Neurocognitive Impairment in Pediatric Patients With Meningoencephalitis and Sepsis-associated Encephalopathy

Incidence and Severity of Neurocognitive Impairment in Pediatric Patients With Meningoencephalitis and Sepsis-associated Encephalopathy

Neurocognitive impairment is frequently observed in pediatric patients with meningoencephalitis (ME) and sepsis-associated encephalopathy (SAE) which represent two relevant central nervous system (CNS) diseases in pediatric patients. It is uncertain, if the the origin of the disease, located primarily in the CNS of patients with ME or secondarily in patients with SAE in the course of sepsis, is of importance for the severity of injury to the brain. Prospective clinical studies combining clinical and laboratory examinations including specific biomarkers of neuroaxonal injury were not performed in a comparative study. Biomarkers of neuroaxonal injury are therefore not only of great interest to detect and monitor neurocognitive impairment but also to quantify the severity of brain injury in patients with ME and SAE.

This is a prospective single-center observational study evaluating the incidence and severity of the neurocognitive impairment in pediatric patients with meningoencephalitis (ME) and sepsis-associated encephalopathy (SAE). All study participants will be assessed by clinical and neurological examination as well as comprehensive laboratory tests using biomarkers of neuroaxonal injury at study day 1 (day of study inclusion), day 3 and day 5. A panel of biomarkers derived from blood and cerebrospinal fluid (CSF) samples (among others NSE, S100B and neurofilament proteins) will be measured. Clinical assessment will be performed using validated scales of severity of disease (e.g. pSOFA score) and validated delirium tests (among others pGCS, pCAM-ICU) to assess the neurocognitive performance of study participants before and three months after study inclusion (among others POPC/PCPC).

A matched group of pediatric patients without evidence for ME or sepsis/SAE will serve as a control group and will undergo the same clinical and laboratory examinations except CSF analysis.

The investigators hypothesize, that:

1. Patients with ME (primary CNS infection) indicate a higher incidence and severity of neurocognitive impairment than patients with SAE (secondary CNS affection)
2. Specific biomarkers of neuroaxonal injury in blood and CSF correlate with the clinical severity of neurocognitive impairment in patients with ME and SAE
3. Specific biomarkers of neuroaxonal injury in blood and CSF correlate with the 3-months neurocognitive outcome of patients with ME and SAE

Inclusion Criteria:

• pediatric patients between 1 day and 17 years of age
• admission to hospital with suspected meningoencephalitis or sepsis <24 hours after admission or time of diagnosis
• admission to hospital for minor surgery (herniotomy, osteosynthesis, adenoidectomy)

Exclusion Criteria:

• preexisting central nervous system diseases (stroke, hemorrhage, tumor, traumatic brain injury, brain surgery, epilepsy, hydrocephalus)
• preexisting immunosuppression
• participation in another interventional study
• no written informed consent from parents or legal representative