The Egyptian Escalator: Gaining access to distal parent vessel in giant and large aneurysms.

Flow-diverter stents have become the mainstay of endovascular treatment for giant and large intracranial aneurysms. However, the local aneurysmal hemodynamics, the incorporation of the parent vessel and the frequent wide-neck configuration render gaining stable distal parent artery access difficult. In this technical video, we present three cases in which we employed the so called "Egyptian Escalator technique" for obtaining and maintaining stable distal access: after looping the microwire and microcatheter inside the aneurysmal sac and exiting in the distal parent artery, we deployed a stent-retriever and utilized a gentle traction on the microcatheter in order to straighten the intra-aneurysmal loop. Afterwards, a flow-diverter stent was deployed, with optimal coverage of the aneurysmal neck. The "Egyptian Escalator" technique provides a useful approach for obtaining stable distal access for flow-diverter deployment in giant and large aneurysm (supplementary mmc1 (Video 1)).

Superselective 3D digital subtraction angiography and magnetic resonance fusion imaging for the management of micro-arteriovenous malformations.

Cerebral micro-arteriovenous malformations (AVM) are defined by an infracentimetric nidus or a nidus solely visible on superselective digital subtraction angiography (DSA).12 While representing a minority of brain AVMs, intracerebral hemorrhage is a frequent manifestation in this subset of AMVs.2 Micro-AVMs are often occult lesions, with superselective DSA being instrumental for increasing diagnostic yield.13 While superselective three-dimensional DSA (3D-DSA)/MR fusion imaging has been employed to better delineate anatomical proximity in cerebral AVMs with a visible nidus on MRI,4 this fusion algorithm has not yet been used for describing the relationship of micro-AVMs nidus and afferent arteries with neighboring structures, in order to guide endovascular and microsurgical procedures. In this technical video (Video 1), we present 3 cases regarding micro-AVM embolization, in which superselective 3D-DSA/MR fusion imaging aided therapeutic decision, by defining the local anatomy and allowing a safer procedure.

Rescue technique for trapped bone needle in cement cast.

Avascular necrosis, or Kummel disease, is a potential complication of vertebral compression fractures. It is believed to arise as a result of a failed fracture healing process,1 2 leading to the formation of an air or fluid filled cavity within the vertebral body.3 Percutaneous vertebroplasty seems to provide both pain relief and increased spinal stability in avascular necrosis.4 In this technical video, we present the case of an osteoporotic patient with a complicated vertebroplasty, caused by trapping of the bone needle inside the intravertebral cement cast. Two methods were used sequentially, leading to retrieval of the bone needle. We identified several technical aspects, such as injection speed, quasi-filling of the vertebral cavity, and frequent rotation of the bone needle as essential for the success of the procedural. We suggest that improving these parameters may prevent intravertebral bone needle trapping in patients with avascular necrosis. neurintsurg;14/11/1158/V1F1V1Video 1.

Anticoagulation-refractory strokes and selective infarction pattern: What's the link?

Stroke etiology in the form of a CAP should be actively explored, especially in the context of previous negative work-up and anticoagulant-refractory strokes. Dual antiplatelet therapy proved superior to anticoagulation for secondary prevention.

Cellular determinants involving mitochondrial dysfunction, oxidative stress and apoptosis correlate with the synergic cytotoxicity of epigallocatechin-3-gallate and menadione in human leukemia Jurkat T cells.

We have investigated the growth-suppressive action of epigallocatechin-3-gallate (EGCG) on human leukemia Jurkat T cells. Results show a strong correlation between the dose-dependent reduction of clonogenic survival following acute EGCG treatments and the EGCG-induced decline of the mitochondrial level of Ca(2+). The cell killing ability of EGCG was synergistically enhanced by menadione. In addition, the cytotoxic effect of EGCG applied alone or in combination with menadione was accompanied by apoptosis induction. We also observed that in acute treatments EGCG displays strong antioxidant properties in the intracellular milieu, but concurrently triggers some oxidative stress generating mechanisms that can fully develop on a longer timescale. In parallel, EGCG dose-dependently induced mitochondrial depolarization during exposure, but this condition was subsequently reversed to a persistent hyperpolarized mitochondrial state that was dependent on the activity of respiratory Complex I. Fluorimetric measurements suggest that EGCG is a mitochondrial Complex III inhibitor and indicate that EGCG evokes a specific cellular fluorescence with emission at 400nm and two main excitation bands (at 330nm and 350nm) that may originate from a mitochondrial supercomplex containing dimeric Complex III and dimeric ATP-synthase, and therefore could provide a valuable means to characterize the functional properties of the respiratory chain.

Novel insights into the antiproliferative effects and synergism of quercetin and menadione in human leukemia Jurkat T cells.

The flavonoid quercetin and menadione (vitamin K3) are known as potent apoptogens in human leukemia Jurkat T cells. We explored some underlying mechanisms and the potential relevance of the combination quercetin-menadione for clinical applications. In acute treatments, quercetin manifested a strong antioxidant character, but induced a transient loss of Δψm, likely mediated by opening of the mitochondrial permeability transition pore. After removal of quercetin, persistent mitochondrial hyperpolarization was generated via stimulation of respiratory Complex I. In contrast, menadione-induced Δψm dissipation was only partially and transiently reversed after menadione removal. Results indicate that Ca(2+) release is a necessary event in quercetin-induced cell death and that the survival response to quercetin is delineated within 1h from exposure. Depending on dose, the two agents exhibited either antagonistic or synergistic effects in reducing clonogenicity of Jurkat cells. 24-h combinatorial regimens at equimolar concentrations of 10-15 µM, which are compatible with a clinically achievable (and safe) scheme, reduced cell viability at efficient rates. Altogether, these findings support the idea that the combination quercetin-menadione could improve the outcome of conventional leukemia therapies, and warrant the utility of additional studies to investigate the therapeutic effects of this combination in different cellular or animal models for leukemia.

Mitochondrial respiratory complex I probed by delayed luminescence spectroscopy.

The role of mitochondrial complex I in ultraweak photon-induced delayed photon emission [delayed luminescence (DL)] of human leukemia Jurkat T cells was probed by using complex I targeting agents like rotenone, menadione, and quercetin. Rotenone, a complex I-specific inhibitor, dose-dependently increased the mitochondrial level of reduced nicotinamide adenine dinucleotide (NADH), decreased clonogenic survival, and induced apoptosis. A strong correlation was found between the mitochondrial levels of NADH and oxidized flavin mononucleotide (FMNox) in rotenone-, menadione- and quercetin-treated cells. Rotenone enhanced DL dose-dependently, whereas quercetin and menadione inhibited DL as well as NADH or FMNox. Collectively, the data suggest that DL of Jurkat cells originates mainly from mitochondrial complex I, which functions predominantly as a dimer and less frequently as a tetramer. In individual monomers, both pairs of pyridine nucleotide (NADH/reduced nicotinamide adenine dinucleotide phosphate) sites and flavin (FMN-a/FMN-b) sites appear to bind cooperatively their specific ligands. Enhancement of delayed red-light emission by rotenone suggests that the mean time for one-electron reduction of ubiquinone or FMN-a by the terminal Fe/S center (N2) is 20 or 284 µs, respectively. All these findings suggest that DL spectroscopy could be used as a reliable, sensitive, and robust technique to probe electron flow within complex I in situ.