Guillain-Barre Syndrome, or acute inflammatory demyelinating polyneuropathy, is a self-limiting disease characterized by areflexia and acute progressive motor weakness of at least one limb. Other symptoms include motor weakness of the extremities and face, loss or reduction of deep tendon reflexes, decreased sensation throughout the body,ophthalmoplegia, and ataxia. In severe cases respiratory failure and autonomic dysfunction may occur. Respiratory failure results from the demyelination of the phrenic and intercostal nerves. Consequently, the person loses the ability to inhale and exhale. Autonomic dysfunction resulting from the demyelination of the sympathetic and vagus nerves can lead to cardiac arrhythmias, tachycardia, postural hypotension, and hypertension. Analysis of the cerebral spinal fluid (CSF) shows increased protein concentration with few cells. Other tests reveal a decreased nerve conduction velocity resulting from segmental demyelination with mononuclear cell infiltration.

In 70% of the afflicted individuals, the symptoms of Guillain-Barre Syndrome (GBS) occur within two weeks following infection. Clinical diagnosis is based on the presence of albumino-cytological dissociation in the CSF. Following the onset, motor weakness progressively deteriorates for four weeks and may lead to respiratory failure and cardiac instability. If either respiratory failure or cardiac abnormalities occur, the patient will be placed in the intensive care unit and closely monitored. Eventually the person's condition will cease to deteriorate, and he/she will enter a plateau period of two to four weeks during which little or no change will occur. Following the plateau stage, the patient will gradually recover. The mean recovery time to independent walking is 85 days, if the person is not on a respirator. If he/she was on a respirator, the mean time doubles to 169 days. The affected individual can usually expect a full recovery; however, some are left with a residual deficit after one year.

0.6 to 1.9 persons per 100,000 people are afflicted with GBS each year. The disease occurs worldwide and can strike anyone. Recent data has shown that white Caucasian males between the ages of 16 to 25 and 45 to 60 are the most prone. 15 to 20% of GBS patients require some form of mechanical ventilation during the course of the disease. Although mortality rate is 2.4 to 6.4%, there is an 80% recovery. Despite the high recovery rate, 15% of the survivors retain some disability.

90% of GBS patients had a viral-like illness and 4.5% received vaccinations within one month of the onset. Most of the illnesses preceding GBS were caused by cytomegalovirus and Epstein-Barr viruses. Strong correlations also occurred with Campylobacter jejuni infections, Lyme disease, and AIDS. IgM and IgG antibodies to C. jejuni were detected in 15 of 38 GBS patients. Of the individuals that contracted GBS following vaccinations, the swine flu vaccine of 1976-77 had the highest correlation rate. On a lesser note, five cases of GBS werereported following vaccinations with Haemophilus influenza's type b diphtheria toxoid-conjugate. Since 14 million doses of the vaccine have been distributed since June 1990, the incidence remains marginal.

Experimental evidence linking GBS in humans with allergic neuritis in animals has attempted to show an immunologic basis for the disease. Allergic neuritis in animals is similar to GBS in humans and is characterized by muscle weakness, flaccid tail, weight loss, ataxia, and paraplegia. This can be induced by immunization with myelin P2 protein and galactocerebroside. The research scientists hypothesized that P2-reactive T cells and anti-galactocerebrocide antibodies caused mononuclear cell infiltration which then demyelinated the peripheral nerves leading to the symptoms of allergic neuritis. Autopsy of the animals later confirmed their hypothesis and revealed axonal degeneration, demyelination of peripheral nerves, lymphocytic infiltration, and chromatolysis of lower motor neurons. Other animal studies have revealed a positive correlation between allergic neuritis in mice and those infected with Campylobacter jejuni. C. jejuni infections have also lead to massive infiltration of mononuclear cells.

Recent evidence supports the idea that autoimmune factors resulting from infection may lead to GBS. More specifically, bacterial toxins released from Campylobacter jejuni, Escherichiacolt, and Vibrio cholerae have the ability to bind to gangliosides to form a hapten-carrier complex. Gangliosides are widely distributed membrane components of all cell types. They are involved in cell to cell recognition, act as receptors for bacterial lectins and toxins, influence cell growth and differentiation, and inhibit T-cell proliferation. Since gangliosides are too small to illicit an immune response alone, they must be conjugated with another protein. When gangliosides are bound to a toxin, the complex is large enough to be recognized by macrophages. The macrophages then engulf the complex and present it to T-helper cells through major histocompatibility complex (MHC) II molecules. This activates B cells and T cells. The T cells and macrophages release a number of factors into the blood including tumor necrosis factor alpha (TNFa). TNFa can induce tissue damage by inflammatory mechanisms. The B cells release anti-ganglioside IgM and IgG antibodies into the blood. The anti-ganglioside antibodies disrupt ganglioside-mediated metabolic functions. Anti-ganglioside antibodies have been found in at least 20% of GBS patients, while serum from healthy individuals contained no such antibodies.

TNFa that is released by macrophages and T lymphocytes causes selective cytotoxic damage to Schwann cells and myelinated fibers. TNFa is associated with the pathogenesis and progression of the disease and increases with the severity of the disease. During the recovery phase TNFa returns to normal pre-GB levels. 54% of patients affected with GBS have increases of TNFa in their serum; however, no detectable levels of TNFa can be identified in the CSF of those individuals. The blood-brain barrier prevents any passage of TNFa into the CSF.

The anti-ganglioside antibodies (AGabs) released by activated B cells disrupt ganglioside functions and cause complement fixation and inflammation in peripheral nervous tissue. This induces an immunological attack on peripheral Schwann cell resulting in extensive demyelination. The AGabs are limited to the peripheral nervous system, because they cannot pass through the blood-brain barrier. No explanation exists to explain why the AGabs attack only nerve cells and not all cells in the periphery, since the ganglioside receptors are widely distributed to all cell types. Equally baffling is the reason why administration of AGabs in animals with allergic neuritis causes no affect on the disease process, since those antibodies already exist.

In addition to questions concerning AGabs activity in GBS, complications have arisen with C. jejuni infections preceding and causing GBS. First, not all C. jejuni bacteria produce ganglioside binding toxins; thus, no immune response should take place. Second, some strains of C. jejuni contain cell walls that are cross-reactive with the gangliosides. The cell walls could themselves act as immunogens. Third, AGabs in GBS patients have appeared without C. jejuni infections. These data seem to indicate that more than one pathogenic mechanism exist in GBS. Also the role of gangliosides serving as the sole antigen has to be questioned.

Treatment of GBS includes one of two mechanisms: plasmapheresis or immune globulin therapy. Plasmapheresis involves the selective removal of plasma from the circulation by centrifugal cell separation or filtration across a semi-permeable membrane. This removes or dilutes "circulating factors" involved in the pathogenesis of GBS. The end result is a more rapid recovery. The patient will also spend less time on a respirator and have a shorter time to un-assisted walking. The disadvantages associated with plasmapheresis include high costs, risks of contamination, and patient discomfort with administration. Immune globulin therapy, on the other hand, is easier to administer, readily available, and has fewer risks. The disadvantages, though, include high costs and a slightly higher relapse rate than with plasmapheresis.

When treating the patient, psychological support and pain management must be given. A therapist may be required to help the patient cope with feelings of demoralization, sadness, fear, anxiety, hopelessness, and isolation. Although the individual is physically helpless, he/she is mentally alert; therefore, effective communication with the patient is mandatory. Television, radio, and photo may help reduce the stress. GBS persons also need privacy, and care must be taken to insure that. Pain is sometimes difficult to manage. Frequent changes in position may provide some relief, and blankets and socks will give warmth. Anti-inflammatory substances, narcotics, and antidepressants are also effective in reducing the pain and discomfort.

After the polio vaccine was discovered, Guillain-Barre Syndrome has become the most prevalent demyelinating nervous disorder. In a struggle to understand the nature of the disease, scientists are trying to discover the exact mechanism by which it acts. Although several antigens such as gangliosides have been linked to GBS, the immunogen(s) that causes the autoimmune response has not been identified. The best hypothes to date is is that some substance, a toxin released from bacteria or viruses, combines with gangliosides to induce an autoimmune response. The organisms that are involved remain a mystery as well as the exact mechanism of action. On a brighter side much has been learned about the pathogenesis of GBS enabling physicians to better care and treat their patients. Despite the enormous disability, the recovery rate remains high.

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