What is NMO?
What is NMOSD?
Neuromyelitis Optica (NMO, also known as Devic’s disease) is an autoimmune condition characterised by inflammation (attacks) of the optic nerves (optic neuritis) and spinal cord (transverse myelitis).
NMO Spectrum Disorder (NMOSD) is when a patient has a single or relapsing course involving just one area (either optic neuritis or transverse myelitis), AND they have the Aquaporin 4 antibodies in their blood.
The Immune System
NMO develops as the result of a defect in the immune system. The immune system has a role in producing antibodies against bacteria and viruses. This allows us, to recognise and destroy bacteria we have already encountered.
Unfortunately, when the immune system is not functioning properly it can produce antibodies against healthy proteins in the body causing an autoimmune disease. The majority of patients with NMO produce antibodies against a normal protein called Aquaporin 4.
Aquaporin 4 Antibodies
Aquaporin 4 (AQP4) is a water channel protein found on cells known as astrocytes that surround the blood-brain barrier, (a layer of cells responsible for preventing dangerous substances in the blood from crossing into the brain). It is presumed that the blood brain barrier is weakened in NMO, allowing the AQP4 antibodies to enter the central nervous system. This causes an inflammation and demyelination.
Most people (approximately 80%) have Aquaporin 4 (AQP4) antibodies present in their blood.
Inflammation and Demyelination in NMO
These words may sound complicated, but they are actually very straightforward.
Inflammation of the nervous system is similar to inflammation anywhere else in the body. It is a biological response to harmful stimuli (such as bacteria), with the aim to removing this stimuli and initiate healing. The bonding of Aquaporin 4 antibodies to Aquaporin 4 signals to the white blood cells to attack the ‘rogue’ protein. The white blood cells release many chemicals that lead to damage and swelling of the affected area causing loss of function. Nerves which make up the optic nerve and spinal cord are protected by a covering of fat and protein called the “myelin sheath”. This provides support for the nerve as well as acting as an insulator for the electrical impulses sent along the nerves. When the Aquaporin 4 antibodies attack the nervous tissue, they also damage the myelin sheath, a process called demyelination.
The combination of these processes causes the damage seen in NMO.
What are the causes of NMO?
The exact cause of Neuromyelitis Optica is not fully understood. NMO is an auto-immune condition similar to rheumatoid arthritis. The body’s immune system does not recognise some of its own cells and therefore attacks them. Attacks or relapses in NMO are usually due to transverse myelitis and/or optic neuritis.
Transverse Myelitis (TM)
Transverse refers to the inflammation being across the width of the spinal cord and myelitis refers to inflammation of the spinal cord. TM in NMO causes ‘long lesions’ (involving at least three vertebrae). The degree of weakness or numbness depends on the location and severity of the inflammation of the spinal cord. When the spinal cord in the neck is affected, all four limbs may be affected (as the nerves to the arms branch off from the spinal cord at the neck). The main symptoms of TM are muscle weakness in the legs (less commonly in the arms), altered sensations (pins and needles, numbness) in lower half of body, pain and bladder and bowel dysfunction. These symptoms may develop quickly over a few hours or gradually over weeks.
Optic Neuritis (ON)
Optic neuritis (ON) – is the inflammation of the optic nerve (which conducts messages picked up by the eyes to the brain to be interpreted into images that we see). It may be associated with eye pain on movement, blurred vision, double vision, problems seeing colours, visual field defects (where a certain section of a patients visual field is disturbed), scotoma (black hole in vision) and sometimes complete visual loss. It causes visual loss, typically in one eye at a time, but can occasionally affect both eyes simultaneously.
In NMO, optic neuritis can affect one eye, but occasionally it can affect both eyes at once.
At the very top of the spinal cord is a structure called the ‘brainstem’ which is an area that can be affected by NMO, an attack in this area is thought to be much rarer. Symptoms that may be associated with the brain stem are prolonged hiccoughs, nausea and vomiting and dizziness.
How could my condition affect me?
Every person has different symptoms and will require different levels of support and advice from different therapists.
Neuropathic (nerve) pain arising directly from damaged nerves in the spine, there are no particular triggers, this pain is described as burning, sharp, electrical shock, shooting or an uncomfortable numbness. Medication suggestions are Amitriptyline, Gabapentin, Pregabalin and Carbamazepine.
Nociceptive (musculoskeletal) pain often has a more obvious cause, such as banging your knee. In NMO, the most common cause is pressure on joints from altered gait (the way you walk). Medication suggestions such as Paracetamol or Ibrufen may be helpful.
Increased muscle tone and spasms arises from damaged nerves in spinal cord that affects the control of muscles, including when they contract and relax. This can present as prolonged contractions of the muscles, which are called spasms. Medication suggestions are Baclofen, Tizanidine, and Gabapentin.
Tonic spasms this is a painful spasm of the muscles that lasts seconds to minutes but frequently. Often it’s controlled by Carbamazepine at low doses.
Joint stiffness is a discomfort after a period of inactivity (such as waking up in the morning or sitting for an extended period of time. Medication suggestions are Baclofen, Tizanidine, Dantrolene. Exercises and stretching are often useful.
Muscle weakness is a reduction in the strength of one or more muscles affecting mobility (legs) or activity (arms). There are no medications to improve weakness. Exercise and stretching are good.
Bladder symptoms include urgency, hesitancy, frequency and nocturia (passing urine at night) and retention (unable to pass urine) due to damage on the spinal cord. Medicines like Oxybutynin, Tolterodine may be helpful or learning self-catheterisation, (a very simple technique).
Bowel symptoms mainly constipation, urgency and sometimes faecal incontinence are also due to damage on the spinal cord and immobility. Laxatives, a high fibre diet and fluids as well as abdominal massage may be useful.
Sexual dysfunction where men may experience difficulty getting an erection, or reaching orgasm, and women may also have difficulty reaching orgasm due to a lack of sensation and numbness.
Osteoporosis (brittle bones) may be the result of long-term use of steroid medication or a lack of weight-bearing activities.
Depression – changes in lifestyle associated with the complications of NMO can increase the risk of developing depression.
Why do Symptoms persist after the relapse has recovered?
When a relapse occurs there is inflammation and swelling in the brain, so messages cannot get from the brain to their target, e.g. a relapse of the spinal cord does not allow nerve messages to pass to the area below the inflammation causing the symptoms of transverse myelitis.
Over time there is some spontaneous recovery and symptoms may improve over 2-6 months. However, if the nerves have been damaged or destroyed new pathways cannot be made, resulting in permanent damage.
Some people will have very few residual symptoms from a relapse, whilst others may have more. The severity will also be different between individuals.
Symptoms such as:
- Loss of vision as a result of damage to the optic nerve.
- Paralysis of limbs due to damage to the spinal cord in the neck, which may affect legs and arms causing weakness and little function.
- Breathing difficulties due to damage in cervical (neck) area of spine causing muscle weakness which, in extreme cases will require artificial ventilation (a machine that helps you breathe).
OR symptoms may be indirectly caused resulting from damage of the nerves.
The symptoms are treated to try and improve your daily living either with medication or therapy. The medications do NOT prevent further relapses. There is no ‘right’ drug as individuals respond differently to different treatments. The overall aim of symptom management is to control or reduce symptoms impairing functional abilities and quality of life. You may have to trial several regimes to find the most suitable drug for you.
What about managing permanent disability?
Many symptoms overlap with each other for example pain interferes with all activities such as housework, work, exercise and consequently has an impact on a person’s mood, affecting family relationships. Though problems can be tackled on their own a multi-disciplinary approach is essential to provide holistic care.
Combined efforts by doctors, nurses, occupational therapists, physiotherapists, orthoptics and social services will help the complex requirements of the individual patient. Visual aids, walking aids, motorised wheelchairs, and home adaptations can improve quality of life remarkably and many patients live an active life.
Can deficits that are present for many years be reversed?
It is rare for this to happen. Physical adaptations (modifications in house, wheelchair etc.) and lifestyle modifications (change of job, moving to a single floor house) should be planned in advance and money spent wisely rather than waiting for ‘miracles to happen’ or trying out costly alternative medicines or exotic cures.
The medical history and clinical examination taken by a neurology specialist will include any previous symptoms or problems in the past to suggest a diagnosis of NMO.
It is also important to confirm the diagnosis by special investigations:
Magnetic Resonance Imaging (MRI) of the brain and spinal cord
MRI has become a key tool in the diagnosis of NMO. Magnetic fields are used to create images of the brain and spinal cord. The person lies in a long tube. The MRI scan takes approximately 30 minutes, it is painless but noisy and you have to lie very still.
The MRI of the brain is often normal in NMO although up to 60% people with NMO may have lesions on the brain, most are asymptomatic. These lesions tend to differ from MS lesions.
The MRI of the spine often shows inflammation extending over three vertebrae, usually affecting the cervical and thoracic areas, especially during a relapse. In MS, the spinal lesions tend to be short-segments (less than two vertebrae).
Cerebral Spinal Fluid (CSF) is the watery liquid that surrounds and protects the brain and spinal cord. A lumbar puncture (LP) requires a small amount of CSF to be drawn from the spinal cord with a needle. This only takes a few minutes and hurts a little and so is normally done under a local anesthetics. Some people can get a headache after the procedure (due to leakage of CSF). It can be avoided by lying flat for a few hours after the test and having plenty to drink.
If done during an acute attack of TM there may be increased white cells and raised proteins. A special pattern of antibody proteins called oligoclonal bands (OCB) are usually absent in NMO.
Aquaporin 4 antibody (blood test)
The presence of Aquaporin 4 antibodies is highly specific to a diagnosis of NMO or NMO spectrum disorder. Most people (approximately 80%) have Aquaporin 4 antibodies present in their blood.
An ophthalmologist is trained to pick up even very small changes in a patient’s vision.
Opthalmoscopy (looking at the back of the eye with an ophthalmoscope) may show swelling of the optic disc. Often swelling is not seen, as the demyelination can be further away from the eye (retro bulbar neuritis).
Visual Evoked Potential (VEP)
Electrodes are placed on the scalp and measure the speed of nerve messages along the optic nerve from the eye to brain in response to being shown a flashing chessboard pattern on a computer screen. Damage to the optic nerve shows slower response time.
Visual Field Tests
These show whether there are any areas of your peripheral vision missing, which can indicate optic neuritis.
Low Contrast Test
By testing a person’s vision against increasingly faded images, it is possible to test how ‘washed out’ a persons vision has become.
This is a series of 13 images that detect minor changes in colour vision sensitivity.
Optical Coherence Tomography (OCT)
This is a very fast scan that can measure the thickness of the nerve fibre in the optic nerve. At present this is more a research tool than a clinical marker.
Diagnostic Criteria of NMO
Two Absolute criteria:
- Optic Neuritis
- Transverse Myelitis
At least 2 of 3 supportive criteria:
- Presence of continuous spinal cord MRI lesion extending over three or more vertebral segments.
- MRI brain not satisfying diagnostic criteria for MS.
- Aquaporin 4 antibody present in serum.
NMO Spectrum Disorder
Optic neuritis OR Transverse myelitis AND presence of Aquaporin 4 antibodies in serum.
What is a relapse?
A relapse, or an ‘attack’ of NMO, occurs when there is inflammation within the nervous system. In NMO, this inflammation is usually within the optic nerve and the spinal cord. The inflammation causes people to experience new symptoms, or recurrence of symptoms that they have had previously.
Why do relapses happen?
We don’t understand what causes or triggers a relapse. Relapses are usually unpredictable and there is nothing that you may have done to cause them. Occasionally, a relapse may be triggered by infection or by stress.
What symptoms do relapses cause?
In people with NMO, relapses usually affect either the optic nerve or the spinal cord.
When relapses affect the optic nerves they cause problems with the vision. Symptoms normally come on over a period of hours or days, or people may wake up one morning with visual symptoms. Some people notice that their eye is painful when they look around, or have pain behind the eye. This may last for a few days. At its mildest, this can cause colours to look faded or ‘washed out’. In more severe attacks, vision may be blurred or be lost completely.
Brief ‘stubbing’ pain in and around the eye lasting only a few seconds or minutes is unlikely to be caused by a relapse. Many people with NMO find that their vision varies from day to day, for example if they are tired.
People with NMO may also experience relapses affecting the spinal cord. The spinal cord controls strength and sensation in the arms, legs and trunk and is also involved in bladder and bowel control. Inflammation in the spinal cord may cause many different symptoms including:
- Weakness in the arms and/or legs,
- Tingling, numbness or abnormal sensations in the arms, legs, groin or trunk
- A band like sensation around the trunk, like being squeezed or wearing a corset
- Severe pain in the neck or between the shoulder blades
- Problems with the bladder such as difficulty or inability to pass urine, feeling of incomplete bladder emptying, or incontinence of urine
- Constipation or loss of control of bowel movement
Each of these symptoms may occur individually, or people may experience a combination of symptoms. Usually symptoms develop over hours or days. They are significant if they last for longer than 24 hours.
What should I do if I think I’m having a relapse?
It is important to remember that most relapses of NMO need to be assessed and treated promptly. Please follow the guidelines below.
If you feel that there is a sustained deterioration in your vision or experience any of the symptoms described above which lasts for longer than 24 hours, please contact your NMO Nurse Specialist.
- Kerry Mutch
NMO Nurse Specialist
Walton Centre for Neurology
0151 529 8357
- Rosie or Sandra
NMO Nurse Specialists
John Radcliffe Hospital
Your NMO nurse will take a history of your current symptoms, take into consideration current treatments, other illness (such as colds, infections) and how the symptoms are currently affecting you.
Following discussion with the medical team, a plan will be devised on how best to assess and treat your relapse. This may involve asking your local neurologist to see you, or if possible ask you to come to your nearest NMO centre.
Every patient, and every relapse will have different features and the treatment will depend upon your individual needs.
It is important that you are assessed quickly during a relapse, as early treatment may prevent long term damage.
Recovery from Relapses
The time taken to recover and the amount of function recovered after a relapse can be affected by many factors and varies hugely from person to person. An important factor to always consider is that any new symptom or sustained worsening of an existing symptom (over 24hrs) should be reported to either a general practitioner or NMO team for further assessment. Early assessment and treatment may prevent long term damage.
Acute Relapse Management
In NMO disability accrues from relapses of the optic nerves or spinal cord.
Most relapses of NMO need to be assessed and treated promptly
If a patient presents in A+E or GP Practice with acute symptoms that have developed over 24 hours.
Optic Neuritis Symptoms
- Pain behind eye
- Vision may be blurred or lost completely
- Loss of colour vision
Transverse Myelitis Symptoms
- Weakness in arms and/or legs
- Numbness or abnormal sensations in arms/legs/trunk
- Severe pain between shoulder blades
- Tight banding around the trunk, like being squeezed
- Retention of urine
Rule out infection and treat with antibiotics if necessary.
Intravenous methylprednisolone 1gram for 5 days
orally methylprednisolone 500mg for 7 days.
Please contact either NMO Centre for further Information and Advice
John Radcliffe Hospital, Oxford 01865 231 905
Walton Centre Foundation Trust, 0151 529 8357
If you have problems out of hours, contact on-call neurologist at either hospital for advice.
In NMO disabilities can accumulate with each acute attack including visual problems and/or paralysis of limbs. Progressive phase in which patients have gradual neurological decline between attacks is rare.
Management of NMO Suggested NMO Treatment Algorithm
At present there is no cure for NMO so management focuses on the following key areas:
- Treating acute attacks/relapses
- Preventing relapses
- Treating the residual symptoms of the relapse
A high dose steroid, Methylprednisolone (solumedrol) is usually given during a relapse. Steroids work by dampening the immune system and reducing inflammation around the site of nerve damage. They are given:
- Intravenously (through a vein) 1g daily for 3-5 days or
- Orally (taken by mouth) 500mg-2g daily for 3-5 days,
- In combination of intravenous and oral, followed by
- A tapering course of oral steroids over several months.
If steroids don’t help, what next?
When attacks progress or do not respond to corticosteroid treatment, Plasma Exchange is most frequently used or sometimes Intravenous Immunoglobulins may be given.
Plasma Exchange (PEX)
This is a technique in which the blood is drawn out of the body and the plasma (which contains the antibodies) is separated. The blood is then returned back into the body with fresh plasma. However this will only remove the antibody from the blood – the white cells that make the antibody (B cells) are still present in the blood.
There is some evidence from controlled clinical trials that this helps patients with NMO.
In NMO disabilities are accumulated from each acute attack including visual problems and/or paralysis of limbs. So it makes sense to try and prevent relapses. Immunotherapies are powerful medicines that dampen down the activity of the body’s immune system. Drugs such as Prednisolone, Azathioprine, Methotrexate or Mycophenolate are used to allow reduction of steroids. All these treatments increase the risk of serious infections therefore blood will be monitored for full blood count, kidney and liver function.
Drugs commonly used in NMO
Oral Prednisolone tablets
Steroids are good immunosuppresants. After a diagnosis of NMO, oral steroids are used until other treatments are in place (Azathioprine for example can take 3-6 months to get to an effective level). In many patients relapses may occur even on gradual reduction of the steroids and they may need to continue on a low dose of steroids for longer periods. Often a maintenance dose is required.
Long-term treatment side effects including; weight gain, acne, indigestion, cataracts, osteoporosis (thinning of the bones), deterioration of the head of the thigh bone and diabetes. To reduce the side effects of Prednisolone other medication is taken such as an antacid Omeprazole or Lansoprazole, tablets for bone protection Alendronic acid and calcium supplements.
Azathioprine (also known as Immuran), Methotrexate and Mycophenolate (cellcept) are all considered to be equally effective at suppressing the immune system. They all have side effects that are well understood, but need to be explained to you before you take the medication.
A certain percentage of patients will either not tolerate or relapse whilst on the above medications. If this happens, your doctor will consider a different medication to try and prevent relapses.
Other treatments available
These medications are considered to be “2nd line” treatments (i.e. used after trying the above medications). As with most medications, the more effective they are, the higher the risk of side effects. This is always a consideration when offering you medications.
This is an intravenous medication. It is from a family of drugs called “monoclonal antibodies” which are capable of depleting B-cells that are responsible for producing NMO antibodies.
This is another well-established chemotherapy that suppresses the immune system. There is very little evidence for its use in NMO.
Complementary therapies can be used to target a specific physical, mental, emotional or spiritual problem, or as a preventative measure or purely for relaxation, and may increase your feeling of well-being. Reflexology, Massage, Reiki or Acupuncture may improve relaxation, sleep patterns, relieve pain or reduce stress and tension.
There is little research to show how effective many of these treatments may be.
Future Treatments for NMO
Over the last few years research has increased worldwide, particularly assessing immunology, radiology, causes and possible future treatments for NMO. However as the condition is so rare, it is difficult to organise clinical trials (and hence the need to identify as many people with NMO as possible).
Please speak to your local NMO team to get the most up to date information on trials and research.
What about stem cells?
Currently, research into stem cell treatment is only in its initial stages. Some researchers are hopeful that stem cell treatments may be helpful for people with Neuromyelitis Optica in the future.
More About NMO
How common is NMO and NMOSD?
NMO is a very rare condition. There are few population-based studies in NMO. In Europe, it is estimated that there is one case of NMO for every 100,000 people potentially affecting less than 1000 people in the UK.
NMO may be more common in people of Asian and African descent.
NMO can affect any age group.
NMO is predominantly a female disease with a ratio of 4 females: 1 male being affected.
Who is at risk of developing NMO?
NMO is not hereditary (it is very rarely found in more than one family member). People who inherit a tendency to develop an autoimmune disease are at increased risk of developing another autoimmune disease, such as diabetes or thyroid disease.
You cannot pass on an increased risk of getting NMO to your family.
It is not possible to catch NMO from another person.
Are there risks for patients with NMO who wish to have sexual intercourse?
There are no risks of passing this disease through bodily contact to a sexual partner. Also there is no specific risk for a patient with mobility issues in having sexual intercourse; it will not make your NMO worse.
Should an NMO patient consider having/fathering children if there is a risk of passing NMO on to children?
NMO is not passed on in genes. Due to NMO being very rare, numbers of pregnancies within the patient group are low. Therefore this decision has to be made by the patient.
How severe can NMO be?
Every person is affected differently. Some may have only a mild attack of optic neuritis and myelitis with near complete recovery and no further relapses with or without treatment. Some people with NMO may lose vision in both eyes or be paralysed in all four limbs due to damage to the spinal cord in the neck. On rare occasions breathing difficulties requiring artificial ventilation and death can occur due to muscle weakness or involvement of the brainstem.
How are people affected 5 years post diagnosis?
In an epidemiology study, about half the patients with relapsing NMO had significant visual loss in at least one eye and/or could not walk due to leg weakness and was reliant on a walking aid such as a walking stick, frame or wheelchair.
However this information was a generalisation drawn from an early study based on patients referred to a major hospital (i.e: they may already have been significantly impaired or had severe disease, and may not be representative of all patients. Furthermore, some patients were not treated. Early treatment may lead to better outcomes. With research and further information, prompt treatment for relapse and preventative relapses the future prognosis is positive in reducing/ minimalist disability.
Are there any dietary considerations/restrictions for people with NMO?
A healthy diet with adequate vegetables, fruits, calcium and vitamin D (remember steroids can cause bones to weaken) vitamins and proteins is needed to keep the body fit. It is often easy to put on weight due to side effects of steroids, and/or lack of exercise.
Is there a link between migraine and NMO?
Migraines do not cause NMO, but there is some anecdotal reports of patients with NMO experiencing migraine like headaches. It is important to remember that headaches and migraine are quite common in the general population.
Is there anywhere that can help with filling out of forms, i.e. DVLA, living allowance etc.?
Citizens Advice Bureau (CAB) are able to help with these forms. We are able to clarify details (i.e. definitions of your disease/physical impairment) and we can be used as referees for DLA reports if needed.
Can immunisation lead to, or exacerbate NMO? Does NMO and immunosuppression restrict my ability to travel abroad?
Providing you have the correct immunisations for the country you are visiting you should be safe to travel. Remember to be vigilant for coughs/colds/urine infections whilst away and ensure your travel insurance company is fully aware of any medical conditions. Please check if the vaccine is a live virus e.g. yellow fever as there may be restrictions
What does the future hold for NMO?
NMO is an uncommon disease. In such diseases clinical studies and trials take a long time. (See section for researchers and collaborators) Such diseases normally go through the stages of:
- Characterisation of features, identifying natural history and risk factors.
- Tests that support the diagnosis evolve such as MRI and tests that actually diagnose the condition like NMO Immunoglobulin Studies on patients and biopsy materials will need to be done.
- When a good number of motivated patients and researchers are available, trials that test the effectiveness of the current and new, medications should be undertaken.
Ultimately we hope that rapid, definitive and easily available diagnostic tests and potent drugs with few side effects will develop and early effective treatment will allow a normal life for people with NMO.