The human immune system is an amazing system that is constantly on the alert protecting us from sicknesses. Thousands of white blood cells travel in our circulatory system destroying all foreign substances that could cause harm to our body or to any of the millions of processes going on inside. Now imagine a condition where this awesome system turns against the most complex organ in the human body, the brain. Deadly as it is, this condition is known as Rasmussens encephalitis.The meaningful research on Rasmussens encephalitis was begun (unintentionally) by Scott Rogers and Lorise Gahring, two neurologists, who were at the time measuring the distribution of glutamate receptors in the brain. Later on when more provocative information was found they enlisted the help of James McNamara and Ian Andrews, epilepsy experts at Duke University Medical Center.
The details on Rasmussens encephalitis were very bleak at the time when the men began their research. All that was known is that Rasmussens encephalitis was a degenerative disease of the brain that caused seizures, hemiparesis, and dementia normally in the first ten years of life. The seizures that were caused by Rasmussens encephalitis were unstoppable by normal anti-seizure drugs used conventionally. What the worst part of the disease was that the pathogenesis for it were not known and even worse was how it developed.The first clue was delivered when Rogers and Gahring were trying to register the distribution of the glutamate receptors using antibodies, that tag on to the receptor itself. The proteins that make up the glutamate receptors(GluR) are only found inside the blood brain barrier(BBB). Glutamate and a few related amino acids are the dominant form of excitatory neurotransmitter in the central nervous system of mammals. If one of these GluRs happens to wander into the actual bloodstream, that is outside the BBB, it would be considered an outsider and destroyed immediately.
So if these GluRs were put into the normal blood stream then the immune system would produce antibodies which could then be used in the searching for the glutamate receptors.In order to test this theory the researchers injected the GluRs into the blood stream of a normal healthy rabbit hoping to produce good results. At this point the experiment took a dramatic turn, after receiving a few doses of the protein two of the three rabbits began to twitch, as though they were suffering the pain of an epileptic seizure. Now the help of McNamara and Andrews was enlisted.When McNamara and Andrews examined the brain tissue of the rabbits, they saw what seemed to be a familiar inflammatory pattern, clumps of immune cells all around blood vessels. This description exactly matched the description of persons suffering from Rasmussens encephalitis, moreover something as this would never be found in a healthy brain.
A healthy brain has its blood capillaries enclosed in the BBB membrane, so such a case as the one mentioned above would not be possible.As protective as the BBB is, it can be breached by something like a head injury. What was happening was that the antibodies which were out to get the GluR proteins were somehow finding a way into the brain and directing an attack towards all GluR receptor proteins in the brain itself.After some more examinations Rogers and McNamara decided that these attacks were the cause of the seizures that are often experienced by sufferers of Ramussens encephalitis. Then if the case is of antibodies in the bloodstream, than sufferers of Ramussens encephalitis should have them in their bloodstream and healthy normal peoples shouldnt. When this was actually tested the results were positive that Rasmussen sufferers did have these antibodies in their bloodstreams and healthy people did not. These were not only the right kind of antibodies but, the very antibodies that caused the seizures in people and rabbits.
Thus when these antibodies were removed by plasma exchange(PEX) it caused a temporary relief from the seizures but soon the body starts making more antibodies of the type and the seizures start once again. After all the examinations two questions remained, why does the body mount an immune response against one of its own brain proteins, and how do these antibodies get through the BBB?What is thought right now is that people get antibodies when they are infected by a microorganism like a bacterium or a virus that is similar in structure to the GluR. When this happens the body mounts an immune response against, and it just so happens that at this stage you suffer a blow to the head. This will open your BBB to the antibodies and they will attack the friendly GluRs in the brain, causing seizures and further opening your BBB to more antibodies.
Now a malicious rhythm begins: antibodies break through the BBB, inflammation is caused due to the break in, seizures are now caused and BBB opens up further, further opening in the BBB cause more seizures. The inflammation is caused by the autoimmune process against the GluR. All the seizures occur where the initial break in the BBB happened due to a blow to the head, explaining why they seizures are confined to just one hemisphere. The only problem with this theory is that the rabbits developed seizures without ever being whacked on the head, but that also could be because a rabbits brain is not as well insulated as a humans.Normally what happens to an individual is that after he or she is involved in this cycle the only thing that can make for relief is the recurrent plasma exchange. This will only cease the seizures temporarily, but they will start again when the body has made more new antibodies. After this has been done many times the hemisphere in which sufferers of Ramussens encephalitis is present will deteriorate to the point where a hemispherectomy has to be performed.
This will render the person to mental disintegration where he or she has no more mental capacity and generally to the point of no return, death.Rasmussens encephalitis is a very deadly disease, but it is also a very rare disease, occurring in only 48 people between 1957 and 1987. As of now there are no FDA approved drugs for the sufferers of Ramussens encephalitis. Now the researchers are working on a drug that will block the activity of this particular antibody, but this could lead to further problems. If this drug is being administered and a bacteria or virus of a similar structure as the GluR is present the body would disregard it and this would cause more health problems. After all this bad news all one can say is, “Good luck” to the ones suffering from this living hell.Atkins,”Rasmussens encephalitis: nueroimaging findings in four patients.”
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