It is a class presentation of slow virus and prion diseases

1. Group D [76-100]
Presented by: Srikanta & Smruti

2. Slow virus diseases and prions are a group of
neurodegenerative conditions affecting both
humans and animals.
Characteristics:
Long incubation period, (months to years)
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Predilection for CNS
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Invariably fatal
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Strong genetic predisposition
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Lack antigenicity
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Does not produce cytopathologic effect in vitro

4. Progressive Multifocal Leukoencephalopathy
(PML):
PML is caused by a polyoma virus called JC virus; named
after the initials of the patient (John Cunningham) in whom it was
described first.
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Pathology:
PML is characterized by multifocal areas of demyelination
distributed throughout the brain, along with deformation of both
astrocytes and oligodendrocytes
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Risk factors:
Most patients are immunodeficient with comorbidity such as AIDS
(80%), hematologic malignancies or transplantation. Up to 5% of
AIDS patients develop PML

5. Manifestations:
Patients often present with visual deficits, mental impairment,
weakness and ataxia and sometimes seizures
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Diagnosis:
„
MRI scan detects multifocal asymmetric, lesions in
the white matter of brain
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PCR targeting JC virus DNA from CSF provides the definitive
tool for diagnosis. It is highly specific, but variably sensitive
(low in patients on antiretroviral therapy)
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CSF is typically normal, with occasional lymphocytic
pleocytosis.
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Treatment:
No definite therapy for PML is available. Cidofovir may be
effective. Antiretroviral therapy is given in case of HIV infection.

7. Subacute Sclerosing Panencephalitis
(SSPE):
It is a slowly progressive disease characterized by
seizures and progressive deterioration of cognitive and motor
functions; caused by a defective measles virus.
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Occurrence:
SSPE is rare, 1 in 1–5 lakh measles cases
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Age:
Children of <2 years of age acquiring the primary measles
infection are usually prone to develop SSPE, than older children.
SSPE usually develops after 7–13 years after primary measles
infection.
™

8. ™
Manifestations:
Patients develop progressive intellectual deterioration, focal
and/or generalized seizures, myoclonus, ataxia, and visual
disturbances. It is fatal within 1–3 years of onset with mortality
rate of 10–20%
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Diagnosis:
The CSF analysis shows markedly elevated gamma globulin level
(>20% of total CSF protein)
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High titers of antibody to measles virus in CSF is diagnostic
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Viral antigen can be identified immunocytochemically
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Viral genome can be detected by in situ hybridization or PCR
amplification
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Measles virus can be cultured from brain tissue using
special co-cultivation techniques.

9. ™
Treatment:
No effective therapy is available.

10. Prion Disease:
Prions are Infectious protein particles that lack any nucleic
acid.
They are filterable like viruses; but are resistant to
wide range of chemical and physical agents of sterilization.
There are several prion diseases of humans and animals;
Scrapie being the prototype.

11. Mechanism of Prion Diseases
It was described by Stanley B Prusiner (Nobel prize winner,1997).
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Following infection, the infectious protein particles are carried to
brain, and induce misfolding of normal cellular prion proteins
(PrPC) to form its disease-causing isoform (PrPSc)
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The PrPSc are aggregated as amyloid-like plaques in the brain
and then internalized by neurons and get accumulated inside the
cytoplasmic vacuoles giving the cell a spongiform appearance
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PrPSc are internalized by neurons and get accumulated inside the
cytoplasmic vacuoles giving the cell a spongiform appearance

12. PrPSc are transmissible (i.e. infectious), capable
selfpropagating either to other individuals or inheritable
to offsprings.

15. Clinical Manifestations of Prion Diseases:
 Incubation period of prion diseases varies from months to
years (longest being 30 years). But once the disease sets in,
progression is fast.
Prodromal phase lasts for 3–5 months, followed by appearance
of manifestations such as loss of muscle control, shivering,
myoclonic jerks, tremors, loss of coordination and rapidly
progressive dementia.
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Death occurs within 1 year of onset of disease.

16. Prion Diseases of Animals
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Scrapie: It is the prototype of prion diseases that has been
extensively studied. It is a prion disease of sheep, which occurs
naturally in sheep (natural scrapie) or can be experimentally
transmitted to various animals by injection of neural tissues of
infected sheep
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Mink encephalopathy: It is a scrapie-like disease of mink
transmitted by feeding the minks on scrapie infected sheep meat
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Mad cow disease: It is also called as bovine spongiform
encephalopathy (BSE); has been enzootic in cattle in Great Britain
since 1986
The epidemic peaked in 1993 infecting over 1 million cattle with
infection spreading to European countries
BSE is transmitted due to feeding the cattle with meat and bone
meal contaminated with scrapie or BSE prions.

17. Scrapie CWD (chronic wasting disease)

18. Human Prion Diseases
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Kuru: It was seen only in the Eastern Highlands of New Guinea and was
spread by customs surrounding ritual cannibalism of dead relatives infected
with the disease.Since this practice has ceased, the disease has disappeared
now
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Creutzfeldt-Jakob disease (CJD): It is the most common form of prion
disease in humans. It typically presents with dementia and myoclonus,is
relentlesslyprogressive, and generallycauses death within a year of onset.
Types of CJD include:
 Classical or sporadic (sCJD): It is caused by the spontaneou misfoldingof
prion-proteinin an individual.This accounts for 85% of cases of CJD
 Familial (fCJD): It accounts for the majority of the other 15% of cases of CJD.
fCJD and its variants GerstmannSträussler-Scheinker syndrome and fatal
familial insomnia are hereditary

19.  Iatrogenic (iCJD): It affects people of 50–75 years age; caused by
contaminationwith tissue from an infected person,usually as the result of a
medical or surgicalprocedures such as blood transfusion,use of human-
derived pituitary growth hormones, gonadotropinhormone therapy, and
corneal and meningeal transplants
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Variant (vCJD): In contrast to the classical CJD, vCJD occurs below 30 years
and is believed to be transmitted through the consumption of contaminated

20. KURU DISEASE
CJD