Persisting symptoms after childhood encephalitis were present for a substantial number of children. Seizures increased the risk of subsequent epilepsy; the only other prognostic marker was admission to the ICU. Even children who were considered fully recovered at discharge reported persisting symptoms at follow-up evaluations. Children who made a full recovery did so within 6 to 12 months, which suggests that all children with encephalitis should be monitored for 1 year after the acute illness.
The mechanism underlying the CNS pathology causing sequelae in TBE appears related to the grade of inflammation in CNS, rather than to direct neuronal destruction. High concentration of IFN-γ, IL-4, IL-6 and IL-8 in CSF might indicate a risk for incomplete recovery in childhood TBE.
Background:
Borrelia burgdorferi and tick-borne encephalitis (TBE) virus are 2 types of tick-borne pathogens that can cause central nervous system infection. Routine diagnostics have so far included analysis of cerebrospinal fluid (CSF) cell numbers, CSF serology for Borrelia burgdorferi and serum serology for TBE virus. However, early diagnosis may be difficult based on antibody detection which takes time to analyze, and with the possibility of false negative results, thus delaying treatment. Cytokine analyses are becoming increasingly available in clinical routine care and may offer important information.
Methods:
Fifteen cytokines and chemokines were measured in the CSF from the diagnostic lumbar puncture of 37 children with TBE, 34 children with neuroborreliosis and 19 children without evidence of central nervous system infection, using Luminex technology.
Results:
Significantly higher levels of proinflammatory interleukin-6 were detected in the samples from TBE-infected children, when compared with neuroborreliosis or controls. In comparison, children with neuroborreliosis had significantly higher levels of interleukin-7, interleukin-8, interleukin-10, and interleukin-13 when compared with TBE infected or controls. Furthermore, the ratio between interleukin-6 and interleukin-10 was significantly different between the 2 types of tick-borne infections.
Conclusions:
The interleukin-6/interleukin-10 ratio can be used as a rapid diagnostic cue upon suspected tick-borne infection, enabling fast and correct treatment. Also, in serology-negative results, such information may strengthen a clinical suspicion.
Childhood encephalitis is a potentially devastating condition with significant morbidity and mortality. Researchers currently lack biomarkers for differentiating infectious encephalitis from those with autoimmune causes which may delay adequate treatment. The authors studied the possibility of using cerebrospinal fluid cytokine and chemokine levels for this purpose. Children admitted to hospital care fulfilling criteria for encephalitis were prospectively included. Children who underwent lumbar puncture but were not classified as central nervous system infections served as controls. Cytokine and chemokine levels in the cerebrospinal fluid obtained upon initial presentation were analyzed using Luminex technology. In children with infectious encephalitis (n = 13), the cerebrospinal fluid displayed markedly elevated mean levels of IL6, IL7, and IL13 as compared to N-methyl-D-aspartate receptor (NMDAR) encephalitis (n = 4) and controls (n = 13). The expression of IL6 appeared to precede that of IL13. Analysis of selected cerebrospinal fluid cytokines may thus allow differential diagnosis of infectious and NMDAR encephalitis already at the initial lumbar puncture and enable immediate therapy.
Understanding the pathophysiological mechanisms of encephalitis is vitally important for developing more efficient treatment regimens. As well as reporting the results of this 40-year study, this study considers possible explanations, addresses current therapeutic options and explores directions for central nervous system infection research.
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