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Published on: February 2, 2024
Persistent dysregulated inflammation in cerebral palsy: a systematic review
Sara Betzhold1, Mariam Cender1, Mustafa Dhuhaibawi1
1Discipline of Paediatrics, Trinity College Dublin, The University of Dublin, Dublin, Ireland.
Insights
Systemic inflammation persists in children with cerebral palsy (CP) into childhood, correlating with disease severity. This review highlights potential therapeutic targets for managing persistent inflammation in CP.
Area of Science:
- Neuroscience
- Immunology
- Pediatrics
Background:
- Systemic inflammation during the perinatal period is linked to cerebral palsy (CP).
- Recent evidence suggests this inflammation persists into childhood and beyond.
- This review focuses on persistent inflammation in CP and potential therapeutic targets.
Purpose of the Study:
- To systematically review evidence on persistent dysregulated inflammation in cerebral palsy (CP).
- To explore potential therapeutic targets for managing persistent inflammation in CP.
Main Methods:
- Systematic review adhering to PRISMA guidelines.
- Searched multiple databases (PubMed, Cochrane Library, Embase, Science Direct, Ovid) on February 27, 2024.
- Assessed study quality using the Newcastle-Ottawa Scale and extracted data for analysis.
Main Results:
- 17 studies were included from 1064 identified.
- 10 studies reported elevated cytokines and immune cells in children with CP.
- Persistent inflammation in CP involves elevated cytokines (e.g., TNF-α, IL-6) and immune cells, found in blood, saliva, CSF, and muscle.
Conclusions:
- Inflammation persists beyond the perinatal period in cerebral palsy (CP).
- Elevated inflammation correlates with CP disease severity (e.g., GMFCS scores).
- Further consensus is needed to address heterogeneity and identify universal therapeutic targets for CP.
Background:
Systemic inflammation in the perinatal period has been linked to cerebral palsy (CP), with recent studies indicating that this inflammation persists into childhood and beyond. This systematic review investigates persistent dysregulated inflammation in CP and explores potential therapeutic targets.
Methods:
This systematic review adhered to PRISMA guidelines. Using specific key words, we extracted studies from multiple databases on 27th February 2024 (including PubMed, Cochrane Library, Embase, "Neuroscience journal" published by Science Direct, and Ovid). The quality of evidence was assessed with the Newcastle-Ottawa Scale. Relevant data was extracted to a Google Sheets spreadsheet for analysis.
Findings:
1064 studies were identified, 17 were included. Of these studies, 10 found elevated levels of cytokines and immune cells in children with CP compared to controls. Persistent inflammation in CP was associated with elevated levels of cytokines (TNF-α, IL-1β, IL-6, and IL-10) and higher baseline levels of certain immune cells. Commonly assessed biomarkers included TNF-α, IL-6, IL-10, and IL-8, with persistent inflammation observed in blood, saliva, CSF, and muscle samples. Potential therapeutic targets include magnesium sulphate, melatonin, immunotherapy, and stem cell treatments.
Correlation With Disease Severity:
Persistent inflammation in CP has been shown to correlate with disease severity, particularly higher gross motor function classification system (GMFCS) scores, across CP subtypes.
Interpretation:
This systematic review indicates that inflammation persists beyond the perinatal period in cerebral palsy. However, Future consensus required to minimise sample and biomarker heterogeneity, variability in reported aetiologies and small sample sizes which confound conclusions and to identify universal therapeutic targets.
Impact:
Patients with CP had inflammation that persisted into childhood compared to controls Elevated inflammation may correlate with disease severity in CP Persistent inflammation in CP is a potential therapeutic target Lack of standardised consensus definition and classification of CP across many studies.
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