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ImaginginHerpesEncephalitis:Overview,ComputedTomography,MagneticResonanceImaging

Thissiteisintendedforhealthcareprofessionals

ImaginginHerpesEncephalitis
Updated:Jul14,2015
Author:MaheshRPatel,MDChiefEditor:JamesGSmirniotopoulos,MDmore...

OVERVIEW

Overview
Herpesencephalitisisthemostcommoncauseofsporadicviralencephalitis,withapredilectionfor
thetemporallobesandarangeofclinicalpresentations,fromasepticmeningitisandfevertoa
severerapidlyprogressiveforminvolvingalteredconsciousness.Inadults,herpessimplexvirus
type1(HSV1)accountsfor95%ofallfatalcasesofsporadicencephalitisandusuallyresultsfrom
reactivationofthelatentvirus.Theclinicalfindingsandneuroimagingappearanceareboth
consistentwithspreadofthevirusfromapreviouslyinfectedganglion.
Morerecently,sporadiccasesofhumanherpesvirus6(HHV6)havebeendescribedin
immunocompromisedpatientsorthosewithlymphoproliferativedisorders.Inchildrenand
neonates,herpessimplexvirustype2(HSV2)accountsfor8090%ofneonatalandalmostall
congenitalinfections.Anisolatedcasereportofanimmunocompromisedadultpatientdeveloping
HSV2infectionhasbeendescribed.Magneticresonanceimaging(MRI)canplayanimportantrole
indeterminingthediagnosisandextentofdisease.[1,2,3,4,5,6,7,8,9,10,11,12]Seetheimage
below.

Magneticresonanceimagedepictingherpesencephalitis.

ViewMediaGallery
Onpathology,herpesvirusescauseafulminanthemorrhagicandnecrotizingmeningoencephalitis,
withtypicalgrossfindingsofsevereedemaandmassivetissuenecrosis,withpetechial
hemorrhagesandhemorrhagicnecrosis.Often,thepetechialhemorrhageisnotobservedon
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computedtomography(CT)scanningorMRI.Onmicroscopy,afocalnecrotizingvasculitisis
observedwithperivascularandmeningeallymphocyticinfiltrationandeosinophilicintranuclear
inclusionsinglialcellsandneurons.TairaetalfoundthatalowerGlasgowComaScalescoreand
agreaternumberoflesionsdetectedonCTscanningwerepredictorsofprolongedacyclovir
therapy[13](seetheGlasgowComaScalecalculator).

Preferredexamination
MRIisthepreferredmodalityforevaluatingthebrain.[14,15,16]However,earlyintheclinical
courseofthedisease,MRIresultsmaybenegative.AnegativeMRIdoesnotruleoutHSV
encephalitis.Therapyshouldbeempiricallycontinueduntillaboratorytestsdefinitelyexcludethe
diagnosis.AcasereportofWestNileViruscausingfocaltemporallobefindingswasdescribedin
theliterature.[17]
EarlyimagingwithCTscanningorradionuclidestudiesmayalsorevealnormalfindings.CT
scanningmaynotrevealabnormalitiesuntil35daysaftersymptomonset,bywhichtimethe
patientmaybestuporousandcomatose.Asnotedabove,intheacutesetting,evencontrast
enhancedMRIsmaybenegative.

ComputedTomography
Inadults,CTscansclassicallyrevealhypodensityinthetemporallobeseitherunilaterallyor
bilaterally,withorwithoutfrontallobeinvolvement.Hemorrhageisusuallynotobserved.Agyralor
patchyparenchymalpatternofenhancementisobserved.Contrastenhancementgenerallyoccurs
laterinthediseaseprocess.[15,18]
Theherpesviruspreferentiallyinvolvesthetemporallobeandorbitalsurfacesofthefrontallobes.
Thisinvolvementmayextendtotheinsularcortex,posterioroccipitalcortex,andcerebral
convexityhowever,thebasalgangliaarespared.Bilateralinvolvementisfrequent.Involvementof
thecingulategyrusoccurslaterinthedisease.Theclassicinvolvementofthemedialtemporaland
frontallobesisconsistentwithintracranialspreadalongthesmallmeningealbranchesofthefifth
cranialnerve.Cingulategyrusinvolvementmayarisefromefferenthippocampalconnections.A
rhomboencephalitisresultingfrompontineinvolvementmayoccurandlikelyarisesfromretrograde
viraltransmissionalongthecisternalportionofthetrigeminalnervetothebrainstem.
Inneonates,involvementisintheperiventricularwhitematter,sparingthemedialtemporaland
inferiorfrontallobes.Inaddition,meningealenhancementmaybeobservedfollowingcontrast.[19,
20]

Tairaetalanalyzedspecificvariablesaspredictorsofaneedforaprolongedcourseofacyclovir
therapyin23patientswithHSVencephalitisandreportedalowerGlasgowComaScalescoreand
agreaternumberoflesionsdetectedonCTscanswerepredictorsofprolongedtherapy[13](see
theGlasgowComaScalecalculator).TheinvestigatorsconcludedthatstandardinitialACV
treatmentmaynotbesufficientforpatientswithsuchpredictorsandthatinitialtreatment
modificationsmaybenecessaryinsuchpatients.[13]
Lateinthediseaseprocess,whentemporalandfrontallobeinvolvementisseen,CTfindingsmay
becharacteristic.ReportsexistofpatientswithnormalCTresultsandcerebrospinalfluid(CSF)
studiesinthepresenceofabnormalMRIandEEGfindings,indicatingthatMRIismoresensitive.
Earlyinthediseaseprocess,limitedsensitivityofapproximately50%wasnoted.Whentypical
findingsofHSVencephalitisareobservedonCTscan,theyoftenareassociatedwithseverebrain
damageandapoorprognosis.[15]
Becauseofboneartifact,thetemporallobescanbedifficulttoassessonCTscanning.Earlyinthe
diseaseprocess,CTscanningmaybenormal.Othercausesofencephalitis,tumor,orlymphoma
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mayappearsimilar.

MagneticResonanceImaging
Thediagnosisofherpesencephalitiscanbestronglysuggestedbythetypicalappearanceof
medialtemporalabnormalitiesthatdonotrespecthippocampalborders.
Inadults,T2weightedMRIrevealshyperintensitycorrespondingtoedematouschangesinthe
temporallobes(seethefirst2imagesbelow),inferiorfrontallobes,andinsula,withapredilection
forthemedialtemporallobes.FociofhemorrhageoccasionallycanbeobservedonMRI(seethe
thirdimagebelow).

Axialprotondensityweightedimageina62yearoldwomanwithconfusionandherpesencephalitisshowsT2
hyperintensityinvolvingtherighttemporallobe.

ViewMediaGallery

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AxialgadoliniumenhancedT1weightedimagerevealsenhancementoftherightanteriortemporallobeand
parahippocampalgyrus.Attherightanteriortemporaltipisahypointense,crescenticregionsurroundedby
enhancementconsistentwithasmallepiduralabscess.

ViewMediaGallery

AxialnonenhancedT1weightedimageshowscorticalhyperintensity(arrows)consistentwithpetechial
hemorrhage.Ingeneral,thisisacommonpathologicfindingbutlesscommonlydepictedinherpes
encephalitis.

ViewMediaGallery
MRIispreferredforimagingandfollowupstudiesofherpesencephalitis.Typically,temporallobe
T2hyperintensitysparesthebasalganglia.Althoughthisappearancewaspreviouslybelievedto
bepathognomonicforherpesinvolvement,similarfindingscanbeobservedinprogressive
multifocalleukoencephalopathyandprimaryCNSlymphoma.Patchyparenchymalorgyral
enhancementcanbeobserved(seetheimagebelow).[21,22,23,24,25,26]

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AxialgadoliniumenhancedT1weightedimagerevealsenhancementoftherightanteriortemporallobeand
parahippocampalgyrus.Attherightanteriortemporaltipisahypointense,crescenticregionsurroundedby
enhancementconsistentwithasmallepiduralabscess.

ViewMediaGallery
Inonestudyof251casesoftemporallobeencephalitisidentifiedbyMRI,43%wereofan
infectiousetiology(60caseswereherpessimplexencephalitis)and16%noninfectious.Therefore,
inadditiontoherpessimplex,otherinfectiousandnoninfectiouscausesshouldbeconsideredin
thedifferentialdiagnosisoftemporallobeencephalitis.[27]
Reportsofrestricteddiffusioninherpesencephalitisexist(seethefirstimagebelow),with
correspondingT2hyperintensityreflectingedema(seethesecondimagebelow).Reportssuggest
diffusionweightedimaging(DWI)maybemoresensitiveinthedetectionofHSVinvolvementthan
conventionalMRIsequencesandmaymimicaninfarctwithinvolvementofthecorticalregionsof
thetemporallobe.[28]

Axialdiffusionweightedimagerevealsrestricteddiffusionintheleftmedialtemporallobeconsistentwith
herpesencephalitis.Thispatientalsohadapositiveresultonpolymerasechainreactionassayforherpes
simplexvirus,whichisbothsensitiveandspecific.Inaddition,thepatienthadperiodiclateralizedepileptiform
dischargesonelectroencephalogram,whichsupportsthediagnosisofherpesencephalitis.

ViewMediaGallery

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CoronalT2weightedimagerevealshyperintensityinthelefttemporallobe(arrows)inadistributionsimilarto
therestricteddiffusionabnormalityseeninthepreviousimage.Thisfindingistypicalforherpesencephalitis.In
patientswithHHV6infection,oneseriesnotedthatinadditiontomesialtemporallobeabnormality,abnormal
T2hyperintensityhasbeenseenintheinsularandinferiorfrontalregion,whichmaysuggestthediagnosis.
Therearefelttobe2typicalimagingappearances:oneseeninolderadultsinvolvesT2hyperintensity
confinedtothemedialtemporallobeinyoungadults,amorevariedpatternhasbeendescribedthatincludes
fociofrestricteddiffusionwithanotherwisenormalmagneticresonance,diffusecorticalnecrosis,orsmallfocal
regionsofabnormalT2hyperintensity.

ViewMediaGallery
Immunocompromisedpatientsmayhaveatypicalmanifestationsincludingwidespreadcortical
involvement,brainsteminvolvement,orcerebellarinvolvement.[29]Inthepediatricpopulation,
diffusionweightedimagesarethoughttobethemostsensitive,andthecingulumwasless
frequentlyeffectedwhencomparedwithadults.[30]
Inneonates,T2weightedMRIshowshyperintensityoftheperiventricularwhitematter,withthe
medialtemporalandinferiorfrontallobesspared.Meningealenhancementalsomaybeobserved.
[31]

Inpatientswhodevelopedneonatalherpessimplexencephalitiswithin28daysafterbirth,cortical
lesionswerethemainfindingsonDWI.Bilateraldeepcerebrallesionsbyday7werehigh
indicatorsofpooroutcomesinmotorandcognitiveabilities.[32]
AdvancedMRtechniquesarebeingincreasinglyusedtostudyherpesencephalitis.MR
spectroscopyusingprotonspectroscopicMRIhasdemonstratedareductionoftheN
acetylaspartate(NAA)tocholineratio.AdecreasedNAApeakhasbeenreported714weeksafter
onset,andinsomecases,anelevatedcholinepeakisseen.Occasionally,thelactatepeakmaybe
elevated.TheNAAdecreaseisbelievedtoreflectneuronalinjury.NAArecoveryhasbeennotedto
parallelclinicalimprovement.[33,34]Diffusiontensorimaginghasanemergingroleindelineating
areasofinvolvementofnormalappearingwhitematterinthecontralateralhemispheretovisible
lesions.[35]
Gadoliniumbasedcontrastagentshavebeenlinkedtothedevelopmentofnephrogenicsystemic
fibrosis(NSF)ornephrogenicfibrosingdermopathy(NFD).Formoreinformation,seethe
MedscapeReferencetopicNephrogenicSystemicFibrosis.NSF/NFDhasoccurredinpatientswith
moderatetoendstagerenaldiseaseafterbeinggivenagadoliniumbasedcontrastagentto
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enhanceMRIorMRAscans.Formoreinformation,seeFDAInformationonGadoliniumBased
ContrastAgentsorMedscape.

Ultrasonography
Theroleforultrasonographyinherpesencephalitisislimited.Forinuteroorneonatalevaluation,
ultrasonographymayhavealimitedroleinidentifyingtheperiventriculardestructiveprocess.

NuclearImaging
Theuseoftechnetium99m(99mTc)hexamethylpropyleneamineoxime(HMPAO)singlephoton
emissionCT(SPECT)scanninginevaluatingherpesencephalitisislimited.Resultsdemonstrate
thattheencephalitismatchesthedistributionofhyperintensityonT2weightedMRIs,with
increasedHMPAOuptakeintheacutestage.Latesequelaearecharacterizedbydecreased
HMPAOuptakeandpostnecroticwideningofthetemporalhorns.Whenabnormaluptakeinvolves
thetemporallobes,withcharacteristicinvolvementofthelimbicsystem,thediagnosisofherpes
encephalitisislikely.
References

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12.MidiI,TuncerN,MidiA,MollahasanogluA,KonyaD,SavA.Effectsofdecompressive
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29.TanIL,McArthurJC,VenkatesanA,NathA.Atypicalmanifestationsandpooroutcomeof
herpessimplexencephalitisintheimmunocompromised.Neurology.2012Nov20.
79(21):212532.[Medline].[FullText].
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31.LeonardJR,MoranCJ,CrossDT3rd,WippoldFJ2nd,SchlesingerY,StorchGA.MR
imagingofherpessimplextype1encephalitisininfantsandyoungchildren:aseparate
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Apr.37(4):42331.[Medline].
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MediaGallery
Magneticresonanceimagedepictingherpesencephalitis.
Axialprotondensityweightedimageina62yearoldwomanwithconfusionandherpes
encephalitisshowsT2hyperintensityinvolvingtherighttemporallobe.
AxialnonenhancedT1weightedimageshowscorticalhyperintensity(arrows)consistentwith
petechialhemorrhage.Ingeneral,thisisacommonpathologicfindingbutlesscommonly
depictedinherpesencephalitis.
AxialgadoliniumenhancedT1weightedimagerevealsenhancementoftherightanterior
temporallobeandparahippocampalgyrus.Attherightanteriortemporaltipisahypointense,
crescenticregionsurroundedbyenhancementconsistentwithasmallepiduralabscess.
Axialdiffusionweightedimagerevealsrestricteddiffusionintheleftmedialtemporallobe
consistentwithherpesencephalitis.Thispatientalsohadapositiveresultonpolymerase
chainreactionassayforherpessimplexvirus,whichisbothsensitiveandspecific.In
addition,thepatienthadperiodiclateralizedepileptiformdischargeson
electroencephalogram,whichsupportsthediagnosisofherpesencephalitis.
CoronalT2weightedimagerevealshyperintensityinthelefttemporallobe(arrows)ina
distributionsimilartotherestricteddiffusionabnormalityseeninthepreviousimage.This
findingistypicalforherpesencephalitis.InpatientswithHHV6infection,oneseriesnoted
thatinadditiontomesialtemporallobeabnormality,abnormalT2hyperintensityhasbeen
seenintheinsularandinferiorfrontalregion,whichmaysuggestthediagnosis.Therearefelt
tobe2typicalimagingappearances:oneseeninolderadultsinvolvesT2hyperintensity
confinedtothemedialtemporallobeinyoungadults,amorevariedpatternhasbeen
describedthatincludesfociofrestricteddiffusionwithanotherwisenormalmagnetic
resonance,diffusecorticalnecrosis,orsmallfocalregionsofabnormalT2hyperintensity.
of6
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BacktoList
ContributorInformationandDisclosures

Author
MaheshRPatel,MDChiefofMRI,DepartmentofDiagnosticImaging,SantaClaraValleyMedical
Center
MaheshRPatel,MDisamemberofthefollowingmedicalsocieties:AmericanRoentgenRay
Society,AmericanSocietyofNeuroradiology,RadiologicalSocietyofNorthAmerica
Disclosure:Nothingtodisclose.
SpecialtyEditorBoard
BernardDCoombs,MB,ChB,PhDConsultingStaff,DepartmentofSpecialistRehabilitation
Services,HuttValleyDistrictHealthBoard,NewZealand
Disclosure:Nothingtodisclose.
ValRunge,MDRobertandAlmaMoretonCentennialChairinRadiology,Professor,Editorin
ChiefofInvestigativeRadiology,DepartmentofRadiology,ScottandWhiteClinicandHospital
ValRunge,MDisamemberofthefollowingmedicalsocieties:AmericanSocietyforBioethicsand
Humanities
Disclosure:Nothingtodisclose.
ChiefEditor
JamesGSmirniotopoulos,MDChiefEditor,MedPix,ListerHillNationalCenterforBiomedical
Communications,USNationalLibraryofMedicineProfessorialLecturer,DepartmentofRadiology,
GeorgeWashingtonUniversitySchoolofMedicineandHealthSciences
JamesGSmirniotopoulos,MDisamemberofthefollowingmedicalsocieties:AmericanCollegeof
Radiology,AmericanSocietyofNeuroradiology,RadiologicalSocietyofNorthAmerica
Disclosure:Nothingtodisclose.
AdditionalContributors
JeffreyLCreasy,MDAssociateProfessor,DepartmentofRadiologyandRadiologicalSciences,
ProgramDirector,NeuroradiologyFellowshipProgram,VanderbiltUniversityMedicalCenter
JeffreyLCreasy,MDisamemberofthefollowingmedicalsocieties:AmericanCollegeof
Radiology,AmericanSocietyofNeuroradiology,RadiologicalSocietyofNorthAmerica
Disclosure:Nothingtodisclose.
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