RATIONALE FOR SURVEILLANCE:
The incidence of Creutzfeldt-Jakob Disease (CJD) and its variants is not currently monitored in many parts of the world. In 1996 a new variant of CJD (nvCJD) was recognized in the United Kingdom. An etiological link has since been confirmed between nvCJD and the agent of bovine spongiform encephalopathy (BSE). The size of the population exposed and susceptible to this agent in the United Kingdom is not known; this, in addition to uncertainties relating to the potential length and distribution of the incubation period, complicate any useful prediction of the future number of nvCJD cases. Other populations may have also been exposed to the agent through importation of live cattle or cattle by-products from BSE-affected countries, or through the use of medicinal or cosmetic products containing affected bovine tissues. Global surveillance of the new variant and other forms of CJD shall lead to a better understanding of the disease, including potential causes of iatrogenic CJD as well as the distribution of various hereditary forms. It shall also provide information towards protection against the risks of disease.
RECOMMENDED CASE DEFINITIONS of CJD and CJD subtypes
1. Sporadic CJD
(a) Possible CJD:
• Progressive dementia; and
• EEG atypical or not known and
• Duration <2 years and
• At least 2 out of the following 4 clinical features: myoclonus, visual or cerebellar disturbance, pyramidal/extrapyramidal dysfunction, akinetic mutism
(b) Probable CJD:
(in the absence of an alternative diagnosis from routine investigation)
• Progressive dementia; and
• At least 2 of the following 4 clinical features:
• Visual or cerebellar disturbance
• Pyramidal/extrapyramidal dysfunction
• Akinetic mutism and
• A typical EEG, whatever the clinical duration of the disease, and/or
• A positive 14-3-3 assay for CSF and a clinical duration to death <2 years
(c) Confirmed (definite) CJD:
• Neuropathological confirmation; and/or
• Confirmation of protease-resistant prion protein (PrP) (immunocytochemistry or Western blot) and/or
• Presence of scrapie-associated fibrils
2. Iatrogenic CJD
• Progressive cerebellar syndrome in a recipient of human cadaver-derived pituitary hormone; or
• Sporadic CJD with a recognized exposure risk
3. Familial CJD
• Confirmed or probable CJD plus confirmed or probable CJD in a first degree relative and/or
• Neuropsychiatric disorder plus disease-specific PrP mutation
Note: For purposes of surveillance, includes Gerstmann-Sträussler-Scheinker (GSS) syndrome and fatal familial insomnia (FFI).
4. New variant CJD (nvCJD)
New variant CJD cannot be diagnosed with certainty on clinical criteria alone at present. On the basis of the few neuropathologically confirmed cases, the diagnosis of nvCJD should be considered as a possibility in a patient with a progressive neuropsychiatric disorder and at least 5 of the following 6 clinical features:
• Early psychiatric symptoms
• Early persistent paraesthaesia/dysaesthesia
• Chorea/dystonia or myoclonus
• Akinetic mutism
The suspicion of nvCJD for surveillance purposes is strengthened by the following:
• No history of potential iatrogenic exposure
• Clinical duration >6 months
• Age at onset <50 years
• No PrP gene mutation
• EEG does not show the typical periodic appearance
• Routine investigations do not suggest an alternative diagnosis
• Magnetic Image Resonance shows abnormal symmetrical and bilateral high signals from the pulvinar on axial T2- and/or proton-density-weighted images
A patient with a progressive neuropsychiatric disorder and 5 out of the 6 clinical criteria mentioned earlier plus all of the criteria of suspicion listed immediately above should be considered as a suspect case of nvCJD for surveillance purposes.
Neuropathology is mandatory for the diagnosis of definite nvCJD: the use of cerebral biopsy in living patients is to be discouraged unless its purpose is to arrive at an alternative diagnosis of a treatable disorder. Autopsy (or postmortem biopsy of the brain where autopsy is not possible) is strongly encouraged in any suspect case of CJD. See under "special aspects" for the neuropathological criteria in CJD and other human transmissible spongiform encephalopathies.
RECOMMENDED TYPES OF SURVEILLANCE
One centre should be identified at central level to carry out surveillance.
All reporting should be case-based.
All definite, probable and possible cases should be notified by the appropriate health care professionals (usually physicians, neurologists, psychiatrists, neuropathologists) to the centre responsible for surveillance.
Note: Death registrations should be checked in order to identify cases not detected by routine surveillance.
RECOMMENDED MINIMUM DATA ELEMENTS
Case-based data for reporting
• Subtype and classification of CJD
• Age, sex, country of birth, geographical information, occupation
• Date of onset, date of death
• Vital status (alive, dead)
RECOMMENDED DATA ANALYSES, PRESENTATION, REPORTS
Number of cases by subtype, classification, occupational group, geographical area.
Number of cases by year of death, by age at death.
PRINCIPAL USES OF DATA FOR DECISION-MAKING
• Plot the trend in incidence of CJD subtypes
• Detect clusters of cases requiring further investigation
• Identify risk factors for disease
Neuropathological criteria for CJD and other human transmissible spongiform encephalopathies can be summarized as follows:
Creutzfeldt-Jakob disease: sporadic, iatrogenic (recognized risk) or familial (same disease in first degree relative or disease-associated PrP gene mutation):
• Spongiform encephalopathy in cerebral and/or cerebellar cortex and/or subcortical grey matter; and/or
• Encephalopathy with prion protein (PrP) immunoreactivity (plaque and/or diffuse synaptic and/or patchy/perivacuolar types)
New variant CJD
• Spongiform encephalopathy with abundant PrP deposition, in particular multiple fibrillary PrP plaques surrounded by a halo of spongiform vacuoles ('florid' plaques, 'daisy-like' plaques) and other PrP plaques, and amorphous pericellular and perivascular PrP deposits especially prominent in the cerebellar molecular layer
Gerstmann-Sträussler-Scheinker (GSS) disease: (in family with dominantly inherited progressive ataxia and/or dementia and one of a variety of PrP gene mutations):
• Encephalo(myelo)pathy with multicentric PrP plaques
• Thalamic degeneration, variable spongiform change in cerebrum
• Spongiform encephalopathy in the Fore population of Papua New Guinea
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Communicable Diseases Surveillance and Response (CSR)
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