Advanced Pediatric Neurosonography Techniques: Contrast‐Enhanced Ultrasonography,Elastography, and Beyond

Recent technical advances in neurosonography continue broadening the diagnostic utility, sensitivity, and specificity of ultrasound for detecting intracranial abnormalities bed side. The clinical and functional applications of neurosonography have significantly expanded since the 1980s when transcranial Doppler sonography first allowed anatomic and hemodynamic delineation of the intracranial vessels through the thin temporal skull. In the past few years, contrast‐enhanced ultrasonography, elastography, 3D/4D reconstruction tools, and high‐resolution microvessel imaging techniques have further enhanced the diagnostic significance of neurosonography. Given these advances, a thorough familiarity with these new techniques and devices is crucial for a successful clinical application allowing improved patient care. It is essential that future neurosonography studies compare these advanced techniques against the current “gold standard” computed tomography and magnetic resonance imaging to assure the accuracy of their diagnostic potential. This review will provide a comprehensive update on currently available advanced neurosonography techniques.     

Delayed injury of hippocampal interneurons after neonatal hypoxia‐ischemia and therapeutic hypothermia in a murine model

Delayed hippocampal injury and memory impairments follow neonatal hypoxia‐ischemia (HI) despite the use of therapeutic hypothermia (TH). Death of hippocampal pyramidal cells occurs acutely after HI, but characterization of delayed cell death and injury of interneurons (INs) is unknown. We hypothesize that injury of INs after HI is: (i) asynchronous to that of pyramidal cells, (ii) independent of injury severity, and (iii) unresponsive to TH. HI was induced in C57BL6 mice at p10 with unilateral right carotid ligation and 45 min of hypoxia (FiO₂ = 0.08). Mice were randomized to normothermia (36 °C, NT) or TH (31 °C) for 4 hr after HI and anesthesia‐exposed shams were use as controls. Brains were studied at 24 hr (p11) or 8 days (p18) after HI. Vglut1, GAD65/67, PSD95, parvalbumin (PV) and calbindin‐1 (Calb1) were measured. Cell death was assessed using cresyl violet staining and TUNEL assay. Hippocampal atrophy and astroglyosis at p18 were used to assess injury severity and to correlate with number of PV + INs. VGlut1 level decreased by 30% at 24 hr after HI, while GAD65/67 level decreased by ～50% in forebrain 8 days after HI, a decrease localized in CA1 and CA3. PSD95 levels decreased in forebrain by 65% at 24 hr after HI and remained low 8 days after HI. PV + INs increased in numbers (per mm²) and branching between p11 and p18 in sham mice but not in NT and TH mice, resulting in 21–52% fewer PV + INs in injured mice at p18. Calb1 protein and mRNA were also reduced in HI injured mice at p18. At p18, somatodendritic attrition of INs was evident in all injured mice without evidence of cell death. Neither hippocampal atrophy nor astroglyosis correlated with the number of PV + INs at p18. Thus, HI exposure has long lasting effects in the hippocampus impairing the development of the GABAergic system with only partial protection by TH independent of the degree of hippocampal injury. © 2018 Wiley Periodicals, Inc.     

Necrostatin decreases oxidative damage,inflammation, and injury after neonatal HI

Necrostatin-1 inhibits receptor-interacting protein (RIP)-1 kinase and programmed necrosis and is neuroprotective in adult rodent models. Owing to the prominence of necrosis and continuum cell death in neonatal hypoxia–ischemia (HI), we tested whether necrostatin was neuroprotective in the developing brain. Postnatal day (P)7 mice were exposed to HI and injected intracerebroventricularly with 0.1 μL of 80 μmol necrostatin, Nec-1, 5-(1H-Indol-3-ylmethyl)-(2-thio-3-methyl) hydantoin, or vehicle. Necrostatin significantly decreased injury in the forebrain and thalamus at P11 and P28. There was specific neuroprotection in necrostatin-treated males. Necrostatin treatment decreased necrotic cell death and increased apoptotic cell death. Hypoxia–ischemia enforced RIP1–RIP3 complex formation and inhibited RIP3–FADD (Fas-associated protein with death domain) interaction, and these effects were blocked by necrostatin. Necrostatin also decreased HI-induced oxidative damage to proteins and attenuated markers of inflammation coincidental with decreased nuclear factor-κB and caspase 1 activation, and FLIP ((Fas-associated death-domain-like IL-1β-converting enzyme)-inhibitory protein) gene and protein expression. In this model of severe neonatal brain injury, we find that cellular necrosis can be managed therapeutically by a single dose of necrostatin, administered after HI, possibly by interrupting RIP1–RIP3-driven oxidative injury and inflammation. The effects of necrostatin treatment after HI reflect the importance of necrosis in the delayed phases of neonatal brain injury and represent a new direction for therapy of neonatal HI.     

Use of Temporary Enteral Access Devices in Hospitalized Neonatal and Pediatric Patients in the United States

Background: Temporary enteral access devices (EADs), such as nasogastric (NG), orogastric (OG), and postpyloric (PP), are used in pediatric and neonatal patients to administer nutrition, fluids, and medications. While the use of these temporary EADs is common in pediatric care, it is not known how often these devices are used, what inpatient locations have the highest usage, what size tube is used for a given weight or age of patient, and how placement is verified per hospital policy. Materials and Methods: This was a multicenter 1‐day prevalence study. Participating hospitals counted the number of NG, OG, and PP tubes present in their pediatric and neonatal inpatient population. Additional data collected included age, weight and location of the patient, type of hospital, census for that day, and the method(s) used to verify initial tube placement. Results: Of the 63 participating hospitals, there was an overall prevalence of 1991 temporary EADs in a total pediatric and neonatal inpatient census of 8333 children (24% prevalence). There were 1316 NG (66%), 414 were OG (21%), and 261 PP (17%) EADs. The neonatal intensive care unit (NICU) had the highest prevalence (61%), followed by a medical/surgical unit (21%) and pediatric intensive care unit (18%). Verification of EAD placement was reported to be aspiration from the tube (n = 21), auscultation (n = 18), measurement (n = 8), pH (n = 10), and X‐ray (n = 6). Conclusion: The use of temporary EADs is common in pediatric care. There is wide variation in how placement of these tubes is verified.