Guillain-Barré Syndrome
Guillain-Barré syndrome
Definition
Guillain-Barré syndrome (GBS) is an inflammation of the covering that surrounds nerve cells of the brain and spinal cord. The basis of the inflammation is not conclusively known, but is generally considered to arise from a malfunctioning immune system that recognizes host tissues as being foreign. The inflammation reaction damages the nerves of the brain and spinal cord, producing weakness in the muscles, loss of sensation (such as the sense of touch in the fingers), or outright paralysis.
GBS is termed a syndrome rather than a disease because there is no conclusive evidence to support the possibility that a specific disease-causing agent such as a bacteria or a virus is the direct cause of the malady. Infections may be a trigger to the development of GBS, however.
Description
The syndrome is named after George Charles Guillen and Jean-Alexandre Barré, French co-authors of a classic paper on the syndrome that was published in 1916. A third author, André Strohl, was not subsequently associated with the syndrome that was the subject of the paper.
GBS is a rare and acute disorder. An acute disorder displays a rapid appearance of symptoms, and a rapid worsening of the symptoms. In the case of GBS, symptoms typically appear over just a single day. Most often, symptoms are first noticed in the feet and legs. The symptoms often progress to involve different parts of the body over the next several days to several weeks. In addition, during that time other more severe symptoms can appear. In more than 90% of cases, the symptoms reach their peak by four weeks.
The syndrome is an inflammatory disorder, in which a person's own immune system attacks the nerves outside the brain and the spinal cord. These nerves are known as peripheral nerves. The nerve inflammation that occurs can damage the nerve cells. The covering (sheath) of a fatty material called myelin that surrounds the cells can be lost. This loss is called demyelination.
Additionally, the elongated portion of the nerve cell called the axon can be killed. This phenomenon is called denervation. The axon conveys electrical impulses to more distant areas of muscles, and from one nerve cell to another. Demyelination and denervation bring about muscle weakness, loss of sensation, or paralysis because the affected nerves cannot transmit signals to muscles. This loss of signal transmission inhibits the muscles from being able to respond to nerve signals. As well, the brain receives fewer signals and the person can become unable to feel heat, cold, or pain .
GBS is also known as Landry-Guillain-Barré syndrome, acute idiopathic polyneuritis, infectious polyneuritis, and acute inflammatory demyelinating polyneuropathy (AIDP). Another malady called chronic inflammatory demyelinating polyradicalneuropathy is possibly related to GBS. It is far less common than GBS (which itself is rare) and persists longer.
Demographics
GBS can occur at any age. However, the syndrome tends to be more prevalent in men and women aged 15–35 years and 50–75 years (a bimodal pattern of age distribution), respectively. Males are slightly more susceptible than females (the ratio of those affected is approximately 1.5 male per female). There is no known racial group that is any more susceptible to GBS, nor any known geographical localization of the syndrome.
In the United States, the syndrome is rare. For example, the annual incidence of GBS in the United States ranges from 0.6 to 2.4 cases per 100,000 people. Nonetheless, GBS is the most common cause of neuromuscular paralysis among Americans.
Causes and symptoms
Causes
The exact cause of GBS is not known. However, bacterial or viral infections may be a trigger for its development. Almost 70% of those who develop GBS have had an infectious illness in the preceding two to four weeks. Examples of infections include sore throat, cold, flu, and diarrhea. Bacteria that have been associated with the subsequent development of GBS include chlamydia, Mycoplasma pneumoniae, and Campylobacter jejuni.
The suspected involvement of Campylobacter is noteworthy, as this bacterium is a common contaminant of poultry. Inadequate cooking can allow the microbe to survive and cause an infection in those who consume the food. Thus, there may be a connection between GBS and food quality. The form of GBS that may be associated with the presence of Campylobacter may be particularly severe. For reasons that are unclear, the peripheral nerves can themselves be directly attacked, rather than just the myelin sheath around the nerves.
Usually, infections such as those caused by Campylobacter have abated before the onset of GBS. As well, chronic infection with the viruses responsible for mononucleosis, herpes, and acquired immunodeficiency syndrome can prelude the appearance of GBS. The latter is also known as HIV-1 associated acute inflammatory demyelinating polyneuropathy.
Other possible associated factors include vaccination (rabies, swine flu, influenza, Group A streptococci), surgery, pregnancy, and maladies such as Hodgkin's disease and systematic lupus erythematosus.
Whether there is direct (causal) connection between infections and maladies and the subsequent development of GBS, or whether the events are only coincidental, is not known. For example, vaccination of Americans against the swine flu in 1976 increased the rate of GBS by less than one case per 100,000 people. Whether this increase was directly due to the vaccine is impossible to determine. Furthermore, more than 99% of people suffering from GBS who have been surveyed by the United States Centers for Disease Control and Prevention (CDC) have not recently been vaccinated. According to the CDC, the chance of developing GBS as a result of vaccination is remote.
It is conceivable that the infections or illnesses disrupt the body's immune system such that autoimmune destruction of nerve cell components occurs. Although this intriguing possibility is favored among many scientists, it remains unsubstantiated.
There is no evidence to indicate that GBS is an infection or that it is a genetically linked (heritable) disorder.
Symptoms
The initial sensation of weakness or paralysis in the toes spreads upward within days to a few weeks to the arms and the central part of the body. In medical terminology, this represents an ascending pattern of spread. The weakness and paralysis can also be accompanied by a tingling sensation, and a cramping or more constant pain in the feet, hands, thighs, shoulders, lower back, and buttocks. Use of the hands and feet can become impaired. More serious development of paralysis can make breathing difficult, even to the point that mechanical ventilation becomes necessary.
Other, less typical symptoms include blurred vision, clumsiness, difficulty in moving facial muscles, involuntary muscle contractions, and a pronounced heartbeat. Symptoms that are indicative of an emergency include difficulty in swallowing, drooling, breathing difficulty, and fainting .
Progression from the early symptoms to the more severe symptoms can occur very quickly (i.e., 24–72 hours). Typically, the exacerbated condition persists for several weeks. Recovery then typically occurs gradually, and can take anywhere from days to six months or more.
In very mild cases, an individual may just have a general feeling of weakness. As the symptoms abate after a few weeks, the person may dismiss the incident as a viral infection, without ever knowing the true nature of the illness.
Diagnosis
GBS is suspected if a patient displays muscle weakness or paralysis that has been increasing in severity, especially if an illness has occurred recently. Loss of reflexes such as the knee jerk reaction can be an early clue to a clinician.
Clinical data can be useful in diagnosis. For example, a hormone that is involved in maintaining the proper chemical balance of urine can be affected in GBS. The result is called the syndrome of inappropriate antidiuretic hormone. Antibodies to nerve cells may be present as a result of the body's immune reaction against its own constituents.
Another clue to the diagnosis of GBS can be the finding of muscle weakness by neurological examination. One such test is known as nerve conduction velocity. In this test, the selected nerve is stimulated, usually with surface electrodes contained in a patch that is applied to the surface of the skin. The nerve can be stimulated using a very mild electrical current put out from one electrode, and the resulting electrical activity is recorded by the other electrodes in the patch. The nerve conduction velocity is calculated knowing the distance between electrodes and measuring the time it takes for the impulses to travel from the generating to the measuring electrodes. A person with GBS whose nerves have usually lost some or most of the myelin sheath will display a slower conduction velocity than that displayed by an unaffected person. Electrical impulses travel along the damaged nerve slower than along an undamaged nerve.
Muscle response to electrical stimulation can also be measured by electromyography (EMG). In this test, a needle electrode is inserted through the skin into the muscle. When the muscle is stimulated, for example, by contracting it, the resulting visual or audio pattern carries the information about the muscle's response. The characteristic pattern of wavelengths produced by a healthy muscle (the action potential) can be compared to a muscle in someone suspected of having GBS.
When paralysis of the heart muscle is suspected, an electrocardiogram can be used to record the electrical activity of the heart. GBS muscle paralysis can alter the normal pattern of the heartbeat.
Finally, an examination of the cerebrospinal fluid by means of a spinal tap (also known as a lumbar puncture) may detect a higher-than-normal level of protein in the absence of an increase in the number of white blood cells (WBCs). An increase in WBCs is a hallmark of an infection.
Treatment team
Neurologists, immunologists, physical therapists, occupational therapists, and nurses figure prominently in GBS treatment. The assistance of support groups such as the Guillen-Barré Syndrome Foundation International can also be a useful adjunct to treatment.
Treatment
As recently as the 1980s, treatment for GBS consisted of letting the syndrome run its course. While most people recovered completely with time, some people were not as lucky. Those who develop severe symptoms such as breathing difficulty are routinely hospitalized.
One medical procedure that can be useful in the treatment of GBS is called plasmaphoresis. It is also known as plasma exchange. In plasmapheresis, antibody-laden blood plasma (the liquid portion of the blood) is removed from the body. Red blood cells are separated and put back into the body with antibody-free plasma or intravenous fluid. The treatment can lessen the symptoms of GBS and hasten recovery time. As of December 2003, it is not known why plasmapheresis works. It is suspected that the removal of antibodies may lessen the effects of the body's immune attack on the nerve cells.
Another procedure that produces similar results involves the administration of intravenous immune globulin (IVIG). Both treatments have been shown to speed up recovery time by up to 50%. IVIG has been shown to be an effective treatment for immune-system-related neuropathies in general. IVIG may act by reducing the amount of anti-myelin antibodies through the binding of the defective antibodies by healthy antibodies contained in the IVIG solution, and in suppressing the immune response.
Other treatments are designed to prevent or lessen complications of GBS. For example, choking during eating, because of throat muscle weakness or paralysis, can be prevented using a feeding tube, and formation of blood clots can be lessened by the use of chemicals that thin the blood. The pain associated with GBS can be treated with anti-inflammatory drugs or, if necessary, stronger-acting narcotic medication. For patients who have breathing difficulties, clinicians may first need to supply oxygen, install a breathing tube (intubation), and/or use a mechanical device that helps in breathing.
Physical therapy is helpful. Caregivers can move a patient's arms and legs to help maintain the flexibility and strength of the muscles. Later in recovery, sessions in a whirlpool (hydrotherapy) can help restore function to arms and legs. Often, therapists will design a series of exercises to be performed when the patient returns home.
Recovery and rehabilitation
More than 95% of people afflicted with GBS survive. In about 20% of people, however, muscle weakness and fatigue may remain. Some people find that wearing highly elastic gradient compression stockings beneficial. The stockings produce the greatest compression at the toes, with a tapering-off upwards to the thigh. The effect is to reduce the volume of veins, which increases the rate of blood flow through the veins. The increased blood flow can reduce the feeling of numbness in the toes.
Clinical trials
As of early 2004, three clinical trials were recruiting patients, including:
- Assessment of chronic Guillain-Barré syndrome improvement with use of 4-aminopyridine. The study, funded by the United States Food and Drug Administration Office of Orphan Products Development, seeks to assess the potential of 4-aminopyridine in increasing the transmission of impulses in damaged nerves. It is hoped that increased nerve activity could restore some lost muscle activity, as has occurred using the drug with those afflicted with multiple sclerosis . The contact is the Spain Rehabilitation Center, University of Alabama at Birmingham, 35249-7330; Jay Meythaler, M.D. (205) 934-2088, (email: [email protected]).
- Safety, tolerability, and efficacy of rituximab in patients with anti-glycoconjugate antibody-mediated demyelinating neuropathy: a double-blind placebo-controlled randomized trial. While not directly related to GBS, the study concerns the loss of the myelin sheath of nerves and so is relevant. The study, sponsored by the National Institute of Neurological Disorders and Stroke (NINDS), is designed to evaluate the usefulness of rituximab in preventing the antibody damage to nerves. The contact is the National Institutes of Health Patient Recruitment and Public Liaison Office, Building 61, 10 Cloister Court, Bethesda, MD, 20892-4754; (800) 411-1222; [email protected].
- Diagnostic evaluation of patients with neuromuscular diseases. This NINDS-sponsored study is designed to screen patients for other studies and to help train clinicians in the diagnosis of maladies including GBS. The contact information is the same as the above item.
Prognosis
Most of those afflicted with GBS recover completely, although the recovery can in some cases be slow (months to years). Complete recovery usually occurs when the symptoms fade within three weeks of appearing. The typical scenario is for a patient to experience the most weakness from 10–14 days after the appearance of symptoms, with complete recovery occurring within weeks or a few months. In contrast, a poor prognosis can be associated with a rapid appearance of symptoms, use of assisted ventilation for a month or more, severe nerve damage, and with advancing age.
While recovery is complete for most of those afflicted with GBS, in 10–20% of cases the symptoms reappear, in 15–20% the neurologic complications can persist and can cause a long-term disability, and 5–10% of those who are afflicted die. The main cause of death historically was from respiratory failure due to muscle paralysis. With mechanical ventilation, respiratory failure in GBS is less often fatal. Currently the main cause of death is malfunctioning of the autonomic nervous system, which controls involuntary processes such as heart rate, blood pressure, and body temperature.
Resources
PERIODICALS
Quarles, R. H., and M. D. Weiss. "Autoantibodies Associated with Peripheral Neuropathy." Muscle Nerve (July 1999): 800–822.
OTHER
Guillain-Barré Syndrome (GBS) and Influenzae Vaccine. Centers for Disease Control and Prevention. CDC. December 15, 2003 (April 4, 2004). <http://www.cdc.gov/nip/vacsafe/concerns/GBS/default.htm>.
Fanion, David, and Daniel M. Joyce. "Guillain-Barré Syndrome." eMedicine. December 12, 2003 (April 4, 2004). <http://www.emedicine.com/EMERG/topic222.htm>.
Mayo Foundation for Medical Education and Research. "Guillain-Barré Syndrome." MayoClinic.com. December 13, 2003 (April 4, 2004). <http://www.mayoclinic.com/invoke.cfm?id=DS00413>.
National Institutes of Health. "Guillain-Barré Syndrome." MEDLINEplus Medical Encyclopedia. December 13, 2003 (April 4, 2004). <http://www.nlm.nih.gov/medlineplus/ency/article/000684.htm>.
NINDS Guillain-Barré Syndrome Information Page. National Institute of Neurological Disorders and Stroke. December 10, 2003 (April 4, 2004). <http://www.ninds.nih.gov/health_and_medical/disorders/gbs.htm>.
ORGANIZATIONS
Centers for Disease Control and Prevention. 1600 Clifton Road, Atlanta, GA 30333. (404) 639-3311 or (800) 311-3435. <http://www.cdc.gov/>.
Guillain-Barré Syndrome Foundation International. P.O. Box 262, Wynnewood, PA 19096. (610) 667-0131; Fax: (610) 667-7036. [email protected]. <http://www.gbsfi.com>.
National Institutes of Health. 9000 Rockville Pike, Bethesda, MD 20892. (301) 496-4000. [email protected]. <http://www.nih.gov>.
National Institute for Neurological Disorders and Stroke. P.O. Box 5801, Bethesda, MD 20824. (301) 496-5761 or (800) 352-9424. <http://www.ninds.nih.gov>.
Brian Douglas Hoyle, PhD
Guillain-Barré Syndrome
Guillain-Barré Syndrome
Definition
Guillain-Barré syndrome (GBS) causes progressive muscle weakness and paralysis (the complete inability to use a particular muscle or muscle group), which develops over days or up to four weeks, and lasts several weeks or even months.
Description
The classic scenario in GBS involves a patient who has just recovered from a typical, seemingly uncomplicated viral infection. Symptoms of muscle weakness appear one to four weeks later. The most common preceding infections are cytomegalovirus, herpes, Epstein-Barr virus, and viral hepatitis. A gastrointestinal infection with the bacteria Campylobacter jejuni is also common and may cause a severe type of GBS from which it is particularly difficult to recover. About 5% of GBS patients have a surgical procedure as a preceding event. Patients with lymphoma, systemic lupus erythematosus, or AIDS have a higher than normal risk of GBS. Other GBS patients have recently received an immunization, while still others have no known preceding event. In 1976–77, there was a vastly increased number of GBS cases among people who had been recently vaccinated against the Swine flu. The reason for this phenomenon has never been identified, and no other flu vaccine has caused such an increase in GBS cases.
Causes and symptoms
The cause of the weakness and paralysis of GBS is the loss of myelin, which is the material that coats nerve cells (the loss of myelin is called demyelination). Myelin is an insulating substance which is wrapped around nerves in the body, serving to speed conduction of nerve impulses. Without myelin, nerve conduction slows or stops. GBS has a short, severe course. It causes inflammation and destruction of the myelin sheath, and it disturbs multiple nerves. Therefore, it is considered an acute inflammatory demyelinating polyneuropathy.
The reason for the destruction of myelin in GBS is unknown, although it is thought that the underlying problem is autoimmune in nature. An autoimmune disorder is one in which the body's immune system, trained to fight against such foreign invaders as viruses and bacteria, somehow becomes improperly programmed. The immune system becomes confused, and is not able to distinguish between foreign invaders and the body itself. Elements of the immune system are unleashed against areas of the body, resulting in damage and destruction. For some reason, in the case of GBS, the myelin sheath appears to become a target for the body's own immune system.
The first symptoms of GBS consist of muscle weakness (legs first, then arms, then face), accompanied by prickly, tingling sensations (paresthesias). Symptoms affect both sides of the body simultaneously, a characteristic that helps distinguish GBS from other causes of weakness and paresthesias. Normal reflexes are first diminished, then lost. The weakness eventually affects all the voluntary muscles, resulting in paralysis. When those muscles necessary for breathing become paralyzed, the patient must be placed on a mechanical ventilator which takes over the function of breathing. This occurs about 30% of the time. Very severely ill GBS patients may have complications stemming from other nervous system abnormalities which can result in problems with fluid balance in the body, severely fluctuating blood pressure, and heart rhythm irregularities.
Diagnosis
Diagnosis of GBS is made by looking for a particular cluster of symptoms (progressively worse muscle weakness and then paralysis), and by examining the fluid that bathes the brain and spinal canal through cerebrospinal fluid (CSF) analysis. This fluid is obtained by inserting a needle into the lower back (lumbar region). When examined in a laboratory, the CSF of a GBS patient will reveal a greater-than-normal quantity of protein, with normal numbers of white blood cells and a normal amount of sugar. Electrodiagnostic studies may show slowing or block of conduction in nerve endings in parts of the body other than the brain. Minor abnormalities will be present in 90% of patients.
Treatment
There is no direct treatment for GBS. Instead, treatments are used that support the patient with the disabilities caused by the disease. The progress of paralysis must be carefully monitored, in order to provide mechanical assistance for breathing if it becomes necessary. Careful attention must also be paid to the amount of fluid the patient is taking in by drinking and eliminating by urinating. Blood pressure, heart rate, and heart rhythm also must be monitored.
A procedure called plasmapheresis, performed early in the course of GBS, has been shown to shorten the course and severity of GBS. Plasmapheresis consists of withdrawing the patient's blood, passing it through an instrument that separates the different types of blood cells, and returning all the cellular components (red and white blood cells and platelets) along with either donor plasma or a manufactured replacement solution. This is thought to rid the blood of the substances that are attacking the patient's myelin.
It has also been shown that the use of high doses of immunoglobulin given intravenously (by drip through a needle in a vein) may be just as helpful as plasma-pheresis. Immunoglobulin is a substance naturally manufactured by the body's immune system in response to various threats. It is interesting to note that corticosteroid medications (such as prednisone), often the mainstay of anti-autoimmune disease treatment, are not only unhelpful, but may in fact be harmful to patients with GBS.
Prognosis
About 85% of GBS patients make reasonably good recoveries. However, 30% of adult patients, and a greater percentage of children, never fully regain their previous level of muscle strength. Some of these patients suffer from residual weakness, others from permanent paralysis. About 10% of GBS patients begin to improve, then suffer a relapse. These patients suffer chronic GBS symptoms. About 5% of all GBS patients die, most from cardiac rhythm disturbances.
Patients with certain characteristics tend to have a worse outcome. These include people of older age, those who required breathing support with a mechanical ventilator, and those who had their worst symptoms within the first seven days.
Prevention
Because so little is known about what causes GBS to develop, there are no known methods of prevention.
Resources
ORGANIZATIONS
American Academy of Neurology. 1080 Montreal Ave., St. Paul, MN 55116. (612) 695-1940. 〈http://www.aan.com〉.
Guillain-Barré Syndrome Foundation International. PO Box 262, Wynnewood, PA 19096. (610) 667-0131. (610) 667-0131. 〈http://www.webmast.com/gbs〉.
KEY TERMS
Autoimmune— The body's immune system directed against the body itself.
Demyelination— Disruption or destruction of the myelin sheath, leaving a bare nerve. Results in a slowing or stopping of impulses traveling along that nerve.
Inflammatory— Having to do with inflammation, the body's response to either invading foreign substances (such as viruses or bacteria) or to direct injury of body tissue.
Myelin— The substance that is wrapped around nerves, and which is responsible for speed and efficiency of impulses traveling through those nerves.