Variant CJD: more detail

Origin and epidemiology

Epidemiological and laboratory evidence supports a causal link between variant CJD and bovine spongiform encephalopathy. Confirmed cases are generally absent from countries where BSE was not present. The spread of BSE in cattle was linked to feeding cattle meat and bone meal derived from other prion-infected cattle, and those practices have changed.

The likely incubation period is around ten years, comparable to classic CJD. From 1996 through 2023, 233 deaths from variant CJD were reported worldwide, most of them in the United Kingdom, with cases also reported in Europe, Asia, Saudi Arabia, Canada and the United States. The four United States cases are all believed to have been acquired abroad: two patients had lived for decades in the United Kingdom, one was raised in Saudi Arabia, and the source for the fourth is unclear but likely outside the country. The NHS reports no recorded UK deaths from variant CJD in 2020.

Clinical features

Median age at death is 28 years, against 68 years for classic CJD, and median duration of illness is 13 to 14 months, against 4 to 5 months.

Onset is typically psychiatric or sensory. The NHS lists severe depression, withdrawal, anxiety, irritability and insomnia, with neurological symptoms beginning around four months later. CDC describes prominent painful dysaesthesia and delayed neurological signs, with dementia and ataxia appearing later in the course than in classic CJD, where dementia dominates the presentation.

The EEG differs usefully. Periodic sharp wave complexes, often present in classic CJD, are often absent in variant CJD, where the recording may be diffusely abnormal without being diagnostic. A referral made on the strength of a normal or non-specific EEG in a young person with psychiatric onset and painful sensory symptoms is therefore appropriate.

Diagnostic criteria

CDC criteria for suspected variant CJD require all of the following: age under 55, psychiatric symptoms at illness onset or persistent painful sensory symptoms, dementia with the development of at least two of five neurological signs, illness duration longer than six months, no alternative diagnosis from routine investigations, and no history of receiving cadaveric human pituitary growth hormone or a dura mater graft. Additional requirements apply when the MRI pulvinar sign is present.

Bilateral pulvinar high signal is reported in more than 75 percent of variant CJD cases and is not reported in classic CJD. In the appropriate clinical context it is highly specific, and it is the single most useful imaging finding in this disease.

No specific test establishes the diagnosis in life. Definite variant CJD requires neuropathological examination of brain tissue from biopsy or autopsy, showing widespread florid plaques in cerebellum and cerebrum together with spongiform change and widespread prion protein deposition. In the United States that examination is performed by the National Prion Disease Pathology Surveillance Center.

One further contrast with classic CJD has practical weight. CDC describes the agent as readily detected in lymphoid tissue in variant CJD and not readily detected in classic CJD, which is the basis for the historical use of lymphoreticular tissue in diagnosis and part of the reason surgical and transfusion precautions differ between the two.

The sequence of investigations as a family experiences it is on how it is diagnosed.

Transmission between people, and at-risk registers

The NHS reports that the prion has been transmitted by blood transfusion five times in the United Kingdom. This is the reason for donor deferral rules in several countries and for continued precautions in blood, plasma and tissue services.

The United Kingdom maintains registers of people identified as at increased risk of CJD through medical exposure. The UKHSA surveillance update for 2024 reports, as of 31 December 2024, 6,073 individuals identified, 5,629 notified and 4,181 notified and alive, compared with 4,245 in 2023. Across all at-risk groups, 86 cases and 2 asymptomatic infections had been recorded. The same document’s year-by-year table gives 4,170 notified and alive for 2024 against the 4,181 in its summary text, so quote the figure with its source if it is going into a letter. UKHSA notes that the bleeding disorder and growth hormone data are slight underestimates, since reporting from haemophilia centres was incomplete and some patients opted out or are not included in the Institute of Child Health follow-up. Dura mater graft recipients and families at risk of genetic prion disease are not held by UKHSA; the latter are held by the National Prion Clinic.

For numbers of CJD case reports themselves, UKHSA directs readers to the National CJD Research and Surveillance Unit.

Counselling someone on an at-risk register is a distinct task from counselling a family with an inherited variant. The exposure is historical and fixed, there is no test that can tell an individual whether they are infected, and the honest position is that the probability for any one person is unknown and believed to be low. Questions about what a specific notification means belong with the service that issued it.

Management

Care is supportive, and the 2026 multidisciplinary recommendations in Age and Ageing apply across the prion diseases. Myoclonus that interferes with function or care or causes distress is treated, with levetiracetam suggested first line and clonazepam reserved for the advanced non-ambulant stage. Neuropsychiatric symptoms are approached on the basis that challenging behaviour is generally the communication of an unmet need, with a watch-and-wait approach often justified because symptoms can resolve quickly.

Pain deserves separate attention here. The recommendations note that pain is generally not a problematic symptom in sporadic CJD, but painful dysaesthesia is intrinsic to variant CJD, so the stepped approach with regular paracetamol first line, and cautious opioid use under palliative care guidance, is more often needed. Swallowing deteriorates over time, and whether clinically assisted nutrition and hydration serves a person’s best interests is decided individually and reviewed at each care review.

Because the illness is longer than classic CJD and affects younger people, the social work is heavier: employment, dependent children, and the involvement of a specialist palliative team over a year or more. Early palliative care involvement is encouraged, and suspected prion disease in the United Kingdom is referred to the National Prion Clinic. Family-facing guidance is on what to expect.

Research

Nothing has yet been shown to modify the course of variant CJD in people. Current laboratory work concentrates on lowering prion protein expression and on blood-based detection, where variant CJD has been the main testbed because the agent is present in blood. Studies open to recruitment are listed under current trials, with the mechanistic account on our research page. The plain version of this page is variant CJD.