Makindo Medical Notes.com

Related Subjects: |Dementias |Gerstmann-Straussler-Scheinker Syndrome (GSS) |Fatal Familial Insomnia (FFI) |Creutzfeldt Jakob disease (CJD) |Variant Creutzfeldt Jakob disease (vCJD) |Kuru

About

• There are 5 Known human Prion diseases.
• A prion is an infectious agent composed of a protein in a misfolded form
• Prion diseases are transmissible spongiform encephalopathies (TSE's) are a group of progressive neurodegenerative conditions.

Features

• Progressive neurodegenerative disorders
• Affect both humans and animals
• Long incubation periods
• Characteristic spongiform changes
• Failure to induce inflammatory response.

Pathology

• Spongiform change, Neuronal loss (particularly of cortical layers III-V) without inflammation
• Accumulation of the abnormal prion protein.

Diseases - Transmissible spongiform encephalopathies

• Creutzfeldt Jakob disease: Commonest prion disease. Rapidly progressive dementia. Most are sporadic and a smaller number are familial. 14-3-3 protein has been advanced as a sensitive and specific diagnostic test for sCJD although false positives have been noted. Creutzfeldt Jakob disease is typified by a rapidly presenting dementia with myoclonus.
• Variant Creutzfeldt Jakob disease: as above but Iatrogenic and Variant types. Less Rapid than sporadic or familial type (Mutation in PRNP gene). Affects younger people.
• Kuru: was endemic in Papua New Guinea. Kuru = Shaking. Related to cannibalism.
• Gerstmann-Straussler-Scheinker syndrome (GSS):Tends to affect certain families with young adults developing Ataxia and later dementia, Parkinsonism and deafness. All have PRNP gene mutations.
• Fatal Familial insomnia: Mutation in PRNP gene. Italians. Unique findings are Autonomic disturbance and endocrine disturbance

Investigations

• CSF: Search for the presence of the 14-3-3 protein which is a marker for some prion diseases, such as Creutzfeldt-Jakob disease (CJD) OR RT-QuIC (real-time quaking-induced conversion) a new test to detect the abnormal prion protein.
• DNA extracted from blood, brain, or other tissues: Search for the presence of mutation in the prion protein gene and determine the polymorphism at codon 129 and at other codons.
• In unfixed brain tissue obtained either at biopsy or autopsy: Search for the presence and establish the type of the abnormal, protease-resistant form of the prion protein, also known as scrapie prion protein (PrPSc).
• On fixed brain tissue: Exclude or confirm and characterize the prion disease by microscopic examination following ordinary histological procedures and immunohistochemical demonstration of the prion protein, as well as pattern of tissue distribution.
• Only frozen brain tissue examination definitely confirms or excludes the diagnosis of prion disease and provides the information to identify the type of prion disease. The immunohistochemical examination provides a definitive diagnosis only when positive. The CSF and blood examinations provide information that may be very helpful to caring physicians in making a clinical diagnosis.

References

• National Prion Disease Pathology Surveillance Center