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Neuromyelitis optica spectrum disorder

What is neuromyelitis optica spectrum disorder (NMOSD)?

NMOSD is a rare neurological condition. Neurological conditions are caused by damage or disease to the brain, spinal cord, or nerves. In the case of NMOSD, the optic nerves (that connect the eye to the brain), the spinal cord, and sometimes certain parts of the brain, become inflamed. [1] This inflammation causes damage to the tissue resulting in different symptoms.

Symptoms of NMOSD vary a lot between individuals but can include: [2]

  • Eyesight problems (vision loss), perceived as blurred vision and loss of colour vision
  • Eye pain
  • Muscle weakness (which can affect mobility if the legs are involved)
  • Numbness (loss of sensation), tingling and/or increased sensitivity to cold and heat
  • Pain and/or muscle spasms
  • Bladder and bowel problems.

Eyesight (vision) problems in people living with NMOSD are usually due to a condition called optic neuritis, which is caused by inflammation of the optic nerve. Optic neuritis can affect one or both optic nerves at the same time. The symptoms of limb weakness, loss of bladder and bowel control, muscle spasms, pain and changes in sensation usually occur as a result of the spinal cord becoming inflamed. This is called transverse myelitis. Both optic neuritis and transverse myelitis are common in people who have NMOSD and either may occur as the first type of attack that a patient experiences. [2] 

What causes NMOSD?

NMOSD is an autoimmune disease of the central nervous system. Autoimmune diseases occur when the body’s natural immune defences attack healthy tissue. NMOSD is not a hereditary disease, so it is rare that there will be more than one person with NMOSD in a family. [2]

In autoimmune diseases, antibodies, which normally target foreign proteins seen as a threat by the immune system (such as those produced by bacteria and viruses), attack proteins in normal, healthy tissue by mistake. In NMOSD, the body produces antibodies that attack proteins in the central nervous system. The most common protein affected is aquaporin-4 (AQP4). [3]

AQP4 proteins are found in the membranes of cells and help to transport water in and out of cells. [3] The antibodies targeting AQP4 proteins cause damage to specific cells called astrocytes. [4] Astrocytes are star-shaped cells found in the optic nerves, brain, and spinal cord. Patients with AQP4 antibodies in their blood are said to be AQP4 seropositive.

Although the exact cause of NMOSD remains unknown, tests have shown that people diagnosed with active NMOSD have higher levels of interleukin-6 (IL-6) in their blood, compared with people with other neurological conditions. [5] IL-6 is a protein that is involved in inflammation and can also weaken the blood-brain barrier (a membrane that prevents harmful substances from entering the brain). [5] A weakened blood-brain barrier allows AQP4 antibodies (as well as cells that cause inflammation) to have direct access to the optic nerves, brain and spinal cord. In response, astrocytes in these tissues are damaged and produce even more IL-6, causing further damage and ultimately leading to the symptoms of NMOSD. [6]

How is NMOSD diagnosed?

NMOSD is usually diagnosed after a patient has experienced some of the symptoms described above. There are different techniques used to diagnose NMOSD and differentiate it from similar diseases: [2, 7]

  • Neurological (nervous system) and ophthalmological (eye) examinations, including vision (eyesight) tests
  • Blood tests to look for certain antibodies, including antibodies against the AQP4 protein
  • Typically, a magnetic resonance imaging (MRI) scan of the brain, optic nerves and/or the spinal cord is also performed. Magnetic fields are used to create images of the brain, the optic nerves and spinal cord while the patient lies in a long tube. The procedure usually takes 30 to 45 minutes
  • A lumbar puncture may be performed to extract a sample of cerebrospinal fluid (CSF; fluid that bathes the brain and spinal cord) for tests. A lumbar puncture usually takes 30 to 45 minutes. It is performed using a local anaesthetic so that the patient does not feel pain while the needle is being inserted to sample the CSF.

Because many of the symptoms of NMOSD are also present in multiple sclerosis (MS), it is important to distinguish between the conditions as early as possible. Treatment is different for NMOSD and MS. [1, 2]

What treatments are there for NMOSD?

There is currently no cure for NMOSD, so treatment focuses on managing the disease by treating acute relapses (attacks), preventing relapses, and managing symptoms during a relapse and those that persist afterwards. [8]

The first line of treatment for acute relapses is usually a high dose of a corticosteroid (steroid), methylprednisolone. This is typically given intravenously (into the veins). Methylprednisolone works by dampening down the immune response and reducing inflammation around the damaged nerves. [8]

The symptoms themselves may also be treated during a relapse. Where possible, non-pharmacological methods such as physiotherapy and occupational therapy may be used, [9] but for symptoms such as problems with muscle function (spasticity), fatigue, bladder and bowel problems, and/or pain, patients may receive medication. [10]

If symptoms get worse or do not respond to steroid treatment, patients may undergo a plasma exchange procedure, which removes the harmful antibodies from the circulation. Plasma exchange involves replacing the plasma in the blood with fresh plasma from a healthy donor (or a purified solution produced in a lab). [2, 10] The procedure involves having two needles attached to thin tubes, called catheters, inserted into two veins. The blood comes out through one of the tubes and goes into a machine that separates the plasma from the blood cells. The blood cells then get mixed with fresh plasma, and the new blood mixture goes back into the patient through the other tube. Most treatments last between 2 to 4 hours.

Another option for patients whose symptoms are getting worse or are not responding to steroid treatment is the use of intravenous immunoglobulin (IVIg). IVIg therapy boosts the body’s ‘healthy’ immune system and is used to treat many other autoimmune diseases. [11] This procedure is also carried out using a catheter inserted into a vein, and usually takes at least a couple of hours.

Because relapses can cause irreversible damage, treatments aimed at preventing relapses have become standard practice. Immunosuppressant medications such as mycophenolate, azathioprine and rituximab are often used and work by suppressing the body’s immune system. [12]

Over recent years, research has focused on developing targeted medications rather than those that generally suppress the body’s immune system. These newer treatments all belong to the class of medicines known as monoclonal antibodies.

Currently approved monoclonal antibody-based medicines for the targeted treatment of NMOSD in adults include eculizumab, inebilizumab and satralizumab (which is also approved for the treatment of adolescents with NMOSD in some countries). [13] These treatments target specific proteins that are involved in the immune response. Eculizumab targets a protein called complement component 5 (C5) and inebilizumab targets a different protein known as CD19. Satralizumab is an antibody targeting the IL-6 receptor. As described above, IL-6 plays a key role in the body’s inflammatory response and leads to increased production of the harmful AQP4 antibodies. [13]

What is the outlook for NMOSD?

In recent years, research into the causes of NMOSD and future treatments has increased worldwide. The focus of most of the research is on the use of monoclonal antibody treatment, and there are clinical trials ongoing to further understand how effective and safe these are.

Patients are currently being recruited to take part in a trial (known as SakuraBonsai) that will further assess the effects of satralizumab in patients with NMOSD who are AQP4 seropositive. The effectiveness and safety of satralizumab have already been shown in previous trials, [14, 15] but this new trial will use larger numbers of newly diagnosed patients and patients who have not responded well to rituximab.

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