Transmissible spongiform encephalopathies (TSE) are a group of rare, fatal diseases that cause rapidly progressive dementia. They have long incubation periods and many years and even decades may pass between the time of infection and the first signs and symptoms of the disease. TSEs have been linked to certain types of proteins called prions. It is believed that when these prions become infectious, they kill nerve tissues (e.g., brain cells) with which they come into contact. According to the National Institutes of Health, TSE occur in about one person per million each year, worldwide. Within the United States, there are about 300 cases per year.

There are several different types of TSE. Some of these affect animals, and some affect humans. The most common human TSE is Creutzfeldt-Jakob disease (CJD). A similar but distinct condition, variant Creutzfeldt-Jakob disease (vCJD), has been linked to the consumption of meat contaminated by bovine spongiform encephalopathy (BSE), or mad cow disease. Other TSEs that may affect humans include Gerstmann-Straussler-Scheinker disease, fatal familial insomnia and kuru.

Most TSEs tend to occur in older individuals. According to the National Institute of Neurological Disorders and Stroke (NINDS), symptoms of CJD tend to first occur around age 60. After symptoms are present, about 90 percent of patients die within 12 months. On the other hand, variant CJD is known to affect younger individuals. According to the Centers for Disease Control and Prevention (CDC), the average age at death for people with this disease is about 29.

In most cases, TSEs spontaneously occur in individuals with no known risk factors (sporadic disease). According to both NINDS and the CDC, about 85 percent of CJD cases occur in this manner. Some cases of TSE may also be hereditary. According to the CDC, about 5 percent to 15 percent of all cases of CJD are inherited. TSEs can also be acquired from other humans. However, this is very rare. According to NINDS, less than 1 percent of all known cases of CJD have been acquired. The only human TSE positively linked to food contamination is vCJD.

Most TSEs have similar symptoms, although the severity of certain symptoms may be greater in one form than in another. The first symptoms of many TSEs are psychiatric problems (e.g., depression, anxiety, insomnia). Eventually, neurological signs (e.g., unpleasant sensations, problems walking, lack of coordination, vision problems) develop. Patients also begin to feel confused, forgetful, and have difficulty thinking and speaking. In later courses of the diseases, patients become unable to speak or move and enter a coma. All TSEs are ultimately fatal.

The only ways to positively diagnose TSEs are by means of a brain biopsy (an invasive and risky procedure) or autopsy. However, a probable diagnosis can be made from the patient’s medical history, signs and symptoms, magnetic resonance imaging (MRI) of the brain and an electroencephalogram (EEG).

There are no known methods to cure TSEs, so current treatment is aimed at making the patient feel as comfortable as possible. While TSEs cannot always be prevented, precautions can be taken to reduce the risks. This is especially true for vCJD. The United States, United Kingdom and many other countries have put several strict regulations in place for the purpose of stopping the spread of BSE and preventing vCJD.

Transmissible spongiform encephalopathies (TSE) are a group of rare, fatal, degenerative brain diseases believed to be caused by proteins called prions that become infectious. These diseases, which are also called prion diseases, typically have long incubation periods. Many years and even decades may pass between the time of infection and the first signs and symptoms of the disease. According to the National Institute of Neurological Disorders and Stroke, this incubation period may even reach as many as 40 years. However, once symptoms do occur, the diseases typically progress quickly, resulting in death after a span of months to a few years.

Proteins are long chains of amino acids that are folded into particular shapes. These shapes allow the proteins to perform their functions in the body. Prions, which are also called proteinaceous infectious particles, are a certain type of harmless protein – they are not viruses, bacteria or other cellular organisms. In their normal state, prions are noninfectious. The purpose of prions is not known, but they are present in a safe form on the membranes of many different types of cells, including brain cells. They may play a role in cell-to-cell communication or transporting minerals into cells.

However, prions can misfold, or fold into abnormal shapes and become infectious. When these infectious prions come into contact with other proteins, they cause them to misfold and become infectious, as well. Eventually, enough abnormal prions are present that symptoms of disease occur. It is believed that abnormal prions kill nerve tissues (e.g., brain cells) that they contact. This can cause tiny holes to form in the brain, giving it the appearance of a sponge when viewed under a microscope. Hence the name, “spongiform (sponge-like) encephalopathy (brain disease).”

Infectious prions are unusual because, unlike viruses or bacteria, they do not appear to have any genetic material (e.g., DNA, RNA). They are also extremely difficult to destroy and can survive many methods normally used to kill harmful bacteria and viruses (e.g., antibiotic medications and sterilization procedures such as boiling or irradiation).

The theory that infectious prions alone are responsible for TSEs is widely accepted, but it has not been definitively proven. One alternate theory claims that a slow-acting virus is the infectious agent responsible for TSE, and that the abnormal prions are a result of the infection, not the cause. However, no actual virus, bacterium or other cellular organism that may cause the disease has been identified.

According to the National Institutes of Health, TSE occurs in about one person per million each year, worldwide. In the United States, there are about 300 cases per year.

There are several different types of transmissible spongiform encephalopathies (TSEs). Some of these affect humans and some only affect animals. One TSE in particular has received a great deal of attention in recent years. Bovine spongiform encephalopathy (BSE), more commonly known as mad cow disease, is a TSE that affects cattle. BSE has been linked to a human TSE called variant Creutzfeldt-Jakob disease (vCJD).

Scientists believe that vCJD infection occurs due to eating meat and meat byproducts from cattle infected with BSE. It appears that the agent (prion) that causes BSE in cattle remains in animal tissue after the animal has been processed as food. When people consume food contaminated with this agent, they may become infected with vCJD. However, the risk of this transmission in the United States is extremely rare.

BSE and vCJD are most common in the United Kingdom, but have also occurred in several other European countries, Japan, Saudi Arabia, Canada and the United States. Since vCJD was first identified in 1996, there have been nearly 200 patients reported with the disease, from 11 different countries. According to the Centers for Disease Control and Prevention (CDC), more than 80 percent of these cases occurred in the United Kingdom. Only two cases had occurred in the United States as of 2006.

Unlike other TSEs, vCJD in the United Kingdom tends to affect people at a younger age. According to the CDC, the average age at death for persons with this disease is about 29 years.

In addition to vCJD, other TSEs that may affect humans include:

• Creutzfeldt-Jakob disease (CJD). While there are similarities, classic CJD and variant CJD (vCJD) are distinctly different conditions. Classic CJD has been known and studied for much longer than vCJD, and it is not linked to BSE. The disease progression of CJD is typically faster than vCJD, and it tends to affect older rather than younger adults. According to the National Institute of Neurological Disorders and Stroke (NINDS), symptoms of CJD tend to first occur around age 60. After symptoms are present, about 90 percent of patients die within 12 months.
  
  CJD does not appear to be transmitted through food. According to the NINDS, it most often develops spontaneously in people with no known risk factors for the disease, a form known as sporadic CJD. In about 5 percent to 10 percent of cases, CJD is genetically inherited. In less than 1 percent of cases, it is transmitted to brain or nervous system tissue during certain types of medical procedures. The nationwide incidence of CJD is rare, affecting about 200 people per year in the United States.
  
  
• Gerstmann-Straussler-Scheinker disease (GSS) and fatal familial insomnia (FFI). These are two very rare, hereditary forms of TSE, only known to occur in a few families worldwide. Unlike other TSEs, FFI causes disturbances in the endocrine system and autonomic nervous system (which regulates body functions). This can lead to excessive sweating, high body temperatures, increased heart rate and high blood pressure.
  
  
• Kuru. This was among the first identified and best studied TSEs in humans. It occurred in an isolated tribe in Papua New Guinea called the South Fore. It appeared to be related to ritual cannibalism. Since cannibalism has been stopped among these people, kuru has practically disappeared.

BSE is the only animal form of TSE directly linked to human disease. While other animal forms of TSE have yet to cross the species barrier to humans, researchers warn that such transmission may eventually be possible. Studies on this possibility and potential methods of preventing it are ongoing.

Beside BSE, additional TSEs that may affect animals include:

• Scrapie. This oldest known TSE occurs in sheep and goats. Unlike BSE, it can be passed from a mother sheep to her lambs. It may also be acquired through contaminated feed. There have been no cases of humans acquiring any TSE from eating lamb or mutton contaminated with scrapie. However, some scientists believe that the use of scrapie-contaminated sheep and goats in supplements and feed for cattle may have caused or accelerated the development of BSE.
  
  
• Chronic wasting disease. The TSE that affects deer and elk appears to be spreading in America. The disease’s cause and how it spreads are not well-known.
  
  
• Transmissible mink encephalopathy, feline spongiform encephalopathy and ungulate spongiform encephalopathy. These TSEs affect farm mink, cats (both domestic and those in zoos) and zoo ruminants (animals that chew food they have already partially digested), respectively. While the cause of these diseases is not positively known, it is likely that they are linked to contaminated feed. Cattle products have often been used as protein supplements in animal feed, and some of these products may have been contaminated with BSE.

Most transmissible spongiform encephalopathies (TSE) tend to occur in older individuals. According to the National Institutes of Health, there is only one case of TSE per million people, worldwide, each year. However, according to the Centers for Disease Control and Prevention (CDC), the incidence of Creutzfeldt-Jakob disease (CJD), the most common form of TSE, increases to about 3.4 cases per million people over the age of 50.

TSE can be caused by a number of different mechanisms, including:

• Sporadic disease. In most cases, TSE occurs in individuals with no known risk factors. It is thought that this occurs due to a spontaneous change in the prion proteins. Some researchers believe that proteins are frequently becoming misfolded as they are created, but that the body breaks these proteins down before they cause problems. However, some may be “missed,” prompting proteins they come into contact with to misfold as well, leading to TSE. According to both the National Institute of Neurological Disorders and Stroke (NINDS) and the CDC, about 85 percent of CJD cases occur in this manner.
  
  
• Hereditary disease. Some cases of TSE may also be hereditary. According to the CDC, about 5 percent  to 15 percent of all cases of CJD are inherited. Genes affect all aspects of the human body. A change, or mutation, in a gene can cause any number of problems. Some gene mutations can lead to TSE, apparently by causing certain proteins to misfold, becoming infectious prions. This abnormal prion protein can be detected using genetic testing, but not all people with the gene develop a TSE.
  
  A genetic change may occur spontaneously in an individual without any known risk factors, or a mutated gene can be passed down by parents. These hereditary forms of TSE are inherited in an autosomal dominant fashion. This means that only one parent needs to pass the gene to the child.
  
  
• Foodborne contamination. The only human TSE positively linked to food contamination is variant Creutzfeldt-Jakob disease (vCJD). It is generally accepted that this infection occurs when food contaminated with bovine spongiform encephalopathy (BSE), also known as mad cow disease, is consumed. In theory, when the infectious prion responsible for BSE is consumed, it is absorbed into the person’s body, where it may cause certain proteins to misfold, creating more infectious prions. However, because the cow and the human are different species, this is not as efficient a transmission process as if the prion had come from another human. Therefore, the potential for a TSE to develop is reduced due to this “species barrier.”
  
  Not all parts of a cow infected with BSE are equally risky to consume. High-risk tissues include certain intestinal tissues, nerve tissues and tissues likely to be contaminated by nerve tissues (e.g., brain, eyes, tonsils). The infectious agents do not appear to be present in milk or muscle meat. However, certain cuts of meat (e.g., t-bone steaks) may have a higher risk of contamination by nervous tissue. Although gelatin is derived from the hides and bones of cattle, the risk that the vCJD agent can be transferred through eating gelatin appears to be very low.
  
  The risk of acquiring vCJD by eating beef and beef products is small, even in areas with high numbers of BSE cases. According to the CDC, this risk in the United Kingdom is only about one in 10 billion servings. This low risk is largely due to public health control measures that have been put in place to stop the spread of BSE.
  
  
• Acquired disease. TSE can also be acquired from other humans. However, this is very rare. According to NINDS, less than 1 percent of all known cases of CJD have been acquired. TSE cannot be transmitted through the air or through casual contact with an infected person. However, it may be transmitted through infected tissue (e.g., brain or other nervous tissue, spinal cord fluid) and contaminated medical instruments (e.g., improperly sterilized electrodes in the brain). Certain transplant procedures, including dura mater (a tissue covering the brain) grafts and cornea transplants, can also transmit the diseases.
  
  When a TSE is transferred due to a medical procedure, it is known as an iatrogenic case. According to the CDC, no iatrogenic cases related to medical equipment have occurred since current routine medical sterilization procedures have been implemented.
  
  Pituitary growth hormone was once derived from the pituitary glands of cadavers. There have been cases of CJD transmission via this process. However, modern growth hormone used in America is synthetic and poses no threat of TSE transmission.
  
  There have also been concerns regarding the potential transmission of CJD through blood transfusions. While there is no evidence that this has ever occurred in humans, transmission of vCJD through blood may have occurred in the United Kingdom. In response to this potential risk, the Food and Drug Administration (FDA) and the American Red Cross have increased donor requirements to safeguard the American blood supply. For example, people who have lived for more than three months in a country or countries where BSE is common cannot donate blood in the United States.

Transmissible spongiform encephalopathies (TSE) are characterized by very long incubation periods before irreversible brain and nerve damage occurs, resulting in progressive dementia and death. There are no signs or symptoms in the early course of the diseases and the first signs or symptoms may not appear for years or even decades after the infection first occurred. After symptoms do appear, the diseases tend to progress very quickly, often leading to death within a year.

Most TSEs have similar symptoms, although the severity of certain symptoms may be greater in one form than in another. The first symptoms of many TSEs are psychiatric problems (e.g., depression, anxiety, insomnia). Personality changes may also occur. Eventually, neurological signs develop. Patients may experience unpleasant sensations, problems walking and a lack of muscle coordination. They may have involuntary jerking motions (myoclonus). Vision problems, which may lead to blindness, are also common. They may feel confused, forgetful, or have difficulty thinking and speaking.

Most TSEs do not cause disturbances in the endocrine system or autonomic nervous system (the part of the nervous system that controls body functions). Fatal familial insomnia (FFI) is the exception. Patients with FFI may experience excessive sweating, high body temperatures, increased heart rate and high blood pressure.

In later courses of the diseases, patients become unable to speak or move muscles as the brain degenerates. They eventually may enter a coma. Infections (e.g., pneumonia) are common and may be the cause of death for many patients. The presence of tiny holes in the brain (giving it a spongy appearance) at autopsy indicates TSE.

Transmissible spongiform encephalopathies (TSE) are difficult to positively diagnose. When a TSE is suspected, treatable forms of dementia (e.g., encephalitis, chronic meningitis) must first be ruled out. This may involve a spinal tap or computerized tomography (CAT scan) of the brain. After other forms of dementia have been ruled out, a probable diagnosis of a TSE can be made by a physician’s evaluation of the patient’s medical history, the presentation of signs and symptoms, magnetic resonance imaging (MRI) of the brain and an electroencephalogram (EEG). Many types of TSEs cause unique abnormalities on EEG or brain MRI.

TSE can be positively diagnosed using a brain biopsy. This is an invasive and risky procedure that removes a small amount of brain tissue for laboratory examination. However, the tissue may be taken from a part of the brain that is not affected by the disease, resulting in a false negative result. TSE can be positively diagnosed with the greatest degree of reliability through a microscopic examination of brain tissue during an autopsy. However, this is only possible after death.

Research on new diagnostic tests for TSE is ongoing.

There are no known methods to cure transmissible spongiform encephalopathies (TSE), although research is ongoing to find potential treatments. Some research shows promise in stopping the progression of TSE, but so far no potential ways of stopping or reversing the damage caused have been discovered.

Current treatments for TSE are entirely palliative (pain-relief related). The goal of this treatment is to make the patient as comfortable as possible. Pain medications are used as necessary. Bed-bound patients may be fed artificially (e.g., feeding tubes) and may receive intravenous fluids. Catheters may be used to drain urine and healthcare workers regularly shift the patient's position to prevent bedsores.

While prevention of TSE is often not possible (particularly with sporadic or inherited forms of the diseases), there are precautions that people can take to reduce their risks. Casual contact with an infected patient cannot spread TSE, but contact with certain infected body tissues (e.g., brain tissues, spinal fluids) can. Contact with these materials from an infected person need to be avoided. For example, direct superficial contact with the body of an autopsied TSE patient is not advised. The same risk of infection is not present if the body has not been autopsied.

No methods have been developed to detect the infectious agents (prions) of a TSE, particularly bovine spongiform encephalopathy (BSE, mad cow disease), in food. When present, these infectious prions are very difficult to destroy. Standard cooking or irradiation techniques, which can kill most viruses and bacteria, are not effective. Since contaminated food cannot be made safe, prevention relies on avoiding contaminated meat and meat byproducts. This includes halting the spread of BSE among cattle. The United States, United Kingdom and many other countries have put several strict regulations in place for this purpose.

While TSE can also be transmitted by contaminated medical supplies, this is very rare. According to the Centers for Disease Control and Prevention, no cases of TSE related to medical equipment have occurred since the current medical sterilization procedures have become routine.

Research on transmissible spongiform encephalopathies (TSE) in the United States is performed and funded largely by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The National Institute of Neurological Disorders and Stroke and the National Institute on Aging are also involved in prion research.

Researchers are investigating many different aspects of TSE, including:

• How prions function and cause TSE
  
  
• Potential treatments to halt the progression of TSE
  
  
• New diagnostic tests to identify TSE
  
  
• Any possible links to other diseases that cause dementia (e.g., Alzheimer’s disease)
  
  
• How TSE may cross the species barrier
  
  
• Whether animal forms of TSE other than bovine spongiform encephalopathy (BSE) are of concern to humans
  
  
• Why some species (e.g., chickens) seem to be immune or resistant to BSE
  
  
• Whether these species, carrying dormant disease, could infect others
  
  
• Possible vaccines for animal forms of TSE (particularly chronic wasting disease)
  
  
• Potential methods to identify TSE in blood samples and remove prions from donated blood

Preparing questions in advance can help patients have more meaningful discussions regarding their conditions. Patients may wish to ask their doctor the following questions related to transmissible spongiform encephalopathies (TSEs):

1. Why do you think I may have a TSE?
   
   
2. Which TSE do I have?
   
   
3. How could I have been infected?
   
   
4. For how long have I probably been infected?
   
   
5. How advanced is my TSE?
   
   
6. What treatments may help to make the rest of my life more comfortable?
   
   
7. How might I tell my friends and loved ones about my condition?
   
   
8. Could my children or other family members be infected, as well?
   
   
9. What symptoms or signs should I immediately report to you?
   
   
10. Will I require the assistance of a specialized medical worker?