Creutzfeldt-Jakob Disease — The Dana Guide

by Stanley B. Pruisner

March, 2007

sections include: what causes CJD?, diagnosis and treatment 

Creutzfeldt-Jakob disease (CJD) is a very rare but fatal brain condition. It causes dementia that rapidly worsens from week to week. The disease may begin with subtle psychiatric signs, such as anxiety, depression, or insomnia. This phase of the illness is followed within a few weeks or months by more obvious abnormalities— most commonly forgetfulness, confusion, and disorientation. Sometimes people experience visual disturbances. Poor balance and loss of coordination also occur in many cases of CJD and may be among the earliest clear signs of the disorder. Of course, all of these symptoms can result from other, far more common conditions.

In CJD, a person’s symptoms usually worsen rapidly and eventually involve all parts and functions of the brain. It is not unusual for an individual to decline from the first subtle symptoms to a state of complete unresponsiveness in a few months. A characteristic feature of the disease is irregular jerking of the extremities, known as myoclonus. The disease progresses relentlessly, and any major fluctuation in severity—in which the symptoms plateau or improve—suggests that the person is actually suffering from another condition. As of now, people with CJD usually die within a year of diagnosis, usually from infectious complications of the disease.

There are also a number of rare, variant forms of CJD. These forms may mimic Alzheimer’s disease or cerebellar degeneration. Severe insomnia is the first major symptom of a variant called fatal insomnia. The variant CJD seen in Great Britain begins with difficulty balancing, pain in the limbs, and psychiatric disturbances.

What Causes CJD?

CJD is the most common form of prion disease. All prion diseases stem from the misshaping of a particular protein called PrP. Proteins are complex molecules that sometimes do not fold up properly after our bodies make them; they therefore cannot function in the brain as they were genetically designed to do. It is not clear how the brain rids itself of misfolded proteins, but most seem to be broken down by enzymes before they cause much damage. Some researchers suspect misfolded proteins to be factors in many brain diseases, including Alzheimer’s, Parkinson’s, and Huntington’s diseases.

A prion refers to misfolded PrP. Prion disease Prion disease is unusual because the misshapen protein causes normal PrP molecules to misfold as well. In other words, the abnormality can be passed from a few affected molecules to much of the brain’s supply of PrP. Because of this property, prion disease can in extraordinary situations be transmitted from one person to another, and in even more unusual cases, from one species to another.

Apparently, any region of the brain can be affected by CJD. The dysfunctions we can see probably result from the accumulation of large amounts of abnormally folded PrP in nerve cells, but we do not know exactly how this occurs. Under a microscope, the brain is seen to be full of little blobs or holes, making it look like a sponge (hence the description “spongiform”). Nerve cells elsewhere in the body are not usually affected.

Fortunately, CJD is a rare disease. There is only about one case per million people each year, and it has been estimated that in our lifetime about 1 person in 10,000 will eventually develop any form of prion disease. For 85 percent of CJD cases, the only known risk factors are age (most victims are between 55 and 70 years old) and a weak genetic predisposition based on a common variation, or “polymorphism,” in the PrP gene. Most cases of prion disease are thus sporadic, meaning there is no factor we can identify that causes the PrP misfolding to begin. Fifteen percent of prion disease is inherited. In these cases, a mutation in the gene for PrP causes it to produce an abnormal form of the protein. This abnormal form seems more likely to spontaneously misfold into the form that causes CJD.

In unusual cases, people develop prion disease because they have been exposed to prion-infected brain tissue or have eaten prion-infected food. In the United States, most of those cases have occurred in people who received growth hormone derived from the human pituitary gland, which is located at the base of the brain. Worldwide, there have been about 100 such cases. Physicians now use a growth hormone that is not extracted from human brains and does not transmit CJD. In Japan, a number of people contracted CJD after they received contaminated grafts of dura mater, a connective tissue derived from the human brain; neurosurgeons are now aware of this danger and take steps to avoid it.

More than 125 people in Great Britain, France, and Ireland, many of them young, have been diagnosed with a variant form of CJD. Since CJD rarely appears in young people with no family history of it, these cases produced great concern. It appears that these people contracted CJD from eating the meat of cattle infected with another form of prion disease—bovine spongiform encephalopathy. This condition received its popular name, “mad cow disease,” from the way cattle behave after contracting it; just as CJD causes dementia and balance problems in humans, farmers observed their cows staggering around. Cattle and human brains both make PrP, but in slightly different forms; the prions in the two species are not exactly the same, but they are similar enough for people to become infected. Bovine spongiform encephalopathy occurs mainly in Great Britain, but newly developed ways to test for the disease have uncovered small numbers of cases in several other European countries, as well as in Israel and Japan. The European Union and the United States have instituted strict measures to quarantine and destroy affected herds.

Other forms of prion disease affect different animals. Scrapie affects sheep and goats in many areas of the world, including Europe and the Americas. Most evidence indicates that scrapie is not transmitted to humans who eat sheep or goat meat. Chronic wasting disease (CWD) is a prion disease of deer, found only in North America. We do not know whether CWD can affect humans who eat venison.

Diagnosis and Treatment

Neurologists must diagnose CJD by recognizing its characteristic symptoms and excluding a number of other illnesses that might mimic the condition. Chief among these are certain drug intoxications (especially with lithium or bismuth), an inflammation of the blood vessels of the brain (vasculitis), certain brain infections, and a rare condition known as Hashimoto’s encephalopathy. Useful diagnostic tests include a magnetic resonance imaging (MRI) scan of the brain, a lumbar puncture (spinal tap), an electroencephalogram (EEG), and a test for antithyroid antibodies. Genetic testing can confirm the diagnosis of the familial forms of the disease, but not the sporadic or infectiously acquired forms. The only test that can conclusively diagnose CJD is a biopsy of brain tissue. Pathologists can see the microscopic changes typically produced by prions in the biopsied tissue, and test directly for misfolded PrP.

Unfortunately, there are no treatments that can cure or slow the progression of prion disease. Currently, it is always fatal. However, despite the rarity of CJD, we know its basic biology better than we understand most other neurodegenerative diseases. Excellent animal models of prion disease exist, allowing us to test treatments effectively. A number of compounds are currently under investigation in laboratories throughout the world. These treatments seek either to block the conversion of the normal form of PrP to a misfolded form or to allow the brain to rid itself of the misfolded proteins. 

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