Creutzfeldt-Jakob disease (subacute spongiform encephalopathy) is a prion disease characterized by progressive deterioration of mental function, leading to dementia, muscle twitching (myoclonus), and staggering when walking. A variant form is acquired by eating contaminated beef.

Sporadic Creutzfeldt-Jakob disease, the most common form, affects 1 in a million people each year throughout the world. It affects adults, mainly in their late 50s and 60s. For this form, no cause is known.

Familial CJD results from a mutation in the gene of PrP^c, which results in conversion of the normal PrP^c molecule to a disease-causing prion. Familial CJD is often inherited and usually starts at an earlier age and lasts longer.

The acquired form includes variant Creutzfeldt-Jakob disease, which is thought to be acquired from the consumption of contaminated beef or beef products. The variant form usually begins around age 30, in contrast to sporadic CJD, which usually begins around age 65. To date, the variant form has been acquired only in Europe, mainly in the United Kingdom, with the exception of two cases acquired in Saudi Arabia. Spread of the disease has been controlled by massive slaughter of cattle in the United Kingdom. Widespread surveillance for the disease in cattle has resulted in a progressively lower number of new cases in the United Kingdom.

External sources for the prion include transplantation of contaminated corneas or possibly other tissues from affected donors and brain surgery using instruments previously used to operate on a person who had CJD. Routine cleansing and sterilization procedures do not destroy prions. However, bleach is effective. Acquiring the disease this way is extremely unlikely.

Another external source is hormones derived from human pituitary glands used for treatment. For example, the disease developed in some children who were treated with growth hormone derived from human pituitary glands. These hormones are now genetically engineered rather than prepared from cadavers, so there is no longer risk of CJD.

Three cases of CJD have been transmitted through blood transfusion. However, in all cases, the disease was acquired from donors affected by the variant form. The type of CJD acquired by medical intervention is called iatrogenic.

CJD has never been reported to be transmitted through casual or even intimate contact with people who have the disease.

Symptoms

The most common early symptoms—memory loss and confusion—may resemble those of other dementias, such as Alzheimer's disease. In some people, loss of muscle coordination occurs first. In about 10 to 20% of people, symptoms appear abruptly, starting with dizziness and double vision. In people with the variant form, the first symptoms tend to be psychiatric symptoms (such as anxiety or depression), rather than memory loss. Later symptoms are similar in both forms.

Whether symptoms develop gradually or abruptly, mental decline progresses, often producing such symptoms as neglect of personal hygiene, apathy, and irritability. Some people tire easily and become sleepy. Others cannot fall asleep.

Muscles usually begin to twitch involuntarily and quickly during the first 6 months after symptoms begin. Trembling and clumsiness may also develop, and muscle coordination is lost. Walking becomes unsteady, resulting in staggering (similar to the walk of a person who is drunk). Movements may be slow. Impairment of muscle control may result in unusual postures, such as twisting of the trunk or limbs forward and sideways. Muscles may jerk when stretched.

The person may startle easily, and the resulting responses, such as jumping when a loud noise is heard, are exaggerated. Startling may trigger muscle twitching. The muscles that control breathing and coughing are usually impaired, increasing the risk of pneumonia. Vision may become blurry or dim.

The symptoms worsen, usually much more rapidly than in Alzheimer's disease, resulting in severe dementia.

Most people with CJD die within 6 months after symptoms appear. About 10 to 20% of people survive for 2 years or more. People with the variant form usually survive for 1½ years. Often, the cause of death is pneumonia.

In people who have acquired the prion from an external source, no symptoms appear for months or years later. In the variant form, the time interval between eating contaminated beef and onset of the disease is estimated to be 6 to 12 years.

Diagnosis and Treatment

Doctors consider CJD when mental function is deteriorating quickly, muscle twitching is present, walking is unsteady and staggering, and other dementias have been ruled out by routine testing. The variant form may be considered in people who have typical symptoms and who have eaten processed beef in the United Kingdom or in other countries at risk for mad cow disease.

Diagnosis is mainly by electroencephalography (EEG), analysis of cerebrospinal fluid, and magnetic resonance imaging. EEG is done to check for specific abnormalities in the electrical activity of the brain, which occur in 70% of people with the disease. A spinal tap is done to obtain a sample of cerebrospinal fluid, which is tested for an unusual protein called 14-3-3. This protein occurs in about 90% of people with typical CJD disease. The EEG abnormalities plus the presence of the 14-3-3 protein in cerebrospinal fluid strongly support the diagnosis of CJD. The absence of the 14-3-3 protein or the characteristic abnormalities on EEG does not rule out CJD. The definitive diagnosis is based on detecting prions in brain tissue by examination of a tissue sample under a microscope or by biochemical analysis at autopsy examination. Diagnostic brain biopsy is occasionally done, generally to rule out a treatable condition, such as inflammation of the brain or encephalitis.

Currently, CJD cannot be cured, and its progress cannot be slowed. The disease is fatal, usually within months or a few years. However, certain drugs may be given to relieve symptoms. For example, the anticonvulsant valproate and the antianxiety drug clonazepam may reduce muscle jerking.

General support and care for the person and family members are important. Day care centers and respite and long-term care may be useful. Speech and occupational therapists can help with specific problems. The CJD Foundation provides support and information

Last full review/revision January 2007 by Pierluigi Gambetti, MD