Prion diseases are neurodegenerative diseases caused by a misfolded protein that causes other proteins to take a similar shape. This protein misfolding leads to the death of nerve cells in the brain, with the appearance of holes in brain tissue that give the brain a sponge-like (spongiform) appearance. Prion diseases have a long incubation period between the time of exposure to a prion and the first appearance of symptoms.
Fortunately, all prion diseases are rare. The most common, called Creutzfeldt-Jakob disease (CJD), afflicts only about one in a million people each year.
How Does Creutzfeldt-Jakob Spread?
There are four known ways to acquire CJD. About 85 to 95 percent of CJD is sporadic (sCJD), meaning that it develops spontaneously with no known inheritance or infectious exposure. Between 5 to 15 percent of CJD cases are inherited, and less than 1 percent of cases are caused by exposure due to a surgical transplant, blood transfusions, use of cadaveric pituitary hormones, or contaminated surgical instruments.
Ingestion of meat contaminated with the CJD prion causes another form of the disease known as variant Creutzfeldt-Jakob disease (vCJD). This is what most people think of when they mention “mad cow” disease. Variant CJD causes somewhat different signs and symptoms from the classical form of the disease. When looking under the microscope, brains infected by vCJD have protein deposits called plaques that are not found in classical CJD.
What Are the Symptoms of CJD?
All forms of CJD cause rapidly progressive loss of cognitive abilities like memory, concentration, and judgment. Mood changes and sleep disturbances are also common. Very fast muscle twitches called myoclonus are also common, especially when the victim is startled. About two-thirds of people with CJD have movement problems, like slow movement and clumsiness (ataxia). 40 to 80 percent of patients may have additional signs, like brisk reflexes. In variant CJD, additional symptoms such as limited eye movements, and sensory changes like numbness and tingling, may also be present.
Sporadic CJD usually comes on after the age of 50. Variant CJD may be more likely if the patient is younger; in addition, variant CJD may be more likely to cause neuropsychiatric problems such as anxiety, depression and psychosis early on in the disease. Variant CJD may progress more slowly than sCJD, which normally leads to death within a year.
There are various subtypes of CJD—each with slightly different symptoms. The Heidenhain variant, for example, causes visual problems, while the Oppenheimer-Brownell variant causes cerebellar problems. Other forms seem to particularly attack the thalamus or basal ganglia.
How is Creutzfeldt-Jakob Disease Diagnosed?
Beyond listening to someone’s story and doing a physical examination, doctors have three main tools in diagnosing CJD: magnetic resonance imaging (MRI), the electroencephalogram (EEG), and analyzing cerebrospinal fluid (CSF) collected during a lumbar puncture. Ultimately, the only way to be certain of a CJD diagnosis is by biopsy or autopsy of the brain.
Magnetic resonance imaging in CJD demonstrates changes in the basal ganglia, which are especially noticeable in more rapidly progressive forms of CJD. Long lesions in the cerebral cortex may also be apparent. Eventually, an MRI also demonstrates atrophy of the brain due to dying tissue.
An EEG may show synchronized, sharply contoured waves that are very specific to CJD, but not all forms of CJD have these EEG changes. Variant CJD, for example, almost never causes such findings on EEG, though some slowing of brain activity may be detected. Other prion diseases, like kuru or fatal familial insomnia, also don't cause these EEG findings.
A lumbar puncture may help with a diagnosis by allowing physicians to measure abnormal proteins in the cerebrospinal fluid (CSF). One such abnormal protein, the 14-3-3 protein, has been purported to be very helpful with the diagnosis of CJD, though other problems such as herpes simplex encephalopathy, metastases, and other encephalopathies can cause the 14-3-3 to be elevated as well. The protein may actually represent the death of brain cells in general rather than CJD specifically, but the protein may not be detected in variant CJD.
Treatment of Creutzfeldt-Jakob
Unfortunately, there is no treatment for CJD. The disease is always fatal, with death usually occurring within a year of first symptoms. Efforts are ongoing to find a cure, but in the meantime, the best physicians can offer is symptomatic relief.
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