Creutzfeldt-Jakob disease (CJD)

Creutzfeldt-Jakob (KROITS-felt YAH-kobe) disease (CJD) is a degenerative brain disorder that leads to dementia and, ultimately, death. Creutzfeldt-Jakob disease symptoms can be similar to those of other dementia-like brain disorders, such as Alzheimer's disease. But Creutzfeldt-Jakob disease usually progresses much more rapidly.

It affects about one person in every one million per year worldwide; in the United States there are about 350 cases per year.

CJD captured public attention in the 1990s when some people in the United Kingdom developed a form of the disease — variant CJD (vCJD) — after eating meat from diseased cattle. However, "classic" Creutzfeldt-Jakob disease hasn't been linked to contaminated beef. All types of CJD are serious, but very rare. Worldwide, about one to two cases of CJD are diagnosed per million people each year, most often in older adults.

• Classic CJD is a human prion disease. It is a neurodegenerative disorder with characteristic clinical and diagnostic features. This disease is rapidly progressive and always fatal. Infection with this disease leads to death usually within 1 year of onset of illness.

Creutzfeldt-Jakob disease (CJD) is a rapidly progressive, invariably fatal neurodegenerative disorder believed to be caused by an abnormal isoform of a cellular glycoprotein known as the prion protein. CJD occurs worldwide and the estimated annual incidence in many countries, including the United States, has been reported to be about one case per million population.

The vast majority of CJD patients usually die within 1 year of illness onset. CJD is classified as a transmissible spongiform encephalopathy (TSE) along with other prion diseases that occur in humans and animals. In about 85% of patients, CJD occurs as a sporadic disease with no recognizable pattern of transmission. A smaller proportion of patients (5 to 15%) develop CJD because of inherited mutations of the prion protein gene. These inherited forms include Gerstmann-Straussler-Scheinker syndrome and fatal familial insomnia.

Physicians suspect a diagnosis of CJD on the basis of the typical signs and symptoms and progression of the disease. In most CJD patients, the presence of 14-3-3 protein in the cerebrospinal fluid and/or a typical electroencephalogram (EEG) pattern, both of which are believed to be diagnostic for CJD, have been reported. However, a confirmatory diagnosis of CJD requires neuropathologic and/or immunodiagnostic testing of brain tissue obtained either at biopsy or autopsy.

There are four major categories of CJD

• In sporadic CJD, the disease appears even though the person has no known risk factors for the disease. This is by far the most common type of CJD and accounts for at least 85 percent of cases.
  • Most cases of sporadic CJD occur in adults aged between 45 and 75. On average, symptoms develop between the ages of 60 and 65.
  • Despite being the most common type of CJD, sporadic CJD is still very rare, affecting only 1 or 2 people in every million each year in the UK.
  • In 2020, there were 131 recorded deaths from sporadic CJD in the UK.
• In variant CJD (vCJD) it is likely to be caused by consuming meat from a cow that had bovine spongiform encephalopathy (BSE, or "mad cow" disease), a similar prion disease to CJD.
  • Since the link between variant CJD and BSE was discovered in 1996, strict controls have proved very effective in preventing meat from infected cattle entering the food chain.
  • But the average time it takes for the symptoms of variant CJD to occur after initial infection (the incubation period) is still unclear.
  • The incubation period could be very long (more than 10 years) in some people, so those exposed to infected meat before the food controls were introduced can still develop variant CJD.
  • The prion that causes variant CJD can also be transmitted by blood transfusion, although this has only happened 5 times in the UK.
  • People with variant CJD tend to be much younger than those with other types of CJD, often in their 20s.
  • Only two Canadians have ever been diagnosed with variant CJD, and both times they were living abroad.
  • In 2020, there were no recorded deaths from variant CJD in the UK.
• In hereditary CJD, the person may have a family history of the disease and test positive for a genetic mutation associated with CJD. About 10 to 15 percent of cases of CJD in the United States are hereditary.
  • Familial CJD is a very rare genetic condition where one of the genes a person inherits from their parent (the prion protein gene) carries a mutation that causes prions to form in their brain during adulthood, triggering the symptoms of CJD.
  • It affects about 1 in every 9 million people in the UK.
  • The symptoms of familial CJD usually first develop in people when they're in their early 50s.
  • In 2020, there were 6 deaths from familial CJD and similar inherited prion diseases in the UK.
• In acquired CJD or iatrogenic CJD, the disease is accidentally transmitted by exposure to brain or nervous system tissue, usually through certain medical procedures.
  • There is no evidence that CJD is contagious through casual contact with someone who has CJD.
  • Since CJD was first described in 1920, fewer than one percent of cases have been acquired CJD.
  • A type of CJD called variant CJD (or vCJD) can be acquired by eating meat from cattle affected by a disease similar to CJD called bovine spongiform encephalopathy (BSE) or, commonly, “mad cow” disease.
  • Most cases of iatrogenic CJD have been found in the United States, United Kingdom, France and Japan. To date, only six people have been diagnosed with iatrogenic CJD in Canada.

Symptoms

Creutzfeldt-Jakob disease is marked by rapid mental deterioration, usually within a few months. Early signs and symptoms typically include:

• Personality changes
• Memory loss
• Impaired thinking
• Blurred vision or blindness
• Insomnia
• Incoordination
• Difficulty speaking
• Difficulty swallowing
• Sudden, jerky movements

As the disease progresses, mental symptoms worsen. Most people eventually fall into a coma. Heart failure, lung (respiratory) failure, pneumonia or other infections are generally the cause of death, which usually occurs within a year.

In people with the rarer vCJD, psychiatric symptoms may be more apparent in the beginning. In many cases, dementia — the loss of the ability to think, reason and remember — develops later in the illness. vCJD also affects people at a younger age and appears to last 12 to 14 months.

Causes

Creutzfeldt-Jakob disease and its variants belong to a broad group of human and animal diseases known as transmissible spongiform encephalopathies (TSEs). The name derives from the spongy holes, visible under a microscope, that develop in affected brain tissue.

The cause of Creutzfeldt-Jakob disease and other TSEs appears to be abnormal versions of a kind of protein called a prion. Normally these proteins are produced in our bodies and are harmless. But when they're misshapen, they become infectious and can harm normal biological processes.

How CJD is transmitted

The risk of CJD is low. The disease can't be spread through coughing or sneezing, touching, or sexual contact. CJD can develop in three ways:

• Sporadically. Most people with classic CJD develop the disease for no apparent reason. This type, called spontaneous CJD or sporadic CJD, accounts for most cases.
• By inheritance. Fewer than 15% of people with CJD have a family history of the disease or test positive for a genetic mutation associated with CJD. This type is referred to as familial CJD.
• By contamination. A small number of people have developed CJD after being exposed to infected human tissue during a medical procedure, such as a cornea or skin transplant. Also, because standard cleaning methods don't destroy abnormal prions, a few people have developed CJD after undergoing brain surgery with contaminated instruments. A small number of people have also developed the disease from eating contaminated beef.

Cases of CJD related to medical procedures are referred to as iatrogenic CJD. Variant CJD is linked primarily to eating beef infected with mad cow disease (bovine spongiform encephalopathy, or BSE).

Risk factors

Most cases of Creutzfeldt-Jakob disease occur for unknown reasons, and no risk factors can be identified. However, a few factors seem to be associated with different kinds of CJD:

• Age. Sporadic CJD tends to develop later in life, usually around age 60. Onset of familial CJD occurs slightly earlier, and vCJD has affected people at a much younger age, usually in their late 20s.
• Genetics. People with familial CJD have a genetic mutation that causes the disease. To develop familial CJD, a child must have one copy of the mutated gene, which is inherited from either parent. If you have the mutation, the chance of passing it on to your children is 50%.
• Exposure to contaminated tissue. People who've received infected manufactured human growth hormone, or who've had transplants of the infected tissues that cover the brain (dura mater), may be at risk of iatrogenic CJD.

The risk of getting vCJD from eating contaminated beef is very low. In general, if countries are effectively implementing public health measures, the risk is virtually nonexistent. Chronic wasting disease (CWD) is a prion disease that affects deer, elk, reindeer and moose. It has been found in some areas of North America. To date, no documented cases of CWD have caused disease in humans.

Several tests can help diagnose CJD.

• Electroencephalography (EEG), which records the brain’s electrical pattern, can be particularly valuable because it shows a specific type of abnormality in major but not all types of CJD.
• Cerebrospinal fluid-based tests. In April 2015, the National Prion Disease Pathology Surveillance Center began reporting a new diagnostic test for human prion diseases, called second generation Real Time-Quaking-Induced Conversion (RT-QuIC). RT-QuIC is based on an ultrasensitive detection of the pathogenic prion protein in the cerebrospinal fluid of individuals affected by CJD and other forms of human prion diseases. This new advanced test demonstrates a very high sensitivity and specificity of the disease. RT-QuIC differs from traditional surrogate markers of prion disease –14-3-3 and tau proteins—in that it detects directly a disease-defining pathogenic prion protein as opposed to a surrogate marker of rapid neurodegeneration. Detection of these traditional surrogate marker proteins is accurate in approximately three-fourths of cases.
• Magnetic resonance imaging (MRI) has recently been found to be accurate in about 90 percent of cases.

The only way to confirm a diagnosis of CJD is by brain biopsy or autopsy. In a brain biopsy, a neurosurgeon removes a small piece of tissue from the person’s brain so that it can be examined by a neuropathologist. This procedure may be dangerous for the individual, and the operation does not always obtain tissue from the affected part of the brain. Because a correct diagnosis of CJD does not help the individual, a brain biopsy is discouraged unless it is needed to rule out a treatable disorder. In an autopsy, the whole brain is examined after death.

Complications

Creutzfeldt-Jakob disease greatly affects the brain and body. CJD usually progresses quickly. Over time, people with CJD withdraw from friends and family and eventually lose the ability to recognize or relate to them. They also lose the ability to care for themselves and many eventually slip into a coma. The disease is always fatal.

Prevention

• There's no known way to prevent sporadic Creutzfeldt-Jakob disease (CJD). If you have a family history of neurological disease, you may benefit from talking with a genetics counselor. He or she can help you sort through the risks associated with your situation.
• The risk of getting vCJD in the United States remains very low. Only four cases have been reported in the U.S. According to the U.S. Centers for Disease Control and Prevention (CDC), strong evidence suggests that these cases were acquired in other countries outside of the U.S.
  • In the United Kingdom, where the majority of vCJD cases have occurred, fewer than 200 cases have been reported. CJD incidence peaked in the U.K. between 1999 and 2000 and has been declining since. A very small number of other vCJD cases also have been reported in other countries worldwide.
  • To date, there is no evidence that people can develop vCJD from consuming meat of animals infected with CWD prions. Nonetheless, the CDC recommends that hunters strongly consider having deer and elk tested before eating the meat in areas where CWD is known to be present. In addition, hunters should avoid shooting or handling meat from deer or elk that appear sick or are found dead.

History

The disease was first described by German neurologist Hans Gerhard Creutzfeildt in 1920 and shortly afterward 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 has been speculated that at least two of the people in initial studies were suffering from a different ailment. An early description of familial CJD stems from the German psychiatrist and neurologist Fredrich Meggendorfer (1880–1953. A study published in 1997 counted more than 100 cases worldwide of transmissible CJD and new cases continued to appear at the time

Resources & additional reading:

• CDC- Creutzfeldt-Jakob disease, classic (CJD)
• Mayo Clinic - Creutzfeldt-Jakob disease
• NIH Creutzfeldt-Jakob Disease Fact Sheet
• Wikipedia - Creutzfeldt–Jakob disease (CJD)
• NHS – Creutzfeldt-Jakob disease
• Doctor Dementia – What is Creutzfeldt-Jakob Disease (CJD)
• Pain Assist - Creutzfeldt-Jakob Disease. Written, edited or reviewed By: Pramod Kerkar, MD, FFARCSI, DA Pain Assist Inc. Last modified on 6/19/2018
• Alzheimer Society of Canada – Creutzfeldt-Jakob disease
• CJD Foundation
• Kuru - National Institutes of Health (NIH)