Creutzfeldt-Jakob Disease (CJD)

Creutzfeldt-Jakob disease (CJD) affects about one in every one million people per year worldwide; in the United States, there are about 200 cases per year. This rare, degenerative, fatal brain disorder leads to a rapid decrease of mental function and movement. Even though CJD usually appears later in life, it can occur at a younger age and runs a rapid course. However, the onset of symptoms usually occurs around the age of sixty. It is estimated that 90 percent of individuals die within one year.

In the early stages of CJD, people have a lack of coordination, behavioral changes, visual disturbances, and memory lapses. As the disease progresses, there is more obvious mental deterioration, blindness, involuntary movements, weakness of extremities, and coma.

There are three major categories of CJD:

1. Sporadic CJD: is the most common type of CJD and accounts for at least 85 % of cases. The sporadic version can occur even though the individual has no known risk factors.
2. Hereditary CJD or familial CJD: is “rare” and only accounts for five to ten percent of cases in the United States. Familial CJD occurs when an individual inherits the abnormal prion and has a family history of the disease and/or tests positive for a genetic mutation associated with CJD.
3. Acquired CJD: was first described in 1920 and since then less than one percent of cases have been acquired CJD.¹ The disease is transmitted by exposure to the brain or nervous system tissue, usually through certain medical procedures. However, there is no evidence that CJD is acquired through casual contact with a CJD patient.¹

CJD is the most common of the known human transmissible spongiform encephalopathies (TSEs). Transmissible spongiform encephalopathies are found in humans and animals. Spongiform refers to the characteristic appearance of infected brains, which become filled with holes until they resemble sponges under a microscope. Human TSEs include Kuru, fatal familial insomnia (FFI), and Gerstmann-Straussler-Scheinker disease (GSS).

Kuru was identified in people of an isolated tribe in Papua New Guinea and is associated with cannibalism practiced by the women at night in a special funerary ritual when someone had died. Their remains in total (brain included) were eaten by the women and their children. Since this practice has diminished so has Kuru among this tribe.² FFI and GSS are extremely rare hereditary diseases found in just a few families around the world.

Some TSEs are found in specific species of animals. These include bovine spongiform encephalopathy (BSE), which is found in cows. This disease is often referred to as “mad cow” disease. Another TSE is known as “scrapie,” which affects sheep and goats. There is also mink encephalopathy and feline encephalopathy. TSE which occurs in elk, deer, and exotic zoo animals is often called, “chronic wasting disease.”

Classic CJD is not related to mad cow disease.³ A new variant, nvCJD, is an infectious form and is related to mad cow disease. NvCJD accounts for less than one percent of cases and affects younger people. If someone is exposed to contaminated products, they can get nvCJD or vCJD. Cases of nvCJD or vCJD have occurred when an individual received a corneal transplant from an infected donor or from contaminated electrodes that were used during brain surgery and had not been effectively disinfected.

Currently, some researchers believe an unusual "slow virus" or another organism causes CJD. However, a virus or other organism in people with the disease has not been isolated.

The agent that causes CJD has several characteristics that are unusual for known organisms such as viruses and bacteria.

• It is difficult to kill,
• It does not appear to contain any genetic information in the form of nucleic acids (DNA or RNA),
• It usually has a long incubation period before symptoms appear.
• In some cases, the incubation period could be as long as 50 years.

The leading scientific theory at this time maintains that CJD and the other TSEs are caused by a type of protein called a prion.⁴

A CJD prion causes normal proteins to fold abnormally. When this occurs, this affects other proteins’ ability to function. Prion proteins 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 have the same sequence of amino acids (the "building blocks" of proteins). Once it becomes an infectious form of protein, there is a different folded shape compared to the normal protein. Sporadic CJD could develop because some of a person’s normal prions spontaneously change into the infectious form of the protein. Once this happens, as in a chain reaction, other prions alter the prions in other cells.⁴

Abnormal prion proteins clump together or aggregate. Scientists think these protein aggregates may lead to the neuron loss and other brain damage seen in CJD. Researchers at present do not know exactly how this damage occurs.

“Hereditary CJD or familial CJD accounts for approximately 5 to 10 percent of all CJD cases. It is thought that these cases arise from a mutation in the gene that controls formation of the normal prion protein. 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 from the body’s normal prion protein. If the prion protein gene is altered in a person’s sperm or egg cells, the mutation can be transmitted to the person’s offspring.  Mutations in the prion protein gene are inherited as dominant traits. Because of this family, history is important in considering the diagnosis.  

Several different mutations in the prion gene have been identified. The specific mutation found in each family affects how frequently the disease appears and what symptoms are most noticeable. Not all people with mutations in the prion protein gene develop CJD.⁴”

How is CJD Transmitted?

• Exposure to brain tissue and spinal cord fluid from an infected individual could result in CJD.
• CJD can spread to other people from grafts of Dura mater, transplanted corneas, and implantation of inadequately sterilized electrodes in the brain.
• Injections of contaminated pituitary growth hormone derived from human pituitary glands taken from cadavers. Since 1985, all human growth hormone used in the United States has been synthesized by recombinant DNA procedures, which eliminates the risk of transmitting CJD by this route.

Laboratory tests have shown a strong similarity between the prions causing BSE and v-CJD. Consequently, still being studied is whether the new variant of CJD (nv-CJD or v-CJD) found in several younger than average individuals in Great Britain and France is related to BSE acquired through the consumption of contaminated beef. However, there is no direct proof to support this theory.

The question people are asking is it possible to transmit CJD through blood and related blood products such as plasma?

• Even though some animal studies suggest that contaminated blood and related products may transmit CJD, this has never been shown to be true in humans. If there are infectious agents in these fluids, they may be at very low concentrations and not enough to cause CJD.
• Millions of people receive blood transfusions, but there are no reported cases of someone contracting CJD from a transfusion. Still, scientists do not know how many abnormal prions a person must receive before he or she develops CJD. It has not been determined whether these fluids are potentially infectious or not.⁴
• CJD is not spread through casual contact or breathing the same air.

• CJD is characterized by rapidly progressive dementia or delirium 
• Profound confusion, disorientation
• Blurred vision (sometimes)
• Changes in gait while walking
• Problems with muscular coordination (Stumbling and falling)
• Hallucinations
• Muscle twitching 
• Muscle stiffness
• Myoclonic jerks or seizures
• Jumpy feeling
• Personality changes, depression, unusual sensations
• Impaired memory, judgment, and thinking
• Insomnia, depression, or unusual sensations
• Blindness
• Sleepiness
• Loss of ability to move
• Loss of ability to speak
• Coma

CJD is rarely confused with other types of dementia (such as Alzheimer's disease) because symptoms progress much more rapidly. Both forms of CJD are distinguished by extremely rapid progression from onset of symptoms to disability and death.

CJD does not cause flu-like symptoms or a fever. However, pneumonia and other infections often occur in these individuals due to their weakened state, and this can lead to death. 

The physician took Melody’s history and discovered that her great-grandmother might have had CJD, but it was never confirmed since she had died within a short time after having signs and symptoms of early dementia, muscle twitching, falling, hallucinations, blurred vision, and seizures. The patient and family were told that presently there is no cure. In an attempt to slow the progression of CJD, Interleukins and other medications may need to be used. She would also be given medications to control aggressive behavior or agitation.

Melody was told what was happening to her and that she may become aggressive and agitated and have trouble with her balance and lack coordination as the disease progressed. She may develop dementia and delirium and have blurred vision. She was determined to make sure that her family was taken care of and requested that a power of attorney was given to her husband and that he would also control all decisions related to her medical care when she was not able to do so. Advance Directives were initiated.

A social worker, working with the family, and admission doctors at the local Veterans Hospital helped to plan and arrange admission into the hospice unit. The hospice unit will be available when the family needs to provide a safer environment as the disease progressed.

The family was given emotional support and educated on what is currently known about CJD and treatment options. Naturally, her daughters were afraid they might have inherited their mother’s disease. A family counseling and support network was given. A resource for additional help can be found from the CJD Foundation located on the internet site: http://www.cjdfoundation.org/

The family was educated on behavior modification and how this can help in controlling unacceptable or dangerous behaviors. Tips of rewarding appropriate or positive behaviors and ignoring inappropriate behaviors will assist the family as the disease progresses. They were taught how to use reality orientation with repeated reinforcement of environmental and other cues to help reduce disorientation.

Presently, there is no treatment that can cure or control CJD. Researchers have tested many drugs, including amantadine, steroids, interferon, acyclovir, antiviral agents, and antibiotics. Studies of a variety of other drugs are now in progress. However, none of these treatments have shown any consistent benefit in humans.

Treatment for CJD is aimed at alleviating symptoms and making the individual as comfortable as possible. Drugs are used to help relieve pain if it occurs as well as treating seizures and muscle spasms. During later stages of the disease, changing the person’s position frequently can help prevent bedsores and make the individual more comfortable. Catheters can be used to drain urine if the individual cannot control bladder function, provide nutritional liquid food supplements, and intravenous fluids.

Complications from CJD include loss of ability to care for oneself, loss of ability to interact with others, and possibly a coma. The cause of death is usually from infection (pneumonia), heart failure, or respiratory failure. 

Prognosis for CJD is usually poor and within six months or less of the onset of symptoms the individual will become incapable of self-care. Fatality usually occurs within eight months. Some people live one to two years after diagnosis. 

There are several known variants of CJD which differ in the degree of symptoms and course of the disease⁵.

• A variant form of the disease which was initially described in Great Britain and France is called new variant or variant (nv-CJD, v-CJD). This variant begins primarily with psychiatric symptoms, and it affects younger individuals than other types of CJD. This variant has a longer than usual duration from onset of symptoms to death⁵.
• Another variant which has a relatively long course with symptoms often progressing for several years occurs primarily in Japan. This variant is known as the panencephalopathic form. Scientists and researchers are trying to learn what causes these variations in symptoms and the course of CJD⁵.

Since some symptoms of CJD are similar to symptoms of other progressive neurological disorders, such as Huntington’s disease or Alzheimer’s, these diseases have to be ruled out. Unique to CJD is that changes in brain tissue, seen at autopsy, cause a more rapid deterioration of a person’s abilities than Alzheimer’s disease or other types of dementia⁵. 

Today, most countries have strict guidelines for management of infected cows and strict restrictions regarding what they are fed.  These restrictions are in place to avoid the potential for transmission of CJD to humans.¹

There is no known way to prevent sporadic CJD from developing. If an individual has a family history of neurological disease, they could benefit from talking with a genetics counselor who can help them sort through the risks associated with their particular situation. 

Caregivers
The National Institutes of Health recommend the following basic precautions:

• Wash hands and exposed skin before eating, drinking or smoking.
• Protect hands and face from exposure to the person's blood or fluids.
• Cover cuts or wounds with waterproof bandages.

Preventing iatrogenic CJD
Hospitals and other medical institutions are monitored and have to follow explicit policies to prevent iatrogenic CJD. These measures may include:

• Destruction of surgical instruments used on the brain or nervous tissue of someone with known or suspected CJD
• Single-use kits for spinal taps (lumbar punctures)
• Exclusive use of synthetic human growth hormone, instead of the kind derived from human pituitary glands

People with a risk of exposure to DJD or vCJD are not eligible to donate blood. 
This includes people who:

• Have a biological relative who has been diagnosed with CJD
• Spent a total of at least three months in the U.K. from 1980 to 1996
• Spent five years or more in France from 1980 to the present
• Received a blood transfusion in the U.K. between 1980 and the present
• Have injected bovine insulin at any time since 1980
• Have received a Dura mater brain graft
• Have received human growth hormone

Researchers are studying CJD and are examining whether the transmissible agent is a prion or a product of the infection. They are trying to discover factors that influence prion infectivity and how the disorder damages the brain.

Scientists are using rodent models of the disease and brain tissue from autopsies to identify factors that influence susceptibility to the disease and factors that govern when in life the disease appears. The knowledge gained from this research will hopefully improve tests to identify CJD and to learn what changes ultimately kill the neurons so that effective treatments can be developed.¹

Creutzfeldt-Jakob disease is one of the cruelest diseases for a family to have to cope with and can affect the young and those in their prime of life. Research is vital in overcoming this disease and in knowing just what is occurring in our bodies, how to identify it, prevent it, how to cure it, and stop it from being passed on from generation to generation.

Researchers and Scientists are conducting biochemical analyses of brain tissue, spinal fluid, blood, serum, and urine to help to determine the nature of the transmissible agent or agents causing Creutzfeldt-Jakob disease. As the world gets smaller, researchers and scientists have many avenues to investigate. Sharing knowledge and keeping an open mind to possibilities, outside the box, is a key in successfully finding a cure for this baffling disease.

1. NIH. Creutzfeldt-Jakob disease | Genetic and Rare Diseases. Published 2015. Accessed October 23, 2016. 
2. Rhodes, R. Deadly Feasts. Touchtone, New York, NY. 1998.
3. MedlinePlus Medical Encyclopedia. Creutzfeldt-Jakob disease. Published 2016. Assessed October 23, 2016
4. NINDS. Creutzfeldt-Jakob Disease Fact Sheet. Published March 2003. Updated February 2, 2016. Assessed October 23, 2016.
5. NINDS. Creutzfeldt-Jacob Disease Information Page. Updated February 2, 2016. Accessed October 23, 2016.

Additional References:

Alzheimer Association. Creutzfeldt-Jakob Disease | Signs, Symptoms, & Diagnosis. (Visit Source) Published 2016. Accessed October 22, 2016.

CDC. Creutzfeldt-Jakob Disease, Classic (CJD). (Visit Source) Updated February 6, 2015. Assessed October 23, 2016.

Creutzfeldt-Jakob Disease Foundation. Creutzfeldt-Jakob disease and other prion diseases. (Visit Source) Published 2009. Assessed October 23, 2016.

Manix M, Kalakoti P, Henry M, et al.Creutzfeldt-Jakob disease: updated diagnostic criteria, treatment algorithm, and the utility of brain biopsy. Neurosurg Focus. 2015; 39(5):E2. doi: 10.3171/2015.8.FOCUS 15328.

NIH. Detecting Human Prion Disease. (Visit Source) Published August 18, 2014. Assessed October 24, 2016.

NIH. Creutzfeldt-Jakob disease | Genetic and Rare. (Visit Source) Updated February 5, 2015. Assessed October 22, 2016.

Public Health England Infection Report Volume 10 Number 26. Creutzfeldt-Jakob disease (CJD) biannual update (August 2016). (Visit Source) Published August 12, 2016. Accessed October 22, 2016.

Vacca VM. Jr. CJD: Understanding Creutzfeldt-Jakob disease. Nursing. 2016; 46(3):36-42; quiz 42-3. doi: 10.1097/01.NURSE.0000480598.84274.0f.