Partial Response to Naxitamab for Brain Metastasis in Neuroblastoma.

Neuroblastoma (NBL) is a common pediatric tumor arising from sympathetic ganglion cells. High-risk NBL is based on age, stage, histology, and MYCN amplification, and is associated with a high mortality rate. The combination of naxitamab (NAX) and granulocyte-macrophage (cerebrospinal fluid) is a new treatment for high-risk and relapsed NBL approved for bone or bone marrow disease. NAX is a monoclonal antibody directed against anti-disialoganglioside, which is overexpressed in neuroblastoma. Under normal circumstances, monoclonal antibodies, such as NAX, cannot cross the blood-brain barrier due to size. We present the case of a patient with high-risk NBL treated with NAX for multiple bony relapses. Unexpectedly, her brain metastasis responded clinically, histologically, and by imaging to the treatment. We believe this is the first documented case of NBL of the brain responding to NAX.

Tethered spinal cord tension assessed via ultrasound elastography in computational and intraoperative human studies.

BACKGROUND: Tension in the spinal cord is a trademark of tethered cord syndrome. Unfortunately, existing tests cannot quantify tension across the bulk of the cord, making the diagnostic evaluation of stretch ambiguous. A potential non-destructive metric for spinal cord tension is ultrasound-derived shear wave velocity (SWV). The velocity is sensitive to tissue elasticity and boundary conditions including strain. We use the term Ultrasound Tensography to describe the acoustic evaluation of tension with SWV. METHODS: Our solution Tethered cord Assessment with Ultrasound Tensography (TAUT) was utilized in three sub-studies: finite element simulations, a cadaveric benchtop validation, and a neurosurgical case series. The simulation computed SWV for given tensile forces. The cadaveric model with induced tension validated the SWV-tension relationship. Lastly, SWV was measured intraoperatively in patients diagnosed with tethered cords who underwent treatment (spinal column shortening). The surgery alleviates tension by decreasing the vertebral column length. RESULTS: Here we observe a strong linear relationship between tension and squared SWV across the preclinical sub-studies. Higher tension induces faster shear waves in the simulation (R2 = 0.984) and cadaveric (R2 = 0.951) models. The SWV decreases in all neurosurgical procedures (p < 0.001). Moreover, TAUT has a c-statistic of 0.962 (0.92-1.00), detecting all tethered cords. CONCLUSIONS: This study presents a physical, clinical metric of spinal cord tension. Strong agreement among computational, cadaveric, and clinical studies demonstrates the utility of ultrasound-induced SWV for quantitative intraoperative feedback. This technology is positioned to enhance tethered cord diagnosis, treatment, and postoperative monitoring as it differentiates stretched from healthy cords.

Tethered spinal cord syndrome occurs when surrounding tissue attaches to and causes stretching across the spinal cord. People with a tethered cord can experience weakness, pain, and loss of bladder control. Although increased tension in the spinal cord is known to cause these symptoms, evaluating the amount of stretching remains challenging. We investigated the ability of an ultrasound imaging approach to measure spinal cord tension. We studied our method in a computer simulation, a benchtop validation model, and in six people with tethered cords during surgery that they were undergoing to reduce tension. In each phase, the approach could detect differences between stretched spinal cords and spinal cords in a healthy state. Our method could potentially be used in the future to improve the care of people with a tethered cord.

Quantitative Assessment of Electroencephalogram Reactivity in Comatose Patients on Extracorporeal Membrane Oxygenation.

Objective assessment of the brain's responsiveness in comatose patients on Extracorporeal Membrane Oxygenation (ECMO) support is essential to clinical care, but current approaches are limited by subjective methodology and inter-rater disagreement. Quantitative electroencephalogram (EEG) algorithms could potentially assist clinicians, improving diagnostic accuracy. We developed a quantitative, stimulus-based algorithm to assess EEG reactivity features in comatose patients on ECMO support. Patients underwent a stimulation protocol of increasing intensity (auditory, peripheral, and nostril stimulation). A total of 129 20-s EEG epochs were collected from 24 patients (age [Formula: see text], 10 females, 14 males) on ECMO support with a Glasgow Coma Scale[Formula: see text]8. EEG reactivity scores ([Formula: see text]-scores) were calculated using aggregated spectral power and permutation entropy for each of five frequency bands ([Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text]. Parameter estimation techniques were applied to [Formula: see text]-scores to identify properties that replicate the decision process of experienced clinicians performing visual analysis. Spectral power changes from audio stimulation were concentrated in the [Formula: see text] band, whereas peripheral stimulation elicited an increase in spectral power across multiple bands, and nostril stimulation changed the entropy of the [Formula: see text] band. The findings of this pilot study on [Formula: see text]-score lay a foundation for a future prediction tool with clinical applications.

Intranasal Orexin After Cardiac Arrest Leads to Increased Electroencephalographic Gamma Activity and Enhanced Neurologic Recovery in Rats.

OBJECTIVES: Prolonged cardiac arrest is known to cause global ischemic brain injury and functional impairment. Upon resuscitation, electroencephalographic recordings of brain activity begin to resume and can potentially be used to monitor neurologic recovery. We have previously shown that intrathecal orexin shows promise as a restorative drug and arousal agent in rodents. Our goal is to determine the electrophysiology effects of orexin in a rodent model of asphyxial cardiac arrest, focusing on the electroencephalographic activity in the gamma and super-gamma bands (indicative of return of higher brain function). DESIGN: Experimental animal study. SETTING: University-based animal research laboratory. SUBJECTS: Adult male Wistar rats. INTERVENTIONS: In an established model of asphyxial cardiac arrest (n = 24), we treated half of Wistar rats with orexin administered intranasally by atomizer 30 minutes post return of spontaneous circulation in one of two dose levels (10 and 50 µM); the rest were treated with saline as control. Continuous electroencephalographic recording was obtained and quantitatively analyzed for the gamma fraction. Gamma and high-frequency super-gamma band measures were compared against clinical recovery according to Neuro-Deficit Score. MEASUREMENTS AND MAIN RESULTS: Compared with the control cohort, the high-dose orexin cohort showed significantly better Neuro-Deficit Score 4 hours after return of spontaneous circulation (55.17 vs 47.58; p < 0.02) and significantly higher mean gamma fraction (0.251 vs 0.177; p < 0.02) in cerebral regions surveyed by rostral electrodes for the first 170 minutes after administration of orexin. CONCLUSIONS: Our findings support early and continuous monitoring of electroencephalography-based gamma activity as a marker of better functional recovery after intranasal administration of orexin as measured by Neuro-Deficit Score in an established animal model of asphyxial cardiac arrest.