Brief overview
- What is neuromyelitis optica (NMO)? A rare disease with mostly episodic inflammation in the central nervous system, especially in the optic nerve, spinal cord and brain stem. Today, medicine speaks of neuromyelitis optica spectrum disorders (NMOSD) and thus refers to closely related clinical pictures.
- Symptoms: inflammation of the optic nerve with reduced vision and even blindness; inflammation of the spinal cord with sensory disturbances, pain, muscle weakness, paralysis and even paraplegia; other possible symptoms include persistent hiccups, nausea, vomiting, etc.
- Diagnosis: Medical history, MRI imaging, blood and cerebrospinal fluid tests, antibody tests, further tests to rule out other diseases (such as multiple sclerosis) if necessary.
- Treatment: Relapse therapy with cortisone and/or “blood washing”; long-term therapy to prevent further relapses (e.g. with artificially produced antibodies such as eculizumab and rituximab or immunosuppressants such as azathioprine). Treatment of symptoms.
- Prognosis and life expectancy: Repeated, sometimes severe relapses, from which patients usually do not fully recover. This can quickly lead to permanent disabilities. If untreated, up to 30 percent of patients die within the first five years.
What is neuromyelitis optica (NMO)?
In addition to the long-known NMO, there are other forms or a number of very similar diseases. Today, doctors summarize them under the term neuromyelitis optica spectrum disorder (NMOSD):
In all cases, these are autoimmune-mediated inflammations in the central nervous system with a mostly relapsing course. The optic nerve, spinal cord and brain stem are particularly affected. The inflammation there causes neurological symptoms that often lead to severe physical disabilities.
You can find out more about the similarities and differences between NMOSD and MS here.
Who suffers from NMOSD?
People with neuromyelitis optica spectrum disorders often also suffer from other autoimmune diseases. These include, for example, a brain disease associated with autoimmune thyroiditis, Sjögren’s syndrome and myasthenia gravis.
Prognosis and life expectancy
Neuromyelitis optica spectrum disorders are chronic diseases and are not yet curable. It is generally important to start treatment as early as possible in every phase of the disease. On the one hand, this makes it easier to manage the often severe relapses. On the other hand, the risk of further relapses can be reduced.
NMOSD can also affect life expectancy: If the disease remains undiagnosed or untreated, up to 30 percent of those affected die of respiratory failure (as a result of the spinal cord inflammation) within the first five years of the onset of the disease.
Neuromyelitis optica (NMO): Symptoms
Neuromyelitis optica spectrum disorders (NMOSD) can cause symptoms such as visual disturbances, muscle weakness, paralysis, sensory disturbances in the skin, incontinence, hiccups or nausea and vomiting.
The exact symptoms depend on which areas of the central nervous system are inflamed.
Spinal cord inflammation (myelitis): Sensory disorders, muscle weakness and paralysis up to paraplegia are consequences of NMOSD of the spinal cord. Patients often also have shooting pains (nerve pain) and may not be able to hold their urine and bowel movements.
Area postrema syndrome: Sometimes parts of the brain also become inflamed in neuromyelitis optica spectrum disease – for example the area postrema at the back of the brain stem. This is reflected in episodes of unexplained hiccups or nausea and vomiting.
Diencephalic syndrome: It manifests itself with sudden sleep attacks (narcolepsy), disorders of body temperature regulation and/or hypofunction of the pituitary gland.
Cerebral syndrome: In some NMOSD patients, nerve tissue in the cerebral hemispheres becomes inflamed. This can manifest itself with incomplete paralysis (paresis), speech disorders, headaches and epileptic seizures.
Mostly relapsing-remitting course
The symptoms of neuromyelitis optica spectrum disorder described above can be more or less severe and usually occur in episodes. The second relapse occurs on average eight to twelve months after the first; however, the time interval can also be years.
The relapses of NMOSD are significantly more aggressive than those of multiple sclerosis. Even after the first relapses, those affected can suffer permanent severe disabilities (e.g. blindness, paralysis).
It is rare for NMOSD patients to have no more relapses after the first one. Doctors then speak of a monophasic neuromyelitis optica spectrum disease.
NMOSD is ruled out if the disease continues to worsen without relapses. Such courses are known from multiple sclerosis, but are at best isolated cases of NMOSD.
Neuromyelitis optica: causes
In the case of neuromyelitis optica spectrum diseases, these are antibodies of the immunoglobulin G type that are directed against aquaporin-4 (AQP-4). This is a protein that serves as a water channel in the membrane of certain cells – primarily in the optic nerve and spinal cord, but also in the brain stem and other regions.
As a result, the inflammation spreads around the affected cells: The protective sheaths (myelin sheaths) of nerve fibres are destroyed (demyelination) and nerve processes (axons) are directly damaged.
Antibodies against AQP-4 can be detected in most, but not all patients. If certain criteria are met, doctors can still diagnose NMOSD (see below).
Neuromyelitis optica: examinations & diagnosis
If you have symptoms that indicate nerve damage, a specialist in diseases of the nervous system is the right person to consult. He or she will first ask about the exact symptoms and previous medical history (anamnesis).
Imaging
Using MRI (magnetic resonance imaging or magnetic resonance imaging), the doctor takes images of the brain (including the optic nerve) and spinal cord. Patients are usually also given a contrast agent. This enables the doctor to better recognize pathological changes (e.g. spots that appear bright due to the contrast agent, which may indicate inflammation).
In the case of NMOSD-related inflammation, the affected area of the spinal cord can extend longitudinally over three or more vertebral body segments (the vertebral bodies/bones surround the spinal cord and therefore serve as a kind of ruler for damage to the spinal cord). Doctors then speak of “longitudinal extensive transverse myelitis” (read more about this in the article Transverse myelitis).
Blood and cerebrospinal fluid examinations
An examination of the cerebrospinal fluid (CSF diagnostics) during an NMOSD episode often shows an increased cell count. However, such pleocytosis can also have many other causes.
In NMOSD, certain protein patterns (so-called oligoclonal bands) can rarely or only temporarily be detected in the cerebrospinal fluid – in contrast to multiple sclerosis, for example, where such protein patterns are almost always present. Oligoclonal bands are also not uncommon in other chronic inflammatory diseases of the central nervous system.
Antibody testing
Aquaporin-4 antibodies are found in very many people with NMOSD (around 80 percent). However, there are also people who do not have AQP-4 antibodies but still have neuromyelitis optica spectrum disorder.
If an initial test for AQP-4 antibodies is negative and doctors still suspect NMOSD, they usually repeat the test. The AQP-4 antibodies are then looked for in a different laboratory and/or with a different test procedure and/or at a different time.
As part of the NMOSD clarification, doctors always have antinuclear antibodies (ANA) determined in the blood. These autoantibodies occur in various autoimmune diseases, such as those of the connective tissue (collagenoses). On the one hand, they are a possible alternative diagnosis (differential diagnosis) for NMOSD. On the other hand, there may also be overlaps between collagenoses and a neuromyelitis optica spectrum disorder with AQP-4 antibodies – in terms of laboratory chemistry and symptoms.
In individual cases, further examinations may be necessary, especially to rule out differential diagnoses. These may include, for example, further blood tests or imaging procedures (such as X-rays).
Diagnostic criteria for NMOSD
NMOSD with AQP-4 antibodies
Doctors speak of neuromyelitis optica spectrum disease with AQP-4 antibodies when all of the following criteria are met:
1. at least one of the six typical disease manifestations (“core symptoms”) is present. These are:
- optic neuritis (inflammation of the optic nerve)
- acute inflammation of the spinal cord (acute myelitis)
- acute area postrema syndrome (hiccups or nausea and vomiting with no other explanation)
- acute brainstem syndrome
- symptomatic narcolepsy or acute diencephalic syndrome with an NMOSD-typical lesion in the diencephalon detectable by MRI
- symptomatic cerebral syndrome with an NMOSD-typical cerebral lesion detectable on MRI
2. AQP-4 antibodies are found in the blood serum.
NMOSD without AQP-4 antibodies or with unknown antibody status
In the absence of AQP-4 antibodies or if the antibody status is unknown, doctors can still diagnose NMOSD – provided the following criteria are met:
1. no AQP-4 antibodies are found in the blood or the antibody status is unknown.
2. other diseases are not a possible cause (differential diagnoses excluded)
3. at least two of the six core symptoms are present as a result of one or more relapses, whereby all three of the following requirements must be met:
- At least one of the core symptoms is optic neuritis or spinal cord inflammation over at least three vertebral body segments (extensive myelitis) or an area postrema syndrome.
- Certain additional MRI criteria must be met (e.g. evidence of damage in the area postrema if the patient has unexplained episodes of hiccups or nausea and vomiting).
Neuromyelitis optica: Treatment
In neuromyelitis optica spectrum disorders, there is both relapse therapy and long-term therapy. In addition, doctors treat NMOSD symptoms such as pain and bladder or bowel dysfunction as required.
Relapse therapy
Relapse therapy for NMOSD is based on that for multiple sclerosis: NMOSD patients receive glucocorticoids (“cortisone”) and/or apheresis (blood washing) as soon as possible after the onset of a disease relapse.
In apheresis (plasma separation), antibodies are removed from the patient’s blood in several cycles. Two methods are available for this (plasmapheresis and immunoadsorption), which are comparable in their effectiveness.
Blood washing in NMOSD patients is independent of whether they have autoantibodies in their blood or not. It can be useful as:
- second-line therapy after cortisone therapy if the neurological symptoms have not improved sufficiently or have even worsened. Sometimes doctors also start apheresis while cortisone therapy is still ongoing.
- First-line therapy if patients have responded well to apheresis in previous relapses or if the NMOSD presents in the form of spinal cord inflammation (myelitis).
Long-term therapy
The exact immunotherapy depends on the individual patient. The decisive factor is sometimes whether or not AQP4 antibodies are found in the patient’s blood. Doctors also take into account other factors such as disease activity and the patient’s age.
In principle, the following active substances, among others, can be considered for long-term treatment of NMOSD:
Eculizumab: This is an artificially produced antibody that inhibits the complement system – the defense mechanism that ultimately damages the nervous system in NMOSD. Eculizumab is administered as an infusion. Side effects often include headaches and upper respiratory tract infections. The most important risk is the occurrence of severe infections.
Tocilizumab: An artificially produced antibody that blocks the docking sites of the messenger substance interleukin-6. This mediates inflammatory reactions in NMOSD and ensures that B lymphocytes mature into plasma cells, which then release (auto)antibodies. The active substance is usually administered as an infusion, sometimes also as an injection under the skin. Possible side effects include increased infections and elevated blood lipid levels.
Inebilizumab: Another artificially produced antibody. Like rituximab, it binds to B lymphocytes, but to a different surface protein (CD19). The effect remains the same: other immune cells destroy the B cell in question. Doctors administer inebilizumab as an infusion. The most common side effects include infections (such as urinary tract infections), joint and back pain and infusion-related reactions (headaches, nausea, drowsiness, shortness of breath, fever, rash, etc.).
Azathioprine: This active substance is an immunosuppressant, i.e. it can suppress immune reactions. You can read more about its mode of action, use and possible side effects here.
Of the active substances mentioned, only eculizumab, satralizumab and inebilizumab have so far been approved for the treatment of NMOSD in the European Union, and eculizumab and satralizumab in Switzerland. Doctors use the non-approved active substances “off-label” in NMOSD patients.
It can take up to several months for the immunotherapy to show its full effect (depending on the active ingredients used). For this reason, patients are also given cortisone tablets in the initial phase to prevent flare-ups. They take the tablets for three to six months in decreasing doses.
Another treatment option, especially for certain cases, is infusions with high doses of antibodies, known as intravenous immunoglobulins (IVIG). Doctors administer them if, for example, a severe infection is an obstacle to immunosuppressive treatment. Those affected, including children, usually receive the IVIG once a month. The immunoglobulins are then intended to positively influence immune reactions.
