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

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.

Study Overview

• Status: Completed
• Conditions: Central Nervous System Diseases; Delirium; Brain Injuries; Critical Illness; Encephalopathy; Inflammatory Disease

Detailed Description

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

• Study Type: Observational
• Enrollment (Actual): 42

Contacts and Locations

Study Locations

• Germany
  • Rostock, Germany, 18059
    • University Medical Center Rostock

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All pediatric patients who are admitted to the study center will be screened for study eligibility according to the inclusion and exclusion criteria.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Meningoencephalitis (ME-PED); pediatric patients between 0 and 17 years of age; admission to hospital with suspected meningoencephalitis; confirmed meningoencephalitis within 24 hours after admission
Sepsis-associated encephalopathy (SAE-PED); pediatric patients between 0 and 17 years of age; admission to hospital with suspected sepsis; confirmed sepsis within 24 hours after admission or time of diagnosis
Control group (CON-PED); pediatric patients between 0 and 17 years of age; exclusion of neurocognitive impairment; admission to hospital for minor surgery (e.g. herniotomy, adenoidectomy, fractures treated by osteosynthesis) or for hemangioma treated by propranolol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of delirium/neurocognitive impairment in pediatric patients with meningoencephalitis compared to patients with sepsis-associated encephalopathy	Assessment of neurocognitive impairment using validated tools	Day 90
Change in neuroaxonal injury biomarker levels in patients with meningoencephalitis compared to patients with sepsis-associated encephalopathy	Measurement of biomarker levels (e.g. NSE, S100B, neurofilament proteins) derived from blood and cerebrospinal fluid samples	Change from baseline biomarker levels at day 5
Neurocognitive 3-months outcome in patients with meningoencephalitis compared to patients with sepsis-associated encephalopathy	Assessment of the neurocognitive performance of patients using validated tests (e.g. pediatric cerebral performance category)	Day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
90-day survival in patients with meningoencephalitis compared to patients with sepsis-associated encephalopathy	Survival after 90 days	Day 90
Length of hospital stay in patients with meningoencephalitis compared to patients with sepsis-associated encephalopathy	Cumulative days in hospital	1 year
Length of intensive care unit stay in patients with meningoencephalitis compared to patients with sepsis-associated encephalopathy	Cumulative days on intensive care unit	1 year

Collaborators and Investigators

• Sponsor: University of Rostock

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 3, 2020
• Primary Completion (ACTUAL): December 31, 2021
• Study Completion (ACTUAL): October 31, 2022

Study Registration Dates

• First Submitted: July 8, 2020
• First Submitted That Met QC Criteria: July 8, 2020
• First Posted (ACTUAL): July 13, 2020

Study Record Updates

• Last Update Posted (ACTUAL): November 3, 2022
• Last Update Submitted That Met QC Criteria: November 1, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Wounds and Injuries; Disease Attributes; Central Nervous System Viral Diseases; Central Nervous System Infections; Craniocerebral Trauma; Trauma, Nervous System; Encephalitis; Meningitis; Brain Injuries; Nervous System Diseases; Brain Diseases; Critical Illness; Central Nervous System Diseases; Meningoencephalitis; Sepsis-Associated Encephalopathy
• Other Study ID Numbers: A 2020-0160

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No