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Persistent Inflammation in Cerebral Palsy: Pathogenic Mediator or Comorbidity? A Scoping Review.

ABSTRACT: Research has established inflammation in the pathogenesis of brain injury and the risk of developing cerebral palsy (CP). However, it is unclear if inflammation is solely pathogenic and primarily contributes to the acute phase of injury, or if inflammation persists with consequence in CP and may therefore be considered a comorbidity. We conducted a scoping review to identify studies that analyzed inflammatory biomarkers in CP and discuss the role of inflammation in the pathogenesis of CP and/or as a comorbidity. Twelve included studies reported a range of analytes, methods and biomarkers, including indicators of inflammatory status, immune function and genetic changes. The majority of controlled studies concluded that one or more systemic biomarkers of inflammation were significantly different in CP versus controls; most commonly serum or plasma cytokines such as tumor necrosis factor, Interleukin (IL)-6 and IL-10. In addition, differences in inflammation were noted in distinct subgroups of CP (e.g., those with varying severity). The available evidence supports the pathogenic role of inflammation and its ongoing role as a comorbidity of CP. This review shows that inflammation may persist for decades, driving functional impairment across development and into adulthood. However, inflammation is complex, thus further research will increase our understanding.

SUBMITTER: Paton MCB

PROVIDER: S-EPMC9783203 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Persistent Inflammation in Cerebral Palsy: Pathogenic Mediator or Comorbidity? A Scoping Review.

Paton Madison C B MCB Finch-Edmondson Megan M Dale Russell C RC Fahey Michael C MC Nold-Petry Claudia A CA Nold Marcel F MF Nold Marcel F MF Griffin Alexandra R AR Novak Iona I

Journal of clinical medicine 20221212 24

Research has established inflammation in the pathogenesis of brain injury and the risk of developing cerebral palsy (CP). However, it is unclear if inflammation is solely pathogenic and primarily contributes to the acute phase of injury, or if inflammation persists with consequence in CP and may therefore be considered a comorbidity. We conducted a scoping review to identify studies that analyzed inflammatory biomarkers in CP and discuss the role of inflammation in the pathogenesis of CP and/or ...[more]

PMID: 36555983

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Project description:BackgroundRemote treatment, or telehealth, has shown promise for children with cerebral palsy (CP) prior to 2020; however, the beginning of the global COVID-19 pandemic limiting access to hospitals for face-to-face treatments has driven the need for telehealth and led to a surge in its development. Due to the recent developments, there has been limited synthesis of the available evidence of telehealth for children with CP.ObjectiveThis study aimed to analyze and summarize the existing evidence for telehealth interventions for the treatment of children with CP and identify any areas requiring further research.MethodsA scoping review was performed. A systematic search of available literature in MEDLINE and PubMed was performed during July 2021. Inclusion criteria for articles were primary research and systematic reviews that investigated telehealth, included children with CP, were published between 2010-2021, and were written in English. Exclusion criteria were secondary research other than systematic reviews; interventions that did not meet the World Health Organization definition of telehealth; or studies where all participants were aged >18 years, children's results were not reported separately, or there were no results reported for children with CP. A scoping review was chosen due to the expected heterogeneity of the participants, as well as the expected small sample sizes and inconsistency of measured outcomes; therefore, a narrative reporting of the results was considered appropriate.ResultsIn all, 5 papers were identified, which included the results of 11 studies-2 of the included articles were systematic reviews, which included the results of 3 studies each. These 6 studies, together with 5 primary research articles, were included in this scoping review. The existing evidence is of low methodological quality, primarily consisting of case series. There is some evidence that the requirements of telehealth differ depending on the children's developmental stage and functional level. Telehealth is reported to reduce caregiver burden. There is mixed evidence on children's compliance with telehealth. Overall, the results of telehealth interventions for the treatment of children with CP were positive, indicating either comparable or improved results compared with children receiving usual face-to-face care.ConclusionsThe evidence base is lacking in breadth and methodological quality to provide robust clinical recommendations. Most studies investigated hand function only, indicating the limited scope of existing research. However, this review shows that telehealth has demonstrated potential to improve function for children with CP while making health care services more accessible and reducing caregiver burden. Areas requiring further research include telehealth interventions for the lower limb, postural management, and pain control and the barriers to implementing telehealth.

Project description:AimTo synthetize studies assessing somatosensory deficits and alterations in cerebral responses evoked by somatosensory stimulation in individuals with cerebral palsy (CP) compared to typically developing individuals.MethodA scoping review of the literature was performed in the MEDLINE, Embase, PsycInfo, CINAHL, Evidence-Based Medicine Reviews, and Web of Science databases (last search carried out on 6th and 7th August 2020) with a combination of keywords related to CP and somatosensory functions. Somatosensory deficits were measured with clinical tests and alterations in cerebral responses were measured with functional magnetic resonance imaging, electroencephalography, and magnetoencephalography.ResultsForty-eight articles were included. Overall, 1463 participants with CP (mean [SD] age 13y 1mo [4y 11mo], range 1-55y; 416 males, 319 females, sex not identified for the remaining participants) and 1478 controls (mean [SD] age 13y 1mo [5y 8mo], range 1-42y; 362 males, 334 females, sex not identified for the remaining participants) were included in the scoping review. For tactile function, most studies reported registration (8 out of 13) or perception (21 out of 21) deficits in participants with CP. For proprioception, most studies also reported registration (6 out of 8) or perception (10 out of 15) deficits. Pain function has not been studied as much, but most studies reported registration (2 out of 3) or perception (3 out of 3) alterations. Neuroimaging findings (18 studies) showed alterations in the somatotopy, morphology, latency, or amplitude of cortical responses evoked by somatosensory stimuli.InterpretationDespite the heterogeneity in the methods employed, most studies reported somatosensory deficits. The focus has been mainly on tactile and proprioceptive function, whereas pain has received little attention. Future research should rigorously define the methods employed and include a sample that is more representative of the population with CP. What this paper adds Most of the papers reviewed found tactile registration and perception deficits in the upper limbs. Proprioceptive deficits were generally observed in cerebral palsy but results were heterogeneous. Pain has received little attention compared to tactile and proprioceptive functions. Neuroimaging studies supported behavioral observations. Alterations were observed for both the most and least affected limb.

Project description:BackgroundInnovative technologies such as game consoles and smart toys used with games or playful approaches have proven to be successful and attractive in providing effective and motivating hand therapy for children with cerebral palsy (CP). Thus, there is an increased interest in designing and implementing interventions that can improve the well-being of these children. However, to understand how and why these interventions are motivating children, we need a better understanding of the playful elements of technology-supported hand therapy.ObjectiveThis scoping review aims to identify the playful elements and the innovative technologies currently used in hand therapy for children with CP.MethodsWe included studies that design or evaluate interventions for children with CP that use innovative technologies with game or play strategies. Data were extracted and analyzed based on the type of technology, description of the system, and playful elements according to the Lenses of Play, a play design toolkit. A total of 31 studies were included in the analysis.ResultsOverall, 54 papers were included in the analysis. The results showed high use of consumer technologies in hand therapy for children with CP. Although several studies have used a combination of consumer technologies with therapeutic-specific technologies, only a few studies focused on the exclusive use of therapeutic-specific technologies. To analyze the playfulness of these interventions that make use of innovative technologies, we focused our review on 3 lenses of play: Open-ended Play, where it was found that the characteristics of ludus, such as a structured form of play and defined goals and rules, were the most common, whereas strategies that relate to paidia were less common. The most commonly used Forms of Play were physical or active form and games with rules. Finally, the most popular Playful experiences were control, challenge, and competition.ConclusionsThe inventory and analysis of innovative technology and playful elements provided in this study can be a starting point for new developments of fun and engaging tools to assist hand therapy for children with CP.

Project description:Objective: Several studies have shown the significance of neuroinflammation in the pathological progress of cerebral palsy (CP). However, the etiology of CP remains poorly understood. Spastic CP is the most common form of CP, comprising 80% of all cases. Therefore, identifying the specific factors may serve to understand the etiology of spastic CP. Our research aimed to find some relevant factors through protein profiling, screening, and validation to help understand the pathogenesis of cerebral palsy. Materials and methods: In the current study, related clinical parameters were assessed in 18 children with spastic CP along with 20 healthy individuals of the same age. Blood samples of the spastic CP children and controls were analyzed with proteomics profiling to detect differentially expressed proteins. On the other hand, after hypoxic-ischemic encephalopathy (HIE) was induced in the postnatal day 7 rat pups, behavioral tests were performed followed by detection of the differentially expressed markers and inflammatory cytokines in the peripheral blood and cerebral cortex of the CP model rats by Elisa and Western blot. Independent sample t-tests, one-way analysis of variance, and the Pearson correlation were used for statistical analysis. Results: Through proteomic analysis, differentially expressed proteins were identified. Among them, tissue-nonspecific alkaline phosphatase (TNAP), the gene expression product of alkaline phosphatase (ALPL), was downregulated in spastic CP. In addition, significantly lower TNAP levels were found in the children with CP and model rats. In contrast, compared with the sham rats, the model rats demonstrated a significant increase in osteopontin and proinflammatory biomarkers in both the plasma and cerebral cortex on the ischemic side whereas serum 25 hydroxyvitamin D and IL-10 were significantly decreased. Moreover, serum TNAP level was positively correlated with serum CRP and IL-10 in model rats. Conclusion: These results suggest that TNAP is the potential molecule playing a specific and critical role in the neuroinflammation in spastic CP, which may provide a promising target for the diagnosis and treatment of spastic CP.

Dataset Information

Persistent Inflammation in Cerebral Palsy: Pathogenic Mediator or Comorbidity? A Scoping Review.

Publications

Persistent Inflammation in Cerebral Palsy: Pathogenic Mediator or Comorbidity? A Scoping Review.

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