Blood based traumatic brain injury (TBI) biomarkers offer additional diagnostic, therapeutic, and prognostic utility. While adult studies are robust, the pediatric population is less well studied. We sought to determine whether plasma osteopontin (OPN) and S100B alone or in combination predict mortality, head Computed tomography (CT) findings, as well as 6-month functional outcomes after TBI in children. This is a prospective, observational study between March 2017 and June 2021 at a tertiary pediatric hospital. The sample included children with a diagnosed head injury of any severity admitted to the Emergency Department. Control patients sustained trauma-related injuries and no known head trauma. Serial blood samples were collected at admission, as well as at 24, 48, and 72 h. Patient demographics, acute clinical symptoms, head CT, and 6-month follow-up using the Glasgow outcome scale, extended for pediatrics (GOSE-Peds), were also obtained. The cohort included 460 children (ages 0 to 21 years) and reflected the race and sex distribution of the population served. Linear mixed effect models and logistic regressions were utilized to evaluate the trajectory of biomarkers over time and predictors of dichotomous outcomes. Both OPN and S100B correlated with injury severity based on GCS. S100B and OPN showed lower AUC values (0.59) in predicting positive head CT. S100B had the largest AUC (0.87) in predicting mortality, as well as 6-month outcomes (0.85). The combination of the two biomarkers did not add meaningfully to the model. Our findings continue to support the utility of OPN as a marker of injury severity in this population. Our findings also show the importance of S100B in predicting mortality and 6-month functional outcomes. Continued work is needed to examine the influence of age-dependent neurodevelopment on TBI biomarker profiles in children.
Intracranial metastasis of neuroblastoma (IMN) is associated with poor survival. No curative therapy for the treatment of IMN currently exists. Unfractionated radiotherapy may be beneficial in the treatment of IMN given the known radiosensitivity of neuroblastoma as well as its proclivity to metastasize as discrete lesions. We present two patients with IMN treated with Gamma Knife stereotactic radiosurgery (SRS). Single-fraction radiotherapy yielded temporary reduction of tumor burden and stability of disease in both patients. SRS may be a useful palliative tool in the treatment of IMN and expands the overall treatment options for this disease.
Introduction: Infant type hemispheric gliomas are a rare tumor with unique molecular characteristics. In many cases these harbor mutations in receptor tyrosine kinase pathways and respond to targeted therapy. Here we describe the case of an infant with this type of tumor with a novel ATIC-ALK fusion that has responded dramatically to the ALK inhibitor lorlatinib, despite being refractory to standard chemotherapy. Case description: The infant was initially treated with standard chemotherapy and found to have an ATIC-ALK fusion. When surveillance imaging revealed progressive disease, the patient was switched to the ALK-inhibitor lorlatinib at 47 mg/m2/day. The patient demonstrated a significant clinical and radiographic response to the ALK inhibitor lorlatinib after just 3 months of treatment and a near complete response by 6 months of therapy. Conclusion: The ALK inhibitor lorlatinib is an effective targeted therapy in infant type hemispheric glioma patients harboring ATIC-ALK fusion.
Objective: To examine levels of plasma osteopontin (OPN), a recently described neuroinflammatory biomarker, in children with abusive head trauma (AHT) compared with children with other types of traumatic brain injury (TBI). Study design: The study cohort comprised children aged <4 years diagnosed with TBI and seen in the intensive care unit in a tertiary children's hospital. Patients were classified as having confirmed or suspected AHT or TBI by other mechanisms (eg, motor vehicle accidents), as identified by a Child Protection Team clinician. Serial blood samples were collected at admission and at 24, 48, and 72 hours after admission. Levels of OPN were compared across groups. Results: Of 77 patients identified, 24 had confirmed AHT, 12 had suspected AHT, and 41 had TBI. There were no differences in the Glasgow Coma Scale score between the patients with confirmed AHT and those with suspected AHT and those with TBI (median score, 4.5 vs 4 and 7; P =.39). At admission to the emergency department, OPN levels were significantly higher in children with confirmed AHT compared with the other 2 groups (mean confirmed AHT, 471.5 ng/mL; median suspected AHT, 322.3 ng/mL; mean TBI, 278.0 ng/mL; P =.03). Furthermore, the adjusted mean trajectory levels of OPN were significantly higher in the confirmed AHT group compared with the other 2 groups across all subsequent time points (P = <.01). Conclusions: OPN is significantly elevated in children with confirmed AHT compared with those with suspected AHT and those with other types of TBI. OPN expression may help identify children with suspected AHT to aid resource stratification and triage of appropriate interventions for children who are potential victims of abuse.