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Neuroanatomy
Cerebellum

CaseScenario
A13yearoldboywithalesioninthecerebellum developedgraduallyworseningheadaches, nausea,vomiting,andunsteadinessoverthe courseof2months.Hisheadacheswereworseat nightandweremainlyintheleftoccipitalarea.A neurologicexaminationrevealedbilateral papilledema,nystagmus,mildlyslurredspeech, andirregular,ataxicmovementsthatwereworse ontheleftsidethantheright. Whatcausedthispatientsproblems?

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Objectives
Toreviewthestructureandfunctionsofthe cerebellum Toreviewsomeofthecommonclinical problemsinvolvingthecerebellum

Cerebellum
controlofpostureandvoluntarymovements influencesthesmoothcontractionofvoluntary musclesandcarefullycoordinatestheiractions, togetherwiththerelaxationoftheirantagonists eachcerebellarhemispherecontrolsmuscular movementsonthesamesideofthebodyand thatthecerebellumhasnodirectpathwaytothe lowermotorneuronsbutexertsitscontrolviathe cerebralcortexandthebrainstem

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Midsagittal sectionthroughthecerebellum.

Mainfunctions
Maintenanceofpostureandbalance Maintenanceofmuscletone Coordinationofvoluntarymuscleactivity

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Duetbetweenthecerebellumandbasal ganglia planningandfinetuningofmovements

cerebellumregulatesmovementsbycomparinganintended performancewithanactualperformance cerebellumattemptstoreduceerrorsintheexecutionofmovements

basalganglia functionintheinitiationofmovementbutalsohave cognitiveandlimbicfunctions boththecerebellumandbasalganglia mediatetheireffectsby influencinguppermotorneurons boththecerebellumandbasalgangliahaveexcitatoryinputsthat useglutamateandinhibitoryoutputsthatusegammaaminobutyric acid(GABA)asneurotransmitters basalgangliaareinfluencedbydopaminergicandcholinergic neurons,whichdonotplayaroleinthefunctionofthecerebellum cerebelluminfluencesuppermotorneuronsmainlyinthe contralateral cerebralcortexandbrainstem basalgangliainfluenceuppermotorneuronsintheipsilateral cerebralcortex

Schematicdiagramshowingthecomplementarityofthecerebellumandbasal gangliainmotorfunction

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Cerebellum:GrossAppearance
situatedintheposteriorcranialfossaandiscovered superiorlybythetentoriumcerebelli liesposteriortothefourthventricle,thepons,andthe medullaoblongata somewhatovoidinshapeandconstrictedinitsmedianpart twocerebellarhemispheresarejoinedbyanarrowmedian vermis connectedtotheposterioraspectofthebrainstembythree symmetricalbundlesofnervefiberscalledthesuperior, middle,andinferiorcerebellarpeduncles

Sagittalsectionthroughthebrainstemandthevermis ofthecerebellum

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Divisions
dividedintothreemainlobes
anteriorlobe:maybeseenonthesuperiorsurfaceofthe cerebellumandisseparatedfromthemiddlelobebya wideVshapedfissurecalledtheprimaryfissure middlelobe(posteriorlobe):largestpartofthe cerebellum,issituatedbetweentheprimaryand uvulonodular fissures flocculonodular lobe:situatedposteriortothe uvulonodular fissure

deephorizontalfissureisfoundalongthemarginofthe cerebellumseparatingthesuperiorfromtheinferior surfaces ofnomorphologicorfunctionalsignificance

Structure
StructureoftheCerebellum
Cortexoutercoveringofgraymatter Innerwhitematter Intracerebellar nucleiarethreemassesofgraymatter embeddedinthewhitematter

Cerebellarcortex
largesheetwithfoldslyinginthecoronalortransverseplane eachfoldorfoliumcontainsacoreofwhitemattercovered superficiallybygraymatter

Sectionmadethroughthecerebellumparallelwiththe medianplanedividesthefoliaatrightangles,andthecut surfacehasabranchedappearance,calledthearborvitae

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Thecerebellum.A:Superiorview.B:Inferiorview.

A:Flattenedviewofthecerebellarcortexshowingthemaincerebellarlobes,lobules,and fissures.B:Relationshipbetweenthediagramin(A)andthecerebellum.

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Layersofthecerebellarcortex
graymatterofthecortexthroughoutits extenthasauniformstructure maybedividedintothreelayers
externallayer(molecularlayer) middlelayer(Purkinjecelllayer) internallayer(granularlayer)

Cellularorganizationofthecerebellarcortex.Notetheafferentandefferentfibers.

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Layers
MolecularLayer
containstwotypesofneurons:theouterstellatecellandtheinnerbasketcell neuronsarescatteredamongdendriticarborizations andnumerousthinaxonsthatrun paralleltothelongaxisofthefolia

PurkinjeCellLayer
largeGolgitypeIneurons,flaskshapedandarearrangedinasinglelayer dendritesofthesecellsareseentopassintothemolecularlayer,wheretheyundergoprofuse branching atthebaseofthePurkinjecell,theaxonarisesandpassesthroughthegranularlayertoenter thewhitematterandterminatesbysynapsingwithcellsofoneoftheintracerebellar nuclei collateralbranchesofthePurkinjeaxonmakesynapticcontactswiththedendritesofbasket andstellatecellsofthegranularlayerinthesameareaorindistantfolia fewofthePurkinjecellaxonspassdirectlytoendinthevestibularnucleiofthebrainstem

GranularLayer
packedwithsmallcellswithdenselystainingnucleiandscantycytoplasm eachcellgivesrisetofourorfivedendrites,whichmakeclawlike endingsandhavesynaptic contactwithmossyfiberinput axonofeachgranulecellpassesintothemolecularlayer,withbranchesrunningparalleltothe longaxisofthecerebellarfoliumknownasparallelfibers mostoftheparallelfibersmakesynapticcontactswiththespinous processesofthedendrites ofthePurkinjecells neuroglial cellsarefoundthroughoutthislayer scatteredthroughoutthegranularlayerareGolgicells

Photomicrographofacrosssectionofacerebellarfolium,showingthethreelayersofthe cerebellarcortex.

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Cerebellarcortexneurons

Functionalareas
Vermis
cortexofthevermis influencesthemovementsofthelong axisofthebody,namely,theneck,theshoulders,the thorax,theabdomen,andthehips

Intermediatezone
Immediatelylateraltothevermis areahasbeenshowntocontrolthemusclesofthedistal partsofthelimbs,especiallythehandsandfeet

lateralzone
concernedwithplanningofsequentialmovementsofthe entirebody involvedwiththeconsciousassessmentofmovement errors

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Topographicarrangementofskeletalmusclescontrolledby partsofthecerebellum

Somatosensoryprojectionareasinthecerebellarcortex

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Cerebellarnuclei
massesofgraymatterareembeddedinthewhitematterofthe cerebellumoneachsideofthemidline
Dentate
largestofthecerebellarnuclei shapedlikeacrumpledbagwiththeopeningfacingmedially interiorofthebagisfilledwithwhitemattermadeupofefferentfibersthat leavethenucleusthroughtheopeningtoformalargepartofthesuperior cerebellarpeduncle

Emboliform
ovoidandissituatedmedialtothedentatenucleusGlobose

globose nucleus
oneormoreroundedcellgroupsthatliemedialtotheemboliform nucleus

Fastigial
liesnearthemidlineinthevermis andclosetotheroofofthefourthventricle largerthantheglobose nucleus

Positionoftheintracerebellar nuclei

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Partsofthecerebellarcortexandthedeepcerebellarnucleilinked togetherbyPurkinjecells

Functionalorganizationofthecerebellarcortex.Thearrowsindicatethedirectiontakenbythe nervousimpulses.

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Nervefibers
Thewhitematterismadeupofthreegroupsoffibers
Intrinsic
donotleavethecerebellumbutconnectdifferentregionsoftheorgan Someinterconnectfoliaofthecerebellarcortexandvermis onthesameside othersconnectthetwocerebellarhemispherestogether

Afferent
formthegreaterpartofthewhitematterandproceedtothecerebellarcortex enterthecerebellummainlythroughtheinferiorandmiddlecerebellarpeduncle

Efferent
constitutetheoutputofthecerebellumandcommenceastheaxonsofthePurkinjecells ofthecerebellarcortex greatmajorityofthePurkinjecellaxonspasstoandsynapsewiththeneuronsofthe cerebellarnuclei(fastigial,globose,emboliform,anddentate)andaxonsoftheneurons thenleavethecerebellum fewPurkinjecellaxonsintheflocculonodular lobeandinpartsofthevermis bypassthe cerebellarnucleiandleavethecerebellumwithoutsynapsing Fibersfromthedentate,emboliform,andglobose nucleileavethecerebellumthrough thesuperiorcerebellar

Inflowtractstothecerebellum
twomainlinesofinputtothecortexthatare excitatorytothePurkinjecells
Climbingfibers
terminalfibersoftheolivocerebellar tracts ascendthroughthelayersofthecortexlikeavineonatree terminateinthemolecularlayerbydividingrepeatedly

Mossyfibers
terminalfibersofallothercerebellarafferenttracts multiplebranchesandexertamuchmorediffuseexcitatory effect singlemossyfibermaystimulatethousandsofPurkinjecells throughthegranulecells

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CerebellarCorticalMechanisms
Climbingfibers provideadirectpowerfulmonosynapticexcitatory inputtoPurkinjecellsandalsoinfluencetheactivityofthedeep cerebellarnucleithroughaxoncollaterals
encirclethecellbodiesandproximaldendritesofPurkinjecells
synapsewithupto10Purkinjecells Purkinjecellreceivesonlyasingleclimbingfiber

fibersareaxonsofneuronsfoundintheinferiorolivary complexof nucleiinthemedulla inferiorolivesamplessomatosensory,visual,auditory,andmotor informationandactsasamovementerrordetectorforPurkinjecells climbingfibersgenerateprolongedcalciumconductanceinPurkinje cells,whichresultsintheproductionofcomplexspikeaction potentialsinPurkinjecellaxons

complexspikesgeneratedinPurkinjecellsmayresultinlongtermdepression inthestrengthofparallelfibers(axonsofgranulecells),whichgeneratesimple spikesatthesametimeinPurkinjecellaxons longtermdepressioneffectsintheparallelfibersarethebasisformotoror nondeclarative learninginthecerebellum

CerebellarCorticalMechanisms
Mossyfibers provideanindirectdiffuseexcitatoryinputtoPurkinje cells
excitegranulecells,whichinturngiverisetoparallelfiberaxonsthat projecttoPurkinjecelldendrites Purkinjecelldendritesmaybecontactedbyasmanyas1million parallelfiberaxons ParallelfibersproduceasteadystreamofsimplespikesinPurkinjecell axons Mossyfiberstothespinocerebellum arisefrommusclestretch receptorsandGolgitendonorgansinskeletalmusclesandprojectto thecerebelluminspinocerebellar tracts
dorsalspinocerebellar tractarisesfromClarkesnucleusfromtheT1through L2spinalcordsegmentsandrelaysinformationaboutthebiomechanicalstate ofmusclespindlesandGolgitendonorgansinskeletalmusclesinthelower limb cuneocerebellar tractarisesfromneuronsintheexternalcuneate nucleusin themedullaandrelaysinformationaboutmusclespindlesandGolgitendon organsinskeletalmusclesintheupperlimb ventralspinocerebellar tract(VSCT)arisesfromspinalbordercellsadjacentto laminaVIIofthespinalcordandconveysinformationtothecerebellumabout skeletalmuscleactivitygeneratedbyuppermotorneurons

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CerebellarCorticalMechanisms
Mossyfiberstothecerebrocerebellum arise frompontine nuclei,whichareinfluencedby axonsofneuronsinthecerebralcortex Mossyfiberstothevestibulocerebellum arise fromthevestibularnerveandthevestibular nuclei

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CerebellarPeduncles
Cerebellumisconnectedtothebrainstembythe inferior,middle,andsuperiorcerebellar peduncles,whichconveyaxonsintoandoutof thecerebellum
superiorcerebellarpedunclemainlyconveysaxons outofthecerebellumfromthedeepcerebellarnuclei middlecerebellarpeduncleconveysaxonsfromthe pontine nucleiintothecerebellum inferiorcerebellarpeduncleconveysaxonsbothinto thecerebellumfromthespinalcordandbrainstem andoutofthecerebellumfromthedeepcerebellar nuclei

Cerebellarpedunclesconnectingthecerebellumtotherestofthecentralnervoussystem

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Cerebellaroutflowtracts
Outputofthecerebellarcortexisprovided exclusivelybyaxonsofPurkinjecells
Purkinjecellaxonsleavethecerebellarcortexand projecttothedeepcerebellarnucleiorthevestibular nucleiinatopographicallyorderedfashion
spinocerebellum (vermis andintermediatehemisphere) influencetheactivityofthefastigial andinterposednuclei. vermis projecttothefastigial nuclei intermediatehemisphereprojecttotheinterposed(globose andemboliform)nuclei cerebrocerebellum (thelateralpartofthehemisphere) projecttothedentatenucleus vestibulocerebellum (flocculonodular lobe)projecttothe fastigial nucleusandtothelateralandmedialvestibular nucle

Cerebellaroutflowtracts
Axonsofdeepcerebellarnucleiexitthecerebellummainly inthesuperiorcerebellarpeduncleandinfluenceupper motorneuronsinthecerebralcortexandbrainstem Axonsfromthedentate,fastigial,andinterposednucleiexit inthesuperiorcerebellarpeduncle,crossthemidlineinthe midbrain,andterminateintheventrallateralnucleusof thethalamus thalamusprojectstothemotorcortexandinfluences corticospinal andcorticobulbar uppermotorneurons Axonsfromtheinterposednucleialsoprojecttothered nucleusandinfluenceuppermotorneuronsinthe rubrospinal tract Axonsfromthefastigial nucleiinfluencereticulospinal and vestibulospinal uppermotorneuronsinthereticular formationandvestibularnuclei

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Cerebellarafferentfibers
AfferentFibersFromtheCerebralCortex
corticopontocerebellar pathway
arisefromnervecellsinthefrontal,parietal,temporal,andoccipitallobesof thecerebralcortexanddescendthroughthecoronaradiata andinternal capsuleandterminateonthepontine nuclei pontine nucleigiverisetothetransversefibersofthepons,whichcrossthe midlineandentertheoppositecerebellar

cerebroolivocerebellar pathway
arisefromnervecellsinthefrontal,parietal,temporal,andoccipitallobesof thecerebralcortexanddescendthroughthecoronaradiata andinternal capsuletoterminatebilaterallyontheinferiorolivary nuclei inferiorolivary nucleigiverisetofibersthatcrossthemidlineandenterthe oppositecerebellarhemispherethroughtheinferiorcerebellarpeduncle

cerebroreticulocerebellar pathway
arisefromnervecellsfrommanyareasofthecerebralcortex,particularlythe sensorimotorareas descendtoterminateinthereticularformationonthesamesideandonthe oppositesideintheponsandmedulla cellsinthereticularformationgiverisetothereticulocerebellar fibersthat enterthecerebellarhemisphereonthesamesidethroughtheinferiorand middlecerebellarpeduncles

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PrincipalAfferentSystemstothe Cerebellum

Cerebellarafferentfibersfromthecerebralcortex.Thecerebellarpedunclesareshownas ovoiddottedlines.

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Cerebellarafferentfibers
Spinalcordsendsinformationtothe cerebellumfromsomatosensoryreceptorsby threepathway
anteriorspinocerebellar tract posteriorspinocerebellar tract cuneocerebellar tract

Cerebellarafferentfibersfromthespinalcordandinternalear.Thecerebellarpedunclesare shownasovoiddottedlines.

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AnteriorSpinocerebellar Tract
axonsenteringthespinalcordfromtheposteriorrootganglion terminatebysynapsingwiththeneuronsinthenucleusdorsalis (Clarke'scolumn)atthebaseoftheposteriorgraycolumn Mostaxonsoftheseneuronscrosstotheoppositesideandascend astheanteriorspinocerebellar tractinthecontralateralwhite column someoftheaxonsascendastheanteriorspinocerebellar tractin thelateralwhitecolumnofthesameside fibersenterthecerebellumthroughthesuperiorcerebellar peduncleandterminateasmossyfibersinthecerebellarcortex collateralbranchesthatendinthedeepcerebellarnucleiarealso givenoff thosefibersthatcrossovertotheoppositesideinthespinalcord couldcrossbackwithinthecerebellum

PosteriorSpinocerebellar Tract
axonsenteringthespinalcordfromtheposteriorrootganglion entertheposteriorgraycolumnandterminatebysynapsingonthe neuronsatthebaseoftheposteriorgraycolumn knowncollectivelyasthenucleusdorsalis (Clarke'scolumn) axonsoftheseneuronsentertheposterolateral partofthelateral whitecolumnonthesamesideandascendastheposterior spinocerebellar tracttothemedullaoblongata thetractentersthecerebellumthroughtheinferiorcerebellar peduncleandterminatesasmossyfibersinthecerebellarcortex collateralbranchesthatendinthedeepcerebellarnucleiarealso givenoff posteriorspinocerebellar tractreceivesmusclejointinformation fromthemusclespindles,tendonorgans,andjointreceptorsofthe trunkandlowerlimbs

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Cuneocerebellar Tract
fibersoriginateinthenucleuscuneatus ofthemedulla oblongataandenterthecerebellarhemisphereonthe samesidethroughtheinferiorcerebellarpeduncle fibersterminateasmossyfibersinthecerebellarcortex collateralbranchesthatendinthedeepcerebellar nucleiarealsogivenoff cuneocerebellar tractreceivesmusclejointinformation fromthemusclespindles,tendonorgans,andjoint receptorsoftheupperlimbandupperpartofthe thorax

CerebellarAfferentFibersFromtheVestibularNerve
receivesinformationfromtheinnerearconcerning motionfromthesemicircularcanalsandposition relativetogravityfromtheutricleandsaccule vestibularnervesendsmanyafferentfibersdirectlyto thecerebellumthroughtheinferiorcerebellar peduncleonthesameside othervestibularafferentfiberspassfirsttothe vestibularnucleiinthebrainstem,wheretheysynapse andarerelayedtothecerebellum alltheafferentfibersfromtheinnerearterminateas mossyfibersintheflocculonodular lobeofthe cerebellum

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CerebellarEfferentFibers
entireoutputofthecerebellarcortexisthroughthe axonsofthePurkinjecells mostaxonsofthePurkinjecellsendbysynapsingon theneuronsofthedeepcerebellarnuclei axonsoftheneuronsthatformthecerebellarnuclei constitutetheefferentoutflowfromthecerebellum fewPurkinjecellaxonspassdirectlyoutofthe cerebellumtothelateralvestibularnucleus efferentfibersfromthecerebellumconnectwiththe rednucleus,thalamus,vestibularcomplex,and reticularformation

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EfferentFibers
GloboseEmboliformRubral Pathway Dentothalamic Pathway Fastigial VestibularPathway Fastigial ReticularPathway

Cerebrocerebellar circuitry illustratinghowPurkinjecellsin theparavermal andlateral hemispheresarelinkedtoupper motorneurons.

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Cerebellarefferentfibers.Thecerebellarpedunclesareshownasovoiddottedlines.

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Cerebellumservingasacomparator

Someofthemainconnectionsofthecerebellum

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Clinicalcorrelations:Signsand symptoms Hypotonia

diminishedmuscletone

PosturalChangesandAlterationofGait
headisoftenrotatedandflexed shoulderonthesideofthelesionislowerthanonthenormalside widebasedgait stiffleggedtocompensateforlossofmuscletone lurchesandstaggerstowardtheaffectedsidewhenwalking

Ataxia
lossofthecoordinatedmuscularcontractionsrequiredfortheproductionofsmooth movements

Dysdiadochokinesia
aninabilitytomakeordifficultymakingrapidlyalternatingorsuccessivemovements

DisturbancesofReflexes
movementproducedbytendonreflexestendstocontinueforalongerperiodoftimethan normal

DisturbancesofOcularMovement
Nystagmus ataxiaoftheEOM

DisordersofSpeech
Dysarthria ataxiaofthelaryngealmuscles

Clinicalcorrelations:Syndromes
Vermis Syndrome(e.g.duetomedulloblastoma)
Involvementoftheflocculonodular loberesultsinsignsandsymptoms relatedtothevestibularsystem vermis isunpairedandinfluencesmidlinestructures,muscle incoordinationinvolvestheheadandtrunkandnotthelimbs tendencytofallforwardorbackward difficultyinholdingtheheadsteadyandinanuprightpositionin holdingthetrunkerect

CerebellarHemisphereSyndrome(e.g.duetotumor)
usuallyunilateralandinvolvemusclesonthesideofthediseased cerebellarhemisphere movementsofthelimbs,especiallythearms,aredisturbed swayingandfallingtothesideofthelesionoftenoccur dysarthriaandnystagmus arealsocommonfindings

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CommonDiseasesInvolvingthe Cerebellum
acutealcoholpoisoning congenitalagenesisorhypoplasia Trauma Infections Tumors multiplesclerosis vasculardisorderssuchasthrombosisofthe cerebellararteries poisoningwithheavymetals

Caseproblemsolving
CHIEFCOMPLAINT A13yearoldboywasbroughttothepediatrician'soffice becauseof2monthsofprogressiveleftoccipitalheadaches,nausea, slurredspeech,andunsteadiness. HISTORY Thepatientwaswelluntil2monthspreviously,whenhebegan havingheadaches,whichwereinitiallyattributedtoasinusinfection. Theheadachesgraduallyworsened,withheadachemainlyintheleft occipitalarea,andsometimesaccompaniedbynauseaandvomiting, butnovisualchanges.Theheadacheswereworseatnightandinthe earlymorninghours.Histeachersnoticedthatoverthepastfew monthshehadhadsomedifficultyconcentratingandlearningnew materialatschool.Duringtheweekpriortopresentationhismother notedincreasinggaitinstabilityandmildlyslurredspeechanddecided tobringhimtothepediatrician.

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PHYSICALEXAMINATION Vitalsigns:T=98'F,P=90,BP=130/88,R=16.Neck:Supple. Lungs:Clear.Heart:Regularratewithnomurmurs.Abdomen:Soft, nontender.Extremities:Normal. Neurologicexam: MENTALSTATUS:Alertandorientedx3.Speechfluentwith normalrepetitionandcomprehension.CRANIALNERVES:Pupilsequal roundandreactivelight.Visualfieldsfull.Fundihadblurreddisc margins(mildpapilledema)bilaterally.Extraocular movementswere full,buttherewashorizontalnystagmus onlateralgazebilaterally, verticalnystagmus onupgaze worsethandowngaze.Inaddition,the vestibuloocularreflexwasnotfullysuppressedbyvisualfixation. Facialsensationandcornealreflexesintact.Facesymmetrical.Hearing intacttowhisperbilaterally.Speechslightlyslurredandwithan irregularrate.Normalpalatemovementsandgagreflex.Normal sternomastoid andtrapeziusstrength.Tonguemidline.Motor:Nodrift. Normaltone.5/5powerthroughout. Reflexes:

COORDINATION:Markeddysmetria onfingertonose testing,worseontheleft,withapproximately2inchesof error.Therewasalsodysdiadochokinesia,withinaccurate rapidalternatingmovements,worseontheleftside.Heel toshinmovementswereataxicontheleftbutnormalon theright. GAIT.Widebased,withfeetapproximately2feetapart, andunsteady,staggeringtotheleft.Unabletoperform tandemgait.OntheRombergtestwithfeet4inchesapart therewasnoworseningofunsteadiness(unabletostand withfeettogetherevenwitheyesopen). SENSORY:Intactlighttouch,pinprick,vibration,andjoint positionsense.Intactgraphesthesia andstereognosis.

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Questions
1.Onthebasisofthesymptomsandsigns mentionedabove,whereisthelesion? 2.Whatisthemostlikelydiagnosis,andwhat aresomeotherpossibilities?

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