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A 5 mo old male Japanese chin was examined 1 mo following the sudden onset of pelvic limb weakness and ataxia immediately after microchip placement. Neurological examination revealed an ambulatory paraparesis, which was worse on the right side, with additional weakness noted in the right thoracic limb. Lesion localization was C6–T2 spinal cord segments, worse on the right. Radiographic imaging of the cervical spine revealed a microchip at the location of the C7–T1 intervertebral space. Computed tomography revealed a microchip within the spinal canal causing spinal cord compression at the level of the C7–T1 intervertebral disc space. Surgical removal of the microchip was performed, and the patient recovered well. A 6 wk follow-up neurologic examination showed persistent mild ataxia in the pelvic limbs. This case supports previously reported cases of permanent spinal cord damage caused by microchip placement. Surgical removal of the microchip resulted in the improvement of neurologic signs. Although extraction of the microchip did not resolve all neurologic deficits, surgery prevented further migration and possible damage to the spinal cord.

Background: Elevated blood pressure after endovascular thrombectomy (EVT) has been associated with an increased risk of hemorrhagic transformation and poor functional outcomes. However, the optimal hemodynamic management after EVT remains unknown, and the blood pressure course in the acute phase of ischemic stroke has not been well characterized. This study aimed to identify patient subgroups with distinct blood pressure trajectories after EVT and study their association with radiographic and functional outcomes. Methods: This multicenter retrospective cohort study included consecutive patients with anterior circulation large-vessel occlusion ischemic stroke who underwent EVT. Repeated time-stamped blood pressure data were recorded for the first 72 hours after thrombectomy. Latent variable mixture modeling was used to separate subjects into five groups with distinct postprocedural systolic blood pressure (SBP) trajectories. The primary outcome was functional status, measured on the modified Rankin Scale 90 days after stroke. Secondary outcomes included hemorrhagic transformation, symptomatic intracranial hemorrhage, and death. Results: Two thousand two hundred sixty-eight patients (mean age [±SD] 69±15, mean National Institutes of Health Stroke Scale 15±7) were included in the analysis. Five distinct SBP trajectories were observed: low (18%), moderate (37%), moderate-to-high (20%), high-to-moderate (18%), and high (6%). SBP trajectory group was independently associated with functional outcome at 90 days ( P P =0.0003 and adjusted odds ratio, 2.2 [95% CI, 1.5–3.2], P P =0.04). No significant association was found between trajectory group and hemorrhagic transformation. Conclusions: Patients with acute ischemic stroke demonstrate distinct SBP trajectories during the first 72 hours after EVT that have differing associations with functional outcome. These findings may help identify potential candidates for future blood pressure modulation trials.

In the USA, around 30% of 795,000 strokes per year are due to proximal large-vessel occlusion, and these are a major cause of death and disability. We review the most recent advances regarding treatment of ischemic stroke amenable to mechanical thrombectomy.In the last four years, clinical trial evidence has expanded the time window for successful endovascular treatment to 24 h. Current research is aimed at expanding patient selection to mild strokes, large ischemic cores and occlusions of smaller, more distal blood vessels. Further, we have developed understanding of how to manage blood pressure after thrombectomy and even had promising results for a neuroprotective agent in these patients. Thrombectomy has transformed the treatment of ischemic stroke due to large-vessel occlusion. Recent research has focused on expanding patient candidacy for endovascular treatment and improving medical management to support better neurologic outcomes.

Introduction: Few clinical features have been associated with delayed diagnosis of cerebral venous thrombosis with variable impact of delay on patient outcomes. We therefore sought to use the data from a recent, multicenter study ACTION-CVT (Anticoagulation in the Treatment of CVT) to identify factors associated with delayed CVT diagnosis and evaluate the effect of delay on functional outcome. Methods: All ACTION-CVT patients with available data on date of neurological symptom onset and date of CVT diagnosis were included. Delayed diagnosis of CVT was defined as diagnosis occurring in the fourth (final) quartile of days from symptom onset. We also report the proportion of patients who were discharged from hospital or ED within 3 months prior to index CVT admission for any neurological symptom without being diagnosed with CVT. The primary study outcome was an excellent functional outcome at 90 days defined as modified Rankin Scale (mRS) ≤1. Secondary outcome was partial or complete CVT recanalization on last available venous imaging. Chi-squared and Student’s t-tests were used to identify variables associated with delayed diagnosis. Logistic regression was used to identify independent predictors of delayed diagnosis in CVT as well as the association of delay with outcomes. Results: We included 935 CVT patients in our analysis. Median time from symptom onset to diagnosis was 4 days (IQR: 1-10). Delayed CVT diagnosis occurred in 212 (23%) patients (median time to diagnosis >10 days). Out of 212 patients with delayed CVT diagnosis, 64 (30.2%) patients were discharged from hospital/ED in the 3 months prior to their index CVT admission. Headache symptoms were a predictor of delayed diagnosis (OR: 2.36 [1.26-4.42]; p Conclusion: In a large, multicenter cohort we found that CVT patients presenting with headache were at increased risk of delayed diagnosis, however, delayed diagnosis was not associated with adverse outcomes. CVT diagnosis should be considered in patients presenting with a new headache.

Prevention of deployment-related injury is critical for readiness of US military working dogs (MWDs). This study evaluated deployment-related injuries to determine if they were potentially preventable and identify possible abatement strategies.Data were collected on 195 MWD injury events that occurred between 11 September 2001 and 31 December 2018. Injuries were reviewed by a panel of veterinarians and categorized into groups based on panel consensus. The panel also established which interventions could have been effective for mitigating injuries. Multipurpose canine (MPC) and conventional MWD injury event characteristics were compared to identify meaningful differences.Of the 195 injuries, 101 (52%) were classified as preventable or potentially preventable. Most (72%) of the potentially preventable injuries occurred in conventional MWDs, with penetrating injuries (64%) being the most common type of trauma. For the preventable/potentially preventable injuries, the most common preventative intervention identified was handler training (53%) followed by protective equipment (46%). There were differences between MPCs and conventional MWDs for injury prevention category, type of trauma, mechanism of injury, and preventative intervention (all p.001).The application of a preventable review process to MWD populations may be beneficial in identifying potentially preventable injuries and preventative intervention strategies.

The management of cerebral venous sinus thrombosis (CVT) is a common problem facing vascular neurologists. American Heart Association/American Stroke Association guidelines suggest the use of heparin followed by vitamin K antagonists (VKAs) for anticoagulation in CVT. In recent years, the evidence base has solidified for the use of non-vitamin K antagonist oral anticoagulants (NOACs) in lower extremity deep vein thrombosis. Because data supporting their use in CVT are limited, with the strongest evidence comprising one randomized controlled trial of dabigatran, we sought to review our experience with NOACs in the treatment of CVT at a tertiary care center to address efficacy and safety. We retrospectively reviewed charts of all patients with CVT treated with an NOAC at our tertiary care facility in the years 2011–2019. We collected data on demographics, risk factors for CVT, clinical features at presentation, imaging results, anticoagulation regimen, bleeding complications, and disability at follow-up. We compared disability at follow-up and major hemorrhagic events with age-matched and sex-matched controls treated with VKAs over the same time period and with historical controls. We identified 29 patients with CVT treated with an NOAC, 27 of whom had follow-up within our system. NOACs that were used for treatment included apixaban (20 patients), rivaroxaban (6 patients) and dabigatran (1 patient). NOAC use was associated with stabilization of a clot or partial recanalization in 55.6% of patients and complete recanalization in 14.8% at a median follow-up time of 6 months. The median modified Rankin Score (mRS) at follow-up was 0, with one death. Three patients (11.1%) had major bleeding complications, including two with symptomatic worsening of intracranial hemorrhage. Comparisons of 27 age-matched and sex-matched controls treated with VKAs showed no significant differences in terms of partial recanalization (55.6% vs. 63.0%, p = 0.29), complete recanalization (14.8% vs. 25.9%, p = 0.73), mRS at follow-up (median 0 vs. 0, p = 0.23), or major bleeding (11.1% vs. 11.1%, p > 0.99). Comparisons with the historical International Study on Cerebral Vein and Dural Sinus Thrombosis cohort showed similar functional outcomes: 92.6% of patients treated with NOACs and 88.9% of patients treated with VKAs at the Washington University School of Medicine in St. Louis, as well as 86.2% of patients treated with VKAs in the historical study cohort, had mRS of 0–2 at follow-up (p = 0.60). Rates of major bleeding compared with this cohort were also similar (11.1% vs. 11.1% vs. 14.5%, p = 0.80). The safety and efficacy results of NOAC use for CVT were similar to those for age-matched and sex-matched controls treated with VKAs, as well as historical published controls. Assessment of NOAC efficacy and safety in CVT in multicenter cohort studies and randomized controlled trials is warranted.

Background and purposeA subset of ischaemic stroke patients with atrial fibrillation (AF) have ischaemic stroke despite anticoagulation. We sought to determine the association between prestroke anticoagulant therapy and recurrent ischaemic events and symptomatic intracranial haemorrhage (sICH).MethodsWe included consecutive patients with acute ischaemic stroke and AF from the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study from eight comprehensive stroke centres in the USA. We compared recurrent ischaemic events and delayed sICH risk using adjusted Cox regression analyses between patients who were prescribed anticoagulation (ACp) versus patients who were naïve to anticoagulation therapy prior to the ischaemic stroke (anticoagulation naïve).ResultsAmong 2084 patients in IAC, 1518 had prior anticoagulation status recorded and were followed for 90 days. In adjusted Cox hazard models, ACp was associated with some evidence of a higher risk higher risk of 90-day recurrent ischaemic events only in the fully adjusted model (adjusted HR 1.50, 95% CI 0.99 to 2.28, p=0.058) but not increased risk of 90-day sICH (adjusted HR 1.08, 95% CI 0.46 to 2.51, p=0.862). In addition, switching anticoagulation class was not associated with reduced risk of recurrent ischaemic events (adjusted HR 0.41, 95% CI 0.12 to 1.33, p=0.136) nor sICH (adjusted HR 1.47, 95% CI 0.29 to 7.50, p=0.641).ConclusionAF patients with ischaemic stroke despite anticoagulation may have higher recurrent ischaemic event risk compared with anticoagulation-naïve patients. This suggests differing underlying pathomechanisms requiring different stroke prevention measures and identifying these mechanisms may improve secondary prevention strategies.

Introduction: Observational studies have found an increased risk of hemorrhagic transformation and worse functional outcomes in patients with higher systolic blood pressure variability (BPV). However, the time-varying behavior of BPV after endovascular thrombectomy (EVT) and its effects on functional outcome have not been well characterized. Patients and methods: We analyzed data from an international cohort of patients with large-vessel occlusion stroke who underwent EVT at 11 centers across North America, Europe, and Asia. Repeated time-stamped blood pressure data were recorded for the first 72 h after thrombectomy. Parameters of BPV were calculated in 12-h epochs using five established methodologies. Systolic BPV trajectories were generated using group-based trajectory modeling, which separates heterogeneous longitudinal data into groups with similar patterns. Results: Of the 2041 patients (age 69 ± 14, 51.4% male, NIHSS 15 ± 7, mean number of BP measurements 50 ± 28) included in our analysis, 1293 (63.4%) had a poor 90-day outcome (mRS ⩾ 3) or a poor discharge outcome (mRS ⩾ 3). We identified three distinct SBP trajectories: low (25%), moderate (64%), and high (11%). Compared to patients with low BPV, those in the highest trajectory group had a significantly greater risk of a poor functional outcome after adjusting for relevant confounders (OR 2.2; 95% CI 1.2–3.9; p = 0.008). In addition, patients with poor outcomes had significantly higher systolic BPV during the epochs that define the first 24 h after EVT ( p Discussion and conclusions: Acute ischemic stroke patients demonstrate three unique systolic BPV trajectories that differ in their association with functional outcome. Further research is needed to rapidly identify individuals with high-risk BPV trajectories and to develop treatment strategies for targeting high BPV.

IntroductionPredictors of long-term ischaemic and haemorrhagic complications in atrial fibrillation (AF) have been studied, but there are limited data on predictors of early ischaemic and haemorrhagic complications after AF-associated ischaemic stroke. We sought to determine these predictors.MethodsThe Initiation of Anticoagulation after Cardioembolic stroke study is a multicentre retrospective study across that pooled data from consecutive patients with ischaemic stroke in the setting of AF from stroke registries across eight comprehensive stroke centres in the USA. The coprimary outcomes were recurrent ischaemic event (stroke/TIA/systemic arterial embolism) and delayed symptomatic intracranial haemorrhage (d-sICH) within 90 days. We performed univariate analyses and Cox regression analyses including important predictors on univariate analyses to determine independent predictors of early ischaemic events (stroke/TIA/systemic embolism) and d-sICH.ResultsOut of 2084 patients, 1520 patients qualified; 104 patients (6.8%) had recurrent ischaemic events and 23 patients (1.5%) had d-sICH within 90 days from the index event. In Cox regression models, factors associated with a trend for recurrent ischaemic events were prior stroke or transient ischemic attack (TIA) (HR 1.42, 95% CI 0.96 to 2.10) and ipsilateral arterial stenosis with 50%–99% narrowing (HR 1.54, 95% CI 0.98 to 2.43). Those associated with sICH were male sex (HR 2.68, 95% CI 1.06 to 6.83), history of hyperlipidaemia (HR 2.91, 95% CI 1.08 to 7.84) and early haemorrhagic transformation (HR 5.35, 95% CI 2.22 to 12.92).ConclusionIn patients with ischaemic stroke and AF, predictors of d-sICH are different than those of recurrent ischaemic events; therefore, recognising these predictors may help inform early stroke versus d-sICH prevention strategies.

Introduction: Telestroke has expanded access to tPA and thrombectomy for acute ischemic stroke and improved neurologic outcomes. A key step in the evaluation of acute stroke is non-contrast head CT (HCT) and head and neck CT angiogram (CTA). These imaging studies can either be bundled at presentation, or a delayed CTA may be performed after a tPA decision based on HCT alone. Bundled imaging may facilitate faster transfer and treatment times, while delaying tPA. We investigated the effect of bundled imaging on thrombectomy transfer and treatment times in our telestroke network. Methods: We reviewed patients in our telestroke network from 2019-2021. We included patients who had received HCT and CTA at a partner hospital prior to transfer to our comprehensive stroke center (CSC) for thrombectomy. We collected baseline clinical variables, and timing of imaging, transfer and treatment relative to time of initial HCT. Patients were divided into a bundled imaging group (simultaneous HCT and CTA) or a delayed CTA group. Wilcoxon Rank sum test was used to compare between the two groups for HCT to tPA needle time, HCT to CSC arrival time, and HCT to Groin Puncture Time Results: 273 patients were assessed via telestroke in the study period. Of these 93 were included. 43 patients received bundled CTA, and 50 patients received a delayed CTA. 20 patients received tPA in the bundled group vs 25 in the delayed CTA group. Median CSC transfer time was lower with a bundled imaging strategy (110 min vs 160 min; p Conclusions: Bundled HCT and CTA at telestroke sites was associated with significantly faster transfer and groin puncture times for patients with large vessel occlusion. Further, obtaining the CTA prior to a tPA decision did not significantly prolong HCT-to-needle times.

Introduction: Stroke is the fifth leading cause of death in the US and a major cause of disability. Atrial fibrillation (AF) increases the risk of ischemic stroke fivefold. Cardioembolic stroke in patients with AF is associated with high mortality. The association of elevated cardiac troponin with mortality in patients with acute ischemic stroke has been studied previously; however, there is limited data in subgroups of ischemic stroke etiology. We sought to determine the association of troponin elevation at presentation with 90-day all-cause mortality in patients with acute ischemic stroke and AF. Methods: The I nitiation of A nticoagulation after C ardioembolic Stroke (IAC) study is a multicenter cohort drawn from eight US Stroke Centers. We included consecutive patients hospitalized with acute ischemic stroke and AF between 2015-2018, who had an initial baseline cardiac troponin I (bcTnI) obtained at presentation. The primary outcome was all-cause mortality at 90 days from stroke onset. We undertook multivariable logistic regression to determine the association between elevated bcTnl (≥0.1 ng/mL) and 90-day mortality. Results: Of the 2084 patients enrolled in IAC, 1889 patients had 90-day follow-up of which 1461 patients had bcTnI available. 239 of the included patients (16.4%) had an elevated bcTnl, and death within 90-days occurred in 323 patients (22.1%). Elevated bcTnI was associated with 90-day mortality in univariable analysis (49.4% vs 24.9%; OR 1.71, 95% CI 1.17-2.50, p Conclusion: In acute ischemic stroke patients with AF, elevated bcTnI was independently associated with 90-day all-cause mortality.

Background: A small randomized controlled trial suggested that dabigatran may be as effective as warfarin in the treatment of cerebral venous thrombosis (CVT). We aimed to compare direct oral anticoagulants (DOACs) to warfarin in a real-world CVT cohort. Methods: This multicenter international retrospective study (United States, Europe, New Zealand) included consecutive patients with CVT treated with oral anticoagulation from January 2015 to December 2020. We abstracted demographics and CVT risk factors, hypercoagulable labs, baseline imaging data, and clinical and radiological outcomes from medical records. We used adjusted inverse probability of treatment weighted Cox-regression models to compare recurrent cerebral or systemic venous thrombosis, death, and major hemorrhage in patients treated with warfarin versus DOACs. We performed adjusted inverse probability of treatment weighted logistic regression to compare recanalization rates on follow-up imaging across the 2 treatments groups. Results: Among 1025 CVT patients across 27 centers, 845 patients met our inclusion criteria. Mean age was 44.8 years, 64.7% were women; 33.0% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times. During a median follow-up of 345 (interquartile range, 140–720) days, there were 5.68 recurrent venous thrombosis, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years. Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization. When compared with warfarin, DOAC treatment was associated with similar risk of recurrent venous thrombosis (aHR, 0.94 [95% CI, 0.51–1.73]; P =0.84), death (aHR, 0.78 [95% CI, 0.22–2.76]; P =0.70), and rate of partial/complete recanalization (aOR, 0.92 [95% CI, 0.48–1.73]; P =0.79), but a lower risk of major hemorrhage (aHR, 0.35 [95% CI, 0.15–0.82]; P =0.02). Conclusions: In patients with CVT, treatment with DOACs was associated with similar clinical and radiographic outcomes and favorable safety profile when compared with warfarin treatment. Our findings need confirmation by large prospective or randomized studies.

Background Intravenous alteplase improves outcome after acute ischemic stroke without a benefit in 90‐day mortality. There are limited data on whether alteplase is associated with reduced mortality in patients with atrial fibrillation (AF)‐related ischemic stroke whose mortality rate is relatively high. We sought to determine the association of alteplase with hemorrhagic transformation and mortality in patients with AF. Methods and Results We retrospectively analyzed consecutive patients with acute ischemic stroke between 2015 and 2018 diagnosed with AF included in the IAC (Initiation of Anticoagulation After Cardioembolic Stroke) study, which pooled data from stroke registries at 8 comprehensive stroke centers across the United States. For our primary analysis, we included patients who did not undergo mechanical thrombectomy (MT), and secondary analyses included patients who underwent MT. We used binary logistic regression to determine whether alteplase use was associated with risk of hemorrhagic transformation and 90‐day mortality. There were 1889 patients (90.6%) who had 90‐day follow‐up data available for analyses and were included; 1367 patients (72.4%) did not receive MT, and 522 patients (27.6%) received MT. In our primary analyses we found that alteplase use was independently associated with an increased risk for hemorrhagic transformation (odds ratio [OR], 2.23; 95% CI, 1.57–3.17) but reduced risk of 90‐day mortality (OR, 0.58; 95% CI, 0.39–0.87). Among patients undergoing MT, alteplase use was not associated with a significant reduction in 90‐day mortality (OR, 0.68; 95% CI, 0.45–1.04). Conclusions Alteplase reduced 90‐day mortality of patients with acute ischemic stroke with AF not undergoing MT. Further study is required to assess the efficacy of alteplase in patients with AF undergoing MT.

Background and Purpose: Mechanical thrombectomy has dramatically increased patient volumes transferred to comprehensive stroke centers (CSCs), resulting in transfer denials for patients who need higher level of care only available at a CSC. We hypothesized that a distributive stroke network (DSN), triaging low severity acute stroke patients to a primary stroke center (PSC) upon initial telestroke consultation, would safely reduce transfer denials, thereby providing additional volume to treat severe strokes at a CSC. Methods: In 2017, a DSN was implemented, in which mild stroke patients were centrally triaged, via telestroke consultation, to a PSC based upon a simple clinical severity algorithm, while higher acuity/severity strokes were triaged to the CSC. In an observational cohort study, data on acute ischemic stroke patients presenting to regional community hospitals were collected pre- versus post-DSN implementation. Safety outcomes and rate of CSC transfer denials were compared pre-DSN versus post-DSN. Results: The pre-DSN cohort (n=150), triaged to the CSC, had a similar rate of symptomatic intracerebral hemorrhage and discharge location compared with the post-DSN cohort (n=150), triaged to the PSC. Time to stroke unit admission was faster post-DSN (2 hours 40 minutes) versus pre-DSN (3 hours 29 minutes; P P =0.02), despite an increase in telestroke consultation volume over the same period (median, 3 calls per day pre-DSN versus 5 calls per day post-DSN; P =0.001). No patients who were triaged to the PSC required subsequent transfer to the CSC. Conclusions: A DSN, triaging mild ischemic stroke patients from community hospitals to a PSC, safely reduced transfer denials to the CSC, allowing greater capacity at the CSC to treat higher acuity stroke patients.

Background and Purpose: Multiple studies have established that intravenous thrombolysis with alteplase improves outcome after acute ischemic stroke. However, assessment of thrombolysis’ efficacy in stroke patients with atrial fibrillation (AF) has yielded mixed results. We sought to determine the association of alteplase with mortality, hemorrhagic transformation (HT), infarct volume, and mortality in patients with AF and acute ischemic stroke. Methods: We retrospectively analyzed consecutive acute ischemic stroke patients with AF included in the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study, which pooled data from 8 comprehensive stroke centers in the United States. 1889 (90.6%) had available 90-day follow up data and were included. For our primary analysis we used a cohort of 1367/1889 (72.4%) patients who did not undergo mechanical thrombectomy (MT). Secondary analyses were repeated in the patients that underwent MT (n=522). Binary logistic regression was used to determine whether alteplase use was independently associated with risk of HT, final infarct volume, and 90-day mortality, respectively, adjusting for potential confounders. Results: In our primary analyses we found that alteplase use was independently associated with an increased risk for HT (adjusted OR 2.14, 95% CI 1.49 - 3.07, p Conclusion: Thrombolysis with intravenous alteplase was associated with reduced 90-day mortality in AF patients with acute ischemic stroke not undergoing MT. Further study is required to assess the safety and efficacy of alteplase in AF patients undergoing MT and those on DOACs.

Background: Emergent treatment with intravenous thrombolysis and mechanical thrombectomy improved outcomes in patients with acute ischemic stroke. We aim to identify differences in acute stroke treatment trends between strokes occurring in the anterior versus posterior circulation. Methods: The IAC (Initiation of Anticoagulation after Cardioembolic stroke) study represents pooled data registry of 8 comprehensive stroke centers across the United States and included patients with cardioembolic stroke in the setting of AFib. In a post hoc analysis, we identified and separated patients into posterior circulation stroke (PCS) and anterior circulation stroke (ACS) groups based on imaging. Patients without infarct locations or those with multi-circulation infarcts were excluded. We compared baseline characteristics, stroke severity and the treatment trends with alteplase (tPA) and mechanical thrombectomy (MT) in PCS vs ACS using Fisher exact test, t-test and non-parametric tests. We then performed multivariable logistic regression adjusted for baseline differences to determine the associations between PCS and tPA or MT. Results: Of the 2084 patients in IAC cohort, 1589 met inclusion criteria for this study, in which 294 (22.7%) had PCS. Mean age was 76.8 years, 29.3% received tPA and 26.9% had MT. When compared to ACS, patients with PCS were more likely to be men (55.4% vs 45.6%, p=0.003), have diabetes (42.8% vs 29.8, p< 0.001) and lower median NIHSS score on admission (4 vs 8, p Conclusion: Posterior circulation strokes are half as likely to receive thrombolytic therapy and almost a third as likely to have thrombectomy, even after adjusting for baseline stroke severity scores. This is possibly due to difficulty in timely identification and diagnostic delays. There is need for better tools incorporating posterior circulation stroke signs and symptoms to allow for early detection and treatment.

Background and purpose: A proportion of patients with ischemic stroke and atrial fibrillation (AF) have an ischemic stroke despite being prescribed anticoagulation therapy. In this study of patients with ischemic stroke in the setting of AF, we aim to determine the association between prior anticoagulant therapy and 90-day recurrent ischemic events and delayed symptomatic intracranial hemorrhage (sICH). Methods: We included consecutive patients with acute ischemic stroke and AF from the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study from 8 comprehensive stroke centers in the United States. We compared recurrent ischemic events and delayed sICH risk using unadjusted and adjusted cox-regression analyses between patients who were prescribed anticoagulation (AC p ) vs. were naïve to anticoagulation therapy prior to the ischemic stroke (AC n ). For ischemic events, we adjusted for CHA 2 DS 2 -Vasc, anticoagulation initiation, and switching anticoagulant (DOAC to Warfarin or Warfarin to DOAC). For delayed sICH, we adjusted for age, sex, NIHSS score, and early hemorrhagic transformation. Results: 2070 patients had home anticoagulation treatment status recorded. When compared to the AC n group, the AC p group were more likely to have higher median (IQR) CHA 2 DS 2 -Vasc score [5 (4-6) vs. 5 (3-6), p = 0.001], lower NIHSS score [8 (3 - 18) vs. 10 (4 - 18), p = 0.015], severe left atrial enlargement (43.5% vs. 34.5%, p < 0.001), and less likely to receive alteplase (14.4% vs. 36.2%, p < 0.001). In the adjusted cox hazard model, AC p was associated with increased risk of 90-day recurrent ischemic events (adjusted HR 1.52 95% CI 1.01 - 2.29, p = 0.047) but not increased risk of 90-day sICH (adjusted HR 1.10 95% CI 0.46 - 2.61, p = 0.838). In a sensitivity analysis, with severe left atrial enlargement added to the model, the association between AC p and recurrent ischemic event risk did not meaningfully change (adjusted HR 1.41 95% CI 0.87 - 2.28, p = 0.162). Conclusion: Patients with AF and ischemic stroke despite being prescribed anticoagulation therapy are at higher risk of recurrent events. Studies are needed to understand mechanisms of ischemic stroke in these patients to improve stroke prevention strategies.

International audience; Abstract BACKGROUND Randomized controlled trials evaluating mechanical thrombectomy (MT) for acute ischemic stroke predominantly studied anterior circulation patients. Both procedural and clinical predictors of outcome in posterior circulation patients have not been evaluated in large cohort studies. OBJECTIVE To investigate technical and clinical predictors of functional independence after posterior circulation MT while comparing different frontline thrombectomy techniques. METHODS In a retrospective multicenter international study of 3045 patients undergoing MT for stroke between 06/2014 and 12/2018, 345 patients had posterior circulation strokes. MT was performed using aspiration, stent retriever, or combined approach. Functional outcomes were assessed using the 90-d modified Rankin score dichotomized into good (0-2) and poor outcomes (3-6). RESULTS We included 2700 patients with anterior circulation and 345 patients with posterior circulation strokes. Posterior patients (age: 60 ± 14, 46% females) presented with mainly basilar occlusion (80%) and were treated using contact aspiration or ADAPT (39%), stent retriever (31%) or combined approach (19%). Compared to anterior strokes, posterior strokes had delayed treatment (500 vs 340 min, P

BackgroundElevated systolic blood pressure (SBP) after mechanical thrombectomy (MT) correlates with worse outcome. However, the association between SBP reduction (SBPr) and outcome after successful reperfusion with MT is not well established.ObjectiveTo investigate the association between SBPr in the first 24 hours after successful reperfusion and the functional and safety outcomes of MT.MethodsA multicenter retrospective study, which included 10 comprehensive stroke centers, was carried out. Patients with acute ischemic stroke and anterior circulation large vessel occlusions who achieved successful reperfusion via MT were included. SBPr was calculated using the formula 100×([admission SBP−mean SBP]/admission SBP). Poor outcome was defined as a modified Rankin Scale (mRS) score of 3–6 at 90 days. Safety endpoints included symptomatic intracerebral hemorrhage, mortality, and requirement for hemicraniectomy during admission. A generalized mixed linear model was used to study the association between SBPr and outcomes.ResultsA total of 1361 patients were included in the final analysis. SBPr as a continuous variable was inversely associated with poor outcome (OR=0.97; 95% CI 0.95 to 0.98; p20%), the rate of poor outcome was highest in the first group.ConclusionSBPr in the first 24 hours after successful reperfusion was inversely associated with poor outcome. No association between SBPr and safety outcome was found.

Spinal cord injury is a devastating condition affecting a person’s independence and quality of life. Nerve transfers are increasingly used to restore critical upper extremity function. Electrodiagnostic studies guide operative planning but the implications for clinical outcomes is not well defined. This case study delineates how clinical examination and electrodiagnostics can define the varying patterns of neuronal injury to guide timing and strategy for optimal outcomes in nerve transfers. We discuss a 20-year-old man with a C6–7 spinal cord injury (SCI). We illustrate how history, physical examination, and electrodiagnostic studies predicted patterns of upper and lower motor neuron injury, confirmed intraoperatively via direct nerve stimulation. We undertook brachialis nerve transfer to the median fascicles supplying flexor digitorum superficialis and anterior interosseous nerve (to restore digit flexion), and supinator nerve transfer to posterior interosseous nerve (to restore digit extension). Preoperative electrodiagnostics of the right upper extremity demonstrated a pure upper motor neuron injury to median innervated muscles, and mixed upper and lower motor neuron injury to radial innervated muscles. These findings were confirmed via intraoperative direct neuromuscular stimulation. The preoperative studies provided important information regarding the anatomic basis and time sensitivity of the proposed nerve transfers. At 2 years post operatively the reconstructed digit flexion and extension resulted in improved hand function and independence. Upper and lower motor neuron injuries can coexist in individuals with SCI. This example provides proof-of-concept that preoperative electrodiagnostic studies predict LMN injury, and surgery can achieve positive outcomes if completed soon after SCI.

Background and Purpose: In patients with acute ischemic stroke and atrial fibrillation, treatment with low molecular weight heparin increases early hemorrhagic risk without reducing early recurrence, and there is limited data comparing warfarin to direct oral anticoagulant (DOAC) therapy. We aim to compare the effects of the treatments above on the risk of 90-day recurrent ischemic events and delayed symptomatic intracranial hemorrhage. Methods: We included consecutive patients with acute ischemic stroke and atrial fibrillation from the IAC (Initiation of Anticoagulation after Cardioembolic) stroke study pooling data from stroke registries of 8 comprehensive stroke centers across the United States. We compared recurrent ischemic events and delayed symptomatic intracranial hemorrhage between each of the following groups in separate Cox-regression analyses: (1) DOAC versus warfarin and (2) bridging with heparin/low molecular weight heparin versus no bridging, adjusting for pertinent confounders to test these associations. Results: We identified 1289 patients who met the bridging versus no bridging analysis inclusion criteria and 1251 patients who met the DOAC versus warfarin analysis inclusion criteria. In adjusted Cox-regression models, bridging (versus no bridging) treatment was associated with a high risk of delayed symptomatic intracranial hemorrhage (hazard ratio, 2.74 [95% CI, 1.01–7.42]) but a similar rate of recurrent ischemic events (hazard ratio, 1.23 [95% CI, 0.63–2.40]). Furthermore, DOAC (versus warfarin) treatment was associated with a lower risk of recurrent ischemic events (hazard ratio, 0.51 [95% CI, 0.29–0.87]) but not delayed symptomatic intracranial hemorrhage (hazard ratio, 0.57 [95% CI, 0.22–1.48]). Conclusions: Our study suggests that patients with ischemic stroke and atrial fibrillation would benefit from the initiation of a DOAC without bridging therapy. Due to our study limitations, these findings should be interpreted with caution pending confirmation from large prospective studies.

The management of cerebral venous sinus thrombosis (CVT) is a common problem facing vascular neurologists. American Heart Association/American Stroke Association guidelines suggest the use of heparin followed by vitamin K antagonists (VKAs) for anticoagulation in CVT. In recent years, the evidence base has solidified for the use of non-vitamin K antagonist oral anticoagulants (NOACs) in lower extremity deep vein thrombosis. Because data supporting their use in CVT are limited, with the strongest evidence comprising one randomized controlled trial of dabigatran, we sought to review our experience with NOACs in the treatment of CVT at a tertiary care center to address efficacy and safety.We retrospectively reviewed charts of all patients with CVT treated with an NOAC at our tertiary care facility in the years 2011-2019. We collected data on demographics, risk factors for CVT, clinical features at presentation, imaging results, anticoagulation regimen, bleeding complications, and disability at follow-up. We compared disability at follow-up and major hemorrhagic events with age-matched and sex-matched controls treated with VKAs over the same time period and with historical controls.We identified 29 patients with CVT treated with an NOAC, 27 of whom had follow-up within our system. NOACs that were used for treatment included apixaban (20 patients), rivaroxaban (6 patients) and dabigatran (1 patient). NOAC use was associated with stabilization of a clot or partial recanalization in 55.6% of patients and complete recanalization in 14.8% at a median follow-up time of 6 months. The median modified Rankin Score (mRS) at follow-up was 0, with one death. Three patients (11.1%) had major bleeding complications, including two with symptomatic worsening of intracranial hemorrhage. Comparisons of 27 age-matched and sex-matched controls treated with VKAs showed no significant differences in terms of partial recanalization (55.6% vs. 63.0%, p = 0.29), complete recanalization (14.8% vs. 25.9%, p = 0.73), mRS at follow-up (median 0 vs. 0, p = 0.23), or major bleeding (11.1% vs. 11.1%, p 0.99). Comparisons with the historical International Study on Cerebral Vein and Dural Sinus Thrombosis cohort showed similar functional outcomes: 92.6% of patients treated with NOACs and 88.9% of patients treated with VKAs at the Washington University School of Medicine in St. Louis, as well as 86.2% of patients treated with VKAs in the historical study cohort, had mRS of 0-2 at follow-up (p = 0.60). Rates of major bleeding compared with this cohort were also similar (11.1% vs. 11.1% vs. 14.5%, p = 0.80).The safety and efficacy results of NOAC use for CVT were similar to those for age-matched and sex-matched controls treated with VKAs, as well as historical published controls. Assessment of NOAC efficacy and safety in CVT in multicenter cohort studies and randomized controlled trials is warranted.

OBJECTIVE Elevated systolic blood pressure (SBP) after successful revascularization (SR) via endovascular therapy (EVT) is a known predictor of poor outcome. However, the optimal SBP goal following EVT is still unknown. Our objective was to compare functional and safety outcomes between different SBP goals after EVT with SR. METHODS This international multicenter study included 8 comprehensive stroke centers and patients with anterior circulation large vessel occlusion who were treated with EVT and achieved SR. SR was defined as modified thrombolysis in cerebral ischemia 2b to 3. Patients were divided into 3 groups based on SBP goal in the first 24 hours after EVT. Inverse probability of treatment weighting (IPTW) propensity analysis was used to assess the effect of different SBP goals on clinical outcomes. RESULTS A total of 1,019 patients were included. On IPTW analysis, the SBP goal of

Spinal cord injury is a devastating condition affecting a person's independence and quality of life. Nerve transfers are increasingly used to restore critical upper extremity function. Electrodiagnostic studies guide operative planning but the implications for clinical outcomes is not well defined. This case study delineates how clinical examination and electrodiagnostics can define the varying patterns of neuronal injury to guide timing and strategy for optimal outcomes in nerve transfers.We discuss a 20-year-old man with a C6-7 spinal cord injury (SCI). We illustrate how history, physical examination, and electrodiagnostic studies predicted patterns of upper and lower motor neuron injury, confirmed intraoperatively via direct nerve stimulation. We undertook brachialis nerve transfer to the median fascicles supplying flexor digitorum superficialis and anterior interosseous nerve (to restore digit flexion), and supinator nerve transfer to posterior interosseous nerve (to restore digit extension). Preoperative electrodiagnostics of the right upper extremity demonstrated a pure upper motor neuron injury to median innervated muscles, and mixed upper and lower motor neuron injury to radial innervated muscles. These findings were confirmed via intraoperative direct neuromuscular stimulation. The preoperative studies provided important information regarding the anatomic basis and time sensitivity of the proposed nerve transfers. At 2 years post operatively the reconstructed digit flexion and extension resulted in improved hand function and independence.Upper and lower motor neuron injuries can coexist in individuals with SCI. This example provides proof-of-concept that preoperative electrodiagnostic studies predict LMN injury, and surgery can achieve positive outcomes if completed soon after SCI.

Background/Aims: Guidelines suggest initiating anticoagulation after cardioembolic stroke within 4-14 days from the index event. Data supporting this suggestion did not account for important factors such as infarct burden or early hemorrhagic transformation. Methods: We pooled data from stroke registries of 8 comprehensive stroke centers across the United States. We included consecutive patients admitted with an acute cardioembolic stroke in the setting of atrial fibrillation. The primary predictor was timing of initiating anticoagulation (0-3 days, 4-14 days, or >14 days) and the primary outcome was the composite endpoint of recurrent stroke/TIA/systemic embolism, symptomatic intracerebral hemorrhage (sICH), or major extracranial hemorrhage (ECH) within 90 days. Results: We enrolled 2090 patients from 8 comprehensive centers in the United States, 1325 met the inclusion criteria (362 were excluded due to non-composite endpoint related death within 90 days, 145 lost to follow up, and 258 were not started on oral anticoagulation or the timing was not reported). Anticoagulation (875 DOAC, 404 Warfarin) was initiated in 0-3 days in 49.7%, 4-14 days in 40.4%, and >14 days in 9.9%. The combined endpoint occurred in 10.7% (142) (98 ischemic events, 21 sICH, and 30 ECH) and did not differ between the three groups: 0-3 days (11.9%), 4-14 days (9.9%), >14 days (9.9%), p=0.525. After adjusting for confounders (such as infarct volume, bridging, CHADS2-Vasc, cardiac thrombus, and hemorrhage on 24-hr imaging), oral anticoagulation timing in the 4-14 day period (vs. >14) was not associated with a reduction in ischemic events (adjusted OR 0.74, p=0.438) and oral anticoagulation timing 4-14 days (vs. 0-3) was not associated with a reduction in sICH (OR 1.28, p=0.638). Factors associated with sICH were bridging (OR 5.36, p=0.001) and hemorrhage on 24-hr imaging (OR 7.26, p Conclusion: In this multicenter real world cohort, the recommended (4-14 days) timeframe to start oral anticoagulation was not associated with reduced ischemic and hemorrhagic outcomes. Randomized trials are required determine the optimal timing of anticoagulation initiation.

Introduction: Endovascular thrombectomy (ET) for treating acute stroke in the real-world has expanded beyond the selection criteria used in major trials, and currently includes posterior circulation strokes. Posterior circulation stroke is believed to have worse outcomes than anterior circulation stroke, and its outcomes following ET are still being studied. We explored the major determinants of functional recovery after ET for posterior circulation stroke in a large cohort of patients from the Stroke Thrombectomy and Aneurysm Registry (STAR). Methods: STAR includes patients undergoing ET for acute ischemic stroke at 12 comprehensive stroke centers in the US and globally. Data on patient demographics, technical and clinical outcomes was reviewed retrospectively from patient charts and procedure notes. Primary outcomes was the modified Ranking Score (mRS) at 90 days dichotomized into favorable (mRS 0-2) and poor outcome (mRS 3-6). Results: A total of 3850 patients were reviewed, of which 345 patients (mean age 60±14) were treated for posterior circulation stroke with predominantly basilar artery occlusion (80%). Patients were treated using aspiration thrombectomy (ADAPT, 39%), stent retriever thrombectomy (31%), combined approach (19%) or intracranial stenting (7%). The overall rate of favorable outcome was 33%. Patients with diabetes, high NIHSS on admission, and proximal occlusions had significantly higher odds of poor functional outcomes on multivariate analysis (p Conclusions: Despite similar rates of functional recovery after ET for anterior circulation stroke between stent retriever and ADAPT, our analysis demonstrates that in posterior circulation stroke, ADAPT may lead to better functional outcomes compared to stent retriever without differences in safety profiles.

Introduction: Hyperacute MRI (hMRI) increases the number of patients eligible for IV tPA in: (1) patients initially suspected to be stroke mimics (SM) and (2) patients with wake-up or unwitnessed stroke onset (WU-UW). Performing hMRI in a time-frame to enable tPA delivery is challenging for many centers; thus, we evaluated which factors were associated with delays in hMRI and hMRI-related tPA treatment at our institution since publication of the WAKE-UP stroke trial in August 2018. Methods: We analyzed 1-year of prospectively collected hMRI data performed between 07.01.2018 to 06.30.2019. We divided the year into three 4-month epochs; the 1 st epoch was before and the 2 nd and 3 rd epochs were after implementing the Wake-up protocol for WU-UW stroke presentations as a new indication to our streamlined hMRI protocol. We compared baseline variables, hMRI indication, hMRI-related tPA utilization, and time metrics for completing hMRI between the 2 nd and 3 rd epochs. We also evaluated discharge outcomes and safety of tPA treatment in this hMRI cohort. Results: Across the 3 epochs, 84 patients underwent hMRI (n=10 vs. 37 vs. 37, respectively), of whom 13 were treated with IV tPA. hMRI-related tPA utilization increased in epochs 2 vs 3 after initiation of the Wake-Up protocol: 8.1% (epoch 2) vs. 21.6% (epoch 3), and number-needed-to-MRI for one tPA treatment dropped from 12.3 to 4.6. In epochs 2 vs. 3, MRI order-to-scan time decreased (28 vs 23 minutes, P=0.039), indicative of process improvement over time. Across all epochs, hMRI indication of WU-UW (vs. SM) was associated with shorter door-to-hMRI completion (68 vs. 83.5 minutes, P=0.041) and shorter door-to-needle time (76 vs. 118 minutes; P=0.030), whereas age, NIHSS, and sex were not associated with hMRI efficiency. None of the 13 patients treated with IV tPA developed symptomatic ICH and 92% were discharged to home or inpatient rehabilitation. Conclusion: In the final epoch, < 5 MRIs were performed for one tPA treatment, suggesting that a hMRI protocol may improve with time and increased utilization, justifying the use of hMRI to increase patient eligibility for IV tPA. WU-UW stroke indications for hMRI may predict shorter hMRI process and faster treatment times.

BackgroundAtrial fibrillation (AF) associated ischemic stroke has worse functional outcomes, less effective recanalization, and increased rates of hemorrhagic complications after intravenous thrombolysis (IVT). Limited data exist about the effect of AF on procedural and clinical outcomes after mechanical thrombectomy (MT).ObjectiveTo determine whether recanalization efficacy, procedural speed, and clinical outcomes differ in AF associated stroke treated with MT.MethodsWe performed a retrospective cohort study of the Stroke Thrombectomy and Aneurysm Registry (STAR) from January 2015 to December 2018 and identified 4169 patients who underwent MT for an anterior circulation stroke, 1517 (36.4 %) of whom had comorbid AF. Prospectively defined baseline characteristics, procedural outcomes, and clinical outcomes were reported and compared.ResultsAF predicted faster procedural times, fewer passes, and higher rates of first pass success on multivariate analysis (pConclusionsIn patients treated with MT, comorbid AF is associated with faster procedural time, fewer passes, and increased rates of first pass success without increased risk of intracranial hemorrhage or worse functional outcomes. These results are in contrast to the increased hemorrhage rates and worse functional outcomes observed in AF associated stroke treated with supportive care and or IVT. These data suggest that MT negates the AF penalty in ischemic stroke.

Objective Guidelines recommend initiating anticoagulation within 4 to 14 days after cardioembolic stroke. Data supporting this did not account for key factors potentially affecting the decision to initiate anticoagulation, such as infarct size, hemorrhagic transformation, or high-risk features on echocardiography. Methods We pooled data from stroke registries of 8 comprehensive stroke centers across the United States. We included consecutive patients admitted with ischemic stroke and atrial fibrillation. The primary predictor was timing of initiating anticoagulation (0-3 days, 4-14 days, or >14 days), and outcomes were recurrent stroke/transient ischemic attack/systemic embolism, symptomatic intracerebral hemorrhage (sICH), and major extracranial hemorrhage (ECH) within 90 days. Results Among 2,084 patients, 1,289 met the inclusion criteria. The combined endpoint occurred in 10.1% (n = 130) subjects (87 ischemic events, 20 sICH, and 29 ECH). Overall, there was no significant difference in the composite endpoint between the 3 groups (0-3 days: 10.3%, 64/617; 4-14 days: 9.7%, 52/535; >14 days: 10.2%, 14/137; p = 0.933). In adjusted models, patients started on anticoagulation between 4 and 14 days did not have a lower rate of sICH (vs 0-3 days; odds ratio [OR] = 1.49, 95% confidence interval [CI] = 0.50-4.43), nor did they have a lower rate of recurrent ischemic events (vs >14 days; OR = 0.76, 95% CI = 0.36-1.62, p = 0.482). Interpretation In this multicenter real-world cohort, the recommended (4-14 days) time frame to start oral anticoagulation was not associated with reduced ischemic and hemorrhagic outcomes. Randomized trials are required to determine the optimal timing of anticoagulation initiation. ANN NEUROL 2020;88:807-816.

International audience; Background and Purpose— Successful reperfusion can be achieved in more than two-thirds of patients treated with mechanical thrombectomy. Therefore, it is important to understand the effect of blood pressure (BP) on clinical outcomes after successful reperfusion. In this study, we investigated the relationship between BP on admission and during the first 24 hours after successful reperfusion with clinical outcomes. Methods— This was a multicenter study from 10 comprehensive stroke centers. To ensure homogeneity of the studied cohort, we included only patients with anterior circulation who achieved successful recanalization at the end of procedure. Clinical outcomes included 90-day modified Rankin Scale, symptomatic intracerebral hemorrhage (sICH), mortality, and hemicraniectomy. Results— A total of 1245 patients were included in the study. Mean age was 69±14 years, and 51% of patients were female. Forty-nine percent of patients had good functional outcome at 90-days, and 4.7% suffered sICH. Admission systolic BP (SBP), mean SBP, maximum SBP, SBP SD, and SBP range were associated with higher risk of sICH. In addition, patients in the higher mean SBP groups had higher rates of sICH. Similar results were found for hemicraniectomy. With respect to functional outcome, mean SBP, maximum SBP, and SBP range were inversely associated with the good outcome (modified Rankin Scale score, 0–2). However, the difference in SBP parameters between the poor and good outcome groups was modest. Conclusions— Higher BP within the first 24 hours after successful mechanical thrombectomy was associated with a higher likelihood of sICH, mortality, and requiring hemicraniectomy.

BACKGROUND AND PURPOSE: Understanding factors associated with ischemic stroke despite therapeutic anticoagulation is an important goal to improve stroke prevention strategies in patients with atrial fibrillation (AF). We aim to determine factors associated with therapeutic or supratherapeutic anticoagulation status at the time of ischemic stroke in patients with AF. METHODS: The Initiation of Anticoagulation after Cardioembolic stroke (IAC) study is a multicenter study pooling data from stroke registries of eight comprehensive stroke centers across the United States. Consecutive patients hospitalized with acute ischemic stroke in the setting of AF were included in the IAC cohort. For this study, we only included patients who reported taking warfarin at the time of the ischemic stroke. Patients not on anticoagulation and patients who reported use of a direct oral anticoagulant were excluded. Analyses were stratified based on therapeutic (INR ≥2) versus subtherapeutic (INR

Introduction: The introduction of thrombectomy into evidence-based stroke care has dramatically increased the volume of stroke patients transferred to comprehensive stroke centers (CSC), often overwhelming their capacity. This has led to increased transfer denials of severe stroke patients who needed thrombectomy. Hypothesis: A “distributive stroke network” (DSN) to triage low severity acute stroke patients to a primary stroke center (PSC) upon initial neurology consultation will be safe, thereby providing additional volume to treat severe strokes at a CSC. Methods: A clinical severity algorithm for external consultations based on NIHSS and time since last known well was created to triage mild acute ischemic stroke patients (both tPA-treated and untreated) to the PSC, while triaging more severe strokes to the CSC. We evaluated clinical outcomes, safety endpoints, stroke consultation volumes, and transfer denials by comparing a stroke cohort after DSN implementation, to a cohort (matched for NIHSS and acuity) admitted to the CSC prior to DSN implementation. Results: The pre-DSN CSC cohort had similar demographics to the post-DSN PSC cohort. Safety outcomes (symptomatic hemorrhage or the need for PSC to CSC transfer) and favorable discharge outcome (home/inpatient rehabilitation vs. nursing home/death) did not differ between pre- and post-DSN cohorts. The post-DSN PSC cohort had a faster time from consult to admission (3 vs. 5 hours) and shorter hospital length of stay (LOS) (2 vs. 3.5 days) compared to the pre-DSN CSC cohort. After DSN implementation, there were fewer CSC stroke transfer denials. Total consultation rates increased over the same period. Conclusion: Triaging external patients to a PSC or CSC during initial consultation (distributive stroke network) based on stroke severity and acuity significantly reduced transfer denials to the CSC. In addition, this DSN algorithm was safe, led to faster admission, and a shorter LOS.

Introduction: Current AHA/ASA guidelines recommend keeping blood pressure (BP) Methods: This was a multicenter international retrospective study that included 7 comprehensive stroke centers. Inclusion criteria were anterior circulation large vessel occlusion (LVO) that was treated with MT, and successful recanalization at the conclusion of the procedure. Patients were divided into three groups based on systolic BP (SBP) goals in the first 24 hours post MT. Group 1) included patients with SBP goal ≤140 mm Hg or ≤120 mm Hg; group 2 included patients with SBP goal ≤160 mm Hg; group 3) included patients with SBP goal ≤220 mm Hg or ≤180 mm Hg. Successful recanalization was defined as TICI 2b-3. Outcome measures included symptomatic intracerebral hemorrhage (sICH), 90-day modified Rankin Scale (mRS), and 90-day mortality. Results: A total of 985 patients were included in the study. More patients in group 3 were white and had Afib than groups 1-2. Likewise, more patients in group 3 received IV tPA. Complete recanalization (TICI 2c-3) was achieved in 88.2%, 53.6%, and 73.2% in groups 1,2,3 respectively (p Conclusion: Blood pressure goals ≤140 and ≤160 were associated with favorable functional outcome.

Introduction: Hypertension is a known predictor of poor outcome and hemorrhagic complications after ischemic stroke. However, the effect of blood pressure (BP) on outcome of those undergoing mechanical thrombectomy and especially after successful recanalization is not well understood. In this study, we investigated the association between BP parameters and outcome measures after successful recanalization with MT. Methods: This was a retrospective, multicenter study, involving 7 comprehensive stroke centers, of patients with acute ischemic stroke due to large vessel occlusion who achieved successful recanalization with MT. Systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure (MAP) were obtained at frequent intervals (at least hourly) for each patient in the first 24 hours following MT. Outcome measures included 90 day-modified Rankin Scale (mRS), 90-day morality, and symptomatic intracerebral hemorrhage (sICH). Successful recanalization was defined as TICI 2b-3, and sICH as any hemorrhage associated with > 4 points increase in NIHSS. A mixed logistic model was used to identify predictors of functional and hemorrhagic outcomes. Results: A total of 989 patients were included, of whom 453 (45.8%) achieved good outcome, defined as an mRS of 0-2. Mean, and maximum SBP were higher in the poor outcome group (131.6 +15 vs. 127 +14.3; p Conclusion: Higher blood pressure was associated with hemorrhagic complications, and worse functional outcome following successful mechanical thrombectomy.

Introduction: blood pressure variability (BPV) in the acute phase following ischemic stroke is associated with worse outcomes, especially in patients with large vessel occlusions. However, the relationship between BPV and outcome after successful recanalization is not well documented. Objective: The aim of this study was to evaluate the association between BPV and outcome after successful recanalization. Methods: This was a retrospective multicenter study of patients with anterior circulation large vessel occlusions who achieved successful recanalization with MT. Successful recanalization was defined as TICI≥2b. BP was recorded in hourly intervals for 24 hours post MT. BPV was defined as the difference between maximum and minimum blood pressure within 24 hours. BPV was calculated for mean arterial pressure (MAP), systolic BP (SBP), and diastolic BP (DBP). Outcome measures included 90 days mRS, symptomatic ICH (sICH), and mortality. sICH was defined based on ECASS criteria. Good outcome was defined as mRS 0-2. Results: A total of 985 patients were included. SBP and MAP variability were higher in poor outcome group (65.2±26 vs. 57± 24.6; p Conclusion: Higher blood pressure variability was associated with worse functional outcomes, higher likelihood of symptomatic hemorrhage, and increased mortality.

Introduction: The management of cerebral venous sinus thrombosis (CVST) is a common problem facing vascular neurologists. AHA/ASA guidelines suggest the use of heparin followed by vitamin K antagonists (VKA) for anticoagulation in CVST. In recent years, the evidence base has solidified for the use of novel oral anticoagulants (NOACs) in lower extremity DVT. Since data supporting their use in CVST is very limited, we sought to review our experience with NOACs in the treatment of CVST at a tertiary care center to address efficacy and safety. Methods: We retrospectively reviewed charts of all patients with CVST treated at our facility with a NOAC between 2014-2018. We collected data on demographics, risk factors for CVST, clinical features at presentation, imaging results, anticoagulation regimen, bleeding complications, and disability at follow up. We compared disability at follow up and major hemorrhagic events with historical controls. Results: We identified 27 patients with CVST treated with a NOAC, 22 of whom had follow up within our system. NOACs included apixaban (68.2%), rivaroxaban (27.3%) and dabigatran (4.5%). NOAC use was associated with stabilization of clot or partial recanalization in 81.8% of patients, and complete recanalization in 18.2%, at a median follow up of 5.5 months. Median mRS at follow up was 0, with one death. Four patients had bleeding complications, including two with symptomatic worsening of ICH. Comparison to historical controls showed no significant differences in terms of disability, death or major hemorrhagic events. Conclusion: Safety and efficacy of NOAC use for CVST were similar to historical controls anticoagulated with other agents. Analyses comparing NOAC-treated patients to 40 contemporary controls treated with vitamin K antagonists at our institution are underway, and prospective assessment of NOAC efficacy and safety in CVST in randomized controlled trials is warranted.

The domestic laying hen is the only non-human animal that spontaneously develops ovarian cancer with a high prevalence. Hens ovulate prolifically, and this has made the hen intuitively appealing as a model of this disease in light of epidemiological evidence that ovulation rate is highly correlated with the risk of human ovarian cancer. As in women, ovarian cancer in the hen is age-related and it is also grossly and histologically similar to that in humans. In both women and hens, the cancer metastasizes to similar tissues with an accumulation of ascites fluid. Some aggressive ovarian cancers in women arise from cells in the oviduct; this is intriguing because ovarian cancers in the hen express an oviductal protein that is normally absent in the ovary.

Macrophage can adopt several phenotypes, process call polarization, which is crucial for shaping inflammatory responses to injury. It is not known if microglia, a resident brain macrophage population, polarizes in a similar way, and whether specific microglial phenotypes modulate cell death in response to brain injury. In this study, we show that both BV2-microglia and mouse bone marrow derived macrophages (BMDMs) were able to adopt different phenotypes after LPS (M1) or IL-4 (M2) treatment in vitro, but regulated cell death differently when added to mouse organotypic hippocampal brain slices. BMDMs induced cell death when added to control slices and exacerbated damage when combined with oxygen-glucose deprivation (OGD), independently of their phenotype. In contrast, vehicle- and M2-BV2-microglia were protective against OGD-induced death. Direct treatment of brain slices with IL-4 (without cell addition) was protective against OGD and induced an M2 phenotype in the slice. In vivo, intracerebral injection of LPS or IL-4 in mice induced microglial phenotypes similar to the phenotypes observed in brain slices and in cultured cells. After injury induced by middle cerebral artery occlusion, microglial cells did not adopt classical M1/M2 phenotypes, suggesting that another subtype of regulatory phenotype was induced. This study highlights functional differences between macrophages and microglia, in response to brain injury with fundamentally different outcomes, even if both populations were able to adopt M1 or M2 phenotypes. These data suggest that macrophages infiltrating the brain from the periphery after an injury may be cytotoxic, independently of their phenotype, while microglia may be protective.

The use of military working dogs (MWDs) in support of military operations has increased dramatically over recent years, as they have proven to be our most reliable deterrent to improvised explosive devices. Healthcare delivery for MWDs in combat presents unique challenges and requires extensive collaboration between veterinarians and human health care providers (HCPs). A successful example is the incorporation of MWD emergency care for nonveterinary HCPs into the Joint Trauma System Clinical Practice Guidelines, which has proven to be a helpful product. Additional challenges that need further solutions include MWDs as patients in human medical treatment facilities (MTFs) and the procurement of appropriate canine blood components in an operational environment. It is often necessary for MWDs to be treated as patients in human MTFs, however, there is no Department of Defense guidance to support this activity. Access to MWD blood products is limited to collection of fresh whole blood in the operational setting. Similar to humans, specific blood component therapy, such as fresh frozen plasma, is often indicated for sick or injured MWDs. Currently there is no formal system in place to deliver any blood products for MWDs or to facilitate collection in theater.

Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that regulates inflammatory responses to injury and infection. IL-1β secretion requires the protease caspase-1, which is activated following recruitment to inflammasomes. Endogenous danger-associated molecular patterns (DAMPs) released from necrotic cells activate caspase-1 through an NLRP3-inflammasome. Here, we show that the endogenous lipid metabolite sphingosine (Sph) acts as a DAMP by inducing the NLRP3-inflammasome-dependent secretion of IL-1β from macrophages. This process was dependent upon serine/threonine protein phosphatases since the PP1/PP2A inhibitors okadaic acid and calyculin A inhibited Sph-induced IL-1β release. IL-1β release induced by other well-characterized NLRP3-inflammasome activators, such as ATP and uric acid crystals, in addition to NLRC4 and AIM2 inflammasome activators was also blocked by these inhibitors. Thus, we propose Sph as a new DAMP, and that a serine/threonine phosphatase (PP1/PP2A)-dependent signal is central to the endogenous host mechanism through which diverse stimuli regulate inflammasome activation.

Summary Background: Neurophobia has been described as a fear of clinical neuroscience, and is known to affect both medical students and junior doctors alike. There is some evidence that it may affect the practice of GPs, who may not feel confident enough to give advice to neurological patients. Context: I am a fourth year undergraduate at The University of Manchester, and have undertaken two four-week placements in neurology at the Greater Manchester Neuroscience Centre in Salford. The first was a student-selected component in movement disorders, and the second was part of the standard undergraduate curriculum at the University. Innovation: In this piece I relate my experience of clinical neuroscience training to the theory surrounding neurophobia. I aim to demonstrate how students and teachers can reduce the effect of the phenomenon through the use of good educational strategies. My experience is divided into individual and group learning opportunities. Five points for teachers of clinical neuroscience are presented as possible ideas to help students venturing into clinical neurology for the first time. Implications: The experience I had during my eight weeks in neurology suggests that neurophobia can be reduced. It is important that clinical teachers have an awareness of the implications of neurophobia in their students so they can both anticipate and counteract its effects.

Faults in a cluster are inevitable. The larger the cluster, the more likely the occurrence of some failure in hardware, in software, or by human error. System-S software must detect and self-repair failures while carrying out its prime directive--enabling stream processing program fragments to be distributed and connected to form complex applications. Depending on the type of failure, System-S may be able to continue with little or no disruption to potentially tens of thousands of interdependent and heterogeneous program fragments running across thousands of nodes. We extend the work we previously presented on the self healing nature of the job manager component in System-S by presenting how it can handle failures of other system components, applications and network infrastructure. We also evaluate the recoverability of the job management orchestrator component of System-S, considering crash failures with and without error propagation.