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Associated with virus:
Subacute Sclerosing Panencephalitis (SSPE)?
Progresive Rubella Panencephalitis?
Progressive Multifocal Leukoencephalopathy (PML)?
- SSPE- Measles virus
- PRP- Rubella Virus
- PML- BK, JC Virus
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Human Diseases
- Kuru
- Creutzfeldt-Jakob Disease
- Gerstmann-Straussler-Scheinker Disease (GSSD)
- Fatal Familial Insomnia (FFI)
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The measles virus from SSPE pts. differs from
the wild type measlres virus and are not derived from vaccine strains in the MMR vaccine (point mutations, deletions, defective interfering particles)
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Most mutations of the measles virus in SSPE had mutations in the
M gene (encoding the Matix protein)
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SSPE directly invades
brain cells -> brain inflammation
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SSPE is more common among patients who had measles at what point in their life?
Before age 2
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Interval btw measles and development of SSPE
~7 years
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SSPE involves
White and gray matter or cerebral hemispheres and brain stem
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Involves white and gray matter of cerebral hemispheres and brain stem
SSPE
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Is SSPE a demyelinating disease?
No, it causes the destruction of all brain tissue elements, not just myelin
*Large quantities of defective virus in brain
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2 things in light microscopy of SSPE
- Perivascular Cuffing
- Nuclear Inclusions
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Perivascular Cuffing
Will see perivascular and diffuse infiltrates of lymphocytes, plasma cells, w/ destruction of nerve cells
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3 Stages of SSPE
- Stage 1: Intellectual decline (poor school performance, abnormal behavior)
- Stage 2: Seizures, visual impairment, continued intellectual decline
- Stage 3: Decorticate state, blind, rigidity
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Optic nerve damage and damage to the retina are characteristic of
SSPE
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SSPE: Tests
- EEG
- Serum Ab titer (showing elevation titer to measles)
- Spinal tap
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SSPE: Tx
No cure; can slow progression of disease with Isopinosine and IFN-a injected directly into brain
SSPE is always fatal
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Progressive Rubella Panencephalopathy follows rubella by
10-20 years
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Increasingly severe neurologic deterioration in patients with previously stable congenital rubella
Progressive Rubella Panencephalopathy (PRPE)
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Pathology of PRPE (very similar to SSPE)
- Subacute encephalitis involving white and gray matter
- Destruction of all brain tissue elements, not demyelinating
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PRPE: Clinical Manifestations
- Spasticity, ataxia, seizures
- Intellecutal deterioration, progresses to death
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PRPE: Preventable?
Preventable
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Major goal of rubella vaccination
Prevention of birth defects in babies infected in uteo
All women of child-bearing age should be re-vaccinated (vaccine is contraindicated in women who are pregnant since the vaccine is a live, attenuated virus)
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Due to latent infxn of polyomaviruses that may be reactivated in immunocompromised patients.
Progressive Multifocal Leukoencephalopathy (PML)
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Time of Onset of PML for pregnant women
3rd trimester
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Usually appears in hypergic adults, majority of pts. btw 40-70 yrs. old
PML
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1/2 of the people who have PML also have had
Lymphoproliferative or Myeloproliferative neoplasms (hodgkin's disease, CLL)
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Rapidly progressive focal neurologic deficits including hemiparesis, visual field deficits, and cognitive impairment
PML
*Can also have aphasia, ataxia, and/ or cranial nerve deficits
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PML: Time from symptoms appearance until death
2-4 months
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PML shows single or multiple confluent lesions w/o mass effects that are seen most frequently in the
Parietooccipital white matter
*Subcortical gray matter or spinal cord may be involved, but this is rare
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Can ressemble lymphoma, toxoplasmosis, or HIV encephalitis
PML
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PML: Nuclear inclusions seen in
Oligodendrocytes
*Astrocytes only have inclusions rarely
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PML prognosis
- PML progresses to severe dementia and death over several months
- Progression is more rapid in AIDS-associated PML
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Spongiform degeneration of neurons
Severe astrocytic cliosis out of proportion with the degree of cell loss
Amyloid plaque formation
Tses
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Neuropathological characteristics of Transmissible Spongiform Encephalopathies
- Spongiform degeneration of neurons
- Severe astrocytic cliosis out of proportion with the degree of cell loss
- Amyloid plaque formation
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Characteristics of TSES
- Long incubation
- No inflammatory response
- No cytopathic effec tin infected cells in vivo
- No IFN production
- No antigenicity
- No virus-like particles or inclusion bodies
- No demonstrable nucleic acid
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Agents that affect _______ inactivate prions
Proteins (NOT DNA)
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Prion consists of
protein
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Prions replicate via
a crystallization event
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Major infectious materia in prion diseases
PrPSC Protein
*Normal proteins are designated as PrPc
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PrPC synthesized in
PRPC synthesized in ER
PrP(SC) resistant to phospholipase
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Refers to the prolongation of the incubation time when prions from one species are transmitted to another species
Species Barrier
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Classic vs. Variant CJD: Mediate age at death
- Classic= 68 years
- vCJD= 28 years
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Classic vs. vCJD: Median duration of illness
- Classic= 4-5 months
- vCJD= 13-14 months
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Classic vs. vCJD: Period sharp waves on electroencephalogram
- Classic= often present
- vCJD= often absent
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Classic vs. vCJD: Plvinar sign on MRI
vCJD: Present in 75% of cases
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Classic vs. vCJD: Presence of "florid plaques" on neuropathology
- Classic= Rare
- vCJD= Present in large numbers
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Classic vs. vCJD: Presence of agent in lymphoid tissue
- Classic= Not readily detected
- vCJD= Readily detected
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Classic vs. vCJD: Increased glycoform ratio on immunoblot analysis of protease-resistance prion protein
- Classic= Not reported
- vCJD= Marked accumulation of protease-resistance prion proteins
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vCJD strains same or different the CJD?
different
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