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Creutzfeldt-Jakob Disease (CJD)

by Pierluigi Gambetti, MD

Creutzfeldt-Jakob disease (CJD) is a sporadic, familial, or acquired (iatrogenically) prion disease. Variant CJD (vCJD) is the form acquired by eating meat from cattle with bovine spongiform encephalopathy (mad cow disease). CJD symptoms include dementia, myoclonus, and other CNS deficits; death occurs in 1 to 2 yr. Transmission can be prevented by taking precautions when handling infected tissues and using appropriate techniques to clean contaminated instruments. Treatment is supportive.

CJD occurs worldwide. Most cases (about 85%) are sporadic (sCJD). About 5 to 15% are familial, with autosomal dominant transmission. sCJD typically affects people > 40 yr (median, about 60 yr). In the familial form, age at onset is usually earlier, and duration of disease is longer. CJD can be transmitted iatrogenically (eg, after cadaveric corneal or dural transplants, use of stereotactic intracerebral electrodes, or use of growth hormone prepared from human pituitary glands); iatrogenic transmission probably accounts for < 1% of CJD cases.

vCJD is rare. Most cases have occurred in the United Kingdom, which had 176 cases through 2011, compared to 49 cases in all other European and non-European countries. In vCJD, symptoms develop at a younger average age (< 30 yr) than in sCJD. In the early 1980s, because of relaxed regulations for processing animal by-products, contaminated tissue, probably from sheep infected with scrapie, introduced the scrapie prion protein (PrP Sc ) into cattle feed. Hundreds of thousands of cattle developed bovine spongiform encephalopathy (BSE), also called mad cow disease. Despite widespread exposure, relatively few people who ate meat from affected cattle developed vCJD.

Because the incubation period in BSE is long, a connection between BSE and contaminated feed was not recognized in the UK until BSE had become an epidemic. The BSE epidemic came under control after a massive slaughter of cattle and after changes in the rendering procedures, which drastically reduced contamination of meat by nervous system tissue. In the UK, the annual number of cases of vCJD, which peaked in 1995, has steadily declined, with only 5 cases in 2011. Only 4 cases of vCJD have been linked to blood transfusion; they occurred in people who received transfusions between 1996 and 1999. Whether there is a latent pool of people who have received blood transfusions and who are thus at risk of later development of vCJD is unclear.

Although no case of vCJD originating in North America has been reported, BSE has been reported in a few North American cattle (4 in the US and 19 in Canada).

Symptoms and Signs

About 70% of patients present with memory loss and confusion, which eventually develop in all patients; 15 to 20% present with incoordination and ataxia, which often develop early in the disease. Myoclonus provoked by noise or other sensory stimuli (startle myoclonus) often develops in the middle to late stages of disease. Although dementia, ataxia, and myoclonus are most characteristic, other neurologic abnormalities (eg, hallucinations, seizures, neuropathy, various movement disorders) can occur.

Ocular disturbances (eg, visual field defects, diplopia, dimness or blurring of vision, visual agnosia) are common.

Diagnosis

  • Diffusion-weighted MRI

  • CSF markers

  • Exclusion of other disorders

CJD should be considered in elderly patients with rapidly progressive dementia, especially if accompanied by myoclonus or ataxia; however, CNS vasculitis; Hashimoto encephalopathy (an autoimmune encephalopathy associated with Hashimoto thyroiditis); intravascular lymphoma (a rare lymphoma); encephalitis that affects the limbic system, brain stem, and cerebellum; Lewy body dementia; and intoxication with lithium or bismuth can mimic CJD and must be considered.

CJD is suspected in symptomatic younger patients who have ingested processed beef in the UK (vCJD) or who have a family history of CJD (familial CJD). Rarely, sCJD develops in young patients, but in such patients, Wilson disease must be excluded.

Diagnosis may be difficult. Diffusion-weighted MRI is the best noninvasive diagnostic test for CJD. It can detect evolving patchy areas of hyperintensity in the cortical ribbon, which strongly suggest CJD. Proteins 14-3-3, brain-specific enolase, and tau are commonly present in CSF but are not specific for CJD. EEG is typically done; about 70% of patients have characteristic periodic sharp waves, but this pattern typically occurs late in the disease and may be transient. Brain biopsy is usually unnecessary.

Prognosis

Death typically occurs after 6 to 12 mo, commonly due to pneumonia. Life expectancy in vCJD is longer (averaging 1.5 yr).

Prevention

Because there is no effective treatment, prevention of acquired CJD is essential. Workers handling fluids and tissues from patients suspected of having CJD must wear gloves and avoid mucous membrane exposure. Contaminated skin can be disinfected by applying 4% Na hydroxide for 5 to 10 min, followed by extensive washing with water. Steam autoclaving of materials at 132° C for 1 h or immersion in 4% Na hydroxide or 10% Na hypochlorite solution for 1 h is recommended. Standard methods of sterilization (eg, exposure to formalin) are ineffective.

The US Department of Agriculture (USDA) currently carries out BSE surveillance for 2000 to 5000 cattle/mo. In 2004, a positive BSE case in the US caused testing to be expanded to an average of 1000 cattle/day, but testing was later reduced to 40,000/yr (0.1% of the cattle that are slaughtered).

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