Objective: To devise a set of clinical signs and laboratory parameters that would help clinicians assess prognosis in patients and plan appropriate management.Methods: Medical records of 147 paediatric cases (with a discharge diagnosis of acute viral encephalitis) admitted over a ten year period from 1987 to 1997 were reviewed and relevant information collected on a data extraction form.Results: Of 147 patients, 24 (16.3%) died and 48 (32.7%) were left with severe neurological deficits. A GCS (Glasgow Coma Scale) score between 6-10 had an association with poor outcome (OR = 2.62, Chi-square = 5.57, p-value = 0.018) and that a GCS score of \u3e or = 5 was even more strongly suggestive of poor outcome (OR = 5.49, Chi-square = 12.08, p-value = 0.0005). A history of having seizures, for more than 3 days, also showed a strong association with poor outcome (OR = 3.66, Chi-square = 5.46, p-value = 0.019).CONCLUSION: Patients with an increased risk of death and severe disability can be identified using a few guidelines. Of these, a history of seizures of \u3e 3 days and/or impaired consciousness (GCS \u3c or = 10), at the time of presentation to the hospital, constitute high risk. These cases must be identified promptly and aggressive therapy initiated in order to improve long term outcome

Bhutto, E

Ehtesham, M

Jehan, I

Naim, M

Rehman, M

Siddique, M A

English

eCommons@AKU

eCommons@AKUCommunity Health Sciences Department of Community Health SciencesDecember 1999Prognostic indicators of childhood acute viralencephalitisE BhuttoAga Khan UniversityM NaimAga Khan UniversityM EhteshamAga Khan UniversityM RehmanAga Khan UniversityM A. SiddiqueAga Khan UniversitySee next page for additional authorsFollow this and additional works at: https://ecommons.aku.edu/pakistan_fhs_mc_chs_chsPart of the Pediatrics CommonsRecommended CitationBhutto, E., Naim, M., Ehtesham, M., Rehman, M., Siddique, M. A., Jehan, I. (1999). Prognostic indicators of childhood acute viralencephalitis. Journal of Pakistan Medical Association, 49(12), 311-316.Available at: https://ecommons.aku.edu/pakistan_fhs_mc_chs_chs/642AuthorsE Bhutto, M Naim, M Ehtesham, M Rehman, M A. Siddique, and I JehanThis article is available at eCommons@AKU: https://ecommons.aku.edu/pakistan_fhs_mc_chs_chs/642Prognostic Indicators of Childhood Acute Viral EncephalitisPages with reference to book, From 311 To 316 Erum Bhutto,Maryam Naim,Moneeb Ehtesham,Meher Rehman,Muhammad Atif Siddique ( Final Year Medical Students,Department of Community Health Sciences, The Aga Khan University, Karachi. ) lmtiaz Jehan ( Senior Instructor, Department of Community Health Sciences, The Aga Khan University, Karachi. ) Abstract Objective: To devise a set of clinical signs and laboratory parameters that would help clinicians assessprognosis in patients and plan appropriate management.Methods: Medical records of 147 paediatric cases (with a discharge diagnosis of acute viralencephalitis) admitted over a ten year period from 1987 to 1997 were reviewed and relevantinformation collected on a data extraction form.Results: Of 147 patients, 24 (16.3%) died and 48 (32.7%) were left with severe neurological deficits. AGCS (Glasgow Coma Scale) score between 6-10 had an association with poor outcome (OR = 2.62,Chi-square = 5.57, p-value = 0.018) and that a GCS score of >5 was even more strongly suggestive ofpoor outcome (OR = 5.49, Chisquare = 12.08, p-value =0.0005). A history of having seizures, for morethan 3 days, also showed a strong association with poor outcome (OR= 3.66, Chi- square = 5.46, p-value = 0.019).Conclusion: Patients with an increased risk of death and severe disability can be identified using a fewguidelines. Of these, a history of seizures of >3 days and/or impaired consciousness (GCS _10), at thetime of presentation to the hospital, constitute high risk. These cases must be identified promptly andaggressive therapy initiated in order to improve long term outcome OPMA 49:311,1999).Introduction Central Nervous System (CNS) infections have tremendous importance because of their potential fordeath and permanent neurological damage. The reported incidence of acute encephalitis is between 3.5-7.5 cases per 100,000 patient years1. In children the incidence is about 16.7 cases per 100,000 patientyears2. Acute encephalitis occurs most commonly in the first decade of life with a peak incidence of 1-2 cases per 1000 in the first 6 months of life3. The mortality rate of children with acute encephalitis is3.8- 28.0%4. Study done in American paediatric population, showed that 40% of children whorecovered from acute encephalitis had persistent non-progressive neurological abnormalities5. Severalstudies have been done to find clinical parameters that could predict poor outcome, one such studydone in U.K. showed clinical predictors as young age at presentation, alow score on the Glasgow ComaScale (GCS), disruption of the occulocephalic response and laboratory evidence of infection in theCNS6. In a study on 462 Finnish children4, the risk of death or severe damage in children less than oneyear of age was five-fold greater than that of older children. There was a 3.9% greater risk of death orsevere damage in those children who had been disoriented on admission versus those who were not. Inaddition those children with Herpes Simplex Virus (HSV) or Mycoplasma pneumoniae typeencephalitis had greater risk (11.7 fold and 7 fold respectively) of death or severe damage versus thoseof other viral aetiologies. In another paediatric study focal neurological signs and abnormalneuroimaging studies were the only two factors that predicted poor short-term outcome7. The GCS wasonly predictive if profoundly depressed (<6) but was otherwise not useful.The impact of acute viral encephalitis on individuals and families can be devastating. As timelyintervention can be life saving, the aim of this study was to determine the clinical signs and laboratoryparameters that could help assess high risk cases of viral encephalitis in our local setting.Patients and Methods The study was conducted at The Aga Khan University Hospital (AKUH), Karachi. A retrospectivereview of records was performed using a pre-tested data extraction form. We included all paediatriccases aged <15 years, admitted during the 10 years between 1987-1997, who presented within onemonth of symptom onset and had a diagnosis at discharge of viral encephalitis4. For the ten yearsperiod of observation, a final study population of 147 was reached.The data extraction form was constructed based on criteria laid out by Western literature4-7, a studyconducted in India8 as well as in-house neurologists. It collected relevant information ondemographics, signs and symptoms at presentation, laboratory and radiological investigations done,treatment given and outcome recorded (both at discharge and at follow up within 6 months).Outcome was expressed in four categories which ranked from 1-4 as follows: 1 = death, 2 = majorneurological sequelae, 3 = minor neurological sequelae, 4 complete recovery with no deficits. Majorsequelae included seizures, frank motor deficits (increased tone, hemiplegias, monoplegias, cerebellarsigns, lower motor neuron signs, extrapyramidal signs), cranial nerve damage, mental retardation8.Minor sequelae were scholastic backwardness, subtle neurological signs (up-going plantars, in-coordinate or brisk reflexes) and behavioural changes8. For the purpose of analysis death and majorsequelae were regrouped as ‘poor outcome’ whereas minor sequelae and recovery were called‘favourable outcome’. EPI Info version 6.0 statistical package was used for data analysis. Pooroutcome (n=72) was compared with favourable outcome (n=75) in terms of clinical variables likesymptoms, signs, laboratory values, radiology and treatment at admission. Age was grouped intodiscrete categories (il, 2-5, 6-10 and 11-15 years), as was duration of symptoms (<3, 4-7 and >7 days )and GCS (<5, 6-10 and 11-15). All other values were grouped as abnormal or normal based on hospitalset protocol. Chi-square analysis was used to determine presence of association and odds ratiocalculated for significant results. Results were considered significant if p-value was <0.05.Results A total of 147 cases fullfilled our case definition, of these 42 (28.8%) were females and 104 (71.2%)male. No age group dominated. Acute encephalitis was not associated with any particular season. Themost common symptoms at presentation were fever in 114 (77.5%), impaired consciousness in 83(56.5%) and seizures in 81(55.1%) cases. Sixty-nine (52.3%) had a GCS of 11-15 at presentation(Table 1).Documentation of physical signs were missing in many files and highly variable in the remaining ones;therefore these could not be assessed.None of the haematological investigations revealed any significant trend (Table 2).Serum sodium was normal in 72.5% cases. Cerebrospinal fluid (CSF) examination was not done in 29(19.7%) cases. In the remaining cases CSF analysis revealed abnormal leukocyte counts in 40.7%.Lymphocytosis was found in 82.6% cases in which a CSF Differential Leukocyte count (DLC) wasperformed. Sixty percent of CSF protein levels fell within the normal range as did CSF glucose levels(60% cases). Of the cases in which CSF culture and sensitivity was performed, 98% showed no growth.Electroencephalogram (EEG) was performed in 89 cases of which 86 (96.6%) had abnormal findingsand CT scan was performed in 83 cases, of which 45 (54.2%) showed abnormalities. Acyclovir wasadministered in 39 patients (27%). Mean hospital stay was of 9.3 days, with 82 (55.8%) staying for aweek or less and 125 (85%) being discharged within two weeks (Table 1).Of 147 cases, 24 (16.3%) died. For the remainder at discharge, 48 (32.7%) had major sequelae, 19(12.9%) had minor sequelae and 56 (38.1%) recovered completely. Of the major sequelae seen, thecommonest was motor deficits in 26 followed by seizures in 14 . The more common minor sequelaeseen at discharge were subtle neurological defects in 11 and behavioural changes in 3. Of those whodied, 5 (20.8%) had complicating systemic diagnoses but this was not statistically significant. Followup records were not available for 62 (50.4%) cases. In those who came for follow up, major sequelaewere found in 16 (26.2%) patients and minor sequelae in 13 (2 1.3%) patients (Table 3).For ease of analysis we combined the groups death and major sequelae as poor outcome and minorsequelae and complete recovery as favourable outcome. No significant association of outcome wasfound with age at presentation (Chi-square = 3.99, p-value = 0.26) or season at presentation (Chi-square = 1.00, p-value = 0.80). A GCS score of 6-10 was significantly associated with poor outcome(OR=2.64, Chi-square=5 .57, p-value=0.0 182). There was a significantly worsening prognosis as GCSfell below 5 (OR = 5.49, Chi-square = 12.08, p-value = 0.0005) and the Chi-square for this linear trendwas significant (p-value 0.00025). Of the presenting symptoms, a history of seizures for >7 days,although showing a strong association with poor outcome (one-tailed Fisher exact p-value = 0.011),failed to generate an Odds ratio due to the fact that no patient presenting with such a prolongedduration had a favourable outcome. To overcome this the duration of symptoms were regrouped intotwo categories of <3 and >3 days and the Odds ratio recalculated. The result then showed that a historyof seizures of >3 days duration suggested poor outcome (OR = 3.66, Chisquare=5.46, p-value = 0.0 19)(Table 4).Hyponatremia was not found to have any relation with outcome (OR=1.10, Chi square=0.06, p-value=0.81), neither did CSF lymphocytosis (OR=5.09, Chi-square=2.49, p-value=0.115) nor CSFprotein (OR=l.39, Chi-square=0.55, p-value=0.46). Despite the fact that EEG abnormalities werepresent in 96.6% tested cases, no significant association with outcome could be established (one-tailedFisher exact p-value=0.086). CT abnormalities also failed to show an association with outcome(OR=1.09, Chi-square=0.04, pO.846) (Table 4). The administration of acyclovir did not affect outcome(OR=0.86, Chi square0.17, p=0.68) (Table 4).Of the patients who did have a follow up record in their file, a strong association was found betweenpoor status at discharge and poor status at follow up (0R72.00, Chi-square=29.63, p Discussion In this study we have taken viral encephalitis caused by infection with any one of several commonviruses as one entity. Although this does not take into account the pathogenesis of individual etiologicalagents this study has the advantage of being applicable in our setting where sophisticated investigationsfor causative organisms are not carried out.Previous studies have shown conflicting views regarding the age at presentation and outcome. Ourfinding was that age at presentation had no relation with the prognosis. This is in accordance with Kleinet al.7 but differs from Rautonen et al.4 and Kennedy et al.6 who found a significantly worse prognosisin those aged <3 and <1 years respectively. Seasonal variation has been seen to have a relation with theonset of viral encephalitis, being more in winter and early spring in the west and following themonsoon season in Lucknow, India8. However, no such correlation was found in this study, but thiscould be due to the absence of well-defined seasons in this part of the sub-continent.The most common clinical presentations were fever, impaired consciousness, seizures, vomiting,behavioural changes, recent rash and a recent history seizures of respiratory infections. Out of these,history of with an onset of greater than 3 days, showed an association with poor outcome. Rautonen etal.4 correlated the duration of symptoms with outcome in their study among Finnish children but wereunable to get results that were statistically significant.One of the most important findings in this study was that those patients with a score of<5 on theGlasgow Coma Scale had a significantly worse prognosis than those with a higher score. This is inaccordance with previous studies, especially those of Kennedy et al.6 and Klein et al.7 We, however,also showed that the prognosis was poor even for a relatively higher score of 6-10 and as GCS fellbelow this the prognosis deteriorated concurrently. Abnormal occulocephalic reflexes have a verystrong correlation with unfavourable outcome6. Unfortunately due to lack of adequate documentationwe were unable to assess this parameter. Previous studies have contemplated the relationship betweenCSF findings and outcome. However no significant associations have been established which is inagreement with our findings.Two other diagnostic modalities analysed were the CT and the EEG. Magnetic Resonance Imaging(MRI) has only been recently introduced at our hospital and therefore this investigation was excludedfrom our analysis. EEG picked up abnormalities in 97% cases compared with CT which picked upabnormalities in 54% (Table 2). In both these cases, however, no statistically significant associationwith outcome could be established.The antiviral drug Acyclovir is used in Herpes Simplex Virus (HSV) encephalitis and if administeredearly drastically improves the course of this potentially fatal illness. In our analysis Acycloviradministration had no relation with outcome. However, the role of this drug cannot be assessed fromthis finding as we did not stratify for HSV.At the time of discharge 49% of patients either died or had major sequelae. This is in contrast withRautonen et al.4 in which 9.5% of cases died or had severe damage. This discrepancy could beexplained by differences in race, etiological agent, the duration of the illness at which the patientpresented and the inability of the family to afford tertiary care resulting in the patient being dischargedonce stabilised (not cured) i.e., before optimum therapy. The latter limitation would make the patientappear worse off than those admitted for a longer period. To overcome this bias it would have beenideal to have documentation of a follow up visit. Unfortunately follow up records were not availablefor half of the cases. However it was seen that in those with a follow up there was a significantcorrelation with poor status at discharge and subsequent follow up. Similarly those with a favourableoutcome on discharge maintained a good status on follow up.We conclude that increased rate of death and severe damage in encephalitis can be identified by a fewbasic factors. Specific attention should be focused on those cases that present with a history of seizuresof >3 days duration prior to admission and especially those which have presented with impairedconsciousness. Being a pilot study we recommend that more research should be directed towards viralencephalitis and other acute central nervous system infections.Acknowledgements We are grateful to Dr. Shahid Masud Baig Associate Professor, Chief of Neurology at Aga KhanUniversity Hospital for his valuable feedback on the data extraction form and his unconditional supportfor the project.References 1. Johnson RT. Acute Encephalitis. Clinical Infectious Diseases, 1996;23:219-26.2. Koskiniemi M, Rautonen J, Lelitenierni E, et aI. Epidemiology of encephalitis in children: A 20 yearsurvey. Annals of Neurology. 199129:492-97.3. Wang D, Bertolussi R. Acute viral infections of the central nervous system: An 8 year review. J. Can.Med. Assoc., 1981:125:585-89.4. Rautonen J, Koskiniemi M. Prognostic factors in childhood acute encephalitis. Paediatric InfectiousDisease Journal. 1991:10:441-46.5. Doachowske JB. Acute manifestation and neurological sequelae of EBV encephalitis in children.The J. Paed. Infect. Dis., 1996:15:871-75.6. Kennedy C, Duffy S, Smith R, et al. Clinical predictors of outcome in encephalitis. Archi. Dis.Child., 1987:62:156-62.7. Klern SK. Predictive factors in short term neurological outcome in children with encephalitis. Paed.Neuro., 994:11:308-12.8. Kurnar, Rashmi et al. Clinical sequelae of Japanese encephalitis in children. lnd. J. Med. Res.,1993,97:9-13.

Prognostic indicators of childhood acute viral encephalitis

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Prognostic indicators of childhood acute viral encephalitis

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