Prion diseases, also known as transmissible spongiform encephalopathies, are rare progressive neurodegenerative disorders caused by prions. Prion diseases affect both humans and animals. There are several types of human prion diseases including Creutzfeldt-Jakob disease, variant Creutzfeldt-Jakob disease, kuru, and Gerstmann-Straussler-Scheinker syndrome. Prion diseases are caused by abnormal folding of the prion protein which forms plaques that damage the brain. There are sporadic, genetic, and acquired forms of prion diseases. Currently, there are no effective treatments for human prion diseases which are universally fatal.
2. INTRODUCTION
word prion is derived into the word infection and protein.
Prion diseases or transmissible spongiform encephalopathies (TSEs) are a family
of rare progressive neurodegenerative disorders (loss of structure or function of
neurons, including death of neurons)
it affect both humans and animals.
3. History
Stanley Prusiner discovered prion in
1982.
Proteinaceous infective particles
Glycosy specific protein of 30-KD
Does not produce any inflammatory or
immune reaction in the host.
Resistance to ultraviolet, standard
disinfectant.
4. PRION DISEASES
IN HUMAN
CREUTZFELDT-JAKOB
DISEASE (CjD)
KURU
Variant CJD
Fatal familial insomnia
Gerstman-Straussler
Scheinker syndrome(GSS)
6. Pathophysiology
A unifying feature of all the prionoses is neuropathy
These illnesses affect the gray matter of the central nervous system (CNS),
producing neuronal loss, Gliosis, characteristic spongiform change
10% of patients with CJD, amyloid is present in the cerebellum or in the cerebral
hemispheres.
All cases of GSS are associated with multicentric cerebellar plaques.
8. Classification of Prion Disease
Prion diseases can be classified into 3 categories:
1) Sporadic (85% to 90%)
2) Genetic (10% to 15%)
3) Acquired (<1%)
9. Sporadic Creutzfeldt-Jakob disease (sCJD
Idiopathic (etiology is unknown but it is believed to be a spontaneous disease).
Typically presents with cognitive complaints, lack of co-ordination or other motor
problems, behavioral/personality changes, and/or abnormalities in vision
10. Genetic prion diseases
Familial CJD
More than 30 mutations found on the prion protein gene (PRNP) on chromosome 20 and are autosomal
dominant, most with complete penetrance.
Presentation varies between type of PRNP mutation and sometimes even within a family.
Course often longer than sCJD, but some mutations may present clinically and pathologically identically to sCJD.
Fatal familial insomnia
Begins with increasing insomnia and psychiatric symptoms, such as anxiety.
Progresses with hallucinations, weight loss, dementia, and eventually death.
11. Genetic prion diseases conti.
Gerstmann-Straussler-Scheinker
Presentation may vary depending on the type of PRNP mutation disease phenotype and
sometimes even within a family.
Early presentations of the disease often include behavioural changes, parkinsonian
features, or ataxia.
Many cases have been misdiagnosed as familial Alzheimer's or Parkinson's disease
12. Iatrogenic CJD
Due to medical procedures such as administration of human GH, or to contaminated surgical instruments
during corneal transplant, dura mater graft, and insertion of EEG deep brain electrodes.
Incubation period can be as short as 1 year but is typically several years and even decades.
Kuru
Endemic to the Fore tribe of Papua New Guinea, where practices of endocannibalism contributed to its
transmission, and was essentially eliminated with end of endocannibalism, although rare cases may still
occur, as incubation period may be as long as 50 years in some cases.
13. Variant CJD (vCJD)
Acquired from consumption of beef contaminated with bovine spongiform encephalopathy (mad
disease), or transfusion of blood or blood products from a patient with pre-symptomatic or latent
Median age of onset is around 29 years, with most cases occurring in patients in their 20s or 30s,
younger than most with sCJD.
Initially presents with psychiatric and behavioural changes, with later symptoms of dysaesthesia,
dementia, ataxia and/or chorea, myoclonus, or dystonia.
14. Clinical Features of Prion Disease
Relatively late in life
Rapidly progressive demetia
Behavioural disturbanses
Ataxia
Death within one year
No effect of antimicrobials
15. Diagnosis
Creutzfeldt—Jakob disease (CJD)
1. In CSF: Search for the presence of 14-3-3 and tau, two proteins
2. In 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.
3. 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
4. On fixed brain tissue: microscopic examination by histological and immunohistochemical demonstration of the
prion protein, as well as pattern of tissue distribution
5. EEG During the course of sporadic CJD, most patients develop a characteristic finding on EEG with periodic or
pseudoperiodic paroxysms of sharp waves or spikes on a slow background
17. Treatment
No effective treatment has been identified for human prion diseases which are universally fatal;
supportive treatment mainstay
Flupirtine maleate is a centrally acting, non-opioid analgesic that has displayed cytoprotective
activity in vitro in neurons treated with a prion protein fragment: better MMSe but survival not
enhanced
Chlorpromazine and quinacrine: inhibit PrPsc formation in vitro: studies needed
Potential targets will include the steps in the conversion of PrPc to PrPsc
