transmissible spongiform encephalopathy transmissible spongiform encephalopathy transmissible spongiform encephalopathies (tses) also known as prion diseases, are a group of progressive and fatal conditions that are associated with prions and affect the brain 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 encephalopathyother namesprion diseasespecialtyinfectious diseases symptomsdementia, seizures, tremors, insomnia, psychosis, delirium, confusionusual onsetmonths to decadestypesbovine spongiform encephalopathy, fatal familial insomnia, creutzfeldt-jakob disease, kuru, scrapie, chronic wasting disease, gerstmann-sträussler-scheinker syndrome, feline spongiform encephalopathy, transmissible mink encephalopathy, exotic ungulate encephalopathycausesprionrisk factorscontact with infected fluids, ingestion of infected flesh, having one or two parents that have the disease (in case of fatal familial insomnia)diagnostic methodcurrently there is no way to reliably detect prions except at post-mortempreventionvariestreatmentpalliative careprognosisinvariably fatalfrequencyrare tses of humans include creutzfeldt–jakob disease, gerstmann–sträussler–scheinker syndrome, fatal familial insomnia, and kuru, as well as the recently discovered variably protease-sensitive prionopathy and familial spongiform encephalopathy. creutzfeldt-jakob disease itself has four main forms, the sporadic (scjd), the hereditary/familial (fcjd), the iatrogenic (icjd) and the variant form (vcjd). 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) in cattle – popularly known as "mad cow disease" – and chronic wasting disease (cwd) in deer and elk. the variant form of creutzfeldt–jakob disease in humans 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. misshapened 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, 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. however, treatment with strong, almost undiluted bleach and/or sodium hydroxide, or heating to a minimum of 134 °c, does destroy prions. classification differences in shape between the different prion protein forms are poorly understood. known spongiform encephalopathies ictvdb code disease name natural host prion name prp isoform ruminant non-human mammals 90.001.0.01.001. scrapie sheep and goats scrapie prion prpsc yes 90.001.0.01.002. transmissible mink encephalopathy (tme) mink tme prion prptme no 90.001.0.01.003. chronic wasting disease (cwd) elk, white-tailed deer, mule deer and red deer cwd prion prpcwd yes 90.001.0.01.004. bovine spongiform encephalopathy (bse)commonly known as "mad cow disease" cattle bse prion prpbse yes 90.001.0.01.005. feline spongiform encephalopathy (fse) cats fse prion prpfse no 90.001.0.01.006. exotic ungulate encephalopathy (eue) nyala and greater kudu eue prion prpeue yes camel spongiform encephalopathy (cse) camel prpcse yes human diseases 90.001.0.01.007. kuru humans kuru prion prpkuru no 90.001.0.01.008. creutzfeldt–jakob disease (cjd) cjd prion prpscjd no variant creutzfeldt–jakob disease (vcjd, nvcjd) vcjd prion prpvcjd 90.001.0.01.009. gerstmann-sträussler-scheinker syndrome (gss) gss prion prpgss no 90.001.0.01.010. fatal familial insomnia (ffi) ffi prion prpffi no familial spongiform encephalopathy features the degenerative tissue damage caused by human prion diseases (cjd, gss, and kuru) is characterised by four features: spongiform change (the presence of many small holes), the death of neurons, astrocytosis (abnormal increase in the number of astrocytes due to the destruction of nearby neurons), 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. early neuropathological reports on human prion diseases suffered from a confusion of nomenclature, in which the significance of the diagnostic feature of spongiform change was occasionally overlooked. the subsequent demonstration that human prion diseases were transmissible reinforced the importance of spongiform change as a diagnostic feature, reflected in the use of the term "spongiform encephalopathy" for this group of disorders. prions appear to be most infectious when in direct contact with affected tissues. for example, creutzfeldt–jakob disease has been transmitted to patients taking injections of growth hormone harvested from human pituitary glands, from cadaver dura allografts and from instruments used for brain surgery (brown, 2000) (prions can survive the "autoclave" sterilization process used for most surgical instruments). it is also believed that dietary consumption of affected animals can cause prions to accumulate slowly, especially when cannibalism or similar practices allow the proteins to accumulate over more than one generation. an example is kuru, which reached epidemic proportions in the mid-20th century in the fore people of papua new guinea, who used to consume their dead as a funerary ritual. laws in developed countries now ban the use of rendered ruminant proteins in ruminant feed as a precaution against the spread of prion infection in cattle and other ruminants. there exists evidence that prion diseases may be transmissible by the airborne route. note that not all encephalopathies are caused by prions, as in the cases of pml (caused by the jc virus), cadasil (caused by abnormal notch3 protein activity), and krabbe disease (caused by a deficiency of the enzyme galactosylceramidase). progressive spongiform leukoencephalopathy (psl)—which is a spongiform encephalopathy—is also probably not caused by a prion, although the adulterant that causes it among heroin smokers has not yet been identified. this, combined with the highly variable nature of prion disease pathology, is why a prion disease cannot be diagnosed based solely on a patient's symptoms. cause genetics mutations in the prnp gene cause prion disease. familial forms of prion disease are caused by inherited mutations in the prnp gene. only a small percentage of all cases of prion disease run in families, however. most cases of prion disease are sporadic, which means they occur in people without any known risk factors or gene mutations. in rare circumstances, prion diseases also can be transmitted by exposure to prion-contaminated tissues or other biological materials obtained from individuals with prion disease. the prnp gene provides the instructions to make a protein called the prion protein (prp). under normal circumstances, this protein may be involved in transporting copper into cells. it may also be involved in protecting brain cells and helping them communicate. 24 point-mutations in this gene cause cells to produce an abnormal form of the prion protein, known as prpsc. this abnormal protein builds up in the brain and destroys nerve cells, resulting in the signs and symptoms of prion disease. familial forms of prion disease are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. in most cases, an affected person inherits the altered gene from one affected parent. in some people, familial forms of prion disease are caused by a new mutation in the prnp gene. although such people most likely do not have an affected parent, they can pass the genetic change to their children. protein-only hypothesis protein could be the infectious agent, inducing its own replication by causing conformational change of normal cellular prpc into prpsc. evidence for this hypothesis: infectivity titre correlates with prpsc levels. however, this is disputed. prpsc is an isomer of prpc denaturing prp removes infectivity prp-null mice cannot be infected prpc depletion in the neural system of mice with established neuroinvasive prion infection reverses early spongeosis and behavioural deficits, halts further disease progression and increases life-span multi-component hypothesis