Endoluminal Biopsy for Vein of Galen Malformation.

BACKGROUND AND OBJECTIVES: Vein of Galen malformation (VOGM), the result of arteriovenous shunting between choroidal and/or subependymal arteries and the embryologic prosencephalic vein, is among the most severe cerebrovascular disorders of childhood. We hypothesized that in situ analysis of the VOGM lesion using endoluminal tissue sampling (ETS) is feasible and may advance our understanding of VOGM genetics, pathogenesis, and maintenance. METHODS: We collected germline DNA (cheek swab) from patients and their families for genetic analysis. In situ VOGM "endothelial" cells (ECs), defined as CD31+ and CD45-, were obtained from coils through ETS during routine endovascular treatment. Autologous peripheral femoral ECs were also collected from the access sheath. Single-cell RNA sequencing of both VOGM and peripheral ECs was performed to demonstrate feasibility to define the transcriptional architecture. Comparison was also made with a published normative cerebrovascular transcriptome atlas. A subset of VOGM ECs was reserved for future DNA sequencing to assess for somatic and second-hit mutations. RESULTS: Our cohort contains 6 patients who underwent 10 ETS procedures from arterial and/or venous access during routine VOGM treatment (aged 12 days to ∼6 years). No periprocedural complications attributable to ETS occurred. Six unique coil types were used. ETS captured 98 ± 88 (mean ± SD; range 17-256) experimental ECs (CD31+ and CD45-). There was no discernible correlation between cell yield and coil type or route of access. Single-cell RNA sequencing demonstrated hierarchical clustering and unique cell populations within the VOGM EC compartment compared with peripheral EC controls when annotated using a publicly available cerebrovascular cell atlas. CONCLUSION: ETS may supplement investigations aimed at development of a molecular-genetic taxonomic classification scheme for VOGM. Moreover, results may eventually inform the selection of personalized pharmacologic or genetic therapies for VOGM and cerebrovascular disorders more broadly.

The tyrosine kinase inhibitor Gefitinib reduces C. elegans stress-induced sleep, but not likely via LET-23/EGFR inhibition.

The anticancer drug Gefitinib is a tyrosine kinase inhibitor with selectivity for the Epidermal Growth Factor Receptor (EGFR/ErbB1). As the C. elegans EGF receptor LET-23 shares notable structural homology over its kinase domain with human EGFR, we wished to examine whether Gefitinib treatment can interfere with LET-23-dependent processes. We show that Gefitinib disrupts C. elegans stress-induced sleep (SIS) but does not impact EGF overexpression-induced sleep nor vulva induction. These findings indicate that Gefitinib does not interfere with LET-23 signaling and impairs SIS through an off-target mechanism.

Pediatric non-galenic pial arteriovenous fistula's characteristics and outcomes: a systematic review.

INTRODUCTION: Pediatric non-galenic pial arteriovenous fistulas (pAVFs) are rare vascular malformations that are characterized by a pial arterial-venous connection without an intervening capillary bed. Outcomes and treatment strategies for pAVFs are highly individualized, owing to the rarity of the disease and lack of large-scale data guiding optimal treatment approaches. METHODS: We performed a systematic review of pediatric patients (< 18 years at diagnosis) diagnosed with a pAVF by digital subtraction angiogram (DSA). The demographics, treatment modalities, and outcomes were documented for each patient and clinical outcome data was collected. Descriptive information stratified by outcome scores were classified as follows: 1 = excellent (no deficit and full premorbid activity), 2 = good (mild deficit and full premorbid activity), 3 = fair (moderate deficit and impaired activity), 4 = poor (severe deficit and dependent on others), 5 = death. RESULTS: A total of 87 studies involving 231 patients were identified. Median age at diagnosis was 3 years (neonates to 18 years). There was slight male preponderance (55.4%), and 150 subjects (81.1%*) experienced excellent outcomes after treatment. Of the 189 patients treated using endovascular approaches, 80.3% experienced excellent outcomes and of the 15 patients surgically treated subjects 75% had an excellent outcome. The highest rate of excellent outcomes was achieved in patients treated with Onyx (95.2%) and other forms of EvOH (100%). High output heart failure and comorbid vascular lesions tended to result in worse outcomes, with only 54.2% and 68% of subjects experiencing an excellent outcome, respectively. *Outcomes were reported in only 185 patients. CONCLUSION: pAVFs are rare lesions, necessitating aggregation of patient data to inform natural history and optimal treatment strategies. This review summarizes the current literature on pAVF in children, where children presenting with heart failure as a result of high flow through the lesion were less likely to experience an excellent outcome. Prospective, large-scale studies would further characterize pediatric pAVFs and enable quantitative analysis of outcomes to inform best treatment practices.

Characteristics and outcomes of pediatric dural arteriovenous fistulas: a systematic review.

BACKGROUND: Dural arteriovenous fistulas (dAVF) are arteriovenous shunts in communication with the dural vasculature in the brain or spine. Apart from single-center series, risk factors and treatment outcomes for pediatric dAVFs are largely undescribed. METHODS: We performed a systematic literature review of pediatric (< 18 years at diagnosis) intracranial and spinal dAVF according to PRISMA guidelines. We queried PubMed, CINAHL, SCOPUS, and Embase databases without time/date restriction. Search strings included a variety of MeSH keywords relating to dural AV fistulas in combination with MeSH keywords related to pediatric cases (see Appendix). Manuscripts describing patients diagnosed with dural sinus malformations or pial AVF were excluded. RESULTS: We identified 61 studies describing 69 individual patients. Overall, dAVF were more common in males (55.1%) with a mean age of diagnosis (5.17 ± 4.42 years). Approximately 20.2% of patients presented with cardiovascular disease (CVD), and 31.9% were discovered incidentally on neuroimaging studies. Transverse-sigmoid junction was the most common location (17.3%). Ninety-three percent (64 patients) were treated, most commonly using endovascular embolization (68.1%) followed by surgery (8.7%) and radiosurgery (2.9%). Almost half (43.8%) of dAVFs were completely obliterated. Of the 64 procedures, there were 19 neurological complications (29.7%) of varying severity where 12.5% were considered transient (i.e., pseudomeningocele) and 17.2% permanent (i.e., mortality secondary to acute sinus thrombosis, etc.). CONCLUSION: There is a paucity of information on pediatric dAVFs. This systematic review summarizes the published cases of dAVFs in the pediatric population. While the rate of missing data is high, there is publication bias, and precise details regarding complications are difficult to ascertain, this review serves as a descriptive summary of pediatric dAVFs.

Endotheliitis and cytokine storm as a mechanism of clot formation in COVID-19 ischemic stroke patients: A histopathologic study of retrieved clots.

BACKGROUND: Studies during the COVID-19 pandemic have demonstrated an association between COVID-19 virus infection and the development of acute ischemic stroke, particularly large vessel occlusion (LVO). Studying the characteristics and immunohistochemistry of retrieved stroke emboli during mechanical thrombectomy for LVO may offer insights into the pathogenesis of LVO in COVID-19 patients. We examined retrieved COVID-19 emboli from the STRIP, EXCELLENT, and RESTORE registries and compared their characteristics to a control group. METHODS: We identified COVID-positive LVO patients from the STRIP, RESTORE, and EXCELLENT studies who underwent mechanical thrombectomy. These patients were matched to a control group controlling for stroke etiology based on Trial of Org 10172 in Acute Stroke Treatment criteria. All clots were stained with Martius Scarlet Blue (MSB) along with immunohistochemistry for interleukin-6 (IL-6), C-reactive protein (CRP), von Willebrand factor (vWF), CD66b, fibrinogen, and citrullinated Histone H3. Clot composition was compared between groups. RESULTS: Nineteen COVID-19-positive patients and 38 controls were included. COVID-19-positive patients had a significantly higher percentage of CRP and vWF. There was no difference in IL-6, fibrin, CD66b, or citrullinated Histone H3 between groups. Based on MSB staining, there was no statistically significant difference regarding the percentage of red blood cells, white blood cells, fibrin, and platelets. CONCLUSIONS: Our study found higher concentrations of CRP and vWF in retrieved clots of COVID-19-positive stroke patients compared to COVID-19-negative controls. These findings support the potential role of systemic inflammation as indicated by elevated CRP and endothelial injury as indicated by elevated vWF as precipitating factors in thrombus development in these patients.

Rapid Ventricular Pacing Facilitates Transarterial Embolization in Vein of Galen Malformations.

Background: Mural type vein of Galen malformation (mVOGM) is a congenital high flow arteriovenous shunt between choroidal arteries and the prosencephalic vein of Markowski leading to heart failure and hydrovenous disorder in children. Embolizing fistulous connections can be challenging and typically requires adjunctive techniques such as induced hypotension, balloon-assisted flow control, and creation of a coil basket. These maneuvers add time, complexity, and unpredictability. Rapid ventricular pacing (RVP) has been proposed as an alternative strategy with fewer drawbacks, but has not been well studied. The approach involves catheterizing the right ventricle with a pacing catheter connected to a temporary external pacemaker. Prior to embolization, RVP is initiated to lower cardiac output. Following embolization, pacing is discontinued, and the heart returns to sinus rhythm. Methods: We performed RVP in five mVOGM patients from 4/2020 through 7/2021. Accounting for multiple procedures, RVP was utilized in ten cases and twenty-six pedicles. Results: Ventricular capture was achieved in all instances and was well tolerated, without arrhythmia. Casting the arterial pedicle with liquid embolic immediately adjacent to, or traversing, the fistulous point was achieved in 9/10 cases. There were no procedural complications. In 1 case, creation of a coil basket in the venous pouch was required to achieve a stable arterial cast Conclusions: This report describes the largest case series utilizing RVP in mVOGM. The technique appears safe and well tolerated.

The effect of procedural end-tidal CO2 on infarct expansion during anterior circulation thrombectomy.

BACKGROUND: Carbon dioxide is a potent cerebral vasodilator that may influence outcomes after ischemic stroke. The objective of this study was to investigate the effect of intraprocedural mean end-tidal CO2 (ETCO2) levels on core infarct expansion and neurologic outcome following thrombectomy for anterior circulation ischemic stroke. METHODS: A retrospective review was conducted of consecutive patients from March 2020 to June 2021 who underwent mechanical thrombectomy for acute anterior circulation ischemic stroke under general anesthesia and achieved successful recanalization (Thrombolysis in Cerebral Infarction [TICI] ≥ 2b). Only patients with CT perfusion, procedural ETCO2, and postoperative MRI data were included. Segmentation software was used for multi-parametric image analysis. Normocarbia defined as mean ETCO2 of 35 mmHg was used to dichotomize subjects. Univariate and multivariate statistics were applied. RESULTS: Fifty-eight patients met criteria for analysis. Of these, 44 had TICI 3 recanalization, 9 had TICI 2c, and 5 had TICI 2b. Within this combined recanalization group, patients with mean ETCO2 > 35 had significantly higher rates of functional independence at 90 days. Although patients tended to salvage more penumbra and experience smaller final infarcts when ETCO2 exceeded 35 mmHg, this did not reach statistical significance. CONCLUSIONS: Stroke patients who underwent successful thrombectomy with general anesthesia achieved higher rates of functional independence when procedural ETCO2 exceeded 35 mmHg. Further studies to confirm this effect and investigate optimal ETCO2 parameters should be considered.

Morphological characteristics of symptomatic and asymptomatic carotid webs.

OBJECTIVE: Carotid webs (CWs) are an increasingly recognized source of recurrent stroke among young patients without conventional vascular risk factors. There have been no previous studies demonstrating that specific web morphological characteristics correlate with a higher stroke risk. The authors aim to report distinct morphological features of symptomatic and asymptomatic CWs. METHODS: The authors performed a cross-sectional study of patients with CWs detected on CT angiography (CTA) of the neck. Patients were categorized based on whether or not they presented with stroke ipsilaterally and if it was likely to be attributable to their web. The following CW morphological variables were recorded and compared based on CTA: length, thickness, angle, and the proportion of carotid bulb lumen occupied by the web (web-to-bulb ratio [WBR]). RESULTS: A total of 86 CWs were identified, 14 of which presented with stroke (16.3%). Patients presenting with stroke had webs that were significantly longer (4.18 mm vs 2.20 mm, p = 0.001) and were situated at more acute angles relative to the carotid wall (73.2° vs 94.9°, p = 0.004). Additionally, patients presenting with stroke had higher WBRs compared to the asymptomatic cohort (0.50 vs 0.36, p = 0.008). The optimal threshold associated with stroke was web length ≥ 3.1 mm (OR 15.2, 95% CI 3.73-61.8; p < 0.001), web angle ≤ 90.1° (OR 5.00, 95% CI 1.42-17.6; p = 0.012), and WBR ≥ 0.50 (OR 30.0, 95% CI 5.94-151; p < 0.001). CONCLUSIONS: Patients with CWs that occupy more than half of the diameter of the carotid bulb lumen and are situated at acute angles relative to the carotid wall are more likely to present with acute ischemic stroke. Additional studies are needed to determine the long-term outcomes of these lesions.

Aneurysm pressure measurement before and after placement of a Pipeline stent: feasibility study using a 0.014†inch pressure wire for coronary intervention.

Flow-diverting stents have provided a new endovascular capacity to reconstruct an intracranial aneurysm with its diseased parent artery. The results of first-generation flow diversion stents have been encouraging, with even large or giant treated aneurysms achieving complete angiographic occlusion at 12-month follow-up. Numerous clinical reports have described a slow progressive thrombosis pattern and gradual increase in rate of complete aneurysm obliteration over time. Despite promising early results, some complications specific to flow-diverting stents have been encountered. Chief among them is delayed aneurysm rupture. This complication did not emerge with stent-assisted coil embolization of intracranial aneurysms, and the underlying cause has not been established. However, new evidence suggests that persistent, or even increased, aneurysm pressure after stent placement may play a role in some delayed ruptures. We sought to evaluate this phenomenon by measuring intrasaccular pressure before and after stent placement using two different 0.014 inch coronary pressure measurement wires. Two patients with giant internal carotid artery aneurysms treated with flow-diverting stents were evaluated. Before and after stent deployment, intrasaccular aneurysm and systemic arterial pressures were recorded for 60 s and compared. In both cases, intrasaccular pressure measurement with the use of 0.014 inch pressure wire system was feasible; the pressure wires could be pushed out of the microcatheter placed in the aneurysms without friction or unexpected microcatheter motion. Despite successful flow-diverting stent deployment and angiographic flow diversion effects with excellent wall opposition across the aneurysm necks, there was no significant difference between intrasaccular and systemic pressures.

Concurrent intracranial and spinal subdural hematoma in a teenage athlete: a case report of this rare entity.

A 15-year-old male high school football player presented with episodes of headache and complete body stiffness, especially in the arms, lower back, and thighs, immediately following a football game. This was accompanied by severe nausea and vomiting for several days. Viral meningitis was suspected by the primary clinician, and treatment with corticosteroids was initiated. Over the next several weeks, there was gradual symptom improvement and the patient returned to his baseline clinical status. The patient experienced a severe recurrence of the previous myriad of symptoms following a subsequent football game, without an obvious isolated traumatic episode. In addition, he experienced a new left sided headache, fatigue, and difficulty ambulating. He was admitted and an extensive workup was performed. CT and MRI of the head revealed concurrent intracranial and spinal subdural hematomas (SDH). Clinical workup did not reveal any evidence of coagulopathy or predisposing vascular lesions. Spinal SDH is an uncommon condition whose concurrence with intracranial SDH is an even greater clinical rarity. We suggest that our case represents an acute on chronic intracranial SDH with rebleeding, membrane rupture, and symptomatic redistribution of hematoma to the spinal subdural space.

Radiation dose from medical imaging: a primer for emergency physicians.

INTRODUCTION: Medical imaging now accounts for most of the US population's exposure to ionizing radiation. A substantial proportion of this medical imaging is ordered in the emergency setting. We aim to provide a general overview of radiation dose from medical imaging with a focus on computed tomography, as well as a literature review of recent efforts to decrease unnecessary radiation exposure to patients in the emergency department setting. METHODS: We conducted a literature review through calendar year 2010 for all published articles pertaining to the emergency department and radiation exposure. RESULTS: The benefits of imaging usually outweigh the risks of eventual radiation-induced cancer in most clinical scenarios encountered by emergency physicians. However, our literature review identified 3 specific clinical situations in the general adult population in which the lifetime risks of cancer may outweigh the benefits to the patient: rule out pulmonary embolism, flank pain, and recurrent abdominal pain in inflammatory bowel disease. For these specific clinical scenarios, a physician-patient discussion about such risks and benefits may be warranted. CONCLUSION: Emergency physicians, now at the front line of patients' exposure to ionizing radiation, should have a general understanding of the magnitude of radiation dose from advanced medical imaging procedures and their associated risks. Future areas of research should include the development of protocols and guidelines that limit unnecessary patient radiation exposure.