An Overview of CIDP

Acknowledgments

This booklet has been written for patients who have been told that they may have CIDP (chronic inflammatory demyelinating polyradiculoneuropathy), and for their relatives and friends. It aims to explain accurately and honestly what CIDP is, and hopefully will answer some of the questions you may have. If you do not understand or are worried by any of the information offered here, do ask your doctor to explain.

The degree of severity of CIDP and the way it effects people vary enormously from one person to another. There is no typical CIDP; therefore one general description and one certain prognosis are not possible. This booklet describes the common symptoms.

'chronic' refers to the gradual course of the illness, often over a long period of time;
'inflammatory' means there is strong evidence that it is inflammation that causes the nerve damage;
'demyelinating' means that the damage is primarily to the insulating myelin sheaths around the nerve fibres and
'polyradiculoneuropathy'; 'poly' means many, 'radiculo' means root, 'neuro' means nerve and 'opathy' means disease; so polyradiculoneuropathy means a disease of many peripheral nerves and their roots (which are the points of origin of the peripheral nerves from the spinal cord). The central nervous system is the brain and spinal cord and the role of the peripheral nerves is to bring in and take out the messages from the central nervous system to all parts of the body.
CIDP is a very rare disease of the peripheral nervous system involving gradual development of weakness and loss of sensation, predominantly in the arms and legs.

The incidence (the number of new cases each year) and prevalence (the total of all people affected at one time) of CIDP are very difficult to determine because of its rarity. The incidence of CIDP is estimated to be between 12 and 15 per year whilst the prevalence is approximately 600 sufferers in any one year in Australia. The incidence of Guillain-Barré Syndrome (GBS) is estimated at 340 per year with a similar amount of prevalence.

The disease may start at any age, but is slightly more common in young adults. It is more common in men than women. For women, relapses are slightly more likely to occur during a pregnancy year. It is not hereditary; ie it is not passed on to children. It is not infectious; meaning it is not caught from, or transmitted to, anybody else. It is not a psychiatric or 'nervous' disorder.

No one is sure what causes CIDP. Current research is investigating the role of preceding infections, immunisations and other events before the onset or relapses of CIDP. To date there is no general agreement on what causes the disease, however it is known that the immune system attacks the nerves but it is not known why.

The severity of CIDP is extremely variable and the symptoms you experience may vary considerably from those suffered by others. Initially your symptoms may be vague and confusing to both yourself and to your doctor. Subjective symptoms such as fatigue and sensory disturbance are difficult to communicate. In the early stages it may be difficult for you to persuade your doctor that there is anything physically wrong.

Early symptoms usually include either tingling (pins and needles) or loss of feeling (numbness) beginning in the toes and fingers, or weakness, so that legs feel heavy and wooden, arms feel limp and hands cannot grip or turn things properly. These symptoms may remain mild and result in only minor disruption to normal life. Alternatively they may become progressively and gradually worse over a period of several weeks, months or even years - sometimes, but very rarely, to the extent that the person is bed bound and has profound weakness of the arms.

CIDP usually presents with both weakness and sensory (meaning altered sensation) symptoms, sometimes with weakness alone and rarely with sensory symptoms alone. The arms and legs are usually affected together, the legs more than the arms. Prickling and tingling sensations in the extremities are common and may be painful. Aching pain in the muscles also occurs. Tendon reflexes are usually lost. As the disease becomes more severe, a tremor may develop, usually in the upper limbs. Very rarely facial weakness may develop.

CIDP can be difficult to diagnose as there is no conclusive diagnostic test for it. The history of symptoms is often vague with varying signs that could be symptoms of a number of conditions. Therefore a long period of time may elapse before a suggestion of CIDP is made.

CIDP is closely related to Guillain-Barré Syndrome (GBS), which is also due to inflammation of the peripheral nerves. Symptoms experienced by those with this condition are similar, but GBS is a more acute condition in which symptoms appear rapidly over a period of days or a few weeks. GBS patients usually make a spontaneous recovery over a period of weeks or months and the symptoms rarely re-occur.

CIDP is a chronic condition and is only distinguished from GBS by virtue of its pattern of progression. In GBS the low point is reached within four weeks whereas in CIDP the initial progressive phase lasts longer, usually much longer. Some CIDP patients are initially diagnosed as having GBS. Only when the deterioration continues over an extended period, or when one or more relapses occur after a period of improvement, is the illness reclassified as CIDP.

The diagnosis is made primarily on clinical grounds not laboratory tests. This means that your doctor has to rely on your history and his clinical examination fitting into the pattern of CIDP. He will particularly want to know of any recent possible toxin exposure (insecticides, solvents), medication, alcohol intake, tick bites, family history of nerve disease, or symptoms of any coincidental illness, such as diabetes or arthritis. Any of these may lead to a different diagnosis.

Essential criteria for a positive diagnosis of CIDP are:
• progressive weakness in two or more limbs due to a polyradiculoneuropathy;
• loss or diminution of tendon reflexes;
• progression for more than eight weeks or recurrence or relapse and
• evidence of damage to peripheral nerve myelin from nerve conduction tests.

Investigations will include blood tests; usually a lumbar puncture and nerve conduction tests with an electromyogram (EMG) machine, and possibly a Magnetic Resonance Image (MRI) scan. A nerve biopsy may also be performed.
The lumbar puncture involves lying on one side and having a needle inserted under local anaesthesia between the vertebrae into the sac of cerebrospinal fluid which surrounds the nerve roots. The idea is worse than the procedure really and it does not usually hurt. The cerebrospinal fluid often contains much more protein than usual while the cell content remains normal. If different changes are found your doctor will have to review the diagnosis with even more care.

The EMG is an electrical recording of the muscle activity. If a nerve is stimulated with a brief electrical pulse (felt like a sharp tap or jolt) muscle activity can be recorded and the speed of nerve conduction worked out. Usually in CIDP nerve conduction is markedly slowed or even blocked. The test lasts about half an hour. It can be uncomfortable but is quite harmless.

The Magnetic Resonance Image (MRI) Scanner is a more recent diagnostic tool and takes pictures, similar to X-rays, of the brain and spinal cord (ie of the central nervous system). The procedure involves your upper body being slid into the tunnel-like scanner and remaining absolutely still during the scanning process which lasts about half an hour. It is entirely painless. MRI scans are used to eliminate the possibility that damage has occurred to the central nervous system that could alter the diagnosis.

Sometimes a nerve biopsy may be performed. This involves a small piece of nerve being removed, usually from the side of the heel of the foot, to be examined in the laboratory. This allows the doctor to see any inflammation and the type of nerve damage. Having the biopsy test involves the use of local anaesthetic and the area may be sore for a week or two afterwards. You may be left with some loss of sensation in a very small area of the foot.

It is helpful to subdivide CIDP into four subcategories that are characterised by the pattern of the disease. These are:
'subacute' where symptoms continue to progress and worsen for at least four weeks but not more than eight weeks before levelling off or improving;
'chronic progressive' where symptoms continue to progress and worsen for a period exceeding eight weeks;
'chronic relapsing' where more than one episode in which symptoms progress and worsen for a period greater than four weeks and
'recurrent GBS' where each bout has a progressive phase of less than four weeks.
Clearly the cut-off points used are somewhat arbitrary.
The most common form of the disease is the chronic relapsing form with spontaneous improvement or remissions. About 80% of patients have this form of the disease. About 10% of patients have the subacute disease, which plateaus and then disappears spontaneously. Those with recurrent GBS form only a small percentage of CIDP patients.

Thus some people only have a single 'bout' of CIDP lasting for several months or years, after which a spontaneous recovery may be made. Others have many bouts in between which spontaneous remission and recovery occurs. After each bout the patient may be left with some residual numbness and weakness and sometimes discomfort. For many this will not seriously interfere with their lives, and they are able to continue with or resume their normal occupation. However a very small number are left severely disabled and may be dependent on a wheelchair or even bed bound. There is only a very unfortunate few for whom the disease continues to progress without remission.

The function of your brain is to interpret sensations and initiate movements and other responses. This activity depends on a complex communication system of nerves running to every part of your body via the spinal cord. Each nerve in this communication system can be compared to an electric cable. The inner part of the nerve, the axon, is made of conductive tissue and carries messages or impulses throughout your body - like the wires in an electric cable. The axon is surrounded by a layer of fatty substance, the myelin sheath, like the insulating cover on a cable. The myelin helps the conduction of messages along the nerves as well as insulating and protecting the nerve.

The symptoms of CIDP are due to inflammation and damage to the peripheral nerves and their roots. The peripheral nerves connect your central nervous system to your skin and muscle. CIDP is probably an autoimmune disease, ie one in which the immune system attacks its own body. The most likely mechanism is that the immune cells, called lymphocytes, somehow or other make a mistake and attack the nerves. The main part of the nerve that is attacked is the insulating sheath, or myelin.

The way in which the lymphocytes are tricked into attacking the body is still the subject of research. The lymphocytes may cause the formation of chemicals called antibodies that circulate in the blood and damage the myelin. Attempts to identify these antibodies have so far been only partially successful.

Fortunately the myelin sheath can be replaced within a few weeks or months by the myelin-forming cells named Schwann cells. If the nerve axons are damaged these can also re-grow, but this is much slower. Research is continuing into the underlying causes and mechanisms of the disease.

Although CIDP is a chronic condition with no known 'cure', several different treatments have been found to be helpful. They all act by suppressing the damaging autoimmune response. This in turn reduces the disabling symptoms of the disease. Examples are steroids, immunosuppressive drugs, plasma exchange and intravenous immunoglobulin.

Obviously suppressing the immune response cannot be undertaken lightly because it runs the risk of suppressing normal immune responses to infections. The decision whether to try these treatments has to be tailored by your doctor to your individual needs. However it is reassuring to know that treatments are available, that demyelinated nerves can repair themselves, and that some patients get better without treatment.

Due to the small number of patients and because most of the treatment methods are quite new, there is limited evidence available of the relative effectiveness of different treatments. Some patients respond to one method and not to others. There is only a very unfortunate few that cannot be helped by any of these treatments.

Controlled trials have demonstrated that cortisone-like steroid are beneficial in CIDP. This group of drugs, which includes Prednisolone, is similar to the normal cortisone made by the adrenal gland as part of the normal mechanisms for coping with stress. A wide range of dosage schedules has been used and no work has been addressed to the question of which is best.

The high risks of serious side effects resulting from the prolonged use of high dose steroids are well known. These include osteoporosis (thinning of bones), cataracts, diabetes, hypertension (raised blood pressure), obesity and myopathy (muscle weakness). Steroid treatment also suppresses your normal production of cortisone, sometimes for up to a year after stopping. If you are undergoing stress such as an operation, your anaesthetist needs to know, as extra cortisone may need to be injected at the time. If the dosage levels required to control CIDP appear unacceptably high or unacceptably prolonged, it may be suggested that other immunosuppressive drugs be used.

Clinical evidence suggests that immunosuppressive drugs help. These include Azathioprine, Cyclo-phosphamide and Cyclosporin. Azathioprine is the most widely used in the treatment of CIDP. Regular blood tests (such as blood count, liver or kidney function) are required to check for side effects that can be avoided by stopping these drugs or reducing the dose. In addition, the use of these drugs carries the theoretical side effect of increased risk of developing cancer, but in practice this increased risk is very small.

Plasma exchange involves being connected to a machine which can separate the blood cells from the fluid or plasma. In an on-line process, blood is continuously taken from the patient, separated, the plasma is discarded, the blood cells are mixed with clean plasma (which has been collected from blood donors) and returned to the patient. (The process is not unlike that used in kidney dialysis). At each session about two or three litres of plasma are exchanged. The procedure is usually repeated several times over about two weeks until sufficient plasma has been exchanged. The procedure is safe and the risks are small. It is uncomfortable but not painful, however some patients find that it leaves them feeling tired for a day or two.

The blood donor plasma carries a small risk of hepatitis and other viruses despite the careful screening process at the Red Cross. Because of this a protein extract of plasma called albumen is usually used as it can be treated to kill viruses. This should be discussed with your doctor. Clinical trials have demonstrated the benefit of plasma exchange for CIDP. For some patients it allows control of the disease to be maintained when immunosuppressive drugs are insufficiently effective. Some patients however do not appear to respond to plasma exchange. For patients who do respond, regular plasma exchange (ie monthly) can help to maintain good function.

There is increasing evidence of the effectiveness against CIDP of intravenous (IV) infusions of immunoglobulin (IG) (- also called gammaglobulin or antibodies). Antibodies usually react with and neutralise germs that get into the body. These are 'good' antibodies. Sometimes antibodies attack the body itself and these 'bad' antibodies, or autoantibodies, may cause CIDP. However there are also anti-autoantibodies, which block these bad antibodies. It may be these anti-autoantibodies in immunoglobulin which help.

Whatever the explanation, some people with CIDP do seem to get better after having immunoglobulin. Research is going on to find out which patients. Unfortunately IVIG is often in short supply. IVIG is given by infusion into a vein, usually every day for 5 days. Each infusion takes about 2 hours. The immunoglobulin used in Australia is very safe, but abroad there have been very rare problems with transmission of hepatitis. There is a rare (about 1 in 40,000) risk of serious allergic reaction at the start of each infusion, so careful monitoring is essential. Some patients only need one course. Others need repeated courses. As with plasma exchange, regular (ie monthly) IVIG helps maintain function in some patients.

Physiotherapy has an important role to play in the assessment and management of CIDP. It helps to maximise a patient's physical potential, particularly where weakness is the predominant problem.
The aims of physiotherapy are to:
maximise muscle strength and minimise muscle wastage by exercise using strengthening techniques;
minimise the development of contractures (or stiffness) around joints; a physiotherapist can advise on passive stretching techniques to help maintain full range movement at joints;
facilitate mobility and function; sometimes, if muscles are very weak, function can be improved by the use of splints and
provide a physical assessment which may help in planning future management.

CIDP may follow a pattern of relapses and remissions or a more gradual increase in symptoms. During a relapse new symptoms may occur or old symptoms that had previously subsided may reoccur. Relapses can last for several months and may be relatively slight or quite severe. A remission occurs when the symptoms experienced during the relapse disappear either partially or completely for a period of time that may last weeks, months or even years.

CIDP does not always have these patterns of being 'better' or 'worse'; sometimes symptoms can gradually increase over a period of many years and it may be difficult to identify 'better' or 'worse' times.
It is impossible to predict with certainty how CIDP is going to affect an individual in the future. The pattern of relapses and remissions varies greatly from person to person. A period of relapse can be very disturbing but many people make a good recovery. Coping with this uncertainty is one of the most difficult aspects of 'living with CIDP'. You should try to accept this variability without getting too worried about it.

A diagnosis such as CIDP of a chronic condition with an uncertain prognosis may well throw a strain on family and other relationships. You may find it difficult to accept help when you need it or your family and friends may feel that they cannot give help or become overprotective towards you. It is difficult to carry on family life as if nothing has happened. Everyone concerned may have to take on new roles. If you and your family and friends are able to speak openly and honestly with each other you will probably find that you are able to help each other through difficult times with the result that the bonds are strengthened.

Instinctively children are aware that something is wrong and that you are worried. It is important that their questions are answered as and when they occur. Older children can become surprisingly mature and a source of strength. Trying to keep your problems to yourself will not spare them any anxiety.
Many chronic illnesses can have a major effect on your sex life and it is important to remember that you are not alone in this. You and your partner should talk to your doctor about it. Referral to an experienced counsellor may be a great help. Don't give up.

It is important to build a good relationship with your doctors, both GP and specialist. Because of the rarity of the illness, many doctors will not have encountered it before. The symptoms are difficult to describe and may not be taken seriously at first. Each case of CIDP is different, and relapses, if they occur, may bring new symptoms and problems. Because of the variability in severity and progression of the disease, the doctor will not be able to give you a definite prognosis.
Although there is not one single overall treatment for CIDP, there is much that your doctor can do to help. Each person responds in different ways to different treatments. A period of experimentation with different treatment regimes is likely to be necessary in order to discover the regime that is most appropriate for you.

It is not just our physical condition which undermines our health. Our emotional and psychological attitudes play a big part in keeping us healthy.

It is likely that your symptoms of CIDP mean that for some months and sometimes years you can no longer follow the same life-style or do all the things you used to do. It is natural to mourn the loss of these. However CIDP does not mean your life has come to a stop. It may mean that you have to adapt to a different life-style that suits your own capabilities and limits. When possible think positively. It is essential to turn ourselves to our capabilities rather than our inabilities. This takes a great deal of effort, determination and often courage. It is far better to achieve the possible than to fail the impossible.

You should follow as healthy a life-style as possible. This will help to prevent other illnesses and infections that have been shown to trigger relapses. A nutritionally balanced diet will ensure you are getting all the vitamins and minerals you require. There is no evidence of any special dietary requirements for CIDP sufferers. It is sensible to keep your weight down, since more weight is more difficult for weak legs to carry.

Regular exercise is important for overall health, and should be taken according to individual limits and capabilities. Over exertion causes fatigue. However, a little regular exercise will help to minimise muscle wastage and give you a good feeling of well being. Any form of exercise that you enjoy and can comfortably follow will prove beneficial. Ask your physiotherapist to show you. Adequate rest periods are essential to avoid fatigue. Stress and tension may irritate the symptoms of CIDP and relaxation will allow you to unwind and recharge.