Possible link between BSE and Creutzfeldt-Jacob Disease

Four cases of CJD among dairy farmers in the UK occurred in 1994-5 These cases resembled typical sporadic CJD . They did, however, highlight concern about the possible transmission of BSE to humans.

In 1995, Britton and Bateman identified cases (2) of CJD in teenagers that had unusually kuru-type plaques. These are normally seen in only 5% of CJD cases. Patients have behavioral and psychiatric disturbances, early and progressive ataxia (failure of muscular coordination). The new cases had extensive plaque formation and identifiable patterns of prion protein immunostaining. These cases had similarities to iatrogenic CJD associated with peripheral inoculation of prions (cadaveric growth-hormone cases) and kuru which are also characterized by progressive ataxia, behavioral and psychiatric disturbances. These patients had no recognized risk factors for CJD (iatrogenic routes or previously recognized prion gene mutations), However, they did have some familial history of dementia (Collinge ).

Subsequently, a consistent and previously unrecognized disease pattern was identified in 10 (currently 14) other cases of CJD. Six of these were diagnosed in 1994 and four in 1995. Some of the features of the disease are different from those of classic CJD and a consideration of the medical histories, genetic analysis, possibility of increased ascertainment and other possible explanations failed to provide an adequate explanation for the pattern. This cluster is being referred to as Variant CJD (vCJD) or new variant CJD (nvCJD).

The link between vCJD and BSE is supported by TSE strain typing. In particular, experimental transmission of BSE and vCJD to macaque monkeys resulted in similar clinical presentation and neuropathology then similar experiments confirmed these findings using mice.

Comparison of the Typical Features for CJD and vCJD
	sporadic (s)CJD	BSE-linked vCJD
average age	63-66 yr	28 yr
duration of illness	4-6 mo	13-14 mo
EEG pattern	periodic complexes	atypical recordings
amyloid plaques (% of cases)	5-10 Kuru plaques	florid multicentric 100%
PrPSc in lymph tissue	absent	present
.	.	.
dementia (% of cases)	100	.
seizures (% of cases)	~12	.
myoclonus (% of cases)	~82	.
dysphasia (% of cases)	~60	.
cerebellar involvement (% of cases)	~64	.
.	.	depression
.	.	ataxia
.	.	involuntary movements
.	.	akinetic mutism
.	.	.
.	.	.
.	.	.

The unique aspects of vCJD allowed for a case definition to be established enabling future surveillance.

The incidence of CJD world wide is approximately 1 per million population.

• The incidence of CJD is not different between meat eating and vegetarian populations
• The incidence in Britain is no higher than other countries
• Concern stemmed from the unusual cluster and characteristics of the CJD cases.

In 1996, the British Spongiform Encephalopathy Advisory Committee (SEAC) concluded that, "the most likely explanation at present is that these cases are linked to exposure to BSE before the introduction of the specified bovine offal (SBO) ban in 1989". The government stressed that there is still no proof of a definite link but accepted that the new evidence was cause for concern.

The new vCJD identified in the UK was suggested to have originated by ingestion of high-titre materials in the mid-1980's before the specified bovine offal (SBO) ban, representing an incubation period of 5-10 years. The shortest incubation period of a human prion disease is for kuru (where no species barrier exists) is 4 - 5 years.

• In experimental models, the time to onset of clinical symptoms is longer if the infectious material is from another species versus the time to onset of symptoms if the infectious material is obtained from the same species
• the time to onset of clinical symptoms shortens once the TSE strain is passaged within the new species; i.e. adapted

UK government ministers announced (3/25/96) new beef safety measures following the report by an independent expert advisory committee of a possible link between bovine spongiform encephalopathy (BSE) and Creutzfeldt-Jacob disease (CJD).

Scientific opinion is not unanimous about the current safety of beef. If there is a real risk it should have been greater for British consumers before the 1989 controls were introduced. The description of vCJD will be used for intense surveillance so that the scale of the problem can be assessed. Because of the lengthy incubation period (in humans) for CJD, 5-15 years, it will be some time before even tentative estimates can be made of the number of people that are likely to have contracted CJD from beef before 1989, assuming that transmission did occur.

Characteristics of variant Creutzfeldt-Jacob Disease - vCJD

Dr. R.G. Will (Mar. 21, 1996) of the (UK) National Creutzfeldt-Jakob Disease Surveillance Unit wrote a letter to neurologists asking them to notify the CJD Surveillance Unit of any cases, past or present, with the following clinical or neuropathological profile:

1. An early age of onset or death
2. A prolonged duration of illness
3. A predominantly psychiatric presentation including
• anxiety
• depression
• withdrawa
• behavioral change which progresses
• presentation with dysaesthesiae in the limbs and/or face.
4. After a period of weeks or months, the development of a cerebellar syndrome with gait and limb ataxia.
5. Forgetfulness and memory disturbance develop, often late in the clinical course but progress with the development of severe cognitive impairment and a state of akinetic mutism
6. Myoclonus develops in the majority of patients and in some is preceded by chroeiform movements, but typical EEG appearances of CJD are absent
7. Neuropathologically
   • spongiform change
   • neuronal loss
   • astrocytic gliosis most evident in the basal ganglia and thalamus
   • the most striking and consistent neuropathological feature is amyloid plaque formation extensively distributed throughout the cerebrum and cerebellum

A more complete description of the (vCJD symptoms or vCJD symptoms) and contact information for the United Kingdom, National Creutzfeldt-Jakob Disease Surveillance Unit is available through the British Medical Journal