Microsurgical clipping versus newer endovascular techniques in treatment of unruptured anterior communicating artery-complex aneurysms: a meta-analysis and systematic review.

The aim of this study is to compare occlusion rate, complication rate, and clinical outcome of microsurgical clipping (MC) and advanced endovascular techniques (EVT) in unruptured anterior communicating artery-complex aneurysms (ACoCAs). We reviewed the scientific literature reporting occlusion rate, time of occlusion assessment, and clinical outcome of MC and EVT in patients with unruptured ACoCAs, from January 2009 to December 2019. We included in our analysis 25 studies and 872 patients with unruptured ACoCAs (434 treated with endovascular techniques and 438 with MC). Ninety-three (10.7%), 320 (36.7%), 21 (2.4%), and 438 (50.2%) were treated with flow diverter (FD), stent-assisted coiling (SAC), endosaccular devices (ES), and microsurgical clipping (MC) respectively. FD, SAC, ES, and MC subgroups presented minor complications in 11.8%, 3.8%, 14.3%, and 7.1% of cases (p=.016), and major complications in 3.2%, 4.4%, 0%, and 7.1% (p=.136) of patients. A total occlusion rate post-treatment has been achieved in 4.3%, 87.1%, 47.6%, and 98.2% of cases (p=.000), while at 12 months' follow-up in 50%, 66%, 83.3%, and 80% of patients (p=.001). FD, SAC, ES, and MC subgroups had a good clinical outcome at 12 months in 93.5%, 90.5%, 100%, and 67.8% of cases. MC is associated with higher post-treatment total occlusion rate, but higher complication and lower good clinical outcome rates. EVT are promising in treating unruptured anterior cerebral artery aneurysms with high margin of safety and good clinical outcome, despite the lower total occlusion rate.

Phase-retrieval method for measuring small contact angles of pentane on water.

Pentane drops on a water surface are predicted to have contact angles of the order of 1 degree or less in the phase of frustrated complete wetting. We have developed an optical method of measuring such small contact angles, applicable to cases where the refractive indices of the substrate and adsorbate are very similar and the fluid dynamics do not allow delay between image acquisitions, by using phase retrieval to map the surface profile of the drops. It is empirically shown that, with our method, a difference of nanometer order can be achieved for the phase-retrieved dimensions relative to their expected value. Results agree with numerical predictions by Weiss and Widom [Physica A292, 137 (2001)PHYADX0378-437110.1016/S0378-4371(00)00619-1].

Use of Pipeline Embolization Devices for treatment of a direct carotid-cavernous fistula.

BACKGROUND: The use of minimally porous endoluminal devices (MPEDs) such as the Pipeline Embolization Device (PED) has been described for the treatment of brain aneurysms. The benefit of using MPEDs to assist embolization of a direct high-flow carotid cavernous fistula resulting from a ruptured cavernous carotid artery aneurysm is not well documented. METHODS: We describe our experience with deploying a tailored multidevice PED construct across the cavernous internal carotid artery (ICA) wall defect in combination with transarterial coil embolization using the "jailed microcatheter" technique. RESULTS: A 59-year-old woman presented with acute left-sided ophthalmoplegia. Diagnostic cerebral angiography demonstrated a ruptured giant cavernous carotid aneurysm with fistulous outflow via the ipsilateral left superior ophthalmic vein and into the pterygoid venous plexi bilaterally. Via the Marksman microcatheter, a total of three PEDs measuring 4.5 mm × 18 mm, 4.5 mm × 20 mm, and 4.75 mm × 16 mm were telescoped within the ICA across the aneurysm neck. Coiling of the aneurysm fundus and cavernous sinus via the "jailed" Rapidtransit microcatheter was subsequently achieved. A 2-year follow-up digital subtraction angiography (DSA) demonstrated stable obliteration of the aneurysm and the fistula, coincident with complete resolution of the patient's symptoms. CONCLUSIONS: Based on our long-term clinical and angiographic results, we advocate that the presented method be a valid treatment option for selected cases.

Outcomes of Preoperative Transophthalmic Artery Embolization of Meningiomas: A Systematic Review with a Focus on Embolization Agent.

BACKGROUND: Transophthalmic artery embolization of intracranial meningiomas is thought to be associated with a high complication risk. PURPOSE: With advances in endovascular techniques, we systematically reviewed the current literature to improve our understanding of the safety and efficacy of transophthalmic artery embolization of intracranial meningiomas. DATA SOURCES: We performed a systematic search using PubMed from inception until August 3, 2022. STUDY SELECTION: Twelve studies with 28 patients with intracranial meningiomas embolized through the transophthalmic artery were included. DATA ANALYSIS: Baseline and technical characteristics and clinical and safety outcomes were collected. No statistical analysis was conducted. DATA SYNTHESIS: The average age of 27 patients was 49.5 (SD, 13) years. Eighteen (69%) meningiomas were located in the anterior cranial fossa, and 8 (31%), in the sphenoid ridge/wing. Polyvinyl alcohol particles were most commonly (n = 8, 31%) used to preoperatively embolize meningiomas, followed by n-BCA in 6 (23%), Onyx in 6 (23%), Gelfoam in 5 (19%), and coils in 1 patient (4%). Complete embolization of the target meningioma feeders was reported in 8 (47%) of 17 patients; partial embolization, in 6 (32%); and suboptimal embolization, in 3 (18%). The endovascular complication rate was 16% (4 of 25), which included visual impairment in 3 (12%) patients. LIMITATIONS: Selection and publication biases were limitations. CONCLUSIONS: Transophthalmic artery embolization of intracranial meningiomas is feasible but is associated with a non-negligible complication rate.

Tumor Embolization through Meningohypophyseal and Inferolateral Trunks is Safe and Effective.

BACKGROUND AND PURPOSE: Skull base tumors are commonly supplied by dural branches of the meningohypophyseal and inferolateral trunks. Embolization through these arteries is often avoided due to technical challenges and inherent risks; however, successful embolization can be a valuable surgical adjunct. We aimed to review the success and complications in our series of tumor embolizations through the meningohypophyseal and inferolateral trunks. MATERIALS AND METHODS: We performed a retrospective review of patients with tumor treated with preoperative embolization at our institution between 2010 and 2020. We reviewed the following data: patients' demographics, tumor characteristics, endovascular embolization variables, and surgical results including estimated blood loss, the need for transfusion, and operative time. RESULTS: Among 155 tumor embolization cases, we identified 14 patients in whom tumor embolization was performed using the meningohypophyseal (n = 13) or inferolateral (n = 4) trunk. In this group of patients, on average, 79% of tumors were embolized. No mortality or morbidity from the embolization procedure was observed in this subgroup of patients. The average estimated blood loss in the operation was 395 mL (range, 200-750 mL). None of the patients required a transfusion, and the average operative time was 7.3 hours. CONCLUSIONS: Some skull base tumors necessitate embolization through ICA branches such as the meningohypophyseal and inferolateral trunks. Our series demonstrates that an effective and safe embolization may be performed through these routes.

Pronounced focal and diffuse brain damage predicts short-term disease evolution in patients with clinically isolated syndrome suggestive of multiple sclerosis.

BACKGROUND: In clinically isolated syndrome (CIS), the role of quantitative magnetic resonance imaging (MRI) in detecting prognostic markers is still debated. OBJECTIVE: To evaluate measures of diffuse brain damage (such as brain atrophy and the ratio of N-acetylaspartate to creatine (NAA/Cr)) in patients with CIS, in addition to focal lesions, as predictors of 1-year disease evolution. METHODS: 49 patients with CIS underwent MRI scans to quantify T2-lesions (T2-L) and gadolinium-enhanced lesion (GEL) number at baseline and after 1 year. Along with 25 healthy volunteers, they also underwent combined MRI/magnetic resonance spectroscopy examination to measure normalized brain volumes (NBVs) and NAA/Cr. Occurrence of relapses and new T2-L was recorded over 1 year to assess disease evolution. RESULTS: Occurrence of relapses and/or new T2-L over 1 year divided patients with CIS into 'active' and 'stable' groups. Active patients had lower baseline NAA/Cr and NBV. Baseline T2-L number, GEL, NAA/Cr and NBV predicted subsequent disease activity. Multivariable logistic regression models showed that both 'focal damage' (based on T2-L number and GEL) and 'diffuse damage' (based on NBV and NAA/Cr) models predicted disease activity at 1 year with great sensitivity, specificity and accuracy. This was best when the four MRI measures were combined (80% sensitivity, 89% specificity, 83% accuracy). CONCLUSIONS: Quantitative MRI measures of diffuse tissue damage such as brain atrophy and NAA/Cr, in addition to measures of focal demyelinating lesions, may predict short-term disease evolution in patients with CIS, particularly when used in combination. If confirmed in larger studies, these findings may have important clinical and therapeutic implications.

Immunostimulatory DNA sequences function as T helper-1-promoting adjuvants.

An adjuvant role for certain short bacterial immunostimulatory DNA sequences (ISSs) has recently been proposed on the basis of their ability to stimulate T helper-1 (Th1) responses in gene-vaccinated animals. We report here that noncoding, ISS-enriched plasmid DNAs or ISS oligonucleotides (ISS-ODNs) potently stimulate immune responses to coadministered antigens. The ISS-DNAs suppress IgE synthesis, but promote IgG and interferon-gamma (IFN-gamma) production. They furthermore initiate the production of IFN-gamma, IFN-alpha, IFN-beta, and interleukins 12 and 18, all of which foster Th1 responses and enhance cell-mediated immunity. Consideration should be given to adding noncoding DNA adjuvants to inactivated or subunit viral vaccines that, by themselves, provide only partial protection from infection.

Arterial and Venous 3D Fusion AV-3D-DSA: A Novel Approach to Cerebrovascular Neuroimaging.

DSA is the standard imaging technique for evaluation of cerebrovascular conditions. However, One drawback is its limitation in depicting a single angiographic phase at a time. We describe a new 3D-DSA algorithm, which we call arterial and venous-3D-DSA, which allows the concurrent yet distinct display of the arterial and venous structures, which may be useful for different clinical and educational purposes.

Diffusion-weighted MRI in patients with non-diagnostic CT in the post-acute phase of cerebral ischemia.

BACKGROUND: Unenhanced computed tomography (CT) is the imaging technique used in acute stroke. In some cases it is unable to detect damage even 24-48 h after symptom onset. The aim of our work was to evaluate the diagnostic value of diffusion-weighted imaging (DWI) in the post-acute phase of cerebral ischemia in patients in whom CT did not yield a definitive diagnosis. METHODS: We retrospectively evaluated DWI findings in 214 patients, out of a series of 1,680 patients admitted to our hospital following the acute onset of focal neurological symptoms, in whom non-contrast CT, performed within 30 h of symptom onset, was normal (123), incongruous, i.e. a marked hypodensity indicative of an old infarct or a slight hypodensity not consistent with the clinical findings (66), or leukoaraiotic, i.e. diffuse chronic hypodensities in the periventricular white matter (25). RESULTS: DWI showed signs of recent brain ischemia in 125/214 (58%) patients: 64/123 (52%) with a normal CT, 41/66 (62%) with an incongruous CT, and 20/25 (80%) with leukoaraiosis (p=0.027). Multiple lesions were detected in 16/125 (16%) patients, while single lesions were

Brain Imaging Use and Findings in COVID-19: A Single Academic Center Experience in the Epicenter of Disease in the United States.

Coronavirus disease 2019 (COVID-19) is a serious public health crisis and can have neurologic manifestations. This is a retrospective observational case series performed March 1-31, 2020, at New York University Langone Medical Center campuses. Clinical and imaging data were extracted, reviewed, and analyzed. Two hundred forty-two patients with COVID-19 underwent CT or MRI of the brain within 2 weeks after the positive result of viral testing (mean age, 68.7 ± 16.5 years; 150 men/92 women [62.0%/38.0%]). The 3 most common indications for imaging were altered mental status (42.1%), syncope/fall (32.6%), and focal neurologic deficit (12.4%). The most common imaging findings were nonspecific white matter microangiopathy (134/55.4%), chronic infarct (47/19.4%), acute or subacute ischemic infarct (13/5.4%), and acute hemorrhage (11/4.5%). No patients imaged for altered mental status demonstrated acute ischemic infarct or acute hemorrhage. White matter microangiopathy was associated with higher 2-week mortality (P < .001). Our data suggest that in the absence of a focal neurologic deficit, brain imaging in patients with early COVID-19 with altered mental status may not be revealing.

Dural Venous Channels: Hidden in Plain Sight-Reassessment of an Under-Recognized Entity.

BACKGROUND AND PURPOSE: Tentorial sinus venous channels within the tentorium cerebelli connecting various cerebellar and supratentorial veins, as well as the basal vein, to adjacent venous sinuses are a well-recognized entity. Also well-known are "dural lakes" at the vertex. However, the presence of similar channels in the supratentorial dura, serving as recipients of the Labbe, superficial temporal, and lateral and medial parieto-occipital veins, among others, appears to be underappreciated. Also under-recognized is the possible role of these channels in the angioarchitecture of certain high-grade dural fistulas. MATERIALS AND METHODS: A retrospective review of 100 consecutive angiographic studies was performed following identification of index cases to gather data on the angiographic and cross-sectional appearance, location, length, and other features. A review of 100 consecutive dural fistulas was also performed to identify those not directly involving a venous sinus. RESULTS: Supratentorial dural venous channels were found in 26% of angiograms. They have the same appearance as those in the tentorium cerebelli, a flattened, ovalized morphology owing to their course between 2 layers of the dura, in contradistinction to a rounded cross-section of cortical and bridging veins. They are best appreciated on angiography and volumetric postcontrast T1-weighted images. Ten dural fistulas not directly involving a venous sinus were identified, 6 tentorium cerebelli and 4 supratentorial. CONCLUSIONS: Supratentorial dural venous channels are an under-recognized entity. They may play a role in the angioarchitecture of dural arteriovenous fistulas that appear to drain directly into a cortical vein. We propose "dural venous channel" as a unifying name for these structures.

Surprise Diagnosis of COVID-19 following Neuroimaging Evaluation for Unrelated Reasons during the Pandemic in Hot Spots.

During the height of the recent outbreak of coronavirus 19 (COVID-19) in New York City, almost all the hospital emergency departments were inundated with patients with COVID-19, who presented with typical fever, cough, and dyspnea. A small number of patients also presented with either unrelated conditions (such as trauma) or other emergencies, and some of which are now known to be associated with COVID-19 (such as stroke). We report such a scenario in 17 patients who were admitted and investigated with CT spine imaging and CT angiography for nonpulmonary reasons (trauma = 13, stroke = 4). Their initial work-up did not suggest COVID-19 as a diagnosis but showed unsuspected/incidental lung findings, which led to further investigations and a diagnosis of COVID-19.

Cerebral Venous Thrombosis Associated with COVID-19.

Despite the severity of coronavirus disease 2019 (COVID-19) being more frequently related to acute respiratory distress syndrome and acute cardiac and renal injuries, thromboembolic events have been increasingly reported. We report a unique series of young patients with COVID-19 presenting with cerebral venous system thrombosis. Three patients younger than 41 years of age with confirmed Severe Acute Respiratory Syndrome coronavirus 2 (SARS-Cov-2) infection had neurologic findings related to cerebral venous thrombosis. They were admitted during the short period of 10 days between March and April 2020 and were managed in an academic institution in a large city. One patient had thrombosis in both the superficial and deep systems; another had involvement of the straight sinus, vein of Galen, and internal cerebral veins; and a third patient had thrombosis of the deep medullary veins. Two patients presented with hemorrhagic venous infarcts. The median time from COVID-19 symptoms to a thrombotic event was 7 days (range, 2-7 days). One patient was diagnosed with new-onset diabetic ketoacidosis, and another one used oral contraceptive pills. Two patients were managed with both hydroxychloroquine and azithromycin; one was treated with lopinavir-ritonavir. All patients had a fatal outcome. Severe and potentially fatal deep cerebral thrombosis may complicate the initial clinical presentation of COVID-19. We urge awareness of this atypical manifestation.

Immunostimulatory DNA sequences necessary for effective intradermal gene immunization.

Vaccination with naked DNA elicits cellular and humoral immune responses that have a T helper cell type 1 bias. However, plasmid vectors expressing large amounts of gene product do not necessarily induce immune responses to the encoded antigens. Instead, the immunogenicity of plasmid DNA (pDNA) requires short immunostimulatory DNA sequences (ISS) that contain a CpG dinucleotide in a particular base context. Human monocytes transfected with pDNA or double-stranded oligonucleotides containing the ISS, but not those transfected with ISS-deficient pDNA or oligonucleotides, transcribed large amounts of interferon-alpha, interferon-beta, and interleukin-12. Although ISS are necessary for gene vaccination, they down-regulate gene expression and thus may interfere with gene replacement therapy by inducing proinflammatory cytokines.

Toward a Better Understanding of Dural Arteriovenous Fistula Angioarchitecture: Superselective Transvenous Embolization of a Sigmoid Common Arterial Collector.

BACKGROUND AND PURPOSE: Our aim was to propose a conceptually new angioarchitectural model of some dural arteriovenous fistulas based on subset analysis of transverse and sigmoid type lesions. The "common collector" notion argues for convergence of multiple smaller caliber arterial vessels on a common arterial collector vessel within the sinus wall. Communication of this single collector (or constellation of terminal collectors) with the sinus proper defines the site of arteriovenous fistula, which can be closed by highly targeted embolization, preserving the sinus and avoiding unnecessary permeation of indirect arterial feeders. MATERIALS AND METHODS: One hundred consecutive dural arteriovenous shunts were examined. Thirty-six transverse/sigmoid fistulas were identified within this group and analyzed for the presence of a common arterial collector as well as other parameters, including demographics, grade, treatment approach, and outcome. RESULTS: A common collector was identified in nearly all Cognard type I lesions (15 fistulas with 14 single collector vessels seen) and progressively less frequently in higher grade fistulas. Identification of the common collector requires careful angiographic analysis, including supraselective and intraprocedural angiographies during treatment, and final embolic material morphology. CONCLUSIONS: Detailed evaluation of imaging studies allows frequent identification of a vascular channel in the sinus wall, which we argue reflects a compound, common arterial channel (rather than a venous collector) with 1 or several discrete fistulous points between this vessel and the sinus proper. Targeted closure of this channel is often feasible, with sinus preservation and avoidance of embolic material penetration into arteries remote from fistula site.

Toward Better Understanding of Flow Diversion in Bifurcation Aneurysms.

BACKGROUND AND PURPOSE: Flow diversion is being increasingly used to treat bifurcation aneurysms. Empiric approaches have generally led to encouraging results, and a growing body of animal and ex vivo literature addresses the fate of target aneurysms and covered branches. Our prior investigations highlighted the dynamic nature of metal coverage provided by the Pipeline Embolization Device and suggested strategies for creating optimal single and multidevice constructs. We now address the geometric and hemodynamic aspects of jailing branch vessels and neighboring target aneurysms. MATERIALS AND METHODS: Fundamental electric and fluid dynamics principles were applied to generate equations describing the relationships between changes in flow and the degree of vessel coverage in settings of variable collateral support to the jailed territory. Given the high complexity of baseline and posttreatment fluid dynamics, in vivo, we studied a simplified hypothetic system with minimum assumptions to generate the most conservative outcomes. RESULTS: In the acute setting, Pipeline Embolization Devices modify flow in covered branches, principally dependent on the amount of coverage, the efficiency of collateral support, and intrinsic resistance of the covered parenchymal territory. Up to 30% metal coverage of any branch territory is very likely to be well-tolerated regardless of device or artery size or the availability of immediate collateral support, provided, however, that no acute thrombus forms to further reduce jailed territory perfusion. CONCLUSIONS: Basic hemodynamic principles support the safety of branch coverage during aneurysm treatment with the Pipeline Embolization Device. Rational strategies to build bifurcation constructs are feasible.

Transposition of the nematode Caenorhabditis elegans Tc3 element in the zebrafish Danio rerio.

BACKGROUND: Transposable elements of the Tc1/mariner family are found in many species of the animal kingdom. It has been suggested that the widespread distribution of this transposon family resulted from horizontal transmission among different species. RESULTS: To test the ability of Tc1/mariner to cross species barriers, as well as to develop molecular genetic tools for studying zebrafish development, we determined the ability of the Tc3 transposon, a member of the Tc1/mariner family, to function in zebrafish. Tc3 transposons carrying sequences encoding the green fluorescent protein (GFP) were able to integrate in the fish genome by transposition. Integrated transposons expressed the GFP marker after germline transmission, and were capable of being mobilized upon introduction of transposase protein in trans. CONCLUSIONS: Our findings support models of horizontal transmission of Tc1/mariner elements between species. The work also establishes the basis for a novel method of transposon-mediated genetic transformation and for transposon-mediated genetic screens in zebrafish and other organisms.

Developmental control by the Drosophila EGF receptor homolog DER.

The identification of receptor tyrosine kinases in Drosophila has provided an opportunity to study the requirement for these proteins during the development of a multicellular organism. Genetic analysis of the function of the Drosophila epidermal growth factor (EGF) receptor homolog (DER) has revealed an extremely diverse set of roles for this protein throughout the life cycle of the organism, for example in eye development and in the establishment of dorsoventral polarity in the oocyte. We discuss the possible basis for the pleiotropic activity of DER, and the similarities and differences in the function of the homologous proteins in other invertebrates and vertebrates.

Immunostimulatory DNA-based vaccines induce cytotoxic lymphocyte activity by a T-helper cell-independent mechanism.

Immunostimulatory DNA sequences (ISS) contain unmethylated CpG dinucleotides within a defined motif. Immunization with ISS-based vaccines has been shown to induce high antigen-specific cytotoxic lymphocyte (CTL) activity and a Th1-biased immune response. We have developed a novel ISS-based vaccine composed of ovalbumin (OVA) chemically conjugated to ISS-oligodeoxynucleotide (ODN). Protein-ISS conjugate (PIC) is more potent in priming CTL activity and Th1-biased immunity than other ISS-based vaccines. Cytotoxic lymphocyte activation by ISS-ODN-based vaccines is preserved in both CD4-/- and MHC class II-/- gene-deficient animals. Furthermore, PIC provides protection against a lethal burden of OVA-expressing tumor cells in a CD8+ cell-dependent manner. These results demonstrate that PIC acts through two unique mechanisms: T-helper-independent activation of CTL and facilitation of exogenous antigen presentation on MHC class I. This technology may have clinical applications in cancer therapy and in stimulating host defense in AIDS and chronic immunosuppression.