Creutzfeldt-Jakob disease
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Creutzfeldt-Jakob Disease (CJD) is a very rare and incurable brain disease that is ultimately fatal. It is the most common of the transmissible spongiform encephalopathies (TSEs). TSEs (also known as prion diseases) are caused by a unique type of infectious agent called a prion, an abnormally-structured form of a protein found in the brain. Other prion diseases include Gerstmann-Sträussler-Scheinker disease (GSS), fatal familial insomnia (FFI) and kuru in humans, and BSE and scrapie in animals.
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Clinical features of CJD
Although CJD is the most common human prion disease, it is still extremely rare and only occurs in about one out of every one million people. It usually affects people aged 45-75, most commonly beginning in people aged 60-65. The exception to this is the more recently-recognised 'variant' CJD (vCJD), which occurs in younger people. The first symptom of CJD is rapidly progressive dementia, leading to memory loss, personality changes and hallucinations. This is accompanied by physical problems such as speech impairment, jerky movements (myoclonus), balance and coordination dysfunction (ataxia) changes in gait, rigid posture, and seizures. The duration of the disease varies greatly, but sporadic (non-inherited) CJD can be fatal within months or even weeks (Johnson, 1998).
The symptoms of CJD are caused by the progressive death of the brain's nerve cells, which is associated with the build-up of abnormal prion protein. When brain tissue from a CJD patient is examined under a microscope, many tiny holes can be seen where whole areas of nerve cells have died. The word 'spongiform' in 'transmissible spongiform encephalopathies' refers to the 'spongy' appearance of the brain tissue.
Prions
The prion that is believed to cause Creutzfeldt-Jakob exhibits (at least) two stable conformations. One, the native state, is water soluble and present in healthy cells. As of 2004, its biological function is unknown. The other conformational state is very poorly water-soluble and readily forms protein aggregates. The CJD prion is dangerous because it promotes refolding of native protein into the diseased state. The number of misfolded protein molecules will increase exponentially and the process leads to a huge load of insoluble prions in affected cells. This mass of insoluble proteins disrupts cell function and causes cell death. Once the prion is transmitted, the defective proteins invade the brain and get produced in a self-sustaining feedback loop, causing exponential spread of the prion. and the patient dies within a few months; a few patients live for about 1-2 years. The defective protein can be transmitted by human growth hormone (HGH) products, corneal grafts or dural grafts (acquired or iatrogenic form, called iCJD) or it can be inherited (hereditary or familial form: fCJD) or it may appear for the first time in the patient (sporadic form: sCJD). In the hereditary and sporadic forms of the disease, the patient will sometimes carry a mutation in the involved protein which makes it more vulnerable to spontaneous misfolding.
Cannibalism has also been implicated as a transmission mechanism for abnormal prions, the disease being known as Kuru found primarily among women and children of the Fore tribe in Papua New Guinea. The disease has also been shown to result from usage of HGH drawn from the pituitary glands of cadavers who died from Creutzfeldt-Jakob Disease [1] (http://www.wired.com/news/medtech/0,1286,62998,00.html), though the known incidence of this cause is (as of April 2004) quite small. Infection through HGH usage is restricted to patients in the U.S. who were treated with HGH during or before 1977, when newer methods of HGH purification were adopted.
Diagnosis
Diagnosis is usually established by clinical symptoms and certain characteristic atypical electroencephalography findings, as well as surrogate markers, including elevation of 14-3-3 protein in the cerebrospinal fluid. In one third of patients with sCJD, deposits of PrpSc are found in the skeletal muscle and/or spleen. Firm diagnosis of vCJD can often be obtained by biopsy of the tonsils, which harbour significant amounts of PrpSc.
Biopsy of living brain tissue is definitive.
There is currently no treatment for the disease, though as of December 2002 the first test of a proposed treatment (injection of pentosan polysulphate directly into the brain) has been approved in Britain.
A new variant of the disease (usually called just variant Creutzfeldt-Jakob Disease (vCJD) but sometimes new variant Creutzfeldt-Jakob Disease (nvCJD)) is distinguished from the classical type by its early onset (usually in the 20s) and a predominance of psychiatric and sensory symptoms. The prions in this form are thought to be transmitted by consuming the meat of bovines with so-called mad cow disease (Bovine Spongiform Encephalopathy), although there is no definite proof of this association as yet. However, over 95% of identified cases of vCJD are in Britain, which suffered a mad cow disease epidemic in the mid-80s.
On September 26, 2003, it was reported that an experimental treatment given to a Northern Irish teenager halted the progress of brain damage caused by variant Creutzfeldt-Jakob disease. The drug, called pentosan polysulphate and commonly used to treat cystitis, was injected into the patient's brain. The patient's weight and heart rate returned to normal levels after receiving the treatment. As of writing, there is no cure for vCJD, a fatal disease. [2] (http://asia.reuters.com/newsArticle.jhtml?type=healthNews&storyID=3515801)
The two German neurologists who first described this disease are Hans Gerhard Creutzfeldt and Alfons Maria Jakob. Most of the clinical findings described in their first papers do not match current criteria for Creutzfeldt-Jakob disease, and it is considered highly likely that the patients in their initial studies were suffering from a completely different disorder.
The United States Centers for Disease Control and Prevention reports the following:
- Creutzfeldt-Jakob Disease (CJD) is a progressive neurological disorder which belongs to a group of degenerative neurologic diseases known as subacute spongiform encephalopathies.
- Clinical features of CJD include a neurological presentation with dementia, and a progressive cerebellar syndrome including ataxia, gait, and speech abnormalities. In most patients, these symptoms are followed by involuntary movements and the appearance of a typical diagnostic electroencephalogram tracing.
- From 10 to 15 percent of CJD cases are inherited, but cases have been associated with the use of contaminated corneal transplants, electrode implants, dura mater grafts, and receipt of human growth hormone.
- CJD occurs worldwide at a rate of about 1 case per million population per year.
- The disease is found most frequently in patients 55-65 years of age, but cases can occur in persons older than 90 years and younger than 55 years of age.
- In more than 85 percent of cases, the duration of CJD is less than 1 year (median: 4 months) after onset of symptoms.
- CDC monitors the occurrence of CJD in the United States through periodic reviews of national mortality data.
- On the basis of mortality surveillance from 1979 to 1994, the annual incidence of CJD remained stable at approximately 1 case per million persons in the United States.
- In the United States, CJD deaths among persons younger than 30 years of age are extremely rare (fewer than 5 deaths per billion per year).
Many Americans first learned about the disease when the famed choreographer George Balanchine died of it in 1983.
In 2004 a new report published in the Lancet medical journal showed that vCJD can be transmitted by blood transfusions (Peden, 2004). The finding alarmed healthcare officials because a large epidemic of the disease might arise in the near future. There is no test to determine if a blood donor is infected and is in the latent phase of vCJD. In reaction to this report, the British government banned anyone who had received a blood transfusion since January 1980, from donating blood in the future.
See also scrapie, a similar disease which affects sheep.
References
- Peden AH, et al (2004). Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 364, 527-29
- Johnson RT, Gibbs CJ (1998). Creutzfeldt-Jakob disease and related transmissible spongiform encephalopathies. N. Engl. J. Med. 339 (27), 1994-2004
External links
- National Creutzfeldt-Jakob Disease Surveillance Unit (http://www.cjd.ed.ac.uk/), UK CJD surveillance unit at Western General Hospital in Edinburgh, Scotland
- US Center for Disease Control (http://www.cdc.gov/ncidod/diseases/cjd/cjd.htm), Creutzfeldt-Jakob disease information
- Mad Cow Facts (http://www.mad-cow-facts.com), Examing any possible link between CJD and BSEda:CJD
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