Creutzfeldt-Jakob Disease

I

Introduction

Creutzfeldt-Jakob Disease (CJD), one of a range of degenerative diseases of the nervous system known as prion diseases or subacute spongiform encephalopathies. Other diseases in the range include kuru in humans (a disease transmitted by cannibalism); scrapie in sheep; and bovine spongiform encephalopathy (BSE) in cattle (“mad cow disease”).

CJD is a rapidly progressive disorder mainly affecting middle-aged and elderly people and causes death within weeks or months of onset. As the term “spongiform encephalopathy” implies, the brain becomes sponge-like and there is considerable loss of neuronal (nerve cell) tissue. The result is serious interference with brain function, producing dementia and a wide range of other neurological defects.

II

Symptoms

The first sign of the disease is usually a rapidly progressive dementia with repeated, sudden, brief involuntary muscle contraction causing jerking of the limbs (myoclonus). Other symptoms are irritability, fatigue, sleeping disorders, and neglect of personal hygiene. Disturbance of most of the functions of the brain then becomes apparent. Loss of all intellectual function, loss of balance, paralysis, sensory loss, speech disorders, disorientation, tremors, twitching, and other signs of progressive destruction of brain function occur. Progress is rapid and 70 per cent of affected people die within six months. Many die within a few weeks of onset. There is currently no effective treatment.

III

Causes and Incidence

The condition occurs sporadically and was originally said to have an incidence of about 1 case per million people each year. Researchers at the British Medical Research Council’s neuropathology unit suggest, however, that a proportion of cases are not correctly diagnosed and that this figure is likely to be an underestimate. While the disease can undeniably be caused by an infective agent, the nature of this agent has been debated for years. There is no evidence supporting the assumption that CJD is a virus. Current thinking is that it is a non-DNA-containing glycoprotein known as a prion, a modified form of a substance that is necessary for normal brain function. Prion protein is found in all cases of spongiform encephalopathy, whether in humans or animals. The gene for the normal glycoprotein is on the short arm of chromosome 20, and mutations of this gene have been shown to have a dominant inheritance, that is, are likely to be inherited. About 15 per cent of cases of CJD are inherited.

Since 1994 much of the attention of scientists has been concentrated on the new variant CJD (vCJD), which has a much shorter incubation period than the earlier form of the disease and which occurs mainly in young people. In 1994, cases of CJD were reported in more than 20 teenagers and young adults with no history of exposure to the then-known risk factors. By November 1996, 14 such cases had been detected; by February 1998, there had been 24 cases. Prior to this, the disease had been considered to be extremely rare in people under the age of 30 years and to have a peak incidence around the age of 65.

By August 2000, 79 cases of vCJD had been reported in the United Kingdom and at least one in France. This figure had risen to 119 by the end of 2002, and as of August 2004, 147 people were known to have died of the disease in Britain. The average age at onset was 29 years and the range was from 16 to 48 years. There was also one case in a child of 12 years. The most striking difference from the earlier form was the frequency of psychiatric symptoms at the start of the illness. In 1998 three people in the small village of Quenisborough in Leicestershire died of vCJD, and in May 2000 a young man died of it in Leicester Royal Infirmary. Another young Leicestershire man was also believed to have the disease. This grouping is thought unlikely to have occurred by chance. Scientific opinion is now veering more strongly in favour of the probability that prion-contaminated food is the cause. The Spongiform Encephalopathy Advisory Committee (SEAC) to the British government reports that the number of cases of vCJD has risen by two or three each year since the new form was first reported. Current predictions by scientists at Oxford University are that a maximum of 136,000 cases of vCJD could occur in the UK. This may be an unduly pessimistic forecast. A tonsil test for vCJD has been developed, and 3,170 tonsil samples, taken between 1996 and 1998, have been examined for vCJD prion protein. In May 2000 it was reported that none of these showed any sign of vCJD prion protein.

IV

BSE and CJD

In March 1996 SEAC suggested that vCJD was probably caused by eating beef contaminated with the prion protein that causes BSE. In October of that year it was announced that a new molecular marker had been detected while studying the prion proteins. This allowed strain-typing of the various forms of CJD to be performed in a matter of days. The new test also showed that the characteristic molecular signature found in vCJD was not found in earlier forms of CJD but was the same as that found in BSE.

It is currently believed that the British outbreak of BSE in the late 1980s was due to the changes from 1979 onward in the system of rendering down abattoir by-products, which entered the animal food chain having been exposed only to temperatures too low to kill off the infective BSE agent. Attempts to transmit prion disease from one animal to another by meat (muscle) ingestion, however, have failed—but transmission by injection of neurological material is known to be possible, although difficult and with a very long incubation period. Prion disease has been observed in other primates; in mink, deer, and elk; and in domestic cats.

Since November 1989 there has been a ban on the use of certain types of bovine offal and this has probably eliminated the material containing the prion protein from the diets of both humans and animals.

As of February 1998, evidence exists that vCJD is caused by the same strain of agent as BSE and that this strain differs from other strains isolated from cases of classic sporadic CJD. At present, definite diagnosis of either form of the disease is possible only after death, but doctors are under pressure to distinguish between the two forms and to be able to identify cases of vCJD as early as possible. It is impossible to predict how many people are now incubating the variant form of disease.

Concern has arisen over plasma-derived products from potentially infected blood donors. Batches of plasma-derived products can be withdrawn if a donor is subsequently suspected of having CJD, particularly vCJD. A method of early identification of cases of vCJD is therefore urgently needed. However, although CJD can, in theory, be transmitted through blood, current research suggests that there is no direct link between blood transfusion and the development of sporadic cases of CJD.