1. Case Study- Prions Group #17 William K. Vincent Sonia Morales

2. Prion Structure: http://www.prions.com/prions. jpg

3. Prion Diseases Known collectively as spongiform encephalopathies. No nucleic acid genome. Examples: –Kuru –Scrapie –BSE (Bovine Spongiform Encephalopathy) –CJD (Creutzfeld-Jacob Disease)

4. 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.

5. 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

6. 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

7. 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.

8. 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.

9. 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.

10. Actual Diagnosis: Creutzfeld- Jacob 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.

11. 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

12. 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)

13. 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

14. Key Features of Post-Mortem Findings Characteristic of a Prion Neuronal vacuolation Spongiosis Neuronal death Explicit glial reactions Deposition, mainly in the brain and lymphoreticular tissues, of PrPSc.

15. Prominent gliosis Sponge-Like Lesions Post-Mortem Findings

16. 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: –confined to the central nervous system –have long incubation periods –show progressive fatal course of disease –characteristically have vacuolization of neurons.

17. 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

18. 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.

19. 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.

20. Stay tuned for new information on Prions… Thank you!

21. 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.http://www.ninds nih.gov/disorders/cjd/cjd.htm>.