Genetic and Environmental Risk Factors in NMOSD

What Is Neuromyelitis Optica Spectrum Disorder?

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disorder (inflammatory demyelinating disease) that mainly affects the central nervous system (spinal cord, optic nerve, and brain stem). In this condition, the immune system attacks the healthy cells of the central nervous system as they appear to threaten them.

Neuromyelitis optica spectrum disorder was previously known as Devic’s disease, named after Devic and Gault, who first described the term neuromyelitis optics in 1894. The condition is more prevalent in females than males (9:1), and globally, NMOSD rarely occurs in five out of 100,000 cases.

NMOSD, for many years, was misdiagnosed or considered a variant or sister disease to multiple sclerosis (MS), as the condition is often found to mimic MS (multiple sclerosis). However, neuromyelitis optica spectrum disorder is currently identified with distinct pathophysiological and clinical characteristics. The condition represents a unique feature that helps differentiate the condition from MS, such as the presence of a water channel (serum autoantibodies specific for aquaporin-4 or AQP4 expression) at the astrocytic foot (a star-shaped cell that holds the brain’s nerve cells at a place).

Therefore, the article discusses NMOSD and the genetic and environmental risk factors associated with this condition.

What Are the Genetic and Environmental Risk Factors in NMOSD?

The risk factors for NMOSD are as follows:

• Genetic Factors - NMOSD has been associated with a genetic marker, HLA, or human leukocyte antigen alleles, which can affect the immune response and increase the susceptibility to neuromyelitis optica spectrum disorder. In addition, any family history of an autoimmune disease, or NMOSD, may also increase the risk to some extent. However, NMOSD is not considered a hereditary disorder.

• Environmental Factors - Disease risk could also be influenced by certain environmental and dietary risk factors, such as ultraviolet radiation exposure, physical activity, fruit and vegetable consumption, seafood intake, low dietary consumption, smoking, and vitamin D insufficiency.

What Are the Causes of Neuromyelitis Optica Spectrum Disorder?

The actual cause of neuromyelitis optica spectrum disorder is not known; however, the condition is often known to occur along with an autoimmune disease or an infection. Generally, an immune system produces some protein in the bloodstream for the body to fight infections; however, in the case of neuromyelitis optica spectrum disorder, the affected body makes an antibody called AQP4, which attacks the proteins of the immune system that helps move water across the cell membranes.

What Are the Symptoms of Neuromyelitis Optica Spectrum Disorder?

Following are the symptoms of neuromyelitis optica spectrum disorder:

• Blurred vision or complete loss of vision.

• Persistent nausea.

• Persistent hiccups.

• Bowel or bladder dysfunction.

• Painful spasms.

• Weakness or paralysis in upper and lower limbs.

• Uncontrollable or persistent vomiting.

• Sleeping disorders.

• Loss of sensation or numbness in the entire body.

What Are the Diagnostic Criteria for Neuromyelitis Optica Spectrum Disorder?

The diagnostic criteria for NMOSD are mainly based on the core characteristics, which include:

• Acute myelitis (spinal cord inflammation).

• Optic neuritis (optic nerve inflammation).

• Acute brainstem syndrome.

• Area postrema syndrome.

• Brain lesion - symptomatic cerebral syndrome.

• MRI (magnetic resonance imaging) lesion - acute diencephalic clinical syndrome with typical diencephalic or symptomatic narcolepsy.

1. Diagnostic Criteria for NMOSD with AQP4-IgG:

• Presence of one core clinical characteristic.

• The AQP4-IgG test should be positive using advanced detection methods.

• It should not include an alternative diagnosis.

2. Diagnostic Criteria for NMOSD without AQP4-IgG:

• Presence of two core clinical characteristics must be present due to one or more attacks and include the following requirements:

  • One of the core clinical characteristics should be acute myelitis, optic neuritis, or area postrema syndrome.

  • Presence of two or more different core clinical features.

  • There are some additional MRI requirements.

• The AQP4-IgG test should be negative, and advanced detection methods should be used.

• It should not include an alternative diagnosis.

3. Additional MRI Features or Requirements for NMOSD with Unknown AQP4-IgG Status or Without AQP4-IgG:

• Acute Myelitis - In patients with a history of acute myelitis, it requires an associated intramedullary MRI (magnetic resonance imaging) lesion extending over greater than or equal to three contiguous segments (LETM) or greater than or equal to three contiguous segments of focal spinal cord atrophy in patients with a history compatible with acute myelitis.

• Acute Optic Neuritis - It requires an MRI of the brain showing normal findings or just nonspecific white matter lesions, a T1-weighted gadolinium-enhancing lesion extending over more than one-half the optic nerve length, or an optic nerve MRI with a T2-hyperintense lesion or involving theoptic chiasm.

• Acute Brainstem Syndrome - This condition requires a peri ependymal brainstem lesion.

• Acute Postrema Syndrome - Requires area postrema lesion or dorsal medulla.

Diagnosis for NMOSD Includes:

• The patient's medical history is taken to rule out any underlying medical condition, such as multiple sclerosis, that may be causing NMOSD.

• A neurological examination is done to evaluate muscle strength and coordination, access vision, speech, thinking, and memory skills, and identify numbness in the body, if present.

• A magnetic resonance imaging (MRI) scan is performed to rule out damage to the brain, spinal cord, and optic nerve.

• An eye examination checks for blurred vision or any other eye condition.

• Lumbar puncture or spinal tap for analyzing the fluid that surrounds the brain and spinal cord.

• Blood test for AQP4-IgG (this antibody is usually present in about 70 percent of cases suffering from NMOSD)

How Is Neuromyelitis Optica Spectrum Disorder Treated?

Antiinflammatory medications, such as methylprednisolone, an intravenous (IV) corticosteroid, are prescribed. Also, PLEX (plasma exchange therapy) is given to the patient just before or after the corticosteroid treatment. In this process, the liquid part of the blood is replaced with artificial plasma to reduce the AQP4-IgG antibody in the blood.

Additionally, immunosuppressive drugs are prescribed to the patient if the inflammation persists. This medication changes the immune system's reaction and, thus, prevents any new attack of NMOSD. However, the patient must be closely monitored for infection or complications in such cases.

Does NMOSD Have an Association With Any Other Disease?

Neuromyelitis optica spectrum disorder (NMOSD) is often associated with autoimmune diseases (antibody-mediated), which include Sjogren syndrome (which causes dry mouth and dry eyes), lupus erythematosus (in which the immune system attacks its tissues), and antiphospholipid antibody syndrome (in which the immune system attacks normal proteins present in the blood).

Conclusion

To conclude, the prognosis of neuromyelitis optica spectrum disorder (NMOSD) is inferior with a greater possibility of relapse or recurrence in almost 90 percent of cases. These frequent attacks can be extremely devastating and cause a person significant disability and loss of vision. Therefore, early diagnosis and aggressive and timely management of the condition can help prevent relapse.