Predicting blunt cerebrovascular injury in pediatric trauma: Validation of the Utah Score

Risk factors for blunt cerebrovascular injury (BCVI) may differ between children and adults, suggesting that children at low risk for BCVI after trauma receive unnecessary computed tomography angiography (CTA) and high-dose radiation. We previously developed a score for predicting pediatric BCVI based on retrospective cohort analysis. Our objective is to externally validate this prediction score with a retrospective multi-institutional cohort. We included patients who underwent CTA for traumatic cranial injury at four pediatric Level I trauma centers. Each patient in the validation cohort was scored using the “Utah Score” and classified as high or low risk. Before analysis, we defined a misclassification rate <25% as validating the Utah Score. Six hundred forty-five patients (mean age 8.6 ± 5.4 years; 63.4% males) underwent screening for BCVI via CTA. The validation cohort was 411 patients from three sites compared with the training cohort of 234 patients. Twenty-two BCVIs (5.4%) were identified in the validation cohort. The Utah Score was significantly associated with BCVIs in the validation cohort (odds ratio 8.1 [3.3, 19.8], p < 0.001) and discriminated well in the validation cohort (area under the curve 72%). When the Utah Score was applied to the validation cohort, the sensitivity was 59%, specificity was 85%, positive predictive value was 18%, and negative predictive value was 97%. The Utah Score misclassified 16.6% of patients in the validation cohort. The Utah Score for predicting BCVI in pediatric trauma patients was validated with a low misclassification rate using a large, independent, multicenter cohort. Its implementation in the clinical setting may reduce the use of CTA in low-risk patients

Endovascular Thrombectomy for Pediatric Acute Ischemic Stroke: A Multi-Institutional Experience of Technical and Clinical Outcomes

Background: Endovascular thrombectomy is a promising treatment for acute ischemic stroke in children, but outcome and technical data in pediatric patients with large-vessel occlusions are lacking. Objective: To assess technical and clinical outcomes of thrombectomy in pediatric patients. Methods: We undertook a retrospective cohort study of pediatric patients who experienced acute ischemic stroke from April 2017 to April 2019 who had immediate, 30-, and 90-d follow-up. Patients were treated with endovascular thrombectomy at 5 US pediatric tertiary care facilities. We recorded initial and postprocedural modified Thrombolysis in Cerebral Infarction (mTICI) grade ≥ 2b, initial and postprocedural Pediatric National Institutes of Health Stroke Scale (PedNIHSS) score, and pediatric modified Rankin scale (mRS) score 0 to 2 at 90 d. Results: There were 23 thrombectomies in 21 patients (mean age 11.6 ± 4.9 yr, median 11.5, range 2.1-19; 52% female). A total of 19 (83%) thrombectomies resulted in mTICI grade ≥ 2b recanalization. The median PedNIHSS score was 13 on presentation (range 4-33) and 2 (range 0-26) at discharge (mean reduction 11.3 ± 6.1). A total of 14 (66%) patients had a mRS score of 0 to 2 at 30-d follow-up; 18/21 (86%) achieved that by 90 d. The median mRS was 1 (range 0-4) at 30 d and 1 (range 0-5) at 90 d. One patient required a blood transfusion after thrombectomy. Conclusion: In this large series of pediatric patients treated with endovascular thrombectomy, successful recanalization was accomplished via a variety of approaches with excellent clinical outcomes; further prospective longitudinal study is needed

High-grade glioma before and after treatment with radiation and Avastin: Initial observations

We evaluate the effects of adjuvant treatment with the angiogenesis inhibitor Avastin (bevacizumab) on pathological tissue specimens of high-grade glioma. Tissue from five patients before and after treatment with Avastin was subjected to histological evaluation and compared to four control cases of glioma before and after similar treatment protocols not including bevacizumab. Clinical and radiographic data were reviewed. Histological analysis focused on microvessel density and vascular morphology, and expression patterns of vascular endothelial growth factor–A (VEGF-A) and the hematopoietic stem cell, mesenchymal, and cell motility markers CD34, smooth muscle actin, D2-40, and fascin. All patients with a decrease in microvessel density had a radiographic response, whereas no response was seen in the patients with increased microvessel density. Vascular morphology showed apparent “normalization” after Avastin treatment in two cases, with thin-walled and evenly distributed vessels. VEGF-A expression in tumor cells was increased in two cases and decreased in three and did not correlate with treatment response. There was a trend toward a relative increase of CD34, smooth muscle actin, D2-40, and fascin immunostaining following treatment with Avastin. Specimens from four patients with recurrent malignant gliomas before and after adjuvant treatment (not including bevacizumab) had features dissimilar from our study cases. We conclude that a change in vascular morphology can be observed following anti-angiogenic treatment. There seems to be no correlation between VEGF-A expression and clinical parameters. While the phenomena we describe may not be specific to Avastin, they demonstrate the potential of tissue-based analysis for the discovery of clinically relevant treatment response biomarkers

The transcriptional network for mesenchymal transformation of brain tumours

The inference of transcriptional networks that regulate transitions into physiological or pathological cellular states remains a central challenge in systems biology. A mesenchymal phenotype is the hallmark of tumour aggressiveness in human malignant glioma, but the regulatory programs responsible for implementing the associated molecular signature are largely unknown. Here we show that reverse-engineering and an unbiased interrogation of a glioma-specific regulatory network reveal the transcriptional module that activates expression of mesenchymal genes in malignant glioma. Two transcription factors (C/EBPbeta and STAT3) emerge as synergistic initiators and master regulators of mesenchymal transformation. Ectopic co-expression of C/EBPbeta and STAT3 reprograms neural stem cells along the aberrant mesenchymal lineage, whereas elimination of the two factors in glioma cells leads to collapse of the mesenchymal signature and reduces tumour aggressiveness. In human glioma, expression of C/EBPbeta and STAT3 correlates with mesenchymal differentiation and predicts poor clinical outcome. These results show that the activation of a small regulatory module is necessary and sufficient to initiate and maintain an aberrant phenotypic state in cancer cells

Morphological and ultrastructural investigation of the posterior atlanto-occipital membrane: Comparing children with Chiari malformation type I and controls.

IntroductionThe fibrous posterior atlanto-occipital membrane (PAOM) at the craniocervical junction is typically removed during decompression surgery for Chiari malformation type I (CM-I); however, its importance and ultrastructural architecture have not been investigated in children. We hypothesized that there are structural differences in the PAOM of patients with CM-I and those without.MethodsIn this prospective study, blinded pathological analysis was performed on PAOM specimens from children who had surgery for CM-I and children who had surgery for posterior fossa tumors (controls). Clinical and radiographic data were collected. Statistical analysis included comparisons between the CM-I and control cohorts and correlations with imaging measures.ResultsA total of 35 children (mean age at surgery 10.7 years; 94.3% white) with viable specimens for evaluation were enrolled: 24 with CM-I and 11 controls. There were no statistical demographic differences between the two cohorts. Four children had a family history of CM-I and five had a syndromic condition. The cohorts had similar measurements of tonsillar descent, syringomyelia, basion to C2, and condylar-to-C2 vertical axis (all p>0.05). The clival-axial angle was lower in patients with CM-I (138.1 vs. 149.3 degrees, p = 0.016). Morphologically, the PAOM demonstrated statistically higher proportions of disorganized architecture in patients with CM-I (75.0% vs. 36.4%, p = 0.012). There were no differences in PAOM fat, elastin, or collagen percentages overall and no differences in imaging or ultrastructural findings between male and female patients. Posterior fossa volume was lower in children with CM-I (163,234 mm3 vs. 218,305 mm3, pConclusionsIn patients with CM-I, the PAOM demonstrates disorganized architecture compared with that of control patients. This likely represents an anatomic adaptation in the presence of CM-I rather than a pathologic contribution

Real-World Preliminary Experience With Responsive Neurostimulation in Pediatric Epilepsy: A Multicenter Retrospective Observational Study

BACKGROUND: Despite the well-documented utility of responsive neurostimulation (RNS, NeuroPace) in adult epilepsy patients, literature on the use of RNS in children is limited. OBJECTIVE: To determine the real-world efficacy and safety of RNS in pediatric epilepsy patients. METHODS: Patients with childhood-onset drug-resistant epilepsy treated with RNS were retrospectively identified at 5 pediatric centers. Reduction of disabling seizures and complications were evaluated for children (\u3c18 \u3eyr) and young adults (\u3e18 yr) and compared with prior literature pertaining to adult patients. RESULTS: Of 35 patients identified, 17 were \u3c18 yr at the time of RNS implantation, including a 3-yr-old patient. Four patients (11%) had concurrent resection. Three complications, requiring additional surgical interventions, were noted in young adults (2 infections [6%] and 1 lead fracture [3%]). No complications were noted in children. Among the 32 patients with continued therapy, 2 (6%) achieved seizure freedom, 4 (13%) achieved ≥90% seizure reduction, 13 (41%) had ≥50% reduction, 8 (25%) had \u3c50% reduction, and 5 (16%) experienced no improvement. The average follow-up duration was 1.7 yr (median 1.8 yr, range 0.3-4.8 yr). There was no statistically significant difference for seizure reduction and complications between children and young adults in our cohort or between our cohort and the adult literature. CONCLUSION: These preliminary data suggest that RNS is well tolerated and an effective off-label surgical treatment of drug-resistant epilepsy in carefully selected pediatric patients as young as 3 yr of age. Data regarding long-term efficacy and safety in children will be critical to optimize patient selection

Endovascular Thrombectomy for Pediatric Acute Ischemic Stroke: A Multi-Institutional Experience of Technical and Clinical Outcomes.

BackgroundEndovascular thrombectomy is a promising treatment for acute ischemic stroke in children, but outcome and technical data in pediatric patients with large-vessel occlusions are lacking.ObjectiveTo assess technical and clinical outcomes of thrombectomy in pediatric patients.MethodsWe undertook a retrospective cohort study of pediatric patients who experienced acute ischemic stroke from April 2017 to April 2019 who had immediate, 30-, and 90-d follow-up. Patients were treated with endovascular thrombectomy at 5&nbsp;US pediatric tertiary care facilities. We recorded initial and postprocedural modified Thrombolysis in Cerebral Infarction (mTICI) grade&nbsp;≥&nbsp;2b, initial and postprocedural Pediatric National Institutes of Health Stroke Scale (PedNIHSS) score, and pediatric modified Rankin scale (mRS) score 0 to 2 at 90 d.ResultsThere were 23 thrombectomies in 21 patients (mean age 11.6&nbsp;±&nbsp;4.9 yr, median 11.5, range 2.1-19; 52% female). A total of 19 (83%) thrombectomies resulted in mTICI grade&nbsp;≥&nbsp;2b recanalization. The median PedNIHSS score was 13 on presentation (range 4-33) and 2 (range 0-26) at discharge (mean reduction 11.3&nbsp;±&nbsp;6.1). A total of 14 (66%) patients had a mRS score of 0 to 2 at 30-d follow-up; 18/21 (86%) achieved that by 90 d. The median mRS was 1 (range 0-4) at 30 d and 1 (range 0-5) at 90 d. One patient required a blood transfusion after thrombectomy.ConclusionIn this large series of pediatric patients treated with endovascular thrombectomy, successful recanalization was accomplished via a variety of approaches with excellent clinical outcomes; further prospective longitudinal study is needed