Consensus Recommendation for Mouse Models of Ocular Hypertension to Study Aqueous Humor Outflow and Its Mechanisms.

Due to their similarities in anatomy, physiology, and pharmacology to humans, mice are a valuable model system to study the generation and mechanisms modulating conventional outflow resistance and thus intraocular pressure. In addition, mouse models are critical for understanding the complex nature of conventional outflow homeostasis and dysfunction that results in ocular hypertension. In this review, we describe a set of minimum acceptable standards for developing, characterizing, and utilizing mouse models of open-angle ocular hypertension. We expect that this set of standard practices will increase scientific rigor when using mouse models and will better enable researchers to replicate and build upon previous findings

Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Importance Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear. Objective To understand the range and severity of neurologic involvement among children and adolescents associated with COVID-19. Setting, Design, and Participants Case series of patients (age <21 years) hospitalized between March 15, 2020, and December 15, 2020, with positive severe acute respiratory syndrome coronavirus 2 test result (reverse transcriptase-polymerase chain reaction and/or antibody) at 61 US hospitals in the Overcoming COVID-19 public health registry, including 616 (36%) meeting criteria for multisystem inflammatory syndrome in children. Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening involvement was adjudicated by experts based on clinical and/or neuroradiologic features. Exposures Severe acute respiratory syndrome coronavirus 2. Main Outcomes and Measures Type and severity of neurologic involvement, laboratory and imaging data, and outcomes (death or survival with new neurologic deficits) at hospital discharge. Results Of 1695 patients (909 [54%] male; median [interquartile range] age, 9.1 [2.4-15.3] years), 365 (22%) from 52 sites had documented neurologic involvement. Patients with neurologic involvement were more likely to have underlying neurologic disorders (81 of 365 [22%]) compared with those without (113 of 1330 [8%]), but a similar number were previously healthy (195 [53%] vs 723 [54%]) and met criteria for multisystem inflammatory syndrome in children (126 [35%] vs 490 [37%]). Among those with neurologic involvement, 322 (88%) had transient symptoms and survived, and 43 (12%) developed life-threatening conditions clinically adjudicated to be associated with COVID-19, including severe encephalopathy (n = 15; 5 with splenial lesions), stroke (n = 12), central nervous system infection/demyelination (n = 8), Guillain-Barré syndrome/variants (n = 4), and acute fulminant cerebral edema (n = 4). Compared with those without life-threatening conditions (n = 322), those with life-threatening neurologic conditions had higher neutrophil-to-lymphocyte ratios (median, 12.2 vs 4.4) and higher reported frequency of D-dimer greater than 3 μg/mL fibrinogen equivalent units (21 [49%] vs 72 [22%]). Of 43 patients who developed COVID-19–related life-threatening neurologic involvement, 17 survivors (40%) had new neurologic deficits at hospital discharge, and 11 patients (26%) died. Conclusions and Relevance In this study, many children and adolescents hospitalized for COVID-19 or multisystem inflammatory syndrome in children had neurologic involvement, mostly transient symptoms. A range of life-threatening and fatal neurologic conditions associated with COVID-19 infrequently occurred. Effects on long-term neurodevelopmental outcomes are unknown

Effects of fuels/fire risk reduction treatments using hydro-mow or thinning on pinyon-juniper ecosystem components within the wildland-urbaninterface.

Pinyon-juniper woodlands are a dominant vegetation type throughout the Interior West on lands managed by the U.S. Forest Service and the USDI Bureau of Land Management. The woodlands have traditionally been viewed as having a low risk of wildfires because of the lack of a continuous and dense ground cover and low tree stand densities. However, stand densities are often high and are increasing in many areas and wildfires, often resulting in loss of lives and property, will occur under conditions of low humidity, high temperatures and wind speeds, and an ignition source. Woodlands commonly surround or are adjacent to many towns in the region; however, in recent years, people have moved into the woodlands to construct individual homes and housing developments. In this decade, the ecology and fire risk in pinyon-juniper woodlands have changed dramatically because of the continuing drought and the region-wide infestation of the pinyon engraver beetle, Ips confusus, which have resulted in high pinyon mortality, increased fuel loadings, and risks of severe wildfires. Managers are attempting to reduce fire hazards and create defensible spaces in the wildland-urban-interface (W.U.I.). They have commonly used hand thinning-piling-burning prescriptions in the W.U.I. but have recently turned to mechanical mastication to accomplish stand reduction goals, especially where slope and soil surface conditions permit the safe operation of heavy equipment. In most situations the goal is to create a mosaic of open and wooded conditions on the landscape. These has advantages of maintaining wildlife habitats, tree and shrub growth, an esthetic landscape, and increasing herbaceous production while improving fire suppression opportunities and reducing fire hazards. However, managers do not know the consequences of mastication on soil nutrient and microbiological populations and on the residual tree, shrub, and herbaceous vegetation. While the number of research studies of the effects mastication on ecosystem components has increased recently, there still are many questions

Case 271: Metronidazole-Induced Encephalopathy

History: An 11-year-old boy taking oral antibiotics for Fusobacterium meningitis diagnosed 3 months earlier presented to the emergency department with a 1-week history of intermittent emesis, dizziness, and vertigo and a 1-day history of wobbly gait and bilateral lower extremity paresthesia without confusion. His metabolic profile was normal. Contrast material-enhanced MRI of the brain was performed

Case 271

History An 11-year-old boy taking oral antibiotics for Fusobacterium meningitis diagnosed 3 months earlier presented to the emergency department with a 1-week history of intermittent emesis, dizziness, and vertigo and a 1-day history of wobbly gait and bilateral lower extremity paresthesia without confusion. His metabolic profile was normal. Contrast material-enhanced MRI of the brain was performed, and selected images are shown ( Fig 1 - 4 ). Figure 1a: (a) Axial fluid-attenuated inversion recovery (repetition time msec/echo time msec, 11 000/125) MRI and (b) axial turbo spin-echo T2-weighted (3000/80) MRI of the brain through the cerebellum at presentation. (c) Axial fluid-attenuated inversion recovery (6000/120) MRI and (d) axial turbo spin-echo T2-weighted (5545/100) MRI through the same level of the cerebellum obtained 6 weeks earlier. Figure 1b: (a) Axial fluid-attenuated inversion recovery (repetition time msec/echo time msec, 11 000/125) MRI and (b) axial turbo spin-echo T2-weighted (3000/80) MRI of the brain through the cerebellum at presentation. (c) Axial fluid-attenuated inversion recovery (6000/120) MRI and (d) axial turbo spin-echo T2-weighted (5545/100) MRI through the same level of the cerebellum obtained 6 weeks earlier. Figure 1c: (a) Axial fluid-attenuated inversion recovery (repetition time msec/echo time msec, 11 000/125) MRI and (b) axial turbo spin-echo T2-weighted (3000/80) MRI of the brain through the cerebellum at presentation. (c) Axial fluid-attenuated inversion recovery (6000/120) MRI and (d) axial turbo spin-echo T2-weighted (5545/100) MRI through the same level of the cerebellum obtained 6 weeks earlier. Figure 1d: (a) Axial fluid-attenuated inversion recovery (repetition time msec/echo time msec, 11 000/125) MRI and (b) axial turbo spin-echo T2-weighted (3000/80) MRI of the brain through the cerebellum at presentation. (c) Axial fluid-attenuated inversion recovery (6000/120) MRI and (d) axial turbo spin-echo T2-weighted (5545/100) MRI through the same level of the cerebellum obtained 6 weeks earlier. Figure 2a: (a) Axial fast spin-echo T1-weighted MRI (496/8) and (b) axial reconstruction of three-dimensional fast field-echo T1-weighted contrast-enhanced (7 mL of gadobutrol, Gadavist; Bayer Healthcare Pharmaceuticals, Berlin, Germany) MRI (7.98/3.72) of regions similar to those in Figure 1 . Figure 2b: (a) Axial fast spin-echo T1-weighted MRI (496/8) and (b) axial reconstruction of three-dimensional fast field-echo T1-weighted contrast-enhanced (7 mL of gadobutrol, Gadavist; Bayer Healthcare Pharmaceuticals, Berlin, Germany) MRI (7.98/3.72) of regions similar to those in Figure 1 . Figure 3a: (a) Axial diffusion-weighted MRI (3090/71) and (b) axial apparent diffusion coefficient map (3090/71) of regions similar to those in Figure 1 . Figure 3b: (a) Axial diffusion-weighted MRI (3090/71) and (b) axial apparent diffusion coefficient map (3090/71) of regions similar to those in Figure 1 . Figure 4: Three-dimensional maximum intensity projection image (25/3.45) of the posterior cerebral circulation obtained with MR angiography of the head

Responsive Neurostimulation Targeting the Anterior, Centromedian and Pulvinar Thalamic Nuclei and the Detection of Electrographic Seizures in Pediatric and Young Adult Patients

BACKGROUND: Responsive neurostimulation (RNS System) has been utilized as a treatment for intractable epilepsy. The RNS System delivers stimulation in response to detected abnormal activity, via leads covering the seizure foci, in response to detections of predefined epileptiform activity with the goal of decreasing seizure frequency and severity. While thalamic leads are often implanted in combination with cortical strip leads, implantation and stimulation with bilateral thalamic leads alone is less common, and the ability to detect electrographic seizures using RNS System thalamic leads is uncertain. OBJECTIVE: The present study retrospectively evaluated fourteen patients with RNS System depth leads implanted in the thalamus, with or without concomitant implantation of cortical strip leads, to determine the ability to detect electrographic seizures in the thalamus. Detailed patient presentations and lead trajectories were reviewed alongside electroencephalographic (ECoG) analyses. RESULTS: Anterior nucleus thalamic (ANT) leads, whether bilateral or unilateral and combined with a cortical strip lead, successfully detected and terminated epileptiform activity, as demonstrated by Cases 2 and 3. Similarly, bilateral centromedian thalamic (CMT) leads or a combination of one centromedian thalamic alongside a cortical strip lead also demonstrated the ability to detect electrographic seizures as seen in Cases 6 and 9. Bilateral pulvinar leads likewise produced reliable seizure detection in Patient 14. Detections of electrographic seizures in thalamic nuclei did not appear to be affected by whether the patient was pediatric or adult at the time of RNS System implantation. Sole thalamic leads paralleled the combination of thalamic and cortical strip leads in terms of preventing the propagation of electrographic seizures. CONCLUSION: Thalamic nuclei present a promising target for detection and stimulation via the RNS System for seizures with multifocal or generalized onsets. These areas provide a modifiable, reversible therapeutic option for patients who are not candidates for surgical resection or ablation

Intravenous Thrombolysis for Treatment of Pediatric Acute Ischemic Stroke: Analysis of 20 Years of Population-Level Data in the United States

BACKGROUND AND AIMS: Although intravenous thrombolysis (IVT) represents standard-of-care treatment for acute ischemic stroke (AIS) in eligible adult patients, definitive evidence-based guidelines and randomized clinical trial data evaluating its safety and efficacy in the pediatric population remain absent from the literature. We aimed to evaluate the utilization and outcomes of IVT for the treatment of pediatric AIS using a large national registry. METHODS: Weighted hospitalizations for pediatric (\u3c18 years of age) AIS patients were identified in the National Inpatient Sample during the period of 2001 to 2019. Complex sample statistical methods were performed to assess unadjusted and adjusted outcomes in patients treated with IVT or other medical management. RESULTS: Among 13,901 pediatric AIS patients, 270 (1.9%) were treated with IVT monotherapy (median age 12.8 years). IVT-treated patients developed any intracranial hemorrhage (ICH) at a rate of 5.6% (n = 15), and 71.9% (n = 194) experienced favorable functional outcomes at discharge (to home or to acute rehabilitation). Following propensity-score adjustment for age, acute stroke severity, infarct location, and etiological/comorbid conditions, IVT was not associated with an increased risk of any ICH (5.6% vs 5.4%, p = 0.931; adjusted odds ratio (aOR) = 1.01, 95% confidence interval (CI) = 0.48-2.14, p = 0.971), nor with favorable functional outcome (71.9% vs 74.5%, p = 0.489; aOR = 0.88, 95% CI = 0.60-1.29, p = 0.511) in comparison with other medical therapy. CONCLUSIONS: Twenty years of population-level data in the United States demonstrate that pediatric AIS patients treated with IVT experienced high rates of favorable outcomes without an increased risk of hemorrhagic transformation

Abstract Number ‐ 2: Intravenous Thrombolysis for Pediatric Ischemic Stroke: Twenty Years of Population‐Level Data in the United States

Introduction Although intravenous thrombolysis (IVT) represents standard‐of‐care treatment for acute ischemic stroke (AIS) in eligible adult patients, definitive evidence‐based guidelines and randomized clinical trial data evaluating its safety and efficacy in the pediatric population remain absent from the literature. We aim to evaluate the utilization and outcomes of IVT for the treatment of pediatric AIS using a large national registry. Methods Weighted hospitalizations for pediatric (<18 years of age) AIS patients were identified in the National Inpatient Sample during the period of 2001 to 2019. Complex samples statistical methods were performed to assess unadjusted and adjusted outcomes in patients treated with IVT or other medical management. Results Among 13,901 pediatric AIS patients, 270 (1.9%) were treated with IVT monotherapy (median age 12.8 years). IVT‐treated patients developed any intracranial hemorrhage (ICH) at a rate of 5.6% (n = 15), and 71.9% (n = 194) experienced favorable functional outcomes at discharge (to home or to acute rehabilitation). Following propensity‐score adjustment for age, acute stroke severity, infarct location, and etiological/comorbid conditions, IVT was not associated with an increased risk of any ICH [5.6% vs. 5.4%, p = 0.931; adjusted odds ratio (aOR) 1.01, 95% confidence interval (CI) 0.48, 2.14, p = 0.971], nor with favorable functional outcome (71.9% vs. 74.5%, p = 0.489; aOR 0.88, 95% CI 0.60, 1.29, p = 0.511) in comparison with other medical therapy. Conclusions Twenty years of population‐level data in the United States demonstrate that pediatric AIS patients treated with IVT experienced high rates of favorable outcomes without an increased risk of hemorrhagic transformation