Neurocognitive Impairment in Pediatric Patients With Meningoencephalitis and Sepsis-associated Encephalopathy
Condition: Critical Illness; Brain Injuries; Encephalopathy; Delirium; Inflammatory Disease; Central Nervous System Diseases
MeSH terms: Meningoencephalitis; Brain Injuries; Brain Diseases; Nervous System Diseases; Central Nervous System Diseases; Sepsis-Associated Encephalopathy; Critical Illness
Study type: Observational

Summary: 
      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.
    

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
    

Observational model: Case-Control
Time perspective: Prospective
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.
      
Biospecimen description: 
      Blood and cerebrospinal fluid samples