NORD gratefully acknowledges Richard Hughes, MD, Cochrane Neuromuscular, MRC Centre for Neuromuscular Disease, National Hospital for Neurology and Neurosurgery, London, UK, for assistance in the preparation of this report.
Guillain-Barré syndrome (GBS) is a rare, rapidly progressive disorder due to inflammation of the nerves (polyneuritis) causing muscle weakness, sometimes progressing to complete paralysis. GBS affects approximately only one or two people each year in every 100,000 population. Although it’s precise cause is unknown, about half the patients have a gastrointestinal or respiratory infection a few days before the onset. There is strong evidence that the immune response to the infection produces a so-called autoimmune response which damages the nerves causing weakness and loss of sensation. In milder disease the damage only affects the nerve sheaths and blocks the passage of nerve impulses. This can recover in a few weeks. In more severe disease the autoimmune response damages the conducting cores of the nerves. This may take longer to recover and some people have permanent weakness.
Weakness usually begins in the feet and spreads up to the arms and trunk. Sometimes it spreads to the breathing muscles, face and throat. In up to a quarter of people with GBS, the breathing muscles become so weak as to require temporary mechanical support of respiration on a breathing machine. Feelings of tingling, pins and needles (paresthesias) and numbness (loss of feeling) are common. These reflect damage to the sensory nerves that convey feeling from the skin and joints. The abnormal feelings are usually worst in the feet and hands. The tingling may be painful and pain in the muscles may occur. The symptoms usually progress over about two weeks but the progression may be as short as one day or as long as four weeks. Symptoms usually affect both sides of the body equally.
Most people only have symptoms in their arms and legs but severely affected people have more serious symptoms. They may have difficulty swallowing and become breathless. They may have difficulty or unable to empty the bladder. Their pulse may go too fast or too slow and the blood pressure may rise too high or fall too low. Modern medical and nursing care can cope with all these problems as explained below.
Symptoms vary widely from patient to patient. Some people only develop mild weakness not affecting walking and lasting only a few weeks. Others become completely paralyzed so that they cannot even move their eyes. Improvement typically starts days to several weeks after the worst has been reached and people go on improving for several months. About 20% of patients still have disability for more than a year, for instance needing aids to walk. In people left with severe weakness, slow improvement continues for at least two years.
The cause of GBS is inflammation of the peripheral nerves, which take messages to and from the skin and muscles to the brain and spinal cord. There is strong evidence that the cause is autoimmune. The immune system produces an immune response to an infection which unfortunately cross-reacts with the nerves. It usually reacts with and damages the outer coating sheath of the nerve fibers, called myelin. In more severely affected people, this damage also affects the central conducting core of the nerve, called the axon. In some people the axon is itself the main target of the autoimmune response.
The infections which trigger the autoimmune response include:
• The bacterium, Campylobacter jejuni which causes diarrhea (often from undercooked infected chicken)
o cytomegalovirus which causes respiratory infection, glandular fever and jaundice
o Epstein-Barr virus which causes glandular fever
o Hepatitis E which causes jaundice
o Zika virus which causes fever, rash and joint pain
Less, usually much less, than 1 in a 1000 of people who catch these infections get GBS.
Guillain-Barré syndrome is only one of many causes of acute weakness and numbness. The diagnosis requires recognition of the characteristic symptoms and signs. Because it is rare this may be difficult for the non-specialist and referral to a neurologist is usually appropriate. Clinical examination shows loss of the tendon reflexes and supports the diagnosis of peripheral nerve disease. Two tests are commonly used to support the diagnosis:
1. Lumbar puncture to examine the fluid which bathes the spinal cord and nerve roots (cerebrospinal fluid). For this the patient lies on their side and has an injection of local anaesthetic to numb a small area in the middle of the lower back (the lumbar region). The doctor pushes a fine needle through the numb area and sucks off a small sample of the cerebrospinal fluid from the hollow canal in the vertebra. Analysis of the fluid supports the diagnosis by showing a raised protein content and normal count of cells.
2. Nerve conduction tests (often called EMG, short for electromyogram which is to say recording of muscle activity) to study the electrical behavior of the nerves. The doctor uses small electrical shocks to stimulate some nerves in the arms and legs and then records the responses in the muscles and in the sensory nerves. The recordings prove the presence of nerve damage and show whether the damage affects the myelin or the axons or both.
The doctor needs to exclude many other causes of neuropathy such as alcohol, poisons, drugs, vasculitis (inflammation of blood vessels) and cancer. (For more information on these disorders, choose “Neuropathy, Peripheral” as your search term in the Rare Disease Database.) This may require blood tests and X-Rays or scans.
The most important parts of treatment are general medical and nursing care, physiotherapy and rehabilitation. Because of the risks of breathing failure and heart-beat instability in the acute stage, people with severe disease need to be in a ward with facilities for monitoring the pulse and breathing. If breathing becomes difficult mechanical ventilation with a breathing machine in an intensive care unit becomes necessary. For this, a special plastic tube, called an endotracheal tube, connects the person to the breathing machine via the mouth or nose. If mechanical ventilation lasts more than a few days it is more comfortable to move the tube to the throat, making a small opening in the windpipe for the purpose (an operation called a tracheostomy). After recovery the tube is removed and the opening closes up. Difficulty swallowing requires insertion of a thin plastic tube through the nose into the stomach for feeding and drinking. Medicines and nursing measures treat pain and reduce the risk of deep vein thrombosis, bed sores and constipation. Physical therapy optimizes muscle strength and function and avoids muscle shortening and joint stiffness. When people become medically stable, they often move to a rehabilitation center for comprehensive physical and occupational therapy. Psychological support is important throughout the illness.
Two treatments accelerate recovery from GBS, plasma exchange (PE, also called plasmapheresis) and intravenous immune globulin (IVIg). PE connects one vein via a thin plastic tube to a machine which separates the plasma (the liquid portion of the blood) from the red blood cells and returns the red blood cells with a plasma substitute into another vein. This removes harmful substances, especially the antibodies which cause GBS. IVIg consists of giving high-doses of immune globulin (the antibodies in the blood) into a vein. The immune globulin comes from highly purified pooled plasma from thousands of healthy people. It probably works by blocking the effects of the harmful antibodies which cause GBS. IVIg is more convenient and more widely available than PE but both are equally helpful. Combining the two does not help more. Early treatment within the first two weeks after the onset of GBS symptoms is preferable. There are no other treatments which hasten recovery. Against expectations steroids have not been effective in clinical trials.
The majority of people recover completely or nearly completely. However many have mild, residual effects such as foot drop or abnormal sensation for more than two years. Persistent fatigue and pain may be problematic. Fewer than 15 percent have substantial long term disability requiring the use of a walker or wheelchair. Death from GBS is rare in countries with intensive care facilities, occurring in fewer than 5 percent of patients.
Most variants of GBS are treated in a similar manner with IVIG or PE. The related condition, CIDP, is also treated with PE and IVIg but, unlike GBS, it also responds to corticosteroids.
Research is ongoing to discover the best dose of IVIg and to find better drugs to prevent damage to the nerves in the acute stage.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact: www.centerwatch.com
For information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
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