Long-Term Outcomes and Risk Factors Associated With Acute Encephalitis in Children

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1 Journal of the Pediatric Infectious Diseases Society ORIGINAL ARTICLE Long-Term Outcomes and Risk Factors Associated With Acute Encephalitis in Children Suchitra Rao, 1,2 Benjamin Elkon, 2 Kelly B. Flett, 3 Angela F. D. Moss, 4 Timothy J. Bernard, 2,5 Britt Stroud, 6 Karen M. Wilson 7 1 Division of Hospital Medicine and Infectious Diseases; 2 Department of Pediatrics, Children's Hospital Colorado, Aurora; 3 Division of Pediatric Infectious Diseases, Department of Medicine, Boston Children's Hospital, Massachusetts; 4 Adult and Child Center for Health Outcomes and Delivery Science, University of Colorado School of Medicine, and 5 Divisions of Neurology, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora; 6 Department of Neurology, Lee Memorial Health System, Fort Myers, Florida, and 7 Hospital Medicine, Department of Pediatrics, University of Colorado School of Medicine, Aurora Background. Factors associated with poor outcomes of children with encephalitis are not well known. We sought to determine whether electroencephalography (EEG) findings, magnetic resonance imaging (MRI) abnormalities, or the presence of seizures at presentation were associated with poor outcomes. Methods. A retrospective review of patients aged 0 to 21 years who met criteria for a diagnosis of encephalitis admitted between 2000 and 2010 was conducted. Parents of eligible children were contacted and completed 2 questionnaires that assessed current physical and emotional quality of life and neurological deficits at least 1 year after discharge. Results. During the study period, we identified 142 patients with an International Classification of Diseases 9th Revision diagnosis of meningitis, meningoencephalitis, or encephalitis. Of these patients, 114 met criteria for a diagnosis of encephalitis, and 76 of these patients (representing 77 hospitalizations) had complete data available. Forty-nine (64%) patients were available for follow-up. Patients admitted to the intensive care unit were more likely to have abnormal EEG results (P =.001). The presence of seizures on admission was associated with ongoing seizure disorder at follow-up. One or more years after hospitalization, 78% of the patients had persistent symptoms, including 35% with seizures. Four (5%) of the patients died. Abnormal MRI findings and the number of abnormal findings on initial presentation were associated with lower quality-of-life scores. Conclusions. Encephalitis leads to significant morbidity and death, and incomplete recovery is achieved in the majority of hospitalized patients. Abnormal EEG results were found more frequently in critically ill children, patients with abnormal MRI results had lower quality-of-life scores on follow-up, and the presence of seizures on admission was associated with ongoing seizure disorder and lower physical quality-of-life scores. Keywords. cerebrospinal fluid; encephalitis; meningoencephalitis; PedsQL; viral infection. INTRODUCTION Encephalitis is a serious illness that affects children worldwide. It is defined by the presence of an inflammatory process of the brain associated with clinical evidence of neurological dysfunction [1]. The initial presentation can include seizures, headache, paresis, vision loss, hearing impairment, and behavioral changes [2, 3]. Diagnosis is made by clinical presentation, cerebrospinal fluid (CSF) findings, and electroencephalography (EEG) or magnetic resonance imaging (MRI) abnormalities. For children, neurological impairment, which can lead to significant morbidity and death and affect long-term quality of life, has been reported in 25% to 60% of cases [3, 4]. Common Received 20 April 2015; accepted 29 September Correspondence: S. Rao, MBBS, Department of Pediatrics, Children's Hospital of Colorado, University of Colorado School of Medicine, B055, E 16th Ave, Aurora, CO (suchitra. rao@childrenscolorado.org). Journal of the Pediatric Infectious Diseases Society 2017;6(1):20 7 The Author Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please journals.permissions@oup.com. DOI: /jpids/piv075 long-term sequelae include epilepsy, developmental delay, learning disabilities, and chronic headaches [5]. The etiological agent is an important predictor of outcomes in patients with encephalitis [6], the epidemiology of which is geographically dependent [1]. Long-term outcomes have been explored for patients with a number of different viruses, such as herpes simplex virus (HSV) [7 10], Japanese encephalitis [11], enterovirus [12, 13], and Epstein Barr virus [14]. However, in up to 75% of cases of encephalitis, an etiology is not found [1, 15]. There have been few published studies regarding the long-term neurological outcome of pediatric patients with encephalitis, accounting for those without an etiology, using standardized outcome measures. The use of standardized measures can enhance our understanding of the outcomes associated with encephalitis and help us to identify potential risk factors for more severe disease; these measures are used also for other pediatric neurological insults, such as traumatic brain injury and stroke [16, 17]. Therefore, there were 2 main objectives of this study. The first objective was to use standardized measures to explore the long-term outcomes of children with encephalitis to further characterize the impact of this disease 20 JPIDS 2017:6 (March) Rao et al

2 state in quantifiable terms. The second objective was to determine whether EEG and MRI abnormalities and the presence of seizures on initial presentation are risk factors for persistent neurological abnormalities or if they impact quality of life. METHODS Study Population We reviewed the medical records of patients admitted to Children's Hospital Colorado, Aurora, between 2000 and 2010 with an International Classification of Diseases 9th Revision (ICD-9) discharge diagnosis code of encephalitis, meningoencephalitis, or meningitis. Patients were eligible for the study if they had a diagnosis of encephalitis, which was defined as documented encephalopathy (depressed or altered level of consciousness lasting >24 hours, lethargy, or personality change) plus 2 or more of the following: temperature of >38 C; new-onset seizure(s); focal central nervous system findings; abnormal EEG findings compatible with encephalitis; abnormal brain computed tomography (CT) scan or MRI results; or CSF pleocytosis >2 standard deviations of the mean for their age [18]. Patients with insufficient data, anti N-methyl D-aspartate receptor encephalitis, or a hematologic/oncologic diagnosis were excluded from the study. Demographic, clinical laboratory, EEG, and neuroimaging data of each patient were obtained. Approval for the study was obtained from the Colorado Multiple Institutions Review Board ( ). Informed written consent was obtained for the follow-up questionnaires. Follow-Up Patients who met the study criteria for a diagnosis of encephalitis were eligible for follow-up if at least 1 year had passed since their original diagnosis. A structured telephone interview was conducted with parents of eligible patients using 2 questionnaires designed to assess quality of life; they were also mailed if requested by a parent. The first questionnaire was the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales [19], which is a 23-item scale designed to measure health-related quality of life in 4 categories: physical functioning (8 items), emotional functioning (5 items), social functioning (5 items), and school functioning (5 items). The psychosocial score is a composite of the emotional, social, and school functioning scores. The PedsQL questionnaire was validated previously, is reliable in patient populations [20], and is suggested as a core global outcome measure by the National Institute of Neurological Disorders and Stroke Common Data Elements [16]. The second questionnaire was used to determine the persistence of specific neurological symptoms or difficulties with areas of daily living such as weakness, speech, headaches, and seizures, and it covered areas relevant to encephalitis follow-up that were not addressed in the PedsQL questionnaire (see Appendix). The questionnaire was pilot tested with parents of children with chronic medical conditions and modified on the basis of results from this testing. Statistical Analysis Summary statistics are reported as medians (interquartile ranges [IQRs]) for continuous data and counts (proportions) for categorical data. The χ 2 and Fisher exact tests for association were used to compare certain clinical factors on admission with persistent abnormalities at least 1 year after the diagnosis of encephalitis. Persistent neurological abnormalities were defined as the presence of seizures, behavioral problems, or 1 or more neurological deficits, such as weakness, speech problems, developmental delay, and learning problems. Comparisons for clinical findings at admission and the presence of neurological deficits, behavioral problems, and seizures at discharge were also examined with the χ 2 and Fisher exact tests for association. Neurological deficits at discharge were defined as the presence of psychiatric problems or at least 1 physical problem, such as motor deficits, ataxia/cerebellar signs, or movement disorder. Spearman partial correlation was used to measure the strength of the association between PedsQL scores and clinical findings at admission and at discharge while controlling for the effect of age at the time that the survey was administered. The following empirical guidelines for interpreting the magnitude of the correlation coefficients were used: values less than 0.2 indicate weak correlation, values between 0.2 and 0.3 indicate moderate correlation, and values greater than 0.3 indicate large correlation. The McNemar test for paired data was used to test for differences in proportions in abnormalities at admission and during hospitalization against those present at discharge. P values were adjusted for multiple comparisons within each subanalysis by using the Hochberg method, which preserved the overall type I error rate for each subanalysis, allowing the adjusted P values to be interpreted at the 0.05 level of significance. Statistics were performed by using SAS version 9.4 statistical software (SAS Institute, Cary, NC) and SPSS version 22 (IBM Corp., Armonk, NY). RESULTS We identified 142 patients with an ICD-9 diagnosis of meningitis, meningoencephalitis, or encephalitis during our study period. Of these patients, 114 met our criteria for a diagnosis of encephalitis and underwent chart review. Twelve patients were excluded because of a diagnosis of anti N-methyl D-aspartate receptor encephalitis, and 26 patients were excluded because of oncologic comorbidity or insufficient data regarding clinical presentation in the medical record. Seventy-six patients (representing 77 hospitalizations) had data available for review. One patient had a repeat hospitalization for encephalitis 3 years after the initial episode; the etiology was not identified for either presentation. An etiology was identified in 29 (38%) of the cases, Outcomes in Children After Encephalitis JPIDS 2017:6 (March) 21

3 Figure 1. Flow diagram showing study participants with encephalitis at Children's Hospital Colorado ( ), from initial assessment through follow-up. Abbreviations: HSV, herpes simplex virus; ICD-9, International Classification of Diseases 9th Revision. 93% of which were from an infectious source. The most common etiologies were HSV, enterovirus, and influenza (Figure 1). The median age at diagnosis was 7 years (IQR, 2 13 years). One patient had a previous history of developmental delay, 1 had a history of seizures, and 2 had a history of migraine. Thirtytwo (42%) patients were admitted to the ICU, and 4 (5%) patients died. Neurological deficits present on admission and persistence of deficits at discharge are summarized in Figure 2. Most patients who presented with motor deficits, personality changes, and/or ataxia/cerebellar signs were likely to have resolution of their symptoms before discharge. Forty-nine patients were available for follow-up. The median time to follow-up was 1.3 years. Subjects with and without follow-up data were similar in terms of demographics and clinical characteristics (Table 1). Persistent neurological outcomes and PedsQL scores with normative data [20] are listed in Tables 2 and 3, respectively. Persistent deficits were reported in 38 (78%) patients. The most common residual neurological symptoms reported were psychiatric abnormalities, weakness, behavioral or cognitive deficits, vision problems, and headaches. Seventeen patients (35%) reported ongoing seizures. Patients with an etiology identified had lower median physical scores than patients without an etiology identified (87.5 vs 97; P =.02), but their overall and psychosocial scores were not significantly different. Patients with HSV and influenza had lower median physical and psychosocial scores, and patients who tested positive for enterovirus had higher median scores, but these differences were not statistically significant. There were no significant associations observed between factors on admission, such as CSF pleocytosis, CT/MRI or EEG abnormalities, or neurological deficits present at discharge. Patients admitted to the ICU were more likely to have had EEG abnormalities (P =.013). Long-term outcomes were assessed by evaluating the PedsQL scores and the presence of neurological symptoms and signs at least 1 year after diagnosis. Having seizures present on admission was significantly associated with ongoing seizures at least 1 year after the diagnosis of encephalitis (94% vs 42%; P =.0036). Partial correlation coefficients of clinical factors on admission with PedsQL scores at least 1 year after diagnosis are presented in Table 4. After removing the effects of age, having abnormal MRI results on admission was associated with lower 22 JPIDS 2017:6 (March) Rao et al

4 Figure 2. Neurological deficits and persistence of symptoms and signs on discharge among patients with encephalitis at Children's Hospital Colorado, (N = 49); significant differences in proportions were evaluated by the χ 2 and Fisher exact tests. psychosocial and physical scores, and the presence of seizures on admission correlated with lower physical scores. The presence of EEG abnormalities on admission did not correlate with PedsQL scores. However, an increase in the number of clinical factors on admission (MRI abnormalities, EEG abnormalities, seizures, and CSF pleocytosis) correlated with lower PedsQL scores. DISCUSSION In our study of long-term outcomes of children with encephalitis, we found that almost 80% of patients with encephalitis had persistent neurological symptoms on long-term follow-up. MRI findings and the presence/absence of seizures on admission were helpful in predicting long-term outcomes. We found that abnormal MRI findings and seizures were correlated with lower quality-of-life scores. The presence of seizures at presentation was associated with patients having ongoing seizure disorder. Finally, although EEG abnormalities were more commonly seen among critically ill patients, EEG findings were not helpful in predicting long-term outcomes. Given the limited data regarding long-term outcomes in children with encephalitis, these findings are important for informing which factors on presentation might predict quality-of-life outcomes. The results of our study suggest a role for MRI for not only diagnosing and assisting with the etiology of encephalitis but also the prognostic information it may provide. Although abnormal MRI findings in our study were not associated with findings at discharge or gross neurological deficits, they were potentially associated with more subtle deficits identified by the PedsQL questionnaire. The strongest correlation was noted for the psychosocial score, which evaluates mental and emotional health and incorporates perception of self and ability to function in the community. Klein et al [2] reported that MRI abnormalities were predictive of abnormal neurological outcome at hospital discharge, but their study did not follow patients to assess long-term outcomes. Wang et al [3] reported that focal cortical parenchymal abnormalities that appeared on MRI predicted poorer long-term outcomes. Despite having detailed radiographic characterization of the lesions in those patients with MRI abnormalities, our study did not find an association between specific MRI abnormalities and adverse outcome, but this finding might have been limited by sample size. In contrast, although EEG is a useful tool for assessing acute brain dysfunction [4], EEG findings do not predict long-term outcomes. The results of our study show that any EEG abnormalities, particularly severe EEG findings, Outcomes in Children After Encephalitis JPIDS 2017:6 (March) 23

5 Table 1. Demographics, Clinical Characteristics, and Hospital Course of Patients With Encephalitis Seen at Children's Hospital Colorado, a Variable Total Patients Follow-Up Group (N = 49) No-Follow-Up Group (N = 27) b Demographics Age at diagnosis, years; median (interquartile range) 7 ( ) 6.8 ( ) 7.9 ( ) Male 41 (54.0) 25 (51.0) 16 (59.3) Ethnicity/race White 47 (61.8) 31 (63.3) 16 (59.3) White (Hispanic) 19 (24.7) 13 (26.5) 5 (18.5) Black 1 (1.3) 1 (2) 0 (0) Asian 3 (4) 2 (4) 1 (4) Other 3 (4) 0 (0) 3 (11) Unknown 3 (4) 2 (4) 1 (4) Total Episodes of Encephalitis Follow-Up Group (N = 49) No-Follow-Up Group (N = 28) b Clinical presentation/comorbidity Any underlying comorbidity 11 (14.5) 8 (16.7) 3 (10.7) History of recent acute illness 37 (49.3) 21 (44.7) 16 (57.1) Headache 30 (39.3) 22 (44.9) 8 (28.6) Behavioral changes 29 (38.2) 20 (41.7) 9 (32.1) Altered mental status 77 (100) 49 (100) 28 (100) Fever 49 (64) 31 (63.3) 18 (64.3) Seizures 47 (62) 29 (60.4) 18 (64.3) Central nervous system abnormality 33 (43) 23 (46.9) 10 (35.7) At least 1 physical finding 45 (59.2) 29 (60.4) 16 (57.1) Motor deficit 37 (48.7) 23 (47.9) 14 (50.0) Ataxia/cerebellar signs 21 (27.6) 14 (29.2) 7 (25.0) Movement disorder 8 (10.7) 6 (12.8) 2 (7.1) Psychiatric problem 22 (28.9) 16 (33.3) 6 (21.4) Laboratory/imaging/EEG findings CSF pleocytosis 61 (80) 40 (83.3) 21 (75.0) MRI/CT abnormalities 39 (51.3) 26 (54.2) 13 (46.4) EEG abnormalities 47 (71.2) 31 (73.8) 16 (66.7) Treatment IVIg 5 (6.8) 4 (8.9) 1 (3.6) Steroids 19 (27.5) 11 (25.0) 8 (32.0) <21 days of acyclovir 37 ( 59.7) 19 (51.4) 18 (72.0) >21 days of acyclovir 25 (40.3) 18 (48.6) 7 (28.0) Hospital course Rehabilitation admission 20 (29.0) 15 (34.1) 5 (20.0) ICU admission 32 (44) 18 (38.3) 14 (56.0) Days in ICU 4 (2 7) 4.5 (2 6) 3.0 (2 7) Length of stay, days; median (interquartile range) 7.0 ( ) 7.2 ( ) 7.0 ( ) Death 4 (5.8) 0 (0) 4 (16) Clinical factors on discharge At least 1 physical finding 18 (23.7) 11 (22.9) 7 (25.0) Motor deficit 16 (21.1) 10 (20.8) 6 (21.4) Ataxia/cerebellar signs 4 (5.3) 2 (4.2) 2 (7.1) Movement disorder 3 (4) 1 (2.1) 2 (7.1) Psychiatric problem 8 (10.5) 5 (10.4) 3 (10.7) Abbreviations: CSF, cerebrospinal fluid; CT, computed tomography; EEG, electroencephalography; ICU, intensive care unit; IQR, interquartile range; IVIg, intravenous immunoglobulin; MRI, magnetic resonance imaging. a Values shown are number (percentage) unless otherwise specified. b There was no statistically significant difference between the follow-up and no-follow-up groups. were more prevalent in patients admitted to the pediatric ICU. We did not, however, find an independent association between EEG abnormalities or ICU stay and poor long-term outcomes, in contrast to the findings of Wang et al [3]. Our findings suggest that patients who present with more severe clinical signs and symptoms at presentation are more likely to have EEG abnormalities, but they do not necessarily correlate with long-term outcomes. Although EEG findings may not be useful for prognosis, our study results show that seizures on initial presentation 24 JPIDS 2017:6 (March) Rao et al

6 Table 2. Persistent Neurological Deficits at Least 1 Year After Diagnosis of Encephalitis Among Patients Seen at Children's Hospital Colorado, (N = 49) Table 3. PedsQL Scores for Patients at Least 1 Year After Diagnosis of Encephalitis Among Patients Seen at Children's Hospital Colorado, (N = 49) Variable n % (95% CI) Neurological deficit Any deficit (66 90) Weakness (20 46) Behavioral problem (18 44) Developmental delay (22 48) Anxiety/depression (23 51) Vision problem (22 48) Speech problem (18 44) Sleep problem 9 18 (7 29) Learning problem (27 55) Swallowing problem 5 10 (2 18) Hearing problem 3 6 (0 13) Headache (22 48) Seizures (22 48) Services/aids/medications required On antiepileptic(s) (12 36) Glasses (15 39) Hearing aid 1 2 (0 6) Speech therapy (35 63) Physical therapy (35 63) Occupational therapy (35 63) Abbreviation: CI, confidence interval. correlated with poorer long-term outcomes, which has been corroborated by other reports [2, 3]. From their study, Misra et al [21] reported that seizures resulting from encephalitis were associated with poor outcomes at 3 months follow-up. The study Age Category PedsQL Score (Median [IQR]) Physical a 94 (75 100) 2 4 y of age 95 (53 100) 5 7 y of age 97 (30 100) 8 12 y of age 89 (63 97) >13 y of age 94 (88 100) Psychosocial a 75 (60 92) 2 4 y of age 73 (56 100) 5 7 y of age 76 (56 91) 8 12 y of age 78 (62 93) >13 y of age 75 (60 79) Abbreviations: IQR, interquartile range; PedsQL, Pediatric Quality of Life Inventory; SD, standard deviation. a Parent proxy-report mean scores for PedsQL physical health among 8696 families of healthy children were (SD, 19.7), and mean scores for psychosocial health among 8714 families were (SD, 15.34) in a study by Varni et al [20]. did not identify specific outcome domains as we did. It should be noted that the most common etiological agents reported by Misra et al, specifically, Japanese encephalitis and dengue, were different than those in our study. In addition, our finding that the presence of seizures at presentation increased the risk of subsequent seizure disorder was described previously [4]. These findings raise questions about whether identifying and optimizing seizure management early in the hospital course could serve as a neuroprotective strategy, and they warrant further study. The majority of previous studies in which long-term outcomes of patients with encephalitis were explored focused on Table 4. Partial Correlations of PedsQL Scores (Obtained at Least 1 Year After Diagnosis) With Clinical Factors on Admission After Adjusting for Age Among Patients With Encephalitis Seen at Children's Hospital Colorado, Physical Score Psychosocial Score Overall Score Clinical Factor on Admission n Median Spearman rho a Median Spearman rho a Median Spearman rho a MRI/CT b 76.5 Abnormal Normal EEG Abnormal Normal Seizures Yes No CSF pleocytosis Yes No No. of clinical factors present Abbreviations: CSF, cerebrospinal fluid; CT, computed tomography; EEG, electroencephalography; MRI, magnetic resonance imaging; PedsQL, Pediatric Quality of Life Inventory. a Values of represent weak correlation; values of represent moderate correlation; and values of >0.3 represent strong correlation. b The adjusted P value is <.05. Outcomes in Children After Encephalitis JPIDS 2017:6 (March) 25

7 a specific etiological agent [7, 11, 13, 14, 22]. However, given that the majority of cases of encephalitis are without an etiology, we sought to explore the long-term outcomes of encephalitis regardless of whether an agent was identified, because it is more relevant to the usual clinical setting. We found that the identification of an etiological agent did not influence quality-of-life scores, but our data are limited by the lack of standardized testing at our institution. Although other studies have explored short-term outcomes during hospitalizations [2] or focused primarily on long-term outcomes [23, 24], a strength of our study is that we report both long-term and short-term outcomes. In addition to reporting initial presentation and outcomes at discharge, we sought to follow patients at least 1 year after their initial diagnosis of encephalitis, by which time their deficits are usually persistent [25]. We selected the PedsQL questionnaire for our study because it was validated for use in studies of neurological disorders, it is brief and reliable, and it can be administered by telephone, which likely contributed to our high response rate. Because this tool does not account for specific deficits, we included an additional questionnaire related to neurological deficits, which provided further insight into the long-term morbidity associated with encephalitis. There are limitations to our study. Our study showed an increase in the number of deficits correlated with lower physical, psychosocial, and overall PedsQL scores. However, we were not able to determine whether they were independent predictors because of our small sample size. There was a significant percentage of patients excluded from analysis because of incomplete medical records, which may have skewed our data. Selection bias exists because of the nature of our follow-up. Also, there were variable times to patient follow-up for the completion of the questionnaires. However, because most patients with encephalitis who show full recovery are likely to do so within 12 months of their initial diagnosis [4], we ensured that follow-up was obtained at least 1 year after their diagnosis, by which time their clinical characteristics were more likely to be persistent. In addition, there are certain neurological deficits that are nonspecific and may not be related to encephalitis (such as the presence of headaches) or may have been present before the diagnosis of encephalitis. We documented in our detailed questionnaire only those symptoms that were new after the diagnosis of encephalitis, but reporting was subject to recall bias and may have influenced the PedsQL scores. A prospective longitudinal study that includes active methods of subject follow-up and formal neuropsychological assessments linking early indicators to etiology, disease progression, and prognosis would yield an improved understanding of long-term outcomes. This study of long-term outcomes of patients hospitalized with encephalitis found that long-term deficits are seen in approximately 80% of patients, and subsequent seizure disorder is seen in 35% of patients. Abnormal MRI findings at presentation correlate with worse quality-of-life outcomes. The presence of seizures on presentation predicts subsequent seizure disorder and is associated also with lower physical quality-of-life scores. Our data suggest that MRI findings might provide some prognostic information. Close follow-up of these patients is advised, because they are at risk of impairment with regards to their quality of life and subsequent epilepsy. Additional prospective studies with larger cohorts and more detailed outcome measures are needed to further determine risk factors that are predictive of poor outcomes. Note Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. References 1. Tunkel AR, Glaser CA, Bloch KC et al. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2008; 47: Klein SK, Hom DL, Anderson MR, Latrizza AT, Toltzis P. Predictive factors of short-term neurologic outcome in children with encephalitis. Pediatr Neurol 1994; 11: Wang IJ, Lee PI, Huang LM et al. The correlation between neurological evaluations and neurological outcome in acute encephalitis: a hospital-based study. 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8 20. Varni JW, Limbers CA, Neighbors K et al. The PedsQL infant scales: feasibility, internal consistency reliability, and validity in healthy and ill infants. Qual Life Res 2011; 20: Misra UK, Kalita J. Seizures in encephalitis: predictors and outcome. Seizure 2009; 18: Engman ML, Adolfsson I, Lewensohn-Fuchs I et al. Neuropsychologic outcomes in children with neonatal herpes encephalitis. Pediatr Neurol 2008; 38: Schmidt A, Buhler R, Muhlemann K, Hess CW, Tauber MG. Long-term outcome of acute encephalitis of unknown aetiology in adults. Clin Microbiol Infect 2011; 17: Mailles A, De Broucker T, Costanzo P et al. Long-term outcome of patients presenting with acute infectious encephalitis of various causes in France. Clin Infect Dis 2012; 54: Fowler A, Stodberg T, Eriksson M, Wickstrom R. Long-term outcomes of acute encephalitis in childhood. Pediatrics 2010; 126:e Swallowing problems no yes Hearing problems or deafness no yes Headaches no yes If you have answered yes to any of the above, was this present before the diagnosis of encephalitis? If so, please circle:since your child's encephalitis, does he or she currently: Use a wheelchair? no yes Wear glasses? no yes Wear hearing aids? no yes APPENDIX TCH Neurological Outcomes Questionnaire Child's Name: Date of Birth: Your Name: Relationship to child: General health: In general, would you say your child's health is: Excellent Very good Good Fair Poor Have you been told by a doctor, nurse, or other health professional that your child has any of the following problems? Weakness of the arms or legs no yes Behavior problems no yes Developmental delay no yes Depression or anxiety problems no yes Vision problems no yes Speech problems no yes Sleep disturbance no yes Learning problems no yes Has your child ever needed any of the following services after discharge from a hospital for encephalitis? Speech therapy no yes Occupational therapy no yes Physical therapy no yes Seizures: 2. Does your child have seizures since having encephalitis? no yes If the answer is yes, answer questions 3 5 below: 3. What best describes the type of seizure pattern your child has: Staring episodes Focal seizures (affecting one part of the body) Generalized seizures (affecting multiple parts of the body) Other (describe) 4. During the past 4 weeks, how many seizures has your child had? 5. Does your child take medication(s) for the seizures? no yes Outcomes in Children After Encephalitis JPIDS 2017:6 (March) 27