Search Results (69)

Background: Traumatic brain injury (TBI) and hypoxic–ischemic encephalopathy (HIE) are major causes of long-term neurological disability in children, with limited options for effective neuronal recovery. Recent research has highlighted the therapeutic potential of nerve growth factor (NGF) in promoting neural repair through mechanisms such as neuroprotection, neurogenesis, and the modulation of neuroinflammation. This review evaluates the current evidence on NGF as a treatment strategy for pediatric brain injury, emphasizing its mechanisms of action and translational clinical applications. Methods: A comprehensive review was conducted using the PubMed, Scopus, and Cochrane CENTRAL databases to identify studies published between 1 January 1978 and 1 March 2025, investigating NGF in the context of brain injury. The inclusion criteria comprised studies assessing neurological outcomes through clinical scales, biochemical markers, neuroimaging, or electrophysiological examinations. Results: Seventeen studies met the inclusion criteria, encompassing both preclinical and clinical research. Preclinical models consistently demonstrated that NGF administration reduces neuroinflammation, enhances neurogenesis, and supports neuronal survival following TBI and HIE. Clinical studies, including case reports of pediatric patients treated with intranasal NGF, reported improvements in motor and cognitive function, neuroimaging findings, and electrophysiological parameters, with no significant adverse effects observed. Conclusions: NGF demonstrates significant promise as a neuroprotective and neuroregenerative agent in pediatric brain injury, with both experimental and early clinical evidence supporting its safety and efficacy. Large-scale controlled clinical trials are warranted to validate these preliminary findings and to determine the optimal dosage regimens and administration schedules for NGF in the treatment of TBI and HIE. Full article

Background/Objectives: Mild traumatic brain injury (mTBI) is a leading cause of pediatric emergency department visits, particularly among children under three years old. Although computed tomography (CT) is the gold standard for diagnosing intracranial injuries, its use in young children poses radiation risks. Identifying reliable clinical indicators that justify CT imaging is essential for optimizing both patient safety and resource utilization. Objective: This study aimed to evaluate CT findings in children under three years of age with mTBI and no focal neurological deficits, as well as to identify clinical predictors associated with skull fractures and intracranial injuries. Methods: A retrospective analysis was conducted on 224 children under 36 months who presented with mTBI to a tertiary pediatric hospital from July 2019 to July 2024. Demographic data, injury mechanisms, clinical presentation and CT findings were evaluated. Univariate and multivariate regression analyses were performed to identify risk factors associated with skull fractures and intracranial injuries. Results: Falls accounted for 96.4% of injuries, with the majority occurring from heights of 0.5–1 m. The parietal region was the most frequently affected site (38%). Skull fractures were present in 46% of cases and were primarily linear (92.8%). Intracranial hematomas were identified in 13.8% of cases, while brain edema was observed in 7.6%. Significant predictors of skull fractures included age under 12 months (p < 0.001), falls from 0.5–1 m (p = 0.005), somnolence (p = 0.030), scalp swelling (p = 0.001) and indentation of the scalp (p = 0.016). Parietal bone involvement was the strongest predictor of both skull fractures (OR = 7.116, p < 0.001) and intracranial hematomas (OR = 4.993, p < 0.001). Conversely, frontal bone involvement was associated with a lower likelihood of fractures and hematomas. Conclusions: The findings highlight key clinical indicators that can guide decision-making for CT imaging in children with mTBI. Infants under 12 months, falls from moderate heights and parietal bone involvement significantly increase the risk of fractures and intracranial injuries. A more refined diagnostic approach could help reduce unnecessary CT scans while ensuring the timely identification of clinically significant injuries. Full article

Mild traumatic brain injury (mTBI) is a leading cause of morbidity in children with both short- and long-term neurological, cognitive, cerebrovascular, and emotional deficits. These deficits have been attributed to ongoing pathophysiological cascades that occur acutely and persist post-injury. Given our limited understanding of the transcriptional changes associated with these pathophysiological cascades, we studied formalin-fixed paraffin-embedded (FFPE) tissues from the frontal cortex (FC) and the hippocampus + amygdala (H&A) regions of swine (N = 40) after a sagittal rapid non-impact head rotation (RNR). We then sequenced RNA to define transcriptional changes at 1 day and 1 week after injury and investigated the protective influence of cyclosporine A (CsA) treatment. Differentially expressed genes (DEGs) were classified into five temporal patterns (Early, Transient, Persistent, Intensified, Delayed, or Late). DEGs were more abundant at 1 week than 1 day. Shared significant gene ontology annotations in both regions included terms associated with neuronal distress at 1 day and neurorecovery at 1 week. CsA (20 mg/kg/day) infused for 1 day (beginning at 6 h after injury) accelerated 466 DEGs in the FC and 2794 DEGs in the H&A, such that the CsA-treated transcriptional profile was associated with neurorecovery. Overall, our data reveal the effects of anatomic region and elapsed time on gene expression post-mTBI and motivate future studies of CsA treatment. Full article

Background: Mild traumatic brain injury (mTBI) in the pediatric population is a significant public health concern, often associated with persistent post-concussion symptoms, including postural instability. Current tools for assessing postural control, such as the Balance Error Scoring System (BESS), lack integration with objective metrics. Incorporating force plate sensors into BESS assessments may enhance diagnostic accuracy and support return-to-play or sports decisions. This study evaluates postural performance in children with mTBI compared to controls using an instrumented BESS and examines recovery trajectories after mTBI. Methods: This prospective, longitudinal study included 31 children with mTBI (12.01 ± 3.28 years, 20 females) and 31 controls (12.31 ± 3.27 years, 18 females). Postural control was assessed using an instrumented BESS protocol during standing on a ground reaction force plate at three timepoints: within 72 h post injury (T1), at two weeks (T2), and three months after trauma (T3). Posturographic parameters derived from the displacement of the center of pressure included the ellipse area, path length, and mean velocity in the anterior–posterior and medio–lateral directions. Symptom burden was monitored using the Post-Concussion Symptom Inventory (PCSI). Results: The BESS total scores did not differ significantly between the groups at any timepoint. A significant reduction in BESS errors over time was observed exclusively in the two-legged stance on a soft surface (p = 0.047). The instrumented BESS revealed higher body swaying in the mTBI group compared to controls, particularly under demanding conditions. Significant between-group differences were most frequently observed in single-leg soft surface (38% of comparisons) and two-legged soft surface stances (29%). In those cases, path length and mean velocity differed between groups, respectively. Ellipse area did not show significant differences across conditions. Conclusions: An instrumented BESS has the potential to enhance the detection of subtle postural deficits in pediatric mTBI patients. Specifically, more demanding conditions with altered sensory-proprioceptive input and path length as an outcome measure should be focused on. This study underscores the need for tailored and age-appropriate objective and quantitative balance assessments to improve diagnostic precision in pediatric mTBI populations. Full article

Mild traumatic brain injury (mTBI) results in a constellation of symptoms commonly referred to as a concussion. It is unclear why certain individuals experience persistent symptoms. Given the growing evidence linking the microbiome with cognition and inflammation, we examined whether longitudinal microbiome patterns were associated with concussion symptoms. A cohort study of 118 children (aged 7–21 years) was conducted. Symptoms were assessed at three timepoints post-injury (4, 11, and 30 days) using the Post-Concussion Symptom Inventory. Saliva microbial activity was measured at each timepoint using RNA sequencing. A linear mixed model assessed the relationship between microbial activity and symptom burden while controlling for age, sex, and days post-mTBI. The participants’ mean age was 16 (±3) years. The symptom burden decreased across all three timepoints (25 ± 22, 13 ± 17, and 5 ± 12). The longitudinal symptom burden was associated with elevated activity of Lactobacillus (F = 5.47; adj. p = 0.020) and Saccharomyces (F = 6.79; adj. p = 0.020) and reduced activity of Micrococcus (F = 7.94, adj. p = 0.015). These results do not establish a causative relationship, or support the use of microbial measures as a concussion test. Further studies are needed to explore the role of the gut–brain axis in mTBI. Full article

Introduction: Traumatic brain injury (TBI) in pediatric population is responsible for significant mortality and morbidity, particularly among children aged 0–4 and young adults aged 15–24. The developing brain’s unique characteristics may increase vulnerability to injuries, potentially leading to long-term cognitive and motor deficits. Current therapeutic options for neuronal regeneration post-TBI are limited, although neurotrophins, especially nerve growth factor (NGF), show promise in enhancing recovery. NGF can mitigate excitotoxicity and promote neuroprotection, particularly by intranasal administration, which is attractive because of its non-invasive nature. Case Presentation: A three-year-old boy suffered from severe TBI due to a car accident, leading to multiple complications, including a basilar skull fracture and cerebral venous sinus thrombosis. Initial assessments revealed significant neurological impairments. After intensive care and rehabilitation, the child exhibited gradual improvements in consciousness and motor functions but continued to face challenges, particularly with left-sided hemiparesis. Nine months post-injury, he began intranasal administration of human-recombinant NGF (hr-NGF) as part of a clinical trial. Discussion: Following hr-NGF treatment, the child demonstrated notable advancements in motor function, achieving independent standing and walking. Cognitive assessments indicated improvements in various domains, including verbal comprehension and executive functioning. EEG results showed reduced epileptiform activity. These findings suggest that hr-NGF may facilitate recovery in pediatric TBI cases by enhancing both motor and cognitive outcomes. Conclusions: This case highlights the potential role of intranasal hr-NGF administration as a therapeutic strategy for improving neurological recovery in children with severe TBI. The positive clinical outcomes support further exploration of NGF as a viable treatment option to mitigate long-term sequelae associated with pediatric brain injuries. Full article

Background/Objectives: Children and adolescents with psoriasis can have severe and long-lasting disease requiring early and effective therapy. The range of associated comorbidities is comparable to adult patients with additional problems deriving from their growth and maturation. Therefore, tailored information and interdisciplinary teamwork is necessary to effectively manage pediatric psoriasis. Methods: We reflected on our experience with therapy management of children and adolescents with psoriasis coming to our university outpatient clinic and summarized the challenges and special features of these patients together with approved medications and recommendations for treatment. We present our algorithm for managing these patients in an interdisciplinary setting. Results: Children can develop psoriasis very early in their life, and they show specific patterns of skin involvement depending on age. Scores such as the cDLQI and the PASI help to quantify the clinical severity and burden of the disease, and the upgraded criteria should reflect that children’s needs are different from adults’. The choice of medication is limited to a few, but increasing approvals for children and the close exchange of information and preparations with pediatricians and other specialties before initiating systemic therapies are crucial for children to support compliance. We emphasize the focus on vaccinations and the treatment of chronic infections, e.g., the management of TBI, which is different from adults. Conclusions: With the increased options for the systemic treatment of children with psoriasis, clear and adapted information for the child, guardian and pediatrician is essential to assure a well-managed environment and to prevent the unnecessary termination of effective therapy. Full article

Background/Objectives: Traumatic brain injury (TBI) is a leading cause of death and disability in children. Currently, no biological test can predict outcomes in pediatric TBI, complicating medical management. This study sought to identify brain-related micro-ribosomal nucleic acids (miRNAs) in saliva associated with moderate-to-severe TBI in children, offering a potential non-invasive, prognostic tool. Methods: A case-control design was used, enrolling participants ≤ 18 years old from three pediatric trauma centers. Participants were divided into moderate-to-severe TBI and non-TBI trauma control groups. Saliva samples were collected within 24 h of injury, with additional samples at 24–48 h and >48 h post-injury from the TBI group. miRNA profiles were visualized with partial least squares discriminant analysis (PLSDA) and hierarchical clustering. Mann–Whitney testing was used to compare miRNAs between groups, and mixed models were used to assess longitudinal expression patterns. DIANA miRPath v3.0 was used to interrogate the physiological functions of miRNAs. Results: Twenty-three participants were enrolled (14 TBI, nine controls). TBI and control groups displayed complete separation of miRNA profiles on PLSDA. Three miRNAs were elevated (adj. p < 0.05) in TBI (miR-1255b-5p, miR-3142, and miR-4320), and two were lower (miR-326 and miR-4646-5p). Three miRNAs (miR-3907, miR-4254, and miR-1273g-5p) showed temporal changes post-injury. Brain-related targets of these miRNAs included the glutamatergic synapse and GRIN2B. Conclusions: This study shows that saliva miRNA profiles in children with moderate-to-severe TBI may differ from those with non-TBI trauma and exhibit temporal changes post-injury. These miRNAs could serve as non-invasive biomarkers for prognosticating pediatric TBI outcomes. Further studies are needed to confirm these findings. Full article

Severe traumatic brain injury (sTBI) is a silent epidemic, causing approximately 300,000 intensive care unit (ICU) admissions annually, with a 30% mortality rate. Despite worldwide efforts to optimize the management of patients and improve outcomes, the level of evidence for the treatment of these patients remains low. The concomitant occurrence of thromboembolic events, particularly pulmonary embolism (PE), remains a challenge for intensivists due to the risks of anticoagulation to the injured brain. We performed a literature review on sTBI and concomitant PE to identify and report the most recent advances on this topic. We searched PubMed and Scopus for papers published in the last five years that included the terms “pulmonary embolism” and “traumatic brain injury” in their title or abstract. Exclusion criteria were papers referring to children, non-sTBI populations, and post-acute care. Our search revealed 75 papers, of which 38 are included in this review. The main topics covered include the prevalence of and risk factors for pulmonary embolism, the challenges of timely diagnosis in the ICU, the timing of pharmacological prophylaxis, and the treatment of diagnosed PE. Full article

Until recently, no disease-specific health-related quality of life (HRQoL) questionnaire existed for pediatric traumatic brain injuries (TBIs). In this revalidation study, the psychometric properties and the validity of the 35-item QOLIBRI-KID/ADO questionnaire in its final German version were examined in 300 children and adolescents. It is the first self-reported TBI-specific tool for measuring pediatric HRQoL in individuals aged between 8 and 17 years. The six-factor model fits the data adequately. The questionnaire’s internal consistency was excellent for the total score and satisfactory to excellent for the scale scores. Intraclass correlations indicated good test–retest reliability, and the measure’s construct validity was supported by the overlap between the QOLBRI-KID/ADO and the PedsQL, which measures generic HRQoL. The discriminant validity tests showed that older children and girls reported a significantly lower HRQoL than comparison groups, and this was also true of children who were anxious or depressed, or who suffered from post-concussion symptoms, replicating the results of the questionnaire’s first developmental study. Our results suggest that the QOLIBRI-KID/ADO is a reliable and valid multidimensional tool that can be used together with the adult version in clinical contexts and research to measure disease-specific HRQoL after pediatric TBI throughout a person’s life. This may help improve care, treatment, daily functioning, and HRQoL after TBI. Full article

Assessment of health-related quality of life (HRQoL) after pediatric traumatic brain injury (TBI) has been limited in children and adolescents due to a lack of disease-specific instruments. To fill this gap, the Quality of Life after Traumatic Brain Injury for Children and Adolescents (QOLIBRI-KID/ADO) Questionnaire was developed for the German-speaking population. Reference values from a comparable general population are essential for comprehending the impact of TBI on health and well-being. This study examines the validity of the German QOLIBRI-KID/ADO in a general pediatric population in Germany and provides reference values for use in clinical practice. Overall, 1997 children and adolescents aged 8–17 years from the general population and 300 from the TBI population participated in this study. The questionnaire was tested for reliability and validity. A measurement invariance (MI) approach was used to assess the comparability of the HRQoL construct between both samples. Reference values were determined by percentile-based stratification according to factors that significantly influenced HRQoL in regression analyses. The QOLIBRI-KID/ADO demonstrated strong psychometric properties. The HRQoL construct was measured largely equivalently in both samples, and reference values could be provided. The QOLIBRI-KID/ADO was considered reliable and valid for assessing HRQoL in a general German-speaking pediatric population, allowing for clinically meaningful comparisons between general and TBI populations. Full article

Purpose: To determine the utility of interferon-gamma-inducible protein 10 (IP-10) for identifying active tuberculosis (TB) and TB infection (TBI) in children in BCG-vaccinated populations, establish its diagnostic performance characteristics, and evaluate changes in IP-10 level during anti-TB chemotherapy. Methods: Concentrations of IP-10 and IFN-γ were measured in QuantiFERON-TB Gold (QFT) supernatants in children with suspected TB or due to recent TB contact. A total of 225 children were investigated: 33 with active TB, 48 with TBI, 83 TB contacts, 20 with suspected TB but other final diagnoses, and 41 controls. In 60 children, cytokine responses were evaluated at a follow-up visit after 2 months of anti-TB treatment. Results: IP-10 expression was significantly higher in infected children (active TB and TBI cases) than in uninfected individuals. IP-10 proved effective in identifying TB infection at its optimal cut-off (>1084.5 pg/mL) but was incapable of differentiating between children with active TB and TBI. Combining IP-10 and IFN-γ increased the QFT sensitivity. IP-10 but not IFN-γ decreased significantly during anti-TB treatment in children with active TB (p = 0.003). Conclusion: IP-10 identifies TB infection and declines during anti-TB chemotherapy in children. Incorporating IP-10 into new immunodiagnostic assays could improve TB diagnosis and allow for treatment monitoring. Full article

Background: The impact of traumatic brain injury (TBI) on the pediatric population is profound. The aim of this study is to unveil the state of the evidence concerning acute neurosurgical intervention, hospitalizations after injury, and neuroimaging in isolated skull fractures (ISF). Materials and Methods: This systematic review was conducted in accordance with PRISMA guidelines. PubMed, Cochrane, Web of Science, and Embase were searched for papers until April 2023. Only ISF cases diagnosed via computed tomography were considered. Results: A total of 10,350 skull fractures from 25 studies were included, of which 7228 were ISF. For the need of acute neurosurgical intervention, the meta-analysis showed a risk of 0% (95% CI: 0–0%). For hospitalization after injury the calculated risk was 78% (95% CI: 66–89%). Finally, for the requirement of repeated neuroimaging the analysis revealed a rate of 7% (95% CI: 0–15%). No deaths were reported in any of the 25 studies. Conclusions: Out of 7228 children with ISF, an almost negligible number required immediate neurosurgical interventions, yet a significant 74% were hospitalized for up to 72 h. Notably, the mortality was zero, and repeat neuroimaging was uncommon. This research is crucial in shedding light on the outcomes and implications of pediatric TBIs concerning ISFs. Full article

Pediatric health-related quality of life (HRQoL) as a measure of subjective wellbeing and functioning has received increasing attention over the past decade. HRQoL in children and adolescents following pediatric traumatic brain injury (pTBI) has been poorly studied, and performing adequate measurements in this population is challenging. This study compares child/adolescent and parent reports of HRQoL following pTBI using the newly developed Quality of Life after Brain Injury in Children and Adolescents (QOLIBRI-KID/ADO) questionnaire. Three hundred dyads of 8–17-year-old children/adolescents and their parents were included in the study. The parent–child agreement, estimated using intraclass correlation coefficients and Cohen’s κ, displayed poor to moderate concordance. Approximately two-fifths of parents (39.3%) tended to report lower HRQoL for their children/adolescents on the total QOLIBRI-KID/ADO score. At the same time, about one-fifth (21.3%) reported higher HRQoL Total scores for their children/adolescents. The best agreement for parents rating adolescents (aged 13–17 years) was found in terms of the Total score and the Cognition and Self scale scores. To date, parent-reported HRQoL has been the preferred choice in pediatric research after TBI. However, with a parent–child disagreement of approximately 60%, our results highlight the importance of considering self-reports for children/adolescents capable of answering or completing the HRQoL measures. Full article