Human Prion Diseases
by André Delacourte and Clive Evers
This form of CJD arises from contamination with tissue from an infected person, usually as the result of a medical procedure.
The first indication that human prion diseases might be transmissible through infected tissue came with the discovery of a strange disease called Kuru among the Fore people of Papua New Guinea in the 1950´s.
Kuru mainly affected women and children. It began with unsteadiness of gait, shakiness and lack of coordination. Eventually the patient would become unable to move and death would occur within a year of onset of symptoms.
On examination the brain would show damage to the cerebellum and spongiform changes characteristic of prion disease. Kuru was eventually linked to the funeral practices of the Fore people in which it was common for women and children to handle the dead body of their relatives including the brain.
Kuru is almost extinct now since the Fore people abandoned their funeral rites. Kuru has been very important in assisting in the understanding of human prion diseases in particular their risks of being transmitted from person to person.
Symptoms and course
Iatrogenic CJD may be transmitted intracerebrally, i.e. directly into the brain (exemple: contamination of surgical instruments).
In this case the symptoms are like sporadic CJD: initially depression, memory lapses, maybe unusual fatigue. However rapid progression to dementia and obvious neurological symptoms distinguish CJD from depression.
Within weeks unsteadiness and lack of coordination are likely. Sometimes these symptoms appear first. There may be sudden jerky movements, rigid limbs, maybe blindness and incontinence; difficulty in speaking and swallowing.
Eventually the patient loses the ability to move or speak and will need full time nursing care. CJD has been transmitted by treatment with human growth hormone. This is known as peripheral transmission because the rote to the brain of the infective agent is through the circulation not direct into the brain. Peripherally acquired CJD may be more like Kuru, with symptoms of ataxia (unsteadiness and lack of coordination) predominating and dementia being a rare feature.
Causes and risk factors
Brain tissue from a person with CJD contains an abnormal form of a protein called PrP. If this abnormal form comes into contact with normal PrP, which is present in the brains of unaffected people, it can change into the abnormal form and thereby transmit the disease. Unless precautions are taken some medical procedures carry a risk of transmitting CJD. For instance a few people contracted CJD from brain operations done with instruments, which were previously used on someone with CJD. In these rare cases the infection was delivered intracerebrally, that is directly into the brain. The prion agent survives the disinfection procedures, which normally destroy bacteria and viruses, but this was not known at the time.
Instruments which have been used on the brain of someone with suspected CJD should be destroyed. Intracerebral transmission of CJD has also occurred with corneal transplants and with grafts of dura mater, the tough membrane that covers the brain and is used in various kinds of surgery. The incubation period for intracerebral iatrogenic CJD is 19-46 months,In tonsil surgery there is a theoretical risk of contracting CJD through unknowingly contaminated surgical instruments previously used on a patient with CJD.
CJD has been transmitted peripherally by treatment with human growth hormone. This drug for the treatment of children with short stature used to be prepared from human pituitary glands. The inclusion, unknowingly, of just one gland from someone with CJD has the potential to infect many people. The incubation period for this type of CJD is around 15 years.
There is no evidence that CJD has been transmitted through blood although there is a theoretical risk. Some countries like the UK have taken precautions with their blood transfusion service to minimise such risk.
The risk of contracting CJD from organ transplants is uncertain but believed to be small. There are appears to be a genetic predisposition to contracting iatrogenic CJD. We all have two copies of the Prp gene, one from our mother and one from our father. These copies exist in different forms; people who inherit two identical forms appear to be at greater risk. It may be that this form of Prp is more susceptible to changing into the abnormal form of PrP.
Care and treatment
There is no treatment at present for CJD. However, there are a number of drugs, which can relieve the symptoms and make the patient more comfortable.
These include valproate and Clonazepam for jerking movements. The patient and their carers will also need much help from social services and nursing services.
In general, EEG and MRI analysis are used to demonstrate an atrophy and the lack of other causes such as vascular pathology, genetic analysis of the prion gene, analysis of biological markers in the CSF, post-mortem examination of prion amyloid plaques help to diagnose and to type the different prion pathologies.
National CJD Surveillance Unit Western General Hospital Crewe Road Edinburgh, EH4 2XU Scotland www.cjd.ed.ac.uk
In addition to surveillance and research they can organise intensive support for the person with CJD and their family.
CJD Support Network Gillian Turner Birchwood, Heath Top, Ashley Heath Market Drayton, Shropshire TF9 4QR England www.cjdsupport.net
Child Growth Foundation 2, Mayfeld Avenue London, W4 1PW United Kingdom Tel: +44 -(0)20- 8995 0257 Fax: +44 -(0)20- 8995 9075 firstname.lastname@example.org
Prion Clinic Department of Neurology St Mary’s Hospita Praed St. London, W2 1NY United Kingdom Tel: +44 -(0)20- 7886 6883
- CJD and prion disease: an introduction and explanation. Alzheimer’s Society CJD Support Network. December 1998.
- Will, RG et al A new variant of Creutzfeldt Jakob disease in the UK. Lancet 1996; 347; pp 921-925
- Douglas, MJ et al Patients with new variant CJD disease and their families:care and information needs. National CJD Surveillance Unit, Edinburgh, Feb 1999.
- Variant CJD:Alzheimer’s Society CJD Support Network. Information Sheet No 4. April 2001
Last Updated: vendredi 09 octobre 2009