In humans and scrapie and bovine spongiform encephalopathy in animals.
The most common form of human prion disease is sporadic C-J disease.
A rare transmissible and genetic neurologic disorder caused by prions, which are a small misfolded proteins that alter the physical confirmation of adjacent proteins and lead to neuronal dysfunction.
A fatal prion-related neurodegenerative disease caused by misfolding of prion proteins leading to neuronal cell death.
There is confirmational change of the normal neuronal host prion prion to its pathological form.
A rapidly progressive disorder that is typically associated with the development of dementia, ataxia, myoclonus, and is inexorably progressive to akinetic mutism and death.
Creutzfeldt Jakob disease characteristically has a rabbit in progressive cognitive decline and associated myoclonus.
Clinical variants of the disease cause cerebellar ataxia, extrapyramida signs, or cortical blindness.
There are forms with basal ganglia abnormalities or hemiparesis.
In advanced stage disease patients are akinetic and mute, with severe spasticity and rigidity.
There are more than 20 pathogenic genetic mutation forms encoding the gene PrP.
Disease outbreaks have been identified related to iatrogenic CJD related to the injection of human derived growth hormone or transplantation of dura mater or cornea obtained from an infected donor.
Variant CJD due to ingestion of cattle beef with prion disease can result in bovine spongiform encephalopathy.
Incidence 1 case per million persons per year worldwide.
The median age of onset is the mid 60s, but there is high variability.
Several variants exist, with sporadic being the most common at 85%, followed by familial and iatrogenic forms.
Genetic forms of the disease exist:autosomal dominant.
The predominant clinical presentation is a rapidly progressive decline in mental status and myoclonus.
Clinically heterogenous and includes psychosis, depression, behavioral and personality changes.
The associated mental deterioration can present like classic dementia, yet at an accelerated rate.
There may be behavioral changes and impaired higher cortical function, memory loss, aphasia disorientation, apraxia, and visuospatial impairment.
Myoclonus, particularly startled-provoked is present in 90% of cases, and cerebellar manifestations such as ataxia and nystagmus may also be present.
Three known cases of transfusion transmission from a small group of known pre-symptomatic donors indicates high likelihood of infection transmission.
MRI of brain associated with restricted diffusion confined to the gray matter of the cortex,(known as a cortical ribbons sign), deep nuclei, or both is a sensitive and specific finding for C-J disease.
Cortical ribbing is a ribbon like signal hyper intensity involving the cerebral cortical gyri seen on MRI.
The most common MRI findings is abnormal increase T2 and fluid-attenuated inversion recovery signal intensity in the putamen and head of the caudate, as well as enhancement pattern of ribboning in the cortex.
Diffusion weighted MRI sequences early in the disease have the sensitivity of 91% and a specificity of 97% for the diagnosis of CJD.
Characteristic EEG findings are generalized, periodic, biphasic or triphasic sharp wave complexes of 3-4 Hz.
The EE changes are characteristic of CJD but can occur with other processes including lithium toxicity, toxic metabolic disorders and certain seizure disorders.
A positive 14-3-3 protein assay of CSF fluid.
Increased CSF levels of 14 – 3-3 and tau protein found in up to 90% of patients with prion disease.
Elevated plasma tao levels correlate with disease progression.
Genetic testing for pathogenic mutations of the prion protein gene (PRNP) help confirm a diagnosis.
Definitive diagnosis includes positive tests that detect prion-related proteins using neuropathological techniques.
Characteristic changes in the brains of patients with CJD arevaggregates of abnormal host derived prion protein and a triad of spongiform changes, neuronal loss, and gliosis without inflammation.
Probable diagnosis requires neuropsychiatric symptoms plus a positive RT-QuIC test in CSF or other tissues.
The prion protein marker testing of CSF has a sensitivity for diagnosis of sporadic C-J disease. (RT-QuIC analysis).
The RT-QuIC has an estimated sensitivity of 80% of the specificity of 98%.
The RT-QuIC testing of olfactory epithelium is accurate in diagnosing C-J disease.
Definitive diagnosis requires neuropathological or immunochemical detection of the prion protein in brain tissue.
Clinically the diagnosis can be made with a presentation of a progressive dementia and at least two of the four clinical features: myoclonus, visual or cerebellar dysfunction, pyramidal/extrapyramidal symptoms, and akinetic mutism plus either a typical electroencephalogram pattern, positive 14-3-3 cerebrospinal fluid assay or distinctive MRI findings.
Heterogeneity of phenotypes influenced by methionine-valine polymorphism at codon 129 of the prion protein gene and the glycoform type of prion protein.
Prion protein arises from conversion of endogenous prion protein with accumulation in nervous system tissue.
Prion protein is the major component of the C-J disease agent and propagates itself by seeding or templating inti misfolded multimers that can take the forms of amyloid fibrils.
No effective treatment is exists and the process is uniformly fatal.
Median survival from diagnosis is about six months.