Circle of Willis integrity in acute middle cerebral artery occlusion: does the posterior communicating artery matter?

BACKGROUND: Collateral circulation is an important determinant of outcome in people with acute ischemic stroke due to large vessel occlusion (LVO). OBJECTIVE: To explore the impact of the circle of Willis (CW) anatomical characteristics ipsilateral to the occlusion site, particularly the posterior communicating artery (PComA) and the A1-portion of the anterior cerebral artery (A1-ACA), on stroke outcomes in a cohort of patients with LVO and middle cerebral artery (MCA) occlusion, undergoing endovascular thrombectomy (EVT). METHODS: This is a retrospective cohort study performed in a comprehensive tertiary stroke center. The study population consisted of consecutive patients with LVO with proximal MCA occlusion (M1) between June 2016 and April 2021, undergoing EVT. Demographic, clinical, and imaging information was extracted from patient files. Patency and diameters of ipsilateral A1-ACA and PComA were manually measured on admission CT angiography images in the core laboratory. RESULTS: One hundred and five patients with LVO comprised the study cohort, mean age 72.3 years, 43.8% were male, mean National Institutes of Health Stroke Scale score at admission 15.2. The cohort was grouped according to CW vessel characteristics. On univariate analysis, a well-developed PComA was associated with lower rates of hemorrhagic transformation (1.8% vs 14.3%, P=0.01) and a trend towards lower mortality rates (8.9% vs 20.4%, P=0.08).On multivariable regression analysis a well-developed PComA emerged as an independent predictor for survival (aOR=0.09, 95% CI 0.01 to 0.4 for survival at discharge, P=0.009, aOR=0.22, 95% CI 0.05 to 0.8 for survival at 90 days, P=0.02). CONCLUSIONS: In a cohort of patients with LVO due to M1 occlusion undergoing EVT, a well-developed PComA was associated with significantly lower hemorrhagic transformation rates, a trend towards better functional outcomes, and independently predicted survival. Larger studies are needed to understand the differential effect of CW collateral conduits on stroke outcome and evaluate the practicality of incorporating such factors in the clinical decision-making process prior to EVT.

Association between intracranial vessel calcifications, structural brain damage, and cognitive impairment after minor strokes: a prospective study.

Background: Vascular calcifications are a hallmark of atherosclerosis, and in the coronary arteries are routinely used as a prognostic marker. Calcifications of intracranial vessels (ICC) are frequently observed on non-contrast CT (NCCT) and their effect on post-stroke cognitive impairment (PSCI) remains unclear. Our aim was to explore the association of ICC with prospective long-term cognitive function and advanced MRI-measures in a large prospective cohort of cognitively intact mild stroke survivors. Methods: Data from the Tel-Aviv brain acute stroke cohort (TABASCO) study [ClinicalTrials.gov #NCT01926691] were analyzed. This prospective cohort study (n = 575) aimed to identify predictors of PSCI, in cognitively intact mild stroke survivors. A quantitative assessment of the intracranial calcium content - The ICC score (ICCS) was calculated semi-automatically on NCCT using a validated calcium quantification application. Participants underwent a 3 T-MRI and prospective comprehensive cognitive clinical and laboratory assessments at enrollment, 6, 12, and 24-months. Results: Data were available for 531 participants (67.4 years, 59.5% males). The incidence of PSCI at two-years doubled in the high ICCS group (26% vs. 13.7%, p < 0.001). The high ICCS group had significantly greater small-vessel-disease (SVD) tissue changes and reduced microstructural-integrity assessed by Diffusion-Tensor-Imaging (DTI) maps (p < 0.05 for all). In multivariate analysis, a higher ICCS was independently associated with brain atrophy manifested by lower normalized white and gray matter, hippocampal and thalamic volumes (ß = -0.178, ß = -0.2, ß = -0.137, ß = -0.157; p < 0.05) and independently predicted PSCI (OR 1.83, 95%CI 1.01-3.35). Conclusion: Our findings suggest that the ICCS, which is a simple and readily available imaging marker on NCCT, is associated with brain atrophy, microstructural damage, the extent of SVD, and may predict PSCI. This finding has implications for identifying individuals at risk for PSCI and implementing targeted interventions to mitigate this risk.

Preventing post-stroke dementia. The MARCH Trial. Protocol and statistical analysis plan of a randomized clinical trial testing the safety and efficacy of Maraviroc in post-stroke cognitive impairment.

Background: Current evidence suggest that 25%-33% of stroke-survivors develop post-stroke cognitive impairment (PSCI). The licensed drug Maraviroc, a CCR5-antagonist, is postulated to act via a neuroprotective mechanism that may offer the potential of preventing progression to vascular dementia. Our hypothesis: Maraviroc may have the potential to augment learning skills and cognitive performance by affecting synaptic plasticity, along with neuro-inflammatory modulation in patients with cerebral small vessel disease (SVD) and PSCI. Design: MARCH is a multi-center, double-blind randomized-control Phase-II trial of Maraviroc 150 or 600 mg/day versus placebo for 12-months in five stroke centers in Israel. Included are patients diagnosed with recent (1-24 months) subcortical stroke who experience mild PSCI and have evidence of white matter lesions and SVD on neuroimaging. Outcomes: Primary outcomes: 1. Change in cognitive scores. 2. Drug related adverse events. Secondary outcomes: change in functional and affective scores, MRI-derived measures, inflammatory markers, carotid atherosclerosis, cerebrospinal-fluid biomarkers in a sub-study. A sample size of 60 in each treatment group and 30 in the placebo group (total - 150 participants) provides 80% power between the treatment and the placebo groups. Conclusions: The results of this work could lead to a novel, readily available, therapeutic avenue to reduce PSCI, and possibly other pathologies. This study will test safety and effectiveness of Maraviroc in limiting cognitive deterioration and/or post stroke cognitive impairment in patients with cerebral small vessel disease. Schedule: First-patient first-visit was May 2021. Recruitment to complete in 2023, follow-up to complete in 2024.

Mothership versus drip and ship for thrombectomy in patients who had an acute stroke: a systematic review and meta-analysis.

BACKGROUND: The effectiveness of mechanical thrombectomy (MT) in acute ischemic stroke due to large vessel occlusion is time-dependent. While only stroke centers with endovascular capabilities perform MT, many patients who had a stroke initially present to the closest primary stroke centers capable of administering earlier intravenous thrombolysis, and then require to be transferred to a comprehensive stroke center for MT. PURPOSE: To compare the outcomes of this care pathway (drip and ship (DS)) with that whereby patients are directly transferred to a comprehensive stroke center (mothership (MS)). METHODS: We performed a systematic review and meta-analysis of published studies using several electronic databases to determine whether successful reperfusion (modified Thrombolysis In Cerebral Infarction ≥2b), functional independence at 90 days (modified Rankin Scale score ≤2), symptomatic intracranial hemorrhage, and 90-day mortality differed between those who underwent MT with the DS or the MS treatment pathway. Outcomes were meta-analyzed and the results expressed as adjusted relative risk (aRR) for the primary analysis and unadjusted relative risk (uRR) for secondary analysis. RESULTS: Eight studies including 2068 patients were selected, including one study reporting results fully adjusted for baseline characteristics. Patients undergoing MS had better functional independence than those undergoing DS (uRR=0.87, 95% CI 0.81 to 0.93; aRR=0.87, 95% CI 0.77 to 0.98). No difference was found between the treatment pathways in successful reperfusion (uRR=1.05, 95% CI 0.95 to 1.15; aRR=1.00, 95% CI 0.92 to 1.10), symptomatic intracranial hemorrhage (uRR=1.37, 95% CI 0.91 to 2.06; aRR, 1.53, 95% CI 0.79 to 2.98), and 90-day mortality (uRR=1.00, 95% CI 0.84 to 1.19; aRR=1.21, 95% CI 0.89 to 1.64). CONCLUSIONS: Patients who had an acute ischemic stroke admitted directly to a comprehensive stroke center (MS patients) with endovascular capacities may have better 90-day outcomes than those receiving DS treatment. However, major limitations of current evidence (ie, retrospective studies and selection bias) suggest a need for adequately powered studies. Multicenter randomized controlled trials are expected to answer this question.

The Woven EndoBridge (WEB) for endovascular therapy of intracranial aneurysms: Update of a systematic review with meta-analysis.

OBJECTIVES: Endovascular treatment of wide-neck intracranial aneurysms (IAs) is challenging, especially in bifurcation location. The intra-saccular flow-disruptor Woven EndoBridge (WEB) offers a new concept of endovascular therapy for wide-neck IAs. We performed an update of a systematic review aimed to report the feasibility, effectiveness and safety of WEB device therapy. PATIENTS AND METHODS: A systematic review was conducted using several electronic databases (including PUBMED and EMBASE), searching for studies published between October 2015 and December 2017 (those published between January 2010 and September 2015 were included in our initial systematic review). Outcomes were: success of implantation, peri-procedural complications, mortality, and adequate occlusion (complete occlusion or neck remnant). RESULTS: In total (initial review + update), 12 uncontrolled case-series studies were included, reporting outcomes for 940 patients (68.6% female; mean age, 57 years) harboring 962 IAs. Most IAs were wide-neck bifurcation aneurysms (75%-100%), mainly at middle cerebral artery (37%) and anterior communicating artery (24.6%). Feasibility was 97% (95% confidence interval [CI], 95%-99%), and 9% (95%CI, 5%-14%) of cases required additional treatment. There were 14% (95%CI, 9%-19%) peri-procedural complications. After a median clinical follow-up of 7 months, mortality was 5% (95%CI, 1%-10%) and was higher in series with larger proportions of ruptured IAs. At last angiographic follow-up (median, 7 months; range, 3-27.9 months), adequate occlusion rate was 81% (95%CI, 73%-88%). CONCLUSION: Although WEB showed high rates of adequate aneurysm occlusion at mid-term, procedure-related complications and mortality rates were not negligible. Future studies should compare the WEB device with other treatment options.

A Phase Ib/II Study Evaluating the Combination of Weekly Docetaxel and Cisplatin Together with Capecitabine and Bevacizumab in Patients with Advanced Esophago-Gastric Cancer.

INTRODUCTION: Current treatment options for advanced esophagogastric cancer (AEGC) are still unsatisfactory. The aim of this prospective phase Ib/II study was to evaluate the safety and efficacy of a novel regimen, AVDCX, consisting of weekly docetaxel and cisplatin together with capecitabine and bevacizumab, in AEGC. METHODS: Patients with AEGC received treatment with different dose levels of AVDCX (cisplatin and docetaxel 25-35 mg/m2, days 1,8, capecitabine 1,600 mg/m2 days 1-14, bevacizumab 7.5 mg/kg, day 1, Q:21 days). The study's primary objectives were to establish the recommended phase II doses of docetaxel and cisplatin in AVDCX (phase Ib part) and to determine the tumor response rate (phase II part). RESULTS: The study was closed early, after the accrual of 22 patients, due to accumulating toxicity-related deaths. The median age was 59 years and 77% of patients had gastric or gastroesophageal adenocarcinomas. Grade ≥3 adverse events were documented in 18 patients (82%), usually neutropenia (36%), fatigue (54%) or diarrhea (23%). There were three fatal toxicities (14%): mesenteric thromboembolism, gastric perforation and pancytopenic sepsis. The recommended phase II doses of cisplatin and docetaxel were determined to be 25 mg/m2 and 30 mg/m2, respectively. Twenty-one patients were evaluable for response: 12 (54%) had partial response (PR), 4 (18%) had stable disease (SD) and none had complete response (CR). Hence, the objective response rate (CR+PR) was 54% and the disease control rate (CR+PR+SD) was 72%. For the 17 patients treated at the MTD, the objective response rate was 41% and the disease control rate was 88%. The median overall survival (OS) for these patients was 13.9 months (range, 1.5-52.2 months) and the median progression-free survival was 7.6 months (range, 1.3-26.6 months). The 2-year OS rate reached 23.7%. CONCLUSIONS: AVDCX was associated with a high rate of regimen related fatal adverse events and is not appropriate for further development in AEGC patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT00845884.

Carotid siphon morphology: Is it associated with posterior communicating aneurysms?

BACKGROUND AND PURPOSE: Posterior communicating artery (PComA) aneurysm seems to behave uniquely compared with other intracranial aneurysms at different locations. The association between the morphology of the carotid siphon and PComA aneurysms is not well known. This study aimed to investigate whether the anatomical characteristics of the carotid siphon are associated with the formation and rupture of PComA aneurysms. METHODS: One hundred and thirty-two patients were retrospectively reviewed in a monocentric case-control study. Sixty-seven consecutive patients with PComA aneurysms were included in the case group, and 65 patients with anterior circulation aneurysm situated in other intracranial locations were included in the control group, matched by age and sex. Morphological characteristics of the carotid siphon were analyzed using angiography images. A univariate analysis was used to investigate the association between the morphological characteristics and the formation of PComA aneurysms. Furthermore, a subgroup analysis within the case group compared ruptured and non-ruptured PComA aneurysms. RESULTS: Patients with PComA aneurysm had a significantly (1.31 ± 0.70 vs. 0.82 ± 0.46; P < 0.001) larger PComA. No association was observed between the morphological characteristics of the carotid siphon and the presence of a PComA aneurysm. Likewise, subgroup analysis showed no significant association between morphological characteristics of the carotid siphon and aneurysm rupture. CONCLUSIONS: This case-control study shows that the carotid siphon morphology seems not to be related to PComA aneurysm formation or rupture.