Clinical Overview of Variant Creutzfeldt-Jakob Disease

Cause

There is strong epidemiologic and laboratory evidence for a causal association between vCJD and BSE. This is supported by the general absence of confirmed vCJD cases in geographic areas that had no BSE activity.

In addition, the likely incubation period is about 10 years, consistent with incubation periods for CJD, another prion disease in people.

Incubation period

The incubation period for prion diseases is measured in years, not days to months. It is believed that people who began showing vCJD symptoms in the mid-1990s, likely ate BSE-contaminated beef in the mid-1980s.

Outbreak and cases

vCJD was discovered after cases emerged in the United Kingdom in 1996. Between 1996 and 2023, 233 vCJD deaths were reported worldwide. The vast majority occurred in the United Kingdom. Cases were also reported in Europe, Asia, Saudi Arabia, Canada and the United States.

Four cases of vCJD have been reported in the United States. It is believed that all contracted the disease in another country. Two of the four patients had lived for decades in the United Kingdom. A third was born and raised in Saudi Arabia before coming to the United States. It's not clear where the fourth patient may have been exposed, but experts agreed it was likely outside the US.

Clinical features

There are a number of substantial differences between vCJD and classic CJD. vCJD predominantly affects younger people. The median age in cases has been 28 years.

Unlike classic CJD, which primarily causes dementia, vCJD begins with psychiatric or sensory symptoms. Dementia and neurologic abnormalities such as ataxia typically occur later in the illness.

Patients were sick for at least 12 months.

They also had a diffusely abnormal non-diagnostic electroencephalogram.

Prevention

The primary way to prevent vCJD is not to consume products from cows infected with BSE. As cases of BSE in cattle is now extremely rare, there is little people need to do to prevent contracting vCJD.

Human and animal health officials determined that meat-and-bone meal made from sick cows had been fed to other cattle. This led to the growth of the BSE outbreak. Feed bans forbidding such practices drastically reduced the number of BSE cases.

Testing and diagnosis

There is no specific diagnostic test for vCJD. vCJD must be confirmed through neuropathologic examination of brain tissue obtained by biopsy or at autopsy. CDC supports the National Prion Disease Pathology Surveillance Center at Case Western Reserve University. This center performs special state-of-the-art diagnostic tests for prion diseases, including post-mortem tests for vCJD.

A "probable case" of vCJD can be diagnosed on the basis of clinical criteria developed in the U.K. The following features should be present for confirmed vs suspected cases:

Definite Variant CJD

1. Numerous widespread kuru-type amyloid plaques surrounded by vacuoles in both the cerebellum and cerebrum – florid plaques.
2. Spongiform change and extensive prion protein deposition shown by immunohistochemistry throughout the cerebellum and cerebrum.

Suspected Variant CJD

1. Current age or age at death <55 years (a brain autopsy is recommended, however, for all physician-diagnosed CJD cases).
2. Psychiatric symptoms at illness onset and/or persistent painful sensory symptoms (frank pain and/or dysesthesia).
3. Dementia, and development ≥4 months after illness onset of at least two of the following five neurologic signs: poor coordination, myoclonus, chorea, hyperreflexia, or visual signs. (If persistent painful sensory symptoms exist, ≥4 months delay in the development of the neurologic signs is not required).
4. A normal or an abnormal EEG, but not the diagnostic EEG changes often seen in classic CJD.
5. Duration of illness of over 6 months.
6. Routine investigations of the patient do not suggest an alternative, non-CJD diagnosis.
7. No history of receipt of cadaveric human pituitary growth hormone or a dura mater graft.
8. No history of CJD in a first degree relative or prion protein gene mutation in the patient.

Notes

1. If a patient has the typical bilateral pulvinar high signal on MRI scan, a suspected diagnosis of variant CJD requires the presence of a progressive neuropsychiatric disorder, d, e, f and g of the above criteria, and four of the following five criteria: 1) early psychiatric symptoms (anxiety, apathy, delusions, depression, withdrawal); 2) persistent painful sensory symptoms (frank pain and/or dysesthesia); 3) ataxia; 4) myoclonus or chorea or dystonia; and 5) dementia.
2. A history of possible exposure to bovine spongiform encephalopathy (BSE) such as residence or travel to a BSE-affected country after 1980 increases the index of suspicion for a variant CJD diagnosis.

Patient management

Treatment of prion diseases remains supportive. No specific therapy has been shown to stop or slow the progression of vCJD.

Similar diseases

Despite having very similar names, vCJD is not the same disease as classic CJD (often simply called CJD).

Both disorders are invariably fatal prion diseases that affect the brain. Both have unusually long incubation periods, measured in years. However, the two diseases have different clinical and pathologic characteristics, median age of onset and genetic profile.

This table shows vCJD characteristics, compared to classic CJD.

Surveillance

vCJD surveillance primarily consists of monitoring trends and cases of classic CJD to make sure they don't resemble vCJD cases.

CDC uses several surveillance mechanisms to do this. CDC prion experts routinely review death certificates of people who died from classic CJD. In addition, CDC reviews and actively investigates reports of possible iatrogenic CJD and variant CJD cases.

CDC also conducts follow-up review of clinical and neuropathology records of high-priority CJD patients (e.g. young age), consistent with those who have died from vCJD cases worldwide. This work is done with the support of the Council of State and Territorial Epidemiologists (CSTE).

These CJD surveillance methods could help identify vCJD cases if and when they occur in the United States.

Case studies

An experimental study published in 1996 looked at macaque monkeys inoculated with brain tissue from BSE-infected cattle. Reserchers found the monkeys exhibited symptoms of illness strikingly similar to those of vCJD in people. (Nature 1996;381:743-4).

Another 1996 study reported on a Western blot analysis of prions obtained from ten vCJD patients and from BSE-infected animals. The authors found similar molecular characteristics in both people and animals. They also found that the characteristics were distinct from prions obtained from patients with classic CJD. (Nature 1996; 383:685-90).

A 1997 experimental study involved inoculating inbred mice with the agents causing BSE and vCJD. (Nature 1997;389:498-501). The mice inoculated with vCJD had latency periods and lesion profiles consistent those inoculated with BSE. This study substantially increased the strength of the scientific evidence for a causal association between vCJD and BSE.

Resources

Recent US Case of Variant Creutzfeldt-Jakob Disease-Global ImplicationsMaheshwari A, Fischer M, Gambetti P, et al. EID. May 2015; 21(5):750-759.

Creutzfeldt-Jakob Disease surveillance and diagnosis. Belay ED, Holman RC, Schonberger LB. CID September 15 2005;41:834-836.

Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient.Peden AH, Head MW, et al. Lancet 2004;264:527-529.

Possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion.Llewelyn CA, Hewitt PE, et al. Lancet 2004;363:417-421.

Probable Variant Creutzfeldt-Jakob Disease in a U.S. Resident—Florida, 2002MMWR. October 18, 2002;51(41):927-929.

CDC and Florida Department of Health investigate a likely case of new variant Creutzfeldt Jakob disease in a U.K. citizen residing in the U.S.CDC Press Release, April 18, 2002.

Bovine Spongiform Encephalopathy and Variant Creutzfeldt-Jakob Disease: Background, Evolution, and Current ConcernsEID. January-February 2001; 7(1):6-16.

Transmissible Spongiform Encephalopathies in Humans pdf icon[PDF – 183KB]Belay E. Annu. Rev. Microbiol. 1999. 53:283–314

Creutzfeldt-Jakob Disease in the United States, 1979-1994: Using National Mortality Data to Assess the Possible Occurrence of Variant CasesEID. October-December 1996;2(4):333-337.

Journal of the American Medical Association on November 8, 2000 (Volume 284, No. 18, pp. 2322-3) and in Clinics of Laboratory Medicine in December 2002 (Volume 22, pp. 849-62).