National Prion Clinic


Acquired prion disease

In the acquired prion diseases, the rogue prion proteins have inadvertently been introduced into the individual as a result of accidental inoculation during medical procedures (termed Iatrogenic CJD (iCJD)) or by exposure to food products contaminated with BSE (variant CJD (vCJD) or human BSE). vCJD is the only type of human prion disease thought to be caused by exposure to BSE. Kuru is also an acquired prion disease (more information can be found about Kuru within the research section of the website).

There are 3 ways iCJD has been acquired:

Growth hormone and gonadotrophin administration
Between 1958 and 1985 thousands of children were treated worldwide with injections of growth hormone to correct growth problems.  Approximately 1,900 children were treated with human derived growth hormone in the UK yet relatively few people have developed CJD.  To date there have been approximately 200 cases world-wide.  The growth hormone in these cases was extracted from large numbers of pituitary glands (a small gland at the base of the brain which produces growth hormone) obtained from bodies after death i.e. cadaver sourced growth hormone.  A number of glands were thought to be derived from patients who, unbeknown at the time of donation, had been suffering from CJD.  Use of this material in the UK and USA ceased in 1985 and a little later in France when artificially synthesised growth hormone, which does not carry this risk, became available. 

A small number of women have also developed CJD after being treated with human derived pituitary gonadotrophin (sometimes used for treatment of infertility).

Growth hormone induced iCJD affects young adults as most treatments were given to children with restricted growth.  The disease has a long incubation period that can exceed three decades.  At present there are 0-6 new cases diagnosed each year in the UK.  In the early stages the illness is predominantly a disorder of co-ordination and balance (ataxia), sometimes with psychiatric disturbances.  The duration of the illness is variable but is usually 8-18 months. 

Implantation of cadaver sourced dura.
The dura is a tough membrane covering the brain and lying immediately under the skull.  Material obtained from several dead patients was used to repair defects in the dura of patients who had undergone surgical procedures on the brain which left substantial defects in the dura and occasionally for other reasons e.g. aneurysm repair.  Since 1992 human dural grafts have not been used, having been replaced with a synthetic substitute.  The majority of iCJD cases as a result of dural grafting have been reported from Japan, where 154  cases had been notified by 2018, with very few from the UK.  Data from Japan indicates a wide age range of onset of CJD in these cases as would be expected from the variable age at which the initial graft was under taken (15-80 years median age 57 years ).  The incubation period is also variable, ranging from 1 to 25years (median approximately 13 years); as a few cases are still occurring it is not possible to given a maximum incubation period.

There are 2 main presentation with iCJD resulting from dural grafting - most frequently the initial symptoms are problems with memory and cognition (dementia), and the subsequent progression is similar to that seen in sCJD (refer to sporadic prion disease section for further information).  Less frequently, ataxia is the predominant initial symptom, affecting people's coordination and ability to carry out purposeful movements.

Other surgical procedures
Historically there have been less than 10 cases of CJD resulting from surgical procedures on the brain using instruments previously used for neurosurgical operations on a patient known to have sCJD.  There have been no such cases for decades in the UK.

Two cases of CJD have been reported in patients who have received corneal grafts to repair damage to the cornea (the transparent part of the front of the eye). The grafted tissue is sourced from deceased patients.  These two cases may represent a chance coincidence of sCJD in a grafted patient. Even if the recipient’s CJD was truly related the risk in general must be very small given the large numbers of grafts done each year.

Variant CJD (vCJD) and Bovine Spongiform Encephalopathy (BSE)

Dietary exposure through consumption of BSE infected food products has resulted in vCJD.  There have been less than 200 cases in the UK.  After ingestion of infected meat the abnormal prion protein invades the lymphatic tissues (tonsils, lymphatic areas of the gut and the spleen).  It then travels in the nerves from the gut (autonomic nervous system) to the spinal cord and brain.  vCJD has been in decline since 1999/2000 and at present there are no known cases in the UK.  There is however considerable uncertainty whether the epidemic is over given the potential for extremely long incubation periods in prion diseases which is partly dependent on genetic factors. All but 2 cases of vCJD were methionine-methionine homozygous at position 129 in the prion gene - in 2008 a patient was clinically diagnosed with a different type of the prion protein gene, methionine-valine at this position.  Also, in 2017 we reported a patient with vCJD with methionine-valine at position 129.

vCJD tends to affect young adults (average 26 years in females and 28 years in males, range 12-74 years) and occurs equally in males and females.  There are early psychiatric and behavioural symptoms, for example, mood disturbance and delusions.  Persistent pain can be experienced in the lower limbs and is unrelated to anxiety levels.  As the disease advances, unsteadiness develops and cognition becomes affected.  All these symptoms progress, culminating in a moribund state in 13 -14 months on average.  The duration of the illness is however variable. 

Five cases of possible infection with vCJD transmitted by blood transfusion have been reported.  Three of the cases developed and died of vCJD and in two cases there was evidence of trasmission, with infection in the lymphatic system, but the brain was normal; these patient died of an unrelated cause.  As a result of these observations a variety of surveillance measures have been instigated to assess the likelihood of silent infection being present in patients who have received a large amount of blood or blood products. Meanwhile, a number of measures have been put in place to minimise the risk of transmission of vCJD from blood or blood product transfusion.  These include, withdrawal and recall of blood or blood components obtained from any individual who later develops vCJD; leukodepletion of blood used for transfusion (the white blood cell fraction which carries a substantial proportion of the infective material, is removed).  From March 2004 recipients of blood transfusions have been excluded from donating blood as an added precaution to protect the blood supply.

For further information on progression of all types of acquired prion disease refer to the signs and symptoms section.