Cerebrovascular Complications of COVID-19 and COVID-19 Vaccination.

The risk of stroke and cerebrovascular disease complicating infection with SARS-CoV-2 has been extensively reported since the onset of the pandemic. The striking efforts of many scientists in cooperation with regulators and governments worldwide have rapidly brought the development of a large landscape of vaccines against SARS-CoV-2. The novel DNA and mRNA vaccines have offered great flexibility in terms of antigen production and led to an unprecedented rapidity in effective and safe vaccine production. However, as mass vaccination has progressed, rare but catastrophic cases of thrombosis have occurred in association with thrombocytopenia and antibodies against PF4 (platelet factor 4). This catastrophic syndrome has been named vaccine-induced immune thrombotic thrombocytopenia. Rarely, ischemic stroke can be the symptom onset of vaccine-induced immune thrombotic thrombocytopenia or can complicate the course of the disease. In this review, we provide an overview of stroke and cerebrovascular disease as a complication of the SARS-CoV-2 infection and outline the main clinical and radiological characteristics of cerebrovascular complications of vaccinations, with a focus on vaccine-induced immune thrombotic thrombocytopenia. Based on the available data from the literature and from our experience, we propose a therapeutic protocol to manage this challenging condition. Finally, we highlight the overlapping pathophysiologic mechanisms of SARS-CoV-2 infection and vaccination leading to thrombosis.

Midterm follow-up after embolization of intracranial aneurysms proximal to the circle of Willis with the Silk Vista flow diverter: the I-MAMA registry.

PURPOSE: The aim of this registry was to assess technical success, procedural safety and mid- to long-term follow-up results of the Silk Vista "Mama" (SVM) flow diverter (BALT, Montmorency, France) for the treatment of proximal intracranial aneurysms. METHODS: Between August 2020 and March 2022, data from nine Italian neurovascular centres were collected. Data included patients' clinical presentation, aneurysms' size, location and status, technical details, overall complications and mid- to long-term angiographic follow-up. RESULTS: Forty-eight aneurysms in 48 patients were treated using the SVM. Most aneurysms were small (≤ 10 mm: no. 29, 60%) and unruptured (no. 31, 65%); 13 aneurysms were recurrent after coiling or clipping. 37/48 aneurysms involved the internal carotid artery (77%). Optimal opening and complete wall apposition of the device were achieved in 46 out of 48 cases (96%). Four intra- or periprocedural complications occurred (two thrombotic complications successfully resolved, one cerebellar ischemia, one perirenal hematoma), without new neurological deficit. No significant intra-stent stenosis or stent displacement was observed during follow-up. No FD-related morbidity nor mortality was reported. At midterm (6-12 months) to long-term (> 12 months) follow-up, complete aneurysm occlusion (OKM D) was achieved in 76% of cases. Eighty-eight percent of patients had complete aneurysm occlusion or entry remnant (OKM D + C). CONCLUSIONS: Our experience suggests that the new generation of low-profile SVM flow diverter for the treatment of proximal intracranial aneurysms is safe and effective, with low rates of intraprocedural complications and acceptable mid- to long-term occlusion rate.

Mechanical thrombectomy in young patients with large vessel occlusion-related ischemic stroke: Data from the Italian Registry of Endovascular Treatment in Acute Stroke.

BACKGROUND AND PURPOSE: The weight of outcome predictors in acute ischemic stroke (AIS) patients older than 60 years is not necessarily mirrored in the younger population, posing the question of whether outcome determinants specific for the latter might vary. Very few data are available on predictors of outcome in young AIS patients receiving endovascular treatment (EVT). METHODS: We analyzed data for patients aged between 16 and 55 years from the Italian Registry of Endovascular Treatment in Acute Stroke. We divided our population into patients <45 years old and patients aged between 45 and 55 years. After testing the differences between groups in terms of 90-day modified Rankin Scale (mRS) 0-2, mortality, and symptomatic intracranial hemorrhage, we looked for predictors of poor outcome (mRS 3-6), death, and symptomatic intracerebral hemorrhage in the two groups. RESULTS: A total of 438 patients younger than 45 years and 817 aged 45-55 years were included; 284 (34.8%) patients aged 45-55 years and 112 (25.6%) patients younger than 45 years old showed poor 90-day functional outcome (p = 0.001). Predictors of poor outcome in the older group were baseline National Institutes of Health Stroke Scale (NIHSS; p < 0.001), diabetes (p = 0.027), poor collateral status (p = 0.036), and groin puncture-to-recanalization time (p = 0.010), whereas Thrombolysis in Cerebral Infarction (TICI) 2b-3 had an inverse association (p < 0.001). Predictors of poor outcome in patients younger than 45 years were baseline NIHSS (p < 0.001) and groin puncture-to-recanalization time (p = 0.015), whereas an inverse association was found for baseline Alberta Stroke Program Early CT Score (p = 0.010) and TICI 2b-3 (p < 0.001). CONCLUSIONS: Approximately one third of young adults treated with EVT do not reach a good functional outcome. Fast and successful recanalization, rather than common risk factors, has a major role in determining clinical outcome.

A transient magnetic resonance spectroscopy peri-ischemic peak: a possible radiological biomarker of post-stroke neurogenesis.

BACKGROUND AND AIMS: In adult human brain, neurogenesis seems to persist throughout life and ischemic stroke was proved to stimulate this process. Using magnetic resonance spectroscopy (MRS), a 1.28-ppm peak, putative biomarker of neural progenitor cells (NPCs), was identified both in vitro and in vivo, i.e., in normal rat and healthy human brain. The aim of our study was to identify a 1.28-ppm peak in adult human ischemic brain by using 3.0 T multivoxel MRS. METHODS: We studied 10 patients, six males, and four females, with a mean (± SD) age of 59.3 (± 17.3), at three different time points from ischemic stroke onset (T0: < 5 days; T14: 14 ± 2 days; T30: 30 ± 2 days). RESULTS: In all patients except one, a 1.28-ppm peak at T14 was detected at the ischemic boundary (all p values < 0.05). MRS performed on six voluntary age-matched healthy subjects did not detect any 1.28-ppm peak. CONCLUSIONS: The nature of this 1.28-pm peak is uncertain; however, our data support the hypothesis that it might represent a marker of NPCs in post-stroke human brain.

No-reflow phenomenon in acute ischemic stroke: an angiographic evaluation.

BACKGROUND: Futile recanalization (FR) is de fined as a poor 90-day outcome or lack of neurological improvement at 24 h despite successful recanalization in acute ischemic stroke (AIS) with large vessel occlusion (LVO) treated by mechanical throbectomy (MT). The No-reflow phenomenon (NRP) could be a possible cause of FR, but its evidence in AIS patients is scarce. METHODS: We retrospectively analyzed 185 digital subtraction angiographies (DSA) of AIS patients with anterior circulation LVO after endovascular treatment. To better define NRP, we designed a score called the modified capillary index score (mCIS). The score is obtained by dividing the middle cerebral artery territory in three segments. For each segment, we gave 2 points if the capillary blush was present without any delay, 1 if delayed, and 0 if absent. The primary endpoint was to use mCIS to identify NRP on post-interventional DSA and to test whether this marker may predict FR and failure of early neurological improvement (fENI). The secondary endpoint was to search for a correlation between NRP, lesion volume, and hemorrhagic transformation. We used the ROC curve to define mCIS ≤ 3 as the cut-off and marker of NRP. RESULTS: NRP was present in 35.1% of patients. NRP predicted fENI at 24 h (aOR 2.825, 95% CI 1.265-6.308, P = 0.011) and at 7 days (aOR 2.191, 95% CI 1.008-4.762, P = 0.048), but not 90-day FR. Moreover, NRP predicted hemorrhagic transformation (aOR 2.444, 95% CI 1.266-4.717, P = 0.008). CONCLUSIONS: The modified capillary index score (mCIS) seems useful in identifying NRP in AIS. In addition, mCIS was able to predict NRP that correlated with early clinical outcome and hemorrhagic transformation of the ischemic lesion. An external validation of the score is warranted.

Treatment of giant intracranial aneurysms: long-term outcomes in surgical versus endovascular management.

Aneurysms with a major diameter > 25 mm are defined as giant intracranial aneurysms (GIAs). Different clinical, pathological, and radiological factors were revealed as playing a role in choosing the best strategy between surgical and endovascular approaches. Despite the improvement of both techniques, the efficacy and safety of these different management are still debated. We evaluated the differences in clinical and radiological outcomes of GIAs treated with surgical and endovascular techniques in a large retrospective mono-centric study. We compared aneurysm location, clinical, morphological features, treatment outcome, and complications on the ground of treatment technique. The final cohort consisted of 162 patients. All the patients were assigned on the ground of the type of eligible treatment: surgical (118 patients) and endovascular procedure (44 patients). The different treatment strategies were made through a multidisciplinary selection whereas clinical parameters, location, and morphologic features of the aneurysm were considered. The surgical group manifested a greater reduction in performance levels and neurological status in the post-operative phases than the endovascular group (p < 0.01) with a higher incidence of complications (p = 0.012) in contrast to a lower recurrence rate (p > 0.01). There is no significant difference in post-operative mortality and survival between surgical and endovascular groups. The surgical group manifested a higher incidence of complications after treatment. The endovascular group has a better post-operative outcome, but a higher risk of recurrence and the necessity of further treatment.

Y-stenting with braided stents for wide-neck intracranial bifurcation aneurysms. A single-center initial experience.

INTRODUCTION: The treatment of wide-neck bifurcation aneurysms is still challenging despite the use of new techniques, such as Y-stenting, the waffle-cone technique and intrasaccular flow disrupters, in recent years. Moreover, the use of flow diverter stents in bifurcation aneurysms has been proposed by several teams, although the results remain controversial. This study aims to evaluate the feasibility and efficacy of Y-stent assisted coiling of bifurcation aneurysms with braided stents. METHODS: We retrospectively reviewed all patients in whom Y-stenting with braided stents had been performed in our center. Six patients were identified and analyzed. Technical success, complications, angiographic outcomes, procedural data, and follow-up controls are reported here. This study was approved by our local ethical committee. RESULTS: Technical success was achieved in all procedures. Overall procedure-related morbidity and mortality was 0%. In the immediate post-treatment angiography, adequate occlusion (neck remnant or total occlusion) was observed in all patients. Short- and long-term follow-up angiography showed adequate occlusion of the aneurysms. CONCLUSIONS: In this small, retrospective single-center analysis we showed that Y-stent assisted coiling with braided stents is a safe and feasible technique. Moreover, it has a high immediate occlusion rate and very good long-term stability.

The PHASES score: To treat or not to treat? Retrospective evaluation of the risk of rupture of intracranial aneurysms in patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The PHASES score was formulated to predict the 5-year risk of rupture for intracranial aneurysms. We retrospectively analyzed all patients treated in our institution for aneurysmal SAH and applied the PHASES score to estimate the probable predicted risk of bleeding in this group of patients. METHODS: Between February 2015 and August 2018, all patients with aneurysmal SAH were retrospectively analyzed and the PHASES score was applied. A total of 155 patients were included with a mean age of 53.8years, including 60 males and 95 females. RESULTS: Of our patients 110 (70.9%) had a PHASES score of below or equal to 5, with a hemorrhagic risk of up to 1.3% over 5years. If we analyze the patients with a risk of below 2% this figure increases to 122 patients (78.7%). Of these 99.3% were European and 0.6% were Japanese (1 patient). In 86 patients (55.4%), the aneurysm was smaller than 5mm and in 10 patients (6.4%) the aneurysm was located in the posterior circulation. CONCLUSION: Of our patients 78.7% had less than a 2% 5-year rupture risk based on their PHASES score, highlighting the discrepancy of the rupture risk calculated with the PHASES score when hypothetically applied to this group of patients. In the hypothetical scenario that our patients had unruptured aneurysms, our retrospective analysis shows that the PHASES score may only provide a weak tool for clinicians to use in the decision-making process as to whether or not to treat these aneurysms.

Clinical and genetic findings in children with central nervous system arteriovenous fistulas.

OBJECTIVE: To assess the spectrum of genetic anomalies in a cohort of children presenting at least one cerebral or spinal pial arteriovenous fistula (AVF), and to describe their clinical characteristics. METHODS: From 1988 to 2016, all consecutive patients with at least one cerebral or spinal pial AVF were screened for genetic disease. All patients aged <18 years were included. Symptoms associated with AVF were recorded: heart failure, neurological deficit/seizure, and hemorrhage. The outcome was assessed using the modified Rankin Scale and school performance in children with cerebral AVF and the American Spinal Injury Association impairment scale in children with spinal AVF. RESULTS: Forty-three children were included. Twenty-five children were male and 18 were female. A germline mutation was identified in 23 probands (53.5 ± 14.9%): 8 in ENG (34.8 ± 14.2%), 1 in ACVRL1 (4.3 ± 6%) leading to a diagnosis of HHT, and 14 in RASA1 (60.9 ± 14.4%) leading to a diagnosis of capillary malformation/arteriovenous malformation type 1. No EphB4 gene mutation was identified. HHT patients presented a significantly lower rate of heart failure at diagnosis (p = 0.047). A trend toward an increased bleeding rate at presentation was observed in HHT (p = 0.069) and an increased rate of giant venous pouch in children in whom no mutation was identified (p = 0.097). Finally, an association with RASA1 mutation was observed in children with associated skin capillary hemangioma (p < 0001). INTERPRETATION: These results highlight the importance of genetic testing in this setting in view of the high frequency of gene mutations in pediatric cerebrospinal AVFs, and show the predominance of RASA1 over HHT mutations. Ann Neurol 2017;82:972-980.

A computational fluid dynamics (CFD) study of WEB-treated aneurysms: Can CFD predict WEB "compression" during follow-up?

BACKGROUND: Recent reports have revealed a worsening of aneurysm occlusion between WEB treatment baseline and angiographic follow-up due to "compression" of the device. OBJECTIVE: We utilized computational fluid dynamics (CFD) in order to determine whether the underlying mechanism of this worsening is flow related. METHODS: We included data from all consecutive patients treated in our institution with a WEB for unruptured aneurysms located either at the middle cerebral artery or basilar tip. The CFD study was performed using pre-operative 3D rotational angiography. From digital subtraction follow-up angiographies patients were dichotomized into two groups: one with WEB "compression" and one without. We performed statistical analyses to determine a potential correlation between WEB compression and CFD inflow ratio. RESULTS: Between July 2012 and June 2015, a total of 22 unruptured middle cerebral artery or basilar tip aneurysms were treated with a WEB device in our department. Three patients were excluded from the analysis and the mean follow-up period was 17months. Eleven WEBs presented "compression" during follow-up. Interestingly, device "compression" was statistically correlated to the CFD inflow ratio (P=0.018), although not to aneurysm volume, aspect ratio or neck size. CONCLUSION: The mechanisms underlying the worsening of aneurysm occlusion in WEB-treated patients due to device compression are most likely complex as well as multifactorial. However, it is apparent from our pilot study that a high arterial inflow is, at least, partially involved. Further theoretical and animal research studies are needed to increase our understanding of this phenomenon.

Assessment of implant position after total knee arthroplasty by dual-energy computed tomography.

BACKGROUND: Correct alignment of prosthetic components is the most important factor for the success of total knee arthroplasty (TKA). Dual-energy computed tomography (DECT) may be a reliable method in determining implant position after TKA. PURPOSE: To evaluate the accuracy and reproducibility of DECT in determining implant position after TKA. MATERIAL AND METHODS: Institutional review board approval was obtained. Forty-five patients (age 75.2 ± 6.4 years) prospectively underwent TKA at our institution between May and December 2012. DECT was performed 1 year after surgery, using an alignment similar to a standing position and generating images at an extrapolated energy of 120 kVp, in order to reduce metal artifacts. Implant position was evaluated by two independent readers. Intra- and inter-observer agreements were calculated. DECT measurements on implant position were compared with the preoperative planning based on radiographs. Additional clinical and DECT findings were taken into account. RESULTS: Metal artifact reduction was judged satisfactory in all cases. Regarding implant position assessed with DECT, good to excellent intra-observer (k: 0.74-0.87 and k: 0.75-0.88, respectively), and inter-observer agreement (k: 0.72-0.82) were found. In the comparison with preoperative planning, the widest limits of agreement were within 3.9° for the sagittal orientation of tibial component. A single patient with postoperative knee pain and stiffness had periprosthetic osteopenia, quadriceps femoris tendon calcifications, articular effusion, and excessive intrarotation of the femoral component. CONCLUSION: DECT is an accurate and reproducible tool for determining implant position after TKA.

Oxidative stress and antioxidant responses to increasing concentrations of trivalent chromium in the Andean crop species Chenopodium quinoa Willd.

Quinoa (Chenopodium quinoa Willd), an ancient Andean seed crop, exhibits exceptional nutritional properties and resistance to abiotic stress. The species' tolerance to heavy metals has, however, not yet been investigated nor its ability to take up and translocate chromium (Cr). This study aimed to investigate the metabolic adjustments occurring upon exposure of quinoa to several concentrations (0.01-5mM) of CrCl3. Young hydroponically grown plants were used to evaluate Cr uptake, growth, oxidative stress, and other biochemical parameters three and/or seven days after treatment. Leaves accumulated the lowest amounts of Cr, while roots and stems accumulated the most at low and at high metal concentrations, respectively. Fresh weight and photosynthetic pigments were reduced only by the higher Cr(III) doses. Substantially increased lipid peroxidation, hydrogen peroxide, and proline levels were observed only with 5mM Cr(III). Except for a significant decrease at day 7 with 5mM Cr(III), total polyphenols and flavonoids maintained control levels in Cr(III)-treated plants, whereas antioxidant activity increased in a dose-dependent manner. Maximum polyamine accumulation was observed in 1mM CrCl3-treated plants. Even though α- and γ-tocopherols also showed enhanced levels only with the 1mM concentration, tyrosine aminotransferase (TAT, EC 2.6.1.5) activity increased under Cr(III) treatment in a dose- and time-dependent manner. Taken together, results suggest that polyamines, tocopherols, and TAT activity could contribute to tolerance to 1mM Cr(III), but not to the highest concentration that, instead, generated oxidative stress.

Deep pelvic endometriosis: don't forget round ligaments. Review of anatomy, clinical characteristics, and MR imaging features.

Deep infiltrating endometriosis is an important gynecologic disease that may develop during the reproductive years and is responsible for severe pelvic pain. Deep pelvic endometriosis can affect the retrocervical region, uterosacral ligament, rectum, rectovaginal septum, vagina, urinary tract, and other extraperitoneal pelvic sites. Surgery remains the best therapeutic treatment for affected patients and an accurate preoperative evaluation of the extension of endometriotic lesions is essential for a successful outcome. However, many atypical locations for deep pelvic endometriosis exist although still lesser known to both gynecologists and radiologists such as endometriosis of the round ligaments of the uterus (RLUs). In this article, we review embryology and anatomy of the RLUs as well clinical characteristics associated with these endometriotic locations. In addition, we describe magnetic resonance (MR) imaging protocol, normal MR imaging appearances of the RLUs and the most common abnormal findings of endometriotic involvement of these ligaments at MR imaging. Radiologists should always keep in mind the RLUs as a possible site of deep pelvic endometriosis localization and should not forget to carefully look for them on MR images.

Can Repetitive Transcranial Magnetic Stimulation (rTMS) Promote Neurogenesis and Axonogenesis in Subacute Human Ischemic Stroke?

BACKGROUND: Ischemic stroke may trigger neuroplastic changes via proliferation, migration towards the lesion, and differentiation of neuroprogenitor cells into mature neurons. Repetitive Transcranial Magnetic Stimulation (rTMS) may promote brain plasticity. This study aimed to assess rTMS's effect on post-stroke endogenous neuroplasticity by dosing plasma miRs 17~92, Netrin-1, Sema3A, and BDNF. METHODS: In this case-controlled study, we randomized 19 ischemic stroke patients within five days from symptoms onset (T0) to neuronavigated-rTMS or sham stimulation. Stimulation was applied on the stroke hemisphere daily between the 7th and 14th day from stroke onset. Blood samples were collected at T0, before the first rTMS section (T7), and at the end of the last rTMS session (T14). Five healthy controls were also enrolled in this study. RESULTS: Of 19 patients, 10 received rTMS and 9 sham stimulation. Compared with the sham group, in the rTMS group, plasma levels of miRs17~92 and Ntn-1 significantly increased whereas Sema3A levels tended to decrease. In multivariate linear regression analyses, rTMS was independently related to Ntn-1 and miR-25 levels at T14. CONCLUSIONS: We found an association between rTMS and neurogenesis/axonogenesis biomarker enhancement. Our preliminary data suggest that rTMS may positively interfere with natural endogenous plasticity phenomena of the post-ischemic human brain.

Lidocaine for headache prevention during chronic subdural hematoma embolization.

BACKGROUND: Middle meningeal artery embolization (MMAE) for the management of chronic subdural hematomas (CSDH) with ethylene vinyl alcohol (EVOH) causes an evident patient discomfort due to meningeal nociceptors stimulation. The aim of this study was to assess safety and efficacy of intra-arterial lidocaine (IAL) before MMAE of CSDH with EVOH. METHODS: We analyzed all consecutive patients with bilateral CSDH undergoing MMAE with EVOH. We used a monolateral IAL injection, with casual allocation. We assessed the headache felt by patients during embolization with the visual analog scale (VAS) and compared scores obtained after embolization of both sides. We followed the STROBE guidelines for case-control studies. Paired t-test and χ2 test were used to compare the distribution of variables in IAL vs control group. RESULTS: Between September 2021 and March 2023, 32 patients underwent bilateral MMAE with EVOH for a CSDH. Lidocaine treatment resulted in a substantially lower VAS score compared to the control group (median 3 vs 7, p < 0.001), with no substantial side effect. Compliance also benefited from lidocaine administration. CONCLUSIONS: In patients with CSDH undergoing MMAE, IAL seems to reduce pain sensation associated with EVOH injection and to increase patients' compliance during treatment.

Predictors for hemorrhagic transformation and cerebral edema in stroke patients with first-pass complete recanalization.

BACKGROUND: Predictors of radiological complications attributable to reperfusion injury remain unknown when baseline setting is optimal for endovascular treatment and procedural setting is the best in stroke patients with large vessel occlusion (LVO). AIMS: To identify clinical and radiological/procedural predictors for hemorrhagic transformation (HT) and cerebral edema (CED) at 24 hr in patients obtaining complete recanalization in one pass of thrombectomy for ischemic stroke ⩽ 6 h from symptom onset with intra-cranial anterior circulation LVO and ASPECTS ⩾ 6. METHODS: We conducted a cohort study on prospectively collected data from 1400 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke. RESULTS: HT was reported in 248 (18%) patients and early CED was reported in 260 (19.2%) patients. In the logistic regression model including predictors from a first model with clinical variables and from a second model with radiological/procedural variables, diabetes mellitus (odds ratio (OR) = 1.832, 95% confidence interval (CI) = 1.201-2.795), higher National Institutes of Health Stroke Scale (NIHSS) (OR = 1.076, 95% CI = 1.044-1.110), lower Alberta Stroke Program Early CT (ASPECTS) (OR = 0.815, 95% CI = 0.694-0.957), and longer onset-to-groin time (OR = 1.005, 95% CI = 1.002-1.007) were predictors of HT, whereas general anesthesia was inversely associated with HT (OR = 0.540, 95% CI = 0.355-0.820). Higher NIHSS (OR = 1.049, 95% CI = 1.021-1.077), lower ASPECTS (OR = 0.700, 95% CI = 0.613-0.801), intravenous thrombolysis (OR = 1.464, 95% CI = 1.061-2.020), longer onset-to-groin time (OR = 1.002, 95% CI = 1.001-1.005), and longer procedure time (OR = 1.009, 95% CI = 1.004-1.015) were predictors of early CED. After repeating a fourth logistic regression model including also good collaterals, the same variables remained predictors for HT and/or early CED, except diabetes mellitus and thrombolysis, while good collaterals were inversely associated with early CED (OR = 0.385, 95% CI = 0.248-0.599). CONCLUSIONS: Higher NIHSS, lower ASPECTS, and longer onset-to-groin time were predictors for both HT and early CED. General anesthesia and good collaterals were inversely associated with HT and early CED, respectively. Longer procedure time was predictor of early CED.

The association of transradial access and transfemoral access with procedural outcomes in acute ischemic stroke patients receiving endovascular thrombectomy: A meta-analysis.

OBJECTIVE: There is an ongoing debate regarding the benefits of using transradial access (TRA) over transfemoral access (TFA) in endovascular therapies including endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) patients. This study sought to investigate the association of TRA and TFA with procedural success, access-site complications, first-pass reperfusion (FPR), puncture-to-recanalisation (PTR) time and hemorrhagic transformation (HT) by performing a meta-analysis. MATERIALS AND METHODS: PubMed, EMBASE and Scopus were searched. Studies with patients aged ≥ 18 years and head-to-head TRA vs TFA comparisons were included. Random-effects modeling was performed to obtain summary effects and forest plots were plotted to study the association of TFA with access site complications, FPR, HT, PTR time and procedural success. RESULTS: Six studies encompassing 945 patients (347 TRA and 598 TFA) were included in the meta-analysis. Meta-analysis revealed that in AIS patients receiving EVT, TRA was significantly associated with a decreased risk of access-site complications (RR 0.17, 95% CI 0.05 0.54; p = 0.003, z = -2.957) and HT (RR 0.07, 95% CI 0.02 0.27; p < 0.0001, z = -3.8841). However, TRA was not significantly associated with procedural success (RR 0.96, 95% CI 0.90 1.01; p = 0.141, z = -1.473), FPR (RR 0.91, 95% CI 0.79 1.05; p = 0.194, z = -1.299) and PTR time (SMD -0.14, 95% CI -0.42 -0.14; p = 0.323, z = -0.989). CONCLUSION: Our meta-analysis demonstrated that TRA is a safe alternative to TFA, in AIS patients receiving EVT, with significantly decreased access-site complications and HT with TRA, albeit with comparable procedural success, FPR and PTR time to TFA. DATA AVAILABILITY STATEMENT: The original contributions presented in the study are included in the article/Supplementary information, further inquiries can be directed to the corresponding author.

Evidence of SARS-CoV-2 spike protein on retrieved thrombi from COVID-19 patients.

The pathophysiology of COVID-19-associated coagulopathy is complex and not fully understood. SARS-CoV-2 spike protein (SP) may activate platelets and interact with fibrin(ogen). We aimed to investigate whether isolated SP can be present in clots retrieved in COVID-19 patients with acute ischemic stroke (by mechanical thrombectomy) and myocardial infarction. In this pilot study, we could detect SP, but not nucleocapsid protein, on platelets of COVID-19 patients' thrombi. In addition, in all three COVID-19 thrombi analyzed for molecular biology, no SARS-CoV-2 RNA could be detected by real-time polymerase chain reaction. These data could support the hypothesis that free SP, besides the whole virus, may be the trigger of platelet activation and clot formation in COVID-19.

SARS-CoV-2 infection predicts larger infarct volume in patients with acute ischemic stroke.

Background and purpose: Acute ischemic stroke (AIS) is a fearful complication of Coronavirus Disease-2019 (COVID-19). Aims of this study were to compare clinical/radiological characteristics, endothelial and coagulation dysfunction between acute ischemic stroke (AIS) patients with and without COVID-19 and to investigate if and how the SARS-CoV-2 spike protein (SP) was implicated in triggering platelet activation. Methods: We enrolled AIS patients with COVID-19 within 12 h from onset and compared them with an age- and sex-matched cohort of AIS controls without COVID-19. Neuroimaging studies were performed within 24 h. Blood samples were collected in a subset of 10 patients. Results: Of 39 AIS patients, 22 had COVID-19 and 17 did not. Admission levels of Factor VIII and von Willebrand factor antigen were significantly higher in COVID-19 patients and positively correlated with the infarct volume. In multivariate linear regression analyses, COVID-19 was an independent predictor of infarct volume (B 20.318, Beta 0.576, 95%CI 6.077-34.559; p = 0.011). SP was found in serum of 2 of the 10 examined COVID-19 patients. Platelets from healthy donors showed a similar degree of procoagulant activation induced by COVID-19 and non-COVID-19 patients' sera. The anti-SP and anti-FcγRIIA blocking antibodies had no effect in modulating platelet activity in both groups. Conclusions: SARS-CoV-2 infection seems to play a major role in endothelium activation and infarct volume extension during AIS.