Long-term Motor and Cognitive Outcome ofAcute Encephalitis

WHATS KNOWN ON THIS SUBJECT: Encephalitis in children cancause signicant neurologic sequelae, such as motor andcognitive impairment. Previous reported data are based mostlyon questionnaires and clinical assessments.

WHAT THIS STUDY ADDS: Signicant cognitive impairment,attention-decit/hyperactivity disorder, and learning disabilitiesare common after childhood encephalitis. Even children who wereconsidered fully recovered may be signicantly affected.Identiable pathogens, abnormal neuroimaging, and abnormalneurologic examination on discharge are risk factors of pooroutcome.

abstractOBJECTIVES: To examine the long-term motor and neurocognitiveoutcome of children with acute encephalitis and to look at possibleprognostic factors.

METHODS: Children who were treated for acute encephalitis in 20002010 were reevaluated. All children and their parents were interviewedby using structured questionnaires, and the children underwent fullneurologic examinations, along with comprehensive neurocognitive,attention, and behavioral assessments.

RESULTS: Of the 47 children enrolled, 1 died and 29 had neurologicsequelae, including motor impairment, mental retardation, epilepsy,and attention and learning disorders. Children with encephalitis hada signicantly higher prevalence of attention-decit/hyperactivitydisorder (50%) and learning disabilities (20%) compared with thereported rate (5%10%) in the general population of Israel (P , .05)and lower IQ scores. Lower intelligence scores and signicantlyimpaired attention and learning were found even in children whowere considered fully recovered at the time of discharge. Riskfactors for long-term severe neurologic sequelae were focal signs inthe neurologic examination and abnormal neuroimaging on admission,conrmed infectious cause, and long hospital stay.

CONCLUSIONS: Encephalitis in children may be associated with signif-icant long-term neurologic sequelae. Signicant cognitive impairment,attention-decit/hyperactivity disorder, and learning disabilities arecommon, and even children who were considered fully recovered atdischarge may be signicantly affected. Neuropsychological testingshould be recommended for survivors of childhood encephalitis.Pediatrics 2014;133:e546e552

AUTHORS: Orli Michaeli, MD,a Imad Kassis, MD,b YaelShachor-Meyouhas, MD,b Eli Shahar, MD,c and Sarit Ravid,MDc

aDepartment of Pediatrics B, bPediatric Infectious Diseases Unit,and cPediatric Neurology Unit, Meyer Childrens Hospital,Rambam Health Care Campus, Haifa, Israel

KEY WORDSattention-decit, encephalitis, intelligence, sequelae

ABBREVIATIONSADHDattention-decit/hyperactivity disorderCIcondence intervalCNScentral nervous systemHSVherpes simplex virusORodds ratio

Dr Michaeli conducted the initial analyses and drafted the initialmanuscript; Dr Kassis conceptualized and designed the study,and reviewed and revised the manuscript; Dr Shachor-Meyouhas conceptualized the study, and reviewed and revisedthe manuscript; Dr Shahar designed the data collectionquestionnaires and reviewed and revised the manuscript; andDr Ravid conceptualized and designed the study, conducted theinitial analyses and examinations, and reviewed and revised themanuscript. All authors approved the nal manuscript assubmitted.

www.pediatrics.org/cgi/doi/10.1542/peds.2013-3010

doi:10.1542/peds.2013-3010

Accepted for publication Dec 13, 2013

Address correspondence to Sarit Ravid, MD, Pediatric NeurologyUnit, Meyer Childrens Hospital, Rambam Health Care Campus,Haifa 31096, Israel. E-mail: s_ravid@rambam.health.gov.il

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright 2014 by the American Academy of Pediatrics

FINANCIAL DISCLOSURE: The authors have indicated they haveno nancial relationships relevant to this article to disclose.

FUNDING: No external funding.

POTENTIAL CONFLICT OF INTEREST: The authors have indicatedthey have no potential conicts of interest to disclose.

e546 MICHAELI et al

Encephalitis is the presence of an in-ammatory process in the brain pa-renchyma associated with clinicalevidence of brain dysfunction.1 Diag-nosis requires evidence of neurologicdysfunction and central nervous sys-tem (CNS) inammation.2 Viruses arethe most frequently diagnosed infec-tious cause of encephalitis; bacteria,fungi, and parasites are less common.3,4

The frequency and distribution of viru-ses or other infectious agents causingencephalitis vary according to geo-graphical region. In Asia, the majoridentied cause of acute encephalitis isthe Japanese encephalitis virus.5 Tick-borne encephalitis virus and enterovi-rus are common in theWesternworld.6,7

Data on long-termneurologic outcomesin childrenwith encephalitis are limitedand vary depending on the differentgeographic areas and endemic agents.In the majority of studies, data weredetermined by using clinical follow-upassessments at outpatient clinics8,9

and structured questionnaires10; onlya few studies used standardized cog-nitive and behavioral tests.1113 Pre-viously reported neurologic sequelaeinclude developmental delay, motordecits, epilepsy, and learning and be-havioral problems.9,10,14

Information regarding prognostic fac-tors of acute encephalitis in children issparse, and data vary between studies.Several factors have been suggested asindicative of poor outcome, such asyoung age,8,11 deteriorating electroen-cephalography (EEG) ndings,11 focalneurologic signs at discharge,9 lowGlasgow Coma Scale score on admis-sion,8,15 and abnormal neuroimagingresults.9,15

The aim of the present study was toevaluate the long-term sequelae ofacute encephalitis in children and tolook for predictors of long-term mor-bidity. Although most previous studieswere based on clinical assessments orquestionnaires, this study is distinctive

because it provides an objective neu-rocognitive performance assessment.This information can help in offeringguidance in anticipatory counseling, aswell as emphasizing important aspectsfor future follow-up.

METHODS

Study Population

Medical records of children and ado-lescents, aged 1 month to 18 years, ad-mitted to Meyer Childrens Hospital inHaifa, Israel, during the years 2000 to2010 with a nal diagnosis of acute en-cephalitis were reviewed. The hospitalis the main tertiary center in the northof Israel and serves a population of280 000 children. Inclusion criteria in-cluded: (1) at least 1 symptom or signof cerebral dysfunction, such as al-tered mental status, motor or sensorydecits, or seizures; and (2) at least 1of the following signs of inammation:fever (.38C), white blood cell count.153 103 cells/mL, C-reactive proteinlevel .10 mg/L, and cerebrospinaluid cell count .6 cells/mL. Childrenwith meningoencephalitis, demyelina-ting disease, or any underlying neuro-logic, systemic, or metabolic diseasewere excluded from the study. All eli-gible patients were contacted, by letterand then by telephone, to ask whetherthey would be willing to be followed up.

Fifty-eight patients fullled the inclu-sion criteria. Of those, 1 died during theacute phase, 8 declined to be assessed,and3couldnotbe located. Therewasnodifference between those children re-garding age at onset, gender, and pre-senting symptoms.

Written informed consentwas obtainedfrom the parents during the follow-upmeeting. The study was approved bythe institutional review board.

Data Collection

A structured form was used to obtaindata from patients hospital records

regarding presenting symptoms andsigns, laboratory examinations, EEGand neuroimaging studies, and clinicalndings at discharge.

The causative organisms were identi-ed according to serum virus antibodytiters (West Nile virus, mycoplasma,Coxiella burnetii, and Bartonella spe-cies), and cerebrospinal uid poly-merase chain reaction (herpes simplexvirus [HSV], herpesvirus 6, and en-terovirus).

Outcome at discharge was classiedfor all survivors as good, moderate, orpoor. Good outcome was dened ashaving no neurologic sequelae. Mod-erate outcome was dened as havingminor to moderate sequelae, includingaltered behavior or clinical signs notaffecting functions. Poor outcome wasdened as having severe neurologic se-quelae that impair everyday functions.

Clinical, Motor, and NeurocognitiveAssessment

All the children were interviewed andunderwent thorough neurologic ex-amination by a pediatric neurologistduring the follow-up visit. A structuredquestionnaire was used to obtain infor-mation from parents regarding comor-bid illnesses, medications, behavioralproblems, school performance, andability to perform daily activities.

The Kaufman Brief Intelligence Test16

was used to assess intelligence. Thisstandardized, individually adminis-tered test yields 3 scores: verbal, non-verbal, and the overall score, known asthe IQ composite. The mean6 SD age-based standard score for each test is100 6 15. Scores lower than 2 SDsfrom the mean were considered asretardation. Scores between 1 and 2SDs from the mean were considered asborderline intelligence.

The diagnosis of attention-decit/hyperactivity disorder (ADHD) was basedon the criteria of the Diagnostic and

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Statistical Manual of Mental Disorders,Fourth Edition.17 Clinical evaluationwas performed by a pediatric neurol-ogist, using the patients history, in-terviews with the parents and child,and examination during the visit. Inaddition, attention and behavior weremeasured by using the Conners ParentRating ScalesRevised.18

Long-term Outcome

The long-term outcome was classiedfor all survivors as good, moderate, orpoor. Good outcome was dened ashaving no neurologic sequelae. Mod-erate outcome was dened as havingmoderate sequelae, including ADHD,learning disabilities, or seizures af-fecting function but compatible withindependent living. Poor outcome wasdened as having severe neurologicsequelae that impaired everyday func-tions, contrary to independent living.

Statistical Analysis

Data were summarized as proportionsor means6 SDs. x2 analysis was usedto test for qualitative variables, andStudents t test was used for quantita-tive variables.

Multivariate analyses of the associa-tions between clinical presentation,pathogen, EEG and neuroimaging stud-ies, and long-term outcome were con-ducted by using logistic regressionswith odds ratios (ORs) and 95% con-dence intervals (CIs). Analyses for thetotal sample were adjusted for age andgender. For all comparisons and anal-yses, a P value of,.05 was used as thecutoff point of statistical signicance.

RESULTS

A total of 46 patients (28 boys and 18girls) were enrolled in our study. Meanage at disease onset was 56 4.88 years(range: 117 years), and mean time tofollow-up was 5.86 3.08 years (range:111 years).

Clinical Presentation, EEG, andNeuroimaging Studies

The most common presenting symp-toms were fever (73%) and alteredmental status (69%). Hemiparesis wasfound in 13 (28%) patients and ataxiain 6 (13%) patients. Eighteen (39%)patients had seizures.

An etiologic agent was identied in 23(50%) patients. The most commonpathogen was enterovirus (9 patients),followed by HSV (6 patients).

EEG was performed on 31 patients; re-sults were normal in only 3 (10%). Ab-normal results on neuroimaging studieswere found in 39% of the patients(Table 1).

At discharge, neurologic examinationwas normal in 27 (58%) patients; 33%ofpatients showed focal motor decits,and 15% of patients had various levelsof cognitive impairment.

Long-term Motor and CognitiveOutcome

Persisting symptoms were reported byparents of 23 (50%) children. The mostcommon residual symptoms were be-havioral problems (52%), recurrent

headaches (22%), tic disorder (22%),andsleepingproblems(19%). Five (11%)children developed long-standing epi-lepsy, which was intractable in 4 (80%).

Only 4 (9%) childrenhad residualmotordecits. Those children suffered fromspastic hemiparesis and were diag-nosed with herpes encephalitis. On theKaufman Brief Intelligence Test, full-scale IQ .85 was found in only 69%of patients, compared with 84% inthe general population, and 22% ofpatients had a full-scale IQ #70, com-pared with 2.2% in the general pop-ulation (Fig 1).

Twenty-three (50%)patients fullled thecriteria for ADHD. This rate is signi-cantly higher than the reported rate(5%10%) in the general population ofIsrael19 (P, .05). A substantial numberof patients had learning disorders(20%) compared with the reported rate(10%) in the general population ofIsrael20 (P , .05), and 8 (17%) wereplaced in special education classes.

Overall, full recovery was found in only17 (37%) patients. Moderate outcomewas found in 35% of children, and 13(28%) children suffered from pooroutcome (Table 2).

Association Between Pathogen andLong-term Neurologic Outcome

Of 23 patients with veried pathogens,patientswithHSVhad thehighest rateofneurologic sequelae, including signi-cant motor decit (66%), mental retar-dation (50%), ADHD (66%), and epilepsy(50%). However, patients with herpesencephalitis were not the only oneswith an adversely affected prognosis.Of the 40 patients excluding those withHSV, ADHD was found in 18 (45%)patients and mental retardation in 7(17%) (Table 3). Overall, having a con-rmed etiologic agent was signicantlyassociated with being at risk for poorlong-term outcome (OR: 3.67 [95% CI:1.115.68]; P = .04).

TABLE 1 Initial Clinical Presentation, EEG,and Neuroimaging Studies inPatients With Encephalitis

Characteristic Value

Age, mean 6 SD, y 5 6 4.88Focal neurologic signs

Hemiparesis 13 (28)Ataxia 6 (13)Cranial nerves 2 (4)

Coma 7 (15)Seizures 18 (39)Conrmed pathogen 23 (50)EEG (n = 31)

Normal 3 (10)Generalized d waves 24 (77)Focal spikes or slow waves 6 (19)

Neuroimaging (n = 38)Normal 25 (66)Leptomeningeal enhancement 9 (24)Cortical hyperdensity 3 (8)Brain edema 1 (2)

Data are N (%), unless otherwise noted.

e548 MICHAELI et al

Association Between ClinicalPresentation, EEG, andNeuroimaging Studies andLong-term Outcome

Predictors of poor long-term outcomeare summarized in Table 4. The stron-gest predictors included long hospitalstay (P = .004), abnormal neurologicexamination results at discharge (P =.03), abnormal results on neuro-imaging studies (P = .04), and con-rmed pathogen (P = .04). Althoughpatients with seizures, abnormal neu-roimaging ndings, and focal neuro-logic signs at presentation displayeda tendency toward increased risk forepilepsy, the number of patients was

too small to give reasonable inter-pretations.

Association Between Outcome atHospital Discharge and Long-termOutcome

Figure 2 shows the distribution of out-come at hospital discharge and at thelong-term follow-up visit. At hospitaldischarge, 27 (59%) patients had ap-parently made a full recovery, whereas6 (13%) had moderate neurologic se-quelae and 13 (28%) had severe neu-rologic sequelae. Of the 13 childrenwith severe sequelae, 6 improved(46%) and 3 (3%) fully recovered.Conversely, of the 27 children whowereconsidered to have made a full re-covery at time of discharge, only 13 hada good long-term outcome. Four (15%)had mental retardation, 4 (15%) hadlearning disabilities, and 11 (41%) hadADHD.

DISCUSSION

The major ndings of the present studyare that encephalitis in children canlead to signicant long-termneurologicsequelae, mainly reduced neurocog-nitive performance, behavioral prob-lems, ADHD, and learning disabilities.Overall, 50% of our patients suffered

from ADHD and 20% from learningdisabilities. These values are signi-cantly higher than the recent estimatesof ADHD (5%10%) and learning dis-ability (10%) rates in Israel (P , .05).Only 37% of the survivors had fully re-covered, and 28% of the children wereleft with severe neurologic disabilitiesthat impaired everyday functions, suchas motor decits, mental retardation,and intractable seizures. Similar stud-ies that investigate the long-term out-come of encephalitis are sparse, andthe results of long-term neurologicsequelae vary with geographic locationand type of infectious pathogen. Asimilar incidence of severe neurologicsequelae was previously reported byWang et al,9 who found 25% signicantmorbidity, such as epilepsy, mental re-tardation, and focal neurologic signs,in children who experienced acute en-cephalitis. In a study by Clarke et al,11

7 (35%) of 20 children who survivedacute encephalitis experienced mod-erate to severe neurologic impairment.In contrast, an older study by Rautonenet al8 found that only 6.7% of childrenwith encephalitis suffered from severedamage and 90.5% were cured with noor only minor sequelae. This study,however, included only clinical follow-upvisits up to 6 months after dischargeand may therefore have underesti-mated neurocognitive sequelae thatcould manifest at a later stage.

As noted earlier, the most commonsequelae in our study was ADHD, whichwas found in 50% of patients. None ofour patients was diagnosed with ADHDbefore the onset of disease, althoughmost were too young at disease onsetto manifest the characteristic clinicalsymptoms. Because all patients werehealthybefore thedisease,weassumedthe same incidence of the disorder inour study as in the general population.Although the association betweenADHDand other brain insults, such as headtrauma,21,22 bacterial meningitis,23 and

FIGURE 1Comparison of full-scale IQ of children with encephalitis versus the general population IQ.

TABLE 2 Long-term Motor and CognitiveOutcomes

Outcome N (%)

Persisting symptoms 23 (50)Motor decit (hemiparesis) 4 (9)Behavioral problems 24 (52)ADHD 23 (50)Learning disabilities 9 (20)Epilepsy 5 (11)Global IQ

Mental retardation (#70) 10 (22)Below average (7184) 4 (9)Average or above average ($85) 32 (69)

Overall long-term outcomeGood 17 (37)Moderate 16 (35)Poor 13 (28)

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brain tumor,24 was previously reported,little is known about its association withinfectious encephalitis. Behavioral anom-alies similar to ADHD were rst de-scribed as a complication of encephalitis

after the inuenza epidemic of 1918.25

In their study on patients recoveringfrom CNS infections due to enterovirus71, Gau et al26 reported a 20% in-cidence of ADHD, compared with 3% in

the control group. They suggested thatthe infection may involve the prefronto-striatum-subcortical area of the brainthat relates to the core symptoms ofADHD.27 After tick-borne encephalitis,children had lower scores than controlsubjects and relative impairment onseveral attention/concentration tests.13

Impairedmemory functionandreducedability to concentrate was reported byFowler et al14 in children who survivedencephalitis. When assessed by usingcomputerized cognitive tests, thesechildren had slower reaction times butno differences in working memory com-pared with control subjects. This as-sociation is important, because ADHDsymptoms may inuence school per-formance as well as peer and familyrelationships. Early diagnosis of ADHDsymptoms will allow early educationalintervention and treatment if necessary.

Another important nding of our studywas the signicantly lower intelligencescores in children after acute enceph-alitis. A full-scale IQ of .85 was foundin only 69% of patients, comparedwith 84% in the general population,whereas 22% of patients had a full-scale IQ of #70, compared with 2.2%in the general population. There is littleinformation regarding cognitive func-tion after viral encephalitis in children.Similar signicantly lower IQ evalua-tions were previously reported byChang et al12 in childrenwho contractedenterovirus 71 encephalitis. In con-trast, in a study from Germany, nosignicant difference was found inintelligence or neuropsychological eval-uations between children who experi-enced tick-borne encephalitis andcontrol subjects.13

Lower intelligence scores and impairedattention and learning were found inour study even in children who wereconsidered as fully recovered at thetime of discharge. Of 27 children whowere considered to have made a fullrecovery at the time of discharge, 4

TABLE 3 Association Between Pathogen and Long-term Neurologic Outcome

Pathogen N Neurologic Sequelae (n) Total N (%)a

Enterovirus 9 Mental retardation (3), ADHD (5), ticdisorder (3), sleep disturbances (2), learningdisabilities (1), epilepsy (1)

7 (78)

HSV 6 Mental retardation (3), ADHD (4), motor decit (4),tic disorder (3), sleep disturbances (3), epilepsy (3)

5 (83)

West Nile virus 3 ADHD (1), headaches (1) 1 (33)Human herpesvirus 6 1 None 0 (0)Mycoplasma pneumonia 1 ADHD (1), tic disorder (1) 1 (100)Coxiella burnetii 1 ADHD and learning disabilities (1), headaches

(1), sleep disturbances (1)1 (100)

Bartonella henselae 1 None 0 (0)Epstein-Barr virus 1 None 0 (0)a Percentage of subjects with neurologic sequelae.

TABLE 4 Prevalence ORs for Poor Prognosis According to Clinical Presentation, EEG, andNeuroimaging Studies

Variable OR (95% CI) P

Female gender 0.49 (0.131.8) .39Age at diagnosis 0.89 (0.751.05) .15Focal neurologic signs at presentation 1.8 (0.56.32) .35Coma at presentation 1.67 (0.377.6) .51Admission to ICU 1.25 (0.334.73) .74Seizures 2.33 (0.638.64) .2Conrmed pathogen 3.67 (1.115.8) .04*Abnormal EEG 2.75 (0.5214.63) .24Abnormal neuroimaging results 3.56 (0.9113.94) .04*Abnormal neurologic examination results at discharge 3.11 (1.0712.89) .03*Hospital stay 1.18 (1.051.32) .004*

* P , .05.

FIGURE 2Association between outcome at hospital discharge and long-term outcome.

e550 MICHAELI et al

(15%) hadmental retardation, 11 (41%)had ADHD, and 4 (15%) had severelearning disability. A possible explana-tion for these ndings is that cognitiverecovery at discharge, especially inyoungchildren, is usually basedon levelof consciousness, awareness, and ori-entation. Neurocognitive parameters,such as memory, attention, or com-prehension, are not assessed, and fu-ture neuropsychological sequelae thatinterfere with intelligence and learningmay thus be underestimated. In addi-tion, cognitive decits at dischargemaynot be evident until the demands in-crease during school years. Similarlate-onset cognitive sequelae were alsoseen in other studies.14,28,29

Epilepsy is a known sequelae of CNSinfections. Furthermore, between 1%and 5% of epilepsy causes have beenpresumed to be due to CNS infections.30

Recurrent seizures, status epilepticus,and multifocal spikes on EEG were pre-viously reported as risk factors forpostencephalitic epilepsy in children.31,32

In our study, 5 children (11%) developedlong-term epilepsy; the condition wasintractable in 4 children (80%). Seizures,abnormal neuroimaging ndings, andfocal neurologic signs at presentationdisplayed a tendency toward increasedrisk for epilepsy, but the number ofpatients was too small to make a mean-ingful interpretation.

Potential risk factors for a poor neu-rologic outcome in our study wereidentiable pathogens, abnormal im-aging, abnormal neurologic examina-tion at discharge, and longer hospitalstay. The cause of encephalitis wasfound in 50% of our patients. This nd-ing is consistent with previous studies,in which an etiologic diagnosis wasmade in 31% to 75% of cases.911,14,15

The most common pathogens in ourstudy were enterovirus, HSV, and WestNile virus. Childrenwith HSVencephalitishad theworst outcome. One patient died,and 5 of 6 survivors had severe neuro-

logic sequelae. These results are in linewith other recent studies that founda high incidence of neurologic sequelaein children with HSV encephalitis3335;these sequelae were probably second-ary to cortical necrosis and infarction.However, all agents, even those pre-viously considered benign, such as en-terovirus,9,14 caused major neurologicsequelae. Some 78% of our patients withenterovirus encephalitis experiencedlong-term neurologic sequelae, such asmental retardation (33%) and ADHD(55%). Enterovirus 71, a distinctive spe-cies of enterovirus that is common in theAsia-Pacic region but not in our region,has also been reported as being asso-ciated with ADHD and reduced cognitivefunctioning.12,26

Several studies, as well as our study,have shown the predictive value of ab-normal neuroimaging on both short-term7,36 and long-term9,10,37 outcomes ofchildhood encephalitis. This ndingmaybe explained by irreversible parenchy-mal damage. Severe brain lesions mayalso cause focal neurologic signs andcorrelate with abnormal neurologicexaminations at discharge, which in-dependently was found to be a predictorfor long-term neurologic sequelae.9

Long hospital stay was also associatedwith poor prognosis in the presentstudy and most likely reects the se-verity of the disease. Other factors thatreect severity of disease, such as lowGlasgow Coma Scale score on admis-sion,15,28,37 deep coma,28 and ICU ad-mission,14 were previously found aspoor prognostic factors in other stud-ies (although not in the present study).Several authors have suggested thatyoung age is associated with a poorlong-term prognosis in children withencephalitis.8,11,38 We did not observethis correlation in our study.

Although the strength of our study isthe clinical examination and neuro-psychological evaluations of the pa-tients, it did have several limitations. As

a retrospective study, it is limited by thequality of information regarding symp-toms and signs, laboratory evaluation,and treatment during admission avail-able in hospital charts. Furthermore,because medications were not givenaccording to a standardized protocol,the impact of certain treatments, suchas steroids and intravenous immuno-globulin, could not be assessed. Simi-larly, because the diagnostic methodsfor causative organismsandantibodiesfor autoimmune encephalitis haveevolved during the last decade, higherrates of causative organisms might befound if those children were beingevaluated today. Nevertheless, the causeof encephalitis was found in 50% of ourpatients, which is consistent with pre-vious studies.911,14,15 In addition, thestudy was also limited by the highlyvariable follow-up period. However, be-cause attention and cognitive decitsmay rst be evident years after diseaseonset, their prevalence could be evenhigher. Another limitation of our study isthe lack of a control group. Because allpatients were healthy before the dis-ease, we compared the incidence ofcognitive impartment, learning dis-abilities, and ADHD with the incidence ofthe general population, but it is not fullycontrolled for age and socioeconomicstatus.

CONCLUSIONS

Encephalitis in children may be asso-ciated with signicant long-term neu-rologic sequelae. Signicant cognitiveimpairment, ADHD, and learning dis-abilitiesarecommon,andevenchildrenwhowere considered fully recovered atdischargemay be signicantly affected.Neuropsychological testing should berecommended for survivors of child-hood encephalitis. Patients with iden-tiable pathogens, abnormal imaging,abnormal neurologic examinations ondischarge, and long hospital stay havean increased risk of a poor outcome.

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