Creutzfeldt-Jakob Disease Signs and Symptoms
- Jun 25, 2011
It is clear that Creutzfeldt-Jakob disease is caused by an infectious agent, but it is not yet clear what type of agent that is. Originally assumed to be a virus, evidence is accumulating that, instead, CJD is caused by a protein called a prion (PREE-on, for “proteinaceous infectious particle”) transmitted from victim to victim. The other spongiform encephalopathies are also hypothesized to be due to prion infection.
If this hypothesis is proved true, it would represent one of the most radical new ideas in biology since the discovery of deoxyribonucleic acid (DNA). All infectious diseases, in fact all life, uses nucleic acids-DNA or ribonucleic acid (RNA)-to code the instructions needed for reproduction. Inactivation of the nucleic acids destroys the capacity to reproduce. However, when these same measures are applied to infected tissue from spongiform encephalopathy victims, infectivity is not destroyed. Furthermore, purification of infected tissue to concentrate the infectious fraction yields protein, not nucleic acid. While it remains possible that some highly stable nucleic acid remains hidden within the purified protein, this is seemingly less and less likely as further experiments are done. The “prion hypothesis,” as it is called, is now widely accepted, at least provisionally, by most researchers in the field. The most vocal proponent of the hypothesis, Stanley Prusiner, was awarded the Nobel Prize in 1997 for his work in the prion diseases.
A prion is an altered form of a normal brain protein. The normal protein has a helical shape along part of its length. In the prion form, a sheet structure replaces the helix. According to the hypothesis, when the normal form interacts with the prion form, some of its helical part is converted to a sheet, thus creating a new prion capable of transforming other normal forms. In this way, the disease process resembles crystallization more than typical viral infection, in which the virus commands the host’s cellular machinery to reproduce more of the virus. Build-up of the sheet form causes accumulation of abnormal protein clumps and degeneration of brain cells, which is thought to cause the disease.
The brain protein affected by the prion, called PrP, is part of the membrane of brain cells, but its exact function is unknown. It is composed of about 250 subunits, called amino acids, coded for by a gene on chromosome 20. Slight genetic differences, called polymorphisms, give rise to two slightly different normal protein forms: sub-unit 129 is a “methionine” in one form, but is “valine” in the other. A person may have all of one, all of the other, or a mixture of the two, depending on their genetic inheritance. Both forms have the normal helical structure, and function normally. However, susceptibility to prion conversion is influenced by subunit 129: a person with a mixture of forms is more resistant to conversion. All the cases of vCJD tested have had just methionine at 129. Exposure to the infectious agent is, of course, still required for disease development. Prion diseases are not contagious in the usual sense, and transmission from an infected person to another person requires direct inoculation of infectious material.
Familial CJD, on the other hand, does not require exposure, but develops through the inheritance of other, more disruptive mutations in the gene for the normal PrP protein. Researchers believe these mutations increase the likelihood that the protein may more spontaneously “flip” to the sheet form; once created, these can then convert other normal-form molecules. The other two inherited human prion diseases, Gerstmann-Straussler-Scheinker disease and fatal familial insomnia, involve different mutations in the same gene.
The large majority of CJD cases are sporadic, meaning they have no known route of infection or genetic link. Causes of sporadic CJD are likely to be diverse and may include spontaneous genetic mutation, spontaneous protein changes, or unrecognized exposure to infectious agents. It is highly likely that future research will identify more risk factors associated with sporadic CJD.
About one in four people with CJD begin their illness with weakness, changes in sleep patterns, weight loss, or loss of appetite or sexual drive. A person with CJD may first complain of visual disturbances, including double vision, blurry vision, or partial loss of vision. Some visual symptoms are secondary to cortical blindness related to death of nerve cells in the occipital lobe of the brain responsible for vision. This form of visual loss is unusual in that patients may be unaware that they are unable to see. These symptoms may appear weeks to months before the onset of dementia.
First symptoms vary widely and may include the following:
* memory losses
* impaired abstraction and planning
* language and comprehension disturbances
* poor judgment
* decreased attention and increased restlessness
* personality changes and psychosis
* Behavioral and personality changes
* Confusion and memory problems
* Lack of coordination
* Strange physical sensations
* Vision problems
As the disease advances, patients may experience a rapidly progressive dementia and in most cases involuntary and irregular jerking movements called myoclonus.
Patients also may appear startled and become rigid. In advanced stages of the disease, patients have difficulties with movement, swallowing and talking. In the final stage, patients lose all mental and physical function and may lapse into a coma. Many patients die from an infection such as pneumonia.
The average duration of disease - from the onset of symptoms to death - is four to six months. Ninety percent of patients die within a year. Some cases progress very rapidly, lasting only a few weeks before the patient’s death, and others may last two or three years, especially if the disease occurs at an early age.
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