Expression of and correlational patterns among neuroinflammatory, neuropeptide, and neuroendocrine molecules from cerebrospinal fluid in cerebral palsy

Cory J Goracke-Postle,Chantel C Burkitt,Patrick Graupman,Frank J Symons,Michael Partington,Angela Panoskaltsis-Mortari,George L Wilcox,Michael Ehrhardt

doi:10.1186/s12883-021-02333-2

Abstract

BackgroundThe underlying pathogenesis of cerebral palsy (CP) remains poorly understood. The possibility of an early inflammatory response after acute insult is of increasing interest. Patterns of inflammatory and related biomarkers are emerging as potential early diagnostic markers for understanding the etiologic diversity of CP. Their presence has been investigated in plasma and umbilical cord blood but not in cerebrospinal fluid (CSF).MethodsA clinical CP sample was recruited using a single-time point cross-sectional design to collect CSF at point-of-care during a standard-of-care surgical procedure (intrathecal pump implant). Patient demographic and clinical characteristics were sourced from medical chart audit.ResultsSignificant (p ≤ 0.001) associations were found among neuroinflammatory, neuroendocrine, and nociceptive analytes with association patterns varying by birth status (term, preterm, extremely preterm). When between birth-group correlations were compared directly, there was a significant difference between preterm and extremely preterm birth subgroups for the correlation between tumour necrosis factor alpha (TNFα) and substance P.ConclusionThis investigation shows that CSF can be used to study proteins in CP patients. Differences in inter-correlational patterns among analytes varying by birth status underscores the importance of considering birth status in relation to possible mechanistic differences as indicated by biomarker signatures. Future work should be oriented toward prognostic and predictive validity to continue to parse the heterogeneity of CP’s presentation, pathophysiology, and response to treatment.

Highlights

The underlying pathogenesis of cerebral palsy (CP) remains poorly understood
The specific correlation pattern represents a novel approach to considering analytes that may shed light on the mechanistic underpinnings of secondary processes that may be ongoing in CP and result in clinical signs and their manifestation
To assess the potential of such protein signatures in cerebrospinal fluid (CSF) to distinguish differences relating to biological variables underlying various subpopulations of CP patients, we assessed analyte correlations between various subgroups

Summary

Introduction

The underlying pathogenesis of cerebral palsy (CP) remains poorly understood. The possibility of an early inflammatory response after acute insult is of increasing interest. Patterns of inflammatory and related biomark‐ ers are emerging as potential early diagnostic markers for understanding the etiologic diversity of CP. Their presence has been investigated in plasma and umbilical cord blood but not in cerebrospinal fluid (CSF). Work investigating infection- and neuroinflammatoryrelated biomarkers related to WMD in neonates has generated evidence mostly supporting a pathway from intrauterine infection to placental inflammation to systemic fetal circulation and the preterm newborn brain [3]. The specifics of the infection-inflammation-brain damage link have been described and documented and are an active area of investigation [4] given cautions about what level of inference is or is not supported by high quality evidence [5]. From a more general perspective, the emerging viewpoint on the role of neuro-inflammation as a pathophysiological contributor to CP has created the possibility of a new therapeutic window through which to view the condition [7, 8]

Results

Discussion

Conclusion