CJD is a rapidly progressive dementing illness, with a typical duration from first onset of subtle changes in memory and behavior to death in only 7 months. It is sporadic in approximately 85% of cases and has a worldwide annual incidence of about 1 per million. While commonly
Fig. 23.21 Pathogenesisofpriondisease.α-HelicalPrPcmayspontaneouslyshifttotheβ-sheetPrPscconformation,aneventthatoccursatamuchhigherrateinfamilialdiseaseassociatedwithgermlinePrPmutations.PrPscmayalsobefromexogenoussources,suchascontaminatedfood,medicalinstrumentation,ormedicines.Oncepresent,PrPscconvertsadditionalmoleculesofPrPcintoPrPscthroughphysicalinteraction,eventuallyleadingtotheformationofpathogenicPrPscaggregates.
http://ebooksmedicine.net affecting individuals older than 70 years of age, familial forms caused by mutations in PRNP may present in younger individuals. In keeping with the infectious nature of PrPsc, there are well-established cases of iatrogenic transmission by contaminated deep implantation electrodes and human growth hormone preparations.
MORPHOLOGYTheprogressiontodeathinCJDusuallyissorapidthatthereislittle,ifany,macroscopicevidenceofbrainatrophy.Onmicroscopicexamination,thepathognomonicfindingisaspongiform transformation of the cerebral cortex and deep gray matter structures (caudate,putamen);thismultifocalprocessresultsintheunevenformationofsmall,apparentlyempty,microscopicvacuolesofvaryingsizeswithintheneuropil(theeosinophilicregionsingreymatterthatcontaindendrites,axons,andsynapses)andsometimesintheperikaryonofneurons(
Fig.
23.22A ).Inadvancedcases,thereissevereneuronalloss,reactivegliosis,andsometimesexpansionofthevacuolatedareasintocystlikespaces(“statusspongiosus”).Noinflammatoryinfiltrateispresent.ImmunohistochemicalstainingdemonstratesthepresenceofproteinaseK–resistantPrPscintissue,whilewesternblottingoftissueextractsafterpartialproteasedigestionallowsdetectionofdiagnosticPrPsc.
Starting in 1995, cases of a CJD-like illness appeared in the United Kingdom. The neuropathologic findings and molecular features of these new cases were similar to those of CJD, suggesting a close relationship between the two illnesses, yet this new disorder differed from typical CJD in several important respects: the disease affected young adults; behavioral disorders figured prominently in early disease stages; and the neurologic syndrome progressed somewhat more slowly than typical CJD. Multiple lines of evidence indicate that this new disease, termed variant Creutzfeldt-Jakob disease (vCJD) is a consequence of exposure to the prion disease of cattle, called bovine spongiform encephalopathy. Also, there is now documentation of transmission by blood transfusion. This variant form has a similar pathologic appearance to that in other types of CJD, with spongiform change and absence of inflammation. In vCJD, however, there are abundant cortical amyloid plaques, surrounded by the spongiform change (see
Fig. 23.22B
Pathogensfromvirusesthroughparasitescaninfectthebrain;inaddition,priondiseaseisaprotein-inducedtransmissiblediseasethatisuniquetothenervoussystem.
Differentpathogensusedistinctroutestoreachthebrain,andtheycausedifferentpatternsofdisease.
Bacterialinfectionsmaycausemeningitis,cerebralabscesses,orachronicmeningoencephalitis.
Viralinfectionscancausemeningitisormeningoencephalitis.