Sanne Hoeks

Chapter 5 66 Relation neuro-imaging and outcome Infants were allocated to three groups; Eight out of seventeen patients had no abnormalities on imaging and a favorable neurodevelopmental outcome (6 EV and 2 HPeV); Three out of seventeen patients were categorized as uncertain affected and showed mild cerebral injury on neuroimaging associated with a favorable early outcome (1 EV and 2 HPeV); Six out of seventeen patients had severe neuro-imaging abnormalities with an adverse clinical outcome with psychomotor retardation or death (1 EV, 1 HPeV and 4 HSV). Three infants were born preterm (2 EV and 1 HPeV) and two of them were infected at (late) preterm age. MRI showed punctate white matter injury in one infant (HPeV) and was normal in the other infant (EV). All preterm born infants had a favorable neurodevelopmental outcome. Immunoprofiles and association with imaging and outcome All measured proteins and their concentration are listed in table 2. We compared the concentration of immune related proteins in two specific matrices, CSF and plasma, between neonates with encephalitis caused by either EV, HPeV or HSV. CSF was available in fourteen infants, plasma was available in thirteen infants. Reciprocal changes in the concentration of different immune related proteins show resemblance across the different viruses in both plasma and CSF, as indicated by spider plots (Fig 2, A and B ). In plasma in EV, HPeV as well as in HSV encephalitis, a relatively low concentration of MIP-3β was correlated to a relatively high concentration of IL-8. One exception was the relatively high concentration of IFNa in plasma of infants with a HSV encephalitis compared to infants with an EV or HPeV infection (Fig 2, A ). This pattern with identical reciprocal relations in the concentration of immune related proteins in different viruses, could also be observed in CSF but was less consistent (Fig 2, B ). Next, we performed a hierarchical cluster analysis, comparing cytokine profiles in plasma at time of diagnosis and without (I), those with uncertain (II) and those with severe (III) neurological sequelae or extensive abnormalities on neuroimaging. This analysis revealed a clear separation in 12 immune-related proteins in plasma specific for an impaired neurodevelopmental outcome or severe injury after neonatal viral encephalitis, as depicted in figure 3. In CSF, multiple clusters of immune related proteins were identified and these clusters were neither related to the virus nor prognostic for neurodevelopmental outcome whereas cell influx in CSF was directly related to the expression of proteins (data not shown).