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

Abstract

Background: 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 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).

Methods: A 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.

Results: Significant (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.

Conclusion: This 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.

Keywords: Biomarkers; CSF; Cerebral palsy; Children; Neuroendocrine; Neuroinflammation; Nociceptive.

Fig. 1

Visual representation of the direction and strength of the Pearson’s correlation coefficients between all 33 analytes assayed. Positive (blue), negative (red), strong (dark shading), and weak (light shading) correlations are depicted

Fig. 2

Visual representation of the direction and strength of the Pearson’s correlation coefficients between all 33 analytes assayed within the Term Birth subgroup. Positive (blue), negative (red), strong (dark shading), and weak (light shading) correlations are depicted. *In instances where the same value was reported for each variable, no correlation was calculated

Fig. 3

Visual representation of the direction and strength of the Pearson’s correlation coefficients between all 33 analytes assayed within the Preterm Birth subgroup. Positive (blue), negative (red), strong (dark shading), and weak (light shading) correlations are depicted

Fig. 4

Visual representation of the direction and strength of the Pearson’s correlation coefficients between all 33 analytes assayed within the Extremely Preterm subgroup. Positive (blue), negative (red), strong (dark shading), and weak (light shading) correlations are depicted. *In instances where the same value was reported for each variable, no correlation was calculated