Transcript Case Study- Prions - Cal State LA

Case Study- Prions
Group #17
William K. Vincent
Sonia Morales
Prion Structure:
http://www.prions.com/prions.
jpg
Prion Diseases
• Known collectively as spongiform
encephalopathies.
• No nucleic acid genome.
• Examples:
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Kuru
Scrapie
BSE (Bovine Spongiform Encephalopathy)
CJD (Creutzfeld-Jacob Disease)
The Prion Hypothesis
• Ability to infect resides in the protein’s
abnormal transformation
• Infectious agent is a specific structural form
of a standard cell protein, PrPc.
– In an unusual prion form, protein has
pathogenic properties.
Case Study
•70-year-old woman
•Severe headaches, dull and apathetic
•Memory loss, moments of confusion
•Abnormal EEG
•Coma-like state
•Occasional spontaneous clonic twitching
of the arms and legs
•Myoclonic jerking response to a loud
noise
•Patient died of pneumonia
Post Mortem Findings
• Died four months after onset.
• Astrocytic gliosis of the cerebral cortex
with fibrils.
• Intracellular vacuolation throughout the
cerebral cortex were seen microscopically.
• No swelling
• No inflammation
Possible Viral Neurological Diagnosis
• Encephalitis
– Symptoms include:
• Headaches
• Confusion
• Unsteady gait
• Coma
• Amnesia
– often caused by a viral infection
– enteroviruses are most common, including poliovirus
and echovirus
– Herpes simplex infection, varicella, measles,
adenovirus, rabies, Eastern Equine Encephalitis Virus,
West Nile virus.
Possible Viral Neurological
Diagnosis Continued…
• Chronic meningitis
– Symptoms:
• Severe headaches
• Decrease in consciousness
– About 90% of cases of viral meningitis are
caused by members of a group of viruses
known as enteroviruses.
– Herpesviruses and the mumps virus can also
cause viral meningitis.
Other Diseases to Consider in
Diagnosis
• Symptoms similar to other progressive
neurological disorders, such as Alzheimer’s or
Huntington’s disease.
• CJD causes unique changes in brain tissue which
can be seen at autopsy.
• Cause more rapid deterioration of a person’s
abilities than Alzheimer’s disease or most other
types of dementia.
Actual Diagnosis: CreutzfeldJacob Disease
• First concern is to rule out treatable forms of
dementia such as encephalitis or chronic
meningitis.
• Standard diagnostic tests will include
– A spinal tap (14-3-3 protein)
– Electroencephalogram (EEG)
– Computerized tomography
– Magnetic resonance imaging (MRI)
• The only way to confirm a diagnosis of CJD is
by brain biopsy or autopsy.
Clinical and Pathological Characteristics of
CJD and its Variant form
• Median age at death
– 68 years (Classical)
– 28 years (Variant)
• Median duration of illness
– 4-5 months (Classical)
– 13-14 months (Variant)
• Clinical signs and symptoms
– Dementia; early neurologic signs (Classical)
– Prominent psychiatric/behavioral symptoms; delayed
neurologic signs (Variant)
Clinical and Pathological Characteristics of
CJD and its Variant form
• Periodic sharp waves on electroencephalogram
– Often present (Classical)
– Often absent (Variant)
• Immunohitochemical analysis of brain tissue
– Variable accumulation (Classical)
– Marked accumulation of protease-resistance prion
protein (Variant)
• Presence in lymphoid tissue
– Not readily detected (Classical)
– Readily detected (Variant)
Possible Modes of Transmission
• Sporadic
– Cases where no known risk factor,
– Infection thought to be acquired by either of the
following two:
• Inherited
– It is an autosomal and dominant trait.
• Iatrogenic
– Acquired infection
• Diet
– Medical procedures
• Surgery
• Growth hormone
• Corneal transplants
Key Features of Post-Mortem Findings
Characteristic of a Prion
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Neuronal vacuolation
Spongiosis
Neuronal death
Explicit glial reactions
Deposition, mainly in the brain and
lymphoreticular tissues, of PrPSc.
Post-Mortem
Findings
Prominent gliosis
Sponge-Like Lesions
What key features distinguish the unconventional
prion diseases from more conventional neurological
viral diseases?
• Conventional neurological diseases are very
small, filterable agents that require host
cells to grow.
• These unconventional agents are:
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confined to the central nervous system
have long incubation periods
show progressive fatal course of disease
characteristically have vacuolization of
neurons.
Differences In Disease Between
Viruses and Prions
• Viruses
– Has a cytopathological
effect
– Incubation period
depends on virus
– Causes an immune
response
– Causes inflammatory
response
• Prions
– No cytopathological
effects
– Long incubation period
– Does not cause an
immune response.
– Does not cause an
inflammatory response
Precautions a Pathologist Should Take for
Protection Against Infection
• Normal sterilization procedures such as cooking,
washing, and boiling do not destroy prions.
• Wash hands and exposed skin before eating,
drinking, or smoking.
• Cover cuts and abrasions with waterproof
dressings.
• Wear surgical gloves when handling a patient's
tissues and fluids or dressing the patient's wounds.
Precautions Continued…
• Avoid cutting or sticking themselves with
instruments contaminated by the blood or other
tissues.
• Use face protection if there is a risk of splashing
blood or cerebrospinal fluid.
• Soak instruments in undiluted chlorine bleach for
an hour or more
– then use an autoclave (pressure cooker) to sterilize
them in distilled water for at least one hour at 132 - 134
degrees Centigrade.
Stay tuned for new information on
Prions…
Thank you!
References
Belay, E. D. and Schonberger, L.B. The Public Health Impact of Prion Diseases.
Annu. Rev. Public Health. 26:191-212 (2005).
Creutzfeldt-Jakob Disease Foundation, Inc. 2006 <http://www.cjdfoundation.org>.
Department of Health and Human Services: Centers for Disease Control and
Prevention. 13 April 2007. CJD (Creutzfeldt-Jakob Disease, Classic).
Retrieved November 24 2007. <http://www.cdc.gov/ncidod/dvrd/cjd/index.htm>.
Dimmock, N.J., Easton, A.J., and Leppard K. N. “Prion Diseases.” Introduction to
Modern Virology. Blackwell Publishing. 2007: 401-415.
Glan Clwyd Hospital DGH NHS Trust. Retrieved November 26 2007.
<http://www.banes-pct.nhs.uk/documents/Board_Papers/2004/May/Agenda
%20item%2014%20-%20Appendix%202%20-%20Guidance%20%20CJD%20%20 2004%20BANES%20PCT.htm>.
Medline Plus. 7 September 2006. Encephalitis. Retrieved November 28, 2007.
<http://www.nlm.nih.gov/medlineplus/ency/article/001415.htm#Definition>.
Narang, H. K. A Critical Review of Atypical Cerebellum-Type Creutzfeldt-Jakob
Disease: Its Relationship to ``New Variant'' CJD and Bovine Spongiform
Encephalopathy. Experimental Biology and Medicine 226:629-639 (2001).
National Institute of Neurological Disorders and Stroke. 19 November 2007.
Creutzfeldt-Jakob Disease. Retrieved November 22, 2007. <http://www.ninds.
nih.gov/disorders/cjd/cjd.htm>.