Sara Betzhold, Mariam Cender, Mustafa Dhuhaibawi, Sophie Keenan, Eoin McDermott, Patrick Moran, Isabel O'Donovan, Valeria Raaft Rezk, Maxime St-Georges, Ailbhe Murphy, James Trayer, Philip Stewart, Aoife Branagan, Edna Roche, Denise McDonald, Judith Meehan, Eleanor J Molloy
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.
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.