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Background: Early palliative/pre-emptive intervention improves clinical outcomes and quality of life for patients with metastatic cancer. A previous signal-seeking randomized controlled trial (RCT) demonstrated that early upfront radiotherapy to asymptomatic or minimally symptomatic high-risk osseous metastases led to reduction in skeletal-related events (SREs), a benefit driven primarily by subgroup of high-risk spine metastasis. The current RCT aims to determine whether early palliative/pre-emptive radiotherapy in patients with high-risk, asymptomatic or minimally symptomatic spine metastases will lead to fewer SREs within 1 year., Methods: This is a single-center, parallel-arm, in-progress RCT in adults (≥ 18 years) with ECOG performance status 0-2 and asymptomatic or minimally symptomatic (not requiring opioids) high-risk spine metastases from histologically confirmed solid tumor malignancies with > 5 sites of metastatic disease on cross-sectional imaging. High-risk spine metastases are defined by the following: (a) bulkiest disease sites ≥ 2 cm; (b) junctional disease (occiput to C2, C7-T1, T12-L2, L5-S1); (c) posterior element involvement; or (d) vertebral body compression deformity > 50%. Patients are randomized 1:1 to receive either standard-of-care systemic therapy (arm 1) or upfront, early radiotherapy to ≤ 5 high-risk spine lesions plus standard-of-care systemic therapy (arm 2), in the form of 20-30 Gy of radiation in 2-10 fractions. The primary endpoint is SRE, a composite outcome including spinal fracture, spinal cord compression, need for palliative radiotherapy, interventional procedures, or spinal surgery. Secondary endpoints include (1) surrogates of health care cost, including the number and duration of SRE-related hospitalizations; (2) overall survival; (3) pain-free survival; and (4) quality of life. Study instruments will be captured pre-treatment, at baseline, during treatment, and at 1, 3, 6, 12, and 24 months post-treatment. The trial aims to accrue 74 patients over 2 years to achieve > 80% power in detecting difference using two-sample proportion test with alpha < 0.05., Discussion: The results of this RCT will demonstrate the value, if any, of early radiotherapy for high-risk spine metastases. The trial has received IRB approval, funding, and prospective registration (NCT05534321) and has been open to accrual since August 19, 2022. If positive, the trial will expand the scope and utility of spine radiotherapy., Trial Registration: ClinicalTrials.Gov NCT05534321 . Registered September 9, 2022., Trial Status: Version 2.0 of the protocol (2021-KOT-002), revised last on September 2, 2022, was approved by the WCG institutional review board (Study Number 1337188, IRB tracking number 20223735). The trial was first posted on ClinicalTrials.Gov on September 9, 2022 (NCT05534321). Patient enrollment commenced on August 19, 2022, and is expected to be completed in 2 years, likely by August 2024., (© 2024. The Author(s).)

Introduction Individuals using cocaine, methamphetamines, cannabis, and other mood-altering drugs (MADs) have been reported to have greater stroke risk when compared to individuals who do not use these drugs. Yet, the impact that MAD use has on stroke outcomes has not been adequately explored, with existing research not agreeing on the extent to which the use of these drugs influences stroke outcomes. This study aimed to determine the impact that the use of common MADs has on stroke outcome factors such as length of stay (LOS), discharge modified Rankin Scale (mRS), and discharge disposition. Methods A retrospective case-matched study was conducted with two adult cohorts treated for cerebrovascular accidents: those who use MADs and those who do not use MADs prior to their stroke. Subjects identified for the users of MADs cohort were matched at a 1:1 ratio to those who do not use MADs (control cohort) by age, sex, and stroke type (e.g., hemorrhagic or ischemic). Logistic regression was used to calculate odds ratios for functional outcomes for stroke patients with and without prior MAD use. Results Active users of MADs had an increased overall risk of poor stroke outcome, i.e., increased length of stay, discharge disposition other than to home or to rehabilitation, discharge modified Rankin scale (mRS) 3-6 after controlling for stroke severity from initial National Institutes of Health Stroke Scale (NIHSS) (X 2 {9}=21.68, p<0.01, Cox adjusted R 2 =0.31). This finding was driven predominately by increased hospital LOS (p=0.006) among the MAD cohort, whereas discharge mRS 3-6 (p=0.24) and discharge disposition to care facility (p=0.27) and expired (p=0.26) did not vary significantly between groups. Conclusion Our study suggests that patients who had actively used MADs prior to their stroke may be at risk of poorer stroke outcomes, namely an increased LOS. Future research should be conducted to further elucidate which factors, such as individual drugs, amount of drug, acute or recreational use versus chronic or long-term use, and route of administration, for instance, specifically contribute to a longer LOS so that they may be targeted for mitigation., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2023, Rogers et al.)

Objective: Stroke is a global public health burden, and therefore it is critical to identify modifiable risk factors to reduce stroke incidence and improve outcomes. Depression is such a risk factor; however, the association between preexisting depression and stroke outcomes, such as independent ambulation, is not well studied, especially among racial-ethnic minority groups. To address this gap in the literature, effects of preexisting depression on ambulatory status at hospital discharge after stroke were evaluated among individuals participating in the racially and ethnically diverse Florida-Puerto Rico Collaboration to Reduce Stroke Disparities project., Methods: Data were analyzed from a total of 42,031 ischemic stroke patients, who were independently ambulatory prior to their stroke, after discharge from 84 hospitals between 2014 and 2017. Preexisting depression was confirmed by medical history or antidepressant medication use. Multilevel multivariate logistic regression analyses were used to assess the association of preexisting depression with independent ambulation at hospital discharge. Effects of sex and race-ethnicity on this association were examined., Results: Of 42,031 participants (mean±SD age=70.4±14.2 years; 48% were female; race-ethnicity: 16% Black, 12% Hispanic living in Florida, and 7% Hispanic living in Puerto Rico), 6,379 (15%) had preexisting depression. Compared with participants without depression, those with preexisting depression were older, were more likely to be female and non-Hispanic White, and had a greater burden of vascular risk factors or comorbid conditions. Independent ambulation at hospital discharge was less frequent among women, Black participants, and individuals with vascular risk factors or comorbid conditions. In multivariate models, preexisting depression decreased the likelihood of independent ambulation at discharge (odds ratio=0.88, 95% CI=0.81, 0.97). No interactions were found between preexisting depression and race-ethnicity or sex., Conclusions: Preexisting depression was independently associated with dependent ambulation at hospital discharge after stroke, regardless of sex and race-ethnicity. Treating depression may contribute to primary stroke prevention and could improve ambulatory status at discharge., Competing Interests: Dr. Starosciak has served as a consultant to Viz.ai. Dr. Gutierrez has received research salary support from the Florida Department of Health. Dr. Rose has received honoraria for serving as a consultant for or on the speaker’s bureau of Boston Scientific, Chiesi USA, CSL Behring, and Medtronic. The other authors report no financial relationships with commercial interests.

Background and Purpose: Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year., Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020)., Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths., Conclusions: During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.

Background: Unprecedented workflow shifts during the coronavirus disease 2019 (COVID-19) pandemic have contributed to delays in acute care delivery, but whether it adversely affected endovascular thrombectomy metrics in acute large vessel occlusion (LVO) is unknown., Methods: We performed a retrospective review of observational data from 14 comprehensive stroke centers in nine US states with acute LVO. EVT metrics were compared between March to July 2019 against March to July 2020 (primary analysis), and between state-specific pre-peak and peak COVID-19 months (secondary analysis), with multivariable adjustment., Results: Of the 1364 patients included in the primary analysis (51% female, median NIHSS 14 [IQR 7-21], and 74% of whom underwent EVT), there was no difference in the primary outcome of door-to-puncture (DTP) time between the 2019 control period and the COVID-19 period (median 71 vs 67 min, P=0.10). After adjustment for variables associated with faster DTP, and clustering by site, there remained a trend toward shorter DTP during the pandemic (β adj =-73.2, 95% CI -153.8-7.4, Pp=0.07). There was no difference in DTP times according to local COVID-19 peaks vs pre-peak months in unadjusted or adjusted multivariable regression (β adj =-3.85, 95% CI -36.9-29.2, P=0.80). In this final multivariable model (secondary analysis), faster DTP times were significantly associated with transfer from an outside institution (β adj =-46.44, 95% CI -62.8 to - -30.0, P<0.01) and higher NIHSS (β adj =-2.15, 95% CI -4.2to - -0.1, P=0.05)., Conclusions: In this multi-center study, there was no delay in EVT among patients treated for intracranial occlusion during the COVID-19 era compared with the pre-COVID era., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To conduct the first item-level exploration of scale and index structure of the self-report Behavior Rating Inventory of Executive Function-Adult version (BRIEF-A) in traumatic brain injury (TBI)., Design: This was an observational cross-sectional study design using secondary data. We conducted exploratory factor analyses (EFA) to explore the index structure and scale structure of the BRIEF-A. We conducted EFA with all 70 items of the BRIEF-A to examine the index structure. Based on the finding of index structure, we conducted EFA on the 30 items of the Behavioral Regulation Index (BRI) and the 40 items of the Metacognitive Index (MI)., Setting: Data were collected through 5 studies in outpatient and community settings in the southeast United States., Participants: Individuals (N=338) aged 18-89 years with a history of mild to severe TBI who were able to speak English fluently., Interventions: Not applicable., Main Outcome Measures: The BRIEF-A., Results: The 2-factor structure aligned with the BRIEF-A manual at the index level. Scale structure for the MI (40 items) resulted in 1 factor, whereas the BRI (30 items) could be represented by either a 2- or 3-factor structure. The 2-factor structure of the BRI is more parsimonious and matched other factor analyses derived from the sum of scale items., Conclusions: We confirmed the manual designated index structure (BRI and MI) of the BRIEF-A but took precautions against using the 9 scales. Instead, we recommend using the 2 designated index scores and 2 newly identified composite scores representing Behavioral Control Trait and Emotional Control Trait., (Published by Elsevier Inc.)

Background: IV alteplase is a primary treatment for acute ischemic stroke (AIS) at a weight-based dose (WBD) of 0.9 mg/kg and maximum dose (MD) of 90 mg. There are conflicting data regarding outcomes for those weighing ≥100 kg. There is also a paucity of data in Hispanics. The prevalence of adult obesity in the US has progressively increased; hence, the percentage of patients receiving the maximum dose also is expected to rise. We examined differences between patients treated with WBD vs. MD., Methods: A retrospective review of our center's Get With The Guidelines-Stroke database was performed for IV alteplase cases between October 2013-February 2017. Selection criteria included age ≥18 years, IV alteplase administration, and a recorded measured weight. Patients were dichotomized into WBD group weighing <100 kg and MD group weighing ≥100 kg. Categorical variables were analyzed using Chi square tests and continuous variables were analyzed using independent samples t-tests. Multivariable logistic regression analysis was performed to determine whether MD in combination with other variables was associated with poor outcomes., Results: There were 328 patients included in the study, 38 (11.6%) received MD. Proportions of younger, male, and non-Hispanic were higher in the MD group. There were no statistically significant differences for initial NIHSS, discharge modified Rankin Scale (mRS), 90-day mRS, symptomatic intracerebral hemorrhage (sICH), or systemic hemorrhage between groups., Conclusion: One in ten patients thrombolysed for the treatment of AIS received MD. In a predominantly Hispanic population, those who received MD and WBD had similar rates of sICH, discharge disposition, and functional outcome (mRS) at discharge and at 90 days. Limitations include small sample size and attrition for the 90-day mRS., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background and Purpose: The National Institutes of Health Stroke Scale (NIHSS) measured at an early time point is an appealing surrogate marker for long-term functional outcome of stroke patients treated with endovascular therapy. However, definitions and analytical methods for an early NIHSS-based outcome measure that optimize power and precision in clinical studies are not well-established., Methods: In this post-hoc analysis of our prospective observational study that enrolled endovascular therapy-treated patients at 12 comprehensive stroke centers across the US, we compared the ability of 24-hour NIHSS, ΔNIHSS (baseline minus 24-hour NIHSS), and percentage change (NIHSS×100/baseline NIHSS), analyzed as continuous and dichotomous measures, to predict 90-day modified Rankin Scale (mRS) using logistic regression (adjusted for age, baseline NIHSS, glucose, hypertension, Alberta Stroke Program Early CT Score, time to recanalization, recanalization status, and intravenous thrombolysis) and Spearman ρ., Results: Of 485 patients in the BEST (Blood Pressure After Endovascular Stroke Therapy) cohort, 446 (92%) with 90-day follow-up data were included. An absolute 24-hour NIHSS, adjusted for baseline in multivariable modeling, had the highest predictive power of all definitions evaluated (aR 2 0.368 and adjusted odds ratio 0.79 [0.75-0.84], P <0.001 for mRS score 0-2; aR 2 0.444 and adjusted odds ratio 0.84 [0.8-0.86] for ordinal mRS). For predicting mRS score of 0-2 with a cut point, the second most efficient approach, the optimal threshold for 24-hour NIHSS score was ≤7 (sensitivity 80.1%, specificity 80.4%; adjusted odds ratio 12.5 [7.14-20], P <0.001), followed by percent change in NIHSS (sensitivity 79%, specificity 58.5%; adjusted odds ratio 4.55 [2.85-7.69], P <0.001)., Conclusions: Twenty-four-hour NIHSS, adjusted for baseline, was the strongest predictor of both dichotomous and ordinal 90-day mRS outcomes for endovascular therapy-treated patients. A dichotomous 24-hour NIHSS score of ≤7 was the second-best predictor. Although ΔNIHSS, continuous and dichotomized at ≥4, predicted 90-day outcomes, absolute 24-hour NIHSS definitions performed better.

Background: Elevated systolic blood pressure (SBP) in the acute phase after endovascular therapy (EVT) is associated with worse outcome. However, the association between systolic blood pressure reduction (SBPr) and the outcome of EVT is not well understood., Objective: To determine the association between SBPr and clinical outcomes after EVT in a prospective multicenter cohort., Methods: A post hoc analysis of the Blood Pressure after Endovascular Stroke Therapy (BEST) prospective observational cohort study was carried out. SBPr was defined as the absolute difference between admission SBP and mean SBP in the first 24 hours after EVT. Logistic regression was used to assess the association between SBPr and poor functional outcome (modified Rankin Scale score 3-6) at 90 days., Results: A total of 259/433 (58.5%) patients had poor outcome. SBPr was higher in the poor outcome group than in the good outcome group (26.6±27.4 vs 19.0±22.3 mm Hg; p<0.001). However, in adjusted models, SBPr was not independently associated with poor outcome (OR=1.00 per 1 mm Hg increase, 95% CI 0.99 to 1.01) or death (OR=0.9 per 1 mm Hg increase; 95% CI 0.98 to 1.00). No association remained when SBPr was divided into tertiles. Subgroup analyses based on history of hypertension, revascularization status, and antihypertensive treatment yielded similar results., Conclusion: The reduction in baseline SBP following EVT was not associated with poor functional outcomes. Most of the cohort (88%) achieved successful recanalization, and therefore, these results mainly apply to patients with successful recanalization., Competing Interests: Competing interests: EAM reports grants from the Society of Vascular and Interventional Neurology, University of Cincinnati Gardner Neuroscience Institute, and Vanderbilt Faculty Research Scholar Program. AdH reports a research grant from NIH/NINDS (K23NS105924)., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Dual antiplatelet therapy (DAP) is necessary to prevent thromboembolic events during carotid stenting, stent-assisted coil embolization, and implant of flow diverters (FD). However, DAP in the acute phase may be challenging. An intravenous alternative, cangrelor, has rapid onset, short plasma half-life, and more reliable antiplatelet action for acute interventions. The study objective was to evaluate feasibility and safety of IV cangrelor during acute neuroendovascular surgery procedures., Methods: We performed a retrospective analysis of our database of patients treated with stent-assisted coil embolization, FD placement for aneurysmal subarachnoid hemorrhage (aSAH), or stenting for acute internal carotid artery (ICA) occlusion where IV cangrelor was used. Morbidity, mortality, incidence of thromboembolic events, hemorrhages, and 90-day outcomes were reported., Results: Ten patients were found in our database from June 2018 through January 2019. Four patients had aSAH, four had middle cerebral artery strokes with tandem lesions, one had an ICA occlusion, and one had a vertebral artery aneurysm. One of the ten patients experienced a thrombotic event. One patient developed new post-procedural bleeding and two had worsening intracranial hemorrhage. Five patients were discharged home in stable condition, two to acute rehabilitation, one to a nursing facility, and two others expired (likely the result of the severe and evolving strokes). Of the eight who were discharged, six (75%) had a good 90-day functional outcome (modified Rankin Scale 0-2)., Conclusion: Acute administration of IV cangrelor with or without oral ticagrelor is a feasible antiplatelet treatment option for acute neuroendovascular procedures., Competing Interests: Competing interests: IL discloses that he is a proctor, consultant, and speaker for Medtronic, he is a consultant and speaker for Stryker, and holds stock in InNeuroCo, and Three Rivers, outside the submitted work. GD discloses that he is a consultant, proctor, and speaker for Medtronic, is a consultant and speaker for Microvention and Penumbra, is a consultant for Cerenovus, and a shareholder for Surpass, outside the submitted work., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: The pandemic caused by the novel coronavirus disease 2019 (COVID-19) has led to an unprecedented paradigm shift in medical care. We sought to evaluate whether the COVID-19 pandemic may have contributed to delays in acute stroke management at comprehensive stroke centers., Methods: Pooled clinical data of consecutive adult stroke patients from 14 US comprehensive stroke centers (January 1, 2019, to July 31, 2020) were queried. The rate of thrombolysis for nontransferred patients within the Target: Stroke goal of 60 minutes was compared between patients admitted from March 1, 2019, and July 31, 2019 (pre-COVID-19), and March 1, 2020, to July 31, 2020 (COVID-19). The time from arrival to imaging and treatment with thrombolysis or thrombectomy, as continuous variables, were also assessed., Results: Of the 2955 patients who met inclusion criteria, 1491 were admitted during the pre-COVID-19 period and 1464 were admitted during COVID-19, 15% of whom underwent intravenous thrombolysis. Patients treated during COVID-19 were at lower odds of receiving thrombolysis within 60 minutes of arrival (odds ratio, 0.61 [95% CI, 0.38-0.98]; P =0.04), with a median delay in door-to-needle time of 4 minutes ( P =0.03). The lower odds of achieving treatment in the Target: Stroke goal persisted after adjustment for all variables associated with earlier treatment (adjusted odds ratio, 0.55 [95% CI, 0.35-0.85]; P <0.01). The delay in thrombolysis appeared driven by the longer delay from imaging to bolus (median, 29 [interquartile range, 18-41] versus 22 [interquartile range, 13-37] minutes; P =0.02). There was no significant delay in door-to-groin puncture for patients who underwent thrombectomy (median, 83 [interquartile range, 63-133] versus 90 [interquartile range, 73-129] minutes; P =0.30). Delays in thrombolysis were observed in the months of June and July., Conclusions: Evaluation for acute ischemic stroke during the COVID-19 period was associated with a small but significant delay in intravenous thrombolysis but no significant delay in thrombectomy time metrics. Taking steps to reduce delays from imaging to bolus time has the potential to attenuate this collateral effect of the pandemic.

Background: Acute stroke outcomes depend on timely reperfusion. In 3/2017, local EMS agencies implemented a prehospital triage algorithm with hospital bypass and field activation of the neurointerventional team using the Field Assessment Stroke Triage for Emergency Destination (FAST-ED). A score ≥4 bypasses to a comprehensive stroke center (CSC) and a score ≥6 also has the interventional team field activated off-hours., Aim: We analyzed effects of this initiative on volume, acute stroke transfers, treatment times, and outcomes and determined the tool's ability to predict large vessel occlusion., Methods: Stroke cases brought to our center by EMS during 3/2016-2/2018 were analyzed, which included one year before and after FAST-ED implementation. Treatment times were compared on- vs. off-hours and to those with field activation., Results: Of 1153 patients, 761 (67%) were coded as stroke and 235 (20%) underwent reperfusion. Age, sex, race/ethnicity, stroke severity, length of stay, door-to-needle, and 90-d mRS were comparable between periods. Scale compliance was 85%. Concordance rate of ±1 between EMS and calculated score was 53%. Compared to the previous year, door-to-puncture (DTP) improved by 17 min (p < 0.01) overall, 25 min (p < 0.001) off-hours, and 33 min (p < 0.05) with field activation. A cutoff of 4 vs. 6 would have led to 140% increase in field activations but only 36% increase in procedures., Conclusions: This prehospital initiative led to faster DTP by up to 33 min. The highest impact was off-hours with field activation. Only 1/3 of activations led to endovascular treatment. FAST-ED≥6 appears to be appropriate for field activation., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective Giant intracranial aneurysms (GIAs) are associated with a high risk of rupture and have a high mortality rate when they rupture (65-100%). The traditional microsurgical approach to secure these lesions is challenging, and as such endovascular embolization has been increasingly selected as a treatment option. Methods We performed a retrospective analysis of consecutive patients with ruptured and unruptured GIAs at three medical centers from October 2008 to April 2016. Clinical follow-up and digital subtraction angiography were conducted at six months post-treatment. Chi-square analysis was used to determine differences in outcomes between anterior and posterior circulation aneurysms and if a pipeline embolization device (PED) provided favorable outcomes in unruptured GIAs. Results A total of 45 consecutive patients (mean/median age = 57/59; range: 16-82 years) were included. The mean/median aneurysm size was 29.9/28.3 mm (range: 25-50 mm). Eight (18%) patients presented with aneurysmal subarachnoid hemorrhage and 37 (82%) with unruptured GIAs. Twenty-eight (62%) were treated with a PED: 11 (24.4%) with one PED, 1 (2.2%) with PED + coils, 11 (24.4%) with more than one PED, and 5 (13.5%) with multiple PED + coils. The overall mortality rate was 3/45 (6.7%). No deaths were procedure-related. Five (11.1%) patients experienced ischemic stroke but only 2 had a 90-day modified Rankin Scale (mRS) score of ≥3. Of 33 patients available for six-month angiography, Raymond scale (RS) scores were 1, 2, and 3 for 23/45 (70%), 7/45 (20.9%), and 3/45 (9.1%), respectively. Chi-square test demonstrated that overall, anterior circulation GIAs had better clinical (mRS score) and radiographic (RS score) outcomes than posterior GIAs. PED alone provided similar clinical mRS outcomes but had a higher rate of complete occlusion at six months compared with PED + coils and coils alone in unruptured GIAs (p < 0.05). Conclusions Endovascular embolization using PED or PED + coils appears to be a moderately safe and effective treatment option for patients with GIAs., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2020, Linfante et al.)

Background and Purpose: The increased severity of white matter disease is associated with worse outcomes and an increased rate of intracerebral hemorrhage in patients with ischemic stroke undergoing thrombolytic treatment. However, whether white matter disease is associated with outcomes in patients undergoing endovascular treatment remains unclear., Materials and Methods: In this prespecified exploratory analysis of our prospective multi-institutional study that enrolled consecutive adult patients with anterior circulation ischemic stroke undergoing endovascular treatment from November 2017 to September 2018, we compared the following outcomes between patients with none-to-minimal (van Swieten score, 0-2) and moderate-to-severe (van Swieten score, 3-4) white matter disease using logistic regression: 90-day mRS 3-6, death, intracerebral hemorrhage, successful recanalization, and early neurologic recovery., Results: Of the 485 patients enrolled in the Blood Pressure after Endovascular Stroke Therapy (BEST) study, 389 had white matter disease graded (50% women; median age, 68 years; range, 58-79 years). A van Swieten score of 3-4 ( n  = 74/389, 19%) was associated with a higher rate of 90-day mRS of 3-6 (45% versus 18%; adjusted OR, 2.73; 95% CI, 1.34-5.93; P = .008). Although the death rate was higher in patients with van Swieten scores of 3-4 (26% versus 15%), the adjusted likelihood was not significantly different (adjusted OR, 1.14; 95% CI, 0.56-2.26; P = .710). Ordered regression revealed a shift toward worse mRS scores with increasing van Swieten scores (adjusted common OR, 3.04; 95% CI, 1.93-4.84; P  < .001). No associations between white matter disease severity and intracerebral hemorrhage, successful recanalization, and early neurologic recovery were observed., Conclusions: Moderate-to-severe white matter disease is associated with worse outcomes in patients undergoing endovascular treatment without a significant increase in hemorrhagic complications. Studies comparing patients with and without endovascular treatment are necessary to determine whether the benefit of endovascular treatment is attenuated with greater white matter disease., (© 2020 by American Journal of Neuroradiology.)

Background and Purpose: The 2018 AHA guidelines recommend perfusion imaging to select patients with acute large vessel occlusion (LVO) for thrombectomy in the extended window. However, the relationship between noncontrast CT and CT perfusion imaging has not been sufficiently characterized >6 hours after last known normal (LKN)., Methods: From a multicenter prospective cohort of consecutive adults who underwent thrombectomy for anterior LVO 0-24 hours after LKN, we correlated baseline core volume (rCBF < 30%) and the Alberta Stroke Program Early CT Scale (ASPECTS) score. We compared perfusion findings between patients with an unfavorable ASPECTS (<6) against those with a favorable ASPECTS (≥6), and assessed findings over time., Results: Of 485 enrolled patients, 177 met inclusion criteria (median age: 69 years, interquartile range [IQR: 57-81], 49% female, median ASPECTS 8 [IQR: 6-9], median core 10 cc [IQR: 0-30]). ASPECTS and core volume moderately correlated (r = -.37). A 0 cc core was observed in 54 (31%) patients, 70% of whom had ASPECTS <10. Of the 28 patients with ASPECTS <6, 3 (11%) had a 0 cc core. After adjustment for age and stroke severity, there was a lower ASPECTS for every 1 hour delay from LKN (cOR: 0.95, 95% confidence of interval [CI]: 0.91-1.00, P = .04). There was no difference in core (P = .51) or penumbra volumes (P = .87) across patients over time., Conclusions: In this multicenter prospective cohort of patients who underwent thrombectomy, one-third of patients had normal CTP core volumes despite nearly three quarters of patients showing ischemic changes on CT. This finding emphasizes the need to carefully assess both noncontrast and perfusion imaging when considering thrombectomy eligibility., (© 2019 by the American Society of Neuroimaging.)

Background: Because of the overwhelming benefit of thrombectomy for highly selected trial patients with large vessel occlusion (LVO), some trial-ineligible patients are being treated in practice., Objective: To determine the safety and efficacy of thrombectomy in DAWN/DEFUSE-3-ineligible patients., Methods: Using a multicenter prospective observational study of consecutive patients with anterior circulation LVO who underwent late thrombectomy, we compared symptomatic intracerebral hemorrhage (sICH) and good outcome (90-d mRS 0-2) among DAWN/DEFUSE-3-ineligible patients to trial-eligible patients and to untreated DAWN/DEFUSE-3 controls., Results: Ninety-eight patients had perfusion imaging and underwent thrombectomy >6 h; 46 (47%) were trial ineligible (41% M2 occlusions, 39% mild deficits, 28% ASPECTS <6). In multivariable regression, the odds of a good outcome (aOR 0.76, 95% CI 0.49-1.19) and sICH (aOR 3.33, 95% CI 0.42-26.12) were not different among trial-ineligible vs eligible patients. Patients with mild deficits were more likely to achieve a good outcome (aOR 3.62, 95% CI 1.48-8.86) and less sICH (0% vs 10%, P = .16), whereas patients with ASPECTS <6 had poorer outcomes (aOR 0.14, 95% CI 0.05-0.44) and more sICH (aOR 24, 95% CI 5.7-103). Compared to untreated DAWN/DEFUSE-3 controls, trial-ineligible patients had more sICH (13%BEST vs 3%DAWN [P = .02] vs 4%DEFUSE [P = .05]), but were more likely to achieve a good outcome at 90 d (36%BEST vs 13%DAWN [P < .01] vs 17%DEFUSE [P = .01])., Conclusion: Thrombectomy is used in practice for some patients ineligible for the DAWN/DEFUSE-3 trials with potentially favorable outcomes. Additional trials are needed to confirm the safety and efficacy of thrombectomy in broader populations, such as large core infarction and M2 occlusions., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Background and Purpose- Although higher blood pressure variability (BPV) is associated with worse functional outcome after stroke, this association is not as well established in large vessel occlusion strokes treated with endovascular treatment (EVT). Methods- In this post hoc analysis of BEST (Blood Pressure after Endovascular Therapy for Ischemic Stroke), a prospective, multicenter cohort study of anterior circulation acute ischemic stroke patients undergoing EVT, we determined the association of BPV with poor outcome or death (90-day modified Rankin Scale, 3-6). We calculated BPV during the first 24 hours after EVT for systolic and diastolic BP using 5 methodologies, then divided BPV into tertiles and compared the highest to lowest tertile using logistic regression. Results- Of the 443 patients included in our analysis, 259 (58.5%) had a poor outcome, and 79 (17.8%) died. All measures of BPV were significantly higher in patients with poor outcome or death, but the difference was more pronounced for systolic than diastolic BPV. In the logistic regression, the highest tertile of systolic BPV consistently predicted poor outcome (odds ratio, 1.8-3.5, all P <0.05). The rate of death within 90 days was 10.1% in the tertile with the lowest systolic BPV versus 25.2% in the tertile with the highest BPV ( P <0.001). Conclusions- In EVT-treated stroke patients, higher BPV in the first 24 hours is associated with worse 90-day outcome. This association was more robust for systolic BPV. The mechanism by which BPV may exert a negative influence on neurological outcome remains unknown, but the consistency of this association warrants further investigation and potentially intervention.

Background and Purpose- To identify the specific post-endovascular stroke therapy (EVT) peak systolic blood pressure (SBP) threshold that best discriminates good from bad functional outcomes (a priori hypothesized to be 160 mm Hg), we conducted a prospective, multicenter, cohort study with a prespecified analysis plan. Methods- Consecutive adult patients treated with EVT for an anterior ischemic stroke were enrolled from November 2017 to July 2018 at 12 comprehensive stroke centers accross the United States. All SBP values within 24 hours post-EVT were recorded. Using Youden index, the threshold of peak SBP that best discriminated primary outcome of dichotomized 90-day modified Rankin Scale score (0-2 versus 3-6) was identified. Association of this SBP threshold with the outcomes was quantified using multiple logistic regression. Results- Among 485 enrolled patients (median age, 69 [interquartile range, 57-79] years; 51% females), a peak SBP of 158 mm Hg was associated with the largest difference in the dichotomous modified Rankin Scale score (absolute risk reduction of 19%). Having a peak SBP >158 mm Hg resulted in an increased likelihood of modified Rankin Scale score 3 to 6 (odds ratio, 2.24 [1.52-3.29], P <0.01; adjusted odds ratio, 1.29 [0.81-2.06], P =0.28, after adjustment for prespecified variables). Conclusions- A peak post-EVT SBP of 158 mm Hg was prospectively identified to best discriminate good from bad functional outcome. Those with a peak SBP >158 had an increased likelihood of having a bad outcome in unadjusted, but not in adjusted analysis. The observed effect size was similar to prior studies. This finding should undergo further testing in a future randomized trial of goal-targeted post-EVT antihypertensive treatment.

Background: Mechanical thrombectomy with stent-retrievers results in higher recanalization rates compared with previous devices. Despite successful recanalization rates (Thrombolysis in Cerebral Infarction (TICI) score ≥2b) of 70-83%, good outcomes by 90-day modified Rankin Scale (mRS) score ≤2 are achieved in only 40-55% of patients. We evaluated predictors of poor outcomes (mRS >2) despite successful recanalization (TICI ≥2b) in the North American Solitaire Stent Retriever Acute Stroke (NASA) registry., Methods: Logistic regression was used to evaluate baseline characteristics and recanalization outcomes for association with 90-day mRS score of 0-2 (good outcome) vs 3-6 (poor outcome). Univariate tests were carried out for all factors. A multivariable model was developed based on backwards selection from the factors with at least marginal significance (p≤0.10) on univariate analysis with the retention criterion set at p≤0.05. The model was refit to minimize the number of cases excluded because of missing covariate values; the c-statistic was a measure of predictive power., Results: Of 354 patients, 256 (72.3%) were recanalized successfully. Based on 234 recanalized patients evaluated for 90-day mRS score, 116 (49.6%) had poor outcomes. Univariate analysis identified an increased risk of poor outcome for age ≥80 years, occlusion site of internal carotid artery (ICA)/basilar artery, National Institute of Health Stroke Scale (NIHSS) score ≥18, history of diabetes mellitus, TICI 2b, use of rescue therapy, not using a balloon-guided catheter or intravenous tissue plasminogen activator (IV t-PA), and >30 min to recanalization (p≤0.05). In multivariable analysis, age ≥80 years, occlusion site ICA/basilar, initial NIHSS score ≥18, diabetes, absence of IV t-PA, ≥3 passes, and use of rescue therapy were significant independent predictors of poor 90-day outcome in a model with good predictive power (c-index=0.80)., Conclusions: Age, occlusion site, high NIHSS, diabetes, no IV t-PA, ≥3 passes, and use of rescue therapy are associated with poor 90-day outcome despite successful recanalization., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background and Purpose: Failure to recanalize predicts mortality in acute ischemic stroke. In the North American Solitaire Acute Stroke registry, we investigated parameters associated with mortality in successfully recanalized patients., Methods: Logistic regression was used to evaluate baseline characteristics and recanalization parameters for association with 90-day mortality. A multivariable model was developed based on backward selection with retention criteria of P<0.05 from factors with at least marginal significance (P≤0.10), then refit to minimize the number of excluded cases (missing data)., Results: Successfully recanalized patients had lower mortality (25.2% [59/234] versus 46.9% [38/81] P<0.001). There was no difference in symptomatic intracranial hemorrhage between patients with successful versus failed recanalization (9% [21/234] versus 14% [11/79]; P=0.205). However, mortality was significantly higher in patients with symptomatic intracranial hemorrhage (72% [23/32] versus 26% [73/281]; P<0.001). Proximal occlusion (internal carotid artery or vertebrobasilar), initial National Institutes of Health Stroke Scale≥18, use of rescue therapy (P<0.05), and 3+ passes (P<0.10) were associated with mortality in recanalized patients. In the multivariate model with good predictive power (c index=0.72), proximal occlusion, initial National Institutes of Health Stroke Scale≥18, and use of rescue therapy remained significant independent predictors of 90-day mortality., Conclusions: Failure to recanalize and presence of symptomatic intracranial hemorrhage resulted in increased mortality. Despite successful recanalization, proximal occlusion, high National Institutes of Health Stroke Scale, and need for rescue therapy were predictors of mortality., (© 2015 American Heart Association, Inc.)

Women constitute half of all smokers and many studies suggest that adult males and females differ in factors that maintain tobacco smoking, yet there is limited information about sex differences in nicotine reward during adolescence. Limited studies suggest that adolescent male rats self-administer more nicotine than adults, suggesting that drug administration during adolescence leads to different behavioral effects than during adulthood. In the present study, male rats developed a significant conditioned place preference (CPP) to lower doses of nicotine than females, regardless of age. In addition, adolescents were more sensitive than adults. In female rats, adolescents exhibited a CPP of greater magnitude than adult females. In males, the magnitude of the CPP did not differ as a function of age, but adolescents exhibited CPP to lower doses than adults. There also were differences in nicotinic acetylcholinergic receptor binding in nucleus accumbens and caudate putamen in response to nicotine across age and sex. These findings suggest that it is necessary to consider sex- and age-specific effects of drugs such as nicotine when developing strategies for improving smoking cessation treatments., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Several neural interface technologies that stimulate and/or record from groups of axons have been developed. The longitudinal intrafascicular electrode (LIFE) is a fine wire that can provide access to a discrete population of axons within a peripheral nerve fascicle. Some applications require, or would benefit greatly from, technology that could provide access to multiple discrete sites in several fascicles., New Method: The distributed intrafascicular multi-electrode (DIME) lead was developed to deploy multiple LIFEs to several fascicles. It consists of several (e.g. six) LIFEs that are coiled and placed in a sheath for strength and durability, with a portion left uncoiled to allow insertion at distinct sites. We have also developed a multi-lead multi-electrode (MLME) management system that includes a set of sheaths and procedures for fabrication and deployment., Results: A prototype with 3 DIME leads was fabricated and tested in a procedure in a cadaver arm. The leads were successfully routed through skin and connective tissue and the deployment procedures were utilized to insert the LIFEs into fascicles of two nerves., Comparison With Existing Method(s): Most multi-electrode systems use a single-lead, multi-electrode design. For some applications, this design may be limited by the bulk of the multi-contact array and/or by the spatial distribution of the electrodes., Conclusion: We have designed a system that can be used to access multiple sets of discrete groups of fibers that are spatially distributed in one or more fascicles of peripheral nerves. This system may be useful for neural-enabled prostheses or other applications., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Rationale: Ecstasy (MDMA) is used predominately by adolescents and young adults. Young MDMA users are more likely than non-users to use other drugs, including cocaine. The response to stimulant drugs can be affected by environmental factors; however, little information exists about the role that housing plays in mediating effects of MDMA in adolescence., Objectives: The present experiment examined whether social and environmental factors alter effects of MDMA on activity and cocaine reward., Methods: Male adolescent rats were housed on PND 23. Isolated rats were housed alone (1 rat/cage) in an impoverished environment with no toys (II) or enriched with toys (IE). Social rats were housed three/cage with (SE3) or without (SI3) toys. Starting on PND 29, 5 mg/kg MDMA or saline was injected and activity was measured for 60 min once daily for five consecutive days. On PND 36-40, cocaine CPP was conducted., Results: Saline vehicle-induced activity of II rats was higher than other groups, and all groups became sensitized to the locomotor-stimulant effects of MDMA. In II rats, maximal CPP was increased after MDMA pre-exposure compared to vehicle. Environmental enrichment blocked this; however, dose-effect curves for cocaine CPP shifted to the left in both IE and SE3 rats. In rats with just social enrichment, there were no effects of MDMA on cocaine CPP., Conclusion: Drug prevention and treatment strategies should take into account different environments in which adolescents live. These findings show that MDMA increases cocaine reward in male adolescents, and social enrichment diminishes, while environmental enrichment enhances this.

Individuals with greater nicotine-reactivity may be more likely to initiate and maintain cigarette-smoking behavior than individuals with less nicotine-reactivity. In rats, behavioral sensitization reflects a progressive increase in the psychomotor response to drugs of abuse thought to result from neuroplasticity in brain regions that mediate their motivational effects. Studying nicotine behavioral sensitization in rats with differential nicotine preference and intake, such as Lewis and Fischer rats, may provide clues about the role of nicotine-reactivity in tobacco use. Rat strain differences in nicotine behavioral sensitization may contribute to strain differences in nicotine preference, sensitivity, and intake. In the present research, nicotine behavioral sensitization to multiple doses was examined in Lewis and Fischer rats. Subjects were 96 late adolescent male (48 Fischer, 48 Lewis) rats. Rats received subcutaneous injections of nicotine (0.2, 0.4, 0.7, 1.4, 2.8 mg/kg) or saline daily, and locomotor activity was measured immediately following injections on alternating days to examine sensitization. Behavioral sensitization occurred in both rat strains at the 0.2, 0.4, 0.7, and 1.4 mg/kg nicotine doses, but did not differ between Lewis and Fischer rats. The pattern of horizontal activity that occurred in response to the 2.8 mg/kg nicotine dose did not reflect behavioral sensitization. Results indicate that nicotine behavioral sensitization occurred in Lewis and Fischer rats, and did not differ between the two rat strains. It can be concluded that reported rat strain differences in nicotine intake, sensitivity, and preference do not result from rat strain differences in nicotine behavioral sensitization.

The startle response of Pantodon buchholzi, the African butterfly fish, is a complete or incomplete ballistic jump resulting from abduction of the pectoral fins. This study analyzed the neuromuscular basis for such a jump by recording in vivo electromyograms (emgs) from the muscles of abduction, the muscularis abductor superficialis (MAS) and the muscularis abductor profundus (MAP). The motor neurons innervating the MAS muscle were localized by retrograde transport of biocytin. The latency between stimulus and the evoked emg in the MAS was less than 5 ms; the latency of the MAP was about 6.5 ms. A single emg was recorded per jump. High speed video demonstrated that onset of a startle movement began within 10 ms of the onset of fin abduction. The emg associated with this movement is short (<2 ms) and followed by a variably-shaped, slower and smaller potential of 10-30 ms duration. The brief period between stimulus and startle response of Pantodon suggests a Mauthner neuron-related response, only with the behavior occurring in the vertical plane. The MAS may act only in a startle response, whereas the MAP might have a role in other behaviors. Elicited jumping habituates after a single trial. Electrophysiological evidence is presented indicating that the innervating motor neurons are suppressed for seconds following a stimulus. The neurons innervating the MAS are located at the medullary-spinal cord junction and possess an average radius of approximately 17.9 mum. These fish have been historically described as 'fresh water' flying fish. As a single emg occurs per startle response, repetitive pectoral activity generating flying cannot be supported. Pantodon 'flight' is ballistic., (Copyright 2007 S. Karger AG, Basel.)