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Muscle contractures are a common complication to cerebral palsy (CP). The purpose of this study was to evaluate whether individuals with CP carry specific gene variants of important structural genes that might explain the severity of muscle contractures. Next‐generation‐sequencing (NGS) of 96 candidate genes associated with muscle structure and metabolism were analyzed in 43 individuals with CP (Gross Motor Function classification system [GMFCS] I, n=10; GMFCS II, n=14; GMFCS III, n=19) and four control participants. In silico analysis of the identified variants was performed. The variants were classified into four categories ranging from likely benign (VUS0) to highly likely functional effect (VUS3). All individuals with CP were classified and grouped according to their GMFCS level: Statistical comparisons were made between GMFCS groups. Kruskal‐Wallis tests showed significantly more VUS2 variants in the genes COL4 (GMFCS I–III; 1, 1, 5, respectively [p< .04]), COL5 (GMFCS I–III; 1, 1, 5 [p< .04]), COL6 (GMFCS I–III; 0, 4, 7 [p< .003]), and COL9 (GMFCS I–III; 1, 1, 5 [p< .04]), in individuals with CP within GMFCS Level III when compared to the other GMFCS levels. Furthermore, significantly more VUS3 variants in COL6 (GMFCS I–III; 0, 5, 2 [p< .01]) and COL7 (GMFCS I–III; 0, 3, 0 [p< .04]) were identified in the GMFCS II level when compared to the other GMFCS levels. The present results highlight several candidate gene variants in different collagen types with likely functional effects in individuals with CP.

Objectives The purpose of the present study was to investigate whether intramuscular BoNT/A injections cause an systemic inflammatory response and a local inflammatory response in the muscle tissue.Methods Thirty-two male Sprague Dawley rats treated with BoNT/A (i.m., 1IU) were divided in four groups, depending on the time of BoNT/A injection (2 days before, 1, 2, and 4 weeks before the experiment). Bio-Plex Pro Rat Cytokine 23-plex Multiplex Assay (Bio-Rad, USA).Results Systemic inflammation: 17 cytokines (IL1-α (p= 0.005), IL-1β (p= 0.01), IL-2 (p= 0.04), IL-4 (p= 0.03), IL-6 (p= 0.03), IL-10 (p= 0.02), IL12(p70) (p= 0.03), IL-13 (p= 0.04), IL-17 (p= 0.03), GM-CSF (p= 0.03), INF-γ (p= 0.03), MIP-1α (p= 0.03), MIP-3α (p= 0.04), RANTES (p= 0.001), TNF-α (p= 0.04), vascular endothelial growth factor (p= 0.03), and MCP-1 (p= 0.02)) showed significantly higher expression levels 2 days after intramuscular BoNT/A injections compared to other time points (1, 2, and 4 weeks). Local inflammation: 12 cytokines (IL-1β (p= 0.02), IL-6 (p= 0.002), IL-10 (p= 0.02), IL-13 (p= 0.04), IL-17 (p= 0.02), TNF-α (p= 0.001), GM-CSF (p= 0.01), M-CSF (p= 0.04), MIP-1α (p= 0.04), MIP-3α (p= 0.002), RANTES (p= 0.02), and MCP-1(p= 0.004)) showed higher expression levels 2 and/or 4 weeks after intramuscular BoNT/A injections compared to the other time points (2 days and 1 week).Conclusion Intramuscular BoNT/A injections result in a rapid systemic inflammatory response that only lasts a couple of days. At the same time, intramuscular BoNT/A injections cause an inflammatory response locally in the muscle with significantly higher cytokine levels 2 and/or 4 weeks after injections.

Individuals with cerebral palsy (CP) develop skeletal muscle contractures that impair muscle function. In turn, contractures affect the ability to ambulate and often promote a sedentary lifestyle. The aim of the present study was to investigate the systemic inflammatory markers transforming growth factor beta-1 (TGFβ1), C-reactive protein (CRP), and interleukin-6 (IL-6) in children and adults with CP. Blood samples of n = 34 participants (24 individuals with CP (n = 14 children with CP age 10.36 ± 1.1 and n = 10 adults with CP age 38.80 ± 3.6) and 10 healthy adults age 36.63 ± 3.8) were analyzed for circulating levels of TGFβ1, CRP, and IL-6 using Sandwich Enzyme linked immunosorbent assay (ELISA) analyses (R&D systems). TGFβ1 and CRP levels were significantly higher in children with CP compared to both adults with CP (TGFβ1: P< 0.0005 and P< 0.0002, respectively) and healthy adults (CRP: P< 0.0001 and P< 0.0001, respectively), while no differences were observed between the adults with CP and healthy adults in TGFβ1 (P= 0.29) and CRP (P= 0.59), respectively. Furthermore, IL-6 levels showed no significant differences between the groups. The present findings indicate that the level of systemic inflammation is increased in children with CP. We speculate that persisting inflammation in children with CP might influence the development of muscle contractures, resulting in reduced muscle mass and marked muscle weakness in adults with CP.