Creutzfeldt-Jakob Disease Health Article

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.