HydrocephalusandAnomaliesoftheCNS

****ForthetopiconNeuroembryology,kindlyfocusonthetableprovided.Thisisjustan
outline,pleasereadyourbook(MENKESCHILDNEUROLOGYChapter5Topicon
MalformationsoftheNervousSystem)
Major Events in Human
Brain Development
Neurulation

Prosencephalic

Neuronal
Proliferation

Neuronal
Migration

Peak Age of Occurence

34wks
(Neuraltube
Brain&Spinalcord
Neuralcrest
PNS&
Leptomeninges)
23mos
(Pairedcerebral
Hemispheres,
LateralVentricle,Basalganglia,Thalami,
OpticNerves/chiasm
CorpusCallosum,
SeptumPellucidum)
34mos
(Fullcompletementof
neuronsin
cerebral
hemispheres)
35mos
(Formationfrom
4layeredembryonic
cortex>6layered
adultcortex)

Organization

5postnatalyears
(Synaptogenesis
programmed
Celldeath)

Myelination

BirthPostnatalyrs
(Formationofmyelin>
electrical
conduction)

Congenital Anomalies
Encephalocoele
Myelomeningocoele
Anencephaly
Dermalsinus
Tetheredcord
Syringomyelia
Diastematomyelia
Holoprosencephaly
Dandywalker

Aqueductal
Stenosis
Hydrocephalus
Schizencephaly
Colpocephaly
Lissencephaly
Agenesisofcorpus
callosum
Porencephaly
PerinatalInsults
ICH/Hypoxic
Ischemic
Encephalopathy(HIE)
Tumors
CNSInfections
PerinatalInsults
ICH
Tumors
CNSInfections

Anencephaly

aftertheonsetofneuralfolddevelopment(16days)butbeforeclosureoftheanterior
neuropore(24to26days).

Thestimulusisnonspecificbecauseavarietyofinsultshavebeenimplicated.These
include:

drugs

Infections

chemicaldisorderssuchasmaternaldiabetesorfolicaciddeficiency

andirradiation

fourbasicdefects:

(a)Adefectivenotochordandprechordalmesoderm

(b)Failureofdevelopmentofthemeningesandcranialbonesexposesthebrain
toamnioticfluid,withsubsequentencephaloclasticdegenerationofforebrain
germinalcells.

c)Paraxialmesodermfailstodifferentiateintowellformedsomitesandhence
intosclerotomes(primordiumforthebaseoftheskullandvertebrae.)

(d)Afailureofprosencephalicandmesencephalicneuralcrestformationand
migrationresultsinmidfacialhypoplasiawithhypotelorism

Examinationofthenervoussystemshows:

SC,brainstem,andcerebellumaresmall.

Descendingtractswithinthespinalcord,particularlythecorticospinaltract,are
absent.

Abovethemidbrain,glialandvasculartissuewithremnantsofmidbrainand
diencephalonexist.

Pituitaryisabsent,withsecondaryadrenalhypoplasia.

Opticnervesareabsentbuttheeyesarenormal,indicatingthattheanterior
cephalicendoftheneuraltube,whencetheopticvesiclesspring,closedand
diverticulatedproperly.

Calvariumfailstodevelop,andthefrontalandparietalbonesarepartiallyabsent;

Epidemiology

AnencephalyisthemostcommonmajorCNSmalformationintheWest

Incidenceincreaseswithincreasingmaternalageanddecreasingsocioeconomic
status.

37xmorefrequentinfemalethaninmalenewborns

Recurrencerateinfamilieswithanaffectedchildis35%

ClinicalManifestations

Anencephalicpatientsdonotsurviveinfancy

Duringtheirfewweeksoflife,theyexhibitslow,stereotypedmovementsand
frequentdecerebrateposturing.

Head,facial,andlimbmovementscanbespontaneousorpaininduced.

TheMororeflexandsomebrainstemfunctionsandautomatisms,suchas
sucking,rooting,andrightingresponses,arepresentandaremorereadilyand
morereproduciblyelicitedthaninhealthyinfants

Thepresenceofanencephalyandotheropenneuraltubedefectscanbe
predictedbymeasuringfetoprotein(AFP)inamnioticfluidormaternalserum.

AFPisthemajorserumproteininearlyembryoniclife,representing90%oftotal
serumglobulin

NormalAFPinadultserumislessthan10ng/mL.Innormalmaternal
serumandamnioticfluid,itrangesfrom15to500ng/mL.

At15to20wksAOG,anAFPconcentrationof1,000ng/mLorgreater
stronglysuggestsanopenneuraltubedefect,andthecurrentscreening
ofserumdetects79%ofcasesofopenspinabifidaat16to18weeks

AmnioticfluidAFPobtainedbetween15and20weeks'gestationismostspecific

however,closedneuraltubedefectssuchasskin covered
lipomyelomeningoceles,encephaloceles, andmeningocelesgo
undetected.

Motherswhohavebornoneormorechildrenwithneuraltubedefects,spinal
dysraphism,ormultiplevertebralanomalies;whohaveafamilyhistoryofanyof
thesedisorders;orwhoaresurvivingpatientswithspinabifidaareatriskfor
bearingchildrenwithneuraltubedefectsandshouldundergoscreening.

Supplementationofthematernaldietwithfolicacidorwithamultivitamin
preparationthatcontainsfolicacidevenbeforeconceptionhasbeenproposed
topreventneuraltubedefects

Folicacid,ascorbicacid,andriboflavin>givenfromatleast28daysbefore
conceptionuptothesecondmissedmenstrualperiod,reducedtherecurrence
ratesforneuraltubedefects

from4.2%to0.5%inmotherswithapreviousneuraltubedefect
pregnancy

from9.6%to2.3%inmotherswhohadgivenbirthtotwoormore
offspringwithneuraltubedefects

Meningomyelocele(SpinaBifida)andEncephalocele(CraniumBifidum)

failureofbonefusion;resultisabonycleftthroughwhichthemeningesand
varyingquantitiesofbrainorspinalcordtissueprotrude.
Incraniumbifidum,theneuralherniationistermedencephaloceleandcan
consistofbrainparenchymaandmeningesoronlyofmeninges.
Inspinabifida,theherniationiscalledmeningoceleormeningomyelocele
TERMINOLOGIES
Spinabifidaoccultaisaminorfusionfailureoftheposteriorvertebral
archesunaccompaniedbyherniationofmeningesorneuraltissue.
Spinabifidacysticacollectivelydesignatesmeningocele,
meningomyelocele,andothercysticlesions
Rachischisisreferstoasevereconditionwithanextensivedefectofthe
craniovertebralbonewithexposureofthebrain,spinalcord,and
meninges.
Myeloschisisisdefectinthetissuesoverthelowerspinalcord.Neural
tissueisexposedatthesurfaceasaflat,redlesionwithavelvety
appearanceoverthesacralregion,withoutprotrudingasa
myelomeningocelesac
Disordersofinduction;theyalsoareassociatedwithmajorabnormalitiesof
cellularmigration
timespecific>whichiswhythemostcommonsitesforthelesionin
survivingchildrenareeitherlumbosacraloroccipital,thesebeingthelast
levelsatwhichneuraltubeclosurenormallyoccurs
Asimplemeningoceleresultswhentheinsultoccursafterthespinalcordhas
formed,whereasamyelomeningocelearisesfromanearlierinsult,whichmust
occurbeforeclosureoftheposteriorneuropore(i.e.,before26to28days'
gestation)
95%aremyelomeningocelesand5%aremeningoceles
Alumbarorlumbosacraldefectismostcommon;itcorrespondstothesiteof
theposteriorneuroporeclosure.

Cervicalandthoracicmeningoceleshavenarrowbasesandareusuallynot
associatedwithhydrocephalus.
Bycontrast,90%ormoreoflumbosacralmyelomeningocelesareaccompanied
byChiaritypeIImalformationsandhydrocephalus
Defectsofcellularmigrationinthecerebralhemispheresareextremelycommon
>heterotopia,schizencephaly,gyralanomalies,agenesisofthecorpus
callosum,andmesodermalectopia
Anumberofmesodermallesionsaccompanytheectodermaldefects>widened
spinalcanal,posteriorarchesmalformed,mishapenvertebralbodieswith
resultingkyphosisorscoliosis.
Ribanomalies
Skulldefectsinthemembranousbonesofthecalvarium>condition
termedlacunarskullorcraniolacunia
Deformitiesofthelowerextremitiesarecommonandareoftwotypes.
Inthefirsttype,thevariousclubfootandrockerbottomfootdeformities
resultfromtheunopposedactionoftheintrinsicfootmusclesorthe
musclesattheanklejoint.
Inthesecondtype,thedeformitiesarepositional;theyresultfrom
intrauterinepressureontheparalyticlimbs.

SpinaBifidaOcculta

Noherniationofthemeningesispresentandtheskinofthebackiscompletely
epithelialized

Radiographyrevealsavarietyofdeformities

Theseskinandboneabnormalitiesareindicationsthatthecordandnerverootsare
malformedalso.

themostcommonofwhicharewideningofthespinalcanal,fusionofthe
vertebralbodies,fusedandmalformedlaminae,spinabifida,and,sometimes,a
midlinebonemasswithinthespinalcanal.

Theremaybealocalizeddoublingofthecord(diplomyelia),asagittalsplittingof
thecord(diastematomyelia),absentoradherentnerveroots,oranintradural
lipomaattachedtothecord.

Theselesionsmustberecognizedbecausetheycancauseprogressivelossofneural
functioningduringthechildhoodgrowthspurt

CraniumBifidum

Severaltypesofsimplemidlineorpairedparamedianskulldefectsaregroupedunder
thetermcraniumbifidumoccultum.

Excessivelylargeanteriorandposteriorfontanelles

Encephaloceleisamuchmoreseriouscondition,postulatedtorepresentadefectinthe
closureoftheanteriorneuropore

Onexamination,isusuallyfullyepithelialized,althoughtheskincanbedysplastic.Its
sizerangesfromtheinsignificanttoasacthatcanrivalthecalvariuminsize.

Pedunculatelesionsarelesslikelytocontainneuraltissuethansessilelesions.

Transilluminationcanprovideanindicationofneuraltissueinthesac

NeuroimagingstudiesaredefinitiveanddetectassociatedCNSabnormalities

Meningocele

Herniationofonlythemeningesthroughthedefectiveposteriorarches

Meningomyelocelesaccontains,inadditiontocutaneousandsubcutaneoustissues,
meninges,fragmentsofbone,cartilage,andfibroustissue,andneuralelements.

Theneuraltissueincludesnerverootsandsometimesdysplasticspinalcordfragments
andpoorlydifferentiatedneuroepithelium.

Ingeneral,meningocelesarefullyepithelializedandtendtobemorepedunculatedthan
sessilelesions

Somemeningocelescontainasignificantcomponentofadiposetissueandare
designatedlipomeningoceles.

Thesehaveapoorerlongtermprognosisbecausethelipomatousportionoften
envelopsnerverootsofthecaudaequinaandisnoteasilydissectedfromthe
rootsatthetimeofsurgerywithoutsacrificingrootsandcreatingamajor
neurologicdeficitinthelowerlimbs

ClinicalManifestationsMeningomyelocele(SpinaBifidaCystica)

Atbirth,spinabifidacysticacanassumeavarietyofappearances.Theserange
fromcompleteexposureofneuraltissuetoapartiallyepithelializedmembrane

Usually,thesaciscoveredbyathinmembranethatispronetotears,through
whichtheCSFleaks.

Ofdefects,95%aremyelomeningocelesandproduceneurologicdysfunction
correspondingtotheiranatomiclevel

Lesion
LevelSpinalRelatedDisability
AboveL3
Completeparaplegiaanddermatomalparaanesthesia

Bladderandrectalincontinence
Nonambulatory
L4andbelow SameasforaboveL3exceptpreservationofhipflexors,hipadductors,knee
extensors
Ambulatorywithaids,bracing,orthopedicsurgery
S1and
SameasforL4andbelowexceptpreservationoffeetdorsiflexorsandpartial
below
preservationofhipextensorsandkneeflexors
Ambulatorywithminimalaids
S3and
Normallowerextremitymotorfunction
below
Saddleanesthesia
Variablebladderandrectalincontinence

MYELOMENINGOCOELE

Hydrocephalusassociatedwithlumbosacralmyelomeningoceles>typeIIChiari
malformation

Itismanifestatbirthin50%to75%ofcases.Inapproximately25%ofinfants
withthiscondition,theheadcircumferenceisbelowthefifthpercentile

Intheseinfantsandinthegroupwhoseheadcircumferenceisnormalatbirth,the
ventriclesaredilatedatbirth.Thisfindingsuggeststhathydrocephalusalmostalways
precedesoperativeclosureofthemyelomeningocelesac

Clinicalmanifestations

Clinicalsignsofprogressivehydrocephalusaccompanyingamyelomeningoceleinclude
an

abnormalincreaseinheadcircumference

fullfontanelle

spreadingofsutures

hyperresonantcalvarialpercussionnote,

dilatedscalpveins

deviationoftheeyesbelowthehorizontal(settingsunsign)

strabismus,andirritability.

MRIstudieshavebecomethedefinitivediagnosticprocedurefortheevaluationofspina
bifidacysticaandthevariousotherdysraphicconditions

Thoughsomeinfantswithlumbosacrallipomahavenoneurologicdeficit,itismore
commontofindthelowerlumbarorsacralsegmentsaffected,withresultantmotoror
sensorylossinthefeetandbladderandboweldysfunction

Surgicalinterventionisadvisedatapproximatelyage3months,notsimplyforcosmetic
reasons,but,moreimportant,todecompressanduntetherasfaraspossiblethespinal
cord,thuspreventingprogressiveneurologicdysfunction.

Aconsiderableproportionpresentwithurologicsymptoms,notablyincontinence,
soiling,andrecurrenturinarytractinfections

Renaldiseaseisthemostcommoncauseofmorbidityandmortalityafterage3years

Thethreefundamentalurologicproblemsareinfection,incontinence,andretrograde
highpressureontheupperurinarytract,producinghydronephrosisandhydroureter.

SpinaBifidaOcculta

Referstoasimplebonyanomalyinwhichtherehasnotbeencompletefusionofthe
laminaeinthemidline

generallyinvolvestheposteriorarchesofL5andS1

itisusuallyasymptomaticandisfoundincidentallyonradiographicexamination,the
skinofthelowmidbackregioncanmanifestahairytuft,dimple,dermalsinus,ormass
causedbyasubcutaneouslipomaorteratoma

CraniumBifidumOccultum

Thedegreeofneurologicanddevelopmentaldamagedependsonthe:

thequantityofprotrudedtissue,

thedegreeofhydrocephalus,

theextentofhindbrainlesionsorcerebralhemispheredysplasiasthatresult
fromtheassociateddisorderofcellularmigrationandorganization

Treatment:SPINABIFIDACYSTICA

Skinclosurewithin24hoursofbirthandnolaterthan1weekofagereducesmortality
andmorbidityfrommeningitisandventriculitis

Earlysurgeryundoubtedlypreventsfurtherlossoffunctioningneuraltissueasaresult
oftraumaandinfection.Additionally,promptclosureresultsinshorterhospitalization,
easiercareoftheinfant,andpsychologicalbenefittothefamilyandnursingstaff

Itisimportanttoemphasizetothefamilythatclosingthedefectdoesnotreversethe
neurologicimpairmentalreadypresent,andthatoftenmuchadditionaltreatmentwill
benecessary.

Treatment:SpinaBifidaOcculta.

Clearindicationsforsurgeryinclude

thefindingofprogressiveneurologicdefects,

thepresenceofanassociatedtumororadermalsinusthatcarriestheriskof
meningitisordeepabscess,

historyofmeningitis

Whenvertebralcolumnmalformationisdisclosedontheradiographicfilms,followup
imagingstudiesarenecessary.

Shouldtheserevealanabnormalattachmentofthecordornerveroots,operative
interventiontoremovethatattachmentisrequiredasaprophylacticmeasure,even
whennohistoryofprogressivedamageexists.

Treatment:Meningocele

IfthemeningoceleisfullyepithelializedandnotdrainingCSFandiftheskinoverthesac
isnotulcerated,immediaterepairisnotneededandsurgerycanbedeferredforseveral
months.

Imagingstudiesofthebrainaresuggestedtoassessventricularsizeandtodetectthose
fewinfantswhodevelophydrocephalus.

Treatment:CraniumBifidumCysticum.

requiresimmediaterepairifCSFisleakingorifthedefectisnotcoveredbyskin.

Ifthedefectiscompletelyepithelialized,itshouldbeclosedbeforetheinfant's
dischargefromthehospital;ifthelesionissmallandlessunsightly,closurecanbe
postponeduntillaterinthefirstyearoflife

Whenthelesionistenderandasourceofdistresstotheinfant,earlysurgicalrepairis
indicated.

Prognosis

Some45%ofinfantswithmyelomeningoceleswhoarenottreatedsurgicallydiewithin
thefirstyearoflife,mostoftenasaconsequenceofhydrocephalusorCNSinfections.

Ofthesurvivors,approximately50%areminimallyhandicapped.Therestareseverely
handicapped.Withoperation,approximately90%surviveintotheirteens,butlessthan
33%oftheseareminimallyhandicapped

Whendeathoccursafterearlychildhood,itisusuallytheresultofurinarytractinfection
withsepsisandrenalfailure.

ChiariMalformations

characterizedbycerebellarelongationandprotrusionthroughtheforamenmagnum
intothecervicalspinalcord.

Pathogenesis

Thetractiontheorysuggeststhattetheringofthespinalcordpullsthecaudalmedulla
oblongataandposteriorcerebellumthroughtheforamenmagnumasthespinalcolumn
growsfasterthanthespinalcord

Thepulsiontheorysuggestsfetalhydrocephaluscausespressureanddisplacement
downwardofthebrainstemandcerebellumduringdevelopment

ThehydrodynamicoroligoCSForsocalledunifiedtheoryofChiarimalformations
attributesapaucityofsufficientfluidtodistendthecerebralvesiclesearlyincerebral
development

Thecrowdingtheoryassertsthattheposteriorfossaitselfistoosmallandtheconfined
neuralstructureswithinitareforcedthroughtheforamenmagnumastheygrow

Thebirthtraumatheory

Themoleculargenetichypothesisthatthemalformationiscausedbyectopicexpression
ofhomeoboxgenes

TypesofChiariMalformations

TypeI.clinicallytheleastsevere,themedullaisdisplacedcaudallytothespinal
canalandtheinferiorpoleofthecerebellarhemispheresisprotrudedthrough
theforamenmagnumintheformoftwoparallel,tonguelikeprocesses.This
cerebellardisplacementcanextendasfardownasthethirdcervicalvertebra.

TypeII.mostcommonoftheChiarimalformationstobediagnosedinchildhood
anycombinationoffeaturesoftypeImalformationcanbeassociatedwith
noncommunicatinghydrocephalusandlumbosacralspinabifida.themedulla

andcerebellum,togetherwithpartorallofthefourthventricle,aredisplaced
intothespinalcanal

TypeIII.canhaveanyofthefeaturesoftypesIorII.Additionally,theentire
cerebellumisherniatedthroughtheforamenmagnumwithacervicalspina
bifidacystica

TypeIV.alsoveryuncommonandinvolvesanincompleteorunderdeveloped
cerebellum.

DiplomyeliaandDiastematomyelia

Diplomyeliaisacompleteduplicationofaregionofspinalcord;diastematomyeliaisa
verticaldivisionofthespinalcordintotwoseparatehalves,usuallybyanabnormal
bony,cartilaginousorfibrousseptumoverseveralsegments.

Progressivesensorimotordeficitsrepresentthemostcommonclinicalmanifestation

Hydromyeliaisanenlargementordilatationofthecentralcanalofthespinalcord,can
occurasadevelopmentalanomaly,associatedwithChiarimalformationsinparticular

Syringomyeliainvolvesextensionofanenlargedcentralcanalintothecordparenchyma,
usuallyoneorbothdorsalhornsanddorsalcolumns,canbeanacquiredlesionofthe
spinalcordsecondarytotrauma,infarction,orintramedullarytumors

NeurodermalSinus

Relativelyfrequentamongcasesofoccultspinaldysraphism

Theyrepresentacommunicationlinedbystratifiedsquamousepitheliumbetweenskin
andanyportionoftheneuraxis.Mostcommonly,thedefectsareinthelumbosacral
region

Thesinusisoftensurroundedbyasmallmoundofskin,thedimple,orothercutaneous
lesionssuchastuftsofhairorangiomas

Thepresenceofanopensinustractcanprovideaportalofentryforbacterialinfections,
andaneurodermalsinusisanimportantcauseforrecurrentmeningitis

Theselesionsrequiresurgicalexplorationandcompleteexcisionofthesinusbeforethe
developmentofsymptoms.

DISORDERSOFPROSENCEPHALICDEVELOPMENT
Holoprosencephaly

disorderofforebraincleavageoftheearlyprosencephalontoformtwodistinct
telencephalichemispheres

TheanatomicformsofholoprosencephalycanbedefinedbyCT,MRI,and
neuropathologicexamination.

TYPESOFHOLOPROSENCEPHALY

Alobarholoprosencephaly

Themostextremeform

characterizedbyamonoventriclecontinuouswiththethirdventricle,sothat
foraminaofMonrocannotberecognized.

Thissinglemidlineventricleislarge,andthecerebralcortexandhippocampiare
continuousacrossthefrontalmidline

Thethirdventriclemaybeatreticbecauseofnonfusionofthethalamusormany
belargeandincorporatedintotheforebrainmonoventricle.

Hydrocephalusmaybepresentbecauseofaqueductalatresia,especiallyin
caseswithmidfacialhypoplasia

Semilobarholoprosencephaly
intermediatedegreeofseverity;anincompletehemisphericfissureisseen
posteriorly,andtheoccipitallobesandtheoccipitalhornsofthelateral
ventriclesarewelldifferentiated

Lobarholoprosencephaly
themildestform;partialfusionofthehemispheresorsometimesofthe
hippocampus,occursfrontally,withcompleteseparationoccipitally.

CLINICALMANIFESTATION

Highlightedbymidlinefacialabnormalities,seeninthelargemajorityofchildrenwith
alobarholoprosencephaly

Inalobarholoprosencephaly:

neurologicpictureischaracterizedbyseveretoprofoundmentalretardation,
seizures,rigidity,apnea,andtemperatureimbalance.

Hydrocephaluscandevelopasaconsequenceofaqueductalobstruction,and
associatedhypothalamicorpituitarymalformationcaninduceendocrine
disorders;epilepsyisvariable

SeptoOpticPituitaryDysplasia

disorderofmidlinecleavageandhypoplasiaofmediandiencephalicandtelencephalic
structures.

Includes:

agenesisoftheseptumpellucidum

hypoplasiaoftheopticnervesandchiasmwithresultantblindnessorsevere
visualimpairment

hypoplasiaoftheinfundibulumwithgrowthhormonedeficiencyandshort
stature,and,

inapproximatelyonethirdofchildren,diabetesinsipidus

Growthhormonedeficiencyisthemostcommonisolatedposteriorpituitary
insufficiency

Insultbeginsatapproximately37days'gestation

DISORDERSOFCELLULARMIGRATION(1TO7MONTHS'GESTATION) Migratorydisorders
developwhenneuroblastsofthesubventricularzone(i.e.,thegerminalmatrix),whichforms
thewallofthelateralventricles,failtoreachtheirintendeddestinationinthecerebralcortex
Schizencephaly

Characterizedbycleftsplacedsymmetricallywithinthecerebralhemispheresand
extendingfromthecorticalsurfacetotheunderlyingventricularcavity

Thecerebralcortexthatsurroundsthecleftmaybenormalorshowareasof
polymicrogyria.

SCHIZENCEPHALYvsPORENCEPHALICCYST

Distinguishedfromporencephalycausedbyavarietyofvascularorinfectiousinsultsto
thebrainduringlatefetalorearlyinfantilelife.

Aporencephaliccystresultsfromthedissolutionofnecroticregionsofbrain,with
cavitationandcystformationwithintheparenchymaofthecerebralhemispheres.

Porencephaliccystscommunicatewiththeventricularsystemormayextendtothe
cerebralcorticalsurfacebutdonotdestroythethinpialmembrane.

Theyareasymmetric,notalignedwiththeprimaryfissures,andunassociatedwith
majorcerebralmigrationdefects.

SCHIZENCEPHALY:CLINICALMANIFESTATION

Characterizedbyawiderangeofneurologicanddevelopmentaldefects.

Epilepsymaybethemostseriouscomplication,andseizuresoftenarethepresenting
symptom.

Hypotonia,hemiparesis,orspasticquadriparesiscanbeaccompaniedbyaseizure
disorderandmicrocephaly.

Imagingstudiesusuallyshowbilateral,symmetric,orasymmetricclefts

Onclinicalgroundsporencephalydiffersfromschizencephalyinthatthepatient
frequentlyhasawelldocumentedhistoryofadestructiveinsulttothebrain,and
neurologicdeficitsareoftenfocal,asymmetric,orsilentandcompatiblewithrelatively
normaldevelopment.

Unlikeschizencephaly,aporencephaliccystcanoccurasaonewayballvalve
typecommunicationwiththeventricularsystem.

Itcanenlargeprogressivelyandbehavelikeanexpandinglesionimpingingon
theventricularsystemtoproducehydrocephalus

Lissencephaly(AgyriaPachygyria,Macrogyria)

Literallymeanssmoothbrain;Thetermisusedsynonymouslywithagyria.

Cerebralhemispheresapproximatethesmooth20weekfetalcerebralcortex,with
absenceofsecondarysulci;Theconditionresultsfromamigratorydefectbelievedto
occurbetween12and16weeks'gestation.

Theinsultpreventssucceedingwavesofmigratingneuronsfromreachingtheirdestined
positionsinthecerebralcortex.Thus,graymatterheterotopia,macrogyria,
polymicrogyria,andschizencephaly,togetherwithdefectivecorticallamination,often
accompanythiscondition

Twomajortypes:

TypeIrevealsthatthecortexisfourlayered;SeeninMillerDiekersyndrome;TheLIS1
geneisstronglyexpressedinCajalRetziusneuronsandperiventricularneuroepithelium
andisessentialforthenormalcourseofradialmigration

TypeIIischaracterizedbyanalmostcompleteabsenceofcorticallayering;Cortical
neuronsarerandomlydisplacedanddisoriented,sothatpyramidalneuronsnormally
confinedtolayers3,5,and6arefoundthroughoutthecortex;SeeninWalkerWarburg
syndromeandinFukuyamacongenitalmusculardystrophy;Accompaniedby
hydrocephalusresultsfrommeningealthickeningandobliterationoftheSASaround
theBSandbaseofbrain

ClinicalManifestation

TheclinicalpictureofcompletelissencephalytypeIishomogeneous.

Allpatientshaveprofoundmentalretardation,markedhypotonia(hypotoniccerebral
palsy),andseizures.Thesemayincludemassivemyoclonusandtonicseizures,which
oftenareprecededbyinfantilespasms.

Microcephalywaspresentinapproximatelyonehalfofpatients

Polymicrogyria

resultsfromaninsulttothenervoussystemsustainedbeforethefifthmonthof
gestation.

Theaffectedbrainresemblesachestnutkernelandischaracterizedbyanexcessof
secondaryandtertiarysulci,resultingingyrithataretoosmallandtoonumerous.

Microscopically,thebrainresemblesthatofa4to6montholdfetus.

SubcorticalLaminarHeterotopia(BandHeterotopia,DoubleCortex)

RaregeneticdisorderthatistransmittedasanXlinkeddominanttrait

Onpathologicexamination,arrestedradialneuroblastmigrationinthecerebrumis
seen,sothatalayerofgraymatterheterotopiaformsbeneaththenormalsurface
cortex

AgenesisoftheCorpusCallosum

Corpuscallosumisthelargestinterhemisphericcommissure.

Thefailureofthiscommissuretoformistraditionallyregardedasaamidlinedefect
becausenormalcallosalfiberscrossthemidline,butitshouldbereclassifiedasa
disorderofaxonalprojection

AnintegralpartofAicardisyndrome.

Thiscondition,describedinfemalepatientsonly,ischaracterizedbysevere
mentalretardation,generalizedtonicclonicandmyoclonicseizuresthathave
theironsetbetweenbirthandage4months,andchorioretinallacunae.

MICROCEPHALY

Headcircumference,asmeasuredaroundtheforeheadandtheoccipitalprotuberance,
thatismorethantwostandarddeviationsbelowthemeanforage,sex,andrace

Headcircumferenceshouldalwaysbecomparedwithotherconcurrentgrowth
parameters:Ifthechildhasaweightandalengthoraheightalsoatorbelow

the2ndcentile,theapparentmicrocephalymaybelesssignificantthanifthese
othermeasuresofgrowthareatorabovethe50thcentile

Exceptincasesofprematureclosureofthesutures(craniosynostosis),thesmallsizeof
theskullreflectsasmallbrain,butitisnotthesizeofthebrainthatdeterminesthe
presenceofmentalretardation,buttheunderlyingstructuralpathologyofthebrain.

Anabnormallysmallbrainresultseitherfromanomalousdevelopmentduringthefirst7
monthsofgestation(primarymicrocephaly)orfromaninsultincurredduringthelast2
monthsofgestationorduringtheperinatalperiod(secondarymicrocephaly).

PrimaryMicrocephaly

Resultsfromavarietyofgeneticandenvironmentalinsultsthatcauseanomaliesof
inductionandmigration.

Micrencephaly,bycontrastwithmicrocephaly,denotesasmallbrainorcerebral
hypoplasiaratherthanasmallhead,andisanimagingorneuropathologic
diagnosis.Micrencephalycancoexistwithmicrocephalyorwithanormalsized
head

DisordersofKaryotypeNumerouschromosomaldisorders,includingtrisomies,
deletions,andtranslocationsyndromes,areassociatedwithprimarymicrocephaly

Irradiationresultfromexposuretoionizingradiationduringthefirsttwotrimesters,
particularlybetween4and20weeks'gestation.Theearliertheinsult,thesmalleristhe
brainandthemoredisablingaretheresultingneurologicabnormalities

InfectionsinUteroAvarietyofinfectiousagents,notablycytomegalovirus,
Toxoplasma,andtherubellavirus

ChemicalAgentsDrugsimplicatedincludecortisone,sulfhydrylenzymeinhibitors,
aminopterin,triethylenemelamine,andnitrogenmustard

SecondaryMicrocephaly

Avarietyofinsults,infectious,traumatic,metabolic,andanoxic,occurringduring
thelastpartofthethirdtrimester,theperinatalperiod,andearlyinfancycause
destructionofbrainwithmultipleareasofcysticdegeneration,
encephalomalacia,andporencephaly,accompaniedbyinflammatorygliotic
scarringandshrinkage.

Diagnosis

Serologicstudiesforintrauterineinfections,cytogenetics,aminoacidscreening

CTforintracranialcalcificationsshouldbeconsidered.

MRIdemonstratesabnormalitiesincorticalarchitecture

Craniosynostosiscanbedistinguishedfrommicrocephalybyanabnormallyshaped
skullandbythepresenceatbirthofbonyunionbetweensutures.
CRANIOSYNOSTOSIS

Prematureclosureatbirthofoneormorecranialsutures.

Simplewhenonlyonesutureisfused

Compoundwhentwoormoresuturesareaffected.

Primarycraniosynostosisresultsfromanabnormalityofthemesenchymalmatrixandis
nottheconsequenceofimpairedbraingrowth.

Secondarycraniosynostosisistheconsequenceofoneofvariousmechanical,metabolic,
orhematologicdisorders.

Severalwelldefinedgeneticdiseasesareknowntoassociatedwithcraniosynostosisand
forwhichthespecificgeneticmutationisdemonstrated;theseincludeApert,Crouzon

Inthehealthynewborn,allsuturesareseparatedbyseveralmillimeters,exceptthe
metopicsuture,whichclosesantenatally.

Metopiccraniosynostosis,whichmanifestsitselfbyamidfrontalridge,is
relativelycommoninsmallinfantsbutisoflittleornoclinicalsignificance.No
knownneurologicconsequencesexist,andsurgeryiscontraindicated.

CROUZONSYNDROME

Prematureclosureofmultiplesuturesisassociatedwithanabnormallyhighforehead,
hypertelorism,shalloworbitswithresultantexophthalmos,micrognathia,choanal
atresia,prognathism,beakednose,andhigharchedpalate

associatedwithnormalintellect.

ChronictonsillarherniationaccompaniesCrouzonsyndrome

Hydrocephalusdevelopsinalargeproportionofpatients

Hereditaryorfamilial,anditsgenehasbeenmappedtothelongarmofchromosome
10(10q26).

APERTSYNDROME

HeadandfacialconfigurationaresimilarCrouzonsyndrome,butsyndactylyor
polydactylyispresent;Sporadic.

Inthemajority,theconditionresultsfromoneoftwomutationsinthegenefor
fibroblastgrowthfactorreceptor2

Nonprogressiveventriculomegaly,hydrocephalus,andmegalencephalyareoften
demonstrated

OnlyasmallproportionofpatientswithApertsyndromehavenormalintelligence,and
malformationsofthelimbicstructures,corpuscallosum,andgyralabnormalitiesare
common

Diagnosis

Inthesmallinfant,thediagnosiscanbesuspectedinthepresenceofanabnormally
shapedheadorface.

CTisusuallydefinitive.Itrevealstheextentofprematurefusionandfrequentlyshows
anincreaseddensityofthefusedsuture.

Theearlyradiologicchangeisalossofthepatternofinterdigitationsofthe
bone,untilthesuturebecomesasimplelineofseparationofthebones

Treatment

Treatedsurgicallyinchildrenwithmultiplesutureclosuretopreventanybrain
damagethatcouldresultfromchronicincreasedintracranialpressureandin
childrenwithsynostosisofonlyonesuturetoaffectagoodcosmeticresult

CommonCausesofMacrocephalyandTimeofClinicalPresentation
EarlyInfantile
Hydrocephalus(progressiveor
(Birthto6moof arrested )
age)
Inductiondisorders
Masslesions
Intrauterineinfections
Perinatalorpostnatalinfections
Perinatalorpostnatalhemorrhage
Hydranencephaly
Subduraleffusion
Hemorrhagic,infectious,cystic
hygroma

Spinabifidacystica,cranium
bifidum,Chiarimalformations
(typesI,II,andIII),aqueductal
stenosis,holoprosencephaly
Neoplasms,atrioventricular
malformations,congenitalcysts
Toxoplasmosis,cytomegalic
inclusiondisease,syphilis,rubella
Bacterial,granulomatous,
parasitic
Hypoxia,vascularmalformation,
trauma

Normalvariant(oftenfamilial)

LateInfantile(6
moto2yrof
age)

Hydrocephalus(progressiveor
arrested )
Spaceoccupyinglesions
Postbacterialorgranulomatous
meningitis
Posthemorrhagic

Tumors,cysts,abscess

Traumaorvascularmalformation

DandyWalkersyndrome
Subduraleffusion
Increasedintracranialpressure
syndrome
Pseudotumorcerebri

EarlytoLate
Childhood
(olderthan2yr
ofage)

Hydrocephalus(progressiveor
arrested )
Spaceoccupyinglesions
Preexistinginductiondisorder
Postinfectious
Hemorrhagic
ChiaritypeImalformation
Megalencephaly
Proliferativeneurocutaneous
syndromes
Familial
Pseudotumorcerebri
Normalvariant

Lead,tetracycline,
hypoparathyroidism,
corticosteroids,excessor
deficiencyofvitaminA,cyanotic
congenitalheartdisease

Aqueductalstenosis

DIAGNOSIS

Shouldultrasonographydemonstrateventricularenlargement,thenextquestiontobe
answerediswhetherventriculomegalyisatrophicoriscausedbyobstructionand
increasedintracranialpressure.

RoutineMRIorcineMRIisusefultoascertainthepresenceofCSFflowthroughthe
foramenofMonro,aqueductofSylvius,andforamenofMagendie.

CTscansareessentialtoassessthepresenceofintracranialcalcificationsproducedby
prenatalinfections,hypoparathyroidism,orparasiticcysts

Megalencephaly

Resultsfromexcessiveamountsofnormalbrainconstituents,cellularproliferation,
inadequatephysiologicapoptosis,orstorageofmetabolites.

Theclassicalclinicalpictureoftruemegalencephalyisoneofmentalretardation,
seizures,hypotoniaormildpyramidaltract,andcerebellardeficits.

Thesesymptomsareoccasionallyprogressive.Theskullbonesarethin,theanterior
fontanelleislarge,andsuturesareslowinclosing.

Althoughtheprevalenceofmegalencephalyisincreasedinchildrenwithlearning
disabilities,themajorityofchildrenwiththisconditionhavenormaltosuperior
intelligence,andalargebrainhasbeenseeninmanygeniuses.

Hydrocephalus

Duringthe2ndAOG,choroidplexiprimordiadevelop,firstasamesenchymal
invaginationoftheroofofthefourthventricle,thenbyasimilarinvaginationofthe
lateralandthirdventricles

3rdAOG,theplexifill75%ofthelateralventricleandthenbegintodecreaseinrelative
size.

Duringthethirdtrimester,theplexibecomecellularandglycogenrich.

Afterbirth,glycogenislostasthecellsbeginaerobicoxidation.

Astheplexidevelopinthe2ndAOG,thefetalventriclesarelargerelativetothe
thicknessofthecorticalwall,andthisrelativedilatationdisappearswithfurther
developmentofwhiteandgraymatter
Completecirculationfromventricletothesubarachnoidspacesdoesnotoccuruntilafter2
months'gestation

MostoftheCSFisproducedwithintheventricularsystembythechoroidplexi;
however,asizableproportion,some10%to20%,evidentlyisformedbythe
parenchymaofcerebrumandspinalcord

CSFflowfromthesiteofitsproductionintheventriclestoitsabsorptioninthe
arachnoid(pacchionian)granulations.

Intheadulthuman,CSFissecretedatarateof500mLper24hours,orbetween0.2%
and0.5%ofthetotalvolumeperminute

TherateofCSFformationrangesfrom0.3to0.4mL/mininchildrenandadults

TotalCSFvolumeinthenewbornis50mLandincreaseswithagetoanadult
volumeof150mL.

ThreefactorscontrolCSFdrainage:

CSFpressure,

Pressurewithintheduralsinusesandthecorticalvenoussystem,and

ResistanceofthearachnoidalvillitoCSFflow

ChangesinanyofthesevariablessignificantlyaffectCSFflow.

ThenormallumbarCSFpressureis150mmH2Ointhelaterallyrecumbentadultandup
to180mmH2Ointhechild,

ThecapacityfordrainageistwotofourtimesthenormalrateofCSFproduction

Pathogenesis

AnyblockintheCSFpathwayfromthesiteofformationtothatofabsorptionresultsin
increasedCSFpressure.

Hydrocephalusisdividedintononcommunicatingandcommunicatingforms.

NoncommunicatinghydrocephalusSASisusuallycompressed;theobstructive
siteiswithintheventricularsystem,includingtheoutletforaminaofthefourth
ventricle.

CommunicatinghydrocephalusSASisenlarged;theobstructionoccursdistalto
thefourthventricleforamina,inthecisternsorcerebralsubarachnoidspace
itself.

EXTERNALHYRDROCEPHALUS

Seenininfantswithenlargedheadsorrapidheadgrowth.

SASarewidenedbilaterallyinthefrontalandsometimesinthefrontoparietalregions.

Theventriclesareofnormalsizeoronlyslightlyenlarged.

Graduallyresolvesduringthesecondyearoflife

Morecommoninprematureinfants,andin88%ofcasesafamilyhistoryofenlarged
headexists

Probablyresultsfromadevelopmentaldelayinarachnoidalfunction,butcouldalsobe
acquiredresiduallyontrauma,spontaneoussubarachnoidhemorrhage,orinfection

Pathology

Thethreegeneralcausesofhydrocephalusare:

Excesssecretioncausedbychoroidplexuspapilloma,

Obstructionwithintheventricularcavity(noncommunicatinghydrocephalus),
and

Absorptiveblockwithinthesubarachnoidspace(communicating
hydrocephalus).

ChoroidPlexusPapilloma

Thepapillomaisalargeaggregateofchoroidalfrondsthataremicroscopicallysimilarto
normalchoroidplexiandproducegreatquantitiesofCSF.

Accountingfor1%to4%ofchildhoodintracranialtumors

Usuallyoccurafterinfancyandareassociatedwithsignsofincreasedintracranial
pressure

ObstructionofCSFflowisresponsibleforhydrocephalus,inatleastsomecases,the
tumorproduceshydrocephalusbyCSFoversecretion

ObstructionwithintheVentricularCavity

AnyobstructionfromtheforaminaofMonroortotheforaminaofMagendieand
Luschkaproducesnoncommunicatinghydrocephalus.

Spaceoccupyinglesionsinthecerebralhemispherestendtocompresstheventricular
system,whereastumorsintheposteriorfossaorarteriovenousmalformationsinvolving
theveinofGalencanproducekinkingorobstructionoftheaqueductorobstructionat
thefourthventricularoutflow.

AqueductalStenosis

Responsiblefor20%ofcasesofhydrocephalus.

Itsincidencerangesfrom0.5to1.0in1,000births,witharecurrenceriskinsiblingsof
1.0%to4.5%.

Normally,theaqueduct,linedbyependyma,is3mminlengthatbirthandits
meancrosssectionis0.5mm2

Theaqueductissmallerbutremainshistologicallynormal.

Constrictionsoftheaqueducttolessthan0.14mm2canoccurattwopoints:

firstisbeneaththemidlineofthesuperiorquadrigeminalbodies

secondisattheintercollicularsulcus

Theonsetofsymptomsisusuallyinsidiousandcanoccuratanytimefrombirthto
adulthood.

Asmallpercentageoftheanomalies(approximately2%)arecausedbyoneormore
sexlinkedrecessivegenes.

Thisentity,morecorrectlyknownasXlinkedhydrocephalus,hasbeenshowntobe
causedbyamutationintheL1gene.

CRASHsyndromecorpuscallosumhypoplasia,retardation,adductedthumbs,
spasticparaplegia,andhydrocephalus.

Thepresenceofthesemalformationshelpstoexplaintheintellectual,cognitive,
andmotorhandicapsevenafterthehydrocephalusiscompensatedbyshunting

AqueductalGliosis

Apostinfectiousnoninflammatoryprocess,isusuallysecondarytoaperinatalinfection
orhemorrhage.

Withtheincreasingsurvivalofnewbornsaffectedwithbacterialmeningitisor
intracranialhemorrhage,thisconditionhasassumedgreaterimportance

Theependymalliningispermanentlydestroyedbecauseitishighlyvulnerabletoinsult
andcannotregenerate;theaqueductisreplacedbymultipleependymalcellclusters
androsettesofblindtubules.

Markedfibrillarygliosisofadjacenttissueisevident,andtheocclusionisprogressive.

Aswithaqueductalstenosis,itsonsetisinsidious.

Occasionallyaccompaniesneurofibromatosis.

Aqueductalstenosisandgliosishavebeenproducedinexperimentalanimalsbyintrauterine
viralinfections,andapatienthasbeenreportedwithaqueductalstenosisaftermumps
encephalitis
DandyWalkerMalformation

Characterizedbyatriadof

completeorpartialagenesisofthecerebellarvermis,

cysticdilatationofthefourthventricle,and

enlargedposteriorfossawithupwarddisplacementofthetransversesinuses,
tentorium,andtorcular

Defectofneuraltubeclosureatthecerebellarleveloccurringatapproximately4
weeks'gestation

Incidenceis1per25,000to30,000births,withtheconditionhavingaslight
predilectionforgirls

Hydrocephalusisnotpresentatbirth;itappearsby3monthsofage

TREATMENTOFHYDROCEPHALUS

Correctionofhydrocephalusinvolvescystoperitoneal,ventriculoperitoneal,orboth
kindsofshunts

Cystoperitonealshunting,becauseitavoidstheriskofanentrappedfourthventricle,is
consideredbymanytobethebestprocedureforthiscondition.

Otherconditionsthatfrequentlyobstructfourthventricularoutflowarespace
occupyinglesions,particularlythoseinvolvingtheposteriorfossa
AbsorptiveBlockwithintheSubarachnoidSpace

Ofallchildhoodhydrocephalus,30%arecommunicating.

AftertheCSFpassesthroughtheexitforaminaofthefourthventricle,itnormally
traversesthebasalcisternsaroundthebrainstemandmidbrainonthewaytothe
corticalsubarachnoidcompartmentandisabsorbedthroughthearachnoidvilli.

Meningealscarringcanresultfromsubarachnoidhemorrhageorbacterialmeningitis.

Whenthisscarringoccludestheexitsfromthecisternsorinvolvesthearachnoidvilli,
theCSFcirculationisimpeded.

NormalPressureHydrocephalus(HakimSyndrome)

IndolentlyprogressivehydrocephalusinwhichCSFpressureiswithinthephysiologic
rangebutinwhichamarkedincreaseinCSFpulsepressureresultsinslowventricular
expansionandprogressivewhitematterdamage

ThepathogenesisofNPH,asitisseenintheelderly,undoubtedlydiffersfromthatin
infantsandchildren,inwhomthemostcommoncauseiscommunicatinghydrocephalus
withincompletearachnoidalobstructiontoCSFdrainage.

Primaryeventsincludeneonatalintraventricularhemorrhage,spontaneous
subarachnoidhemorrhage,intracranialtrauma,infections,andsurgery.

Theclinicalpresentationinchildhoodresemblesthatseeninadultlife>psychomotor
retardation,psychoticlikebehavior,gaitabnormalities,andsphincterdisturbances

Arrested(Compensated)Hydrocephalus

OccurswhenCSFformationandabsorptionareinbalanceandnomoreCSF
accumulates.

Milhoratdefinedarrestedhydrocephalusasthesurgicalorspontaneous
terminationofahydrocephaliccondition,withsubsequentreturntonormalof
thepressuregradientacrossthecerebralmantle.

Headcircumferenceisusuallynearorabovethe97thpercentile

Neuroimagingstudies,theventriclesaremoderatelytomarkedlydilated.Thelargerthe
ventricles,thelesslikelyitisthatventricularsizewillfurtherincrease.

Onevaluation,thesechildrentendtobeclumsyanduncoordinated,withverbalIQbetterthan
performanceIQ.Toneanddeeptendonreflexesareoftenincreased,andopticatrophy,
papilledema,andvisualfielddefectscanbepresent.

ClinicalManifestations

Fourmajorfactorsinfluencetheclinicalcourseinhydrocephalus:

thetimeofonset,

thedurationofincreasedintracranialpressure,

therateatwhichintracranialpressureincreases,and

anypreexistingstructurallesions.

Diagnosis

Ininfants,theinitialdiagnosisofhydrocephalusisbasedonaheadcircumferencethat,
regardlessofabsolutesize,crossesoneormoregridlines

Suchinfantsrequirepromptdiagnosticevaluation,evenwhenovertneurologic
signsareabsent.

Ultrasonographyhasproventobeinvaluableinmonitoringtheventricularsystemin
infantswithhydrocephalus

AlthoughinthepastCTscanshaveprovenofvalueinthediagnosticevaluationofthe
infantorchildwithhydrocephalus,MRIisthepreferredprocedure.

Treatment

ThegeneralprinciplesoftreatmentaresurgicalcorrectionofCSFobstruction,reduction
ofCSFproductionbydrugsorsurgicaltherapy

Childrenolderthan3yearsofagewithstableventricularsizebemonitoredif
theirintellectualperformanceiswithinthenormalrangeandappearsstable.

Childrenyoungerthan3yearsofagewithlargeventriclesshouldbeshuntedif
doubtexists,becausetheoutcomeofnontreatmentisuncertain.

Hydranencephaly
Pathology

Thegreaterportionsofboththecerebralhemispheresandthecorpusstriatumare
reducedtomembranoussacscomposedofglialtissuecoveredbyintactmeningesand
encompassingacavityfilledwithclearCSF.

Atypeofhydrocephalusthathasrunitscourseinutero.

Inotherinstances,hydranencephalycanbetheconsequenceofintrauterineinfections
orothergestationalinsults

ClinicalManifestations

Infantsappearhealthyatbirthorhaveasomewhatlargeheadthatenlarges
progressively.

Spontaneousandreflexactivityisoftennormal.

However,failureinthedevelopmentofcerebrocorticalinhibitionresultsinthe
persistenceandexaggerationofreflexes,whichbecomesapparentbythesecondor
thirdpostnatalweek.

Diagnosis

Inaninfantwithanenlargedheadorabnormallyacceleratingheadgrowth,
ultrasonographyismandatorytoexcludeseverehydrocephalusandexpandingbilateral
porencephaliccystsunderincreasedpressure.

Mostinfantswithhydranencephalydonotsurvivebeyondthesecondyearoflife;they
succumbtointercurrentinfectionsortoanunexplaineddeficitofvitalfunction.

Treatment

Notreatmentisavailableforhydranencephaly.