Transmissible spongiform encephalopathy

Transmissible spongiform encephalopathies (TSEs) are a group of progressive, invariably fatal, conditions that are associated with prions and affect the brain (encephalopathies) and nervous system of many animals, including humans, cattle, and sheep. According to the most widespread hypothesis, they are transmitted by prions, though some other data suggest an involvement of a Spiroplasma infection. Mental and physical abilities deteriorate and many tiny holes appear in the cortex causing it to appear like a sponge when brain tissue obtained at autopsy is examined under a microscope. The disorders cause impairment of brain function, including memory changes, personality changes and problems with movement that worsen chronically. Transmissible spongiform encephalopathies (TSEs) are a group of progressive, invariably fatal, conditions that are associated with prions and affect the brain (encephalopathies) and nervous system of many animals, including humans, cattle, and sheep. According to the most widespread hypothesis, they are transmitted by prions, though some other data suggest an involvement of a Spiroplasma infection. Mental and physical abilities deteriorate and many tiny holes appear in the cortex causing it to appear like a sponge when brain tissue obtained at autopsy is examined under a microscope. The disorders cause impairment of brain function, including memory changes, personality changes and problems with movement that worsen chronically. TSEs of humans include Creutzfeldt–Jakob disease—which has four main forms, the sporadic (sCJD), the hereditary/familiar (fCJD), the iatrogenic (iCJD) and the variant form (vCJD)—Gerstmann–Sträussler–Scheinker syndrome, fatal familial insomnia, kuru, and the recently discovered variably protease-sensitive prionopathy. These conditions form a spectrum of diseases with overlapping signs and symptoms. TSEs in non-human mammals include scrapie in sheep, bovine spongiform encephalopathy (BSE)—popularly known as 'mad cow's disease'—in cattle and chronic wasting disease (CWD)—also known as 'zombie deer disease'—in deer and elk. The variant form of Creutzfeldt–Jakob disease is caused by exposure to bovine spongiform encephalopathy prions. Unlike other kinds of infectious disease, which are spread by agents with a DNA or RNA genome (such as virus or bacteria), the infectious agent in TSEs is believed to be a prion, thus being composed solely of protein material. Misshapen prion proteins carry the disease between individuals and cause deterioration of the brain. TSEs are unique diseases in that their aetiology may be genetic, sporadic, or infectious via ingestion of infected foodstuffs and via iatrogenic means (e.g., blood transfusion). Most TSEs are sporadic and occur in an animal with no prion protein mutation. Inherited TSE occurs in animals carrying a rare mutant prion allele, which expresses prion proteins that contort by themselves into the disease-causing conformation. Transmission occurs when healthy animals consume tainted tissues from others with the disease. In the 1980s and 1990s, bovine spongiform encephalopathy spread in cattle in an epidemic fashion. This occurred because cattle were fed the processed remains of other cattle, a practice now banned in many countries. In turn, consumption (by humans) of bovine-derived foodstuff which contained prion-contaminated tissues resulted in an outbreak of the variant form of Creutzfeldt–Jakob disease in the 1990s and 2000s. Prions cannot be transmitted through the air or through touching or most other forms of casual contact. However, they may be transmitted through contact with infected tissue, body fluids, or contaminated medical instruments. Normal sterilization procedures such as boiling or irradiating materials fail to render prions non-infective. In the 5th century BCE, Hippocrates described a disease like TSE in cattle and sheep, which he believed also occurred in man. Publius Flavius Vegetius Renatus records cases of a disease with similar characteristics in the 4th and 5th centuries AD. In 1755, an outbreak of scrapie was discussed in the British House of Commons and may have been present in Britain for some time before that. Although there were unsupported claims in 1759 that the disease was contagious, in general it was thought to be due to inbreeding and countermeasures appeared to be successful. Early-20th-century experiments failed to show transmission of scrapie between animals, until extraordinary measures were taken such as the intra-ocular injection of infected nervous tissue. No direct link between scrapie and disease in man was suspected then or has been found since. TSE was first described in man by Alfons Maria Jakob in the 1921. Daniel Carleton Gajdusek's discovery that Kuru was transmitted by cannibalism accompanied by the finding of scrapie-like lesions in the brains of Kuru victims strongly suggested an infectious basis to TSE. A paradigm shift to a non-nucleic infectious entity was required when the results were validated with an explanation of how a prion protein might transmit spongiform encephalopathy. Not until 1988 was the neuropathology of spongiform encephalopathy properly described in cows. The alarming amplification of BSE in the British cattle herd heightened fear of transmission to humans and reinforced the belief in the infectious nature of TSE. This was confirmed with the identification of a Kuru-like disease, called new variant Creutzfeldt–Jakob disease, in humans exposed to BSE. Although the infectious disease model of TSE has been questioned in favour of a prion transplantation model that explains why cannibalism favours transmission, the search for a viral agent is being continued in some laboratories. The degenerative tissue damage caused by human prion diseases (CJD, GSS, and kuru) is characterised by four features: spongiform change, neuronal loss, astrocytosis, and amyloid plaque formation. These features are shared with prion diseases in animals, and the recognition of these similarities prompted the first attempts to transmit a human prion disease (kuru) to a primate in 1966, followed by CJD in 1968 and GSS in 1981. These neuropathological features have formed the basis of the histological diagnosis of human prion diseases for many years, although it was recognized that these changes are enormously variable both from case to case and within the central nervous system in individual cases. The clinical signs in humans vary, but commonly include personality changes, psychiatric problems such as depression, lack of coordination, and/or an unsteady gait (ataxia). Patients also may experience involuntary jerking movements called myoclonus, unusual sensations, insomnia, confusion, or memory problems. In the later stages of the disease, patients have severe mental impairment (dementia) and lose the ability to move or speak.