Guillain-Barre Syndrome Research Paper
Guillain-Barre syndrome is a rare but serious autoimmune disorder that affects the peripheral nervous system. The peripheral nervous system is the portion of the nervous system that is outside the brain and spinal cord. Autoimmune means the patient's immune system begins to attack healthy tissue, which in this case are nerve cells which communicate with muscles. Specifically, they attack the mylein sheaths surrounding the axons of nerve cells. In some cases they even attack the axons themselves.
The first incident of Guillain Barre syndrome was reported on 1859 by Frenchman Jean Baptiste Octave Landry de Thezillat. Landry de Thezillat published a report from an analysis of 10 patients with “ascending paralysis”. Until 1876, ”Landry”s ascending paralysis” was the only term used for this illness at the time. Then Jean-Alexander Barre, Georges Charles Guillain and Andre Strohl researched on this life threatening disease during World War I. These three French physicians carefully recorded and interpreted the muscle reflexes of their patients. They identified the illness to be associated with the peripheral nerves. In 1916 they published the very first comprehensive detailed classic paper on this syndrome. In 1927 the disease was later named Guillain Barre Syndrome.
One famous individual who had Guillain Barre syndrome was one of our very own president. That was our 32nd president, Franklin D. Roosevelt. Originally he was diagnosed with polio, but new analysis proves that he actually had Guillain Barre syndrome. In 1921, at the beginning of his political career, Roosevelt became feverish and developed paralysis, which started in his legs and moved up to his neck. Although he recovered partially, he remained permanently wheelchair-bound. In fact, “Immunological pediatrician Armond Goldman of the University of Texas Medical Branch in Galveston now says FDR's symptoms are more concordant with Guillain-Barré syndrome, a bacterially induced autoimmune disease” (Science Now, 2003). His condition was Guillain Barre syndrome instead of polio because polio paralyzes limbs unevenly and doesn't move up the body. He also felt intense pain when people touched his leg which wasn’t common with polio. Also, it would be highly unusual for polio to strike someone well into adulthood. Other than that, he was our president who faced the Great Depression as well as introduced minimum wage. He helped cultivate the American workforce we have today.
No one knows exactly why Guillain-Barré syndrome appears in some people and while not being apparent in others. Also, it is not clear on what actually 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 (2008). Ordinarily, the cells of the immune system attack only foreign material and invading organisms. But because Guillain-Barré syndrome is an autoimmune disease, it causes your immune system to produce antibodies against your own tissues. Guillain-Barré is referred to as a syndrome rather than a disease because it is not clear that a specific disease-causing agent is involved. The signs and symptoms of the syndrome can vary, which can make it difficult for doctors to diagnose Guillain-Barré in its earliest stages.
Several disorders have symptoms similar to those found in Guillain-Barré, so doctors examine and question patients carefully before making a diagnosis. Collectively, the signs and symptoms help form a certain pattern that will help the doctors differentiate Guillain-Barré from other kinds of disorders. Because the signals traveling along the nerve are now slower, a nerve conduction velocity test can give a doctor clues to aid the diagnosis. To perform this test, doctors place patches called surface electrodes, on the skin over nerves at various locations. Each patch gives off a very mild electrical impulse, which then stimulates the nerve. The nerve's resulting electrical activity is recorded by the other electrodes. The distance between electrodes and the time it takes for electrical impulses to travel between electrodes are used to determine the speed of the nerve signals which can lead to diagnosis because of delayed nerve signals in Guillain-Barré syndrome.
Symptoms of this syndrome begin five days to three weeks following the seemingly ordinary viral infection. The first symptoms of Guillain-Barré syndrome consist of muscle weakness accompanied by prickly, tingling sensations. Symptoms are symmetric, another important characteristic that helps distinguish the syndrome from other causes of weakness. Normal reflexes are first diminished, and then finally lost. The weakness ultimately affects all the voluntary muscles, eventually resulting in paralysis for the patient. When those muscles necessary for breathing become paralyzed, the patient must be placed on a mechanical ventilator, which takes over the function of breathing (2007). Very severely ill patients may have complications stemming from other nervous system abnormalities that result in problems with fluid balance in the body, and blood pressure and heart rhythm irregularities which may result in death.
In fact, about 5% of all Guillain-Barré syndrome patients die, most from cardiac rhythm disturbances. While the majority of patients recover fully, there are some patients who have some degree of residual weakness, or even permanent paralysis (2008). It should be noted that, most people reach the stage of greatest weakness within the first 2 weeks after symptoms appear, and by the third week of the illness 90 percent of all patients are at their weakest. Also, according to statistics, “On average, in any given year, GBS affects about one to two people in every 100,000 people in the United States, a relatively rare rate. It is equally prevalent both genders, and in any age bracket” (The Gale Encyclopedia of Science, 2008). Though, adults over 50 years of age are 2-3 times more likely to get the syndrome than younger people. Each year, between 6,000 and 9,100 people in the United States get Guillain-Barré syndrome. This means that about 140 people get it every week.
Treatment of Guillain-Barré syndrome consists of carefully monitoring and paying attention to the patient's fluid, respiration, and cardiovascular status. Although, performing Plasmapheresis early in the course of Guillain-Barré syndrome, has been shown to shorten the course and severity of the syndrome, and consists of withdrawing the patient's blood, passing it through a cell separator, and returning all the cellular components along with either donor plasma or a manufactured replacement solution. This action is thought to get rid of the blood of the antibodies that are attacking the patient's myelin (2007). Recently, it has been shown that the use of high doses of immunoglobulin given through a needle may be just as helpful as plasmapheresis. Immunoglobulin is a substance naturally manufactured by the body's immune system in response to various threats. Patients with certain characteristics tend to have a generally worse outcome from Guillain-Barré syndrome. 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 as mentioned above. Possible theoretical cures for this disease would include genetic engineering or gene therapy. Gene therapy aims at treating mutations by genetically modifying specific genes that are causing disruptions and relieves the syndromes symptoms. These genetic modifications can either increase or reduce the expression of specific genes and restore the normal function of the product of these genes. This would decrease the affects of Guillain Barre syndrome effects and make for a possible cure for the syndrome itself.
The cause of the weakness and paralysis of Guillain-Barré syndrome is demyelination of the nerve pathways. This means that the immune system of the body 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 is an insulating substance that is wrapped around nerves in the body which speeds up the transmission of nerve signals and allows the transmission of signals over long distances.
In diseases in which the peripheral nerves' myelin sheaths are injured or degraded such as Guillain-Barré syndrome, the nerves cannot transmit signals efficiently. Guillain-Barré syndrome can affect the motor neurons that control muscle movement and sensory neurons that transmit sensory signals such as pain, temperature, and touch. That is why the muscles begin to lose their ability to respond to the brain's commands, commands 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. Also, the brain may receive inappropriate signals that result in tingling or painful sensations to the patient. Because the signals to and from the arms and legs must travel the longest distances in the body, they are most vulnerable to interruption. Therefore, muscle weakness and tingling sensations usually first appear in the hands and feet and progress upwards.
There are several types of Guillain-Barré syndrome, classified by the part of the peripheral nerve involved in the condition. The most common type of Guillain-Barré syndrome is acute inflammatory demyelinating polyradiculoneuropathy (AIDP). In AIDP, the immune response damages myelin, which is the covering that protects axons and promotes the efficient transmission of nerve impulses. 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. In AMAN, only the axons of motor neurons are damaged. In AMSAN, the axons of sensory neurons are also damaged. All these kinds of syndromes affect the peripheral nervous system.
Some studies show that normal variations in certain genes may be associated with an increased risk of developing Guillain-Barré syndrome (2009). However, more research is necessary to identify and confirm associated genes. Many of the genes that may increase the risk of Guillain-Barré syndrome are involved in the immune system, and their roles in fighting infection may contribute to the development of the condition. The one related gene associated with Guillain-Barré syndrome has been found to be “TNF” or “tumor necrosis factor”. The molecular location of this gene on chromosome 6 and its base pairs are 31,543,343 to 31,546,112. This gene encodes a multifunctional proinflammatory cytokine (2009). A cytokine being a number of substances, secreted by certain cells of the immune system and having an effect on other cells. This cytokine is involved in the regulation of a wide spectrum of biological processes and the cytokine has been implicated in a variety of diseases, including autoimmune diseases. It also induces cell death. When the gene is mutated, the function of the cytokine begin to counter and target nerve myelin sheaths.
Most people who develop Guillain-Barré syndrome have a bacterial or viral infection prior to developing the signs and symptoms of the condition. However, only a very small percentage of people who have an infection develop Guillain-Barré syndrome. In order to fight the infection, specialized immune cells produce proteins called antibodies that recognize specific proteins or molecules on the pathogen. Some research shows that antibodies that recognize molecules on some pathogens may also recognize proteins on the body's own nerves. As a result, the immune system attacks the nerves, causing inflammation and damaging the axons and myelin, which can lead to the signs and symptoms of Guillain-Barré syndrome.