A piece of well-oiled machinery consists of an intricate and complex system: there are well-organized processes, mechanisms within the device work efficiently, and multiple processes function simultaneously to subsequently perform various functions. What happens when there is a glitch in the machine? When there is something wrong, such as connections between intricate processes, which do not follow through, the machine fails to function properly. In some cases, there are not any adjustment or fallback mechanisms. At that point, the damage can be irreversible and the machinery is no longer salvageable. [However, this can illustrate the interactions and processes within the complex machinery.]
The human brain can react in much the same way. Neurodegenerative diseases are telltale signs of a "glitch" in the neural mechanical processes within the brain. Thus, pathological problems of the brain demonstrate how the brain controls movement and behavior. It is evident in the physical as well as emotional behavior. (5) It also illustrates the interaction between the central nervous system to the peripheral nervous system. There must be connections between neural activity within the brain and the rest of the central and peripheral nervous systems. One can also understand an illustration of the brain as being a "box" composed of interconnected smaller boxes. These integrated boxes in turn demonstrate the concept that, "Brain=Behavior=Being."
The purpose of this essay is to provide a general overview, as well as neurological overview, of the neurodegenerative disease, Creutzfeldt-Jakob Disease. In doing so, it will show how the brain proves to be the center of behavior and creates the individual's sense of "the Self."
Creutzfeldt-Jakob Disease (CJD) is a horrendous fatal brain-deteriorating disease for which there is no cure or treatment. CJD occurs worldwide. There is approximately one new case per two million people per year, and about 30 cases occur per year in Great Britain. The most common age of onset is over the age of 55, although it is rare over the age of 80. (3) However, CDJ is more common than reported. In one study, 13 percent Alzheimer patients autopsied were found to really had CJD. (2)
In 1920, German neurologist, H.G.Creutzfeldt, was credited with the first clinical description of the degenerative disorder. A year later another neurologist, A.Jakob separately described four cases that had clinical characteristics suggestive of what is now referred to as Creutzfeldt-Jakob Disease.
Creutzfeldt-Jakob is caused by a prion. One strain of CJD is linked to Mad Cow Disease in England. People get CJD through three means: familial (10-15%), sporadic (85%) and iatrogenic (remainder inadvertently exposed through a medical procedure.)(4) An example of an iatrogenic CJD is, those who had received treatment with human growth hormone developed Creutzfeldt-Jakob disease. In the past, growth hormone was gathered from the pituitary glands of dead people. It is speculated that some of these deceased people had died of CJD. Another iatrogenic CJD example, is the contamination of surgical instruments. Since normal sterilization methods did not kill the CJD infectious agent, it spread by surgical instruments. Three cases occurred in people who underwent brain surgery. Apparently, Creutzfeldt-Jakob patient was operated on prior and the same surgical instruments were used. Presumably, this was how the infectious disease was transferred from one patient to another. Therefore, "friendly fire" incidents like these, are more a danger to public health than mere number of cases would suggest. (3) Most recently, there is much debate whether neurodegenerative disease such as bovine spongiform encephalopathy (mad cow disease) in cows can be spread to humans through consumption of contaminated beef. Already a number of studies have been done and overall the results show no indication of BSE transmission via consumption. However, there may be a link between bovine spongiform encephalopathy and a new variant of CJD. (3)
A step towards treatment of this Creutzfeltz-Jakob disease is to find the cause of the disease. Scientists' research priorities are identification of the transmissible agent and then to develop a test to detect antibodies to and the antigen of the transmissible agent for use in examination.
Four features characterize CJD deterioration: spongiform change, neuronal loss, astrocytosis and amyloid plaque formation. (1) Prion diseases are also referred to as spongiform encephalopathies because of the evident numerous holes found in the spongy brain tissue. (1,2,4) When spongiform change is present in human brain tissue a numerous small holes are present in histological samples of the affected tissue. The frequency and morphology of these holes are not a normal feature of brain tissue, but a feature of CJD affected brain tissue. These changes may be due to various forms of infection. Cortical change is found in most cases of CJD. Spongiform change is detectable in the basal ganglia, thalamus and cerebella cortex as well. Astrocytosis is found throughout CJD infected tissue. It is the proliferation of astrocytes in the cerebral cortex.
Degenerative brain diseases are caused predominately by the presence or absence of particular hormones. In the amyloid plaque formation, brain cells produce this particular protease-resistant protein (PrP) in larger amounts than normal. (2) As stated earlier, Creutzfeldt-Jakob disease-causing agent is proteinaceous infectious particles (prion). Identification of a protein normally produced by the brain cells that had been altered. The purpose of PrP protein is not even known in its normal form. Using a high power microscope, one is able to see the protein as it clumped together to form miniature stick-like structures which are known as "scrapie-associated-fibril" or "prion rods." Apparently, the prion induces a protease-sensitive protein (PrPc) to form prion protein (PrPsc). (2)
Other histological changes in CJD brain tissue involve, status spongiosus, which is disintegration of "the cerebral cortical cytoarchitecture," microgliosis in both astrocytes (supports function of neurons) and microglia (CNS immune cells), white matter necrosis and cavitation. (1) However bear in mind, some of these histological abnormalities may not be due to a human prion diseases, but are due to aging processes. Some brain aging characteristics are swollen cortical neurones, and white matter necrosis and cavitation. (1, 3)
Since the agent that causes CJD is obviously minute, some scientists believe that it may be a virus. However, if this is the case it should be able to detect some reaction of the body to it, in the same way that body forms antibody. It should also be detectable under powerful electron microscopes. Neither of these occurs. Therefore it is assumed that this is some very small virus, or perhaps a virus that had become altered in some way. As of now, this theory remains unproven. Extensive neurodegenerative disease research continues.
Other such spongiform encephalopathies are Scrapie, a disease of sheep, Kuru, a disease of Fore people in New Guinea and Bovine spongiform encephalopathy (BSE), otherwise know as "Mad Cow Disease." All of these degenerative brain diseases show similar changes and effects on specimen as CJD does.
Research into spongiform encephalopathies. In 1967, brain extract from a person from a person who died of Kuru was injected into the brain of a monkey. Within a few years, the monkey developed a disease similar to Kuru, and when the monkey's brain was examined microscopically, it showed similar spongy changes. This therefore showed that at least artificially, the illness could be transmitted from one species to another. A year later, Creutzfeldt-Jakob disease was transmitted to a laboratory animal by inoculating extracts of brain from a person who had died from CJD (4). This research concludes that these disease are related in that they cause the same type of illness, share similar microscopic features, and are caused by infectious properties agents. However they are different from normal bacteria and viruses.
Since the brain is the communication center of the central and peripheral nervous system, the are not only neural observations, but also observable signs in the CJD patients. In other words, chemical and cellular malfunctions within the CJD affected brain regions result subsequently change the individual's behavior.
CJD victims' first symptoms are often visual, coordination and psychological problems. It can take decades after exposure for the patient to show symptoms. The exact time of onset of the illness can be very difficult to determine. Mercifully, only in the very early stages are the patients aware of anything amiss. They usually complain of clumsiness, feeling muddled and/or blurring of eyesight. In the beginning, there may be subtle lapses of memory for daily events, sometimes there are mood changes, in particular, loss of interest and withdrawal from involvement in social activities is apparent. Ability to work dwindles away. It is often noted that a task that was once simple, becomes a difficult one. At this beginning stage, others may pass off the sickness as a mild depression. However, the disease hinders more than mood rapidly after and can no longer be passed off as depression. (4) As the disease progresses, the patients lose awareness of their surroundings and of their disabilities. Within a few weeks, other features appear quickly: an unsteadiness and hesitancy in motor functions, like walking, deteriorating vision, slurring and slowing of speech and difficulty in diction. (4) Usually, there is a rapid downhill course of bodily malfunctions, such as the development of shakiness, stiffness of the limbs, jerky movements, incontinence and the loss of the ability to speak or move. (4)
Do CJD patients suffer pain in the degenerative process? Individuals with CJD may sometimes feel discomfort from, for example, remaining in one position for too long, but there is no physical pain associated with the disease itself. However, there is tremendous emotional pain. Those who know the patient may feel the most distress, as they see a loved one so seriously ill. Individuals affected by CJD usually succumb within 6 months of the onset of the disease. CJD patients often die at home and therefore have home health services. A CJD patient's spouse heavy-heartedly describes her husband's futile condition:
"CJD...take a brief walk with me while I tell you of the most horrifying disease known to mankind. The horror of CJD is two-foldfirst no one knows they actually have CJDendless neurological tests are performed when someone has trouble with balance/coordination, personality/behavioral changes, fearfulness, loss of memory, visual problems, insomnia. The irony is that test results show nothing. But there is something seriously wrong, neurological problems/symptoms increase and it is the beginning of the end. Because when diagnosis of CJD is confirmed by either brain biopsy or cerebrospinal fluid testingthere is nothing under God's heaven that can save anyone. The complete CNS is shutting down, slowly, but surely, and a person is trapped inside their won body with no way out." (6)
Cruetzfeldt-Jakob disease clearly demonstrates how the brain is the center of body processes. Precise cellular communication is vital for the individual. The brain collects sensory input from complex neural connections and then interacts with different parts of the nervous and motor system to create behavioral and motor patterns. The consequence of these sensory inputs and sensory and motor outputs is the individual's behavior. In CJD, there is sensory input and outputs malfunction because crucial regions of the brain, such as the basal ganglia, thalamus and cerebella cortex, are eaten away. Unfortunately in CJD cases, like that of the spouse's husband, these crucial cellular pathways to, from and within the brain are destroyed.
In light of the information presented, "the Self" seems lost with the degeneration of the brain. The malfunctions of the brain in Creutzfeldt-Jakob disease, show how the brain = "the Self." Creutzfeldt-Jakob Disease severs basic behavioral patterns, such as perception and movement. The fact that one's neural communication is severed and eventually shuts down all body function control, is evident. The knowledge that one's brain is "riddled with holes" due to a proteinaceous infectious particle is speculative. Although many think that an individual is much more than mere neural connections, firing motor symphonies, neurotransmitters, and selective permeability, Creutzfeldt-Jakob disease puts a new spin on individual identity. Ultimately, the patients or their loved ones do not focus on the CJD facts and figures. Their reality is that an individual slowly disintegrates before their eyes, the sense of "the Self" is lost.
1. The Neuropathology of CJD
2. Intro to Creutzfeldt-Jakob Disease
3. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 1996; 347: 921-25.
4. Creutzfeldt-Jakob Disease
5. Delcomyn, Fred. Foundations of Neurobiology , W.H.Freeman and Company Copyright 1997, pg.437.
6. CJD Voice Homepage
6. CJD Voice Homepage
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This paper reflects the research and thoughts of a student at the time the paper was written for a course at Bryn Mawr College. Like other materials on Serendip, it is not intended to be "authoritative" but rather to help others further develop their own explorations. Web links were active as of the time the paper was posted but are not updated.