Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.

Eyes front and ears open. Class is now in session.

The disease that we will be learning about today is:

Neuromyelitis Optica Spectrum Disorder

Sometimes called Devic’s disease or simply neuromyelitis optica.

What is Neuromyelitis Optica Spectrum Disorder?

• Neuromyelitis optica spectrum disorder (NMOSD), also known as Devic disease, is a chronic disorder of the brain and spinal cord dominated by inflammation of the optic nerve (optic neuritis) and inflammation of the spinal cord (myelitis).​
• Neuromyelitis optica spectrum disorder causes inflammation of the optic nerve (optic neuritis). One or both eyes may be affected. The disorder causes episodes of eye pain and dim, blurred, or lost vision.
• The damage to the spinal cord causes weakness or paralysis in the legs or arms, loss of sensation, and problems with bladder and bowel function.​​
• NMOSD occurs in individuals of all races. The prevalence of NMOSD is approximately 1-10 per 100,000 individuals and seems to be similar worldwide, although somewhat higher rates have been reported in countries with a higher proportion of individuals of African ancestry.​
• Anti-aquaporin-4 (AQP4) antibody-positive Neuromyelitis Optica Spectrum Disorder (NMOSD) is a rare autoimmune disease that causes your immune system to attack your central nervous system. These attacks, also known as relapses, can cause permanent damage to your optic nerves and spinal cord.
• Relative to MS that it mimics, it occurs with greater frequency in individuals of Asian and African descent, but the majority of patients with this illness in Western countries are Caucasian. ​
• Individuals of any age may be affected, but typically NMOSD, especially cases seropositive for AQP4-IgG, occur in late middle-aged females.​
  • The reported incidence of NMOSD in females is up to 10 times higher than in males
  • In monophasic NMOSD (1 to 10 percent of patients) males and females are affected equally, but in typical recurrent NMOSD, females predominate over males by 5:1 to 10:1. ​
• The median age of onset is 32 to 41 years, but cases are described in children and older adults. Comparatively, multiple sclerosis has a median age of onset of 24 years and an estimated female to male incidence of 2.3:1.​
• Aquaporin-4, also known as AQP4, is a water channel protein encoded by the AQP4 gene in humans.​
  •  AQP4 belongs to the aquaporin family of integral membrane proteins that conduct water through the cell membrane.​
  • Aquaporin-4’s overall function is to provide fast water transportation as well as maintain homeostatic balance within the central nervous system. It is the primary water channel protein that reconciles the homeostasis of water in the CNS.​
  • Aquaporin-4 is the predominant autoimmune target in neuromyelitis optica, or NMO, since a specific AQP4 IgG autoantibody, or NMO-IgG, binds to the extracellular surface of AQP4.​
  • People living with anti-AQP4 antibody-positive NMOSD have a high risk of relapse​
  • Antibodies are naturally produced by your immune system to defend against infections and other threats​
  • 73% of people with NMOSD test positive for anti-AQP4 antibodies​
  • With anti-AQP4 antibody-positive NMOSD, you have abnormally high levels of these antibodies, which can cause your body to attack itself​

How Do You Get It?

• Neuromyelitis optica spectrum disorder is an autoimmune disorder. ​
• Autoimmune disorders occur when the immune system malfunctions and attacks the body’s own tissues.​
• In neuromyelitis optica spectrum disorder, the target of the autoimmune attack is a protein called aquaporin 4, which is present on the surface of support cells (called astrocytes) in the brain, spinal cord, and optic nerves. ​
• Damage to astrocytes is thought to lead to demyelination. In some people with neuromyelitis optica spectrum disorder, the immune system targets another protein called myelin oligodendrocyte glycoprotein (MOG), which is present on the outer layer of myelin.​

What Are The Symptoms?

• Neuromyelitis optica spectrum disorder causes inflammation of the optic nerve (optic neuritis). One or both eyes may be affected. ​
• The disorder causes episodes of eye pain and dim, blurred, or lost vision.​
• Days to weeks (sometimes years) later, the limbs are affected. ​
• People may temporarily lose sensation. ​
• They may have painful muscle spasms, and the arms and legs may become weak and sometimes paralyzed. ​
• People may be unable to control the bladder (urinary incontinence) and bowels (fecal incontinence).
• Sometimes the brainstem can be impacted, leading to lesions that can cause respiratory problems, pain, hiccups, and vomiting.​

How Is It Treated?

• There is no cure for neuromyelitis optica spectrum disorder. However, treatments can stop episodes, control symptoms, and prevent episodes from recurring.​
• For acute attacks, the standard treatment is high-dose intravenous corticosteroids, typically methylprednisolone.​
• Plasma exchange may be effective in patients who experience acute severe attacks that do not response to intravenous corticosteroids. ​
• Soliris (eculizumab) is approved for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive. ​
  • Soliris® (eculizumab) is the first and only medication approved by the FDA to treat adults with Neuromyelitis Optica Spectrum Disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody positive. It is not known if Soliris is safe and effective in children with NMOSD.​
• For long-term suppression of the disease, no specific treatment has been studied in controlled clinical trials, but a variety of immunosuppressive drugs are regarded by many clinicians as first-line therapy.
  • Corticosteroids, azathioprine, mycophenolate mofetil and rituximab are the treatments most widely prescribed treatments. 
  • Typically, azathioprine or mycophenolate mofetil are prescribed along with low doses of corticosteroids. ​
  • Rituximab has been shown to be helpful in retrospective studies, including in patients who fail first-line immunosuppressive treatments. ​
• There is no cure for neuromyelitis optica spectrum disorder. However, treatments can stop episodes, control symptoms, and prevent episodes from recurring.​
• Immunomodulatory drugs for multiple sclerosis are ineffective, and in the case of interferon beta, there is some evidence that suggest that it may be harmful.​
• Symptom treatment may also involve the use of low doses of carbamazepine to control paroxysmal (sudden) tonic spasms that often occur during attacks of NMOSD and antispasticity agents to treat long term complication of spasticity that frequently develops in those with permanent motor deficits.​

Where Can I Learn More???

• Check out our cornerstone on this disease here.
• Learn more about this illness from the Guthy-Jackson Charitable Foundation.