Rheological Properties of Non-Adhesive Embolizing Compounds-The Key to Fine-Tuning Embolization Process-Modeling in Endovascular Surgery.

The study of polymers' rheological properties is of paramount importance both for the problems of their industrial production as well as for their practical application. Two polymers used for embolization of arteriovenous malformations (AVMs) are studied in this work: Onyx-18® and Squid-12®. Viscosity curve tests and computational fluid dynamics (CFD) were used to uncover viscosity law as a function of shear rate as well as behavior of the polymers in catheter or pathological tissue models. The property of thermal activation of viscosity was demonstrated, namely, the law of dependence of viscosity on temperature in the range from 20 °C to 37 °C was established. A zone of viscosity nonmonotonicity was identified, and a physical interpretation of the dependence of the embolic polymers' viscosity on the shear rate was given on the basis of Cisco's model. The obtained empirical constants will be useful for researchers based on the CFD of AVMs. A description of the process of temperature activation of the embolic polymers' viscosity is important for understanding the mechanics of the embolization process by practicing surgeons as well as for producing new prospective embolic agents.

High-Frequency versus Low-Frequency Spinal Cord Stimulation in Treatment of Chronic Limb-Threatening Ischemia: Short-Term Results of a Randomized Trial.

INTRODUCTION: The objective of the study is to determine if high-frequency (1 kHz) spinal cord stimulation (SCS) is better than low-frequency SCS for pain relief in chronic limb-threatening ischemia (CLTI). METHODS: HEAL-SCS trial was designed as an open-label, parallel-group, single-center randomized study with a 1:1 allocation ratio. The trial was conducted in Meshalkin National Medical Research Center between August 2018 and February 2020. Total 56 patients underwent screening, 50 were enrolled, 6 were rejected. The participants were randomized into 2 cohorts of 25 patients each by an external coordinator using an online tool. A neurosurgeon and a vascular surgeon both examined all patients and estimated the pain intensity using visual analog scale (VAS), quality of life with short-form-36 health survey (SF-36), and functional status by walking impairment questionnaire (WIQ) at 3 and 12 months. Tissue perfusion was evaluated for 34 patients using transcutaneous oxygen tension measurement (TcPO2) at baseline and in 12 months. RESULTS: All 50 patients (84% men, median age 66.5 y.o) were available for primary outcome assessment 3 and 12 months after implantation. Intention-to-treat analysis demonstrated comparative advantage of HF-SCS over LF-SCS at 3 months with mean VAS score 2.8 (95% CI, 2.4; 3.2) and 3.3 (95% CI, 3.0; 3.6), respectively (p = 0.031). Clinical superiority of HF-SCS persisted at 12-month follow-up (p < 0.001). HF-SCS produced significantly greater pain relief by WIQ at 3 (p < 0.001) and 12 months (p = 0.009). Despite stair-climbing ability was better in HF-SCS group (p = 0.02), no significant difference between groups was found at 1-year post-op in terms of speed (p = 0.92) and distance scores (p = 0.68). Accordingly, the general and mental health domains of SF-36 were significantly better in HF-SCS at 12 months. Despite a tendency toward better resting oxygen pressure in HF-SCS group, there was no intergroup difference by TcPO2 (p = 0.076). Only 1 patient (2%) required above-the-knee amputation at 10 months after LF-SCS implantation. CONCLUSION: High-frequency SCS provides better pain relief, life quality, and functional performance in patients with CLTI during short-term follow-up. The lack of perfusion difference between high-frequency and conventional SCS requires further examination to the possible long-term advantages of the method.

Huge cerebral pial arteriovenous fistula in a newborn: illustrative case.

BACKGROUND: Pediatric arteriovenous malformations (AVMs) and pial/dural arteriovenous fistulas (AVFs) are rare but life-threatening complications that can lead to congestive heart failure and hemorrhagic stroke in newborns and pediatric patients. The pronounced shunting in these conditions is associated with early complications and necessitates aggressive surgical management. Here, the authors describe endovascular treatment of an atypical cerebral pial AVF in a newborn. OBSERVATIONS: This AVF formed direct communication between a major cerebral artery (basilar artery) and a large draining vein (dilated deep cerebral vein). The authors performed earlier subtotal embolization of the AVF using 0.020-inch coils, which led to progressive thrombosis of the fistula with restoration of normal arterial blood flow. The patient was discharged 18 days after surgery, examination at 1.5 and 6 months showed magnetic resonance imaging signs of blood flow absence through the fistula and satisfactory condition of the infant without physical and mental developmental delay. LESSONS: Subtotal coiling of a high-flow pial AVF in a newborn can result in a good clinical outcome.

Numerical Assessment of the Risk of Abnormal Endothelialization for Diverter Devices: Clinical Data Driven Numerical Study.

Numerical modeling is an effective tool for preoperative planning. The present work is devoted to a retrospective analysis of neurosurgical treatments for the occlusion of cerebral aneurysms using flow-diverters and hemodynamic factors affecting stent endothelization. Several different geometric approaches have been considered for virtual flow-diverters deployment. A comparative analysis of hemodynamic parameters as a result of computational modeling has been carried out basing on the four clinical cases: one successful treatment, one with no occlusion and two with in stent stenosis. For the first time, a quantitative assessment of both: the limiting magnitude of shear stresses that are necessary for the occurrence of in stent stenosis (MaxWSS > 1.23) and for conditions in which endothelialization is insufficiently active and occlusion of the cervical part of the aneurysm does not occur (MaxWSS < 1.68)­has been statistacally proven (p < 0.01).

Middle Cerebral Artery Aneurysm Trial (MCAAT): A Randomized Care Trial Comparing Surgical and Endovascular Management of MCA Aneurysm Patients.

BACKGROUND: Whether the best management of middle cerebral artery (MCA) aneurysm patients is surgical or endovascular remains uncertain, with little evidence to guide decision-making. A randomized care trial offering MCA aneurysm patients a 50% chance of surgical and a 50% chance of endovascular management may optimize outcomes in the presence of uncertainty. METHODS: The Middle Cerebral Artery Aneurysm Trial (MCAAT) is an investigator-initiated, multicenter, parallel group, prospective, 1:1 randomized controlled clinical trial. All adult patients with MCA aneurysms, ruptured or unruptured, amenable to surgical and endovascular treatment can be included. The composite primary outcome is "Treatment Success": (i) occlusion or exclusion of the aneurysm using the allocated treatment modality; (ii) no intracranial hemorrhage during follow-up; (iii) no retreatment of the target aneurysm during follow-up, (iv) no residual aneurysm on angiographic follow-up; and (v) independence (mRS <3) at 1 year. The trial tests 2 versions of the same hypothesis (one for ruptured and one for unruptured MCA aneurysm patients): Surgical management will lead to a 15% absolute increase in the proportion of patients reaching Treatment Success from 55% to 70% (ruptured) or from 75% to 90% (unruptured aneurysm patients) compared with endovascular treatment (any method). In this pragmatic trial, outcome evaluations are by treating physicians, except for 1-year angiographic results which will be core lab assessed. The trial will be monitored by an independent data safety monitoring committee to assure safety of participants. MCAAT is registered at clinicaltrials.gov: NCT05161377. CONCLUSIONS: Patients with MCA aneurysms can be optimally managed within a care trial protocol.

Silent EEG-Speech Recognition Using Convolutional and Recurrent Neural Network with 85% Accuracy of 9 Words Classification.

In this work, we focus on silent speech recognition in electroencephalography (EEG) data of healthy individuals to advance brain-computer interface (BCI) development to include people with neurodegeneration and movement and communication difficulties in society. Our dataset was recorded from 270 healthy subjects during silent speech of eight different Russia words (commands): 'forward', 'backward', 'up', 'down', 'help', 'take', 'stop', and 'release', and one pseudoword. We began by demonstrating that silent word distributions can be very close statistically and that there are words describing directed movements that share similar patterns of brain activity. However, after training one individual, we achieved 85% accuracy performing 9 words (including pseudoword) classification and 88% accuracy on binary classification on average. We show that a smaller dataset collected on one participant allows for building a more accurate classifier for a given subject than a larger dataset collected on a group of people. At the same time, we show that the learning outcomes on a limited sample of EEG-data are transferable to the general population. Thus, we demonstrate the possibility of using selected command-words to create an EEG-based input device for people on whom the neural network classifier has not been trained, which is particularly important for people with disabilities.

A DELPHI consensus statement on antiplatelet management for intracranial stenting due to underlying atherosclerosis in the setting of mechanical thrombectomy.

PURPOSE: There is little data and lack of consensus regarding antiplatelet management for intracranial stenting due to underlying intracranial atherosclerosis in the setting of endovascular treatment (EVT). In this DELPHI study, we aimed to assess whether consensus on antiplatelet management in this situation among experienced experts can be achieved, and what this consensus would be. METHODS: We used a modified DELPHI approach to address unanswered questions in antiplatelet management for intracranial stenting due to underlying atherosclerosis in the setting of EVT. An expert-panel (19 neurointerventionalists from 8 countries) answered structured, anonymized on-line questionnaires with iterative feedback-loops. Panel-consensus was defined as agreement ≥ 70% for binary closed-ended questions/≥ 50% for closed-ended questions with > 2 response options. RESULTS: Panel members answered a total of 5 survey rounds. They acknowledged that there is insufficient data for evidence-based recommendations in many aspects of antiplatelet management for intracranial stenting due to underlying atherosclerosis in the setting of EVT. They believed that antiplatelet management should follow a standardized regimen, irrespective of imaging findings and reperfusion quality. There was no consensus on the timing of antiplatelet-therapy initiation. Aspirin was the preferred antiplatelet agent for the peri-procedural period, and oral Aspirin in combination with a P2Y12 inhibitor was the favored postprocedural regimen. CONCLUSION: Data on antiplatelet management for intracranial stenting due to underlying atherosclerosis in the setting of EVT are limited. Panel-members in this study achieved consensus on postprocedural antiplatelet management but did not agree upon a preprocedural and intraprocedural antiplatelet regimen. Further prospective studies to optimize antiplatelet regimens are needed.

Stent-assisted coiling of cerebral aneurysms: multi-center analysis of radiographic and clinical outcomes in 659 patients.

INTRODUCTION: The endovascular stent-assisted coiling approach for the treatment of cerebral aneurysms is evolving rapidly with the availability of new stent devices. It remains unknown how each type of stent affects the safety and efficacy of the stent-coiling procedure. METHODS: This study compared the outcomes of endovascular coiling of cerebral aneurysms using Neuroform (NEU), Enterprise (EP), and Low-profile Visualized Intraluminal Support (LVIS) stents. Patient characteristics, treatment details and angiographic results using the Raymond-Roy grade scale (RRGS), and procedural complications were analyzed in our study. RESULTS: Our study included 659 patients with 670 cerebral aneurysms treated with stent-assisted coiling (NEU, n=182; EP, n=158; LVIS, n=330) that were retrospectively collected from six academic centers. Patient characteristics included mean age 56.3±12.1 years old, female prevalence 73.9%, and aneurysm rupture on initial presentation of 18.8%. We found differences in complete occlusion on baseline imaging, defined as RRGS I, among the three stents: LVIS 64.4%, 210/326; NEU 56.2%, 95/169; EP 47.6%, 68/143; P=0.008. The difference of complete occlusion on 10.5 months (mean) and 8 months (median) angiographic follow-up remained significant: LVIS 84%, 251/299; NEU 78%, 117/150; EP 67%, 83/123; P=0.004. There were 7% (47/670) intra-procedural complications and 11.5% (73/632) post-procedural-related complications in our cohort. Furthermore, procedure-related complications were higher in the braided-stents vs laser-cut, P=0.002. CONCLUSIONS: There was a great variability in techniques and choice of stent type for stent-assisted coiling among the participating centers. The type of stent was associated with immediate and long-term angiographic outcomes. Randomized prospective trials comparing the different types of stents are warranted.

The Clinical Outcomes in Patients with Critical Limb Ischemia One Year after Spinal Cord Stimulation.

BACKGROUND: The aim of this study was to evaluate the long-term outcomes of spinal cord stimulation in patients with critical limb ischemia and to test the hypothesis that the dynamics of clinical changes one year after therapy depend both on the clinical determinants associated with the underlying disease and on factors related to systemic atherosclerosis. METHODS: This prospective cohort study included 56 patients with critical limb ischemia. All patients before and after spinal cord stimulation were examined in terms of the dynamics of their clinical changes using the Rutherford scale and transcutaneous oxygen tension (TcPO2, mm Hg) in the affected foot. The active orthostatic test was used to assess the functional state of peripheral perfusion. RESULTS: One year after spinal cord stimulation, 74% of patients showed positive clinical outcomes. No changes were observed in 9.3% of patients, whereas adverse clinical outcomes were revealed in 16.7% of cases. The TcPO2 values were significantly reduced before spinal cord stimulation: 10.5 (6.4-16.0) mm Hg. The functional status of the peripheral microvasculature was also disturbed. One year after therapy, TcPO2 significantly increased and the adaptive mechanisms of the microvasculature were improved in more than 70% of patients. Logistic regression analysis showed that the initially low TcPO2 values (<10 mm Hg) with a lack of gain in TcPO2 during the orthostatic test are associated with the negative clinical outcomes after spinal cord stimulation. The gain in TcPO2 during the orthostatic test to >10 mm Hg is associated with the positive clinical outcomes after spinal cord stimulation. The age-adjusted Charlson Comorbidity Index >5 and duration of critical ischemic symptoms also had a negative effect on the clinical outcomes after spinal cord stimulation. CONCLUSIONS: The positive clinical outcomes were revealed in most patients with critical limb ischemia one year after spinal cord stimulation. The low values of peripheral tissue metabolism with the disturbed functional status of the microvasculature are associated with the negative clinical outcome. The patients with baseline TcPO2 <10 mm Hg can recover if they still have a sufficient microcirculatory reserve capacity. Duration of critical ischemic symptoms and high comorbidity burden with allowance for age are negative factors affecting the clinical outcome.

Safety and efficacy of intracranial aneurysm embolization using the "combined remodeling technique": low-profile stents delivered through double lumen balloons: a multicenter experience.

PURPOSE: Since appearance of the balloon-remodeling technique and stent-assisted coiling, complex aneurysms have been treated successfully by endovascular means worldwide. Although these two techniques have been widely proven, the combination of both traditionally made the procedures more complicated technically. The aim of our study was to determine the technical success, safety, and efficacy of the low-profile stents delivered through double lumen balloons. METHODS: Clinical, procedural, and angiographic data were analyzed. RESULTS: Eighty-four patients (55 women; age range 20-81 years) harboring 86 aneurysms were included in this study. Aneurysm maximal diameter ranged from 2 to 26 mm, with mean 7.5 mm. There were 62 unruptured, 15 recanalized, and 9 acutely ruptured aneurysms. Aneurysm locations were ACoA (31), MCA (36), supraclinoid ICA (4), carotid bifurcation (2), basilar (7), PCA (3), PICA (2), and VA (1). Ninety-three devices were implanted (63 LVIS jr, 15 LEO Baby, 14 ACCLINO Flex and 1 Neuroform Atlas) through the double lumen balloons (Scepter C or XC and Eclipse 2 L). We found 2 minor clinical events (2.4%) and 1 major event (1.2%). Total intra-procedural technical complication rate was 11.6%. Follow-up was available for 71 patients with an average follow-up of 7 months. Complete and near complete occlusion was 90.1%. Residual aneurysms were seen in 9.9%. CONCLUSION: The "combined remodeling technique" with low-profile stents delivered through double-lumen balloons is technically feasible, safe, and effective for the treatment of intracranial aneurysms. This technique allows the operator to avoid extra maneuvers.

A2, M2, P2 aneurysms and beyond: results of treatment with pipeline embolization device in 65 patients.

BACKGROUND: Intracranial aneurysms located in the distal vessels are rare and remain a challenge to treat through surgical or endovascular interventions. OBJECTIVE: To describe a multicenter approach with flow diversion using the pipeline embolization device (PED) for treatment of distal intracranial aneurysms. METHODS: Cases of distal intracranial aneurysms defined as starting on or beyond the A2 anterior cerebral artery, M2 middle cerebral artery, and P2 posterior cerebral artery segments were included in the final analysis. RESULTS: 65 patients with distal aneurysms treated with the PED were analyzed. Median aneurysm size at the largest diameter was 7.0 mm, 60% were of a saccular morphology, and 9/65 (13.8%) patients presented in the setting of acute rupture. Angiographic follow-up data were available for 53 patients, with a median follow-up time of 6 months: 44/53 (83%) aneurysms showed complete obliteration, 7/53 (13.2%) showed reduced filling, and 2/53 (3%) showed persistent filling. There was no association between patient characteristics, including aneurysm size (P=0.36), parent vessel diameter (P=0.27), location (P=0.81), morphology (P=0.63), ruptured status on admission (P=0.57), or evidence of angiographic occlusion at the end of the embolization procedure (P=0.49). Clinical outcome data were available for 60/65 patients: 95% (57/60) had good clinical outcome (modified Rankin Scale score of 0-2) at 3 months. CONCLUSIONS: This large multicenter study of patients with A2, M2, and P2 distal aneurysms treated with the PED showed that flow diversion may be an effective treatment approach for this rare type of vascular pathology. The procedural compilation rate of 7.7% indicates the need for further studies as the flow diversion technology constantly evolves.

Transvenous Treatment of Carotid Aneurysms Through Transseptal Access.

BACKGROUND: Transseptal puncture has been widely used by cardiologists to reach the left side of the heart through a transvenous access. Rarely, it also can be used to pass into the supra-aortic arteries from the venous side when conventional transarterial access pathways (transfemoral, transradial/brachial routes, or direct carotid puncture) are likely to fail. CASE DESCRIPTION: We report 2 cases of transvenous femoral access followed by transseptal access to aorta to treat dissecting carotid artery aneurysms at the level of the skull base with flow diverters. In one case, multiple cervical arterial bypass operations and in the other a rare anomaly of the aortic arch precluded endovascular treatment through conventional routes. CONCLUSIONS: Transvenous-transseptal access enabled treatment of both cases easily and without complications. On follow-up computed tomography angiograms, both flow diverters were patent, there were no residual aneurysms, and no neurologic or cardiac adverse events in either patient.

Initial experience with precipitating hydrophobic injectable liquid in cerebral arteriovenous malformations.

BACKGROUND: Precipitating hydrophobic injectable liquid is a newly introduced liquid embolic agent for endovascular embolization with some technical advantages over other liquid embolic agents. We present our initial experience with precipitating hydrophobic injectable liquid in the endovascular treatment of cerebral arteriovenous malformations. METHODS: From October 2015 to January 2018, 27 patients harboring cerebral arteriovenous malformations underwent endovascular embolization with precipitating hydrophobic injectable liquid 25. Clinical features, angiographic results, procedural details, complications, and follow-up details were retrospectively analyzed. RESULTS: Twenty-seven patients with cerebral arteriovenous malformations were included. Total obliteration in one endovascular session was confirmed for 14/27 (52%) patients. Partial embolization was attained in 13 patients (48%) in whom staged treatment with following radiosurgery or surgery was planned. No mortality was recorded in this series. Complications during or after the embolization occurred in six of 27 (22.2%) patients. CONCLUSION: In our initial experience, precipitating hydrophobic injectable liquid has acceptable clinical outcome comparable to other liquid embolic agents. Although this is the largest reported study in arteriovenous malformation treatment with precipitating hydrophobic injectable liquid, further studies are needed to validate its safety and efficacy.

Flow diversion versus parent artery occlusion with bypass in the treatment of complex intracranial aneurysms: Immediate and short-term outcomes of the randomized trial.

OBJECTIVE: We performed prospective randomized comparison of clinical and surgical outcomes of flow diversion versus PVO and bypass in patients with complex anterior circulation aneurysms. PATIENTS AND METHODS: Open, prospective, randomized, parallel group, multicenter study of complex intracranial aneurysms treatment was conducted. Patients with complex intracranial aneurysms of anterior circulation with neck is more than 4 mm wide, dome/neck ratio is equal or less than 2:1, which is suitable for flow diversion and occlusion with bypass were included in the study. A total of 111 potential participants were enrolled since March 2015. Additional propensity score matching was performed with 40 patients in each group selected for analysis. RESULTS: 39 out of 40 patients (97.5%) from matched FD group reached good clinical outcome. In the matched bypass group acceptable outcome was achieved in 32 (80%) out of 40 patients (difference between groups p = 0.029). The morbidity and mortality rates were 15% and 5%, respectively. Difference in the rates of favorable outcomes, compared by χ2 met statistical significance (p = 0.014). The rate of complete aneurysm occlusion at 6 months was 42.5% in the FD group and 95% in surgical group (p < 0.0001). The rate of complete occlusion at 12 months was 65% in the FD group and 97.5% in surgical group. The difference between groups was still significant (p = 0.001). There were no significant differences between groups by occurrence of ischemic (p = 0.108) and hemorrhagic (p = 0.615) complications. CONCLUSION: The study demonstrated superior clinical outcomes for endovascular flow diversion in comparison with bypass surgery in treatment of complex aneurysms. Though, both techniques grant similar percentage of major neurologic complications and comparable cure rate for cranial neuropathy. Nevertheless, flow diversion is associated with significantly lower early obliteration rate, thus possesses patient for risks of prolonged dual antiplatelet regimen and delayed rupture. Hence, it's important to stratify patient by the natural risk of aneurysm rupture prior to treatment selection.

Experience using pipeline embolization device with Shield Technology in a patient lacking a full postoperative dual antiplatelet therapy regimen.

Utilization of flow diverting devices is accompanied with dual antiplatelet therapy to reduce the risk of thromboembolic events, even though this increases the risk of hemorrhagic complications. The updated Pipeline Flex embolization device with Shield Technology has been created using a phosphorylcholine coating that reduces thrombogenicity and possibly reduces the need for dual antiplatelet therapy. However, because of the potential risk to patients of utilizing a pipeline embolization device without dual antiplatelet therapy, the pipeline embolization device with Shield Technology has not been tested in human subjects without dual antiplatelet therapy, and its contribution to preventing thromboembolic events is therefore unknown. We report a case in which a patient, following complications that limited his absorption of dual antiplatelet therapy, had low levels of dual antiplatelet therapy medications in his bloodstream following treatment for an intracranial aneurysm with a pipeline embolization device with Shield Technology. The patient recovered without signs of luminal stenosis or thromboembolic event.

Angiopoietin-Like Proteins 4 (ANGPTL4) Gene Polymorphisms and Risk of Brain Arteriovenous Malformation.

BACKGROUND: Brain arteriovenous malformations (BAVMs) are formed by hypertrophied arterial vessels (afferents, feeders), a large number of arteriovenous shunts which become tangled to form a body (nidus) of malformation, which then expands draining proximal veins. The aim of this study was a replication of single nucleotide polymorphism (SNP) rs11672433 association with BAVM development with the subsequent meta-analysis of published data. METHODS: A total of 252 Russian patients with brain BAVMs and 480 control subjects were included in the present study. Genotyping was performed using real-time polymerase chain reaction with competitive hydrolysis probes. RESULTS: In our case-control study, we found no significant association with brain arteriovenous malformation for the SNP rs11672433 of ANGPTL4 gene (odds ratio .82, 95% confidence interval = .57-1.17 P value = .27) as well as in meta-analysis (odds ratio 1.18, 95% confidence interval = .81-1.73, P value = .39). CONCLUSIONS: Our data showed that SNP rs11672433 was not associated with the BAVM Russian population and the following meta-analysis did not detect an association in total. Thus, in spite of the fact that ANGPTL4 (protein) participates in the angiogenesis regulation processes, we consider that SNP rs11672433, a high-frequency locus in the ANGPTL4 gene, does not influence the predisposition to BAVM or its effect is too small to be detected in the present size sample set.