DiseaseofCentralNervousSystemThenervoussystem（神经系统）神经系统）centralnervoussystem(CNS)brainspinalcordperipheralnervoussystem(PNS)2DiseaseofCNSnIntroductionnBasicpathologicalchangesNeurodegenerativedisease:AD;PD.nCommoncomplicationsnHemodynamicDerangement&CerebralVascularDisordersnTumornInfectiondisease31.Delicatestructure,morethan50%humangenesareneuronalrelated：structureormetabolism;complexorarcaneIntroduction:DiseaseofCNS42.Lesionsmayhavelocationindication(selectivedysfunction)signaltoandfromdifferentregionsofthebodyarecontrolledbyveryspecificareaswithinthenervoussystemnervoussystemvulnerabletofocallesionsIntroduction : Disease of CNS53.Dualinfluencesofsomestructuressuchasskullanddura,protectionofbrainandmayfacilitateincreasedintra-cranialpressure.6Introduction : Disease of CNS4.Specialdisease:DegenerativediseaseDemyelinationdiseasePsychiatricdiseaseslessunderstandingCongenitalanomalies:highincidence7CellsinCNSNeurongliacellsastrocyteoligodendrocytemicroglialcellsBasicpathologicalchangesofcellsinCNSNeuropil:processofthecellsintheCNStoformadelicatefibrillarybackgroundBasicChangesofCells Neuron（神经元）神经元）9BasicChangesofCells Neuron（神经元）神经元）1.CentralChromatolysis(中央性尼氏小体溶解中央性尼氏小体溶解)Cause：axonalinjury,Viralinfection,deficiencyofVit.B,anoxia.Morphology:Sequalae:Inearlystage,increaseddissociatedribosomefromRERmayfacilitateproteinsynthesis.Thechangewouldbereversible, if cause abolished. Insistent change may lead toneuronaldeath.NormalNeuronCentralChromatolysis101. 1. 尼氏体尼氏体 ( (Nissl bodies)Nissl bodies)roughendoplasmicreticulum(RER)BasicChangesofCells Neuron（神经元）神经元）11BasicChangesofCells Neuron（神经元）神经元）1.CentralChromatolysis(中央性尼氏小体溶解中央性尼氏小体溶解)Cause：axonalinjury,Viralinfection,deficiencyofVit.B,anoxia.Morphology:Sequalae:Inearlystage,increaseddissociatedribosomefromRERmayfacilitateproteinsynthesis.Thechangewouldbereversible, if cause abolished. Insistent change may lead toneuronaldeath.NormalNeuronCentralChromatolysis102.IschemicChanges（AcuteNecrosis）Cause：ischemia,anoxia,hypoglucemia,lowerbloodpressure,epilepsyMorphology：vacuolation,redneuron,ghostcellBasicChangesofCells NeuronVacuolationRedNeuron12BasicChangesofCells Neuron3.Neurophagia(嗜神经元现象）嗜神经元现象）deadneuronengulfedandphagocytosedbyM.134.InclusionBodies(包涵体包涵体)viralinfections;neurodegenerativedisease(1)Rabies:NegribodydiagnostichallmarkofrabiesHSV;EncephalitisBJap.virus;PoliovirusBasicChangesofCells NeuronNegriBody144.InclusionBodies(包涵体包涵体)ParkinsonDis.：LewybodyMuhammaoAliSubstantianigraBasicChangesofCells Neuron15Neurodegenerativechanges:SP,NFTsvSenilePlaque(SP,老年斑老年斑)：the core composed with -amyloid protein,surrounded by a halo and swollen degenerativeaxonsBasicChangesofCells Neuron4.InclusionBodies(包涵体包涵体)16神经原纤维（神经原纤维（neurofibrilneurofibril）Normal structure Normal structure 17vNeurofibrillaryTangle(NFTs,神经原纤维缠结神经原纤维缠结):a.thetanglecomposedbydoublespiralstrandsofneurofibilswithabnormalphosphorylatedtauproteinb.markerofdyingneuronc.seeninAlzheimersDis.,boxerbrain,post-encephalitis,ParkinsonismBasicChangesofCells Neuron4.InclusionBodies(包涵体包涵体)HEHESliver impregnationSliver impregnation18SenilePlaqueNeurofibrillaryTangleAlzheimersdiseaseADHighdensityandwidespreaddistributionofplaquesandtanglesintheneocorticalareasinthesettingofdementiathatallowsonetomakeadiagnosisofAD195.WallerianDegeneration(华勒变性）华勒变性）usuallyoccurintraumatictransfectionofanerveBasicChangesofCells Neuron20NeuronWallerian degeneration of descending tracts in the brainstemWallerian degeneration of descending tracts in the brainstemImmunofluorescenceAntiglialfibrillaryacidprotein(GFAP)AstrocytearethemajorsupportingcellsinthebrainBasicChangesofCellsastrocyteHEstainingnakednucleiSliverimpregnation21BasicChangesofCells Astrocyte（星形胶质细胞）星形胶质细胞）vHypertrophy：ThecytoplasmisshownwithHEstain.TheprocesseselongateThecellanditsnuclearareenlargedwithbinuclei,multinucleiorbizarrenucleivProliferation：reactiveastrogliosis:repairprocessafterinsultsformingglialscar.Seeninlocalanoxia,edema,infarctandattheperipheryofabscessortumor.22BasicChangesofCells Astrocyte（星形胶质细胞）星形胶质细胞）-RosenthalfibernHE:athick,elongated,worm-likeorcorkscreweosinophilic(pink)bundlethatisfoundonH&EstainingofthebrainnThefibersarefoundinastrocyticprocessesandarethoughttobeclumpedintermediatefilamentproteins(GFAP).nlongstandinggliosis,occasionaltumors(pilocyticastrocytoma),andsomemetabolicdisorders(Alexandersdisease).pilocyticastrocytomavCorporaamylacea(淀粉样小体）淀粉样小体）:increasedwith aging glycoprotein-rich material located at the end process of astrocytes , especially in the subpil and perivascular zonesBasicChangesofCells Astrocyte（星形胶质细胞）星形胶质细胞）23BasicChangesofCells Oligodendrocyte( (少突胶质细胞少突胶质细胞 ) )MyelinformationcellsinCNS(inPNS:SchwanncellsHEstaining:insizeandshapelikelymphocytevLeucodystrophy(白质营养不良白质营养不良)myelinsheathformationdisturbancedifferentcongenitalenzymedeficiencyvDemyelination(脱髓鞘病变脱髓鞘病变)formedmyelinsheathdestroyedduetoallergy,anoxiaortoxificationPerivasculardemyelination(Luxolfastbluestaining )24nProgressivemultifocalleukocephalopathy(PML)-DemyelinatingdiseasenThecauseofPMLisatypeofpolyomaviruscalledtheJCvirus(JCV)nSevereimmunedeficiency,suchastransplantpatientsonimmunosuppressivemedications,patientsreceivingcertainkindsofchemotherapyorAIDSpatients(5%)BasicChangesofCellsOligodendrocyte(少突胶少突胶质细质细胞胞)-intranuclearinclusionsnPMLdestroysoligodendrocytes;producesintranuclearinclusionsMicroglia(小胶质细胞）小胶质细胞）RestingmicrogliamayactivatedandturnintoM(1)Focalproliferationformingmicroglialnodule(2)Rodlikemicrogliaseeninadvancedsyphilis25Gitter cell/foam cells26Microglial nodule - rod cells27 normallylinetheventricularcavitiesandthecentralcanalofthespinalcordSilence,Oncogenesis,Deficiencyafterinjurymayrepairedbyastrocyte,formingsocalledgranularependymitis(颗粒性室管膜炎颗粒性室管膜炎)BasicChangesofCells Ependymalcells(室管膜细胞室管膜细胞)28CommonComplicationsn脑水肿脑水肿 （BrainEdema)n脑积水（脑积水（hydroceplus)n颅内压升高及脑疝（颅内压升高及脑疝（herniation)20CommonComplications脑水肿脑水肿 （BrainEdema)IncreasedwatercontentswithinbrainparenchymaCause:anoxia,infarction,inflammation,injury,toxificationandtumor.Mechanism:1.Vasogenic:disruptednormalBBBinterstitialedemawhitemattergraymatter2.Cytotoxic:cytomembranouspump(ATPase)intracellularedemawhitematter=graymatterusuallymixedtypenComponentsComponents nEndothelial cellsEndothelial cellsnBasal membraneBasal membranenpericytepericytenAstrocytic feet Astrocytic feet 血脑屏障（血脑屏障（Blood-Brain Barrier, BBBBlood-Brain Barrier, BBB）Functions protection EdemaEdemaMorphology:brainvolume,weight,narrowsulci,widenedgyri,cuttingsurfaceshowedsmallventricle,increasedreflection.Herniationmayensure.CommoncomplicationsHydrocephalus（脑积水脑积水) )AccumulationofexcessiveCSFwithventriculardilatationasaresultofadisturbanceofitssecretion,circulationandabsorptionCSF:cerebrospinalfluidThreelayersofthemeningesvduramaterleptomeningesvthearachnoidmater(arachnoidvilli)thesubarachnoidspace(CSF)vthepiaCirculationofCSFChoroidsplexus-ventricularsystem-arachnoidvilliTherateofformationandabsorptionofCSFremaininbalanceFunction:actasthelymphocyticdrainageinthebrain1.Over-secretionofCSF(tumorofchoroidplexus)2.AbsorptiondisturbancesofCSF1)Noncomunicating(obstructive)：tumor,inflammatory,adhesion,hemorrhage,ordeformityinIIIventricle.2)Communicating:meningitis,subarachnoidhemorrhage,withsubsequentorganization,orcausingscarringofarachnoidgranulationorVilli.Cause&PathogenesisMorphology:Dilationofventricleswithatrophyofparenchymaofbrain,duetocompressionofCSF.CPC:headache,vomiting,papilloedemaofopticN.CommoncomplicationsHydrocephalus（脑积水脑积水) )CommoncomplicationHypertensionofintracranialpressure(ICP)andHerniation(颅内压升高和脑疝形成）颅内压升高和脑疝形成）TheCSFpressuremorethan2kPa(normally0.6-1.8kPa)withlateralrecumbentpositionCause：（1）cerebraledema,hydrocephalus（2）occupyinglesion:tumor,hemorrhage,hematoma（3）inflammation:meningitis,cerebralabscess,encephalitis（4）braininfarctionThefactorsinfluencetheresults:（1）thesizeofthelesionanditsdevelopmentrapidity.（2）existedcranialcavitysituationsenileatrophyorunclosureoffontanelleallowingmorespaceforexpendingofbrainCommoncomplicationsHypertensionofICP&HerniationSequalae：（1）headache,vomiting,papilloedema,coma,deathCommoncomplicationsHypertensionofICP&HerniationSequalae：(2）herniation1)Subfalcine(cingulategyrus)herniation：vlocaltissuehemorrhagicandnecrotic,vweaknessandsensorydysfunctionoflegCommoncomplicationsHypertensionofICP&HerniationAnterior cerebral arteryHerniation:displacementofbraintissuefromoneintracranialcomponentintoanother,orintothespinalcanal1.Subfalcine(cingulategyrus)herniation2.Transtentorial(uncinategyrus)herniation3.Tonsillarherniation4.Externalcerebralherniation2)Transtentorial(uncinategyrus)herniation：vipsilateralIIINcompressedleadingtopupilsconstricteddilatedvKernohanincisionvparalysisofipsilateralextremities(falselocalizationsign)vperiaquaductalhemorrhagethecerebralpedunclethecorticospinaltractIIIoculomotornerve海马钩回疝海马钩回疝Transtentorial(uncinategyrus)herniation：Transtentorial(uncinategyrus)herniation：vipsilateralIIINcompressedleadingtopupilsconstricteddilated“blownpupil”IIIoculomotornerveIIIoculomotornerve Transtentorial(uncalgyrus)herniation：vKernohanKernohan切迹切迹切迹切迹vparalysisofipsilateralextremities(falselocalizationsign)thecerebralpedunclethecerebralpedunclethecorticospinaltractthecorticospinaltractthecorticospinaltractthecorticospinaltractKernohansnotchKernohansnotch Transtentorial(uncalgyrus)herniation：vperiaquaductalhemorrhageperiaquaductalhemorrhage-tearingofpenetratingV.A.-tearingofpenetratingV.A.小脑扁桃体疝小脑扁桃体疝TonsillarherniationforamenmagnumHypertensionofICP&Herniation3)Tonsillarherniation,life-threateningpressrespirationcentersinmedullaoblongatasuddendeath virtalrespiratoryandcardiccentersinthemedullaforamenmagnumHemodynamicDerangement&CerebralVascularDisordersHemodynamicDerangement&CerebralVascularDisordersCirculationdisturbances:ischemicencephalopathyinfarction(thromboticorembolitic)hemorrhageVasculardisorders:arteriolosclerosis,atherosclerosis,arteritis,aneurysm,ateriovenousmalformation(AVM)widespreadischemia/hypoxiainjuryoccursduetoageneralizedreductionofcerebralperfusioncausedbyhypertension,cardiacarrest,hemorrhageandshock.thebrain:1%2%ofbodyweightoxygenconsumptionabout20%systolicpressurelessthan50mmHgwillcauseseverebraininjuryHemodynamic Derangement & Cerebral Vascular Disordersglobalcerebralischemia/ischemicEncephalopathyPredisposingfactors：vhighermetabolicrate：moresusceptibleNeuronAsOligoEndoGrayMatterWhiteMatter3rd、5th、6thlayersofcortexaremostvulnerablevPersistenceandseverityofischemiamildischemia:noremarkablechangesevereischemia,survivefewhoursbeforedeath:notremarkablemoderateischemia,survivemorethan12hours：typicalchangesvArchitectureofcerebralarteriesthelocationattheborderzoneofcerebralarteriesismuchmorevulnerable.BorderzoneofcortexCshapeArchitectureofCerebralArteriesChanges:vlaminarcorticalnecrosis:neuronsin3rd,5th,6thlayersofcortexinvolvedvhippocampussclerosis：pyramidalneurondeathvborderzoneinfarction：earlystage：“C”shapedinfarctlaterstage:astrogliosis(granularatrophy)cardiopetaldevelopmentglobalnecrosis(respiratorbrain)HemodynamicDerangement&CerebralVascularDisordersIschemicEncephalopathyLaminarCorticalNecrosisHemodynamicDerangement&CerebralVascularDisordersIschemicEncephalopathyFreshborderzoneinfarctGranularatrophy(gliosis)CuttingsurfaceofgranularatrophyRespiratorbrainHemodynamicDerangement&CerebralVascularDisordersIschemicEncephalopathyCPC：weaknesssensationabnormalitiescoma,persistentvegetativestatedeathclinicalcriteriaforbraindeathrespiratorbrain:autolyticprocessbrowndiscolorationandunfixedbrainpersoninavegetativestate/vegetablecanwakeup?HemodynamicDerangement&CerebralVascularDisordersFocalCerebralIschemiaCause：thrombosis,embolism,spaceoccupyinglesion,localvesselscompressedbyherniationTypes:thrombotic:onthesitesofatherosclerosisinnercarotidA,basilarA,cerebralarteries,Thesymptoms:insidiousandgradualdevelopmentfromweaknessofmusclestosemiplegiaorcomaembolic:theembolioftenarecardiogenic,orfromatheroscleroticplaque,withsuddenonsetandpoorprognosis.HemodynamicDerangement&CerebralVascularDisordersCerebralInfarctionThemostcommonformofcerebrovasculardisease,accountingfor70%80%ofallcerebralvascularaccidents“stroke”Changes:extentofischemia:vOcclusionininnercarotidartery:circlewillismaycompensatecompletely,noinfarctionvOcclusioninmid-sizeartery:asmiddlecerebralA,theinfarctsmallerthanitssupplyareaduetopartialanastomosis.vOcclusioninterminalarteries:leadingtosuppliedareainfraction.HemodynamicDerangement&CerebralVascularDisordersCerebralInfarctionTypes:vwhiteinfarctvredinfarct:incompleteocclusionorfrangibleemboligoingfurthertosmallvessels,resultinginbloodescapefrominjuredvascularwall.Morphologychanges:vfirst412h:normalvthen:ischemicneuronalchangesv36-48h:swollenandsoft;demarcationbetweengrayandwhitematterbecomesblurredduetoedemavthethirdday:macrophage,progressivemarkeddemarcationofthelesionv1month:liquefaction,irregularcavitiesv6month:completelyliquefiedwithgliosis(scar)Pathologicalchangesischemicneuronalchangesliquefaction,irregularcavitiesreactivegliosisTwoimportanttermsofBraininfarctionvLacunae(腔隙性梗死）腔隙性梗死）:sharplydefinednecrosislessthan1.5cmindiameter,correspondingtotheterritoryofasingleperforatingartery,themaincauseoflacunaewasconsideredtobehypertensionTwoimportanttermsofBraininfarctionvLacunae(腔隙性梗死）腔隙性梗死）:sharplydefinednecrosislessthan1.5cmindiameter,correspondingtotheterritoryofasingleperforatingartery,themaincauseoflacunaewasconsideredtobehypertensionvTIAs(transientischemicattacks一过性脑缺血一过性脑缺血)transientepisodeofneurologicdysfunctionlastingseveralminutes24hoursanimportantpredictorofsubsequentinfarcts1/3patientswithTIAdevelopingclinicallysignificantinfarctswithin5yearsInfarctionareasuppliedbymiddlecerebralA.HemodynamicDerangement&CerebralVascularDisordersBrainHemorrhageIntracerebralHemorrhageCause:hypertension*congenitalsaccularaneurysms,tumors,hemorrhagicdiathesis,vasculitis,AVM,traumaHypertensionaccountsforabouthalfofSpontaneousbrainhemorrhagePathogenesis:anoxiaofvascularwallanoxiaofperivasculartissueCharcotBouchardmicroaneurysmsmicro-softeningfocivesselsrupturedspasmofvesselsB.PhemorrhagenOccurinsmallbloodvessels(lessthan300micrometrediameter)nOftenlocatedinthelenticulostriatevesselsofthebasalgangliaandareassociatedwithchronichypertensionnAcommoncauseofstroke Charcot Bouchard microaneurysmsCommonlocations:theputamen,caudate,thalamus,pons,andcerebellum.Changes:Inthecenteroffoci,normalstructureisdestroyedandfilledwithRBC，atperipherymultifociofhemorrhageTheoldhemorrhagefocibecomescavitated&withhemosiderin.HemodynamicDerangement&CerebralVascularDisordersBrainHemorrhageHypertensiveHemorrhagesCPC：vB.Ghemorrhage:directedtoinsularcontralateralsemiplegiadirectedtoventricle,thalamusdeathvPonshemorrhage:pin-likepupils,persistenthighfeverorsuddendeathvCerebellarhemorrhage:severeoccipitalheadache,frequentvomitingHemodynamicDerangement&CerebralVascularDisordersBrainHemorrhageCerebralHemorrhageSubarachnoidhemorrhagenThemostcommoncauseofspontaneous(nontraumatic)nRuptureofasaccular(berry)aneurysmapproximately1%ofthegeneralpopulationdifferentfromthefusiformdialtioninatheroslcerosisorinfectious(mycotic)aneurysm80%ariseatthearterialbifurcationsintheterritoryoftheinternalcarotidartery:MCA,ACMnDevelopedtheinfarctofbrainparenchymaCPC:Abrupt,severeheadache,vomitting,lossofconsciousnessMeningealsignsBloodyCSF50%diedinseveraldaysacutehydrocephalusherniationbraininfarctionchronic:hydrocephalusVascularmalformationnAbnormalitiesinangiogenesisinthedevelopingbrainnAVM:themostcommoncausedvesselsofvariablecaliberincludingA,VHemorrhagic,calcification,reactivegliosisTumorsofCNSAstrocytoma（星形胶质细胞瘤星形胶质细胞瘤)ThemostcommoncategoriesofbraintumorsinCNSGliomasshares40%ofbraintumors，astrocytomashares70%ofgliomasMostastrocytomasareofdiffuseinfiltrativeAstrocytomasinChildrenandAdultsLocationdifferentiationdemarcationofteninbrainstemcerebellumbeneathtentoriumwell,gelatinousingrossappearanceChildrenpoormostoftenabovetentoriuminhemispheresrelativelypoorgranularingrossappearancewellAdultsPage 417Morphology:npilocyticastrocytoma:commoninchildren,elongatedprocessesextendfromtwopoplars(gradeI)nfibrillaryastrocytomaandcytoplasmicastrocytoma:mimictheiroriginalastrocytes(gradeII)ngemistocyticastrocytoma:(gradeIIIII)nanaplasticastrocytoma:(gradeIII)nglioblastomamultiform:(gradeIV)GFAP(+)TumorsofCNSAstrocytoma（星形胶质细胞瘤星形胶质细胞瘤)GrossinspectionofastrocytomaAstrocytoma (WHO Grade II)CytoplasmicastrocytomaAnaplastic astrocytoma WHO Grade IIIAnaplastic astrocytoma WHO Grade IIIglioblastomamultiform(GBM)WHOGradeIVglioblastomamultiform(GBM)WHOGradeIVGlioblastomaMultiform(GBM)Thetumororiginatesfrommenigoepitheliumofarachoidgranulesvillaorfibroblasts.Itsgrowsoutsidethebrain,pressingthebrainparenchymaandmayberesectedcomplete.Grossly:tumorshowssphericalorlobulated,expandingingrowthHistology:MenigothelialorsyncytialtypeFibroblasticvariantsTransitionaltypeOthersPrognosis:mostbenign,afew(15%)recursafterresection,fewundergoesmalignanttransformationEMA(+)Vimentin(+)TumorsofCNSMeningioma（脑膜瘤脑膜瘤)Meningioma（脑膜瘤脑膜瘤)GrossinspectionMicroscopicappearancepsammomabodyvEmbryogenictumor,malignant,mostlyseeninchildrenundertenwithpoorprognosisvThetumororiginatesfromprimitiveneuroecdermalcellsofvermisoroutlayersofgranularcellsofcerebellum.vThetumorshowswhitishpinkorgrayincolor,locatedatIVventricleorcerebellarhemisphere.vThecellsaresmall,primitivewithscantycytoplasm.Thenucleiareroundorcarrot-shapedwithfrequentmitoses.Sometimes,maysurroundafibrillarycorehavingrosetteformationvMutualdifferentiation:GFAP（+）NF（+）TumorsofCNSMeduloblastoma（髓母细胞瘤髓母细胞瘤)Medulloblastoma（髓母细胞瘤髓母细胞瘤)GrossinspectionMicroscopicappearancevThebenigntumororiginatesfromschwanncell,oftenlocatedat8thnerve(acousticneurilermmoma听神经瘤）听神经瘤）ortrunkofperipheralN.vSlowgrowth,veryraremalignanttransformationvSpherical,orlobulatedmass,white-grayincoloroncutsurface,orshowslightyellowcolorwhenmucinousdegenerationoccur.quiteoftencavitationvSpindleshapedcells,inwhirlortightarrangement(AntoniAtype)orinreticulararrangement（AtoniB型）型）TumorsofCNSSchwannoma（神经鞘瘤神经鞘瘤,施万氏瘤施万氏瘤)Schwannoma（神经鞘瘤神经鞘瘤,施万氏瘤施万氏瘤)MicroscopicappearanceGrossinspection1.Etiology:thediseasecausebylivingpathogens,whichareinfective,endemicincertaingeographicareasandincertainseasons(传染性，流行性，地方性，季节性）传染性，流行性，地方性，季节性）2.Uniquerouteofinvasion,agivenpathogenhas:vuniqueentranceofinvasionvuniquemodeofspreadingamonghostvuniqueaffinityforspecialtissueororgans,causingspecialpathologicalchanges3.Pathogenesisvbacteria:endotoxinand/orexotoxinvviruses:cellularand/orhumoralimmunityInfectiousDiseaseCommonFeatures(共同特性）共同特性）4.Basicpathologicchanges:inflammation(acute/chronic)dependingonhostpathogenhost:immunitypathogen:invasionability,toxins,metabolicsubstanceevocationofallergicreactionofhost5.ClinicalcoursevIncubationperiod:vPredromeperiod:nonspecificsymptomsandsignsvDominantperiod:diagnosticsymptomsandsignspeakvRecoveryperiod:thediseasesubsidestypical/atypical/subclinicalcourseInfectiousDiseaseCommonFeatures(共同特性）共同特性）免疫性免疫性6.ConsequencesvCompleterecoverythehostgainstemporaryorpermanentimmunityvChroniccoursevRecurrenceofdiseasevDeathInfectiousDiseaseCommonFeatures(共同特性）共同特性）InfectiousDiseaseCommonFeaturesinCNS(共同特性）共同特性）vSkullvMeningesdura硬脑膜硬脑膜arachnoid蛛网膜蛛网膜pia软脑膜软脑膜vBBBeffectivelyprotectedCNSfromtheinfectiveagentsPre-existingimmunodeficiencyconditionsSpecialvirulencefactorsofpathogensHostdefensemechanismaresuboptimaltocontrolpathogeninfectioninCNSleptomenige（软脑膜）软脑膜）Page 410vRouteofinfectionHematogenic:septicema,viremiaLocaldisseminated:openedskullfracture,sinusitis,mastoiditisDirectinfected:trauma,iatrogenicinterference(lumbarpuncture)Throughperipheralnervoussystem:rabies,HSVInfectiousDiseaseCommonFeaturesinCNS(共同特性）共同特性）InflammationfeatureStereotypedReactionvneurons:degeneration,necrosisvsecondarydemyelinationvlimitedexudationwithperivascularcuffingformationPresenceofBBB(bloodbrainbarrier)andV-RspacelimitsthespreadofinflammationAbsenceofintrinsiclymphaticandlymphoidtissueT/Bcellsarebloodborn(exogenic)vglianoduleformationmicroglialnoduleinearlystage.astrocyticnoduleinlaterstage,repairPathogens:vPyogenicmeningitis:meningococci,Hinfluenza,Pneumococci,Streptococci,Staphylococci,EColivGranulomatousmeningitis:T.B.mycobacterium,FungivLymphocyticmeningitis:viruses,spirochetesMeningitisEpidemicMeningococcicMeningitis(流行性脑膜炎双球菌性脑膜炎流行性脑膜炎双球菌性脑膜炎)vAntonWeichselbaumin1887vPathogen:meningococcusSpherical,0.61.0mindiameter,gramnegativeonlyinfecthumanoftencarriedinthenoseandthroatwithoutsymptomsvSpreadbydropletcoughorsneezedoutvEpidemicseasons:Winter&SpringvBacteria spread by air (sneeze and spray), located atnasopharynx,mostarebacteriacarrier(15%population,inepidemicseason:7080%)vVictimsarechildren,mostyoungerthan10yrsoldvBasicchanges：acutepurulentinflammation(Leptomeninge&CSF)vClinical symptoms & signs: fever, headache, vomiting,petechia&ecchymosisontheskin&mucosa,meningealirrigativesigns,shockinseverecasesvTemporaryimmunityafterrecoveryEpidemicMeningococcicMeningitis(流行性脑膜炎双球菌性脑膜炎流行性脑膜炎双球菌性脑膜炎)MeningitisPathogen:meningococci,endotoxinandcapsulearepathogenicRouteofinfection:SprayfromcarrierMucosaofnasopharyxBlood(septicemiaorbacteremia)leptomenigesmeningitisUsually5%30%,7080%inepidemicperiodURI,catarrh(sorethroatredandedematousmucosa,mucousdischarge)PetechiaecchymosisBacterialemboliVascularparalysis,dilation,thrombosisshockbilateralseverehemorrhageofadrenalcortex(Waterhouse-Friderichsensyndrome)(+)MeningitisPathologicalChanges:Vassels:bacterialthrombi,thrombosis,focalhemorrhageMeninge:acutepurulentinflammation Gross:vdura:tense,hyperemicvSubarachnoidspacefilledwithgrayishyellowpusespeciallyatconvexofhemisphereatthebaseincisternaealongcircleWillis,rootsofcranial&spinalNervesPurulentMeningitisLM：vStrikinglyenlargedsubarachnoidspacewithlargeamountofpurulentexudation,mainlypolys.vVascularcongestionvAdjacentbrainparenchymabeedematousMeningitisClinicalPathologicalCorrelation(CPC)MeningealirritationsignsinflammationSwellingofrootsofcranial&spinalNCompressionatostioleorintervertebralholesPreventivemuscularspasmatbackinordertofixthepositionofnerverootatholesKernigsSign(+)BrudzinskiSign(+)neckstiffnessoropisthotonus(角弓反张）角弓反张）Opisthotonosfrom Greek roots, opistho meaning behind and tonos meaning tension, an individuals head, neck and spinal column enter into a complete bridging or arching position. This abnormal posturing is an effect and is caused by spasm of the axial muscles along the spinal column.BrudzinskiSign(+)An involuntary flexion of the hip and knee when the neck is passively flexed. It can occur in patients with meningitis.Kernigssign(+)Inability to completely extend the leg when sitting or lying with the thigh flexed upon the abdomenMeningitisCPCHypertentionofICPInflammatoryexudeadhesionofarachnoidgranulesdecreasingabsorptionofCSFvascularcongestioncerebraledemaProjectilevomitingheadachecomaCSFchangesMeningitisCPCCSFChangesIncreasingpressureTurbid,protein，cellcountPus(+),bacteria(+)SugarMeningitisCPCWaterhouse-Friderichsen syndrome(华佛氏综合症华佛氏综合症) ) severesepticemialargeamountofendotoxinreleasedDICshockbilateralhemorrhageofadrenalcortexExtensiveecchymosispurpuraMildornomeningealchangesPrognosis:quitegood.Theusageofantibioticsmakesmorethan90%patientsrecovered.Complications:quitefew1.focaladhesivearachnoiditis2.hydrocephalus: due to inflammatory adhesion,decreasingabsorptionofCSF3.cranial nerve injury: palsy, blindness, deafnessstrabismus(III、IV、V、VII)4.cerebralinfarction:inflammationvesselsinflammatoryinjuryandoccludedMeningitisConsequenceandprognosisSuspicionofmeningitisisamedicalemergencyandimmediatemedicalassessmentisrecommended.CurrentguidanceintheUnitedKingdomisthatanydoctorwhosuspectsacaseofmeningococcalmeningitisorsepticaemia(infectionoftheblood)shouldgiveintravenousantibiotics(benzylpenicillinorCefotaxime)andadmittheillpersontothehospital.ThismeansthatlaboratorytestsmaybelesslikelytoconfirmthepresenceofNeisseria meningitidisastheantibioticswilldramaticallylowerthenumberofbacteriainthebody.TheUKguidanceisbasedontheideathatthereducedabilitytoidentifythebacteriaisoutweighedbyreducedchanceofdeath.vaccineRemarksonviralinfectionvAbsolute parasitism in host cells, selective vulnerability of differentgroupofneuron.vInvadesneuron:cytolysis,inclusionbodyformationvGliacellproliferation,multinucleargiantcell(HIV)vT/BcellimmunityInflammationfeatureStereotypedReactionvneurons:degeneration,necrosisvsecondarydemyelinationvlimitedexudationwithperivascularcuffingformationPresenceofBBB(bloodbrainbarrier)andV-RspacelimitsthespreadofinflammationAbsenceofintrinsiclymphaticandlymphoidtissueT/Bcellsarebloodborn(exogenic)vglianoduleformationmicroglialnoduleinearlystage.astrocyticnoduleinlaterstage,repairEpidemicJapaneseBEncephalitis(流行性乙型脑炎流行性乙型脑炎)Conceptv1934JapanvJapaneseBEncephalitis(RNA)virusvGlobalincidence,highmorbidityandmortalityvChina:morethan10000casesannuallyvArboviralencephalitisvmostcasesshowacuteclinicalcourse,tropicalregion:epidemicthroughtheyeartemperateregion:summerandautumn.vVictimsarechildren,teenagers,withdrowsiness,higherfever,severeheadache,convulsion,vomiting,deepcoma.vBasicpathologicalchangeisneuronaldegenerationvPermanentimmunityaftersufferingofdiseasenMortality:70%beforeto10%nowEpidemicJapaneseBEncephalitis(流行性乙型脑炎流行性乙型脑炎)ConceptEncephalitisBJap.nPathogen：Encephalitis B Jap. Virus (RNA)nRoute of InfectionbiteofmosquitovirusEndotheliumoflocalbloodvesselsMfurthermultiplicationviremianormalimmunity&BBBincompetentBBBsubclinicalinfectionneuronencephalitisEncephalitisBJap.PathologynGraymatterinvolved.mainlyCerebralCortexB.G. ThalamusnGrossInspection:CongestionofMeningesBrainEdemanMicroscopicfindings:Sieve-likesofteningfoci,welldemarcatedNecrosisofneuronsCongestionandperivascularcuffingProliferationofglialcellsMicrogliaproliferation(acutestage)withfoamycellformationAstrocyteproliferation(chronicstage)SievelikesofteningMicroglialnodulePerivascularlymphocyticcuffingEncephalitisBJapClinicopathologicalCorrelation(CPC)inflammationcongestiondamageofendotheliumhypertensionofICPcerebraledemaHeadachevomitingtonsilarherniationDrosinessconvulsioncoma(+)pneumoniaandothercomplicationssuddendeathdegenerationandnecrosisofneuronEncephalitisBJapConsequencesandComplicationsnHighmortalityascompareswithepidemicmeningitisnComplications:mentalretardation,dementia,aphasia,paralysisofcranialorperipheralN.vImplementationofmeasures:eradicatemosquitoesandamassimmunizationprogrammehavereducedtheincidenceofJEinJapantounder20casesperyearEncephalitisBJapSpongiformEncephalopathy(PrPDisease)( (海绵状脑病，朊蛋白病）海绵状脑病，朊蛋白病）Creutzfeld-Jacobdisease（CJD，克雅氏病）克雅氏病）Kuru（枯颅病）枯颅病）Fatalfamilialinsomnia（FFI,致死性家族性失眠症）致死性家族性失眠症）Gerstmann-straussletsyndrome(GSS)Scrapi(羊瘙痒症羊瘙痒症)Madcowdisease(疯牛病疯牛病newvariantCJD)Catscratchdisease(猫抓病猫抓病)SpongiformEncephalopathy(PrPdisease)-PathogennormalPrPc:va30KDtransmembranousproteinofneuron.vunknownfunctionvwithhelices(spiralconfiguration)vcodedbyageneonchromosome20,completelydisintegradedpathogenicPrPsc:vwithmoresheets(foldedconfiguration)vincompletelydisintegrated&depositinbraincausingKuruvPlaqueandspongiformchangesvPrPsc can duplicate itself by transformation from PrPc( achallengetocentraldogma?)vCasesfromgenemutation(85%)andfrominfection(15%)coexistGross:inearlystage,noglosschangeswithlongstandingduration,severeatrophyLM:SpongiformEncephalopathy:Vacuolesinneuropilandneuronbodyingraymatter,mostlyfocidistributionNeuronaldeficitwithgliosis,withoutinflammationPrognosisFetal,with1yearsurvivalperiodonaverageSpongiformEncephalopathy(PrPdisease)PathologyCJDHEPrPscimmunostainSummarynBasicpathologicchangesinCNSredneuron,centralchromatolysis,WallerianDegeneration,neurophagia,reactiveastrogliosis,demyelinationnThethreeimportantcomplicationsnThecerebrovasculardiseaseGlobalcerebralischemiaFocalcerebralischemiathemostfrequentcause:Atherosclerosis)hemorrhagic/nonhenorrhagicinfarctionsIntracranialhemorrhagethemostfrequentcause:hypertensionnInfectionsofCNSacutepyogenicmenigitisviralencephalitisHomeworkPlease compare the different features of epidemic cerebrospinal meningitis and epidemic encephalitis type B?