51

Interesting Case

Casereport

AThai43-year-oldmanwithhistory

of amphetamine abuse for 6 years, pre-

sentedwithchronicintermittentoccipital

headachewithlowgradefeverforamonth.

FirstadmissionatKhonKaenhospital,his

physical examinationwasunremarkable.

HisbrainCTwithcontrastwasnormal.CSF

analysishadnopleocytosis,normalprotein

andsugar.Onemonthlater,hedeveloped

progressiveconfusionandaggression.He

wasdiagnosedwithacutepsychosisand

admitted in Khon Kaen Rajanagarindra

psychiatrichospitalfor2months.Although

hereceivedantipsychoticagentconcurrent

withelectroconvulsivetherapy,hegotde-

teriorated,didnottakeanyfoodnordrink

and still had occasional headache. Re-

peated brain CTwith contrast showed

gyral enhancementwith localized efface-

mentofcerebralsulciathighfronto-parietal

regions (figure 1). Subsequent brainMRI

Dr. Salintip Kunadison

Department of Medicine, Khon Kaen Hospital, Khon Kaen Province, Thailand

Corticosteroid-Induced Psychosis Following

Anti-NMDAR Meningoencephalitis

Abstract Anti-NMDARencephalitisisthemost

commonformofautoimmuneencephalitis

andaffectsyoungpatientsandtheymay

haveclinicallydetectable tumors.We re-

portedacaseofanti-N-methyl-D-aspartate

receptor encephalitiswith relapsingpsy-

chosiscausedbyhigh-dosecorticosteroid

treatment.

Keywords: antiN-methyl-D-aspartate

receptor encephalitis; autoimmune en-

cephalitis;corticosteroid;relapsepsychosis

Introduction Autoimmuneencephalitiswasfound

about5to8casesper100,000personsand

themostcommonformwasthetypewith

antibodyagainsttheN-methyl-D-aspartate

receptor (NMDAR).1Here,we reported a

caseofanti-N-methyl-D-aspartatereceptor

encephalitiswith relapsingpsychosis fol-

lowinghigh-dosecorticosteroidtreatment.

5252

Vol.13 No.3

demonstrated leptomeningeal enhance-

mentalongleftfrontallobeandrightpar-

asagittal regionswith0.6cmofmeningi-

omaatmidpart of falx cerebri (figure2).

ThenhewasreferredtoKhonKaenhospital

for etiology evaluation.At that time, his

medicationswererisperidone2mg/dayand

benzhexol2mg/day.Hisphysicalexamina-

tion revealed fever (T 39.3 oC), elevated

bloodpressure(BP158/113mmHg),tachyp-

nea (RR 20/minute), HR 90/minute, no

lymphadenopathynorhepatosplenomegaly.

Therewas a sacral round pressure sore

(grade2)withadiameterof3centimeters

withoutsuperimposedinfection.Helooked

drowsy,confusedandpoorlycooperative.

Neck stiffnesswas present. The cranial

nerveswere normal.Hismuscle power,

motortone,deeptendonreflexesandcorti-

calsignswerenormal.

Figure 1.BrainCTwithcontrast:A.plainCTB.CTwithcontrast(backcoverpage)

5353

Vol.13 No.3

A.

B.

C.

D.

Figure 2.BrainMRIwithcontrast:AT2B.FLAIRC.T1D.T1withcontrast(backcoverpage)

The complete blood count showed

normochromicmicrocytic anemia (MCV

68.3fL),hemoglobinof9.4g/dLandhema-

tocritof28.2%,withreactivethrombocyto-

sisof555,000.Hisbloodchemistryshowed

mildhypokalemiaof3.34mEq/L,hypoalbu-

minemiaof 3.3g/dLandnormal thyroid,

renal and hepatic functions. Anti-HIV,

hepatitisB antigen andhepatitisC anti-

bodywereall negative.Antinuclear anti-

bodywaspositivewithfinespecklepattern

andtiterof1:100.

CSFanalysisshowedclearfluidwith

opening pressure of 47mmH2Owithout

pleocytosis, normal protein and glucose

level,andnoevidenceofinfection.TheCSF

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andserumparaneoplasticantibodieswere

checked andpending.After sepsis from

hospital-acquiredpneumonia (multidrug-

resistantEscherichia coli) hadbeencon-

trolled,hewasinitiallytreatedasautoim-

mune encephal i t is by intravenous

dexamethasone for 3days, thenhis con-

sciousness was improved. He looked

drowsy but responded better to simple

command.Thenhewasdischargedwith

oralprednisolone1mg/kg/dayandawaited

hisparaneoplasticantibodypanel report.

Tendays later, he developed aggressive

behavior,bawledandhurthiswife.Neither

headachenorfeverwasobserved.Hewas

hospitalizedandprednisolonedosagewas

rapidlytaperedto10mg/daywithinaweek

anddaily50mgofazathioprinewasintro-

duced.Firstfewdaysofthisadmission,he

hadlessagitationbutgotpoorcooperation,

perplexity,andmutism.Aweeklater,his

aggressionwasmarkedly improved, then

antipsychoticdrugusagewasdeescalated

foroccasionalagitation.Afterdischarge,he

coulddoactivitiesofdailylivingbyhimself.

Hisbehaviorandmoodwerenearlynormal.

Thenegativismwasdisappeared.Hiscog-

nitivefunctionswerenormalexceptslight-

ly impaired recentmemory. He tolerated

wellwith100mgofazathioprineand10mg

ofprednisoloneperdayanddidnotneed

antipsychoticmedicationanymore.

The paraneoplastic antibody panel

wasreportedthatbothCSFandserumanti-

NMDARantibodywaspositive.The final

diagnosiswas anti-NMDARencephalitis.

His psychotic symptoms after high dose

corticosteroid treatmentwas consistent

with diagnosis of corticosteroid-induced

psychosis. Subsequently, the chest and

abdominalcomputerizedtomographywas

performedandreportednoexistenttumor.

Discussion Here, I reported a case of a Thai

43-year-oldmanwithforchronicintermit-

tentoccipitalheadachewithlowgradefe-

ver, followed by progressive behavioral

changeandpsychoticfeaturefor3months.

Thebrainimagingdemonstratedleptome-

ningealenhancementalongleftfrontallobe

andrightparasagittal regions.Thediffer-

ential diagnosiswas autoimmune-related

meningoencephalitis,suchasprimaryau-

toimmunemeningoencephalitis, central

nervous system involvement of systemic

autoimmune disease (e.g. SLE, Sjögrensyndrome2 or paraneoplastic limbic en-

cephalitis,CNSvasculitisandCNSdemy-

elinatingdisease.Thedefinite diagnosis

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wasmadeafterNMDARantibodyhadbeen

doneandotheretiologieswereexcluded.

Iriondo,etal.reportedamphetamine

inhalationrelatedanti-NMDARencephali-

tis.Theystatedthatacutemethampheta-

mine poisoning caused similar clinical

symptomstoanti-NMDARencephalitisand

mightstimulateimmuneresponsebringing

onpathologyprogression.3Thiswasdiffer-

ent from this case because he took oral

amphetamine for years. The explanation

mightbethatamphetamineinducedproin-

flammatory effect causing initiation and

propagationof autoimmune inflammation

andbroughtdopaminergicneurondamage.4

The anti-NMDAR encephalitis is

clinical-baseddiagnosiscombinewiththe

demonstration of brain structural abnor-

malities and/or inflammation inCSFand

confirmedbythedetectionofCSFantibod-

iesagainsttheGluN1subunitoftheNM-

DAR.1,5,6(serumtestingislessreliable.)1 This

case, thediagnosiswasmadeof clinical

signs and symptoms of neuropsychiatric

features,CSFandserumNMDARantibody

after exclusion of infectious causes and

othersystemicautoimmunediseases.

Becauseofnoclinicaldataofmalig-

nancies, neuropathologic nor radiologic

evidence of limbic system involvement

(couldbe foundonly 25-55%),5,6 this case

wasnotcompletelycompatiblewithPara-

neoplasticNeurologicalSyndromeEuronet-

work diagnostic criteria.6 Hemust be

closelymonitoredonmalignancyforatleast

4to5year.

Thepatienthadrelapsingpsychotic

featuresandcatatoniaabout1weekafter

highdosecorticosteroid(16mg/dayofin-

travenous dexamethasone followed by 1

mg/kg/dayof oral prednisolone).Thedif-

ferentialdiagnoseswerecorticosteroid-in-

ducedpsychosis and relapsing anti-NM-

DARencephalitis.Thefirstwasmorelikely

duetohissymptomsgotworseningduring

he highdose prednisolone course7-9, the

onsetwaswithin1to2weeksaftertreat-

ment7,9)and the clinical signsweremark-

edlyimproveafterrapidcorticosteroidta-

per ing especia l ly be low 40 mg o f

prednisolone.7-9Hypoalbuminemiamightbe

apredisposing factorofcorticosteroid-in-

ducedpsychosis.10

Conclusion This is thefirstcasereportofcorti-

costeroid-inducedpsychosisfollowinganti-

NMDARmeningoencephalitis treatedby

highdosecorticosteroid(intravenousdexa-

methasonefollowedbyoralprednisolone).

Therecurrenceofpsychosisafteritstreat-

5656

Vol.13 No.3

HMGB1mediatestheneuroinflamma-

tory effects of methamphetamine.

BrainBehavImmun2016;51:99-108.

5. DalmauJ,GleichmanAJ,HughesEG,

Rossi JE, PengX, LaiM, et al.Anti-

NMDA-receptorencephalitis:casese-

riesandanalysisoftheeffectsofanti-

bodies.LancetNeurol2008;7:1091-8.

6. TüzünE,DalmauJ.Limbicencephalitis

andvariants:classification,diagnosisand

treatment.Neurologist2007;13:261-71.

7. WarringtonTP,BostwickJM.Psychi-

atricadverseeffectsofcorticosteroids.

MayoClinProc2006;81:1361-7.

8. CiriacoM,VentriceP,RussoG,Scic-

chitanoM,MazzitelloG,ScicchitanoF,

et al. Corticosteroid-related central

nervoussystemsideeffects.JPharma-

colPharmacother2013;4:S94-8.

9. KennaHA,PoonAW,de losAngeles

CP,KoranLM.Psychiatric complica-

tionsoftreatmentwithcorticosteroids:

reviewwith case report. Psychiatry

ClinNeurosci2011;65:549-60.

10.AppenzellerS,CendesF,CostallatLT.

Acutepsychosisinsystemiclupusery-

thematosus.Rheumatol Int 2008; 28:

237-43.

menthadtobeclarifywhetheritwasdis-

ease relapse, treatment-relatedcomplica-

tionor otherdissociatedconditions.The

certain diagnosiswasmade after other

conditions had been exclude and dose

decrementhadimprovedinclinicalmani-

festations.

Disclosure Financialsupport:none

Conflictofinterest:none

References1. DalmauJ,GrausF.Antibody-Mediated

Encephalitis.NEnglJMed2018;378:

840-51.

2. RosenfeldMR,DalmauJO.Paraneoplas-

tic disorders of theCNSand autoim-

munesynapticencephalitis.Continuum

(MinneapMinn)2012;18:366-83.

3. IriondoO, Zaldibar-Gerrikagoitia J,

RodríguezT,García JM,AguileraL.

Anti-NMDA (a-NMDAR) receptoren-

cephalitisrelatedtoacuteconsumption

ofmetamphetamine:relevanceofdif-

ferentialdiagnosis.RevEspAnestesiol

Reanim2017;64:172-6.

4. FrankMG,Adhikary S, Sobesky JL,

WeberMD,WatkinsLR,MaierSF.The

danger-associatedmolecular pattern