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Prion diseases
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SPONGIFORM ENCEPHALOPATHIES
1. Human transmissible spongiform encephalopathies (including Creutzfeldt-Jakob
(C-J) disease and kuru) have been transmitted to primates and to other animals
through cell-free injections of infected brain tissue. Spongiform encephalopathies
occur in several mammalian species. Scrapie affects sheep, and bovine spongiform
encephalopathy occurs primarily in cows. Kuru, which affects humans, is associated
with cannibalism in New Guinea natives. C-J syndrome and Gerstmann-Straussler-Schenker
syndrome, which affect humans, appear to occur through both genetic and infectious
routes, as known for scrapie.
The infectious agent has been characterized and is
resistant to inactivation by ultraviolet radiation,
formalin, heat and enzymes which denature nucleic
acids. It can be inactivated (i.e. its infectivity destroyed) by proteases
and other treatments that denature proteins.
The term "prion" was used to describe this small proteinaceous infectious
particle. Abnormal forms of the prion protein (a ubiquitous protein of
unknown function) cause these neurodegenerative diseases.
The disease occurs when the normal cellular prion protein undergoes a
conformational change to the abnormal form. This may occur spontaneously
at an extremely low rate or at a higher rate if there is a defect in
the gene. The agent can "replicate" when
the abnormal form crosses the path of the normal, cellular prion protein
and the abnormal prion induces the normal form to adopt a similar abnormal
form.
MORE INFORMATION: http://www.nmia.com/~mdibble/prion.html
OR http://www.kcc.com.msu.edu/CAI/Pathology/CNS_Infections_F/CNS_2a.html
General outline
Synonyms CJD Most frequent Human prion disease (Kuru, Gerstmann),
Classical sporadic CJD, Iatrogenic CJD, Familial CJD, Variant CJD (affects younger
people)
Symptoms Classic form of CJD: initial neurological symptoms
including ataxia, visual difficulty (optical ataxia), in addition a rapidly progressive
dementia featuring memory, orientation, language, praxis impairment leading to
severe impairment of activities of daily living. Variant CJD features psychiatric
symptoms including withdrawal, mood swings preceding the occurrence of neurological
symptoms, unsteadiness on the feet, coordination difficulty, later language and
word finding difficulty. Eventually they become demented.
Course Sporadic: 6 month to a year; Onset: 65-70
Variant: Onset - Average age 28, rare cases 16-78
Caregiver problems Caregiver requires special and quick support,
because the disease is extremely distressing; the support needs to be intensive,
multidisciplinary and coordinated.
Epidemiology 1 / 1.000.000
Variant form: 120 cases in UK, 4 in France, 1 in Italy.
Heredity One form familial - mutation in prion protein
GSS: genetic also mutation in prion protein
Aetiology An abnormally folded protein called prion protein
is involved in the spreading of the neuro-degeneration. Mechanism of neuro-degeneration
should be explained in the different variants of the disease. Mutation in the
prion protein gene in familial forms.
Diagnostic procedures Classic form: In the CSF proteins of
neuronal origins are significantly elevated (14/3/3). Tau protein in the CSF
is also dramatically increased. In part of the patients the EEG shows typical
tri-phasic complexes. CT, MRI, and PET / SPECT are non-specific.
Variant form: Tonsil biopsy demonstrates presence of prions in the lymphatic
system. MRI shows typical changes in the variant (which).
Treatment and rehabilitation None so far
Ongoing research / Clinical trials Number of clinical trials
in UK
Vaccination being examined as possible strategy
Available services CJD Network
National CJD Surveillance Unit in Edinburgh
Special funding available for care and information in UK
Units: Prion Clinic, Paddington, London
National CJD Surveillance Unit in Rome
CJD Network in France
Also in Germany
Further reading
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