Why Are Prion Diseases So Fatal?

Prions are pathologic agents that produce abnormal folding in the brain. These changes cause rapidly progressive neurological diseases that are difficult to treat and always fatal. Prions can be caused by hereditary or spontaneous mutations. They may also be acquired from an outside source, and some are transmitted from animal to human. Prion diseases are rare, affecting about 300 people every year in the U.S.

What Makes a Prion Unique?

A proteinaceous infection particle or prion consists of only a protein. It does not have any genetic components that enable it to reproduce, like a virus or bacteria. Instead, prions consist of proteins present in normal cell membranes — but the protein is distorted. Researchers believe that this abnormal protein binds to proteins in healthy cells to propagate and spread the disease.

Prevention and Risk Factors

In the case of inherited genetic mutations, prion diseases cannot be prevented. A family history of prion disease is one of the most significant risk factors. Others include eating infected meat and receiving contaminated corneas in a transplant. Prion diseases can also spread through contaminated medical equipment. People who have or believe they have certain prion diseases should not donate tissue or organs.

Signs and Symptoms

Prion diseases directly affect the brain, and they present with a wide range of neurological symptoms. Signs include confusion, fatigue, hallucinations, muscle stiffness, rapidly worsening dementia, and difficulty walking or speaking. Other motor and cognitive symptoms may appear depending on the specific disease and how quickly it progresses.

Diagnosis

Healthcare providers should suspect prion disease in any patient with rapidly progressing dementia. Various tests will rule out other conditions or help narrow down the diagnosis and include brain MRIs, vision exams, blood tests, neurologic exams to assess nerve damage, and electroencephalogram (EEG) to analyze brain function. Doctors may also take spinal fluid samples for analysis, but prion disease is only confirmed through a brain tissue biopsy or an autopsy performed after death.

Treatment

There are no treatments that reverse or stop the damage of prion disease. Some antimicrobials show promise in slowing down prion disease progression but do not seem to affect mortality. Small molecule compounds have shown some promise in mice, and they may improve cognitive function in humans, although they have not increased survival. Current research is focusing on immunotherapy and developing vaccines. Another promising area of research is in developing inhibitors that prevent the disruption of healthy proteins.

Creutzfeldt-Jakob Disease (CJD)

Creutzfeldt-Jakob disease (CJD) is a rapidly progressing prion disease that leads to death within one year of onset. It is rare, with only one case per million people in the U.S. About 85 percent of cases occur sporadically, with the remaining caused by inherited mutations. CJD is suspected when a specific protein appears in the cerebrospinal fluid and an EEG shows a pattern of periodic spikes typical of the disease.

Variant Creutzfeldt-Jakob Disease (vCJD)

Variant Creutzfeldt-Jakob disease (vCJD) appeared in the United Kingdom in 1996 and is believed to be caused by the same agent responsible for mad cow disease. vCJD is not the same as CJD — vCJD presents with a flat EEG. Large numbers of plaques appear in the brain, and the agent appears in the patient’s lymphoid tissue, neither of which occurs with CJD. vCJD is fatal, though it takes between 13 and 14 months for the disease to run its course.

Gerstmann-Straussler-Scheinker Disease

Another prion disease is Gerstmann-Straussler-Scheinker disease (GSS). It primarily affects the cerebellum. Symptoms usually develop between 30 and 50. They vary from person to person and include weakness in the legs, slurred speech, spasticity, visual disturbances, slurred speech, and cognitive dysfunction. People with GSS typically live between two and ten years after diagnosis.

Fatal Familial Insomnia

Fatal familial insomnia (FFI) is a prion disease that affects the thalamus. This part of the brain controls the sleep-wake cycle, and FFI causes sleep disturbances, balance problems, weight loss, and psychiatric issues. Symptoms begin between 40 and 60, and the disease is usually fatal six months to three years after they appear. Almost all cases of FFI are inherited, and genetic testing can confirm a diagnosis.

Kuru

Kuru is an extremely rare prion disease caused by a prion in contaminated brain tissue consumed in a cannibalistic funeral ritual some New Guinean groups practiced until 1960. Even though the practice has ceased, cases are still appearing because of the long incubation period. Typically, kuru has a ten to 13-year incubation, but incubation periods of 50 years have been reported.