Mayo researchers, AQP4 IgG was discovered to cause nerve cell damage and it is now widely considered a cause of NMOSD. Researchers discovered that not every person with NMOSD has the AQP4 IgG antibody; only up to 72% of NMOSD patients are AQP4 IgG positive.
  2. The antibody to myelin oligodendrocyte glycoprotein (MOG IgG1) is found in some people diagnosed with NMOSD (particularly for those with the monophasic form). These people are more likely to experience less severe attacks than those with the relapsing form of NMOSD. They also recover better (than those with the relapsing form of NMOSD who have an antibody to the AQP4 IgG) with a lower incidence of long-term disabilities.

Multiple Autoimmune Disorders

An autoimmune disorder is considered a chronic, complex inflammatory disease. NMOSD is sometimes linked with other autoimmune diseases (such as systemic autoimmune diseases involving the entire body) or brain autoimmune diseases. When a person has one autoimmune disorder, it results in an increased risk of having another type of autoimmune disorder. In fact, some sources report that there is a 25% rate of a second autoimmune disorder being present.

A common type of systemic autoimmune disease that is linked with NMOSD is called lupus erythematosus. But it is not well understood what the causative factor or specific link is when a person has more than one autoimmune disorders.

Genetics

Although some experts feel there is a genetic link to having an autoimmune disease, such as NMOSD, it has not yet been proven. When it comes to NMOSD, over 95% of those diagnosed report that there are no known relatives with the specific disorder. However, there is a strong link between having a family history of some type of autoimmunity (other than NMOSD). In fact, in 50% of NMOSD cases, some type of autoimmune disorder has been reported in a family member.  This indicates a strong familial/genetic link to NMOSD.

Lifestyle Risk Factors

There are no proven lifestyle factors that lend themselves to the development of NMOSD. However, scientists are beginning to gather some clues as to some possible associations between diet and lifestyle factors and NMOSD.

For example, a 2018 study discovered that several factors, including long-term smoking, passive smoking, and long-term consumption of whiskey or vodka may be risk factors for NMO-IgG positivity. Studies have shown a link between smoking and the development of autoantibodies.

Another study discovered a possible link between a high level of saturated fatty acids (bad fats such as animal fats and trans fats) in the diet and multiple sclerosis (MS) and NMOSD. The study also discovered that those with NMOSD who ate large amounts of polyunsaturated fats (such as from olives, olive oil, and avocados), forgoing saturated fats, experienced lower levels of fatigue and a lower incidence of developing long-term disabilities.

A person with NMOSD should consult with their health care provider before employing any type of diet or exercise change.

A Word From Verywell

NMOSD is an incurable condition that may result in severe, debilitating symptoms (like paralysis or blindness). A person with any type of debilitating disorder will be faced with some adjustments as the disease progresses. 

For newly diagnosed people with NMOSD, searching for information on what caused their disorder, the first step in coping with such a devastating diagnosis is to start employing a support system—perhaps involving many different resources. 

There are many online resources that can help, such as those that offer live support to answer questions, or websites that can get you in touch with local groups. For example, the National Organization of Rare Diseases (NORD) offers an online resource guide for finding local support groups. NORD also offers information on how to organize your own local support groups.

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  1. National Organization for Rare Disorders. Neuromyelitis optica spectrum disorder. Updated 2018.

  2. Johns Hopkins Medicine. Neuromyelitis optica.

  3. Levinson JB, Alvarez MR, Koci K, Feoktistov A, Mcfarlane IM. Epstein - Barr virus infection in a patient with neuromyelitis optica spectrum disorder and Sjögren's syndrome: A case report and review of literature. Clin Case Rep Rev. 2018;4(5). doi:10.15761/CCRR.1000411

  4. Pittock SJ, Berthele A, Fujihara K, et al. Eculizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. N Engl J Med. 2019;381:614-625. doi:10.1056/NEJMoa1900866

  5. Melamed E, Levy M, Waters PJ, et al. Update on biomarkers in neuromyelitis opticaNeurol Neuroimmunol Neuroinflamm. 2015;2(4):e134. doi:10.1212/NXI.0000000000000134

  6. Glisson CC. Neuromyelitis optica spectrum disorders. UpToDate. Updated December 11, 2019.

  7. Cojocaru M, Cojocaru IM, Silosi I. Multiple autoimmune syndrome. Maedica (Buchar). 2010;5(2):132-4.

  8. Eskandarieh S, Moghadasi AN, Sahraiain MA, Azimi AR, Molazadeh N. Association of cigarette smoking with neuromyelitis optica-immunoglobulin G sero-positivity in neuromyelitis optica spectrum disorderIran J Neurol. 2019;18(3):93–98.

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