Use of the Woven EndoBridge Device for Sidewall Aneurysms: Systematic Review and Meta-analysis.

BACKGROUND: The Woven EndoBridge device was originally approved to treat intracranial wide-neck saccular bifurcation aneurysms. Recent studies have suggested its use for the treatment of sidewall intracranial aneurysms with variable success. PURPOSE: Our aim was to evaluate the safety and efficacy of the Woven EndoBridge device for sidewall aneurysms using a meta-analysis of the literature. DATA SOURCES: We performed a systematic review of all studies including patients treated with the Woven EndoBridge device for sidewall aneurysms from inception until May 2022 on Scopus, EMBASE, MEDLINE, the Web of Science, and the Cochrane Central Register of Controlled Trials. STUDY SELECTION: Ten studies were selected, and 285 patients with 288 sidewall aneurysms were included. DATA ANALYSIS: A random-effects meta-analysis of proportions using a generalized linear mixed model was performed as appropriate. Statistical heterogeneity across studies was assessed with I2 statistics. DATA SYNTHESIS: The adequate occlusion rate at last follow-up was 89% (95% CI, 81%-94%; I2, = 0%), the composite safety outcome was 8% (95% CI, 3%-17%; I2 = 34%), and the mortality rate was 2% (95% CI, 1%-7%; I2 = 0%). Aneurysm width (OR = 0.5; P = .03) was the only significant predictor of complete occlusion. LIMITATIONS: Given the level of evidence, our results should be interpreted cautiously until confirmation from larger prospective studies is obtained. CONCLUSIONS: The initial evidence evaluating the use of the Woven EndoBridge device for the treatment of wide-neck sidewall intracranial aneurysms has demonstrated high rates of adequate occlusion with low procedural complications. Our findings favor the consideration of the Woven EndoBridge device as an option for the treatment of sidewall aneurysms.

3D Enhancement Color Maps in the Characterization of Intracranial Atherosclerotic Plaques.

BACKGROUND AND PURPOSE: High-resolution MR imaging allows the identification of culprit symptomatic plaques after the administration of gadolinium. Current high-resolution MR imaging methods are limited by 2D multiplanar views and manual sampling of ROIs. We analyzed a new 3D method to objectively quantify gadolinium plaque enhancement. MATERIALS AND METHODS: Patients with stroke due to intracranial atherosclerotic disease underwent 7T high-resolution MR imaging. 3D segmentations of the plaque and its parent vessel were generated. Signal intensity probes were automatically extended from the lumen into the plaque and the vessel wall to generate 3D enhancement color maps. Plaque gadolinium (Gd) uptake was quantified from 3D color maps as gadolinium uptake = (µPlaque T1 + Gd -µPlaque T1/SDPlaque T1). Additional metrics of enhancement such as enhancement ratio, variance, and plaque-versus-parent vessel enhancement were also calculated. Conventional 2D measures of enhancement were collected for comparison. RESULTS: Thirty-six culprit and 44 nonculprit plaques from 36 patients were analyzed. Culprit plaques had higher gadolinium uptake than nonculprit plaques (P < .001). Gadolinium uptake was the most accurate metric for identifying culprit plaques (OR, 3.9; 95% CI 2.1-8.3). Gadolinium uptake was more sensitive (86% versus 70%) and specific (71% versus 68%) in identifying culprit plaques than conventional 2D measurements. A multivariate model, including gadolinium uptake and plaque burden, identified culprit plaques with an 83% sensitivity and 86% specificity. CONCLUSIONS: The new 3D color map method of plaque-enhancement analysis is more accurate for identifying culprit plaques than conventional 2D methods. This new method generates a new set of metrics that could potentially be used to assess disease progression.

Quantifying Intra-Arterial Verapamil Response as a Diagnostic Tool for Reversible Cerebral Vasoconstriction Syndrome.

BACKGROUND AND PURPOSE: There is mounting evidence supporting the benefit of intra-arterial administration of vasodilators in diagnosing reversible cerebral vasoconstriction syndrome. We prospectively quantified the degree of luminal diameter dilation after intra-arterial administration of verapamil and its accuracy in diagnosing reversible cerebral vasoconstriction syndrome. MATERIALS AND METHODS: Patients suspected of having intracranial arteriopathy on noninvasive imaging and referred for digital subtraction angiography were enrolled in a prospective registry. Intra-arterial verapamil was administered in vascular territories with segmental irregularities. The caliber difference (Caliberpost - Caliberpre) and the proportion of caliber change ([(Caliberpost - Caliberpre)/Caliberpre] × 100%) were used to determine the response to verapamil. The diagnosis of reversible cerebral vasoconstriction syndrome was made on the basis of clinical and imaging features at a follow-up appointment, independent of the reversibility of verapamil. Receiver operating characteristic curve analysis was performed to determine the best threshold. RESULTS: Twenty-six patients were included, and 9 (34.6%) were diagnosed with reversible cerebral vasoconstriction syndrome. A total of 213 vascular segments were assessed on diagnostic angiography. Every patient with a final diagnosis of reversible cerebral vasoconstriction syndrome responded to intra-arterial verapamil. The maximal proportion of change (P < .001), mean proportion of change (P = .002), maximal caliber difference (P = .004), and mean caliber difference (P = .001) were statistically different between patients with reversible cerebral vasoconstriction syndrome and other vasculopathies. A maximal proportion of change ≥32% showed a sensitivity of 100% and a specificity of 88.2% to detect reversible cerebral vasoconstriction syndrome (area under the curve = 0.951). The Reversible Cerebral Vasoconstriction Syndrome-2 score of ≥5 points achieved a lower area under the curve (0.908), with a sensitivity of 77.8% and a specificity of 94.1%. CONCLUSIONS: Objective measurement of the change in the arterial calibers after intra-arterial verapamil is accurate in distinguishing reversible cerebral vasoconstriction syndrome from other vasculopathies. A proportion of change ≥32% has the best diagnostic performance.

Changes on Dynamic Cerebral Autoregulation Are Associated with Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Early identification of vasospasm prior to symptom onset would allow prevention of delayed cerebral ischemia (DCI) in aneurysmal subarachnoid hemorrhage (aSAH). Dynamic cerebral autoregulation (DCA) is a noninvasive means of assessing cerebral blood flow regulation by determining independence of low-frequency temporal oscillations of systemic blood pressure (BP) and cerebral blood flow velocities (CBFV). METHODS: Eight SAH patients underwent prospectively a median of 7 DCA assessments consisting of continuous measurements of BCFV and BP. Transfer function analysis was applied to calculate average phase shift (PS) in low (0.07-0.2 Hz) frequency range for each hemisphere as continuous measure of DCA. Lower PS indicated poorer regulatory response. DCI was defined as a 2-point decrease in Glasgow Coma Score and/or infarction on CT. RESULTS: Three subjects developed symptomatic vasospasm with median time-to-DCI of 9 days. DCI was significantly associated with lower PS over the entire recording period (Wald = 4.28; p = 0.039). Additionally, there was a significant change in PS over different recording periods after adjusting for DCI (Wald = 15.66; p = 0.001); particularly, a significantly lower mean PS day 3-5 after bleed (14.22 vs 27.51; p = 0.05). CONCLUSIONS: DCA might be useful for early detection of symptomatic vasospasm. A larger cohort study of SAH patients is currently underway.

Endovascular treatment of intracranial aneurysms using the Pipeline Flex embolization device: a case series of 30 consecutive patients.

BACKGROUND: The Pipeline Flex embolization device has some peculiarities in comparison with the previous generation device. Despite recent reports of the modified delivery system, its safety is still unknown. OBJECTIVE: To illustrate the intraprocedural and periprocedural complication rate with this new device in 30 consecutive patients. MATERIAL AND METHODS: Clinical, procedural, and angiographic data, including aneurysm size and location, device or devices used, angiographic and clinical data were analyzed. RESULTS: 30 patients harboring 30 aneurysms were analyzed. 39 devices were placed properly. Multiple Pipeline embolization devices (PEDs) were used in 7 cases. In 28 devices the distal end opened fully from the beginning with a complete wall apposition. In the remaining 11 devices, distal-end opening of the devices was instant but partial, but fully opened easily after recapture. Among the 30 procedures, recapture and reposition of the Pipeline Flex was performed four times owing to proximal migration/malposition of the device during delivery. Four intraprocedural/periprocedural complications occurred, of which 2 resulted in major complications, with neurologic deficits persisting for longer than 7 days. The 30-day morbidity rate was 6.6%, with no deaths. No aneurysm rupture or parenchymal hemorrhage was seen. CONCLUSIONS: The Pipeline Flex embolization device allows more precise and controlled deployment than the first-generation device. The number of devices and the complication rate during the learning curve are lower than reported with the first-generation PED. The new delivery system and the resheathing maneuvers do not seem to increase the intraprocedural complication rate in comparison with the first-generation PED.

Endocannabinoids drive the acquisition of an alternative phenotype in microglia.

The ability of microglia to acquire diverse states of activation, or phenotypes, reflects different features that are determinant for their contribution to homeostasis in the adult CNS, and their activity in neuroinflammation, repair or immunomodulation. Despite the widely reported immunomodulatory effects of cannabinoids in both the peripheral immune system and the CNS, less is known about how the endocannabinoid signaling system (eCBSS) influence the microglial phenotype. The general aim of the present study was to investigate the role of endocannabinoids in microglia polarization by using microglia cell cultures. We show that alternative microglia (M2a) and acquired deactivated microglia (M2c) exhibit changes in the eCB machinery that favor the selective synthesis of 2-AG and AEA, respectively. Once released, these eCBs might be able to act through CB1 and/or CB2 receptors in order to influence the acquisition of an M2 phenotype. We present three lines of evidence that the eCBSS is critical for the acquisition of the M2 phenotype: (i) M2 polarization occurs on exposure to the two main endocannabinoids 2-AG and AEA in microglia cultures; (ii) cannabinoid receptor antagonists block M2 polarization; and (iii) M2 polarization is dampened in microglia from CB2 receptor knockout mice. Taken together, these results indicate the interest of eCBSS for the regulation of microglial activation in normal and pathological conditions.

Preliminary experience with the Pipeline Flex Embolization Device: technical note.

BACKGROUND: Clinical experience with the Pipeline Embolization Device (PED) has been widely described in the literature since it obtained its European CE and FDA approvals in 2008 and 2011, respectively. The new generation of PED, the Pipeline Flex Embolization Device, received the CE mark of approval in March 2014. While the implant composition has not changed, its new delivery system has some differences. One of the main changes from the previous generation is a new delivery system that makes the device resheathable until deployed over 90% of its length. We present our preliminary experience using this device. METHODS: Between May and June 2014, six patients with six aneurysms were treated with the Pipeline Flex device. RESULTS: All devices were placed properly, without technical difficulties. We successfully resheathed and repositioned the device in two cases. Minor and major intraprocedural or periprocedural events were noted. CONCLUSIONS: The Pipeline Flex device allows more precise and controlled deployment than the current PED device. Although this preliminary experience seems positive, multicenter larger series will be needed to confirm the safety and durability of this new device.

Measurement of antiplatelet inhibition during neurointerventional procedures: the effect of antithrombotic duration and loading dose.

BACKGROUND/OBJECTIVE: Symptomatic thromboembolic events are the most common complications associated with aneurysm coiling, and carotid and intracranial stenting. Our objective is to assess the effect of aspirin (ASA) and clopidogrel dose and duration on platelet inhibition using a point of care assay in neurointerventional (NI) suite. METHOD: The dose, duration, and point of care platelet function assay data for clopidogrel and aspirin therapy were prospectively collected between February 2006 and November 2007. Inadequate platelet inhibition for ASA was defined as >or=550 ASA reaction units (ARU), and for clopidogrel was defined as or=7 days, 300 mg for 24 hours, and 600 mg same day load had a mean P2Y12/ADP inhibition of 45%, 35% (P-value = .09), and 16%, respectively (P-value = .005). CONCLUSION: Premedication with clopidogrel, in contrast to aspirin, does not achieve adequate platelet inhibition in about two-third of the patients. Same day antiplatelet loading may be insufficient to achieve adequate platelet inhibition and should be avoided if clinically feasible.

Efecto protector de la melatonina frente a la toxicidad de la mitomicina C / No disponible

No disponible

Protective effect of melatonin against mitomycin C-induced genotoxic damage in peripheral blood of rats.

Mitomycin C (MMC) generates free radicals when metabolized. We investigated the effect of melatonin against MMC-induced genotoxicity in polychromatic erythrocytes and MMC-induced lipid peroxidation in brain and liver homogenates. Rats (N = 36) were classified into 4 groups: control, melatonin, MMC, and MMC + melatonin. Melatonin and MMC doses of 10 mg/kg and 2 mg/kg, respectively, were injected intraperitoneally. Peripheral blood samples were collected at 0, 24, 48, 72, and 96 hours posttreatment and homogenates were obtained at 96 hours posttreatment. The number of micronucleated polychromatic erythrocytes (MN-PCE) per 1000 PCE was used as a genotoxic marker. Malondialdehyde (MDA) plus 4-hydroxyalkenal (4-HDA) levels were used as an index of lipid peroxidation. The MMC group showed a significant increase in MN-PCE at 24, 48, 72, and 96 hours that was significantly reduced with melatonin begin coadministrated. No significant differences were found in lipid peroxidation. Our results indicate that MMC-induced genotoxicity can be reduced by melatonin.

El sistema cannabinoide en situaciones de neuroinflamación: perspectivas terapéuticas en la esclerosis múltiple / Cannabinoid system and neuroinflammation: therapeutic perspectives in multiple sclerosis

Introducción. El sistema endocannabinoide está constituidopor los receptores cannabinoides, los ligandos endógenos y loselementos enzimáticos implicados en su síntesis y degradación.Objetivo. Describir el estado actual de conocimiento sobre la funcióndel sistema como modulador de los procesos neuroinflamatoriosasociados con enfermedades crónicas como la esclerosis múltiple.Desarrollo. Los cannabinoides se sintetizan y se liberan en demanda y su producción aumenta en situaciones de neuroinflamacióny de daño neural. En este contexto, sus acciones en la microglía y enlos astrocitos se caracterizan por una disminución en la expresión demediadores inflamatorios y de citocinas proinflamatorias. Además,los cannabinoides pueden ejercer acciones neuroprotectoras a travésde diferentes tipos de mecanismos y en modelos experimentalesde esclerosis múltiple atenúan la sintomatología, disminuyen lainflamación y pueden favorecer la remielinización. Conclusiones. Eluso clínico de cannabinoides o agentes farmacológicos que incidenen el sistema endógeno cannabinoide durante la inflamación del sistemanervioso central y en la esclerosis múltiple está actualmentesometido a consideración y debate. El análisis detallado de los resultadosobtenidos en la última década ha permitido establecer que sonmúltiples los mecanismos de actuación de los cannabinoides en patologíasdel sistema nervioso central que cursan con inflamación crónicay ponen de manifiesto el interés del sistema cannabinoide comonueva herramienta terapéutica

Introduction. The endocannabinoid system consists of cannabinoid receptors, endogenous ligands and the enzymaticelements involved in their synthesis and breakdown. Aim. To report on currently held knowledge about the functioning of thesystem as a modulator of the neuroinflammatory processes associated with chronic diseases such as multiple sclerosis.Development. Cannabinoids are synthesised and released on demand and their production increases in times of neuroinflammationand neural damage. In this context then, their actions in the microglial cells and in the astrocytes arecharacterised by a lowered expression of inflammatory mediators and pro-inflammatory cytokines. Furthermore,cannabinoids can play a role as neuroprotectors by means of different types of mechanisms and, in experimental models ofmultiple sclerosis, they slow down the symptoms, reduce inflammation and can favour remyelination. Conclusions. Theclinical use of cannabinoids or pharmacological agents that affect the endogenous cannabinoid system during inflammationof the central nervous system and in multiple sclerosis is currently under consideration and subject to debate. Detailedanalysis of the results obtained over the past decade has made it possible to establish the existence of several mechanisms ofaction of cannabinoids in pathologies affecting the central nervous system that are accompanied by chronic inflammation.Likewise, they also clearly show that the cannabinoid system is an interesting proposal as a new therapeutic tool

[Cannabinoid system and neuroinflammation:therapeutic perspectives in multiple sclerosis]. / El sistema cannabinoide en situaciones de neuroinflamación: perspectivas terapéuticas en la esclerosis múltiple.

INTRODUCTION: The endocannabinoid system consists of cannabinoid receptors, endogenous ligands and the enzymatic elements involved in their synthesis and breakdown. AIM: To report on currently held knowledge about the functioning of the system as a modulator of the neuroinflammatory processes associated with chronic diseases such as multiple sclerosis. DEVELOPMENT: Cannabinoids are synthesised and released on demand and their production increases in times of neuroinflammation and neural damage. In this context then, their actions in the microglial cells and in the astrocytes are characterised by a lowered expression of inflammatory mediators and pro-inflammatory cytokines. Furthermore, cannabinoids can play a role as neuroprotectors by means of different types of mechanisms and, in experimental models of multiple sclerosis, they slow down the symptoms, reduce inflammation and can favour remyelination. CONCLUSIONS: The clinical use of cannabinoids or pharmacological agents that affect the endogenous cannabinoid system during inflammation of the central nervous system and in multiple sclerosis is currently under consideration and subject to debate. Detailed analysis of the results obtained over the past decade has made it possible to establish the existence of several mechanisms of action of cannabinoids in pathologies affecting the central nervous system that are accompanied by chronic inflammation. Likewise, they also clearly show that the cannabinoid system is an interesting proposal as a new therapeutic tool.

Melatonin improves deferoxamine antioxidant activity in protecting against lipid peroxidation caused by hydrogen peroxide in rat brain homogenates.

Deferoxamine (DF) is an antioxidant molecule because of its ability to chelate iron. This study compared the ability of DF alone or in combination with melatonin, 5-methoxytryptophol or pinoline in preventing lipid peroxidation due to hydrogen peroxide (H(2)O(2)) in rat brain homogenates. Malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) in the homogenates were measured as indices of lipid peroxidation. Incubation of homogenates with DF reduced, in a dose-dependent manner, MDA+4-HDA formation due to H(2)O(2). When melatonin, 5-methoxytryptophol or pinoline were added to the incubation medium, the efficacy of DF in preventing lipid peroxidation was enhanced. These cooperative effects between DF, melatonin, and related pineal products may be important in protecting tissues from the oxidative stress due to iron overload.

Design, synthesis and biological evaluation of novel arachidonic acid derivatives as highly potent and selective endocannabinoid transporter inhibitors.

In the present work, we have designed and synthesized a series of arachidonic acid derivatives of general structure I which have been characterized as highly potent and selective inhibitors of anandamide transporter (IC(50) = 24-0.8 microM, K(i) > 1000-5000 nM for CB(1) and CB(2) cannabinoid receptors and vanilloid VR(1) receptor). Among them, N-(3-furylmethyl)eicosa-5,8,11,14-tetraenamide deserves special attention as being the most potent endocannabinoid transporter inhibitor (IC(50) = 0.8 microM) described to date.