Intravenous administration of ultrasound contrast to critically ill pediatric patients.

BACKGROUND: The off-label use of contrast-enhanced ultrasound has been increasingly used for pediatric patients. OBJECTIVE: The purpose of this retrospective study is to report any observed clinical changes associated with the intravenous (IV) administration of ultrasound contrast to critically ill neonates, infants, children, and adolescents. MATERIALS AND METHODS: All critically ill patients who had 1 or more contrast-enhanced ultrasound scans while being closely monitored in the neonatal, pediatric, or pediatric cardiac intensive care units were identified. Subjective and objective data concerning cardiopulmonary, neurological, and hemodynamic monitoring were extracted from the patient's electronic medical records. Vital signs and laboratory values before, during, and after administration of ultrasound contrast were obtained. Statistical analyses were performed using JMP Pro, version 15. Results were accepted as statistically significant for P-value<0.05. RESULTS: Forty-seven contrast-enhanced ultrasound scans were performed on 38 critically ill patients, 2 days to 17 years old, 19 of which were female (50%), and 19 had history of prematurity (50%). At the time of the contrast-enhanced ultrasound scans, 15 patients had cardiac shunts or a patent ductus arteriosus, 25 had respiratory failure requiring invasive mechanical oxygenation and ventilation, 19 were hemodynamically unstable requiring continual vasoactive infusions, and 8 were receiving inhaled nitric oxide. In all cases, no significant respiratory, neurologic, cardiac, perfusion, or vital sign changes associated with IV ultrasound contrast were identified. CONCLUSION: This study did not retrospectively identify any adverse clinical effects associated with the IV administration of ultrasound contrast to critically ill neonates, infants, children, and adolescents.

Magnetic Resonance Imaging-Based Distribution and Reversibility of Lesions in Pediatric Vigabatrin-Related Brain Toxicity.

BACKGROUND: We aimed to systematically characterize the magnetic resonance imaging (MRI) findings in vigabatrin-related neurotoxicity in children and determine the reversibility of lesions based on follow-up images. METHODS: We evaluated children with a history of refractory seizures who had a brain MRI while on vigabatrin therapy. We included available brain MRI studies before vigabatrin therapy initiation, during vigabatrin treatment, and after vigabatrin was discontinued. A pediatric neuroradiologist systematically assessed images on T2/fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging /apparent diffusion coefficient sequences to identify hyperintense lesions and/or restricted diffusion. The frequency of abnormal signal at each location was determined, as well as the reversibility of these after vigabatrin discontinuation. RESULTS: MRIs of 43 patients were reviewed: 13 before vigabatrin initiation, 18 during treatment, and 12 after vigabatrin discontinuation. In the MRIs acquired during vigabatrin treatment, most lesions on T2/FLAIR occurred in the globus pallidi, thalami, and midbrain. Correspondingly, the most common locations for restricted diffusion were the globus pallidi, thalami, and subthalamic nuclei. On MRI after vigabatrin discontinuation, complete resolution of lesions on T2/FLAIR in all patients was seen in the midbrain, dentate nuclei, subthalamic nuclei, and hypothalami. Complete resolution of restricted diffusion was observed in the globus pallidi, midbrain, dentate nuclei, hippocampi, anterior commissure, and hypothalami. CONCLUSION: Globus pallidi and thalami are the most commonly affected structures in vigabatrin-related toxicity, and most vigabatrin-related neuroimaging findings are reversible.

Advanced Neuromonitoring Modalities on the Horizon: Detection and Management of Acute Brain Injury in Children.

Timely detection and monitoring of acute brain injury in children is essential to mitigate causes of injury and prevent secondary insults. Increasing survival in critically ill children has emphasized the importance of neuroprotective management strategies for long-term quality of life. In emergent and critical care settings, traditional neuroimaging modalities, such as computed tomography and magnetic resonance imaging (MRI), remain frontline diagnostic techniques to detect acute brain injury. Although detection of structural and anatomical abnormalities remains crucial, advanced MRI sequences assessing functional alterations in cerebral physiology provide unique diagnostic utility. Head ultrasound has emerged as a portable neuroimaging modality for point-of-care diagnosis via assessments of anatomical and perfusion abnormalities. Application of electroencephalography and near-infrared spectroscopy provides the opportunity for real-time detection and goal-directed management of neurological abnormalities at the bedside. In this review, we describe recent technological advancements in these neurodiagnostic modalities and elaborate on their current and potential utility in the detection and management of acute brain injury.

It's Like a Death.

In this narrative medicine essay, a neurosurgeon works through his grief over ending his surgical career due to intractable pain from an elbow injury by appreciating what he can do instead of focusing on what he lost.

Distribution of IntraThalamic Injury According to Nuclei and Vascular Territories in Children With Term Hypoxic-Ischemic Injury.

BACKGROUND: Term hypoxic-ischemic injury (HII) on magnetic resonance imaging (MRI) is described as the basal ganglia thalamus [BGT], watershed [WS], or combined [BGT/WS] groups. We aimed to determine differences between HII groups in intrathalamic distribution. METHODS: Delayed MRIs of children with HII and thalamic injury were reviewed. Custom tools were placed over T2-weighted and/or fluid-attenuated inversion recovery axial images to determine distribution of intrathalamic injury: (1) six subjective (whole/near-whole, central, anterior, posterior, lateral, medial); (2) four nuclear (anterior [AN], ventrolateral [VLN], medial [MN], and pulvinar [PN]); and (3) three arterial (thalamoperforating arteries [TPA], thalamogeniculate arteries [TGA], and posterior choroidal arteries [PCA]) locations. We compared the frequency of injury of the aforementioned intrathalamic locations between HII groups. RESULTS: The 128 children (mean age at MRI 7.35 ± 3.6 years) comprised 41% (n = 53) BGT, 26% (n = 33) WS, and 33% (n = 42) BGT/WS. The VLN was the most frequent injured nuclear region (66%, n = 85), and the TGA (93%, n = 128) was the most frequent arterial region involved. VLN injury occurred more frequently in the BGT group (P < 0.001), PN in the WS group (P < 0.001), and AN (P < 0.001), MN (P < 0.001), PN (P = 0.001), and all nuclei together (P < 0.001) in the BGT/WS group. The combination of all vascular territories was significantly associated with BGT/WS (P < 0.001). CONCLUSIONS: There are significant differences in intrathalamic nuclear and arterial injuries between the different types of HII.

Frequency of ulegyria on delayed MRI scans in children with term hypoxic-ischemic injury.

BACKGROUND: Ulegyria is an under-recognized and underreported potential sequela of hypoxic-ischemic injury (HII) in full-term neonates. Ulegyria is a unique form of parenchymal scarring that leads to a mushroom-shape of the affected gyri resulting from volume loss at the deep portions of the sulci during HII in this specific period in infantile neurodevelopment. Identifying ulegyria is important for ascribing cause and timing of HII on delayed magnetic resonance imaging (MRI) scans and because of its close association with pharmaco-resistant epilepsy. OBJECTIVE: The purpose of this study was to determine the frequency of ulegyria and characterize the anatomical distribution of watershed injury in a large database of patients who developed cerebral palsy with term HII pattern and underwent delayed MRI. MATERIALS AND METHODS: Patients with term HII patterns on MRI were analyzed for ulegyria. The frequency of ulegyria overall and for each pattern of HII distribution was determined as was the anatomical distribution of watershed injury. RESULTS: Of the 731 children with term HII and cortical injury, 484 (66%) had ulegyria. Ulegyria was most common in those cases with a combined watershed/basal ganglia-thalamic pattern (56%) and isolated watershed pattern (40%). Watershed injury in patients with ulegyria was most common at the posterior watershed (80.6%) and perisylvian watershed (76.7%). CONCLUSION: Ulegyria was present in nearly two-thirds of patients with term HII and cortical injury and should be sought to support the diagnosis of previous perinatal HII, especially in posterior and perisylvian watershed regions. The implications of ulegyria can be significant for clinical decision-making and for ascribing timing of injury to the perinatal period.

An alternative reduced dose regimen of ticagrelor for neuroendovascular patients.

OBJECTIVE: There is a growing use of ticagrelor in patients undergoing neuroendovascular procedures, especially those who demonstrate clopidogrel resistance. While multiple dosages are studied in the cardiology literature, the optimal dose for patients with neurological pathology has yet to be established. Here, we describe a single center experience involving 39 patients who underwent neuroendovascular procedures that then received an adjusted lower dose of ticagrelor. METHODS: A retrospective chart review was performed between 2013 and 2017 for patients on dual anti-platelet therapy (DAPT) for either cervical or intracranial vascular pathologies, as well as stenting of the neurovasculature, including carotid arteries. Patients were placed on ticagrelor if their measured P2Y12 reaction units (PRU) responses to clopidogrel were outside the expected range in our center using the VerifyNow™ P2Y12 test. All patients were maintained on a dose of 45 mg twice daily except for one patient who received 22.5 mg twice daily. Responsiveness to ticagrelor were measured utilizing the VerifyNow™ P2Y12 test. RESULTS: The mean number of days for follow-up post treatment initiation was 532 days. A total of 39 patients were included in the analysis. Of these, 8 patients (21%) received implantation of intracranial stents (5 patients received pipeline embolization devices, 1 patient received stent-assisted coiling, and 2 patients received intracranial stents for atherosclerotic disease). Fourteen patients (35%) received carotid angioplasty and stenting. Seventeen patients (44%) did not receive permanent implantation of a stent. All patients on the lower dose ticagrelor of 45 mg twice daily achieved responsiveness (i.e., PRU < 194). Hemorrhagic transformation of ischemic stroke occurred in one patient (2.5%). No other hemorrhagic complications were encountered. No thromboembolic events were recorded aside from one patient (2.5%) with intracranial atherosclerotic disease who had an ischemic event. CONCLUSIONS: A lower dose of ticagrelor (45 mg twice daily) appears to be safe and effective in this small cohort of patients who are resistant to clopidogrel per P2Y12 testing and who have increased risk of ischemic or hemorrhagic strokes due to neurovascular pathologies and implants. Further randomized studies are required to confirm these findings.

State-of-the-art imaging for lymphatic evaluation in children.

The lymphatic system has been poorly understood and its importance neglected for decades. Growing understanding of lymphatic flow pathophysiology through peripheral and central lymphatic flow imaging has improved diagnosis and treatment options in children with lymphatic diseases. Flow dynamics can now be visualized by different means including dynamic contrast-enhanced magnetic resonance lymphangiography (DCMRL), the current standard technique to depict central lymphatics. Novel imaging modalities including intranodal, intrahepatic and intramesenteric DCMRL are quickly evolving and have shown important advances in the understanding and guidance of interventional procedures in children with intestinal lymphatic leaks. Lymphatic imaging is gaining importance in the radiologic and clinical fields and new techniques are emerging to overcome its limitations.

Utility of Cerebral Microvascular Imaging in Infants Undergoing ECMO.

PURPOSE: Infants who require extracorporeal membrane oxygenation (ECMO) therapy have an increased risk of neurological complications and mortality. Microvascular imaging (MVI) is an advanced Doppler technique that allows high-resolution visualization of microvasculature in the brain. We describe the feasibility and utility of MVI for the evaluation of cerebral microvascular perfusion in patients undergoing ECMO. METHODS: We retrospectively analyzed brain MVI scans of neonates undergoing ECMO. Two pediatric radiologists qualitatively assessed MVI scans to determine the presence or absence of tortuosity, symmetry, heterogeneity, engorgement, and hypoperfusion of the basal ganglia-thalamus (BGT) region, as well as the presence or absence of white matter vascular engorgement and increased peri-gyral flow in the cortex. We tested the association between the presence of the aforementioned brain MVI features and clinical outcomes. RESULTS: We included 30 patients, 14 of which were male (46.7%). The time of ECMO duration was 11.8 ± 6.9 days. The most prevalent microvascular finding in BGT was lenticulostriate vessel tortuosity (26/30, 86.7%), and the most common microvascular finding in the cortex was increased peri-gyral flow (10/24, 41.7%). Cortical white matter vascular engorgement was significantly associated with the presence of any poor outcome as defined by death, seizure, and/or cerebrovascular events on magnetic resonance imaging (p = 0.03). CONCLUSION: MVI is a feasible modality to evaluate cerebral perfusion in infants undergoing ECMO. Additionally, evidence of white matter vascular engorgement after ECMO cannulation could serve as a predictor of poor outcomes in this population.

Preoperative Radiosurgery for Resected Brain Metastases: The PROPS-BM Multicenter Cohort Study.

PURPOSE: Preoperative radiosurgery (SRS) is a feasible alternative to postoperative SRS, with potential benefits in adverse radiation effect (ARE) and leptomeningeal disease (LMD) relapse. However, previous studies are limited by small patient numbers and single-institution designs. Our aim was to evaluate preoperative SRS outcomes and prognostic factors from a large multicenter cohort (Preoperative Radiosurgery for Brain Metastases [PROPS-BM]). METHODS AND MATERIALS: Patients with brain metastases (BM) from solid cancers who had at least 1 lesion treated with preoperative SRS and underwent a planned resection were included from 5 institutions. SRS to synchronous intact BM was allowed. Radiographic meningeal disease (MD) was categorized as either nodular or classical "sugarcoating" (cLMD). RESULTS: The cohort included 242 patients with 253 index lesions. Most patients (62.4%) had a single BM, 93.7% underwent gross total resection, and 98.8% were treated with a single fraction to a median dose of 15 Gray to a median gross tumor volume of 9.9 cc. Cavity local recurrence (LR) rates at 1 and 2 years were 15% and 17.9%, respectively. Subtotal resection (STR) was a strong independent predictor of LR (hazard ratio, 9.1; P < .001). One and 2-year rates of MD were 6.1% and 7.6% and of any grade ARE were 4.7% and 6.8% , respectively. The median overall survival (OS) duration was 16.9 months and the 2-year OS rate was 38.4%. The majority of MD was cLMD (13 of 19 patients with MD; 68.4%). Of 242 patients, 10 (4.1%) experienced grade ≥3 postoperative surgical complications. CONCLUSIONS: To our knowledge, this multicenter study represents the largest cohort treated with preoperative SRS. The favorable outcomes previously demonstrated in single-institution studies, particularly the low rates of MD and ARE, are confirmed in this expanded multicenter analysis, without evidence of an excessive postoperative surgical complication risk. STR, though infrequent, is associated with significantly worse cavity LR. A randomized trial between preoperative and postoperative SRS is warranted and is currently being designed.

A multi-institutional analysis of presentation and outcomes for leptomeningeal disease recurrence after surgical resection and radiosurgery for brain metastases.

BACKGROUND: Radiographic leptomeningeal disease (LMD) develops in up to 30% of patients following postoperative stereotactic radiosurgery (SRS) for brain metastases. However, the clinical relevancy of this finding and outcomes after various salvage treatments are not known. METHODS: Patients with brain metastases, of which 1 was resected and treated with adjunctive SRS, and who subsequently developed LMD were combined from 7 tertiary care centers. LMD pattern was categorized as nodular (nLMD) or classical ("sugarcoating," cLMD). RESULTS: The study cohort was 147 patients. Most patients (60%) were symptomatic at LMD presentation, with cLMD more likely to be symptomatic than nLMD (71% vs. 51%, P = 0.01). Salvage therapy was whole brain radiotherapy (WBRT) alone (47%), SRS (27%), craniospinal radiotherapy (RT) (10%), and other (16%), with 58% receiving a WBRT-containing regimen. WBRT was associated with lower second LMD recurrence compared with focal RT (40% vs 68%, P = 0.02). Patients with nLMD had longer median overall survival (OS) than those with cLMD (8.2 vs 3.3 mo, P < 0.001). On multivariable analysis for OS, pattern of initial LMD (nodular vs classical) was significant, but type of salvage RT (WBRT vs focal) was not. CONCLUSIONS: Nodular LMD is a distinct pattern of LMD associated with postoperative SRS that is less likely to be symptomatic and has better OS outcomes than classical "sugarcoating" LMD. Although focal RT demonstrated increased second LMD recurrence compared with WBRT, there was no associated OS detriment. Focal cranial RT for nLMD recurrence after surgery and SRS for brain metastases may be a reasonable alternative to WBRT.