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Creutzfeldt-Jakob disease

 
Medical Encyclopedia: Creutzfeldt-Jakob Disease
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Definition

Creutzfeldt-Jakob disease (CJD) is a transmissible, rapidly progressing, fatal neurodegenerative disorder called a spongioform degeneration that seems to be related to "mad cow disease."

Description

Before 1995, Creutzfeldt-Jakob disease was little-known outside of the medical profession; even within it, many practitioners did not know much about it. Most doctors had never seen a case. With the recognition of a so-called "new variant" or simply variant form of CJD with the strong possibility that those with it became infected simply by eating contaminated beef, CJD has become one of the most talked-about diseases in the world. Additionally, the radical theory that the infectious agent is a normal protein that has been changed in its form has also sparked much interest.

First described in the first part of the twentieth century independently by Cretzfeldt and Jakob, CJD is a neurodegenerative disease causing a rapidly progressing dementia ending in death, usually within eight months of the onset of symptoms. It is also a very rare disease, affecting only about one in every million in the population through out the world. In the United States, CJD is thought to affect about 250 people each year. CJD affects adults primarily between ages 50 and 75.

Spongiform encephalopathies

The most obvious pathologic feature of CJD is the formation of numerous fluid-filled spaces in the brain (vacuoles) resulting in a sponge-like appearance. CJD is one of several human "spongiform encephalopathies," diseases that produce this characteristic change in brain tissue. Others are kuru; Gerstmann-Straussler-Scheinker disease, a genetic predominantly characterized by cerebellar ataxia (a kind of movement disorder); and fatal familial insomnia, associated with progressive insomnia, autonomic system disfunction, and weakness caused by motor system dysfunction.

Kuru was prevalent among the Fore people in Papua, New Guinea, and spread from infected individuals after their deaths through the practice of ritual cannibalism, in which the relatives of the dead person honored him by consuming his organs, including the brain. Discovery of the infectious nature of kuru won the Nobel Prize for Carleton Gadjusek in 1976. The incubation period for kuru was between four to 30 years or more. While kuru has virtually disappeared following the cessation of these cannibalistic practices, several new cases continue to arise each year.

Cases of CJD have been grouped into three types: familial, iatrogenic, and sporadic.

  • Familial CJD, representing 5–15% of cases, is inherited in an autosomal dominant manner, meaning that either parent may pass along the disease to a child, who may then develop CJD later in life.
  • Iatrogenic CJD occurs when a person is infected during a medical procedure, such as organ donation, blood transfusion, or brain surgery. The rise in organ donation has increased this route of transmission; grafts of infected corneas and dura mater (the tissue covering the brain) have been shown to transmit CJD. Another source is hormones concentrated from the pituitary glands of cadavers, some of whom carried CJD, for use in people with growth hormone deficiencies. Iatrogenic infection from exposure to nerve-containing tissue represents a small fraction of all cases. The incubation period between exposure to the infectious agent is very long and is estimated to be from less than 10 to more than 30 years. It remains unlikely, but not impossible, that blood from patients with CJD is infectious to others by transfusion.
  • Sporadic CJD represents at least 85% of all cases. Sporadic cases have no identifiable source of infection. Death usually follows first symptoms within eight months.
Animal forms and "mad cow disease"

Six forms of spongiform encephalopathies are known to occur in other mammals: scrapie in sheep, recognized for more than 200 years; chronic wasting disease in elk and mule deer in Wyoming and Colorado; transmissible mink encephalopathy; exotic ungulate encephalopathy in some types of zoo animals; feline spongiform encephalopathy in domestic cats; and bovine spongiform encephalopathy (BSE) in cows.

BSE was first recognized in Britain in 1986. Besides the spongiform changes in the brain, BSE causes dementia-like behavioral changes—hence the name "mad cow disease." BSE was thought to be an altered form of scrapie, transmitted to cows when they were fed sheep offal (slaughterhouse waste) as part of their feed, but it is now thought to be more likely to be a primary cattle disease spread by contaminated feed.

The use of slaughterhouse offal in animal feed has been common in many countries and has been practiced for at least 50 years. The trigger for the BSE epidemic in Great Britain seems to have come in the early 1980s, when the use of organic solvents for preparation of offal was altered there. It is possible that these solvents had been destroying the agent called a prion, thereby preventing infection, and that the change in preparation procedure opened the way for the agent to "jump species" and cause BSE in cows that consumed scrapie-infected meal. The slaughter of infected (but not yet visibly sick) cows at the end of their useful farm lives, and the use of their carcasses for feed, spread the infection rapidly and widely. For at least a year after BSE was first recognized in British herds, infected bovine remains continued to be incorporated into feed, spreading the disease still further. Although milk from infected cows has never been shown to pass the infectious agent, passage from infected mother to calf may have occurred through unknown means.

Beginning in 1988, the British government took steps to stop the spread of BSE, banning the use of bovine offal in feed and other products and ordering the slaughter of infected cows. By then, the slow-acting agent had become epidemic in British herds. In 1992, it was diagnosed in over 25,000 animals (1% of the British herd). By mid-1997, the cumulative number of BSE cases in the United Kingdom had risen to more than 170,000. The feeding ban did stem the tide of the epidemic; however, the number of new cases each week fell from a peak of 1,000 in 1993 to less than 300 two years later.

The export of British feed and beef to member countries was banned by the European Union, but cases of BSE had developed in Europe by then as well; however, by mid-1997, only about 1,000 cases had been identified. In 1989, the United States banned import of British beef and began monitoring United States herds in 1990. To date, no BSE has been detected in the United States, and only one case has been reported in North America in a cow imported to Canada from Great Britain.

Variant CJD: The human equivalent of mad cow disease?

From the beginning of the BSE epidemic, scientists and others in Britain feared that BSE might jump species again to infect humans who had consumed infected beef. This, however, had never occurred in scrapie from sheep, a disease known from hundreds of years. In 1996, the first report of this possibility occurred and this fear seemed to be realized with the first cases of a new variant of Creutzfeldt-Jacob disease, termed nvCJD, now just vCJD. Its victims are much younger than the 60–65 year old average for CJD, and the time from symptom onset to death has averaged 12 months or more instead of eight. The disease appears to cause more psychiatric symptoms early on. EEG abnormalities characteristic of CJD are not typically seen in vCJD.

As of July 2001, the total number of human cases of vCJD is 102. It is of major concern that the number of cases per year seems to be increasing by a factor of 1.35 each year. Almost all the cases have been found in Great Britain with three in France, one in Ireland, and one suspected in Hong Kong (who spent time in Great Britain).

Evidence is growing stronger that vCJD is in fact caused by BSE:

  • almost all of the cases so far have occurred in Great Britain, the location of the BSE epidemic.
  • BSE injected into monkeys produces a disease very similar to vCJD
  • BSE and vCJD produce the same brain lesions after the same incubation period when injected into laboratory mice
  • brain proteins isolated from vCJD victims, but not from the other forms of CJD, share similar molecular characteristics with brain proteins of animals that died from BSE

Many researchers now treat the BSE-vCJD connection as solidly established.

Assuming that BSE is the source, the question that has loomed from the beginning has been is how many people will eventually be affected. Epidemiological models of infectious disease produce estimates ranging from less than one hundred (a level already broken) to tens of thousands or more, depending on the assumptions used by the modelers. The incubation period of vCJD in humans is not known, nor are the genetic and environmental risk factors that influence susceptibility, nor the quantity of infectious agent needed to cause the disease. It is estimated that between one and two million infected cattle have been eaten by humans, most in the earliest stages of the epidemic. Estimates cannot be based on the very few cases that have developed so far. These cases could represent the very few people with the right combination of exposure and susceptibility to a relatively fast-developing infection, or they could be the first few victims of a slower-acting, more highly infectious agent.

— Larry I. Lutwick, MD


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Dictionary: Creutz·feldt-Ja·kob disease   (kroits'fĕlt-yä'kôp) pronunciation
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n.
A rare, usually fatal disease of the brain, characterized by progressive dementia and gradual loss of muscle control, that occurs most often in middle age and is caused by a slow virus. Also called Jakob-Creutzfeldt disease.

[After Hans G. Creutzfeld (1883-1964) and and Alfons M. Jakob (1884-1931), German psychiatrists.]


Britannica Concise Encyclopedia: Creutzfeldt-Jakob disease
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Rare fatal disease of the central nervous system. It destroys brain tissue, making it spongy and causing progressive loss of mental functioning and motor control. The disease commonly arises in adults between the ages of 40 and 70. Patients usually die within a year. There is no known cure. The disease is caused by a prion that builds up in neurons. Inherited or random mutation accounts for 99% of cases; the rest come from prion exposure during medical procedures and possibly from eating the meat of cattle with mad cow disease.

For more information on Creutzfeldt-Jakob disease, visit Britannica.com.

Neurological Disorder:

Creutzfeldt-Jakob disease

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Definition

Creutzfeldt-Jakob disease (CJD) is a rapidly progressive disease causing damage to the brain. It is one of a group of rare diseases that affects humans and animals, known as transmissible spongiform encephalopathies (TSE) and is believed to be caused by a prion, a newly identified type of disease-causing agent. Creutzfeldt-Jakob disease is characterized by dementia and walking difficulties. Death can occur up to two years after the first symptoms; however, most people die within seven months. There is no treatment or cure.

Description

Creutzfeldt-Jakob disease is a serious progressive degenerative disorder of the brain that was first described in the 1920s by two German researchers, and is characterized by sudden development of rapidly progressive neurological and neuromuscular symptoms. When symptoms begin, affected individuals may develop confusion, depression, behavioral changes, impaired vision, and/or impaired coordination. As the disease progresses, there may be rapidly progressive deterioration of thought processes and memory (dementia), resulting in confusion and disorientation, impairment of memory control, personality disintegration, agitation, and restlessness. Affected individuals also develop neuromuscular abnormalities such as muscle weakness and loss of muscle mass (wasting); irregular, rapid, shock-like muscle spasms (myoclonus); and/or relatively slow, involuntary, continual writhing movements, particularly in the arms and legs. Later stages of the disease may include further loss of physical and intellectual functions, a state of unconsciousness (coma), and increased susceptibility to repeated infections of the respiratory tract. In many affected individuals, life-threatening complications may develop less than a year after the disorder becomes apparent.

There are three main forms of CJD, each one with its distinctive basic features. The sporadic CJD, which accounts for approximately 85% of all cases worldwide and occurs by chance, is associated with the presence of a misshapen protein in the brain, known as a prion ("proteinaceous infectious particle"). Sporadic CJD cannot be caught from another person or animal, is not related to diet, nor can it be inherited. On the contrary, inherited (or familial) CJD accounts for 5–10% of all cases of CJD and is caused by a faulty gene called prion-related protein (PRPN) that is passed down from parents to their children in a dominant inheritance, which means patients will develop the disease if they inherit a defective gene from just one parent. Symptoms are similar to sporadic CJD, but they appear earlier and have a longer time course.

Unlike the previous two CJD forms, acquired CJD affects those people who have not inherited the condition by two other ways. The iatrogenic CJD occurs due to accidental infection after medical procedures such as human pituitary hormone injection or dura mater transplantation. The variant CJD (vCJD), a type of CJD that was first identified in 1996, is passed from cows with bovine spongiform encephalopathy (BSE, or "mad cow disease") to humans. The variant form affects mostly younger adults and has different clinical and pathological characteristics.

All forms of CJD can be present in a person for long periods (often more than 20 years) during which there are no symptoms. The duration of the illness before death varies from a matter of weeks (typical of sporadic CJD) to three to twelve months (typical of variant CJD). However, there have been exceptions in both types.

Demographics

CJD appears to affect males and females in equal numbers. It occurs worldwide with an incidence rate that has remained stable at approximately one case per million people, annually. It usually first appears in mid-life, beginning between ages 20 and 68, with the average age at onset of symptoms being around age 50. The onset of the iatrogenic form depends on the age of exposure.

Causes and symptoms

All forms of CJD are caused by the presence of a faulty protein in the brain, called prion. Prions occur in both a normal form, which is a harmless protein found in the body's cells, and in an infectious form, which causes disease. The harmless and infectious forms of the prion protein are nearly identical, but the infectious form takes a different folded shape. Sporadic CJD may develop because some of a person's normal prions spontaneously change into the infectious form of the protein and then alter the prions in other cells in a chain reaction by a mechanism that is not yet understood. Misfolded protein molecules then spread through the brain and stick together to form fibers and/or clumps called plaques that can be seen with powerful microscopes. These bundles of twisted protein disrupt brain cells and eventually leave large holes in the brain tissue, giving the brain a spongy appearance. Fibers and plaques may start to accumulate years before symptoms of CJD begin to appear. It is still unclear what role these abnormalities play in the disease or how they might affect symptoms.

About 5–10% of all CJD cases are inherited. These cases arise from a mutation, or change, in the gene PRPN that controls formation of the normal prion protein. While prions themselves do not contain genetic information and do not require genes to reproduce themselves, infectious prions can arise if a mutation occurs in the gene for the body's normal prions. If the prion gene is altered in a person's sperm or egg cells, the mutation can be transmitted to the person's offspring. Several different mutations in the prion gene have been identified. The particular mutation found in each family affects how frequently the disease appears and what symptoms are most noticeable. However, not all people with mutations in the prion gene develop CJD. This suggests that the mutations merely increase susceptibility to CJD and that other, still-unknown factors also play a role in the disease.

CJD does not cause any symptoms at first. The first symptoms to appear include slow thinking, difficulty concentrating, impaired judgment, memory loss, personality and behavioral changes, and difficulties with coordination and vision. These symptoms rapidly give way to increasing mental deficits leading to severe, progressive dementia (mental decline) associated with self-neglect, apathy or irritability, and prominent muscle spasms (myoclonus). Seizures commonly occur as the disease progresses. Symptoms continue to worsen until both mental and physical functions are lost; patients are completely bedridden, and eventually lapse into coma. Comatose patients may die as a result of infection associated with being immobile, such as pneumonia.

Diagnosis

There is currently no single diagnostic test for CJD. Indeed, the only definitive diagnosis can be assessed by a postmortem examination (autopsy) of the brain or examining a sample of brain tissue (brain biopsy). However, CJD should be considered in adults who experience a sudden onset of rapidly progressive dementia and neuromuscular symptoms such as myoclonus.

An electroencephalogram (EEG) and a magnetic resonance imaging (MRI) scan may be useful in determining abnormalities in the brain. People may be diagnosed as having "probable CJD." Although not definitive, all those who have been diagnosed as probable CJD in life, and who subsequently had an autopsy, were found to have been a CJD patient. Genetic testing can be carried out in people suspected of having the inherited form of CJD, in order to increase certainty of diagnosis. Such people usually report a family history of the disease.

Iatrogenic CJD is usually diagnosed on the basis of the affected person's medical history. Those at risk include people having received hormones derived from humans before 1992, or dura mater transplant grafts before 1985.

Treatment team

A neurologist or a psychiatrist is normally the primary consultant for CJD, and continual nursing care may be necessary as disease progresses. Physical therapist may also be required.

Treatment

As of 2004, no treatment has been shown to be effective against CJD. Treatments are available to alleviate some symptoms, such as morphine for muscle pain, and clonazepam (Rivotril) or sodium valproate (Epilim) for jerky movements. A wide range of drugs has been tested for their ability to slow the progress of the disease, but none has been shown to be useful.

At present, care consists of managing the specific problems faced by patients with CJD. Speech therapy and occupational therapy may help, and the support of district nurses and social services is often invaluable for people with CJD and their caregivers.

Recovery and rehabilitation

Because CJD is an incurable, fatal disease with a fast progression, recovery and rehabilitation are not possible. The emphasis in treatment is placed upon comfort and support of the affected individual and the caregivers.

Clinical trials

As of mid 2004, there are no ongoing clinical trials for CJD.

Prognosis

The outcome for a person with CJD is usually very poor. Complete dementia commonly occurs within six months or less after the appearance of the first symptoms, with the person becoming totally incapable of self-care. The disorder is fatal in a short time, usually within seven months, but a few people survive as long as one or two years after diagnosis. The cause of death is usually infection, heart failure, or respiratory failure.

Special concerns

Hospitals and health care providers take special precautions to minimize the risk of transferring prions from surgical equipment or donated tissues. Medical histories of potential cornea donors that indicate a familial history of possible Creutzfeldt-Jacob disease rule out the use of those corneas for transplantation. Additionally, regulations and records regarding livestock feed and transfer of livestock are maintained by the United States Department of Agriculture.

Resources

BOOKS

Staff. The Official Patient's Sourcebook on Creutzfeldt-Jakob Disease: A Revised and Updated Directory for the Internet Age. San Diego: Icon Group International, 2003.

PERIODICALS

Mastaglia, F. L., M. J. Garllep, B. A. Phillips, and P. J. Zilko. "Inflammatory Myopathies: Clinical, Diagnostic and Therapeutic Aspects." Muscle & Nerve (April 2003): 407–425.

"U.S. to Expand Testing of Cattle for Disease." New York Times March 16, 2004: pA25.

OTHER

"New 'Mad Cow' Link to Humans and Livestock." CNN.com. August 29, 2000 (May 27, 2004). http://edition.cnn.com/2000/HEALTH/08/29/britain.madcow/.

NINDS Creutzfeldt-Jakob Disease Information Page. National Institute of Neurological Disorders and Stroke. April 20, 2004 (May 27, 2004). http://www.ninds.nih.gov/health_and_medical/disorders/cjd.htm.

ORGANIZATIONS

Creutzfeldt-Jakob (CJD) Foundation Inc. P.O. Box 5312, Akron, OH 44334. (330) 668-2474 or (800) 659-1991. crjakob@aol.com. http://www.cjdfoundation.org.


Marcos do Carmo Oyama


Iuri Drumond Louro, MD, PhD


Food and Fitness: Creutzfeldt-Jakob disease
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A fatal disease characterized by spongy degeneration of the brain and progressive dementia. It is thought to be caused by peculiar proteins called prions that can be transmitted in human growth hormone extracted from human pituitary glands. Creutzfeldt-Jakob disease may be related to BSE (see bovine spongiform encephalopathy).

Veterinary Dictionary: Creutzfeldt–Jakob disease (CJD)
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A rare, fatal spongiform encephalopathy of humans caused by a prion.

  • variant C.-J. d. (vCJD) — a fatal neurological disease of humans caused by infection with the agent of bovine spongiform encephalopathy.
Wikipedia: Creutzfeldt–Jakob disease
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 This article's introduction section may not adequately summarize its contents. To comply with Wikipedia's lead section guidelines, please consider expanding the lead to provide an accessible overview of the article's key points. (July 2009)
Creutzfeldt–Jakob disease
Classification and external resources

Tonsil biopsy in variant CJD. Prion Protein immunostaining.
ICD-10 A81.0, F02.1
ICD-9 046.1
OMIM 123400
DiseasesDB 3166
eMedicine neuro/725
MeSH D007562

Creutzfeldt–Jakob disease or CJD (pronounced /ˈkrɔɪtsfɛlt ˈjɑkɔp/) (sometimes incorrectly referred to as mad cow disease) is a degenerative neurological disorder (brain disease) that is incurable and invariably fatal.[1] It is the most common among the types of transmissible spongiform encephalopathy found in humans.[2]

Contents

History

The disease was first described by German neurologist Hans Gerhard Creutzfeldt in 1920 and shortly afterwards by Alfons Maria Jakob, giving it the name Creutzfeldt–Jakob. Some 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 at least two of the patients in initial studies were suffering from a different ailment.[citation needed]

Causes

Pathophysiology

Transmissible spongiform encephalopathy diseases are caused by prions. The diseases are thus sometimes called prion diseases. Other prion diseases include Gerstmann–Sträussler–Scheinker syndrome (GSS), fatal familial insomnia (FFI) and kuru in humans, as well as bovine spongiform encephalopathy (BSE, commonly known as mad cow disease) in cattle, chronic wasting disease (CWD) in elk and deer, and scrapie in sheep. Alpers' syndrome in infants is also thought to be a transmissible spongiform encephalopathy caused by a prion.[3][4]

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 2007, its biological function is presumably in transmembrane transport or signaling. The other conformational state is very poorly water-soluble and readily forms protein aggregates.

People can also acquire CJD genetically through a mutation of the gene that codes for the prion protein (PRNP). This only occurs in 5–10% of all CJD cases.

The CJD prion is dangerous because it promotes refolding of native proteins into the diseased state (Step 1: UNFOLDING of alpha-helices; Step 2: REFOLDING to beta-pleated sheets.). The number of misfolded protein molecules will increase exponentially,[citation needed] and the process leads to a large quantity of insoluble prions in affected cells. This mass of misfolded proteins disrupts cell function and causes cell death. Mutations in the gene for the prion protein can cause a misfolding of the dominantly alpha helical regions into beta pleated sheets. This change in conformation disables the ability of the protein to undergo digestion. Once the prion is transmitted, the defective proteins invade the brain and are produced in a self-sustaining feedback loop, causing exponential spread of the prion, leading to death within a few months, although a few patients have lived as long as two years.

Stanley B. Prusiner of University of California, San Francisco (UCSF) was awarded the Nobel Prize in physiology or medicine in 1997 for his discovery of prions. For more than a decade, Yale University neuropathologist Laura Manuelidis has been challenging this explanation for the disease. In January 2007 she and her colleagues published an article in the Proceedings of the National Academy of Science and reported that they have found a virus-like particle (but without finding nucleic acids so far) in less than 10% of the cells a scrapie-infected cell line and in a mouse cell line infected by a human CJD agent.[5]

Types

Types include:

  • sporadic (sCJD)[6]
  • variant (vCJD)[7] This type is more likely to be acquired. It can be iatrogenic.[8] It was first identified in 1996.[9]
  • familial (fCJD)[10]

Incidence and prevalence

Although CJD is the most common human prion disease, it is still rare, occurring in about one out of every one million people every year. It usually affects people aged 45–75, most commonly appearing in people between the ages of 60–65. The exception to this is the more recently-recognised 'variant' CJD (vCJD), which occurs in younger people.

CDC monitors the occurrence of CJD in the United States through periodic reviews of national mortality data: According to the CDC:

  • CJD occurs worldwide at a rate of about 1 case per million population per year.
  • 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 five deaths per billion per year[citation needed]).
  • The disease is found most frequently in patients 55–65 years of age, but cases can occur in people older than 90 years and younger than 55 years of age.
  • In more than 85% of cases, the duration of CJD is less than 1 year (median: four months) after onset of symptoms.[1][11]

New concerns on incidence and prevalence

In The Lancet (June 2006), a University College London team suggested that it may take more than 50 years for vCJD to develop, from their studies of kuru, a similar disease in Papua New Guinea.[12] The reasoning behind the claim is that kuru was possibly transmitted through cannibalism in Papua New Guinea when family members would eat the body of a dead relative as a sign of mourning. In the 1950s, the practice was banned, thereby preventing any further possible transmission. In the late 20th century, however, kuru reached epidemic proportions in certain Papua New Guinean communities, therefore suggesting that vCJD may also have a similar incubation period of 30 to 50 years. A critique to this theory is that while mortuary cannibalism was banned in Papua New Guinea in the 1950s, that does not necessarily mean that the practice ended. Fifteen years later Jared Diamond was informed by Papuans that the practice continued.[13] There is dispute as to whether the Fore ever practiced cannibalism, due to the fact that nobody ever observed them and that Kuru could have passed to the Fore through the preparing of the dead body for burial.

These researchers noticed a genetic variation in some kuru patients that has been known to promote long incubation periods. They have also proposed that individuals who contracted CJD in the early 1990s represent a distinct genetic subpopulation, with unusually short incubation periods for BSE. This means that there may be many more vCJD patients who have longer incubation periods, which may surface many years later.[12]

In 1997 a number of Kentuckians contracted the disease. It was discovered that all the victims had a penchant for squirrel brains.[14] See: http://www.guardian.co.uk/uk/2008/aug/03/bse.medicalresearch for recent concerns.

Symptoms

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). In some people, the symptoms can continue for years. In most patients, these symptoms are followed by involuntary movements and the appearance of an atypical diagnostic electroencephalogram tracing.

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 proteins. 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.

Diagnosis

The diagnosis of CJD is suspected when there are typical clinical symptoms and signs such as rapidly progressing dementia with myoclonus. Further investigation can then be performed to support the diagnosis including

Diffusion Weighted Imaging (DWI) images are the most sensitive. In about 24% of cases DWI shows only cortical hyperintensity; in 68%, cortical and subcortical abnormalities; and in 5%, only subcortical anomalies.[15] The involvement of the thalamus can be found in sCJD, is even stronger and constant in vCJD.[16]

Clinical testing for CJD has always been an issue. Diagnosis has mostly been based on clinical and physical examination of symptoms. In recent years, studies have shown that the tumour marker Neuron-specific enolase (NSE) is often elevated in CJD cases[citation needed].

In one third of patients with sporadic CJD, deposits of "prion protein (scrapie)," PrPSc, can be found in the skeletal muscle and/or the spleen[citation needed]. Diagnosis of vCJD can be supported by biopsy of the tonsils, which harbour significant amounts of PrPSc; however, biopsy of brain tissue is the definitive diagnostic test.

  • Clinical and Pathologic Characteristics:[17]
Characteristic Classic CJD Variant CJD
Median age at death 68 years 28 years
Median duration of illness 4–5 months 13–14 months
Clinical signs and symptoms Dementia; early neurologic signs Prominent psychiatric/behavioral symptoms; painful dysesthesias;

delayed neurologic signs
Periodic sharp waves on electroencephalogram Often present Often absent
Signal hyperintensity in the caudate nucleus and putamen on diffusion-weighted and FLAIR MRI Often present Often absent
"Pulvinar sign"[specify] on MRI Not reported Present in >75% of cases
Immunohistochemical analysis of brain tissue Variable accumulation. Marked accumulation of protease-resistant prion protein
Presence of agent in lymphoid tissue Not readily detected Readily detected
Increased glycoform ratio on immunoblot analysis of

protease-resistant prion protein

 Not reported Marked accumulation of protease-resistant prion protein
Presence of amyloid plaques in brain tissue May be present May be present
  • An abnormal signal in the posterior thalami on T2- and diffusion-weighted images and fluid-attenuated inversion recovery sequences on brain magnetic resonance imaging (MRI); in the appropriate clinical context, this signal is highly specific for vCJD. (Source: CDC)

Treatment

There is currently no cure for CJD; the disease is invariably fatal, though the search for viable treatments continues. An experimental treatment was given to a Northern Irish teenager, Jonathan Simms, beginning in January 2003.[18] The medication, called pentosan polysulphate (PPS) and used to treat interstitial cystitis, is infused into the patient's lateral ventricle within the brain. PPS does not seem to stop the disease from progressing, and both brain function and tissue continue to be lost. However, the treatment is alleged to slow the progression of the otherwise untreatable disease, and may have contributed to the longer than expected survival of the seven patients who were studied.[19] The CJD Therapy Advisory Group to the UK Health Departments advises that data are not sufficient to support claims that pentosan polysulphate is an effective treatment and suggests that further research in animal models is appropriate.[20] A 2007 review of the treatment of 26 patients with PPS finds no proof of efficacy because of the lack of accepted objective criteria.[21]

Scientists have investigated using RNA interference to slow the progression of scrapie in mice. The RNA blocks production of the protein that the CJD process transforms into prions. This research is unlikely to lead to a human therapy for many years.[22]

Both amphotericin B and doxorubicin have been investigated as potentially effective against CJD, but as yet there is no strong evidence that either drug is effective. Further study has been taken with other medical drugs, but none are effective.

Dr. Michael Geschwind, Dr. Bruce Miller and Dr. Stanley Prusiner from University of California, San Francisco are currently running a treatment trial for sporadic CJD using quinacrine, a medicine originally created for malaria. Pilot studies showed quinacrine permanently cleared abnormal prion proteins from cell cultures, but results have not yet been published on the clinical study.

Transmission

The defective protein can be transmitted by human growth hormone (hGH) products, Immunoglobulins (IVIG), corneal grafts, dural grafts or electrode implants (acquired or iatrogenic form: iCJD); 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 form, a mutation occurs in the gene for PrP, PRNP. Ten to fifteen percent of CJD cases are inherited. (CDC)

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,[23] though the known incidence of this cause is (as of April 2004) quite small. The risk of infection through cadaveric HGH usage in the US only ceased when the medication was withdrawn in 1985.

It is thought that humans can contract the disease by consuming material from animals infected with the bovine form of the disease. The only suspected cases to arise thus far have been vCJD, although there are fears — based on animal studies — that consuming beef or beef products containing prion particles can also cause the development of classic CJD. When BSE material infects humans the resulting disease is known as (new) variant CJD Disease (nvCJD).[4]

Cannibalism has also been implicated as a transmission mechanism for abnormal prions, causing the disease known as kuru, found primarily among women and children of the Fore tribe in Papua New Guinea. While the men of the tribe ate the body of the deceased and were not affected, the women and children ate the brain and contracted the disease from infected brain tissue.

Prions, the infectious agent of CJD, may not be inactivated by means of routine surgical instrument sterilization procedures. The World Health Organization and the US Centers for Disease Control and Prevention recommend that heat and chemical decontamination be used in combination to process instruments that come in contact with high-infectivity tissues. No cases of iatrogenic transmission of CJD have been reported subsequent to the adoption of current sterilization procedures, or since 1976.[24][25][26] Copper–hydrogen peroxide has been suggested as an alternative to the current recommendation of sodium hydroxide or sodium hypochlorite.[27] Thermal depolymerization also destroys prions in infected organic and inorganic matter, since the process dissolves protein at the molecular level.

Blood donor restrictions

In 2004 a new report published in the Lancet medical journal showed that vCJD can be transmitted by blood transfusions.[28] 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 during 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.[29] From 1999 there was a ban in the UK for using UK blood to manufacture factional products such as albumin.[30]

On May 28, 2002, the United States Food and Drug Administration instituted a policy that excludes from donation anyone who spent at least six months in certain Western European countries, (or three months in the United Kingdom), from 1980 to 1996. Given the large number of U.S. military personnel and their dependents residing in Europe, it was expected that over 7% of donors would be deferred due to the policy. Later changes to this policy have relaxed the restriction to a cumulative total of five years or more of civilian travel in Western European countries (six months or more if military). The three-month restriction on travel to the UK, however, has not been changed.[31]

The American Red Cross's policy is as follows: During the period January 1, 1980 to December 31, 1996, spending a total time of three months or more in the Channel Islands, England, the Falkland Islands, the Isle of Man, Gibraltar, Northern Ireland, Scotland, and Wales precludes individuals from donating. Since January 1, 1980 to present, spending a total time of five years or more in the above countries and countries in Europe. (For complete listing, please go to Redcross.org)

A similar policy applies to potential donors to the Australian Red Cross' Blood Service, precluding people who have spent a cumulative time of six months or more in the United Kingdom between 1980 and 1996.

The Singapore Red Cross precludes potential donors who have spent a cumulative time of three months or more in the United Kingdom between 1980 and 1996.

In New Zealand anyone who has lived in the UK, France or the Republic of Ireland for a total of six months or more between 1980 and 1996 is prohibited from donating blood.

Similar regulations are in place in Germany, where anyone who has spent six months or more living in the UK or Northern Ireland between January 1980 and December 1996 is permanently barred from donating blood.[32]

As of 1999, Health Canada announced a policy to defer individuals from donating blood if they have lived within the United Kingdom for one month or more from January 1, 1980 to December 31, 1996. In 2000, the same policy was applied to people who have resided in France, for at least three months from January 1980 to December 1996. Canada will not accept blood from a person who has spent more than six months in a Western European country since January 1, 1980.[33]

The Association of Blood Donors of Denmark precludes potential donors who have spent a cumulative time of at least twelve months in the United Kingdom between 1 January 1980 and 31 December 1996.

The Swiss Blutspendedienst SRK precludes potential donors who have spent a cumulative time of at least six months in the United Kingdom between 1 January 1980 and 31 December 1996.

Sperm donor restrictions

In the U.S., the FDA has banned import of any donor sperm, motivated by a risk of Creutzfeldt–Jakob disease, inhibiting the once popular[34] import of, for example, Scandinavian sperm. The risk, however, is not known, since artificial insemination has not been studied as a route of transmission.[35] It is also not known whether prions cross the blood–testis barrier.[35]

Cultural references

 Lists of miscellaneous information should be avoided. Please relocate any relevant information into appropriate sections or articles. (May 2009)

The disease was featured in an episode of The X-Files, "Our Town", in which a group of cannibals eat the entire body (including the brain) of their fellow humans in order to stay young forever. They contract the disease from one of their victims, and it passes through a part of the town, killing 28.

During the fourth season of the TV series House, in episode four "Guardian Angels", House's job applicants suspect the patient of having contracted CJD after doing cosmetic work on a cadaver with similar symptoms at a funeral parlor. To test the diagnosis, the team dig up the grave and carry out a brain biopsy, which is negative. In the end she is revealed to have ergotism.

See also

References

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  2. ^ "UW Hospital warns 53 patients about possible exposure to fatal disease". Wisconsin State Journal. 2009-07-24. http://www.madison.com/wsj/topstories/459435. Retrieved 2009-07-24. 
  3. ^ Chakraborty C, Nandi S, Jana S (April 2005). "Prion disease: a deadly disease for protein misfolding". Current Pharmaceutical Biotechnology 6 (2): 167–77. doi:10.2174/1389201053642321. PMID 15853695. 
  4. ^ a b Obi RK, Nwanebu FC (2008). "Prions And Prion Diseases". African Journal of Clinical and Experimental Microbiology 9 (1): 38–52. ISSN 1595-689X. http://ajol.info/index.php/ajcem/article/view/7481. Retrieved 2009-06-20. 
  5. ^ Manuelidis L, Yu ZX, Barquero N, Banquero N, Mullins B (February 2007). "Cells infected with scrapie and Creutzfeldt-Jakob disease agents produce intracellular 25-nm virus-like particles". Proceedings of the National Academy of Sciences of the United States of America 104 (6): 1965–70. doi:10.1073/pnas.0610999104. PMID 17267596. 
  6. ^ Niimi Y, Iwasaki Y, Umemura T (December 2008). "MM2-cortical-type sporadic Creutzfeldt–Jakob disease with early stage cerebral cortical pathology presenting with a rapidly progressive clinical course". Neuropathology 28 (6): 645–51. doi:10.1111/j.1440-1789.2008.00904.x. PMID 18410280. http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0919-6544&date=2008&volume=28&issue=6&spage=645. 
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  9. ^ Will RG, Ironside JW, Zeidler M (April 1996). "A new variant of Creutzfeldt–Jakob disease in the UK". Lancet 347 (9006): 921–5. doi:10.1016/S0140-6736(96)91412-9. PMID 8598754. 
  10. ^ Wang XF, Dong CF, Zhang J (March 2008). "Human tau protein forms complex with PrP and some GSS- and fCJD-related PrP mutants possess stronger binding activities with tau in vitro". Mol. Cell. Biochem. 310 (1–2): 49–55. doi:10.1007/s11010-007-9664-6. PMID 18038270. 
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  13. ^ Diamond, JM (7 September 2000). "Archaeology: Talk of cannibalism". Nature 407 (25-26): 25. doi:10.1038/35024175. 
  14. ^ Berger JR, Waisman E, Weisman B (August 1997). "Creutzfeldt-Jakob disease and eating squirrel brains". Lancet 350 (9078): 642. doi:10.1016/S0140-6736(05)63333-8. PMID 9288058. 
  15. ^ Young, Geoffrey S.; G; F; M; H; L; L; W et al. (June–July 2005). "Diffusion-Weighted and Fluid-Attenuated Inversion Recovery Imaging in Creutzfeldt–Jakob Disease: High Sensitivity and Specificity for Diagnosis". American Journal of Neuroradiology (American Society of Neuroradiology) 26 (6): 1551–1562. PMID 15956529. http://www.ajnr.org/cgi/content/full/26/6/1551. Retrieved 2007-10-30. 
  16. ^ Tschampa, Henriette J.; M; F; P; S; U (01 May 2003). "Thalamic Involvement in Sporadic Creutzfeldt–Jakob Disease: A Diffusion-Weighted MR Imaging Study". American Journal of Neuroradiology (American Society of Neuroradiology) 24 (5): 908–915. PMID 12748093. http://www.ajnr.org/cgi/content/full/24/5/908. Retrieved 2007-10-30. 
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  19. ^ Bone, Ian (12 July 2006). "Intraventricular Pentosan Polysulphate in Human Prion Diseases: A study of Experience in the United Kingdom". Medical Research Council. http://www.mrc.ac.uk/NewsViewsAndEvents/News/MRC001707. Retrieved 2007-01-01. 
  20. ^ "Use of Pentosan Polysulphate in the treatment of, or prevention of, vCJD". Department of Health:CJD Therapy Advisory Group. http://www.dh.gov.uk/en/Policyandguidance/Healthandsocialcaretopics/CJD/CJDgeneralinformation/DH_4031039. Retrieved 2007-10-30. 
  21. ^ Rainov NG, Tsuboi Y, Krolak-Salmon P, Vighetto A, Doh-Ura K (2007). "Experimental treatments for human transmissible spongiform encephalopathies: is there a role for pentosan polysulfate?". Expert opinion on biological therapy 7 (5): 713–26. doi:10.1517/14712598.7.5.713. PMID 17477808. 
  22. ^ Pfeifer A, Eigenbrod S, Al-Khadra S (December 2006). "Lentivector-mediated RNAi efficiently suppresses prion protein and prolongs survival of scrapie-infected mice". The Journal of Clinical Investigation 116 (12): 3204–10. doi:10.1172/JCI29236. PMID 17143329. Lay summary – BBC News (2006-12-04). 
  23. ^ Mills JL, Schonberger LB, Wysowski DK (April 2004). "Long-term mortality in the United States cohort of pituitary-derived growth hormone recipients". The Journal of Pediatrics 144 (4): 430–6. doi:10.1016/j.jpeds.2003.12.036. PMID 15069388. Lay summary – Wired (2004-04-09). 
  24. ^ "Questions and Answers: Creutzfeldt–Jakob Disease Infection-Control Practices". Infection Control Practices/CJD (Creutzfeldt–Jakob Disease, Classic). Centers for Disease Control and Prevention. January 4, 2007. http://www.cdc.gov/ncidod/dvrd/cjd/qa_cjd_infection_control.htm#sterilization. Retrieved 2007-06-09. 
  25. ^ "WHO Infection Control Guidelines for Transmissible Spongiform Encephalopathies". World Health Organization: Communicable Disease Surveillance and Control. 26 March 1999. http://www.who.int/csr/resources/publications/bse/WHO_CDS_CSR_APH_2000_3/en/. Retrieved 2007-06-09. 
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  27. ^ Solassol J, Pastore M, Crozet C (2006). "A novel copper–hydrogen peroxide formulation for prion decontamination". J Infect Dis 194 (6): 865–869. doi:10.1086/506947. PMID 16941355. 
  28. ^ Peden AH, Head MW, Ritchie DL, Bell JE, Ironside JW (2004). "Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient". Lancet 364 (9433): 527–9. doi:10.1016/S0140-6736(04)16811-6. PMID 15302196. 
  29. ^ "Variant CJD and blood donation" (PDF). National Blood Service. August 2004. http://www.blood.co.uk/pdfdocs/vcjd.pdf. Retrieved 2009-06-20. 
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  32. ^ "Permanent exclusion criteria" (in German). Blutspendedienst Hamburg. http://www.blutspendehamburg.de/blutspender-gesucht/ausschluss. Retrieved 2009-06-20. 
  33. ^ "Donor Qualification". Héma-Québec. 2009-03-26. http://www.hema-quebec.qc.ca/anglais/dondesang/qualifidonneurs.htm. Retrieved 2009-06-20. 
  34. ^ Stein, Rob (August 13, 2008). "Mad Cow Rules Hit Sperm Banks' Patrons". washingtonpost.com (The Washington Post Company). http://www.washingtonpost.com/wp-dyn/content/article/2008/08/12/AR2008081203131.html. Retrieved 2008-10-04. 
  35. ^ a b Kotler, Steven (2007-09-27). "The God of Sperm". LA Weekly. http://www.laweekly.com/2007-09-27/news/the-god-of-sperm/. Retrieved 2009-06-20. 

External links

v • d • e
Infectious diseases - Prion diseases / Transmissible spongiform encephalopathy (A81, 046)
Prion diseases in humans

inherited/PRNP: fCJD · Gerstmann-Sträussler-Scheinker syndrome · Fatal familial insomnia

sporadic: sCJD

acquired/transmissible: Kuru · vCJD
Prion diseases in animals


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