corticosteroid-induced psychosis following anti-nmdar ... · interesting case case report a thai...
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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.
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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)
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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-
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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
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