About Guillain-Barré Syndrome

What is Guillain-Barré Syndrome?

Guillain-Barré Syndrome (GBS) includes several subtypes, the most common of which is a multifocal demyelinating disorder of the peripheral nerves referred to as an acute inflammatory demyelinating polyneuropathy (AIDP). Some cases of GBS are associated with a primarily motor axonal process (acute motor axonal neuropathy; AMAN) with axonal degeneration (axons are long, thin extensions of the nerve cells and carry nerve signals) and sparing of the myelin (the myelin is an electrically insulating phospholipid layer that surrounds the axons of many neurons). Other cases appear to involve both sensory and motor axons and such cases are termed acute motor and sensory axonal neuropathy (AMSAN). More than 90% of patients with GBS in Europe and North America have AIDP. AMAN occurs in less than 10% of persons with GBS in the western hemisphere but in more than 40% of those affected in China and Japan. The incidence of AMSAN is very low (less than 10% of that of AMAN). Miller Fisher syndrome (MFS) is another GBS variant that occurs in about 5% of people affected by GBS. It is characterized by opthalmoplegia (eye muscle weakness), areflexia (absence of reflexes), ataxia (the inability to coordinate voluntary muscular movements such as walking), and, in some cases, facial and bulbar palsy (affecting vital functions, like breathing, and swallowing or speech).

GBS can affect anybody. It can strike at any age; men may be more likely to develop GBS than women. Although this syndrome is rare (affecting about one to two persons in 100,000) it is the most common cause of acute neuromuscular paralysis in the world.

Sources of Guillain-Barré Syndrome

GBS often occurs a few days or weeks after a person has had symptoms of a respiratory or gastrointestinal viral or bacterial infection; in fact, two-thirds of affected individuals have had a preceding infection. Campylobacter jejuni, cytomegalovirus, Epstein-Barr virus, and Mycoplasma pneumoniae are commonly identified antecedent pathogens, although C. jejuni is the most common pathogen that elicits GBS. Occasionally surgery or vaccinations will trigger the syndrome.  GBS is not contagious.  It has been reported that GBS occurs more in men than in women and more often in the elderly.  Seasonality has not been reported in developed countries like the United States (Church Potter & Kaneene, 2003). 
 
No one yet knows why GBS strikes some people and not others. Nor does anyone know exactly what sets the disease in motion. What scientists do know is that the body's immune system begins to attack the body itself, causing what is known as an autoimmune disease. Usually the cells of the immune system attack only foreign material and invading organisms. In GBS, however, the immune system starts to destroy the myelin sheath that surrounds the axons of many peripheral nerves, or even the axons themselves. The myelin sheath surrounding the axon speeds up the transmission of nerve signals and allows the transmission of signals over long distances. In diseases in which these myelin sheaths are injured or degraded, the nerves cannot transmit signals efficiently. That is why the muscles begin to lose their ability to respond to commands from the brain that must be carried through the nerve network. The brain also receives fewer sensory signals from the rest of the body, resulting in an inability to feel textures, heat, pain, and other sensations. Alternately, the brain may receive inappropriate signals that result in tingling, "crawling-skin," or painful sensations. Because the signals to and from the arms and legs must travel the longest distances they are most vulnerable to interruption. Therefore, muscle weakness and tingling sensations usually first appear in the hands and feet and progress upwards. 

Symptoms

The first symptoms of GBS include varying degrees of weakness or tingling sensations in the legs. The weakness and abnormal sensations may spread to the arms and upper body. These symptoms can increase in intensity until certain muscles cannot be used at all and, when severe, the affected 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—and is considered a medical emergency. Bladder dysfunction and constipation may occur. 

After the first clinical manifestations of GBS, the symptoms can progress over the course of hours, days, or weeks. Most people reach the stage of greatest weakness within the first two weeks after symptoms appear, and by the third week of the illness 90% of affected individuals are at their weakest. 

Persons with GBS are often hospitalized and closely monitored while diagnostic tests are performed.  Although both sides of the body are reported to have symmetrical involvement, a lack of symmetry of clinical and electrophysiological findings has been reported (Logullo et al., 2006).  In contrast to the relatively uniform speed of recovery among those with AIDP, two patterns of recovery are found with AMAN. Some individuals recover quickly within days and others experience slow and poor recovery. AMSAN tends to be associated with severe illness and slow recovery. The prognosis for MFS is generally good.

Risks

GBS can be a devastating disorder because of its sudden and unexpected onset. In addition, recovery is not necessarily quick. As noted above, affected persons usually reach the point of greatest weakness or paralysis days or weeks after the first symptoms occur. Symptoms then stabilize at this level for a period of days, weeks, or, sometimes, months. The recovery period may be as little as a few weeks or as long as a few years. About 30% of those with GBS still have residual weakness after three years. About 3% may suffer a relapse of muscle weakness and tingling sensations many years after the initial attack.  Those affected by GBS face not only physical difficulties, but emotionally painful periods as well. It is often extremely difficult for patients to adjust to sudden paralysis and dependence on others for help with routine daily activities. Patients sometimes need psychological counseling to help them adapt.

Diagnosis

GBS is called a syndrome rather than a disease because it is not clear that a specific disease-causing agent is involved. A syndrome is a medical condition characterized by a collection of symptoms (what the affected person feels) and signs (what a health care provider can observe or measure). The signs and symptoms of GBS can be quite varied, so, on rare occasions, it may be difficult to diagnose in its earliest stages.

Several disorders have symptoms similar to those found in GBS. Collectively, the signs and symptoms form a certain pattern that helps to differentiate GBS from other disorders. For example, if the symptoms appear on both sides of the body (most common in GBS) and symptoms appear rapidly (in other disorders, muscle weakness may progress over months rather than days or weeks), it is more likely to be GBS. In addition, reflexes such as knee jerks are usually lost. Because the signals traveling along the nerve are slower, a nerve conduction velocity test can give clues to aid in the diagnosis. The cerebrospinal fluid that bathes the spinal cord and brain contains more protein than usual in GBS (Levin, 2004). Therefore, a spinal tap (a procedure in which the doctor inserts a needle into the patient's lower back to draw cerebrospinal fluid from the spinal column) may need to be performed.
The two most common forms can be differentiated with specific tests. AMAN is diagnosed when nerve conduction studies show a reduction of compound muscle action potential without significant conduction slowing. In the AIDP form, immune system reactions result in demyelination. It is diagnosed when nerve conduction studies show slowing of nerve conduction suggestive of demyelination in two or more motor nerves. 

Treatment

There is no known cure for GBS. However, there are therapies that lessen the severity of the illness and accelerate the recovery in most people. There are also a number of ways to treat the complications of the disease.

Currently, plasma exchange (also known as plasmapheresis) and high-dose immunoglobulin therapy are used. Both of them are equally effective, but immunoglobulin is easier to administer. Plasma exchange is a method by which whole blood is removed from the body and processed so that the red and white blood cells are separated from the plasma, or liquid portion of the blood. The blood cells are then returned to the patient without the plasma, which the body quickly replaces. Scientists still don't know exactly why plasma exchange works, but the technique seems to reduce the severity and duration of the GBS episode. This may be because the plasma portion of the blood contains elements of the immune system that may be toxic to the myelin.

In high-dose immunoglobulin therapy, doctors give intravenous injections of the proteins that, in small quantities, the immune system uses naturally to attack invading organisms. Immunoglobulines are derived from a pool of thousands of normal donors.  Investigators have found that giving high doses of these immunoglobulins to GBS patients can lessen the immune attack on the nervous system.

The use of steroid hormones has also been tried as a way to reduce the severity of GBS, but controlled clinical trials have demonstrated that this treatment not only is not effective but may even have a harmful effect.

The most critical part of the treatment for this syndrome consists of keeping the person’s body functioning during recovery of the nervous system. This can sometimes require placing the affected person on a respirator, a heart monitor, or other machines that assist body function. The need for this sophisticated machinery is one reason why people are usually treated in hospitals, often in an intensive care ward. In the hospital, doctors can also look for and treat the many problems that can afflict any paralyzed person—complications such as pneumonia or bed sores.

Often, even before recovery begins, caregivers may be instructed to manually move the affected person’s limbs to help keep the muscles flexible and strong. Later, as the individual begins to recover limb control, physical therapy begins. Carefully planned clinical trials of new and experimental therapies are the key to improving the treatment of persons with GBS.

Prevention

Since GBS is not a disease itself, and it is not known exactly why it occurs, it is difficult to say how GBS could be prevented. Scientists are concentrating on finding new treatments and refining existing ones. Scientists 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 so many cases of GBS 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. 

Guillain Barre Syndrome Research

Bamford NS, Trojaborg W, Sherbany AA, De Vivo DC.  (2002).  Congenital Guillain-Barré syndrome associated with maternal inflammatory bowel disease is responsive to intravenous immunoglobulin.  European Journal of Paediatric Neurology.  6(2):115-119.

Church Potter R, Kaneene JB.  (2003).  A descriptive study of Guillain-Barré Syndrome in high and low Campylobacter jejuni incidence regions of Michigan:  1992-1999.  Neuroepidemiology.  22:245-248.
 
Ghezzi A, Zaffaroni M.  (2001).  Neurological manifestations of gastrointestinal disorders, with particular reference to the differential diagnosis of multiple sclerosis.  Neurological Sciences.  22(Suppl 2):S117-122.

Gondim FA, Brannagan TH 3rd, Sander HW, Chin RL, Latov N.  (2005).  Peripheral neuropathy in patients with inflammatory bowel disease.  Brain.  128(Pt 4):867-879.

Hughes RA, Rees JH.  (1997).  Clinical and epidemiologic features of Guillain- Barré syndrome.  Journal of Infectious Diseases 176:392-8.

Levin KH.  (2004).  Variants and mimics of Guillain-Barré syndrome.  Neurologist.  10:61-74. 

Logullo F, Manicone M, Di Bella P, Provinciali L.  (2006).  Asymmetric Guillain-Barré syndrome.  Neurological Sciences.  27:355-359.

Navarro F, Hanauer SB.  (2003).  Treatment of inflammatory bowel disease: safety and tolerability issues.  American Journal of Gastroenterology.  98(12 Suppl):S18-23.  Su CG, Judge TA, Lichtenstein GR. (2002).  Extraintestinal manifestations of inflammatory bowel disease.  Gastroenterology Clinics of North America.  31(1):307-327.

Zimmerman J, Steiner I, Gavish D, Argov Z. (1985).  Guillain-Barré syndrome: a possible extraintestinal manifestation of ulcerative colitis.  Journal of Clinical Gastroenterology.  7(4):301-303.