Infrasellar Nasopharyngeal Craniopharyngiomas: An Individual Participant Data Meta-Analysis and Review of the Literature.

BACKGROUND: Craniopharyngiomas are benign tumors of the anterior skull base arising from epithelial remnants of Rathke pouch. They mainly occur in the suprasellar space, can be incredibly debilitating, and remain difficult to resect as they frequently involve critical neurovascular structures. Although it is embryologically possible for craniopharyngiomas to arise extracranially along the entire migrational path of Rathke pouch, these remain exceedingly rare, especially among adults, and can be mistaken for nasopharyngeal cancer. As such, minimal data exist evaluating the management and outcomes of such lesions. We evaluated our institutional experience with purely infrasellar nasopharyngeal craniopharyngiomas and obtained individual patient data reported in the contemporary literature to better characterize the demographics, presentation, surgical management, and long-term outcomes of these lesions. METHODS: A systematic review of the literature was performed to identify previously published cases of purely infrasellar nasopharyngeal craniopharyngioma in 3 electronic databases: MEDLINE (PubMed), Embase, and Scopus. Search terms were "infrasellar craniopharyngioma" and "nasopharyngeal craniopharyngioma." RESULTS: We identified 25 cases, in which 72% of patients presented with symptoms of nasal obstruction, epistaxis, or headache. An endoscopic approach was performed in 40% of cases; 83.3% of all patients had gross total resection, with 60% having no recurrence at a median follow-up of 13 months. No postoperative complications were reported. Tumor location involving the cavernous sinus was associated with incomplete resection (100%) compared with tumors not involving the cavernous sinus (87%) (P = 0.033). CONCLUSIONS: While uncommon, infrasellar nasopharyngeal craniopharyngiomas appear to have better perioperative and long-term surgical outcomes than their suprasellar counterparts.

Balloon-mounted covered stent as endovascular management of a traumatic cervical internal carotid artery pseudoaneurysm in a 23-year-old: a case report.

Background: Distal cervical internal carotid artery (cICA) pseudoaneurysms are uncommon. They may lead to thromboembolic or hemorrhagic complications, especially in young adults. We report one of the first cases in the literature regarding the management via PK Papyrus (Biotronik, Lake Oswego, Oregon, USA) balloon-mounted covered stent of a 23-year-old male with an enlarging cervical carotid artery pseudoaneurysm and progressive internal carotid artery stenosis. Case Description: We report the management of a 23-year-old male with an enlarging cervical carotid artery pseudoaneurysm and progressive internal carotid artery stenosis. Based on clinical judgment and imaging analysis, the best option to seal the aneurysm was a PK Papyrus 5×26 balloon-mounted covered stent. A follow-up angiogram showed no residual filling of the pseudoaneurysm, but there was some contrast stagnation just proximal to the stent, which is consistent with a residual dissection flap. We then deployed another PK Papyrus 5×26 balloon-mounted covered stent, providing some overlap at the proximal end of the stent. An angiogram following this subsequent deployment demonstrated complete reconstruction of the cICA with no residual evidence of pseudoaneurysm or dissection flap. There were no residual in-stent stenosis or vessel stenosis. The patient was discharged the day after the procedure with no complications. Conclusions: These positive outcomes support the use of a balloon-mounted covered stent as a safe and feasible modality with high technical success for endovascular management of pseudoaneurysm.

Outcomes in patients with large vessel occlusion strokes undergoing mechanical thrombectomy with concurrent COVID-19: a nationwide retrospective analysis.

BACKGROUND: Preliminary studies show that patients with large vessel occlusion (LVO) acute ischemic strokes have worse outcomes with concurrent COVID-19 infection. We investigated the outcomes for patients with LVO strokes undergoing mechanical thrombectomy (MT) with concurrent COVID-19 infection. METHODS: The National Inpatient Database (NIS) was used for our analysis. Patients in the year 2020 with an ICD-10 diagnosis code for acute ischemic stroke and procedural code for MT were included with and without COVID-19. Odds ratios (OR) were calculated using a logistic regression model with age, sex, stroke location, Elixhauser comorbidity score, and other patient variables deemed clinically relevant as covariates. RESULTS: Patients in the COVID-19 group were younger (64.3±14.4 vs 69.4±14.5 years, P<0.001), had a higher rate of inpatient mortality (22.4% vs 10.1%, P<0.001), and a longer length of stay (10 vs 6 days, P<0.001). Patients with COVID-19 had higher odds of death (OR 2.78, 95% CI 2.11 to 3.65) and lower odds of a routine discharge (OR 0.65, 95% CI 0.48 to 0.89). There was no difference in the odds of subsequent stroke and cerebral hemorrhage, but patients with COVID-19 had statistically significantly higher odds of respiratory failure, pulmonary embolism, deep vein thrombosis, myocardial infarction, acute kidney injury, and sepsis. CONCLUSIONS: Patients with LVOs undergoing MT within the 2020 NIS database had worse outcomes when co-diagnosed with COVID-19, likely due to non-neurological manifestations of COVID-19.

Impact of COVID-19 pandemic on treatment and outcomes of cerebral arteriovenous malformations.

BACKGROUND: There has been a recent decrease in interventional management of cerebral arteriovenous malformations (AVMs). The objective of our study was to evaluate the changing patterns in management of AVMs in the first year of the COVID-19 pandemic. METHODS: The National Inpatient Sample (NIS) database was used. From 2016 to 2020, patients with an International Classification of Diseases, 10th revision (ICD-10) diagnosis code for a cerebral AVM were included. An intervention was defined as ICD-10 code for surgical, endovascular, or stereotactic radiosurgery treatment. Odds ratios (ORs) were calculated using a logistic regression model with covariates deemed to be clinically relevant. RESULTS: 63 610 patients with AVMs were identified between 2016 and 2020, 14 340 of which were ruptured. In 2020, patients had an OR of 0.69 for intervention of an unruptured AVM (P<0.0001) compared with 2016-19. The rate of intervention for unruptured AVMs decreased to 13.5% in 2020 from 17.6% in 2016-19 (P<0.0001). The rate of AVM rupture in 2020 increased to 23.9% from 22.2% in 2016-19 (P<0.0001). In 2020, patients with ruptured AVMs had an OR for inpatient mortality of 1.72 compared with 2016-19. Linear regression analysis from 2016 to 2020 showed an inverse relationship between intervention rate and rupture rate (slope -0.499, R2=0.88, P=0.019). CONCLUSION: In 2020, the rate of intervention for unruptured cerebral AVMs decreased compared with past years, with an associated increase in the rate of rupture. Patients with ruptured AVMs also had a higher odds of mortality.

Perioperative Outcomes in Transcarotid Artery Revascularization Versus Carotid Endarterectomy or Stenting Nationwide.

BACKGROUND AND OBJECTIVES: Transcarotid artery revascularization (TCAR) is a newer treatment for carotid stenosis where the carotid artery is accessed directly in the neck for stenting. It is less invasive than carotid endarterectomy (CEA) and has less embolic potential than carotid artery stenting (CAS), but population-level utilization of TCAR and outcomes are currently unknown. Our study compares outcomes of TCAR with those of CEA and CAS. METHODS: The National Inpatient Database was used for years 2015 to 2019. A multivariate logistic regression model was used to compare CEA, CAS, and TCAR outcomes with age, sex, race, hospital teaching status, symptomatic carotid disease status, side of procedure, intraoperative monitoring, and the weighted Elixhauser comorbidity score as covariates. RESULTS: TCAR comprised 0.69% of these procedures in 2016, rising to 1.35% in 2019. The inpatient rates of death, stroke, and myocardial infarction for TCAR were 0.63% (95% confidence interval: 0.36%, 1.06%), 0.42% (0.21%, 0.80%), and 1.46% (1.04%, 2.05%), respectively. Compared with CEA, TCAR had statistically insignificant difference odds of death, odds ratio (95% CI) for stroke was 0.47 (0.25, 0.87), and for myocardial infarction, it was 0.66 (0.37, 0.94). Compared with CAS, for TCAR, the odds ratio for death was 0.41 (0.24, 0.71), and for stroke, it was 0.48 (0.26, 0.91). CONCLUSION: TCAR is underutilized relative to other revascularization techniques yet has favorable outcomes compared with CEA and CAS. TCAR may be preferred to CAS in patients not surgical candidates for CEA and has a less invasive possibility for those eligible for CEA.

Concurrent bacterial endocarditis is associated with worse inpatient outcomes for large vessel occlusions.

BACKGROUND: Neurological complications of bacterial endocarditis (BE) are common, including acute ischemic stroke (AIS). Although mechanical thrombectomy (MT) is effective for large vessel occlusion (LVO) stroke, data are limited on MT for LVOs in patients with endocarditis. We assess outcomes in patients treated with thrombectomy for LVOs with concurrent BE. METHODS: The National Inpatient Sample (NIS) was used. The NIS was queried from October 2015-2019 for patients receiving MT for LVO of the middle cerebral artery. Odds ratios (OR) were calculated using a multivariate logistic regression model. RESULTS: A total of 635 AIS with BE patients and 57 420 AIS only patients were identified undergoing MT. AIS with BE patients had a death rate of 26.8% versus 10.2% in the stroke alone cohort, and were also less likely to have a routine discharge (10.2% vs 20.9%, both P<0.0001). AIS with BE patients had higher odds of death (OR 3.94) and lower odds of routine discharge (OR 0.23). AIS with BE patients also had higher rates of post-treatment cerebral hemorrhage, 39.4% vs 23.7%, with an OR of 2.20 (P<0.0001 for both analyses). These patients also had higher odds of other complications, including hydrocephalus, respiratory failure, acute kidney injury, and sepsis. CONCLUSION: While MT can be used to treat endocarditis patients with LVOs, these patients have worse outcomes. Additional investigations should be undertaken to better understand their clinical course, and further develop treatments for endocarditis patients with stroke.

Thrombosed orbital varix of the inferior ophthalmic vein: A rare cause of acute unilateral proptosis.

Background: Orbital varices are rare, accounting for only 0-1.3% of orbital masses. They can be found incidentally or cause mild to serious sequelae, including hemorrhage and optic nerve compression. Case Description: We report a case of a 74-year-old male with progressively painful unilateral proptosis. Imaging revealed the presence of an orbital mass compatible with a thrombosed orbital varix of the inferior ophthalmic vein in the left inferior intraconal space. The patient was medically managed. On a follow-up outpatient clinic visit, he demonstrated remarkable clinical recovery and denied experiencing any symptoms. Follow-up computed tomography scan showed a stable mass with decreased proptosis in the left orbit consistent with the previously diagnosed orbital varix. One-year follow-up orbital magnetic resonance imaging without contrast showed slight increase in the intraconal mass. Conclusion: An orbital varix may present with mild to severe symptoms and management, depending on case severity, ranges from medical treatment to escalated surgical innervation. Our case is one of few progressive unilateral proptosis caused by a thrombosed varix of the inferior ophthalmic vein described in the literature. We encourage further investigation into the causes and epidemiology of orbital varices.

Firearm legislation: The association between neighboring states and crude death rates.

BACKGROUND: Few studies have examined the impact of interstate differences in firearm laws on state-level firearm mortality. We aim to study the association between neighboring states' firearm legislation and firearm-related crude death rate (CDR). METHODS: The CDC Web-based Injury Statistics Query and Reporting System was queried for adult all-intent (accidental, suicide, and homicide) firearm-related CDR among the 50 states from 2012 to 2020. States were divided into five cohorts based on the Giffords Law Center Annual Gun Law Scorecard, and two groups were constructed: Strict (A, B, C) and Lenient (D, F). We examined the effect of (1) a single incongruent neighbor, defined as "Different" if the state is bordered by ≥1 state with a grade score difference >1, and (2) the average grade of all neighboring states, defined as "Different" if the average of all neighboring states resulted in a grade score difference >1. RESULTS: Strict states with similar average neighbors had significantly lower CDR compared with Strict states with different average neighbors (2.98 [1.91-5.06] vs. 3.87 [2.37-5.94], p = 0.02), while Lenient states with similar average neighbors had significantly higher CDR compared with Lenient states with different average neighbors (6.02 [4.56-8.11] vs. 4.7 [3.95-5.35], p = 0.002). Lenient states surrounded by all similar Lenient states had the highest CDR, which was significantly higher than Lenient states with ≥1 different neighbor (6.52 [5.09-8.96] vs. 5.19 [3.85-6.61], p < 0.001). However, Strict states with ≥1 different neighbor did not have higher CDR compared with Strict states surrounded by all similar Strict states (3.39 [2.17-5.35] vs. 3.14 [1.91-5.38], p = 0.5). CONCLUSION: We report a lopsided neighboring effect whereby Lenient states may benefit from at least one Strict neighbor, while Strict states may be adversely affected only when surrounded by mostly Lenient neighbors. These findings may assist policymakers regarding the efficacy of their own state's legislation in the context of incongruent neighboring states. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Transradial Access Failures During Neuroangiography for Patients With Moyamoya.

BACKGROUND: Despite studies continuing to demonstrate the utility of transradial access (TRA) in neuroangiography, minimal data exist regarding predictors of TRA failure. Furthermore, although many patients with moyamoya disease/syndrome will require life-long angiographic evaluation, even less has been reported on the usage of TRA in this population. OBJECTIVE: To perform a matched analysis at our high-volume moyamoya center to determine predictors of TRA failure in these patients. METHODS: A total of 636 patients undergoing TRA for neuroangiography were identified from 2018 to 2020. Demographic and angiographic characteristics including radial artery spasm (RAS), radial anomalies, and access site conversion were compared between patients with moyamoya and the rest of the cohort. A 4:1 matched analysis, based on age and sex, was also performed to eliminate confounding variables. RESULTS: Patients with moyamoya were younger (40 vs 57 years, P < .0001), had smaller radial diameters (1.9 vs 2.6 mm, P < .0001), more commonly had a high brachial bifurcation (25.9% vs 8.5%, P = .008), more frequently experienced clinically significant RAS (40% vs 8.4%, P < .0001), and more often required access site conversion (26.7% vs 7.8%, P = .002). Increasing age was associated with less TRA failures in patients with moyamoya (odds ratio = 0.918) but more failures in the rest of the cohort (odds ratio = 1.034). In the matched analysis, patients with moyamoya continued to experience more radial anomalies, RAS, and access site conversions. CONCLUSION: Patients with moyamoya, when controlling for age and sex, have higher rates of TRA failure during neuroangiography. Increasing age in Moyamoya is inversely correlated with TRA failures suggesting that younger patients with moyamoya are at higher risk of extracranial arteriopathy.

Imaging High-Risk Atherothrombosis Using a Novel Fibrin-Binding Positron Emission Tomography Probe.

BACKGROUND AND PURPOSE: High-risk atherosclerosis is an underlying cause of cardiovascular events, yet identifying the specific patient population at immediate risk is still challenging. Here, we used a rabbit model of atherosclerotic plaque rupture and human carotid endarterectomy specimens to describe the potential of molecular fibrin imaging as a tool to identify thrombotic plaques. METHODS: Atherosclerotic plaques in rabbits were induced using a high-cholesterol diet and aortic balloon injury (N=13). Pharmacological triggering was used in a group of rabbits (n=9) to induce plaque disruption. Animals were grouped into thrombotic and nonthrombotic plaque groups based on gross pathology (gold standard). All animals were injected with a novel fibrin-specific probe 68Ga-CM246 followed by positron emission tomography (PET)/magnetic resonance imaging 90 minutes later. 68Ga-CM246 was quantified on the PET images using tissue-to-background (back muscle) ratios and standardized uptake value. RESULTS: Both tissue-to-background (back muscle) ratios and standardized uptake value were significantly higher in the thrombotic versus nonthrombotic group (P<0.05). Ex vivo PET and autoradiography of the abdominal aorta correlated positively with in vivo PET measurements. Plaque disruption identified by 68Ga-CM246 PET agreed with gross pathology assessment (85%). In ex vivo surgical specimens obtained from patients undergoing elective carotid endarterectomy (N=12), 68Ga-CM246 showed significantly higher binding to carotid plaques compared to a D-cysteine nonbinding control probe. CONCLUSIONS: We demonstrated that molecular fibrin PET imaging using 68Ga-CM246 could be a useful tool to diagnose experimental and clinical atherothrombosis. Based on our initial results using human carotid plaque specimens, in vivo molecular imaging studies are warranted to test 68Ga-CM246 PET as a tool to stratify risk in atherosclerotic patients.

Positron Emission Tomography-Magnetic Resonance Imaging Pharmacokinetics, In Vivo Biodistribution, and Whole-Body Elimination of Mn-PyC3A.

OBJECTIVES: Mn-PyC3A is an experimental manganese (Mn)-based extracellular fluid magnetic resonance imaging (MRI) contrast agent that is being evaluated as a direct replacement for clinical gadolinium (Gd)-based contrast agents. The goals of this study were to use simultaneous positron emission tomography (PET)-MRI to (1) compare the whole-body pharmacokinetics, biodistribution, and elimination of Mn-PyC3A with the liver-specific contrast agent mangafodipir (Mn-DPDP), (2) determine the pharmacokinetics and fractional excretion of Mn-PyC3A in a rat model of renal impairment, and (3) compare whole-body elimination of Mn-PyC3A to gadoterate (Gd-DOTA) in a rat model of renal impairment. METHODS: Mn-PyC3A and Mn-DPDP were radiolabeled with the positron emitting isotope Mn-52 via Mn2+ exchange with 52MnCl2. Dynamic simultaneous PET-MRI was used to measure whole-body pharmacokinetics and biodistribution of Mn-52 immediately and out to 7 days after an intravenous 0.2 mmol/kg dose of [52Mn]Mn-PyC3A to normal or to 5/6 nephrectomy rats or a 0.01 mmol/kg dose of [52Mn]Mn-DPDP to normal rats. The fractional excretion and 1- and 7-day biodistribution in rats after the injection of 2.0 mmol/kg [52Mn]Mn-PyC3A (n = 11 per time point) or 2.0 mmol/kg Gd-DOTA (n = 8 per time point) were quantified by gamma counting or Gd elemental analysis, respectively. Comparisons of Mn-PyC3A pharmacokinetics and in vivo biodistribution in normal and 5/6 nephrectomy rats and comparisons of ex vivo Mn versus Gd biodistribution data in 5/6 nephrectomy were made with an unpaired t test. RESULTS: Dynamic PET-MRI data demonstrate that both [52Mn]Mn-PyC3A and [52Mn]Mn-DPDP were eliminated by mixed renal and hepatobiliary elimination but that a greater fraction of [52Mn]Mn-PyC3A was eliminated by renal filtration. Whole-body PET images show that Mn-52 from [52Mn]Mn-PyC3A was efficiently eliminated from the body, whereas Mn-52 from [52Mn]Mn-DPDP was retained throughout the body. The blood elimination half-life of [52Mn]Mn-PyC3A in normal and 5/6 nephrectomy rats was 13 ± 3.5 minutes and 23 ± 12 minutes, respectively (P = 0.083). Area under the curve between 0 and 60 minutes postinjection (AUC0-60) in the bladder of normal and 5/6 nephrectomy rats was 2600 ± 1700 %ID/cc*min and 750 ± 180 %ID/cc*min, respectively (P = 0.024), whereas AUC0-60 in the liver of normal and 5/6 nephrectomy rats was 33 ± 13 %ID/cc*min and 71 ± 16 %ID/cc*min, respectively (P = 0.011), indicating increased hepatobiliary elimination in 5/6 nephrectomy rats. The %IDs of Mn from [52Mn]Mn-PyC3A and Gd from Gd-DOTA recovered from 5/6 nephrectomy rats 1 day after injection were 2.0 ± 1.1 and 1.3 ± 0.34, respectively (P = 0.10) and 7 days after injection were 0.14 ± 0.11 and 0.41 ± 0.24, respectively (P = 0.0041). CONCLUSIONS: Mn-PyC3A has different pharmacokinetics and is more efficiently eliminated than Mn-DPDP in normal rats. Mn-PyC3A is efficiently eliminated from both normal and 5/6 nephrectomy rats, with increased fractional hepatobiliary excretion from 5/6 nephrectomy rats. Mn-PyC3A is more completely eliminated than Gd-DOTA from 5/6 nephrectomy rats after 7 days.

Tumor Contrast Enhancement and Whole-Body Elimination of the Manganese-Based Magnetic Resonance Imaging Contrast Agent Mn-PyC3A.

OBJECTIVES: The goals of this study were to compare the efficacy of the new manganese-based magnetic resonance imaging (MRI) contrast agent Mn-PyC3A to the commercial gadolinium-based agents Gd-DOTA and to Gd-EOB-DTPA to detect tumors in murine models of breast cancer and metastatic liver disease, respectively, and to quantify the fractional excretion and elimination of Mn-PyC3A in rats. METHODS: T1-weighted contrast-enhanced MRI with 0.1 mmol/kg Mn-PyC3A was compared with 0.1 mmol/kg Gd-DOTA in a breast cancer mouse model (n = 8) and to 0.025 mmol/kg Gd-EOB-DTPA in a liver metastasis mouse model (n = 6). The fractional excretion, 1-day biodistribution, and 7-day biodistribution in rats after injection of 2.0 mmol/kg [Mn]Mn-PyC3A or Gd-DOTA were quantified by Mn gamma counting or Gd elemental analysis. Imaging data were compared with a paired t test; biodistribution data were compared with an unpaired t test. RESULTS: The postinjection-preinjection increases in tumor-to-muscle contrast-to-noise ratio (ΔCNR) 3 minutes after injection of Mn-PyC3A and Gd-DOTA (mean ± standard deviation) were 17 ± 3.8 and 20 ± 4.4, respectively (P = 0.34). Liver-to-tumor ΔCNR values at 8 minutes postinjection of Mn-PyC3A and Gd-EOB-DTPA were 28 ± 9.0 and 48 ± 23, respectively (P = 0.11). Mn-PyC3A is eliminated with 85% into the urine and 15% into the feces after administration to rats. The percentage of the injected doses (%ID) of Mn and Gd recovered in tissues after 1 day were 0.32 ± 0.12 and 0.57 ± 0.12, respectively (P = 0.0030), and after 7 days were 0.058 ± 0.051 and 0.19 ± 0.052, respectively (P < 0.0001). CONCLUSIONS: Mn-PyC3A provides comparable tumor contrast enhancement to Gd-DOTA in a mouse breast cancer model and is more completely eliminated than Gd-DOTA; partial hepatobiliary elimination of Mn-PyC3A enables conspicuous delayed phase visualization of liver metastases.

Molecular Magnetic Resonance Imaging Using a Redox-Active Iron Complex.

We introduce a redox-active iron complex, Fe-PyC3A, as a biochemically responsive MRI contrast agent. Switching between Fe3+-PyC3A and Fe2+-PyC3A yields a full order of magnitude relaxivity change that is field-independent between 1.4 and 11.7 T. The oxidation of Fe2+-PyC3A to Fe3+-PyC3A by hydrogen peroxide is very rapid, and we capitalized on this behavior for the molecular imaging of acute inflammation, which is characterized by elevated levels of reactive oxygen species.  Injection of Fe2+-PyC3A generates strong, selective contrast enhancement of inflamed pancreatic tissue in a mouse model (caerulein/LPS model). No significant signal enhancement is observed in normal pancreatic tissue (saline-treated mice). Importantly, signal enhancement of the inflamed pancreas correlates strongly and significantly with ex vivo quantitation of the pro-inflammatory biomarker myeloperoxidase. This is the first example of using metal ion redox for the MR imaging of pathologic change in vivo. Redox-active Fe3+/2+ complexes represent a new design paradigm for biochemically responsive MRI contrast agents.

Manganese-Based Contrast Agents for Magnetic Resonance Imaging of Liver Tumors: Structure-Activity Relationships and Lead Candidate Evaluation.

Gd-based MRI contrast agents (GBCAs) have come under intense regulatory scrutiny due to concerns of Gd retention and delayed toxicity. Three GBCAs comprising acyclic Gd chelates, the class of GBCA most prone to Gd release, are no longer marketed in Europe. Of particular concern are the acyclic chelates that remain available for liver scans, where there is an unmet diagnostic need and no replacement technology. To address this concern, we evaluated our previously reported Mn-based MRI contrast agent, Mn-PyC3A, and nine newly synthesized derivatives as liver specific MRI contrast agents. Within this focused library the transient liver uptake and rate of blood clearance are directly correlated with log P. The complex Mn-PyC3A-3-OBn emerged as the lead candidate due to a combination of high relaxivity, rapid blood clearance, and avid hepatocellular uptake. Mn-PyC3A-3-OBn rendered liver tumors conspicuously hypo-intense in a murine model and is wholly eliminated within 24 h of injection.