2/19/2017 Acutehemorrhagicencephalitis:AnunusualpresentationofdengueviralinfectionNadarajahJ,MadhusudhanKS,YadavAK,GuptaAK,VikramNK

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Year:2015|Volume:25|Issue:1|Page:5255 NadarajahJ
Acutehemorrhagicencephalitis:Anunusualpresentationofdengueviralinfection MadhusudhanKS
YadavAK
GuptaAK
VikramNK
JeyaseelanNadarajah1,KumbleSeetharamaMadhusudhan1,AjayKumarYadav1,
ArunKumarGupta1,NavalKishoreVikram2 SearchinGoogleScholar
1DepartmentofRadiodiagnosis,AllIndiaInstituteofMedicalSciences(AIIMS), for
NewDelhi,India
2DepartmentofMedicine,AllIndiaInstituteofMedicalSciences(AIIMS),New NadarajahJ
MadhusudhanKS
Delhi,India
YadavAK
GuptaAK
Clickhereforcorrespondenceaddressandemail
VikramNK
DateofWeb 28Jan Relatedarticles
Publication 2015
Cerebralhemorrhage
denguediffusion
weightedimages
Denguehemorrhagic
encephalopathy
encephalitis
Abstract
EmailAlert*
Dengueisacommonviralinfectionworldwidewithpresentationvaryingfrom AddtoMyList*
clinicallysilentinfectiontodenguefever,denguehemorrhagicfever,andsevere *Registrationrequired(free)
fulminantdengueshocksyndrome.Neurologicalmanifestationusuallyresultsfrom
multisystemdysfunctionsecondarytovascularleak.Presentationashemorrhagic
encephalitisisveryrare.Herewepresentthecaseofa13yearoldfemaleadmitted
withgeneralizedtonicclonicseizures.Plaincomputedtomography(CT)scanof
headrevealedhypodensitiesinbilateraldeepgraymatternucleiandrightposterior
parietallobewithoutanyhemorrhage.Cerebrospinalfluid(CSF)andserologywere Abstract
positiveforIgMandIgGantibodiestodengueviralantigen.Contrastenhanced
Introduction
magneticresonanceimaging(MRI)revealedmultifocalT2andfluidattenuated
inversionrecovery(FLAIR)hyperintensitiesinbilateralcerebralparenchyma CaseReport
includingbasalganglia.Nohemorrhagewasseen.Shewasmanagedwithsteroids. Discussion
Asherclinicalconditiondeteriorated,afterbeingstablefor2days,repeatMRIwas Conclusion
donewhichrevealeddevelopmentofhemorrhagewithinthelesions,anddiagnosis References
ofacutehemorrhagicencephalitisofdengueviraletiologywasmade. ArticleFigures
Keywords:CerebralhemorrhagedenguediffusionweightedimagesDengue
hemorrhagicencephalopathy,encephalitis
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NadarajahJ,MadhusudhanKS,YadavAK,GuptaAK,VikramNK.Acute
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JRadiolImaging[serialonline]2015[cited2017Feb19]25:525.Available
from:http://www.ijri.org/text.asp?2015/25/1/52/150145

Introduction

Denguefeverisacommonviralinfectionworldwide,especiallyintropicalregions.
Presentationofdengueviralinfectionisoftenunpredictable,varyingfromclinically
silentinfectiontouncomplicateddenguefever,denguehemorrhagicfever,and
http://www.ijri.org/article.asp?issn=09713026year=2015volume=25issue=1spage=52epage=55aulast=Nadarajah 1/5
2/19/2017 Acutehemorrhagicencephalitis:AnunusualpresentationofdengueviralinfectionNadarajahJ,MadhusudhanKS,YadavAK,GuptaAK,VikramNK
severefulminantdengueshocksyndrome.Neurologicalmanifestationindengue Adsby Google

hemorrhagicfeverusuallyresultsfrommultisystemdysfunctionsecondarytoliver
ViralEncephalitis
failure,cerebralhypoperfusion,electrolyteimbalance,shock,cerebraledema,and
hemorrhagerelatedtovascularleak.[1],[2]Presentationasviralencephalitisisrare DengueFeverTreatment
asthevirusisnotconsideredneurotrophic.[3]Herewepresentacaseofdengue
feverdevelopingacutehemorrhagicencephalitisduringthecourseofthedisease.

CaseReport

A13yearoldgirlpresentedtotheemergencydepartmentwithhistoryoffever,
severeheadache,andvomitingof3daysduration.Shehadanepisodeof
generalizedtonicclonicseizureatthetimeofpresentation.Onexamination,shewas
conscious,orientedandhervitalparameterswerestable.Neurologicaland
fundoscopicexaminationswerewithinnormallimits.Laboratoryinvestigations
revealedbloodhemoglobinof14g/dl,neutrophilcountof12,000cells/mm3,and
plateletcountof50,000cells/mm3.LiverandrenalparametersandDdimerlevel
werewithinnormallimits.USG(GEhealthcare,LogiqP6,Milwaukee,USA)ofthe
abdomenrevealedmildbilateralpleuraleffusionandminimalfreefluidinpelvis.
Noncontrastcomputedtomography(CT)(SiemensSomatomSensation,Erlangen,
Germany)scanoftheheadshowedasymmetrichypodensityinbilateraldeepgray
matternucleiandrightposteriorparietallobewithoutanyhemorrhage.
Cerebrospinalfluid(CSF)examinationrevealedmildlyelevatedproteinwith
lymphocytosisandnoredbloodcells(RBC).Serologictestingformalariaand
leptospirawasnegative.SerologyandCSFanalysisfordengue(IgMandIgG
antibodies)waspositive,confirmingtheetiology.

Magneticresonanceimaging(MRI)(SiemensAvanto,Erlangen,Germany)was
performedthenextdaywhichrevealedmultifocalT2weighted(T2W)andfluid
attenuatedinversionrecovery(FLAIR)hyperintensitiesinbilateralcerebral
hemispheresincludingbasalganglia[Figure1].Someoftheseregionsshowed
restricteddiffusionandsubtleperipheralcontrastenhancement[Figure2].Noneof
thelesionsrevealedhemorrhage.Diagnosisofacuteviralencephalitiswasmade
basedontheclinicalandimagingfindings.Patientwasstartedonmethyl
prednisolone(15mg/kg/dayfor5days).Patientwasclinicallystablefornext2
days.Onthe3rdday,shehadanotherepisodeofgeneralizedseizurewithsevere
headache.Repeatlaboratoryinvestigationsrevealedbloodhemoglobinof13.5g/dl,
neutrophilcountof11,000cells/mm3,andplateletcountof35,000cells/mm3.
Liverandrenalparameterswerewithinnormallimits.Neurologicalexaminationat
thattimerevealedweaknessofrightupperandlowerlimbswithamotorpowerof
3/5.RepeatMRIwasperformedwhichrevealedhemorrhages[Figure3]inthe
lesionsthatwerenotedpreviously.Nonewlesionswereseen.Shewasmanaged
conservativelywithIVsteroidsandIVimmunoglobulins.Sheimprovedclinically
andwasdischargedaweeklater.Atthetimeofdischarge,themotorpowerwas4/5.
Followupafter1monthrevealedcompletemotorrecoveryintherightupperlimb
andapowerof4/5inthelowerlimb.
Figure1(AandB):(A)AxialFLAIRand(B)
gradientecho(GRE)MRimagesatthelevelof
basalgangliashowmultifocalFLAIR
hyperintenselesionsatgraywhitematterjunction
andinbilateralbasalganglia.Noneofthelesions
showsevidenceofhemorrhage(B)

Clickheretoview
Figure2(AandB):(A)AxialDWIMRimageat
thelevelofbasalgangliashowsrestricted
diffusionwithintheselesions.(B)Contrast
enhancedT1WMRimageshowsperipheralrim
enhancementofthelesions

Clickheretoview

Figure3:FollowupGREMRimage,doneafter
72h,showsmultifocalareasofbloomingwithin
thelesions,suggestiveofhemorrhage

Clickheretoview

Discussion

DenguevirusisasinglestrandedRNAvirusoftheFlavivirusgenusclassifiedinto
fourserotypes.[1],[2],[3],[4]Neurologicalmanifestations,commonlyseenwith
serotypes2and3,occurin0.521%ofpatientsandusuallyresultfrommultisystem
http://www.ijri.org/article.asp?issn=09713026year=2015volume=25issue=1spage=52epage=55aulast=Nadarajah 2/5
2/19/2017 Acutehemorrhagicencephalitis:AnunusualpresentationofdengueviralinfectionNadarajahJ,MadhusudhanKS,YadavAK,GuptaAK,VikramNK
dysfunctionsecondarytoliverfailure,cerebralhypoperfusion,electrolyte
imbalance,shock,cerebraledema,andhemorrhagerelatedtovascularleakwhich
leadstoencephalopathy.[4],[5]Patientspresentwiththefollowingneurological
complaints:stroke,mononeuropathies,polyneuropathies,GuillainBarresyndrome
(GBS),myelitis,meningitis,acutedisseminatedencephalomyelitis(ADEM),
encephalopathy,encephalitis,neuromyelitisoptica,andopticneuritis.[6],[7],[8],[9],
[10]Denguehasclassicallybeenthoughtnottobeneurotrophichowever,presence
ofdenguevirusandantidengueIgMantibodiesinpatient'sCSFwithencephalitis
suggeststhepossibilityofdirectcerebralinvasion.Althoughtheexactmechanism
bywhichdengueviruscrossesthebloodbrainbarrierisunclear,ithasbeen
proposedthattheentryoccursthroughinfectedmacrophages.[6]Inourpatient,IgM
antibodywasstronglypositiveintheCSF.However,polymerasechainreaction
(PCR)fordengueviralRNAwasnotperformed.Bothdengueencephalitisand
encephalopathycanpresentwithdiminishedlevelofconsciousness,headache,
seizure,disorientation,andbehavioralsymptoms.Hence,clinicaldifferentiationis
notpossible.However,fewstudieshaveshownthatpresentationasseizureismuch
morecommoninencephalitisthaninencephalopathy.Itisalsonecessarytoruleout
precipitatingfactorsforencephalopathy,includingacuteliverfailure,hypovolemic
shock,andmetabolicdisorientation.[5]Ourpatientalsopresentedwithseizure,and
detailedexaminationrevealedthrombocytopeniawithoutsignificantsystemic
manifestationsexceptforminimalbilateralpleuraleffusionandminimalpelvicfree
fluid.DiagnosisrequiredCSFexamination.

Multiplecasereportsandcaseseriesofdengueencephalitishavebeenpublishedin
literature.Solomonetal.[4]reportedaseriesofninecasesofdengueencephalitis,
whereinallpatientswerepositivefordengueserology,butvirus/antibodywasfound
intheCSFinonlytwopatients.Intheirstudy,sevenpatientsdidnotshowthe
classicclinicalfeaturesofdengue.Ourpatientalsodidnotshowtypicalclinical
featuresofdengue.

Althoughdiagnosisismainlybasedonclinicalandlaboratoryinvestigations,
imaging(MRI)playsasupportiveroleinconfirmingthediagnosisofencephalitis.
Thenumberofstudiesdescribingtheimagingfeaturesofdengueislimited.Kamble
etal.[11]describedacaseofdengueencephalitiswithimagingfeaturessimilarto

JapaneseencephalitisonCT.Fewothercasereportsdescribedinvolvementof
hippocampus,temporallobe,andpons.Fewcasereportshavedescribed
involvementofbilateralgangliocapsularlocation,midbrain,andspinalcordon
MRI.[12]MRIfindingsareoftennonspecific,andnotmuchdataonMRIfindings
areavailablebecauseoftherarityofthiscondition.Japaneseandherpes
encephalitisarecommoninthesubcontinentandshouldbeconsideredin
differentialdiagnosis,andimagingwithMRIhelpsindifferentiatingthesefrom
DHE(Denguehemorrhagicencephalopathy).AlthoughMRIappearancesare
typicalintheseconditions(bilateralthalamicandbasalgangliainvolvementin
Japaneseencephalitisbilateraltemporalandbasifrontallobesinherpes
encephalitis),itmaybedifficulttodifferentiatefromDHEinagivencaseandCSF
analysismayberequired.[11],[12]Chikungunyafeverwithencephalitiscanalsobea
clinicaldifferentialinthiscase.However,MRIinChikungunyaencephalitisshows
T2Whyperintensewhitematterlesionswithrestricteddiffusion.[13]No
hemorrhageorbasalgangliainvolvementhasbeenreported.

Inourstudy,therewaswidespreadinvolvementofbilateralcerebralhemispheres
includingdeepgraymatternuclei.ThisfindingcanalsobeseeninADEM.Changes
ofADEMindenguefeveraresimilartoDHEonMRIandmaynotbepossibleto
differentiateonMRI.[14]AsADEMisimmunemediated,thereistemporal
relationshipbetweenexposuretodengueandmanifestationofclinicalsymptoms.
Typically,thereismonophasiccourseofillnesswitheventualrecovery,asagainst
encephalitiswhererecoveryisunpredictable.Ourpatientalsohadhemorrhage
withinthelesiononrepeatMRI,probablyrelatedtothrombocytopeniacausedby
dengue,thoughtheplateletlevelneverdroppedbelow20,000cells/mm3.Although
intracerebralhemorrhagecanoccurindengueduetoprofoundthrombocytopenia,
hemorrhageduetoinfectionitselfisrarelyreported.Autopsystudieshaveshown
focalhemorrhagesinfivediagnosedcasesofdenguefever.Ofthese,threehad
dengueviralantigeninthebraintissuesample.[15]However,detailsofplatelet
countwerenotavailable.Inanotherprovencaseofdengueencephalitis,
hemorrhageduetodecreasedplateletcounthasbeenreported.[16]

Thereisnospecifictreatmentfordengueencephalitis.Treatmentismainly
supportive.Studieshaveshowninhibitionofviralreplicationincellcultureby
manypromisingagentslikeribavirinandgeneticin.[17]Infuture,theseagentsmay
playaroleintreatment.

Conclusion

http://www.ijri.org/article.asp?issn=09713026year=2015volume=25issue=1spage=52epage=55aulast=Nadarajah 3/5
2/19/2017 Acutehemorrhagicencephalitis:AnunusualpresentationofdengueviralinfectionNadarajahJ,MadhusudhanKS,YadavAK,GuptaAK,VikramNK
Inconclusion,thoughthepresentationofdenguefeverasencephalitisisveryrare,
diagnosisshouldbesuspectedinapatientfromanendemicregionwithtypical
clinicalandimagingfeaturesofencephalitis.

References

1. CamBV,FonsmarkL,HueNB,PhuongNT,PoulsenA,HeegaardED.
Prospectivecasecontrolstudyofencephalopathyinchildrenwithdengue
hemorrhagicfever.AmJTropMedHyg200165:84851.

2. HendartoSK,HadinegoroSR.Dengueencephalopathy.ActaPediatrJpn
199234:3507.

3. NathansonN,ColeGA.Immunosuppressionandexperimentalvirusinfection
ofthenervoussystem.AdvVirusRes197016:397428.

4. SolomonT,DungNM,VaughnDW,KneenR,ThaoLT,RaengsakulrachB,et
al.Neurologicalmanifestationsofdengueinfection.Lancet2000355:10539.

5. CarodArtalFJ,WichmannO,FarrarJ,GascnJ.Neurologicalcomplications
ofdenguevirusinfection.LancetNeurol201312:90619.

6. MisraUK,KalitaJ,SyamUK,DholeTN.Neurologicalmanifestationsof
denguevirusinfection.JNeurolSci2006244:11722.

7. MiagostovichMP,RamosRG,NicolAF,NogueiraRM,CuzziMayaT,
OliveiraAV,etal.Retrospectivestudyofdenguefatalcases.ClinNeuropathol
199716:2048.

8. PancharoenC,ThisyakornU.Neurologicalmanifestationsindenguepatients.
SoutheastAsianJTropMedPublicHealth200132:3415.

9. ThisyakornU,ThisyakornC,LimpitikulW,NisalakA.Dengueinfectionwith
centralnervoussystemmanifestations.SoutheastAsianJTropMedPublic
Health199930:5046.

10. YamamotoY,TakasakiT,YamadaK,KimuraM,WashizakiK,YoshikawaK,et
al.Acutedisseminatedencephalomyelitisfollowingdenguefever.Jinfect
Chemother20028:1757.

11. KambleR,PeruvambaJN,KovoorJ,RavishankarS,KolarBS.Bilateral
thalamicinvolvementindengueinfection.NeurolIndia200755:4189.
[PUBMED]
12. AcharyaS,ShuklaS,ThakreR,KothariN,MahajanSN.Dengueencephalitis
Arareentity.JDentMedSci20135:402.

13. GanesanK,DiwanA,ShankarSK,DesaiSB,SainaniGS,KatrakSM.
Chikungunyaencephalomyeloradiculitis:Reportof2caseswithneuroimaging
and1casewithautopsyfindings.AJNRAmJNeuroradiol200829:16367.

14. GeraC,GeorgeU.Acutedisseminatingencephalomyelitiswithhemorrhage
followingdengue.NeurolIndia201058:5956.
[PUBMED]
15. ChimelliL,HahnMD,NettoMB,RamosRG,DiasM,GrayF.Dengue:
Neuropathologicalfindingsin5fatalcasesfromBrazil.ClinNeuropathol
19909:15762.

16. KhannaA,AtamV,GuptaA.Acaseofdengueencephalitiswithintracerebral
hemorrhage.JGlobInfectDis20113:2067.

17. DeClercqE.Yetanothertenstoriesonantiviraldrugdiscovery(PartD):
Paradigms,paradoxesandparaductions.MedResRev201030:667707.

CorrespondenceAddress:
KumbleSeetharamaMadhusudhan
DepartmentofRadiodiagnosis,AllIndiaInstituteofMedicalSciences(AIIMS),
NewDelhi110029
India

SourceofSupport:None,ConflictofInterest:None

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http://www.ijri.org/article.asp?issn=09713026year=2015volume=25issue=1spage=52epage=55aulast=Nadarajah 4/5
2/19/2017 Acutehemorrhagicencephalitis:AnunusualpresentationofdengueviralinfectionNadarajahJ,MadhusudhanKS,YadavAK,GuptaAK,VikramNK

DOI:10.4103/09713026.150145

Figures

[Figure1],[Figure2],[Figure3]

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