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Serum Biomarkers of Regeneration and Plasticity are Associated with Functional Outcome in Pediatric Neurocritical
Catherine Madurski1,2, Jessica M Jarvis3, Sue R Beers4
1Department of Critical Care Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
Insights
Biomarkers like BDNF and VEGF in children with acquired brain injury may predict functional impairment. Lower levels of these regeneration markers correlate with worse outcomes, suggesting their prognostic value.
Area of Science:
- Pediatric Neurocritical Care
- Biomarker Discovery
- Acquired Brain Injury
Background:
- Pediatric neurocritical care survivors often experience functional impairments.
- A lack of prognostic biomarkers hinders early identification and management of these impairments.
- This study investigates blood biomarkers associated with functional impairment in children with acute acquired brain injury.
Purpose of the Study:
- To explore the association between specific blood biomarkers and functional impairment in pediatric patients with acute acquired brain injury.
- To identify potential prognostic biomarkers for functional outcomes in this population.
Main Methods:
- Secondary analysis of a randomized control trial involving 44 children with acute acquired brain injury.
- Serum samples collected on multiple days (admission, day 1, 3, 5, discharge) analyzed for biomarkers (NSE, S100b, IL-6, CRP, BDNF, VEGF).
- Functional impairment assessed using Functional Status Scale (FSS) scores; correlations and mixed-effects models used for analysis.
Main Results:
- Lower levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) at multiple time points were significantly associated with greater functional impairment.
- Neuron-specific enolase (NSE) levels on admission positively correlated with new functional impairment.
- Repeated measures of BDNF and VEGF also showed inverse correlations with new functional impairment.
Conclusions:
- Blood-based biomarkers related to regeneration and plasticity, such as BDNF and VEGF, show prognostic utility for functional impairment in pediatric neurocritical care.
- Further investigation into these biomarkers is warranted for improved patient management and outcome prediction.
Background/Objective:
Pediatric neurocritical care survivorship is frequently accompanied by functional impairments. Lack of prognostic biomarkers is a barrier to early identification and management of impairment. We explored the association between blood biomarkers and functional impairment in children with acute acquired brain injury.
Methods:
This study is a secondary analysis of a randomized control trial evaluating early versus usual care rehabilitation in the pediatric intensive care unit (PICU). Forty-four children (17 [39%] female, median age 11 [interquartile range 6-13] years) with acute acquired brain injury admitted to the PICU were studied. A single center obtained serum samples on admission days 0, 1, 3, 5, and the day closest to hospital discharge. Biomarkers relevant to brain injury (neuron specific enolase [NSE], S100b), inflammation (interleukin [IL-6], C-reactive protein), and regeneration (brain-derived neurotrophic factor [BDNF], vascular endothelial growth factor [VEGF]) were collected. Biomarkers were analyzed using a Luminex® bioassay. Functional status scale (FSS) scores were abstracted from the medical record. New functional impairment was defined as a (worse) FSS score at hospital discharge compared to pre-PICU (baseline). Individual biomarker fluorescence index (FI) values for each sample collection day were correlated with new functional impairment using Spearman rank correlation coefficient (ρ). Trends in repeated measures of biomarker FI over time were explored graphically, and the association between repeated measures of biomarker FI and new functional impairment was analyzed using covariate adjusted linear mixed-effect models.
Results:
Functional impairment was inversely correlated with markers of regeneration and plasticity including BDNF at day 3 (ρ = - 0.404, p = .015), day 5 (ρ = - 0.549, p = 0.005) and hospital discharge (ρ = - 0.420, p = 0.026) and VEGF at day 1 (ρ = - 0.282, p = 0.008) and hospital discharge (ρ = - 0.378, p = 0.047), such that lower levels of both markers at each time point were associated with greater impairment. Similarly, repeated measures of BDNF and VEGF were inversely correlated with new functional impairment (B = - 0.001, p = 0.001 and B = - 0.001, p = 0.003, respectively). NSE, a biomarker of acute brain injury, showed a positive correlation between day 0 levels and new functional impairment (ρ = 0.320, p = 0.044).
Conclusions:
Blood-based biomarkers of regeneration and plasticity may hold prognostic utility for functional impairment among pediatric patients with neurocritical illness and warrant further investigation.
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