ROTEM and von Willebrand Factor in COVID patients presenting with acute ischemic stroke: A case series: ROTEM and von Willebrand Factor in COVID-19 Related Stroke.

OBJECTIVES: SARS-CoV-2 (COVID) induces systemic thrombotic complications including acute ischemic stroke. In this case series, we report markers of inflammation, coagulation factors including von Willebrand factor antigen, and rotational thromboelastometry (ROTEM) data. MATERIALS AND METHODS: Retrospective case series of COVID patients seen at a single comprehensive stroke center between 2020-2022. For patients undergoing mechanical thrombectomy (MT), ROTEM data was collected during the procedure and analyzed on ROTEM delta system. RESULTS: Fifteen patients (33.3% female) median age 65-years-old presented with COVID and acute ischemic stroke. Thirteen had LVO. The mean NIHSS was 15 (range 0-35) on admission and 18 (0-42) at discharge. Most were cryptogenic (N=7, 46.7%), followed by cardioembolic (N=6, 40%) and large artery-to-artery embolization (N=2, 13.3%). mRS was < 3 in 8 (53%) patients at discharge. None of the patients were on anticoagulation, and five were on antiplatelet therapy pre-hospitalization. Seven received thrombolytics with alteplase (tPA), and 10 had MT. Baseline platelet count was 102 K/uL (range 102-291 K/uL). vWF was measured in 12 patients, all elevated, with seven having levels >400 (180%). ROTEM data was collected in six patients. Three who received tPA had abnormal EXTEM and FIBTEM data (CT extem > 85secs, A10 EXTEM < 45mm, and A10 FIBTEM < 10mm). Notably, INTEM (CT INTEM >208secs) was abnormal in five of the six patients, two of whom did not receive tPA. CONCLUSIONS: Elevated vWF antigen levels with abnormal ROTEM data suggests that COVID induces changes in the clotting cascade. More robust research is needed to investigate these findings. Thrombolytics, MT, and antiplatelet agents should be utilized to treat COVID-related ischemic stroke based on current clinical guidelines.

Decompressive craniectomy in symptomatic intracerebral hemorrhage after ischemic stroke: a multicenter retrospective cohort study.

OBJECTIVE: Symptomatic intracerebral hemorrhage (sICH) after stroke is a devastating neurological complication. Current guidelines support a "possible benefit" of decompressive craniectomy (DC) for large supratentorial sICH with significant mass effect. METHODS: The authors conducted a retrospective study of 8 comprehensive stroke centers. They included all patients who sustained an sICH after acute ischemic stroke (AIS), as defined by the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST), from January 2016 to December 2020. They compared patients who underwent DC to those who were treated with standard medical treatment to measure functional outcome at 90 days, primarily as defined by the modified Rankin Scale (mRS) and secondarily by the Glasgow Outcome Scale-Extended (GOS-E). RESULTS: Eighty-five patients were identified, 26 of whom (30.5%) underwent DC. Patients who underwent DC were younger (58 years [DC] vs 76 years [no DC], p < 0.001). No patient with a previous history of cancer underwent DC (n = 14, p = 0.004). Twenty-five patients (96.2%) in the DC group underwent thrombectomy versus 54 (91.5%) in the non-DC group (p = 0.443). Patients who underwent DC had a longer ICU stay (median [IQR] 240 [38-408] hours vs 24 [5-96] hours in non-DC patients, p = 0.002). At 90 days, 3 patients (4.1%) had obtained an mRS score of 0-2 and 10 patients (11.7%) an mRS score of 0-3. Patients who had improved functional outcome were younger (mRS score, OR 1.06, 95% CI 1.01-1.10, p = 0.012). Patients with a history of cancer had worse 90-day mRS scores (OR 8.49, 95% CI 1.54-159, p = 0.046). The rate of in-hospital mortality or discharge to hospice was significantly higher in the non-DC cohort (10 [38.5%] patients in the DC cohort vs 38 [64.4%] in the non-DC cohort, p = 0.026). Ninety days later, patients who underwent DC were more likely to have improved outcome (mRS mean rank 30.0 vs 40.0, p = 0.027). In multivariable analysis, history of cancer (OR 12.2, 95% CI 1.26-118, p = 0.031) and older age (OR 1.07, 95% CI 1.02-1.13, p = 0.011) increased the odds of worse mRS outcomes while DC did not (OR 1.34, 95% CI 0.357-5.03, p = 0.665). CONCLUSIONS: DC after sICH did not improve functional outcome at 90 days according to multivariable analysis, although younger age and absence of previous cancer history were associated with improved outcomes.

Endovascular treatment to improve outcomes for medium vessel occlusions: The ESCAPE-MeVO trial.

RATIONALE: Clinical outcomes in acute ischemic stroke due to medium vessel occlusion (MeVO) are often poor when treated with best medical management. Data from non-randomized studies suggest that endovascular treatment (EVT) may improve outcomes in MeVO stroke, but randomized data on potential benefits and risks are hitherto lacking. Thus, there is insufficient evidence to guide EVT decision-making in MeVO stroke. AIMS: The primary aim of the ESCAPE-MeVO trial is to demonstrate that acute, rapid EVT in patients with acute ischemic stroke due to MeVO results in better clinical outcomes compared to best medical management. Secondary outcomes are to demonstrate the safety of EVT, its impact on self-reported health-related quality of life, and cost-effectiveness. SAMPLE SIZE ESTIMATES: Based on previously published data, we estimate a sample size of 500 subjects to achieve a power of 85% with a two-sided alpha of 0.05. To account for potential loss to follow-up, 530 subjects will be recruited. METHODS AND DESIGN: ESCAPE-MeVO is a multicenter, prospective, randomized, open-label study with blinded endpoint evaluation (PROBE design), clinicaltrials.gov: NCT05151172. Subjects with acute ischemic stroke due to MeVO meeting the trial eligibility criteria will be allocated in a 1:1 ratio to best medical care plus EVT versus best medical care only. Patients will be screened only at comprehensive stroke centers to determine if they are eligible for the trial, regardless of whether they were previously treated at a primary care center. Key eligibility criteria are (1) acute ischemic stroke due to MeVO that is clinically and technically eligible for EVT, (2) last-known well within the last 12 h, (3) National Institutes of Health Stroke Scale > 5 or 3-5 with disabling deficit, (4) high likelihood of salvageable tissue on non-invasive neuroimaging. STUDY OUTCOMES: The primary outcome is the modified Rankin scale 90 days after randomization (shift analysis), whereby modified Rankin Score 5 and 6 will be collapsed into one category. Secondary outcomes include dichotomizations of the modified Rankin Score at 90 days, 24 h National Institutes of Health Stroke Score, difference between 24 h and baseline National Institutes of Health Stroke Score, mortality at 90 days, health-related quality of life (EQ-5D-5 L), Lawton scale of instrumental activities of daily living score, reperfusion quality (MeVO expanded Thrombolysis in Cerebral Infarction Score) and infarct volume at 24 h, and cost-effectiveness of endovascular recanalization. Safety outcomes include symptomatic and asymptomatic intracranial hemorrhage and procedural complications. DISCUSSION: The ESCAPE-MeVO trial will demonstrate the effect of endovascular thrombectomy in addition to best medical management vis-à-vis best medical management in patients with acute ischemic stroke due to MeVO and provide data for evidence-based treatment decision-making in acute MeVO stroke. DATA ACCESS STATEMENT: The raw data discussed in this mansucript will be made available by the corresponding author upon reasonable request.

The Brain Injury Guidelines (BIG) and emergency department observation and admission rates: A retrospective cohort study.

BACKGROUND: Emergency Department (ED) Observation Units (OU) can provide safe, effective care for low risk patients with intracranial hemorrhages. We compared current ED OU use for patients with subdural hematomas (SDH) to the validated Brain Injury Guidelines (BIG) to evaluate the potential impact of implementing this risk stratification tool. METHODS: Retrospective cohort of patients ≥18 years old with SDH of any cause from 2014 to 2020 to evaluate for potential missed OU cases. Missed OU cases were defined as patients with an initial Glasgow Coma Score (GCS) of 15 with hospital length of stays (LOS) <2 days, who did not meet the composite outcome and were not cared for in the OU or discharged from the ED. Composite outcome included in-hospital death or transition to hospice care, neurosurgical intervention, GCS decline, and worsening SDH size. Secondary outcomes were whether application of BIG would increase ED OU use or reduce CT use. RESULTS: 264 patients met inclusion criteria over 5.3 year study timeframe. Mean age was 61 years (range 19-93) and 61.4% were male. SDH were traumatic in 76.9% and 60.2% of the cohort had additional injuries. The admission rate was 81.4% (n = 215). Fourteen (6.5%) missed OU cases were identified (2.6/year). Retrospective application of BIG resulted in 82.6% (n = 217) at BIG 3, 10.2% (n = 27) at BIG 2 and 7.6% (n = 20) at BIG 1. Application of BIG would not have decreased admission rates (82.6% BIG 3) and BIG 1 and 2 admissions were often for medical co-morbidities. The composite outcome was met in 50% of BIG 3, 22% of BIG 2, and no BIG 1 patients. CONCLUSION: In a level 1 trauma center with an established observation unit, current clinical care processes missed very few patients who could be discharged or placed in ED OU for SDH. Hospital admissions in BIG 1/2 were driven by co-morbidities and/or injuries, limiting applicability of BIG to this population.

Diffusion-Weighted Imaging Fluid-Attenuated Inversion Recovery Mismatch on Portable, Low-Field Magnetic Resonance Imaging Among Acute Stroke Patients.

OBJECTIVE: For stroke patients with unknown time of onset, mismatch between diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) can guide thrombolytic intervention. However, access to MRI for hyperacute stroke is limited. Here, we sought to evaluate whether a portable, low-field (LF)-MRI scanner can identify DWI-FLAIR mismatch in acute ischemic stroke. METHODS: Eligible patients with a diagnosis of acute ischemic stroke underwent LF-MRI acquisition on a 0.064-T scanner within 24 h of last known well. Qualitative and quantitative metrics were evaluated. Two trained assessors determined the visibility of stroke lesions on LF-FLAIR. An image coregistration pipeline was developed, and the LF-FLAIR signal intensity ratio (SIR) was derived. RESULTS: The study included 71 patients aged 71 ± 14 years and a National Institutes of Health Stroke Scale of 6 (interquartile range 3-14). The interobserver agreement for identifying visible FLAIR hyperintensities was high (κ = 0.85, 95% CI 0.70-0.99). Visual DWI-FLAIR mismatch had a 60% sensitivity and 82% specificity for stroke patients <4.5 h, with a negative predictive value of 93%. LF-FLAIR SIR had a mean value of 1.18 ± 0.18 <4.5 h, 1.24 ± 0.39 4.5-6 h, and 1.40 ± 0.23 >6 h of stroke onset. The optimal cut-point for LF-FLAIR SIR was 1.15, with 85% sensitivity and 70% specificity. A cut-point of 6.6 h was established for a FLAIR SIR <1.15, with an 89% sensitivity and 62% specificity. INTERPRETATION: A 0.064-T portable LF-MRI can identify DWI-FLAIR mismatch among patients with acute ischemic stroke. Future research is needed to prospectively validate thresholds and evaluate a role of LF-MRI in guiding thrombolysis among stroke patients with uncertain time of onset. ANN NEUROL 2024;96:321-331.

Assessment of the safety and efficacy of the Zoom 45 and 55 reperfusion catheters for medium and distal mechanical thrombectomies: A multi-institutional study.

INTRODUCTION: The Zoom aspiration catheters harbor novel dimensions and construction to enhance trackability and deliverability. In addition, a beveled tip may improve thrombus interaction and aspiration force for a set inner diameter. This study evaluates their utility in medium and distal vessel occlusions. OBJECTIVE: To evaluate the safety and efficacy of Zoom 45 and 55 aspiration catheters in medium and distal vessel thrombectomy. METHODS: Patients treated for distal vessel occlusions via mechanical thrombectomy utilizing either the Zoom 45/55 catheter or a historical control catheter between 2021-2022 at two institutions were included in this study. Medium and distal occlusions were defined as any anterior or posterior cerebral artery branch as well as the M2-4 segment of the middle cerebral artery (MCA). Preprocedural, procedural, and postprocedural variables were obtained. RESULTS: Thirty-eight patients underwent thrombectomy with Zoom 45 or 55 catheters; four had multiple occluded vessels. Occlusion location included the M2 in 32 cases, M3-4 in 7 cases, A2 in 2 cases and P2 in 1 case. The mean number of passes per occlusion was 1.6 and overall successful reperfusion (TICI 2b or greater) was achieved in 84 % of cases. There were no symptomatic procedure-related complications such as perforation or post-procedural symptomatic ICH. Modified Rankin scores rates of 0-2, 3-5, and 6 at three months post-procedure were 35.7 %, 21.4 %, and 42.9 %, respectively. CONCLUSIONS: The Zoom beveled tip aspiration catheters are safe and effective for more challenging medium and distal vessel occlusions.

Preoperative prescription opioid use as an independent predictor of 90-day mortality and adverse events in craniotomy and craniectomy patients.

OBJECTIVE: A growing body of literature suggests that preoperative opioid exposure is an independent predictor of poor outcomes in surgical patients. No outcomes data exist on preoperative opioid use and craniotomies/craniectomies. The objective of this study was to determine the impact of preoperative opioid use on 90-day adverse events after craniotomy or craniectomy. METHODS: A single-center retrospective cohort study of 2445 patients undergoing a craniotomy/craniectomy between January 1, 2013, and October 1, 2018, was conducted. Baseline demographics, pre- and postoperative opioid use (morphine milligram equivalents [MMEs]), and surgical metrics were recorded. Patients were categorized based on whether they took prescription opioids preoperatively, defined as within 1 month of surgery, or were opioid naive. The outcomes were mortality and adverse events 90 days after craniotomy/craniectomy. RESULTS: Overall, 26.6% of patients composed the preoperative opioid group. The median daily MME intake among this group was 34.6 (IQR 14.1-90) MMEs. Lower employment rates (p < 0.001), uninsured status (p = 0.016), and intravenous drug use (p = 0.006) were associated with preoperative opioid use. Preoperative opioid use was associated with increased venous thromboembolism (p = 0.001), acute kidney injury (p = 0.002), acute respiratory failure (p < 0.001), myocardial infarction (p = 0.002), delirium (p < 0.001), and infection (p < 0.001). Preoperative opioid use was an independent predictor of overall 90-day adverse events (OR 1.643, 95% CI 1.289-2.095; p < 0.001) and 90-day mortality (OR 1.690, 95% CI 1.254-2.277; p < 0.001). CONCLUSIONS: Preoperative opioid use was independently associated with 90-day postoperative adverse events and mortality. Opioid use increases vulnerability in craniotomy/craniectomy patients and necessitates close monitoring to improve outcomes.

Patients' perceptions on outcomes after mechanical thrombectomy in acute ischemic stroke.

BACKGROUND: The modified Rankin Scale (mRS) is a clinician-reported scale that measures the degree of disability in patients who suffered a stroke. Patients' perception of a meaningful recovery from severe stroke, expected value of a stroke intervention, and the effect of disparities are largely unknown. METHODS: We conducted a survey of patients, their family members, and accompanying visitors to understand their personal preferences and expectations for acute strokes potentially eligible for acute endovascular intervention using a hypothetical scenario of a severe stroke in a standardized questionnaire. RESULTS: Of 164 survey respondents, 65 (39.6%) were the patient involved, 93 (56.7%) were a family member, and six (3.7%) were accompanied visitors (friends, other). Minimally acceptable disability after a stroke intervention was considered as mRS 2 by 42 respondents (25.6%), as mRS 3 by 79 (48.2%), and as mRS 4 by 43 (26.2%) respondents. Race was associated with different views on this question (p < 0.001; Hispanic and Black patients being more likely to accept disability than Caucasian and Asian patients), while sex (p = 0.333) and age (p = 0.560) were not. Sixty-three respondents (38.4%) viewed minimally acceptable probability of improvement with an intervention as over 50%, 57 (34.8%) as 10-50%, and 44 (26.8%) as less than 10%. CONCLUSIONS: A wide range of acceptable outcomes were reported regardless of gender or age. However, race was associated with different acceptable outcome. This is an important finding to demonstrate because of the persistent racial and ethnic disparities in the utilization of endovascular therapy for acute stroke in the United States.

Direct Versus Indirect Revascularization for Moyamoya: a Large Multicenter Study.

BACKGROUND: Moyamoya is a chronic occlusive cerebrovascular disease of unknown etiology causing neovascularization of the lenticulostriate collaterals at the base of the brain. Although revascularization surgery is the most effective treatment for moyamoya, there is still no consensus on the best surgical treatment modality as different studies provide different outcomes. OBJECTIVE: In this large case series, we compare the outcomes of direct (DR) and indirect revascularisation (IR) and compare our results to the literature in order to reflect on the best revascularization modality for moyamoya. METHODS: We conducted a multicenter retrospective study in accordance with the Strengthening the Reporting of Observational studies in Epidemiology guidelines of moyamoya affected hemispheres treated with DR and IR surgeries across 13 academic institutions predominantly in North America. All patients who underwent surgical revascularization of their moyamoya-affected hemispheres were included in the study. The primary outcome of the study was the rate of symptomatic strokes. RESULTS: The rates of symptomatic strokes across 515 disease-affected hemispheres were comparable between the two cohorts (11.6% in the DR cohort vs 9.6% in the IR cohort, OR 1.238 (95% CI 0.651 to 2.354), p=0.514). The rate of total perioperative strokes was slightly higher in the DR cohort (6.1% for DR vs 2.0% for IR, OR 3.129 (95% CI 0.991 to 9.875), p=0.052). The rate of total follow-up strokes was slightly higher in the IR cohort (8.1% vs 6.6%, OR 0.799 (95% CI 0.374 to 1.709) p=0.563). CONCLUSION: Since both modalities showed comparable rates of overall total strokes, both modalities of revascularization can be performed depending on the patient's risk assessment.

A canine thromboembolic model of anterior circulation large vessel occlusion stroke.

Purpose: To develop a large animal preclinical model of thromboembolic stroke with stable, protracted large vessel occlusion (LVO) utilizing an autologous clot. Materials and methods: A reproducible canine model of large vessel occlusion stroke was established by endovascular placement of an autologous clot into the middle cerebral artery (MCA) of six adult hounds and confirmed using digital subtraction angiography (DSA). Infarct volume and evidence of hemorrhage were determined by magnetic resonance imaging (MRI) 7 h after occlusion and Thrombolysis in Cerebral Infarction scale (TICI) was assessed before and after clot placement and at 1, 6, 7, and 9 h after middle cerebral artery occlusion (MCAO). Heart rate (HR) and blood pressure (BP) were monitored continuously and invasively through an arterial sheath throughout the procedures and complete blood count and blood gas analysis completed at time of sacrifice. Histopathological findings at time of sacrifice were used to confirm stroke volume and hemorrhage. Results: MCAO with resulting TICI 0 flow was observed in all six animals, verified by serial DSA, and lack of collateral flow persisted for 9 h after clot placement until time of sacrifice. The mean infarct volume was 47.0 ± 6.7% of the ipsilateral hemisphere and no events of spontaneous recanalization or clot autolysis were observed. Conclusion: We demonstrate a thromboembolic canine model of MCAO that is both feasible and results in consistent infarct volumes to generate a clinically relevant LVO. This model is important to evaluate treatment of LVO in acute ischemic stroke (AIS) outside the established 4.5 h recombinant tissue plasminogen activator (rTPA) therapeutic window utilizing a prolonged occlusive thrombus.

Neoadjuvant Arterial Embolization of Spine Metastases Associated With Improved Local Control in Patients Receiving Surgical Decompression and Stereotactic Body Radiotherapy.

BACKGROUND: Spine metastases often cause significant pain, instability, and/or neurological morbidity. Local control (LC) of spine metastases has been augmented with advances in systemic therapies, radiation, and surgical technique. Prior reports suggest an association between preoperative arterial embolization and improved LC and palliative pain control. OBJECTIVE: To further elucidate the role of neoadjuvant embolization on LC of spine metastases and the potential for improved pain control in patients receiving surgery and stereotactic body radiotherapy (SBRT). METHOD: A retrospective single-center review between 2012 and 2020 identified 117 patients with spinal metastases from various solid tumor malignancies managed with surgery and adjuvant SBRT with or without preoperative spinal arterial embolization. Demographic information, radiographic studies, treatment characteristics, Karnofsky Performance Score, Defensive Veterans Pain Rating Scale, and mean daily doses of analgesic medications were reviewed. LC was assessed using magnetic resonance imaging obtained at a median 3-month interval and defined as progression at the surgically treated vertebral level. RESULTS: Of 117 patients, 47 (40.2%) underwent preoperative embolization, followed by surgery and SBRT and 70 (59.8%) underwent surgery and SBRT alone. Within the embolization cohort, the median LC was 14.2 months compared with 6.3 months among the nonembolization cohort ( P = .0434). Receiver operating characteristic analysis suggests ≥82.5% embolization predicted significantly improved LC (area under the curve = 0.808; P < .0001). Defensive Veterans Pain Rating Scale mean and maximum scores significantly decreased immediately after embolization ( P < .001). CONCLUSION: Preoperative embolization was associated with improved LC and pain control suggesting a novel role for its use. Additional prospective study is warranted.

Rapid molecular imaging of active thrombi in vivo using aptamer-antidote probes.

Pathological blood clotting, or thrombosis, limits vital blood flow to organs; such deprivation can lead to catastrophic events including myocardial infarction, pulmonary embolism, and ischemic stroke. Prompt restoration of blood flow greatly improves outcomes. We explored whether aptamers could serve as molecular imaging probes to rapidly detect thrombi. An aptamer targeting thrombin, Tog25t, was found to rapidly localize to and visualize pre-existing clots in the femoral and jugular veins of mice using fluorescence imaging and, when circulating, was able to image clots as they form. Since free aptamer is quickly cleared from circulation, contrast is rapidly developed, allowing clot visualization within minutes. Moreover, administration of an antidote oligonucleotide further enhanced contrast development, causing the unbound aptamer to clear within 5min while impacting the clot-bound aptamer more slowly. These findings suggest that aptamers can serve as imaging agents for rapid detection of thrombi in acute care and perioperative settings.

Correlation of von Willebrand factor and platelets with acute ischemic stroke etiology and revascularization outcome: an immunohistochemical study.

BACKGROUND: Platelets and von Willebrand factor (vWF) are key components of acute ischemic stroke (AIS) emboli. We aimed to investigate the CD42b (platelets)/vWF expression, its association with stroke etiology and the impact these components may have on the clinical/procedural parameters. METHODS: CD42b/vWF immunostaining was performed on 288 emboli collected as part of the multicenter STRIP Registry. CD42b/VWF expression and distribution were evaluated. Student's t-test and χ2 test were performed as appropriate. RESULTS: The mean CD42b and VWF content in clots was 44.3% and 21.9%, respectively. There was a positive correlation between platelets and vWF (r=0.64, p<0.001**). We found a significantly higher vWF level in the other determined etiology (p=0.016*) and cryptogenic (p=0.049*) groups compared with cardioembolic etiology. No significant difference in CD42b content was found across the etiology subtypes. CD42b/vWF patterns were significantly associated with stroke etiology (p=0.006*). The peripheral pattern was predominant in atherosclerotic clots (36.4%) while the clustering (patchy) pattern was significantly associated with cardioembolic and cryptogenic origin (66.7% and 49.8%, respectively). The clots corresponding to other determined etiology showed mainly a diffuse pattern (28.1%). Two types of platelets were distinguished within the CD42b-positive clusters in all emboli: vWF-positive platelets were observed at the center, surrounded by vWF-negative platelets. Thrombolysis correlated with a high platelet content (p=0.03*). vWF-poor and peripheral CD42b/vWF pattern correlated with first pass effect (p=0.03* and p=0.04*, respectively). CONCLUSIONS: The vWF level and CD42b/vWF distribution pattern in emboli were correlated with AIS etiology and revascularization outcome. Platelet content was associated with response to thrombolysis.

Stroke and Neurogenesis: Bridging Clinical Observations to New Mechanistic Insights from Animal Models.

Stroke was the 2nd leading cause of death and a major cause of morbidity. Unfortunately, there are limited means to promote neurological recovery post-stroke, but research has unearthed potential targets for therapies to encourage post-stroke neurogenesis and neuroplasticity. The occurrence of neurogenesis in adult mammalian brains, including humans, was not widely accepted until the 1990s. Now, adult neurogenesis has been extensively studied in human and mouse neurogenic brain niches, of which the subventricular zone of the lateral ventricles and subgranular zone of the dentate gyrus are best studied. Numerous other niches are under investigation for neurogenic potential. This review offers a basic overview to stroke in the clinical setting, a focused summary of recent and foundational research literature on cortical neurogenesis and post-stroke brain plasticity, and insights regarding how the meninges and choroid plexus have emerged as key players in neurogenesis and neuroplasticity in the context of focal cerebral ischemia disrupting the anterior circulation. The choroid plexus and meninges are vital as they are integral sites for neuroimmune interactions, glymphatic perfusion, and niche signaling pertinent to neural stem cells and neurogenesis. Modulating neuroimmune interactions with a focus on astrocyte activity, potentially through manipulation of the choroid plexus and meningeal niches, may reduce the exacerbation of stroke by inflammatory mediators and create an environment conducive to neurorecovery. Furthermore, addressing impaired glymphatic perfusion after ischemic stroke likely supports a neurogenic environment by clearing out inflammatory mediators, neurotoxic metabolites, and other accumulated waste. The meninges and choroid plexus also contribute more directly to promoting neurogenesis: the meninges are thought to harbor neural stem cells and are a niche amenable to neural stem/progenitor cell migration. Additionally, the choroid plexus has secretory functions that directly influences stem cells through signaling mechanisms and growth factor actions. More research to better understand the functions of the meninges and choroid plexus may lead to novel approaches for stimulating neuronal recovery after ischemic stroke.

Dose-Dependent Von Willebrand Factor Inhibition by Aptamer BB-031 Correlates with Thrombolysis in a Microfluidic Model of Arterial Occlusion.

Von Willebrand Factor (VWF) plays a critical role in thrombus formation, stabilization, and propagation. Previous studies have demonstrated that targeted inhibition of VWF induces thrombolysis when administered in vivo in animal models of ischemic stroke. The study objective was to quantify dose-dependent inhibition of VWF-platelet function and its relationship with thrombolysis using BB-031, an aptamer that binds VWF and inhibits its function. VWF:Ac, VWF:RCo, T-TAS, and ristocetin-induced impedance aggregometry were used to assess BB-031-mediated inhibition of VWF. Reductions in original thrombus surface area and new deposition during administration of treatment were measured in a microfluidic model of arterial thrombolysis. Rotational thromboelastometry was used to assess changes in hemostasis. BB-031 induced maximal inhibition at the highest dose (3384 nM) in VWF:Ac, and demonstrated dose-dependent responses in all other assays. BB-031, but not vehicle, induced recanalization in the microfluidic model. Maximal lytic efficacy in the microfluidic model was seen at 1692 nM and not 3384 nM BB-031 when assessed by surface area. Minor changes in ROTEM parameters were seen at 3384 nM BB-031. Targeted VWF inhibition by BB-031 results in clinically measurable impairment of VWF function, and specifically VWF-GPIb function as measured by VWF:Ac. BB-031 also induced thrombolysis as measured in a microfluidic model of occlusion and reperfusion. Moderate correlation between inhibition and lysis was observed. Additional studies are required to further examine off-target effects of BB-031 at high doses, however, these are expected to be above the range of clinical targeted dosing.

Technical and clinical success after venous sinus stenting for treatment of idiopathic intracranial hypertension using a novel guide catheter for access: Case series and initial multi-center experience.

INTRODUCTION: Venous sinus stenting is a well established alternative to cerebrospinal fluid diversion for the treatment of idiopathic intracranial hypertension (IIH) with associated venous sinus stenosis. During this procedure, distal guide catheter placement within the venous sinuses may be desirable to facilitate stent delivery. We report our initial experience using the TracStar LDP™ (Imperative Care, Campbell, USA, 0.088-inch inner diameter) as the guide catheter for intracranial access during venous sinus stenting. METHODS: A multi-institutional retrospective chart review of a prospectively maintained IRB-approved database was performed. Consecutive patients who underwent venous sinus stenting from 1/1/2020-9/6/2021 for IIH were included. Patient characteristics, procedural details, TracStar distal reach, outcomes, and complications were collected and analyzed. RESULTS: Fifty-eight patients were included. The mean age was 33.8 years and 93.1% of patients were female. Visual changes prompted evaluation in 86.2% of patients. Stent placement was successful in all patients. The TracStar LDP catheter was advanced to the location of stent placement in 97.9% of cases in which it was attempted. The large 0.088-inch inner diameter lumen enabled compatibility with all desired stent sizes ranging from six to 10 millimeters. Gradient pressure across transverse sinus stenosis dropped from an average of 19.5 mmHg pre-procedure to 1.7 mmHg post-stent placement (p < 0.001). Clinical improvement was achieved in 87.9% (51/58) of patients. There were no catheter-related complications. CONCLUSION: The TracStar LDP is a safe and effective access platform for reaching treatment locations in patients who present with idiopathic intracranial hypertension and who are candidates for venous sinus stent placement.

International controlled study of revascularization and outcomes following COVID-positive mechanical thrombectomy.

BACKGROUND AND PURPOSE: Previous studies suggest that mechanisms and outcomes in patients with COVID-19-associated stroke differ from those in patients with non-COVID-19-associated strokes, but there is limited comparative evidence focusing on these populations. The aim of this study, therefore, was to determine if a significant association exists between COVID-19 status with revascularization and functional outcomes following thrombectomy for large vessel occlusion (LVO), after adjustment for potential confounding factors. METHODS: A cross-sectional, international multicenter retrospective study was conducted in consecutively admitted COVID-19 patients with concomitant acute LVO, compared to a control group without COVID-19. Data collected included age, gender, comorbidities, clinical characteristics, details of the involved vessels, procedural technique, and various outcomes. A multivariable-adjusted analysis was conducted. RESULTS: In this cohort of 697 patients with acute LVO, 302 had COVID-19 while 395 patients did not. There was a significant difference (p < 0.001) in the mean age (in years) and gender of patients, with younger patients and more males in the COVID-19 group. In terms of favorable revascularization (modified Thrombolysis in Cerebral Infarction [mTICI] grade 3), COVID-19 was associated with lower odds of complete revascularization (odds ratio 0.33, 95% confidence interval [CI] 0.23-0.48; p < 0.001), which persisted on multivariable modeling with adjustment for other predictors (adjusted odds ratio 0.30, 95% CI 0.12-0.77; p = 0.012). Moreover, endovascular complications, in-hospital mortality, and length of hospital stay were significantly higher among COVID-19 patients (p < 0.001). CONCLUSION: COVID-19 was an independent predictor of incomplete revascularization and poor functional outcome in patients with stroke due to LVO. Furthermore, COVID-19 patients with LVO were more often younger and had higher morbidity/mortality rates.