Table 1.
Clinical, investigations, treatment and outcome details of ADEM, anti-NMDAR encephalitis and enteroviral encephalitis cohorts.
Fig 1.
CSF concentrations of cytokine/chemokines with >75% sensitivity to detect intrathecal inflammation in all children with acute encephalitis- acute disseminated encephalomyelitis (ADEM), anti-NMDAR encephalitis (anti-NMDAR E) and enteroviral encephalitis (EVE).
Dotted lines represent medians. The statistical analysis was performed using Kruskal Wallis test. The 95% centile of the control values are presented (P95 control).
Table 2.
The sensitivity of CSF cytokine/chemokines in ADEM, anti-NMDAR E, EVE and all encephalitis patients compared to controls.
The molecules are presented in descending order of sensitivity in all encephalitis groups.
Fig 2.
Heat map of elevated CSF cytokine/ chemokines# in encephalitis groups compared to controls presented according to T and B cell subsets.
There is a broad elevation of cytokine/chemokines related to all Th helper subsets (Th1, Th2, T reg, Th17, B cell and other cytokines and chemokines) in ADEM patients unlike anti-NMDAR E and EVE. # Cytokine/chemokines were shaded only if these molecules were statistically significantly elevated in different encephalitis groups compared to controls (p<0.05).
Fig 3.
CSF cytokine/chemokine levels that were more elevated in ADEM compared to EVE and anti-NMDAR E.
Th17 (IL-21, IL-17A) and Th2 (CCL17, and IL-4) related cytokine/chemokines showed statistically significant elevation in ADEM compared to both EVE and anti-NMDAR E. CXCL12 showed paradoxical decrease in EVE and anti-NMDAR E, in contrast to elevation noted in ADEM.
Fig 4.
Hierarchical cluster analysis heat-map showing nearest-neighbour correlations of cytokines and chemokines in ADEM, anti-NMDAR E, EVE and controls.
Cytokines with positive correlations are represented in graded shades of black and negative correlations in graded shades of red. The same order of the analytes along axis is used for all the three heatmaps to allow comparisons. The clustering pattern showed some similarities (cluster A) in immune mediated encephalitis (ADEM and anti-NMDAR E), which was less observed in viral encephalitis and controls.
Fig 5.
Heat map representation of cytokine/chemokine molecule interaction in the CSF of patients with all encephalitis with severe encephalopathy at admission (modified Rankin scale, MRS 5) and worse disability at follow up (MRS >2).
The cluster B molecules showed similar positive correlations between those with higher severity of encephalopathy and those with disability in follow up.