One of versatile Canadian actor William Shatner’s most memorable characters was Boston Legal’s Denny Crane. In the final season of the series, Crane becomes convinced that he has been infected with Mad Cow disease, often using the utterance “Mad cow” to explain the bewildering statements he makes. In actuality, contracting Bovine Spongiform Encephalopathy, or BSE, is incredibly rare, with only 3 cases involving U.S. citizens, none of which occurred in the U.S. (2 cases in the UK, 1 case in Saudi Arabia). BSE or transmissible spongiform encephalopathies (TSEs), rare progressive neurodegenerative disorders affecting humans and animals. Commonalities include long incubation periods, characteristic spongiform changes in the brain associated with neuronal loss, and a failure to induce inflammatory response. The causal agents of these diseases are thought to be prions.
Prions are abnormal, pathogenic agents, transmissible and are able to induce abnormal folding of specific normal cellular proteins called prion proteins. The proteins are found abundantly in the brain. While the functions of these normal prion proteins are not fully understood, the abnormal folding of these prion proteins leads to brain damage, with the characteristic symptoms of the disease. All of the prion diseases share commonalities including rapid progression. They are always fatal. There are currently 4 recognized prion diseases that infect humans.
Classic Creutzfeldt-Jakob disease causes the characteristic neurodegenerative clinical and diagnostic features. CJD is rapidly progressive, resulting in death within 1 year of onset of symptoms. While the majority of CJD cases occur as sporadic disease, a small proportion of patients (15%) develop CJD due to inherited mutations of the prion protein gene.
Variant CJD was first described in 1996 in the United Kingdom. vCJD has somewhat different clinical and pathologic characteristics from classic CJD. vCJD also has a particular genetic profile of the prion protein gene. Of the 3 cases of U.S. citizens found to have contracted vCJD, all were found to be epidemiologically associated with beef from cattle with BSE.
Another prion-linked disease is Gerstmann-Straussler-Scheinker disease, or GSS. GSS is extremely rare, and almost always inherited. The variant gene is found in only a few families around the world. Onset of GSS occurs in early middle age. The early stages are marked by varying levels of ataxia, including clumsiness, unsteadiness, and difficulty walking. The ataxia becomes more pronounced as the disease progresses, often leading to dementia. Other late stage symptoms include deafness, dysarthria, nystagmus, spasticity, and blindness, and patients may experience psychosis or severe depression. GSS is the slowest progressing of the prion diseases.
Fatal Familial Insomnia (FFI) is a genetic sleep disorder caused by a genetic mutation, which leads to prion disease related to CJD but more rare. FFI has been diagnosed in only about 40 families. FFI begins as an unexplained sleeplessness during middle age, rapidly progressing into a fatal insomnia. It is related to other prion diseases and Alzheimer’s disease.
Kuru is the only prion disease known to have been epidemic in modern times. During the 1950s-60s, the Fore people in the highlands of New Guinea suffered from Kuru (meaning “to shake” in the Fore language). At first, anthropologists and researchers believed the disease was infections, possibly through insect bites (Vector-born). Through epidemiological investigations it was discovered that the disease resulted from the practice of ritualistic cannibalism. The Fore relatives prepared and consumed the tissues (including brain) of deceased family members. Brain tissue from individuals with prion disease transmitted the disease to those who consumed the infected brain matter. The disease can also be transmitted by contact with open sores or wounds. The New Guinea Government actively discouraged the practice of cannibalism, after which the disease went into steep decline. Kuru has mostly disappeared.
All of the prion diseases or transmissible spongiform encephalopathies have a long incubation period, and it is often years or even decades before an infected person begins to show symptoms. Currently there are is no cure for any of the TSEs. Poor Denny. Or James T. Kirk. Or whatever.