Chapter16：

DiseaseofCentral

NervousSystemDepartmentofShanghaiMedicalCollege,FudanUniversityZhurongYe,YingLiu1Introduction1.Delicatestructure,morethan50%humangenesareneuronalrelated：complexorarcane2.Lesionsmayhavelocationindication(selectivedysfunction)silentarea3.Dualinfluencesofsomestructures,suchasskullanddura,protectionofbrainandmayfacilitateincreasedintra-cranialpressure.4.Specialdisease:degenerativedisease,demyelinationdisease,psychiatricdiseaseslessunderstandingCongenitalanomalies:highincidence2BasicChangesofCells

Neuron（神經(jīng)元）3BasicChangesofCells

Neuron（神經(jīng)元）1.CentralChromatolysis(中央性尼氏小體溶解)Cause：axonalinjury,Viralinfection,deficiencyofVit.B,anoxia.Morphology:

dispersionofthecentralNissalsubstanceandswellingoftheneuronalbodySequalae:Inearlystage,increaseddissociatedribosomefromRERmayfacilitateproteinsynthesis.Thechangewouldbereversible,ifcauseabolished.Insistentchangemayleadtoneuronaldeath.4CentralChromatolysis52.IschemicChanges（AcuteNecrosis）

Cause：ischemia,anoxia,hypoglucemia,lowerbloodpressure,epilepsyMorphology：vacuolation,redneuron

BasicChangesofCells

Neuron6redneuron7SimpleDegeneration(單純性萎縮）

Cause:uncertain,seenindegenerativeDis.Morphology:neuronalprogressive,chronicdeath,withoutglialreactionBasicChangesofCells

Neuron8Neurophagia(嗜神經(jīng)元現(xiàn)象）

deadneuronengulfedandphagocytosedbyMΦ.SatellitePhenomenon(衛(wèi)星現(xiàn)象)morethan5OligodendrocytessurroundingoneneuronuncertainsignificanceBasicChangesofCells

Neuron9InclusionBodies(包涵體)

Rabies:NegribodydiagnostichallmarkofrabiesHSV;EncephalitisBJap.virus;Poliovirus

Parkinson

Dis.：Lewybody

BasicChangesofCells

Neuron10Rabies11Lewybody12WallerianDegeneration(華勒變性）

BasicChangesofCells

Neuron13SenilePlaque(老年斑)：

thecorecomposedwithβ-amyloidprotein,surroundedbyahaloandswollendegenerativeaxons

NeurofibrillaryTangle(神經(jīng)原纖維纏結(jié)):thetanglecomposedbydoublespiralstrandsofneurofibilswithabnormalphosphorylatedtauprotein markerofdyingneuronseeninAlzheimer’sDis.,boxerbrain,post-encephalitis,Parkinsonism

BasicChangesofCells

Neuron14SenilePlaque15NeurofibrillaryTangle16BasicChangesofCells

Astrocyte（星形膠質(zhì)細(xì)胞）Hypertrophy：ThecytoplasmisshownwithHEstain.Thecellanditsnucleiareenlargedwithbinuclei,multinucleiorbizarrenucleiSeeninlocalanoxia,edema,infarctandattheperipheryofabscessortumor.

Proliferation：

reactive:

repairprocessafterinsults,formingglialscar.Corporaamylacea(淀粉樣小體）:withageglycoprotein-richmaterial

17BasicChangesofCells

Oligodendrocyte

(少突膠質(zhì)細(xì)胞)Leucodystrophy(白質(zhì)營養(yǎng)不良)myelinsheathformationdisturbance

differentcongenitalenzymedeficiencydifferenttypeofleukodystrophyDemyelination(脫髓鞘病變)formedmyelinsheathdestroyedduetoallergy,anoxiaortoxification18Demyelination19Demyelination20

Ependymalcells

(室管膜細(xì)胞)Silence,Oncogenesis,DeficiencyafterinjurymayrepairedbyAs,formingsocalledgranularependymitis(顆粒性室管膜炎)BasicChangesofCells

21Microglia(小膠質(zhì)細(xì)胞）

RestingmicrogliamayactivatedandturnintoMΦFocalproliferationformingmicroglialnoduleRodlikemicrogliaseeninadvancedsyphilis22Demyelination23CommonComplications

腦水腫（BrainEdema)Morphology:

brainvolume↑,weight↑,narrowsulci,widenedgyri,cuttingsurfaceshowedsmallventricle,

increasedreflection.

Herniationmayensure. 24CommonComplications

腦水腫（BrainEdema)IncreasedwatercontentswithinbrainparenchymaCause:anoxia,infarction,inflammation,injury,toxificationandtumor.Mechanism:Vasogenic:disruptednormalBBB,

allowingincreasingpermeability

andfluidescapingfromvesselsintotheinterstitialspaceofbrain(interstitialedema)

whitematter>graymatter2.

Cytotoxic:cytomembranouspump↓(ATPase)leadingtoironsandwateraccumulationincells(intracellularedema)whitematter=graymatter

3.Usuallymixedtype25Commoncomplications

Hydrocephalus

（腦積水)

AccumulationofexcessiveCSFwithventriculardilatation

2627Over-secretionofCSF(tumorofchoroidplexus)

AbsorptiondisturbancesofCSFNoncomunicatingtype(obstructive)：obstructionoccursinventricularsystem,e.g.tumor,inflammatory,adhesion,hemorrhage,ordeformityinIIIventricle.Communicatingtype:obstructionexistsinCSFcirculation,butoutofventricles.Itmaycausedbymeningitis,subarachnoidhemorrhage,withsubsequentorganization,scarfomattionofarachnoidgranulationorVilli.

Cause&Pathogenesis28Morphology:

Dilationofventricleswithatrophyofparenchymaofbrain,

duetocompressionofCSF.CPC:

headache,vomiting,edemaofpapilloedemaofopticN.

Commoncomplications

Hydrocephalus

（腦積水)

29CommoncomplicationHypertensionofintracranialpressure(ICP)andHerniation(顱內(nèi)壓升高和腦疝形成）TheCSFpressuremorethan2kPa(normally0.6-1.8kPa)withlateralrecumbentposition

30Cause：（1）cerebraledema,

hydrocephalus（2）occupyinglesion:

tumor,hemorrhage,hematoma（3）inflammation:meningitis,cerebralabscess,encephalitis（4）braininfarctionThefactorsinfluencetheresults:（1）thesizeofthelesionanditsdevelopmentrapidity. （2）existedcranialcavitysituation senileatrophyorunclosureoffontanelleallowingmorespaceforexpendingofbrainCommoncomplications

HypertensionofICP&Herniation31Sequalae：（1）headache,vomiting,papilloedema,coma,death

（2）herniationSubfalcine(cingulategyrus)herniation：localtissuehemorrhagicandnecrotic,weaknessandsensorydysfunctionofleg2)Transtentorial(uncalgyrus)herniation：ipsilateralIIINcompressedleadingtopupilsconstricteddilatedKernohanincisionparalysisofipsilateralextremities(falselocalizationsign)periaquaductalhemorrhageTonsillarherniation,life-threatening

pressrespirationcentersinmedullaoblongata→suddendeathCommoncomplications

HypertensionofICP&Herniation3233Transtentorial(uncal

gyrus)herniation34Tonsillar

herniation35HemodynamicDerangement&CerebralVascularDisorders36HemodynamicDerangement&CerebralVascularDisordersCirculationdisturbances:

ischemicencephalopathy infarction(thromboticorembolitic) hemorrhageVasculardisorders:arterosclerosis,atherosclerosis,arteritis,aneurysm,ateriovenousmalformation(AVM)37Cerebralinjurycausedbyhypertension,cardiacarrest,hemorrhageandshock.Predisposingfactors：highermetabolicrate：moresusceptibleNeuron>As>Oligo>EndoGrayMatter>WhiteMatter3rd、5th、6thlayersofcortexaremostvulnerableHemodynamicDerangement&CerebralVascularDisordersIschemicEncephalopathy38Peresistenceandseverityofischemia

mildischemia:noremarkablechange severeischemia,survivefewhoursbeforedeath:notremarkablemoderateischemia,survivemorethan12hours：typicalchangesArchitectureofcerebralarteriesthelocationattheborderzoneofcerebralarteriesismuchmorevulnerable.

HemodynamicDerangement&CerebralVascularDisordersIschemicEncephalopathy3940Changes:laminarcorticalnecrosis:neuronsin3rd,5th,6thlayersofcortexinvolvedhippocampalsclerosis：pyramidalneurondeathborderzoneinfarction：

earlystage：“C”shapedinfarctlaterstage:astrogliosis(granularatrophy) cardiopetaldevelopment→globalnecrosis(respiratorbrain)CPC：weaknesssensationabnormalities→coma,vegetablestatus→deathHemodynamicDerangement&CerebralVascularDisordersIschemicEncephalopathy41LaminarCorticalNecrosisHemodynamicDerangement&CerebralVascularDisorders

IschemicEncephalopathy42FreshborderzoneinfarctGranularatrophyCuttingsurfaceofgranularatrophyRespiratorbrainHemodynamicDerangement&CerebralVascularDisordersIschemicEncephalopathy43Respiratorbrain44Cause：

thrombosis,embolism,spaceoccupyinglesion,localvesselscompressedbyherniaTypes:

※thrombotic:onthesitesofatherosclerosisinnercarotidA,basilarA,cerebralarteries,post-communicatingA,superiorcerebellarA.insidiousandgradualdevelopmentthesymptoms:fromweaknessofmusclestosemiplegiaorcoma※embolic:theembolioftenarecardiogenic,orfromatheroscleroticplaque,withsuddenonsetandpoorprognosis.HemodynamicDerangement&CerebralVascularDisordersCerebralInfarction45Themostcommonformofcerebrovasculardisease,accountingfor70%~80%ofallcerebralvascularaccidents“stroke”Changes:extentofischemia:

Occlusionininnercarotidartery:circlewillismaycompensatecompletely,noinfarctionOcclusioninmid-sizeartery:asmiddlecerebralA,theinfarctsmallerthanitssupplyareaduetopartialanastomosis.Occlusioninterminalarteries:leadingtosuddenareainfracted.HemodynamicDerangement&CerebralVascularDisordersCerebralInfarction46Types:

whiteinfarctredinfarct:incompleteocclusionorfrangibleemboligoingfurthertosmallvessels,resultinginbloodescapefrominjuredvascularwall.Morphologychanges:first4~12h:normalthen:ischemicneuronalchanges36-48h:swollenandsoft;demarcationbetweengrayandwhitematterbecomesblurredduetoedemathethirdday:macrophage,progressivemarkeddemarcationofthelesion1month:liquefaction,irregularcavities6month:completelyliquefied

47Braininfarctionlacunae:necrosislessthan1.5cmindiameter.TIAs(transientischemicattacks)

transientepisodeofneurologicdysfunctionlastingseveralminutes~24hoursanimportantpredictorofsubsequentinfarcts1/3patientswithTIAdevelopingclinicallysignificantinfarctswithin5years/48HemodynamicDerangement&CerebralVascularDisorders

BrainHemorrhageIntracerebralHemorrhageCause:

hypertension*congenitalsaccularaneurysms,tumors,hemorrhagicdiathesis,vasculitis,AVM,traumaPathogenesis:anoxiaofvascularwallanoxiaofperivasculartissue

CharcotBounchardmicroaneurysmsmicro-softeningfocivesselsrupturedspasmofvesselsB.P↑

hemorrhage49Changes:

Inthecenteroffoci,normalstructureisdestroyedandfilledwithRBC，atperipherymultifociofhemorrhageTheoldhemorrhagefocibecomescavitated&withhemosiderin.HemodynamicDerangement&CerebralVascularDisorders

BrainHemorrhage50CPC：B.Ghemorrhage:directedtoinsular→contralateralsemiplegiadirectedtoventricle,thalamus→deathPonshemorrhage:

pin-likepupils,persistenthighfeverorsuddendeathCerebellarhemorrhage:

severeoccipitalheadache,frequentvomitingHemodynamicDerangement&CerebralVascularDisorders

BrainHemorrhage51SubarachnoidhemorrhageThemostcommoncauseofspontaneous(nontraumatic)Ruptureofasaccular(berry)aneurysmapproximately1%ofthegeneralpopulationdifferentfromthefusiformdialtioninatheroslcerosisorinfectious(mycotic)aneurysm80%ariseatthearterialbifurcationsintheterritoryoftheinternalcarotidartery:MCA,ACMDevelopedtheinfarctofbrainparenchyma52

CPC:Abrupt,severeheadache,vomitting,lossofconsciousness

Meningealsigns

BloodyCSF50%diedinseveraldaysacutehydrocephalusherniationbraininfarctionchronic:hydrocephalus53VascularmalformationAbnormalitiesinangiogenesisinthedevelopingbrainAVM:themostcommoncausedvesselsofvariablecaliberincludingA,VHemorrhagic,calcification,reactivegliosis54TumorsofCNS

Astrocytoma（星形膠質(zhì)細(xì)胞瘤)

ThemostcommoncategoriesofbraintumorsinCNSGliomasshares40%ofbraintumors，astrocytomashares70%ofgliomas MostastrocytomasareofdiffuseinfiltrativeAstrocytomasinChildrenandAdultsLocationdifferentiationdemarcation

ofteninbrainstemcerebellumbeneathtentoriumwell,gelatinousingrossappearanceChildrenpoormostoftenabovetentoriuminhemispheresrelativelypoorgranularingrossappearancewellAdults55Morphology:pilocyticastrocytoma:commoninchildren,elongatedprocessesextendfromtwopoles(gradeI)fibrillaryastrocytomaandcytoplasmicastrocytoma:minictheiroriginalastrocytes(gradeII)gemistocyticastrocytoma:(gradeII~III)anaplasticastrocytoma:(gradeIII)glioblastomamultiform:(gradeIV)

GFAP(+)TumorsofCNS

Astrocytoma（星形膠質(zhì)細(xì)胞瘤)56Thetumororiginatesfrommenigotheliumofarachoidgranulesvillaorfibroblasts.Itsgrowsoutsidethebrain,pressingthebrainparenchymaandmayberesectedcomplete.Grossly:tumorshowssphericalorlobulated,expandingingrowthHistology:MenigothelialorsyncytialtypeFibroblasticvariantsTransitionaltypeOthersPrognosis:mostbenign,afew(15%)recursafterresection,fewundergoesmalignanttransformationEMA(+)Vimentin(+)TumorsofCNS

Meningioma（腦膜瘤)57Embryogenictumor,malignant,mostlyseeninchildrenundertenwithpoorprognosisThetumororiginatesfromprimitiveneuroecdermalcellsofvermisoroutlayersofgranularcellsofcerebellum.Thetumorshowswhitishpinkorgrayincolor,locatedatIVventricleorcerebellarhemisphere.Thecellsaresmall,primitivewithscantycytoplasm.Thenucleiareroundorcarrot-shapedwithfrequentmitoses.Sometimes,maysurroundafibrillarycorehavingrosetteformationMutualdifferentiation:GFAP（+）NF（+）TumorsofCNS

Meduloblastoma

（髓母細(xì)胞瘤)58Thebenigntumororiginatesfromschwanncell,oftenlocatedat8thnerve(acousticneurilermmoma聽神經(jīng)瘤）ortrunkofperipheralN.Slowgrowth,veryraremalignanttransformationSpherical,orlobulatedmass,white-grayincoloroncutsurface,orshowslightyellowcolorwhenmucinousdegenerationoccur.quiteoftencavitationSpindleshapedcells,inwhirlortightarrangement(AntoniAtype)orinreticulararrangement（AtoniB型）TumorsofCNS

Schwannoma（神經(jīng)鞘瘤,施萬氏瘤)59Etiology

thediseasecausebylivingpathogens,whichareinfective,endemicincertaingeographicareasandincertainseasons(傳染性，流行性，地方性，季節(jié)性）Uniquerouteofinvasion,agivenpathogenhasuniqueentranceofinvasionuniquemodeofspreadinginhostuniqueaffinityforspecialtissueororgans,causingspecialpathologicalchangesPathogenesisbacteria:endotoxinand/orexotoxinviruses:cellularand/orhumoralimmunityInfectiousDisease

CommonFeatures(共同特性）60Basicpathologicchanges:inflammation(acute/chronic)dependingonhostpathogenhost:immunitypathogen:invasionability,toxins,metabolicsubstanceevocationofallergicreactionofhostClinicalcourseIncubationperiod:

Predromalperiod:nonspecificsymptomsandsigns

Dominantperiod:diagnosticsymptomsandsignspeak

Recoveryperiod:thediseasesubsidestypical/atypical/subclinicalcourseInfectiousDisease

CommonFeatures(共同特性）免疫性61ConsequencesCompleterecoverythehostgainstemporaryorpermanentimmunityChroniccourseRecurrenceofdiseaseDeathInfectiousDisease

CommonFeatures(共同特性）62InfectiousDisease

CommonFeaturesinCNS(共同特性）Meningesdura硬腦膜

arachnoid蛛網(wǎng)膜

pia軟腦膜leptomenige（軟腦膜）63RouteofinfectionHematogenic:septicema,viremiaLocaldisseminated:openedskullfracture,sinusitis,mastoiditisDirectinfected:trauma,iatrogenicinterference(lumbarpuncture)Throughperipheralnervoussystem:rabies,HSVInfectiousDisease

CommonFeaturesinCNS(共同特性）64InflammationfeatureStereotypedReaction

neurons:degeneration,necrosissecondarydemyelinationlimitedexudationwithperivascularcuffingformation

PresenceofBBB(blood–brainbarrier)andV-RspacelimitsthespreadofinflammationAbsenceofintrinsiclymphaticsandlymphoidtissueT/Bcellsarebloodborn(exogenic)glianoduleformation

microglialnoduleinearlystage.astrocyticnoduleinlaterstage,repair65Pathogens:

Pyogenicmeningitis:

Meningococci,Hinfluenza,Pneumococci,Streptococci,

Staphylococci,EColiGranulomatousmeningitis:T.B.mycobacterium,FungiLymphocyticmeningitis:viruses,spirochetesMeningitis66EpidemicMeningococcicMeningitis

(流行性腦膜炎雙球菌性腦膜炎)ConceptPathogen:meningococci,epidemicseasons:Winter&SpringBacteriaspreadbyair(sneezeandspray),locatedatnasopharyx,mostarebacteriacarrier(15%population,inepidemicseason:70~80%)Victimsarechildren,mostyoungerthan10yrsoldBasicchanges：acutepurulentinflammation(Leptomeninge&CSF)Clinicalsymptoms&signs:fever,headache,vomiting,petechia&ecchymosisontheskin&mucosa,meningealirrigativesigns,shockinseverecasesTemporaryimmunityafterrecovery67MeningitisPathogen:

meningococci,endotoxinandcapsulearepathogenicRouteofinfection:SprayfromcarrierMucosaofnasopharyxBlood(septicemiaorbacteremia)leptomenigesmeningitisUsually5%~30%,70~80%inepidemicperiodURI,catarrh(sorethroatredandedematousmucosa,mucousdischarge)PetechiaecchymosisBacterialemboliVascularparalysis,dilation,thrombosisshockbilateralseverehemorrhageofadrenalcortex(Waterhouse-Friderichsensyndrome)(+)68MeningitisPathologicalChanges:Vassels:bacterialthrombi,thrombosis,focalhemorrhageMeninge:acutepurulentinflammation

Gross:

dura:tense,hyperemicSubarachnoidspacefilledwithgrayishyellowpusespeciallyatconvexofhemisphereatthebaseincisternaealongcircleWillis,rootsofcranial&spinalNervesLM：

Strikinglyenlargedsubarachnoidspacewithlargeamountofpurulentexudation,mainlypolys.VascularcongestionAdjacentbrainparenchymabeedematous697071Meningitis

ClinicalPathologicalCorrelation(CPC)Meningealirritationsigns

inflammationSwellingofrootsofcranial&spinalNCompressionatostioleorintervertebralholesPreventivemuscularspasmatbackinordertofixthepositionofnerverootatholesKernig’sSign(+)BrudzinskiSign(+)neckstiffnessoropisthotonus72Meningitis

CPC

HypertentionofICPInflammatoryexudeadhesionofarachnoidgranulesdecreasingabsorptionofCSFvascularcongestioncerebraledemaProjectilevomitingheadachecomaCSFchanges73Meningitis

CPCCSFChanges

Increasingpressure Turbid,protein，cellcount Pus(+),bacteria(+) Sugar74Meningitis

CPCWaterhouse-Friderichsensyndrome(華佛氏綜合征)

severesepticemialargeamountofendotoxinreleasedDICshockbilateralhemorrhageofadrenalcortexExtensiveecchymosispurpuraMildornomeningealchanges75Prognosis:quitegood.Theusageofantibioticsmakesmorethan90%patientsrecovered.Complications:

quitefewhydrocephalus:duetoinflammatoryadhesion,decreasingabsorptionofCSFcranialnerveinjury:palsy,blindness,deafnessstrabismus(III、IV、V、VII)cerebralinfarction:inflammationvesselsinflammatoryinjuryandoccludedfocaladhesivearachnoiditisMeningitis

Consequenceandprognosis

76RemarksonviralinfectionAbsoluteparasitisminhostcells,selectivevulnerabilityofdifferentgroupofneuron.Invadesneuron:cytolysis,inclusionbodyformationGliacellproliferation,multinucleargiantcell(HIV)T/Bcellimmunity77EpidemicJapaneseBEncephalitis

(流行性乙型腦炎)

Concept

ThediseaseiscausedbyJapaneseBEncephalitis(RNA)virus,mostcasesshowacuteclinicalcourse,epidemicinsummerandautumn.Victimsarechildren,teenagers,withdrowsiness,higherfever,severeheadache,convulsion,vomiting,deepcoma.BasicpathologicalchangeisalterationdominantinflammationPermanentimmunityaftersufferingofdisease78EncephalitisBJap.Pathogen：EncephalitisBJap.Virus(RNA)RouteofInfection

biteofmosquitovirusEndotheliumoflocalbloodvesselsMΦfurthermultiplicationviremianormalimmunity&BBBincompetentBBBsubclinicalinfectionneuronencephalitis79EncephalitisBJap.

PathologyGraymatterinvolved.mainlyCerebralCortex—B.G. Thalamus GrossInspection:CongestionofMeninges BrainEdemaMicroscopicfindings: Sieve-likesofteningfoci,welldemarcated Necrosisofneuronswithfoamycellformation Congestionandperivascularcuffing Proliferationofglialcells Microgliaproliferation(acutestage) Astrocyteproliferation(chronicstage)808182EncephalitisBJap

ClinicopathologicalCorrelation(CPC)inflammationcongestiondamageofendotheliumhypertensionofICPcerebraledemaHeadachevomitingtonsilarherniationDrosinessconvulsioncoma(+)pneumoniaandothercomplicationssuddendeathdegenerationandnecrosisofneuron83EncephalitisBJap

ConsequencesandComplications

HighmortalityascompareswithepidemicmeningitisComplications:mentalretardation,dementia,aphasia,paralysisofcranialorperipheralN.84SpongiformEncephalopathy(PrPDisease)

(海綿狀腦病，朊蛋白?。〤reutzfeld-Jacobdisease（CJD，克雅?。㎏uru（枯顱?。〧atalfamilialinsomnia（FFI,致死性家族性失眠癥）Gerstmann-straussletsyndrome

(GSS)Scrapi

(羊瘙癢癥)Madcowdisease

(瘋牛病newvariantCJD)Catscratchdisease

(貓抓病)

85SpongiformEncephalopathy(PrPdisease)----PathogennormalPrPc:

a30KDtransmembranousproteinofneuron.unknownfunctionwithαhelices(spiralconfiguration)codedbyageneonchromosome20,completelydisintegradedpathogenicPrPsc:

withmoreβsheets(foldedconfiguration)incompletelydisintegrated&depositinbraincausingKuruPlaqueandspongiformchangesPrPsccanduplicateitselfbytransformationfromPrPc(achallengetocentraldogma?)Casesfromgenemutation(85%)andfrominfection(15%)coexist86Gross:

inearlystage,noglosschangeswithlongstandingduration,severeatrophyLM:SpongiformEncephalopathy:Vacuolesinneuropilandneuronbodyingraymatter,mostlyfocidistributionNeuronaldeficitwithgliosis,without