Guillain-Barré Syndrome (GBS)

Guillain-Barré syndrome (GBS) is a rare neurological disorder in which the body’s own immune system mistakenly attacks part of its peripheral nervous system—the network of nerves located outside of the brain and spinal cord. GBS can range from very mild cases, with brief weakness, to nearly devastating paralysis, leaving the person unable to breathe independently. Fortunately, most people eventually recover from even the most severe cases of GBS. After recovery, some people will continue to have some degree of weakness. Guillain-Barré syndrome can affect anyone. It can strike at any age (although it is more frequent in adults and older people). GBS is estimated to affect about one in 100,000 individuals each year.

There are four types of GBS, and diagnosis is based on symptoms:

• Acute motor axonal neuropathy: affects axons of the nerves connected to the muscles. 
• Acute inflammatory demyelinating polyradiculoneuropathy: this is the most common syndrome; affects the myelin (protective sheath surrounding the nerves)
• Acute sensory and motor axonal neuropathy
• Miller-Fisher variant: characterized by ophthalmoplegia, ataxia and areflexia

The exact cause of GBS is not known. Researchers don’t know why it strikes some people and not others. It is neither contagious nor inherited. What they do know is that the affected person’s immune system begins to attack the body itself. It is thought that, at least in some cases, this autoimmune attack is initiated to fight an infection, and that some chemicals from the infecting bacteria and viruses resemble those on nerve cells, which, in turn, also become targets of attack.

Since the body’s own immune system does the damage, GBS is called an autoimmune disease (“auto” meaning “self”). Normally the immune system uses antibodies (molecules produced in an immune response) and special white blood cells to protect us by attacking infecting microorganisms (bacteria and viruses). In Guillain-Barré syndrome, however, the immune system mistakenly attacks the healthy nerves. Most cases usually start a few days or weeks following a respiratory or gastrointestinal viral infection. Occasionally surgery will trigger the syndrome. In rare cases vaccinations may increase the risk of GBS. Recently, some countries worldwide reported an increased incidence of GBS following infection with the Zika virus.

Various ideas have been proposed to explain how GBS develops. One of them is the “molecular mimicry/innocent bystander” theory. According to this theory, molecules on some nerves are very similar to, or mimic, molecules on some microorganisms. When those microorganisms infect someone, the immune system correctly attacks them. However, if the microbe and myelin look similar, the immune system can make a mistake and attack the myelin sheath instead.

Different mechanisms may explain how the molecular mimicry concept may work. When Guillain-Barré syndrome is preceded by a viral or bacterial infection, it is possible that the infecting agent has changed the chemical structure of some nerves. The immune system treats these nerves as foreign bodies and mistakenly attacks them. It is also possible that the virus makes the immune system itself less discriminating and no longer able to recognize its own nerves. Some parts of the immune system—special white blood cells called lymphocytes and macrophages—perceive myelin as a foreign body and attack it. Specialized white blood cells called T lymphocytes (from the thymus gland) cooperate with B lymphocytes (originated in the bone marrow) to produce antibodies that fight the affected person’s own myelin, and damage it. 

In some forms of GBS, antibodies made by the person to fight Campylobacter jejuni bacterial infections, attack axons in the motor nerves instead. This causes acute motor axonal neuropathy, which is a variant of GBS that includes acute paralysis and a loss of reflexes without sensory loss. Campylobacter infections can be caused by ingesting contaminated food or from other exposures. The infected person’s body then makes antibodies against Campylobacter. Some Campylobacter molecules resemble molecules in the person’s nerve axons, so when the person’s antibodies fight the Campylobacter bacteria they also attack the look-alike axons. This slows nerve conduction and causes paralysis. Scientists are investigating various GBS subtypes to find why the immune system reacts abnormally in this and other autoimmune diseases. 

Guillain-Barré syndrome is one of several disorders involving weakness caused by peripheral nerve damage in the person’s own immune system. While GBS comes on rapidly over days to weeks, and the person usually recovers, other disorders develop slowly and can linger or recur.

The most common type of GBS in the United States is acute inflammatory demyelinating polyneuropathy (AIDP). In AIDP, the immune response damages the myelin coating and interferes with the transmission of nerve signals. In two other types of Guillain-Barré syndrome—acute motor axonal neuropathy (AMAN) and acute motor sensory axonal neuropathy (AMSAN)—the axons themselves are damaged by the immune response.

Miller-Fisher syndrome is a rare, acquired nerve disease that is a variant of Guillain-Barré syndrome. It is characterized by abnormal muscle coordination with poor balance and clumsy walking, weakness or paralysis of the eye muscles, and absence of the tendon reflexes. Like GBS, symptoms may follow a viral illness. Additional symptoms include generalized muscle weakness and respiratory failure. Most individuals with Miller Fisher syndrome have a unique antibody that characterizes the disorder.

Related peripheral nerve disorders with slow onset and persisting or recurrent symptoms, include chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy. CIDP features weaknesses that can recur, repeatedly, over the course of years. Multifocal motor neuropathy typically affects many different muscles in a small are of one limb or more. Usually the symptoms are more severe on one side of the body.

Risk of contracting Guillain-Barré Syndrome (GBS) increases with age, and is more common among men than women. Onset may be triggered by one of the following conditions:

• COVID-19 virus
• Trauma
• Surgery
• Certain viruses, including influenza, Epstein-Barr and Zika virus
• Mycoplasma pneumonia
• Hepatitis A, B, C and E
• Cytomegalovirus
• Bacteria found in undercooked poultry (Campylobacter)
• Hodgkin’s lymphoma

In rare cases GBS is linked to certain immunizations, including childhood and influenza vaccinations, and the Johnson & Johnson and AstraZeneca COVID-19 vaccines.

As Guillain-Barré syndrome (GBS) is often challenging to diagnose in its early stages, doctors will usually start with a thorough medical history and physical examination. Depending on the symptoms, your doctor may suggest one of the following screening tools for diagnosis:

• Nerve conduction studies: A small shock is applied to nerves using electrodes taped to the skin. The speed of each signal is measured.
• Spinal tap (also known as a lumbar puncture): Fluid from the spinal canal in the lower back is tested for changes commonly found in GBS.
• Electromyography: Using electrodes inserted into the muscles, nerve activity is measured to detect any abnormalities.

Many of the body’s nerves are like household wires. There is a central conducting core in the nerves called the axon that carries an electric signal. The axon (an extension of a nerve cell) is surrounded by a covering, like insulation, called myelin. The myelin sheath surrounding the axon speeds up the transmission of nerve signals and allows the transmission of signals over long distances. When we move, for example, an electric signal from the brain travels through and out of the spinal cord to peripheral nerves along muscles of the legs, arms and elsewhere; these are called the motor nerves. In most cases of GBS, the immune system damages the myelin sheath that surrounds the axons of many peripheral nerves; however, it also may also damage the axons themselves. As a result, the nerves cannot transmit signals efficiently, and the muscles weaken as they begin to lose their ability to respond to the brain’s commands. 

The weakness caused by GBS usually comes on quickly and worsens over hours or days. Symptoms are usually symmetric or equal on both sides of the body . In addition to weak limbs, muscles controlling breathing can weaken to the point that the person must be attached to a machine to help support breathing. 

Since GBS damages nerves, the brain may receive abnormal sensory signals from the rest of the body. This results in unexplained, spontaneous sensations (paresthesias) that may be experienced as tingling, a sense of insects crawling under the skin (formications) and pain. Deep muscular pain may be experienced in the back and legs.

The first symptoms are usually unexplained sensations, such as tingling in the feet or hands, or even pain (especially in children), which often start in the legs or back.

Children experience difficulty walking and may refuse to walk. These sensations tend to disappear before the major, longer-term symptoms manifest themselves. 

Weakness on both sides of the body is a major symptom that prompts most people to seek medical attention. The weakness may first appear as difficulty climbing stairs or with walking. 

Symptoms often affect the arms, breathing muscles and even the face, which reflect more widespread nerve damage. Occasionally, symptoms start in the upper body and move down to the legs and feet. Most people reach the greatest stage of weakness within the first two weeks after symptoms appear; by the third week 90 percent of affected individuals are at their weakest. 

In addition to muscle weakness, symptoms may include:

• Difficulty with eye muscles and vision
• Difficulty swallowing, speaking or chewing
• Pricking or pins and needles sensations in the hands and feet
• Pain that can be severe, particularly at night
• Coordination problems and unsteadiness
• Abnormal heart beat/rate or blood pressure
• Problems with digestion and/or bladder control

These symptoms can increase in intensity over a period of hours, days or weeks until certain muscles cannot be used at all and, when severe, the person is almost totally paralyzed. In these cases, the disorder is life-threatening, potentially interfering with breathing and, at times, with blood pressure or heart rate.

The initial signs and symptoms of GBS are varied, and there are several disorders with similar symptoms. Therefore, doctors may find it difficult to diagnose GBS in its earliest stages. Physicians will note whether the symptoms appear on both sides of the body (which is common in GBS) and the speed with which the symptoms appear; in other disorders, muscle weakness may progress over months rather than days or weeks. 

In GBS, deep tendon reflexes in the legs, such as knee jerks, are usually lost. Reflexes may also be absent in the arms. Because the signals traveling along the nerve are slow, a nerve conduction velocity test (NCV) which measures the nerve’s ability to send a signal, can provide clues to aid the diagnosis.  In people with GBS, there is a change in the cerebrospinal fluid that bathes the spinal cord and brain. Researchers have found the fluid contains more protein than usual, but very few white blood cells. Therefore, a physician may decide to perform a spinal tap or lumbar puncture to obtain a sample of spinal fluid to analyze. In this procedure, a needle is inserted into the person’s lower back and a small amount of cerebrospinal fluid is withdrawn from the spinal cord. This procedure is usually safe, with rare complications. 

Key diagnostic findings include:

• Recent onset, within a few days to a maximum of four weeks of symmetric weakness, usually starting in the legs
• Abnormal sensations such as pain, numbness and tingling in the feet that accompany or even occur before weakness
• Absent or diminished deep tendon reflexes in weak limbs
• Elevated cerebrospinal fluid protein without elevated cell count. This may take up to ten days to develop from the onset of symptoms. 
• Abnormal nerve conduction velocity findings, such as slow signal conduction
• Sometimes, a recent viral infection or diarrhea

There is no known cure for Guillain-Barré syndrome. However, some therapies can lessen the severity of the illness and shorten recovery time. There are also several ways to treat the complications of the disease. Because of the possible complications of muscle weakness, problems that can affect any paralyzed person (such as pneumonia or bed sores), and the need for sophisticated medical equipment, individuals with Guillain-Barré syndrome are usually admitted and treated in a hospital’s intensive care unit.

There are currently two treatments commonly used to interrupt immune-related nerve damage. One is plasma exchange (PE, also called plasmapheresis); the other is high dose immunoglobulin therapy (IVIg). Although both treatments are equally effective if started within two weeks of the first GBS symptoms, immunoglobulin is easier to administer. Using both treatments in the same person has no proven benefit.

In the process of plasma exchange, a plastic tube (catheter) is inserted into a person’s vein, through which some blood is removed. The blood cells from the liquid part of the blood (plasma) are extracted and returned to body. This technique seems to reduce the severity and duration of the Guillain-Barré episode. Plasma contains antibodies and PE removes some plasma; PE may work by removing the bad antibodies that have been damaging the nerves.

Immunoglobulins are proteins that the immune system naturally makes to attack infecting organisms. IVIg therapy involves intravenous injections of these immunoglobulins. The immunoglobulins are developed from a pool of thousands of normal donors. When IVIg is given to people with GBS, the result can be a lessening of the immune attack on the nervous system. The IVIg can also shorten recovery time. Investigators believe this treatment also lowers the levels, or effectiveness, of the antibodies that attack the nerves by, both, “diluting” them with non-specific antibodies and providing other antibodies that bind to the harmful ones taking them out of commission.

Miller-Fisher syndrome is also treated with plasmapheresis and IVIg.

Anti-inflammatory steroid hormones (corticosteroids) have also been tried to reduce the severity of Guillain-Barré syndrome. However, controlled clinical trials have demonstrated that this treatment is not effective.

Supportive care is very important to address the many complications of paralysis, as the body recovers and the damaged nerves begin to heal. Respiratory failure can occur in GBS, so close monitoring of a person’s breathing should be instituted initially. Sometimes a mechanical ventilator is used to help support or control breathing. The autonomic nervous system (which regulates the functions of the internal organs and some muscles) can also be disturbed, causing changes in heart rate and blood pressure, as well as toileting and sweating. Therefore, the person should be put on a heart monitor or equipment that measures and tracks body function. Occasionally GBS-related nerve damage can lead to difficulty handling secretions in the mouth and throat. In addition to the person choking and/or drooling, secretions can get into the airways and cause pneumonia.

As individuals begin to improve, they are usually transferred from the acute care hospital to a rehabilitation setting, where they can regain their strength, and receive physical rehabilitation and other therapies to resume activities of daily living, and prepare to return to their pre-illness life.

Complications in GBS can affect several parts of the body. Often—even before recovery begins—caregivers may use several methods to prevent or treat complications. For example, a therapist may be instructed to manually move and position the person’s limbs to help keep the muscles flexible and prevent muscle shortening. Injections of blood thinners can help prevent dangerous blood clots from forming in leg veins. Inflatable cuffs may also be placed around the legs to provide intermittent compression. All or any of these methods helps prevent blood stagnation and sludging—the buildup of red blood cells in veins, which could lead to reduced blood flow—in the leg veins. In a process called substitution, muscle strength may not return uniformly; some muscles that get stronger faster may tend to take over a function that weaker muscles normally perform. The therapist should select specific exercises to improve the strength of the weaker muscles so their original function can be regained.

Occupational and vocational therapy help individuals learn new ways to handle everyday functions that may be affected by the disease. It also helps regain work skills and teaches how to use assistive devices and other adaptive equipment and technology.

Guillain-Barré syndrome can be a devastating disorder because of its sudden and rapid onset of weakness, which often leads to actual paralysis. Fortunately, 70 percent of people with GBS eventually experience full recovery. With careful intensive care and successful treatment of infection, autonomic dysfunction and other medical complications, even those individuals with respiratory failure usually survive.

Typically, the point of greatest weakness occurs within days to a maximum of four weeks after the first symptoms occur. Symptoms then stabilize at this level for a period of days, weeks or, sometimes, months. Recovery, however, can be slow or incomplete. The recovery period may be as little as a few weeks and up to a few years. Some individuals report ongoing improvement after two years. About 30 percent of those with Guillain-Barré Syndrome have residual weakness after three years. About three percent may suffer a relapse of muscle weakness and tingling sensations many years after the initial attack. About 15 percent of individuals experience long-term weakness; some may require ongoing use of a walker, a wheelchair or ankle support. Muscle strength may not return uniformly.

Ongoing fatigue, pain and other annoying sensations can sometimes be troublesome. Fatigue is best handled by pacing activities and providing time for rest when fatigue sets in. Those with Guillain-Barré syndrome face not only physical difficulties, but emotionally painful periods as well.

It is often extremely difficult for individuals to adjust to sudden paralysis and dependence on others for help with routine daily activities. Individuals sometimes need psychological counseling to help them adapt. Support groups can often ease emotional strain and provide valuable information.

The mission of the National Institute of Neurological Disorders and Stroke (NINDS) is to seek fundamental knowledge of the brain and nervous system and to use that knowledge to reduce the burden of neurological diseases. The NINDS conducts research on disorders including Guillain-Barré syndrome and funds research at major institutions and universities. The NINDS is a component of the National Institutes of Health (NIH), the leading supporter of biomedical research in the world.

Neuroscientists, immunologists, virologists and pharmacologists are working collaboratively to learn how to prevent GBS and to make better therapies available when it strikes.

Scientists are concentrating on finding new treatments and refining existing ones. They are also looking at the workings of the immune system to find which cells are responsible for beginning and carrying out the attack on the nervous system. The fact that many cases of Guillain-Barré syndrome begin after a viral or bacterial infection suggests that certain characteristics of some viruses and bacteria may activate the immune system inappropriately.

Investigators are searching for those characteristics. Certain proteins or peptides in viruses and bacteria may be the same as those found in myelin, and the production of antibodies to neutralize the invading viruses or bacteria could trigger the attack on the myelin sheath.

Some studies show that normal variations in certain genes could increase the risk of developing Guillain-Barré syndrome; however, more research is necessary to identify and confirm associated genes. Since many of the genes that may increase the risk of Guillain-Barré syndrome are involved in the immune system, their roles in fighting infection might contribute to the development of the condition.

NINDS-funded researchers have developed a mouse model with an altered autoimmune regulator gene that generates autoimmunity against the peripheral nervous system (PNS). Using this model, scientists hope to identify which PNS proteins are at greatest risk of autoimmune attack and which components of the immune system contribute to the autoimmune response against the PNS. A greater understanding of how the immune system damages the PNS could lead to better treatments for autoimmune disorders, such as GBS.

Other NINDS-funded researchers are investigating the mechanisms by which IVIg treatment lessens the symptoms of GBS. By understanding these mechanisms, it may be possible to develop more effective treatments.