Childhood encephalopathy: viruses, immune response, and outcome

Abstract

This study examined children with an acute encephalopathy illness for evidence of viral infection, disordered blood‐brain barrier function, intrathecal immunoglobulin synthesis, and interferon (IFN) production, and related their temporal occurrence to outcome. A prospective study of 22 children (13 males, 9 females; age range 1mo to 13y, median 2y 4mo), recorded clinical details, with serum and cerebrospinal fluid (CSF) analysis near presentation and then on convalescent specimens taken up to day 39 of the neurological illness. Outcome was assessed with standard scales between 18 months and 3 years after presentation. A history consistent with viral infection was given in 17 children but laboratory evidence of viral infection was found in only 7 (7/17). In 18 out of 21 children, an elevated CSF: serum albumin ratio indicative of impairment of the blood—CSF and blood—brain barriers was detected at some stage of the illness. In 14 of the 15 children with a raised immunoglobulin G index, and in 12 of the 14 children where the CSF was positive for oligoclonal bands, this was preceded by, or was observed at the same time as, an abnormal albumin ratio. Sixteen children (16/18) had elevated IFN‐α levels in serum, or CSF, or in both. We conclude that these findings indicate an initial disruption of the blood‐brain barrier followed by intrathecal antibody production by activated lymphocytes, clonally restricted to a few antigens. This is the first in vivo study to show this as an important pathogenetic mechanism of encephalitis in children. Poor outcome was associated with young age, a deteriorating electroencephalogram pattern from grade 1 to grade 2, and the degree of blood‐brain barrier impairment, particularly when prolonged, but not with Glasgow Coma Scale score. The persistence of IFN‐α was associated with a good prognosis.

Long-term Motor and Cognitive Outcome of Acute Encephalitis

“…Several authors have suggested that young age is associated with a poor long-term prognosis in children with encephalitis. 8,11,38 We did not observe this correlation in our study.…”

“…This finding is consistent with previous studies, in which an etiologic diagnosis was made in 31% to 75% of cases. [9][10][11]14,15 The most common pathogens in our study were enterovirus, HSV, and West Nile virus. Children with HSV encephalitis had the worst outcome.…”

“…A similar incidence of severe neurologic sequelae was previously reported by Wang et al, 9 who found 25% significant morbidity, such as epilepsy, mental retardation, and focal neurologic signs, in children who experienced acute encephalitis. In a study by Clarke et al, 11 7 (35%) of 20 children who survived acute encephalitis experienced moderate to severe neurologic impairment. In contrast, an older study by Rautonen et al 8 found that only 6.7% of children with encephalitis suffered from severe damage and 90.5% were cured with no or only minor sequelae.…”

“…In the majority of studies, data were determined by using clinical follow-up assessments at outpatient clinics 8,9 and structured questionnaires 10 ; only a few studies used standardized cognitive and behavioral tests. [11][12][13] Previously reported neurologic sequelae include developmental delay, motor deficits, epilepsy, and learning and behavioral problems. 9,10,14 Information regarding prognostic factors of acute encephalitis in children is sparse, and data vary between studies.…”

“…9,10,14 Information regarding prognostic factors of acute encephalitis in children is sparse, and data vary between studies. Several factors have been suggested as indicative of poor outcome, such as young age, 8,11 deteriorating electroencephalography (EEG) findings, 11 focal neurologic signs at discharge, 9 low Glasgow Coma Scale score on admission, 8,15 and abnormal neuroimaging results. 9,15 The aim of the present study was to evaluate the long-term sequelae of acute encephalitis in children and to look for predictors of long-term morbidity.…”