Impact of meningoencephalitis and sepsis on delirium and subsequent neurological impairment in pediatric patients: a prospective proof-of-concept biomarker and EEG study

To assess the incidence and severity of delirium and subsequent neurological impairment in pediatric intensive care unit (PICU) patients with meningoencephalitis (ME) and sepsis. Prospective study enrolling PICU patients with sepsis or meningoencephalitis (ME) and healthy controls. Daily delirium assessment, repeated electroencephalography, blood sampling at days 1, 3, 5 and lumbar puncture, if clinically indicated, for cerebrospinal fluid (CSF) sampling were performed. Biomarkers of inflammation (CRP, PCT, IL-6), endothelial activation (NT-proCNP), neurodegeneration (NSE, tau), neuroaxonal damage (NfL, NfH, UCHL-1) and glial injury (GFAP, S100B) were measured. Neurological status was assessed using the Functional Status Scale (FSS), the pediatric overall performance category (POPC) and the pediatric cerebral performance scale (PCPC) before admission and after three months. Twenty-four PICU patients (ME n = 9, sepsis n = 15) and eleven controls were enrolled. The delirium incidence was not statistically higher in patients with sepsis (60%, n = 9/15) compared to ME (33%, n = 3/9, p = 0.105). Children with delirium (n = 12) had a higher FSS (10.0 [9.8, 12.0] vs. 7.5 [7.0, 9.0], p = 0.009) at day 1 than children without delirium (n = 12), without significant differences in blood and CSF biomarker levels. Patients with ME presented higher levels of blood NfL compared to sepsis patients at day 3 (16.8 [12.9, 77.5] vs. 10.7 [8.6, 12.2] pg/ml, p = 0.011) and day 5 (16.2 [6.8, 170.4] vs. 12.0 [7.9, 14.3] pg/ml, p = 0.005). Routine EEG results did not differ between the groups, but quantitative EEG parameters representing encephalopathy correlated with biomarkers of brain injury. FSS, POPC and PCPC after three months were identical between in all patients. Independent from the origin of inflammatory stimulation by sepsis or ME delirium is associated with transient neurological dysfunction in PICU patients, without neurological impairment after three months, as confirmed by biomarker levels.