What is Creutzfeldt-Jakob disease (CJD) , how can u diagnose and treat it

Introduction:

Creutzfeldt-Jakob disease (CJD) is a rare, degenerative, invariably fatal brain disorder. It affects about one person in every one million people per year worldwide; in the United States there are about 300 cases per year. CJD usually appears in later life and runs a rapid course. Typically, onset of symptoms occurs about age 60, and about 90 percent of individuals die within 1 year. In the early stages of disease, people may have failing memory, behavioral changes, lack of coordination and visual disturbances. As the illness progresses, mental deterioration becomes pronounced and involuntary movements, blindness, weakness of extremities, and coma may occur.

There are three 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.
• In hereditary CJD, the person has a family history of the disease and/or tests positive for a genetic mutation associated with CJD. About 5 to 10 percent of cases of CJD in the United States are hereditary.
• In acquired CJD, the disease is 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 a CJD patient. Since CJD was first described in 1920, fewer than 1 percent of cases have been acquired CJD.

CJD belongs to a family of human and animal diseases known as the transmissible spongiform encephalopathies (TSEs). Spongiform refers to the characteristic appearance of infected brains, which become filled with holes until they resemble sponges under a microscope. CJD is the most common of the known human TSEs. Other 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 has now almost disappeared. FFI and GSS are extremely rare hereditary diseases, found in just a few families around the world. Other TSEs are found in specific kinds of animals. These include bovine spongiform encephalopathy (BSE), which is found in cows and is often referred to as “mad cow” disease; scrapie, which affects sheep and goats; mink encephalopathy; and feline encephalopathy. Similar diseases have occurred in elk, deer, and exotic zoo animals.

Infectious agent:

The infectious agent is a unique abnormal prion protein, designated as PrP. This protein is an insoluble, proteaseresistant amyloid form of a normal cellular protein designated PrPc. PrP acts on normal prions, causing them to change into the abnormal infectious form in a cascade like manner.

Identification:

Clinical features:

CJD belongs to a group of rare diseases known to affect humans and animals called transmissible spongiform encephalopathies (TSE). CJD presents in humans in either a classical or a variant form.

Classical CJD:

Classical CJD (cCJD) is one of four rare prion diseases that affect humans. The others are Kuru, Gerstmann-Straussler- Scheinker disease and fatal familial insomnia.

Classical CJD occurs in sporadic, familial and iatrogenic forms. Sporadic cases account for 85–90% of CJD cases and have an unknown cause. Familial cases make up 5–10% and are associated with a genetic mutation. Less than 5% are iatrogenic. The symptoms of classical CJD usually begin at an average age of 65 years. Most cases occur between 45 and 75 years. The onset is commonly a rapidly progressing dementia, however one third of people may present with cerebellar symptoms such as dysarthria. With disease progression there may be pyramidal or spinal cord involvement, muscle atrophy or fasciculations and frequently myoclonus. Survival beyond one year is unusual with death ensuing after a median of 4.5 months.

Variant CJD:

Variant CJD (vCJD) was first described in the United Kingdom in 1996. The disease is strongly linked to the consumption of cattle products infected with the prion protein that causes bovine spongiform encephalopathy (BSE), or mad cow disease. There are clinical differences between vCJD and cCJD. vCJD affects younger people (average 29 years) and the duration of illness is longer (median 14 months). Unlike cCJD, it commonly begins with psychiatric symptoms such as depression and anxiety. Involuntary movements and sensory symptoms such as pain are usually present.

Method of diagnosis:

Diagnosis is suspected by the clinical presentation, disease progression and exclusion of other causes. EEG and MRI scans yield distinct results between classical and variant CJD. CSF tests assist diagnosis. Definitive diagnosis is usually made by brain biopsy or at autopsy by detection of the PrP and demonstration of the typical pathological spongiform changes in the brain. However, the diagnosis can also be confirmed by the detection of PrP in other human tissue such as tonsillar tissue by biopsy.

Incubation period:

The incubation period is difficult to ascertain and varies from 15 months up to 30 years in iatrogenic cases.

Reservoir:

Prion disease is present in cattle (BSE), sheep, goats, mink, mule deer and elk, cats and exotic zoo animals. Transmission of variant CJD in humans has only been linked to the consumption of meat and meat products from cattle with BSE. Infected humans with variant CJD and classical CJD are potential sources of infection for other humans by iatrogenic means.

Mode of transmission:

The majority of cases of cCJD appear to occur spontaneously with no source identified. In very rare cases transmission of cCJD has occurred through iatrogenic means. This has included direct or indirect contact with brain tissue and cerebrospinal fluid. For example, corneal or dural grafts or injections of contaminated pituitary hormone obtained from cadavers. Growth hormone is now made artificially.

There is no evidence of risk to people in close casual contact with a person infected with CJD.

Variant CJD is believed to be transmitted to humans through consumption of cattle infected with BSE. There have been no cases of vCJD linked to the receipt of infected blood products. As there is a theoretical risk of infection from blood products, blood donors are screened with respect to their possible exposure in areas affected by vCJD, particularly the United Kingdom.

Period of communicability:

The central nervous system tissues are infectious during symptomatic illness of CJD. Animal studies suggest that the lymphoid and other organs are probably infectious long before symptoms develop.

Susceptibility and resistance:

Genetic mutations have been found in familial CJD. Genetic susceptibility also occurs for vCJD for humans who are homozygous for methionine at codon129 of the prion gene.

Control measures:

Preventive measures:

Precautionary measures instituted in Australia to reduce the risk of vCJD importation include:

• a ban on the importation of beef and beef products from the UK since 1996. Extended to other affected European

countries

• monitoring and restriction by the Therapeutic Goods Administration (TGA) of the source of materials of

animal origin used in the manufacture of medicines and medical devices

• a ban on blood products from people who have lived in the UK for six months or more since 1980 until 1996, commenced in 2000

• surveillance for vCJD by the Australian National CJD Registry based at the University of Melbourne

• active surveillance of cattle for BSE by the Australian Government

Department of Agriculture, Fisheries and Forestry. Control of case There is no specific treatment except for supportive care. Hospitalised patients should be managed using standard precautions. Tissues, surgical instruments and all wound drainage should be considered contaminated and must be inactivated.

The PrP is very resistant to destruction by normal methods including standard sterilisation and because of this instruments used on CJD patients, particularly in surgery involving the brain, spine or eye, may need to be destroyed. It is important to obtain an accurate history of travel, any previous surgical or dental procedures, and any history of exposure to human growth hormone or transplanted tissue.

If there is no travel history, obtain details of any past procedure or surgery. Inform the Australian Government Department of Agriculture, Fisheries and Forestry to monitor Australian cattle if de

novo vCJD occurs.

Control of contacts:

Individuals who have may have shared a common exposure with a case or who may have been exposed to infected material from a case, such as transplanted tissue, should be counseled by a specialist infectious diseases physician.

Control of environment:

All wound drainage, tissues and surgical equipment should be considered to be contaminated.  The World Health Organization has advised that no part or product of any animal which has shown signs of a TSE should enter a human or animal food chain.

Additional sources of information

·         http://www.ninds.nih.gov

• Australian Government Department of Health and Ageing 2003, ‘How Australia will respond to our first case of vCJD. A guide for the public’,

www.health.gov.au

• Australian Government Department of Agriculture, Forestry and Fisheries,

www.affa.gov.au

• Brown, P 2001, ‘Bovine spongiform encephalopathy and variant Creutzfeld-Jakob disease’, British Medical Journal, vol. 322, no. 7290, pp841–844.

• Creutzfeld-Jakob Disease Foundation Inc, www.cjdfoundation.org

• Coulthart, M, Cashman N 2001, ‘Variant Creutzfeldt-Jakob disease: a summary of current scientific knowledge in relation to public health’, Canadian Medical Association, vol. 165.

• Health Canada Online 2003, Classical Creutzfeld-Jakob disease, www.hc-sc.gc.ca

• National Institute of Neurological Disorders and Stroke 2003, Creutzfeldt-Jakob disease fact sheet,

Bethesda USA, www.ninds.nih.gov

• Smith, P 2003, ‘The epidemics of bovine spongiform encephalopathy and variant Creutzfeld-Jakob disease: current status and future prospects’, Public Health Reviews, Bulletin of the World Health Organization, vol. 81, no. 2.

• Therapeutic Goods Administration (for specific TGA measures to minimise the risk of exposure to TSEs through medicines and medical devices), www.tga.health.gov.au

• Turner, M 2001, ‘Variant Creutzfeldt- Jakob disease and blood transfusion’, Current Opinion in Hematology, vol. 8, no. 6, pp. 372–379.

• World Health Organization 2002, Variant Creutzfeld-Jakob Disease -fact sheet 180, www.who.int

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