Search

Background: Stroke is an important cause of morbidity in pediatrics. Large studies are needed to better understand the epidemiology, pathogenesis and risk factors associated with pediatric stroke. Large administrative datasets can provide information on risk factors in perinatal and childhood stroke at low cost. The aim of this hypothesis-generating study was to use a large administrative dataset to assess for prevalence and odds-ratios of rare exposures associated with pediatric stroke., Methods: The data for patients aged 0-18 with a diagnosis of either ischemic stroke or intracranial hemorrhage were extracted from the Cerner Health Facts EMR Database from 2000 to 2018. Prevalence of various possible risk factors for pediatric and adult stroke was assessed using ICD 9 and 10 codes. Odds ratios were calculated using a control group of patients without stroke., Results: 10,688 children were identified with stroke. 6339 (59 %) were ischemic and 4349 (41 %) were hemorrhagic. The most frequently identified risk factors for ischemic stroke across age groups were hypertension (29-44 %), trauma (19-33 %), and malignancy (11-24 %). The most common risk factors seen with hemorrhagic stroke were trauma (32-64 %), malignancy (5-19 %) and arrhythmia (9-12 %). Odds ratios across all age groups for dyslipidemia (17-64), hypertension (20-63), and tobacco exposure (3-59) were high in the ischemic stroke cohort., Conclusion: This is the largest retrospective study of pediatric stroke of its kind from hospitals across the US in both academic and non-academic clinical settings. Much of our data was consistent with prior studies. ICD codes for tobacco exposure, hyperlipidemia, diabetes, and hypertension all had high odds ratios for stroke in children, which suggest a relationship between these conditions and pediatric stroke. However, ascertainment bias is a major concern with electronic health record-based studies. More focused study is needed into the role of these exposures into the pathogenesis of pediatric stroke., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: The incidence of stroke and stroke-related hemiparesis has been steadily increasing and is projected to become a serious social, financial, and physical burden on the aging population. Limited access to outpatient rehabilitation for these stroke survivors further deepens the healthcare issue and estranges the stroke patient demographic in rural areas. However, new advances in motion detection deep learning enable the use of handheld smartphone cameras for body tracking, offering unparalleled levels of accessibility., Methods: In this study we want to develop an automated method for evaluation of a shortened variant of the Fugl-Meyer assessment, the standard stroke rehabilitation scale describing upper extremity motor function. We pair this technology with a series of machine learning models, including different neural network structures and an eXtreme Gradient Boosting model, to score 16 of 33 (49%) Fugl-Meyer item activities., Results: In this observational study, 45 acute stroke patients completed at least 1 recorded Fugl-Meyer assessment for the training of the auto-scorers, which yielded average accuracies ranging from 78.1% to 82.7% item-wise., Conclusion: In this study, an automated method was developed for the evaluation of a shortened variant of the Fugl-Meyer assessment, the standard stroke rehabilitation scale describing upper extremity motor function. This novel method is demonstrated with potential to conduct telehealth rehabilitation evaluations and assessments with accuracy and availability.

Introduction: Pediatric stroke is among the top 10 causes of death in pediatrics. Rapid recognition and treatment can improve outcomes in select patients, as evidenced by recent retrospective studies in pediatric thrombectomy. We established a collaborative protocol involving the vascular neurology and pediatric neurology division in our institution to rapidly diagnose and treat pediatric suspected stroke. We also prospectively collected data to attempt to identify predictors of acute stroke in pediatric patients., Methods: IRB approval was obtained to prospectively collect clinical data on pediatric code stroke activations based on timing metrics in resident-physician note templates. The protocol emphasized magnetic resonance imaging over computed tomography imaging when possible. We analyzed performance of the system with descriptive statistics. We then performed a Bayesian statistical analysis to search for predictors of pediatric stroke., Results: There were 40 pediatric code strokes over the 2.5-year study period with a median age of 10.8 years old. 12 (30%) of patients had stroke, and 28 (70%) of code stroke patients were diagnosed with a stroke mimic. Median time from code stroke activation to completion of imaging confirming or ruling out stroke was 1 h. In the Bayesian analysis, altered mental status, hemiparesis, and vasculopathy history were associated with increased odds of stroke, though credible intervals were wide due to the small sample size., Conclusion: A trainee developed and initiated pediatric acute stroke protocol quickly implemented a hospital wide change in management that led to rapid diagnosis and triage of pediatric stroke and suspected stroke. No additional personnel or resources were needed for this change, and we encourage other hospitals and emergency departments to implement similar systems. Additionally, hemiparesis and altered mental status were predictors of stroke for pediatric acute stroke activation in our Bayesian statistical analysis. However credible intervals were wide due to the small sample size. Further multicenter data collection could more definitively analyze predictors of stroke, as well as the help in the creation of diagnostic tools for clinicians in the emergency setting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Phelps, Silos, De La Torre, Moreno, Lapus, Sanghani, Koenig, Savitz, Green and Fraser.)

Aims: The aim of this rapid review and opinion paper is to present the state of the current evidence and present future directions for telehealth research and clinical service delivery for stroke rehabilitation., Methods: We conducted a rapid review of published trials in the field. We searched Medline using key terms related to stroke rehabilitation and telehealth or virtual care. We also searched clinical trial registers to identify key ongoing trials., Results: The evidence for telehealth to deliver stroke rehabilitation interventions is not strong and is predominantly based on small trials prone to Type 2 error. To move the field forward, we need to progress to trials of implementation that include measures of adoption and reach, as well as effectiveness. We also need to understand which outcome measures can be reliably measured remotely, and/or develop new ones. We present tools to assist with the deployment of telehealth for rehabilitation after stroke., Conclusion: The current, and likely long-term, pandemic means that we cannot wait for stronger evidence before implementing telehealth. As a research and clinical community, we owe it to people living with stroke internationally to investigate the best possible telehealth solutions for providing the highest quality rehabilitation.

Since the 2019 novel coronavirus disease (COVID-19) outbreak in 2019 and the pandemic continues for more than one year, a vast amount of drug research has been conducted and few of them got FDA approval. Our objective is to prioritize repurposable drugs using a pipeline that systematically integrates the interaction between COVID-19 and drugs, deep graph neural networks, and in vitro/population-based validations. We first collected all available drugs (n = 3635) related to COVID-19 patient treatment through CTDbase. We built a COVID-19 knowledge graph based on the interactions among virus baits, host genes, pathways, drugs, and phenotypes. A deep graph neural network approach was used to derive the candidate drug's representation based on the biological interactions. We prioritized the candidate drugs using clinical trial history, and then validated them with their genetic profiles, in vitro experimental efficacy, and population-based treatment effect. We highlight the top 22 drugs including Azithromycin, Atorvastatin, Aspirin, Acetaminophen, and Albuterol. We further pinpointed drug combinations that may synergistically target COVID-19. In summary, we demonstrated that the integration of extensive interactions, deep neural networks, and multiple evidence can facilitate the rapid identification of candidate drugs for COVID-19 treatment., (© 2021. The Author(s).)

Introduction: Post-stroke depression (PSD) is a severe complication of cerebrovascular stroke affecting about one-third of stroke survivors. Moreover, PSD is associated with functional recovery and quality of life (QOL) in stroke survivors. Screening for PSD is recommended. There are, however, differences in the literature on the impact of early screening on functional outcomes. In this systematic review, we synthesise the currently available literature regarding the associations between timing and setting of PSD screening and mortality, QOL and functional outcomes in stroke survivors., Methods and Analysis: We will systematically search electronic databases including PubMed, Embase, APA PsycINFO, Web of Science, Scopus and CINAHL from inception to August 2021. Four reviewers will screen the title and abstract and full-text level records identified in the search in a blinded fashion to determine the study eligibility. Any selection disagreements between the reviewers will be resolved by the study investigator. Data extraction of eligible studies will be conducted by two reviewers using a predefined template. We will complete the quality assessment of included articles independently by two reviewers using the Newcastle Ottawa Scale. Eventual discrepancies will be resolved by the principal investigator., Ethics and Dissemination: Due to the nature of the study design, ethical approval is not required. The systematic review and meta-analysis findings will be published and disseminated in a peer-reviewed journal. Our results will also be disseminated through posters and presentations at appropriate scientific conferences., Prospero Registration Number: CRD42021235993., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Neuroinflammation plays a key role in PD pathogenesis, and allogeneic bone marrow-derived mesenchymal stem cells can be used as an immunomodulatory therapy., Objective: The objective of this study was to prove the safety and tolerability of intravenous allogeneic bone marrow-derived mesenchymal stem cells in PD patients., Methods: This was a 12-month single-center open-label dose-escalation phase 1 study of 20 subjects with mild/moderate PD assigned to a single intravenous infusion of 1 of 4 doses: 1, 3, 6, or 10 × 10 6 allogeneic bone marrow-derived mesenchymal stem cells/kg, evaluated 3, 12, 24, and 52 weeks postinfusion. Primary outcome safety measures included transfusion reaction, study-related adverse events, and immunogenic responses. Secondary outcomes included impact on peripheral markers, PD progression, and changes in brain perfusion., Results: There were no serious adverse reactions related to the infusion and no responses to donor-specific human leukocyte antigens. Most common treatment-emergent adverse events were dyskinesias (20%, n = 4) with 1 emergent and 3 exacerbations; and hypertension (20%, n = 4) with 3 transient episodes and 1 requiring medical intervention. One possibly related serious adverse event occurred in a patient with a 4-year history of lymphocytosis who developed asymptomatic chronic lymphocytic leukemia. Peripheral inflammation markers appear to be reduced at 52 weeks in the highest dose including, tumor necrosis factor-α (P < 0.05), chemokine (C-C motif) ligand 22 (P < 0.05), whereas brain-derived neurotrophic factor (P < 0.05) increased. The highest dose seems to have demonstrated the most significant effect at 52 weeks, reducing the OFF state UPDRS motor, -14.4 (P < 0.01), and total, -20.8 (P < 0.05), scores., Conclusion: A single intravenous infusion of allogeneic bone marrow-derived mesenchymal stem cells at doses of 1, 3, 6, or 10 × 10 6 allogeneic bone marrow-derived mesenchymal stem cells/kg is safe, well tolerated, and not immunogenic in mild/moderate PD patients. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Objective: To evaluate the comparative safety and efficacy of direct endovascular thrombectomy (dEVT) compared to bridging therapy (BT; IV tissue plasminogen activator + EVT) and to assess whether BT potential benefit relates to stroke severity, size, and initial presentation to EVT vs non-EVT center., Methods: In a prospective multicenter cohort study of imaging selection for endovascular thrombectomy (Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke [SELECT]), patients with anterior circulation large vessel occlusion (LVO) presenting to EVT-capable centers within 4.5 hours from last known well were stratified into BT vs dEVT. The primary outcome was 90-day functional independence (modified Rankin Scale [mRS] score 0-2). Secondary outcomes included a shift across 90-day mRS grades, mortality, and symptomatic intracranial hemorrhage. We also performed subgroup analyses according to initial presentation to EVT-capable center (direct vs transfer), stroke severity, and baseline infarct core volume., Results: We identified 226 LVOs (54% men, mean age 65.6 ± 14.6 years, median NIH Stroke Scale [NIHSS] score 17, 28% received dEVT). Median time from arrival to groin puncture did not differ in patients with BT when presenting directly (dEVT 1.43 [interquartile range (IQR) 1.13-1.90] hours vs BT 1.58 [IQR 1.27-2.02] hours, p = 0.40) or transferred to EVT-capable centers (dEVT 1.17 [IQR 0.90-1.48] hours vs BT 1.27 [IQR 0.97-1.87] hours, p = 0.24). BT was associated with higher odds of 90-day functional independence (57% vs 44%, adjusted odds ratio [aOR] 2.02, 95% confidence interval [CI] 1.01-4.03, p = 0.046) and functional improvement (adjusted common OR 2.06, 95% CI 1.18-3.60, p = 0.011) and lower likelihood of 90-day mortality (11% vs 23%, aOR 0.20, 95% CI 0.07-0.58, p = 0.003). No differences in any other outcomes were detected. In subgroup analyses, patients with BT with baseline NIHSS scores <15 had higher functional independence likelihood compared to those with dEVT (aOR 4.87, 95% CI 1.56-15.18, p = 0.006); this association was not evident for patients with NIHSS scores ≥15 (aOR 1.05, 95% CI 0.40-2.74, p = 0.92). Similarly, functional outcomes improvements with BT were detected in patients with core volume strata (ischemic core <50 cm 3 : aOR 2.10, 95% CI 1.02-4.33, p = 0.044 vs ischemic core ≥50 cm 3 : aOR 0.41, 95% CI 0.01-16.02, p = 0.64) and transfer status (transferred: aOR 2.21, 95% CI 0.93-9.65, p = 0.29 vs direct to EVT center: aOR 1.84, 95% CI 0.80-4.23, p = 0.15)., Conclusions: BT appears to be associated with better clinical outcomes, especially with milder NIHSS scores, smaller presentation core volumes, and those who were "dripped and shipped." We did not observe any potential benefit of BT in patients with more severe strokes., Trial Registration Information: ClinicalTrials.gov Identifier: NCT02446587., Classification of Evidence: This study provides Class III evidence that for patients with ischemic stroke from anterior circulation LVO within 4.5 hours from last known well, BT compared to dEVT leads to better 90-day functional outcomes., (© 2021 American Academy of Neurology.)

Background: Tissue plasminogen activator (tPA) refusal is 4%-6% for acute ischemic stroke (AIS) in the emergency department. Telestroke (TS) has increased the use of tPA for AIS but is accompanied by barriers in communication that can affect tPA consent. We characterized the incidence of tPA refusal in our TS network and its associated reasons., Methods: Patients with AIS who were offered tPA within 4.5 hours from symptom onset according to American Heart Association guidelines were identified within our Lone Star Stroke Consortium Telestroke Registry from September 2015 to December 2018. We compared baseline characteristics and clinical outcomes between patients who refused tPA and patients who accepted tPA., Results: Among the 1,242 patients who qualified for tPA and were offered treatment, 8% refused tPA. Female and non-Hispanic Black patients and patients with a prior history of stroke were more likely to decline tPA. Patients who refused tPA presented with a lower NIHSS and were associated with a final diagnosis of stroke mimic (odds ratio [OR] 0.23; 95% confidence interval [CI] 0.15-0.36). Good outcome (90-day modified Rankin Scale 0-2) was the same among patients who received tPA and those who refused (OR 0.80; 95% CI 0.42-1.54). The most common reasons for refusal were rapidly improving and mild/nondisabling symptoms and concern for potential side effects., Conclusion: tPA refusal over TS is comparable to previously reported rates; there was no difference in outcomes among patients who received tPA compared with those who refused. Sex and racial differences associated with an increased tPA refusal warrant further investigation in efforts to achieve equity/parity in tPA decisions., (© 2021 American Academy of Neurology.)

Background: Web-based interventions have shown promise for chronic disease management but have not been widely applied to populations with stroke. Existing barriers may inhibit the adoption of web-based interventions among stroke survivors and necessitate the involvement of informal caregivers. However, limited information is available on internet accessibility and usability among stroke survivors and their caregivers., Objective: This study aims to investigate internet access and usage in a cohort of stroke survivors and their caregivers., Methods: A cross-sectional survey was conducted with 375 participants (248 stroke survivors and 127 caregivers). Descriptive statistics were generated using cross-tabulation. Comparisons with categorical data were conducted using the chi-square test, whereas the Mann-Whitney U test was used for comparisons involving ordinal variables., Results: Overall, 86.1% (323/375) of the participants reported having internet access. Caregivers were more likely than stroke survivors to access the internet (N=375, χ 2 1 =18.5, P<.001) and used text messaging (n=321, χ 2 1 =14.7, P<.001). Stroke survivors and caregivers with internet access were younger than stroke survivors and caregivers without internet access. The highest number of participants who reported internet access were non-Hispanic White. Smartphones were the most common devices used to access the internet. Email was the most common type of internet usage reported. Patients who survived for >12 months after a stroke reported higher internet access than those who survived <3 months (P<.001). The number of hours per week spent using the internet was higher for caregivers than for stroke survivors (P<.001)., Conclusions: Future feasibility and acceptability studies should consider the role of the informal caregiver, participant age, race and ethnicity, the use of smartphone apps, email and text correspondence, and the amount of time elapsed since the stroke event in the design and implementation of web-based interventions for populations with stroke., (©Imama Ali Naqvi, Tahani Casameni Montiel, Yazan Bittar, Norma Hunter, Munachi Okpala, Constance Johnson, Mark G Weiner, Sean Savitz, Anjail Sharrief, Jennifer Elizabeth Sanner Beauchamp. Originally published in JMIR Formative Research (http://formative.jmir.org), 08.03.2021.)

Background: Informal caregiving of stroke survivors often begins with intensity compared with the linear caregiving trajectories in progressive conditions. Informal caregivers of stroke survivors are often inadequately prepared for their caregiving role, which can have detrimental effects on their well-being. A greater depth of understanding about caregiving burden is needed to identify caregivers in most need of intervention. The purpose of this study was to examine caregiver burden and associated factors among a cohort of informal caregivers of stroke survivors., Methods: A cross-sectional study of 88 informal caregivers of stroke survivors was completed. Caregiver burden was determined with the Zarit Burden Interview, caregiver depressive symptoms were measured with the Patient Health Questionnaire-9, and stroke survivor functional disability was assessed with the Barthel Index. Ordinal logistic regression was used to identify independent factors associated with caregiver burden., Results: Forty-three informal caregivers (49%) reported minimal or no caregiver burden, 30 (34%) reported mild to moderate caregiver burden, and 15 (17%) reported moderate to severe caregiver burden. Stroke survivor functional disability was associated with informal caregiver burden (P = .0387). The odds of having mild to moderate caregiver burden were 3.7 times higher for informal caregivers of stroke survivors with moderate to severe functional disability than for caregivers of stroke survivors with no functional disability. The presence of caregiver depressive symptoms was highly correlated with caregiver burden (P < .001)., Conclusion: Caregivers of stroke survivors with functional disabilities and caregivers experiencing depressive symptoms may have severer caregiver burden. Trials of interventions aimed at decreasing informal caregiver burden should consider the potential impact of stroke survivors' functional disability and the presence of depressive symptoms.

Background and Purpose- Timely access to endovascular thrombectomy (EVT) centers is vital for best acute ischemic stroke outcomes. Methods- US stroke-treating centers were mapped utilizing geo-mapping and stratified into non-EVT or EVT if they reported ≥1 acute ischemic stroke thrombectomy code in 2017 to Center for Medicare and Medicaid Services. Direct EVT-access, defined as the population with the closest facility being an EVT-center, was calculated from validated trauma-models adapted for stroke. Current 15- and 30-minute access were described nationwide and at state-level with emphasis on 4 states (TX, NY, CA, IL). Two optimization models were utilized. Model-A used a greedy algorithm to capture the largest population with direct access when flipping 10% and 20% non-EVT to EVT-centers to maximize access. Model-B used bypassing methodology to directly transport patients to the nearest EVT centers if the drive-time difference from the geo-centroid to hospital was within 15 minutes from the geo-centroid to the closest non-EVT center. Results- Of 1941 stroke-centers, 713 (37%) were EVT. Approximately 61 million (19.8%) Americans have direct EVT access within 15 minutes while 95 million (30.9%) within 30 minutes. There were 65 (43%) EVT centers in TX with 22% of the population currently within 15-minute access. Flipping 10% hospitals with top population density improved access to 30.8%, while bypassing resulted in 45.5% having direct access to EVT centers. Similar results were found in NY (current, 20.9%; flipping, 34.7%; bypassing, 50.4%), CA (current, 25.5%; flipping, 37.3%; bypassing, 53.9%), and IL (current, 15.3%; flipping, 21.9%; bypassing, 34.6%). Nationwide, the current direct access within 15 minutes of 19.8% increased by 7.5% by flipping the top 10% non-EVT to EVT-capable in all states. Bypassing non-EVT centers by 15 minutes resulted in a 16.7% gain in coverage. Conclusions- EVT-access within 15 minutes is limited to less than one-fifth of the US population. Optimization methodologies that increase EVT centers or bypass non-EVT to the closest EVT center both showed enhanced access. Results varied by states based on the population size and density. However, bypass showed more potential for maximizing direct EVT-access. National and state efforts should focus on identifying gaps and tailoring solutions to improve EVT-access.

Objective: The primary imaging modalities used to select patients for endovascular thrombectomy (EVT) are noncontrast computed tomography (CT) and CT perfusion (CTP). However, their relative utility is uncertain. We prospectively assessed CT and CTP concordance/discordance and correlated the imaging profiles on both with EVT treatment decisions and clinical outcomes., Methods: A phase 2, multicenter, prospective cohort study of large-vessel occlusions presented up to 24 hours from last known well was conducted. Patients received a unified prespecified imaging evaluation (CT, CT angiography, and CTP with Rapid Processing of Perfusion and Diffusion software mismatch determination). The treatment decision, EVT versus medical management, was nonrandomized and at the treating physicians' discretion. An independent, blinded, neuroimaging core laboratory adjudicated favorable profiles based on predefined criteria (CT:Alberta Stroke Program Early CT Score ≥ 6, CTP:regional cerebral blood flow (<30%) < 70ml with mismatch ratio ≥ 1.2 and mismatch volume ≥ 10ml)., Results: Of 4,722 patients screened from January 2016 to February 2018, 361 patients were included. Two hundred eighty-five (79%) received EVT, of whom 87.0% had favorable CTs, 91% favorable CTPs, 81% both favorable profiles, 16% discordant, and 3% both unfavorable. Favorable profiles on the 2 modalities correlated similarly with 90-day functional independence rates (favorable CT = 56% vs favorable CTP = 57%, adjusted odds ratio [aOR] = 1.91, 95% confidence interval [CI] = 0.40-9.01, p = 0.41). Having a favorable profile on both modalities significantly increased the odds of receiving thrombectomy as compared to discordant profiles (aOR = 3.97, 95% CI = 1.97-8.01, p < 0.001). Fifty-eight percent of the patients with favorable profiles on both modalities achieved functional independence as compared to 38% in discordant profiles and 0% when both were unfavorable (p < 0.001 for trend). In favorable CT/unfavorable CTP profiles, EVT was associated with high symptomatic intracranial hemorrhage (sICH) (24%) and mortality (53%) rates., Interpretation: Patients with favorable imaging profiles on both modalities had higher odds of receiving EVT and high functional independence rates. Patients with discordant profiles achieved reasonable functional independence rates, but those with an unfavorable CTP had higher adverse outcomes. Ann Neurol 2020;87:419-433., (© 2020 American Neurological Association.)

Background: Effective medical record documentation is required to support accurate capture of diagnoses, patient acuity (case mix index [CMI]), and justify resource utilization for reimbursement. Billing code complexity and a lack of formal documentation education in training programs have created a need for academic medical centers to incorporate training for trainees (residents, fellows, and new nurse practitioners). We hypothesized that standardized stroke note templates, trainee education, and feedback from chart audits would improve documentation accuracy., Purpose: To improve the accurate/complete capture of expected (E) length of stay (LOS) and CMI by designing/implementing ischemic and hemorrhagic stroke templates containing high-frequency complication and comorbidity diagnoses with the greatest impact on stroke populations, combined with trainee education and chart audits., Methods: Descriptive statistics were used for outcomes before/after implementation of the templates. Primary outcomes include ELOS and CMI. Wilcoxon rank-sum test or chi-square test was used for group comparison., Results: The post-template group demonstrated a significant improvement in ELOS from 5.84 to 8.27 days (p < .0001). Case mix index increased (1.73-1.75; p < .0001) in the post-template group., Conclusions: Stroke-specific templates, trainee education, and chart audits were associated with significant improvement in documentation accuracy and an improved business model of stroke care in our hospital.

Importance: The efficacy and safety of endovascular thrombectomy (EVT) in patients with large ischemic cores remains unknown, to our knowledge., Objective: To compare outcomes in patients with large ischemic cores treated with EVT and medical management vs medical management alone., Design, Setting, and Participants: This prespecified analysis of the Optimizing Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT) trial, a prospective cohort study of imaging selection that was conducted in 9 US comprehensive stroke centers, enrolled patients between January 2016 and February 2018, and followed them up for 90 days. Patients with moderate to severe stroke and anterior circulation large-vessel occlusion presenting up to 24 hours from the time they were last known to be well were eligible for the cohort. Of these, patients with large ischemic cores on computed tomography (CT) (Alberta Stroke Program Early CT Score <6) or CT perfusion scanning (a volume with a relative cerebral blood flow <30% of ≥50 cm3) were included in analyses., Exposures: Endovascular thrombectomy with medical management (MM) or MM only., Main Outcomes and Measures: Functional outcomes at 90 days per modified Rankin scale; safety outcomes (mortality, symptomatic intracerebral hemorrhage, and neurological worsening)., Results: A total of 105 patients with large ischemic cores on either CT or CT perfusion images were included: 71 with Alberta Stroke Program Early CT Scores of 5 or less (EVT, 37; MM, 34), 74 with cores of 50 cm3 or greater on CT perfusion images (EVT, 39; MM, 35), and 40 who had large cores on both CT and CT perfusion images (EVT, 14; MM, 26). The median (interquartile range) age was 66 (60-75) years; 45 patients (43%) were female. Nineteen of 62 patients (31%) who were treated with EVT achieved functional independence (modified Rankin Scale scores, 0-2) vs 6 of 43 patients (14%) treated with MM only (odds ratio [OR], 3.27 [95% CI, 1.11-9.62]; P = .03). Also, EVT was associated with better functional outcomes (common OR, 2.12 [95% CI, 1.05-4.31]; P = .04), less infarct growth (44 vs 98 mL; P = .006), and smaller final infarct volume (97 vs 190 mL; P = .001) than MM. In the odds of functional independence, there was a 42% reduction per 10-cm3 increase in core volume (adjusted OR, 0.58 [95% CI, 0.39-0.87]; P = .007) and a 40% reduction per hour of treatment delay (adjusted OR, 0.60 [95% CI, 0.36-0.99]; P = .045). Of 10 patients who had EVT with core volumes greater than 100 cm3, none had a favorable outcome., Conclusions and Relevance: Although the odds of good outcomes for patients with large cores who receive EVT markedly decline with increasing core size and time to treatment, these data suggest potential benefits. Randomized clinical trials are needed.

Introduction: The Lone Star Stroke Consortium Telestroke Registry (LeSteR) currently consisting of 3 academic hub centres and 27 partner spokes is a statewide initiative organised by leading academic health centres in the State of Texas to understand practice patterns of acute stroke management via telestroke (TS) in Texas, a state with one of the largest rural populations in the USA., Methods and Analysis: All patients who had presumed stroke for whom a TS consultation has been obtained in the network are entered into a web-based, Health Insurance Portability and Accountability Act-compliant database from September 2013 to present. Spokes were enrolled into LeSteR in a staggered approach in two data collection phases: a retrospective phase and a prospective phase. Basic clinical, demographic data and relevant time metrics are collected in the retrospective phase. Starting 1 September 2015, additional outcome data including 90-day modified Rankin score, readmission and 90-day disposition are obtained by a standard phone interview. From the registry initiation to 31 December 2017, there are 8089 patients who had suspected stroke in the registry. Over 60% of patients enrolled after 1 September 2015 have reported outcome data. Enrolment is still active for this registry., Ethics and Dissemination: LeSteR is a statewide TS registry organised by academic health centres that will provide significant insight regarding the impact of TS in the State of Texas. Findings from LeSteR will provide data that can be analysed to improve the allocation of healthcare resources using TS to treat stroke in a state with one of the largest rural populations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Perihematomal edema (PHE) occurs in patients with intracerebral hemorrhage (ICH) and is often used as surrogate of secondary brain injury. PHE resolves over time, but little is known about the functional integrity of the tissues that recover from edema. In a pig ICH model, we aimed to assess metabolic integrity of perihematoma tissues by using non-invasive magnetic resonance spectroscopy (MRS)., Materials and Methods: Fourteen male Yorkshire pigs with an average age of 8 weeks were intracerebrally injected with autologous blood to produce ICH. Proton MRS data were obtained at 1, 7, and 14 days after ICH using a whole-body 3.0T MRI system. Point-resolved spectroscopy (PRESS)-localized 2D chemical shift imaging (CSI) was acquired. The concentration of N -Acetylaspartate (NAA), Choline (Cho), and Creatine (Cr) were measured within the area of PHE, tissues adjacent to the injury with no or negligible edema (ATNE), and contralesional brain tissue. A linear mixed model was used to analyze the evolution of metabolites in perihematomal tissues, with p -value < 0.05 indicating statistical significance., Results: The perihematoma volume gradually decreased from 2.38 ± 1.23 ml to 0.41 ± 0.780 ml ( p < 0.001) over 2 weeks. Significant ( p < 0.001) reductions in NAA, Cr, and Cho concentrations were found in the PHE and ATNE regions compared to the contralesional hemisphere at day 1 and 7 after ICH. All three metabolites were significantly ( p < 0.001) restored in the PHE tissue on day 14, but remained persistently low in the ATNE area, and unaltered in the contralesional voxel., Conclusion: This study highlights the potential of MRS to probe salvageable tissues within the perihematoma in the sub-acute phase of ICH. Altered metabolites within the PHE and ATNE regions in addition to edema and hematoma volumes were explored as possible markers for tissue recovery. Perihematomal tissue with PHE demonstrated a more reversible injury compared to the tissue adjacent to the injury without edema, suggesting a potentially beneficial role of edema.

Background and Purpose- Telemedicine is increasingly utilized for intravenous tPA (tissue-type plasminogen activator) delivery. The comparative safety of leaving tPA-treated patients at a presenting (spoke) hospital (drip-and-stay) or transferring patients to a central treating (hub) hospital (drip-and-ship) is not established. We sought to compare outcomes between drip-and-ship and drip-and-stay patients treated with tPA via telemedicine. We hypothesized that there would be no differences in short-term outcomes of in-hospital mortality, length of stay, or discharge disposition or in 90-day outcomes between groups. Methods- We retrospectively identified patients treated with tPA at 17 spoke hospitals between September 2015 and December 2016. Demographic, clinical, and outcome data were obtained from a prospective telemedicine registry. We used negative binomial, multinomial, and logistic regression analyses to evaluate length of stay, discharge disposition, and inpatient mortality, respectively. We compared the proportion of patients with 90-day modified Rankin Scale score <2 by group. Results- Among 430 tPA-treated patients, 232 (53.9%) were transferred to the hub after treatment. The median arrival National Institutes of Health Stroke Scale score was higher for drip-and-ship (10; interquartile range, 5-18) compared with drip-and-stay patients (6; interquartile range, 4-10; P<0.001). Unadjusted length of stay was longer in drip-and-stay patients (incidence rate ratio, 0.82; 95% CI, 0.71-0.95). There were no significant differences in adjusted length of stay, hospital mortality, or discharge disposition. Among the 64% of patients with complete 90-day modified Rankin Scale score, the proportion with good outcomes (modified Rankin Scale score <2) did not differ between groups. Conclusions- We found no differences in measured outcomes between drip-and-ship and drip-and-stay patients treated in our network, although our study may be underpowered to detect small differences.

Purpose: Ongoing post-stroke structural degeneration and neuronal loss preceding neuropsychological symptoms such as cognitive decline and depression are poorly understood. Various substructures of the limbic system have been linked to cognitive impairment. In this longitudinal study, we investigated the post-stroke macro- and micro-structural integrity of the limbic system using structural and diffusion tensor magnetic resonance imaging. Materials and Methods: Nineteen ischemic stroke patients (11 men, 8 women, average age 53.4 ± 12.3, range 18-75 years), with lesions remote from the limbic system, were serially imaged three times over 1 year. Structural and diffusion-tensor images (DTI) were obtained on a 3.0 T MRI system. The cortical thickness, subcortical volume, mean diffusivity (MD), and fractional anisotropy (FA) were measured in eight different regions of the limbic system. The National Institutes of Health Stroke Scale (NIHSS) was used for clinical assessment. A mixed model for multiple factors was used for statistical analysis, and p -values <0.05 was considered significant. Results: All patients demonstrated improved NIHSS values over time. The ipsilesional subcortical volumes of the thalamus, hippocampus, and amygdala significantly decreased ( p < 0.05) and MD significantly increased ( p < 0.05). The ipsilesional cortical thickness of the entorhinal and perirhinal cortices was significantly smaller than the contralesional hemisphere at 12 months ( p < 0.05). The cortical thickness of the cingulate gyrus at 12 months was significantly decreased at the caudal and isthmus regions as compared to the 1 month assessment ( p < 0.05). The cingulum fibers had elevated MD at the ipsilesional caudal-anterior and posterior regions compared to the corresponding contralesional regions. Conclusion: Despite the decreasing NIHSS scores, we found ongoing unilateral neuronal loss/secondary degeneration in the limbic system, irrespective of the lesion location. These results suggest a possible anatomical basis for post stroke psychiatric complications.

Background and Purpose- Psychological stressors, including poststroke depression, poststroke anxiety, and posttraumatic stress disorder, are highly prevalent in stroke survivors. These symptoms exact a significant toll on stroke survivors. Clinical and research efforts in stroke recovery focus on motor disability, speech and language deficits, and cognitive dysfunction while largely neglecting psychological stressors. Evidence suggests mind-body interventions in other chronic illness populations decrease symptoms of depression, regulate immune responses, and promote resilience, yet similar studies are lacking in stroke populations. This review aims to synthesize evidence of the effects of mind-body interventions on psychological stressors, quality of life, and biological outcomes for stroke survivors. Methods- A systematic search of PubMed, PsycINFO, and CINAHL was conducted from database inception to November 2017. Results- Eight studies were included in the review, with a total of 292 participants. Mind-body interventions included yoga or tai chi. Of the 5 included randomized controlled trials, most were pilot or feasibility studies with small sample sizes. Psychological stressors, including poststroke depression and anxiety, along with the quality of life, improved over time, but statistically significant between-group differences were largely absent. The 3 included studies with a qualitative design reported themes reflecting improvement in psychological stressors and quality of life. No included studies reported biological outcomes. Conclusions- Studies of mind-body interventions suggest a possible benefit on psychological stressors and quality of life; however, rigorously designed, sufficiently powered randomized controlled trials with mixed-methods design are warranted to delineate specific treatment effects of these interventions. Studies with both biological and psychological stressors as outcomes would provide evidence about interaction effects of these factors on stroke-survivor responses to mind-body interventions.

Background: Dysphagia is a common complication of stroke and can have a lasting impact on morbidity and mortality; yet there are no standards to guide dysphagia management in stroke patients. We assessed predictors of percutaneous endoscopic gastrostomy (PEG) placement in an ischemic stroke cohort and sought to determine the utility of an objective scale in predicting PEG placement in a high-risk sub-set., Methods: Consecutive cases of ischemic stroke were retrospectively, identified and demographic and clinical variables were collected. Penetration-Aspiration (PAS) scores (1-2 normal; 3-5 penetration; 6-8 aspiration) were calculated for patients undergoing Fiberoptic Endoscopic Evaluation of Swallowing (FEES) or Modified Barium Swallowing Studies (MBSS). Multiple logistic regression analysis was used to assess predictors of PEG placement., Results: Among 724 patients, 131 underwent PEG placement. In univariate analysis of the overall cohort, sex, age, insured payer status, arrival National Institute of Health Stroke Scale (NIHSS), NIHSS level of consciousness severity, NIHSS dysarthria severity, diabetes mellitus, and prior International Conference for Harmonization (ICH) were all significantly associated with PEG placement. Among 197 high-risk patients undergoing FEES or MBSS, the multivariate logistic regression analysis showed that PAS scores 6-8 versus 1-2 (odds ratio [OR] 13.2; 95% confidence interval [CI] 4.58, 38.2), PAS score 3-5 versus 1.2 (OR 33.8; 95% CI 11.6, 98.3), Hispanic race (OR, 5.73; 95% CI 1.82, 18.0), male sex (OR, 2.59; 95% CI 1.05, 6.34), and arrival NIHSS (OR, 1.11; 95% CI 1.05, 1.18) were associated with PEG placement., Conclusions: Use of an objective dysphagia scale simplified the prediction model among acute ischemic stroke patients undergoing instrumental assessments of dysphagia with FEES or MBSS. Male sex and Hispanic race were also significantly associated with PEG placement in this analysis. These findings support the need for rigorously designed prospective studies to assess biological and social factors that influence PEG placement and to determine, how to best evaluate and manage patients with dysphagia., (Published by Elsevier Inc.)

Background and Purpose- The aims of this study were to investigate the effect of an intervention to unblind data on r-tPA (recombinant tissue-type plasminogen activator) administration and sharing data with chief executive officers of participating hospitals, on r-tPA administration rates postintervention and on potential healthcare cost savings implemented at 26 Southeast Texas Regional Advisory Council hospitals. Methods- Retrospective analysis of prospective data on thrombolytic therapy from 26 Southeast Texas Regional Advisory Council hospitals, collected between April 2014 and June 2016. The control (blinded) period (Q2-2014 to Q2-2015) was followed by unblinding (Q3-2015). Results- Intervention was associated with 21.1% increase in r-tPA administration rates, with 38.5% increase in r-tPA administration with door-to-needle time ≤60 minutes. An absolute increase in r-tPA administration of 2.1% was seen with an average lifetime cost savings of $3.6 million. Conclusions- Transparent regional data sharing was associated with improved r-tPA administration and healthcare cost savings.

For many years, quasicrystals were observed only as solid-state metallic alloys, yet current research is now actively exploring their formation in a variety of soft materials, including systems of macromolecules, nanoparticles and colloids. Much effort is being invested in understanding the thermodynamic properties of these soft-matter quasicrystals in order to predict and possibly control the structures that form, and hopefully to shed light on the broader yet unresolved general questions of quasicrystal formation and stability. Moreover, the ability to control the self-assembly of soft quasicrystals may contribute to the development of novel photonics or other applications based on self-assembled metamaterials. Here a path is followed, leading to quantitative stability predictions, that starts with a model developed two decades ago to treat the formation of multiple-scale quasiperiodic Faraday waves (standing wave patterns in vibrating fluid surfaces) and which was later mapped onto systems of soft particles, interacting via multiple-scale pair potentials. The article reviews, and substantially expands, the quantitative predictions of these models, while correcting a few discrepancies in earlier calculations, and presents new analytical methods for treating the models. In so doing, a number of new stable quasicrystalline structures are found with octagonal, octadecagonal and higher-order symmetries, some of which may, it is hoped, be observed in future experiments.

Introduction: The aftermath of stroke leaves many consequences including cognitive deficits and falls due to imbalance. Stroke survivors and families struggle to navigate the complex healthcare system with little assistance posthospital discharge, often leading to early hospital readmission and worse stroke outcomes. Telemedicine Guided Education on Secondary Stroke and Fall Prevention Following Inpatient Rehabilitation feasibility study examines whether stroke survivors and their caregivers find value in telerehabilitation (TR) home visits that provide individualised care and education by a multidisciplinary team after discharge from inpatient rehabilitation., Methods and Analysis: A prospective, single arm, pilot study is designed to evaluate the feasibility of weekly TR home visits initiated postdischarge from inpatient rehabilitation. Newly diagnosed patients with stroke are recruited from a Houston-based comprehensive stroke centre inpatient rehabilitation unit, loaned an iPad with data plan and trained to use information technology security-approved videoconferencing application. After hospital discharge, six weekly TR home visits are led by rotating specialists (pharmacist, physical/occupational therapist, speech therapist, rehabilitation physician, social worker, geriatrician specialised in fracture prevention) followed by satisfaction survey on week 7. Specialists visually assess patients in real time, educate them on secondary stroke and fall prevention and suggest ways to improve function including direct medical interventions when indicated. Primary outcomes are proportion of eligible patients consenting to the study, participation rate in all six TR home visits and satisfaction score. The study started 31 December 2015 with plan to enrol up to 50 patients over 24 months. Feasibility study results will inform us as to whether a randomised controlled trial is warranted to determine efficacy of TR home visit intervention in improving stroke outcomes., Ethics and Dissemination: Ethics approval obtained by the Institutional Review Board (IRB), Committee for the Protection of Human Subjects, IRB number: HSC-MS-14-0994. Study results will be submitted for publication in a peer-reviewed journal., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Stroke recovery is the next frontier in stroke medicine. While growth in rehabilitation and recovery research is exponential, a number of barriers hamper our ability to rapidly progress the field. Standardized terminology is absent in both animal and human research, methods are poorly described, recovery biomarkers are not well defined, and we lack consistent timeframes or measures to examine outcomes. Agreed methods and conventions for developing, monitoring, evaluating and reporting interventions directed at improving recovery are lacking, and current approaches are often not underpinned by biology. We urgently need to better understand the biology of recovery and its time course in both animals and humans to translate evidence from basic science into clinical trials. A new international partnership of stroke recovery and rehabilitation experts has committed to advancing the research agenda. In May 2016, the first Stroke Recovery and Rehabilitation Roundtable will be held, with the aim of achieving an agreed approach to the development, conduct and reporting of research. A range of methods will be used to achieve consensus in four priority areas: pre-clinical recovery research; biomarkers of recovery; intervention development, monitoring and reporting; and measurement in clinical trials. We hope to foster a global network of researchers committed to advancing this exciting field. Recovery from stroke is challenging for many survivors. They deserve effective treatments underpinned by our evolving understanding of brain recovery and human behaviour. Working together, we can develop game-changing interventions to improve recovery and quality of life in those living with stroke.

Background and Purpose: The aim of this study is to determine agreement among vascular neurology fellows and faculty in treating patients with acute ischemic stroke with intravenous tissue-type plasminogen activator and intra-arterial thrombectomy (IAT)., Methods: Patients were evaluated simultaneously by at least 2 vascular neurology. Agreement was determined using kappa (κ) and intraclass correlation coefficients., Results: In 60 patients, agreement was substantial for tissue-type plasminogen activator (κ=0.75 [95% confidence interval, 0.57-0.92]) and IAT (κ=0.63 [95% confidence interval, 0.30-0.96]), with no difference between fellow-fellow versus fellow-faculty. Intraclass correlation coefficient for National Institutes of Health Stroke Scale was 0.94 (95% confidence interval, 0.90-0.97) and κ for Alberta Stroke Program Early CT Score was 0.53 (95% confidence interval, 0.20-0.78). Rapidly improving or mild deficits caused disagreement for both tissue-type plasminogen activator and IAT, whereas interpretation of computed tomographic perfusion led to disagreement for IAT., Conclusions: We found substantial agreement between vascular neurology fellows and faculty in treating with tissue-type plasminogen activator or IAT. Areas for improvement include recognition of stroke mimics, consensus on treating less severe strokes, and use/interpretation of imaging., (© 2016 American Heart Association, Inc.)

Background: As a comprehensive stroke center (CSC), we accept transfer patients with intracerebral hemorrhage (ICH) in our region. CSC guidelines mandate receipt of patients with ICH for higher level of care. We determined resource utilization of patients accepted from outside hospitals compared with patients directly arriving to our center., Methods: From our stroke registry, we compared patients with primary ICH transferred to those directly arriving to our CSC from March 2011-March 2012. We compared the proportion of patients who utilized at least one of these resources: neurointensive care unit (NICU), neurosurgical intervention, or clinical trial enrollment., Results: Among the 362 patients, 210 (58%) were transfers. Transferred patients were older, had higher median Glasgow Coma Scale scores, and lower National Institutes of Health Stroke Scale scores than directly admitted patients. Transfers had smaller median ICH volumes (20.5 cc versus 15.2 cc; P = .04) and lower ICH scores (2.1 ± 1.4 versus 1.6 ± 1.3; P < .01). A smaller proportion of transfers utilized CSC-specific resources compared with direct admits (P = .02). Fewer transferred patients required neurosurgical intervention or were enrolled in trials. No significant difference was found in the proportion of patients who used NICU resources, although transferred patients had a significantly lower length of stay in the NICU. Average hospital stay costs were less for transferred patients than for direct admits., Conclusions: Patients with ICH transferred to our CSC underwent fewer neurosurgical procedures and had a shorter stay in the NICU. These results were reflected in the lower per-patient costs in the transferred group. Our results raise the need to analyze cost-benefits and resource utilization of transferring patients with milder ICH., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Heat stress results in multiorgan failure and CNS injury. There a few case reports in the literature on the neurological consequences of heat stress., Case Presentation: We describe a patient with heat stress presenting with encephalopathy and bilateral cerebral, cerebellar, and thalamic lesions and intraventricular hemorrhage on MRI., Conclusion: Heat stress should be in the differential diagnosis of patients presenting with encephalopathy and elevated serum inflammatory markers especially if the history suggests a preceding episode of hyperthermia.

Background: In animal models, the spleen contracts after acute ischemic stroke, followed by release of inflammatory cells leading to secondary brain injury., Aims: We aim to characterize splenic responses in patients with acute ischemic stroke., Methods: In this prospective observational study, we measured daily spleen sizes with abdominal ultrasound in 30 patients with suspected acute ischemic stroke. Splenic ultrasounds were also performed in 20 healthy individuals., Results: A generalized estimating equation, longitudinal regression model for adjusted spleen measurements showed the difference between baseline spleen volume (within six-hours of stroke onset) and the volume at the last measured time point (up to seven-days) to be statistically significant (volume difference of 51·9 cm(3) , P = 0·04). Healthy controls had significantly smaller day-to-day variations; the maximum observed difference in mean spleen volume between any two time points was 9·5 cm(3) , with the average change over the period of observation being 1·24 cm(3) . A statistically significant negative association was also observed between the pattern of change of total white blood cell count and spleen volume (P = 0·01). An analysis of individual cases demonstrated possible associations between daily spleen volume changes and clinical course., Conclusions: We hypothesize that the spleen may initially contract after ischemic stroke followed by a re-expansion and that it contributes to ischemic brain injury mediated via cellular components. Characterization of the splenic response after stroke and its contribution to cerebral ischemic injury has the potential to provide new opportunities for the development of novel stroke therapies., (© 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.)

Stroke-related translational research is multifaceted. Herein, we highlight genome-wide association studies and genetic studies of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, COL4A1 mutations, and cerebral cavernous malformations; advances in molecular biology and biomarkers; newer brain imaging research; and recovery from stroke emphasizing cell-based and other rehabilitative modalities.

Background and Purpose: ET is considered in selected patients with AIS with persistent arterial occlusion after receiving IVT. Limited data exist on the safety of IA high doses of UK and RT for ET. We investigated any correlation between IA doses of UK or RT and safety outcomes in patients who underwent ET., Materials and Methods: We identified all patients from our stroke registry who received UK or RT for ET from 1998 to 2008. Demographics, baseline National Institutes of Health Stroke Scale scores, recanalization rates, rates of attempted MT, mortality, SICH, and discharge modified Rankin Scale scores were collected., Results: Of 197 patients; 72 received UK and 125 received RT. More than 90% of patients in both groups had received prior IVT. The median IA dose of UK was 200,000 U (range, 25,000-1,500,000 U) and of RT was 2 mg (range, 1-8 mg). Concurrent MT was attempted in 59.7% of UK-treated patients and 72.0% of RT-treated patients, with SICH rates of 4.2% and 8.0%, respectively. Logistic regression adjusting for prior IVT and MT revealed no correlation between SICH and doses of UK (OR, 1.00; 95% CI, 0.99-1.00; P = .94) or RT (OR, 0.803; 95% CI, 0.48-1.33; P = .39). There was no correlation between mortality and doses of UK (OR, 1.00; 95% CI, 0.99-1.00; P = .51) or RT (OR, 1.048; 95% CI, 0.77-1.42; P = .75)., Conclusions: High IA doses of UK and RT may be safe when given with or without MT in patients with AIS despite receiving a full dose of intravenous recombinant tissue plasminogen activator. These results need prospective validation.

Background and Purpose: Several studies suggest that various types of cellular therapies enhance recovery after stroke in animal models. IA-based delivery of cells to the brain is under investigation for stroke, but it is unknown whether cells are injured as a result of being injected through a catheter or exposed to iodinated contrast medium or solutions containing heparin., Materials and Methods: We assessed the effect of catheterization with the Excelsior SL-10 catheter or exposure to heparin or iodine contrast on human bone marrow MNCs. Viability and cell injury were assessed by trypan blue exclusion, caspase-3 activity, and lipid peroxidation. Cellular function of MNCs was assessed by their production and release of VEGF, IL-10, and IGF-1., Results: Flow rates of 10 million cells from 0.5 to 2 mL/min did not alter MNC viability; however, 5 mL/min of MNCs did reduce viability by 19%. Iodine and low-dose heparin exposure did not affect cell viability; however, high-dose heparin was cytotoxic. Catheter delivery at 2 mL/min did not affect levels of VEGF, IL-10, or IGF-1., Conclusions: MNCs do not appear to be damaged by heparin, iodine contrast, and the Excelsior SL-10 catheter at flow rates up to 2 mL/min. However, higher flow rates did reduce viability, and high-dose heparin did cause cell death.

Our objectives were to document and to analyze the U.S. Navy's smallpox vaccination program before Operation Iraqi Freedom, discerning lessons for future mass vaccination programs. This research scrutinized the challenges inherent in vaccinating approximately 40,000 personnel at diverse locations within a few weeks. We interviewed and observed participants at multiple locations throughout the vaccination process, while also collecting documentation. Subsequently, we analyzed how the Navy addressed the challenges of mass vaccination on a compressed timeline. We found that the population was vaccinated with no significant logistical challenges, few medical complications, almost no refusals, and minimal operational impact. Our analysis led us to conclude that two primary factors contributed to the vaccination program's success; both of these can be replicated in future mass vaccination programs. The first factor was a strong educational program, which repeated consistent messages via multiple communications channels. The second factor was vocal, demonstrative, high-level support for vaccination.

Background: Recent trials suggest that angiotensin-converting enzyme inhibitors (ACEI) are effective in prevention of ischemic stroke, as measured by reduced stroke incidence. We aimed to compare stroke severity between stroke patients who were taking ACEI before their stroke onset and those who were not, to examine the effects of pretreatment with ACEI on ischemic stroke severity., Methods: We retrospectively studied 126 consecutive patients presenting within 24 hours of ischemic stroke onset, as confirmed by diffusion-weighted magnetic resonance imaging (DWI). We calculated the NIHSS score at presentation, as the primary measure of clinical stroke severity, and categorized stroke severity as mild (NIHSS [less than or equal to] 7), moderate (NIHSS 8-13) or severe (NIHSS [greater than or equal to] 14). We analyzed demographic data, risk-factor profile, blood pressure (BP) and medications on admissions, and determined stroke mechanism according to TOAST criteria. We also measured the volumes of admission diffusion- and perfusion-weighted (DWI /PWI) magnetic resonance imaging lesions, as a secondary measure of ischemic tissue volume. We compared these variables among patients on ACEI and those who were not., Results: Thirty- three patients (26%) were on ACE-inhibitors. The overall median baseline NIHSS score was 5.5 (range 2-21) among ACEI-treated patients vs. 9 (range 1-36) in non-ACEI patients (p = 0.036). Patients on ACEI prior to their stroke had more mild and less severe strokes, and smaller DWI and PWI lesion volumes compared to non-ACEI treated patients. However, none of these differences were significant. Predictably, a higher percentage of patients on ACEI had a history of heart failure (p = 0.03). Age, time-to-imaging or neurological evaluation, risk-factor profile, concomitant therapy with lipid lowering, other antihypertensives or antithrombotic agents, or admission BP were comparable between the two groups., Conclusion: Our results suggest that ACE-inhibitors may reduce the clinical severity of stroke, as measured by NIHSS score. Further, larger-scale, prospective studies are needed to validate our findings, and to elucidate the mechanism(s) of ACEImediated benefits in patients with ischemic stroke.

Harvey Cushing revolutionized modern neurosurgery and pioneered the field of neuroendocrinology. This second of a two-part series on Harvey Cushing's contributions to neuroscience discusses his pivotal discoveries of the function and clinical disorders of the anterior pituitary. A review of his 20-year obsession with the pituitary reveals Cushing's ingenuity, keen sense of observation, and persistent stubborness. His enthusiasm to test his ideas, however, led to risky experimentation. Despite his foibles, his work opened up new frontiers of research for a number of investigators, whose efforts resulted in the identification of specific pituitary hormones, the hypothalamic regulation of the pituitary, and the practical applications of endocrinology.

Emerging evidence supports an important role for caspases in neuronal death following ischemia-reperfusion injury. This study assessed whether cell specific caspases participate in neuronal degeneration and whether caspase inhibition provides neuroprotection following transient retinal ischemia. We utilized a model of transient global retinal ischemia. The spatial and temporal pattern of the active forms of caspase 1, 2 and 3 expression was determined in retinal neurons following ischemic injury. Double-labeling with cell-specific markers identified which cells were expressing different caspases. In separate experiments, animals received various caspase inhibitors before the induction of ischemia. Sixty minutes of ischemia resulted in a delayed, selective neuronal death of the inner retinal layers at 7 days. Expression of caspase 1 was not detected at any time point. Maximal expression of caspase 2 was found at 24 h primarily in the inner nuclear and ganglion cell layers of the retina and localized to ganglion and amacrine neurons. Caspase 3 also peaked at 24 h in both the inner nuclear and outer nuclear layers and was predominantly expressed in photoreceptor cells and to a lesser extent in amacrine neurons. The pan caspase inhibitor, Boc-aspartyl fmk, or an antisense oligonucleotide inhibitor of caspase 2 led to significant histopathologic and functional improvement (electroretinogram) at 7 days. No protection was found with the caspase 1 selective inhibitor, Y-vad fmk. These observations suggest that ischemia-reperfusion injury activates different caspases depending on the neuronal phenotype in the retina and caspase inhibition leads to both histologic preservation and functional improvement. Caspases 2 and 3 may act in parallel in amacrine neurons following ischemia-reperfusion. These results in the retina may shed light on differential caspase specificity in global cerebral ischemia.

Antithrombotic and thrombolytic agents form the cornerstone of stroke prevention and treatment. Large, randomized trials have also highlighted the effectiveness and safety of early and continuous antiplatelet therapy in reducing atherothrombotic stroke recurrence. Aspirin is the antiplatelet treatment standard against which several other antiplatelet agents (ticlopidine, clopidogrel, aspirin-dipyridamole) have been shown to be more effective. The prevention of cardioembolic stroke is best accomplished with oral anticoagulation, barring any contraindications. The thrombolytic agent, rt-PA, improves outcome in ischemic stroke patients treated within 3 hours of onset. The risk-benefit ratio is narrow because of an increased risk for bleeding but studies do not support a higher risk in the geriatric population.

Increasing evidence supports a role for oxidative stress, proinflammatory cytokines, and apoptosis in the pathophysiology of focal ischemic stroke. Previous studies have found that the multi-action drug, carvedilol, is a mixed adrenergic antagonist, and that it behaves as an antioxidant and inhibits apoptosis. In the current study, the authors investigated whether carvedilol provides protection in focal cerebral ischemia and whether this protection is associated with reduced apoptosis and the downregulation of the inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin- 1beta (IL-1beta). Male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion (MCAO) by an intraluminal filament technique. Carvedilol (1, 3, and 10 mg/kg) was injected daily subcutaneously 2 or 4 days before the induction of ischemia. Neurologic scores, infarct volumes, TUNEL staining, and mRNA levels of TNF-alpha and IL-1beta were assessed at 24 hours reperfusion. The effect of carvedilol on microvascular cortical perfusion was studied with continuous laser-Doppler flowmetry. Twenty-four hours after MCAO, carvedilol at all three doses reduced infarct volumes by at least 40% and reduced neurologic deficits on average by 40% compared with vehicle-treated controls when given 2 or 4 days before the induction of ischemia. This protection was not mediated by changes in temperature or blood flow. Treatment with all three dose regimens resulted in fewer TUNEL positive cells compared with controls. At 24 hours reperfusion, carvedilol decreased TNF-alpha and IL-1beta expression by 40% to 50% in the ipsilateral ischemic cortex compared with the contralateral controls. The results of the current study indicate that carvedilol is neuroprotective in focal cerebral ischemia and may protect the ischemic brain by inhibiting apoptosis and attenuating the expression of TNF-alpha and IL-1beta.

Apoptosis may result either from positive induction by ligand binding to a plasma membrane receptor or from negative induction attributable to loss of a suppressor signal. For example, apoptosis of developing sympathetic neurons may be induced in culture either by exposure to leukemia inhibitory factor (LIF) or by deprivation of nerve growth factor. This study compared the cell death pathways activated in sympathetic neurons by these two different stimuli. Both types of cell death were developmentally regulated; both were maximal in the immediate postnatal period and disappeared over the next 2 weeks. Both types of cell death were reduced by genetic deletion of Bax or by virally mediated overexpression of Bcl-2. Similarly both were reduced by inhibition of caspase activity or by inhibition of Nedd-2 synthesis with antisense oligonucleotides. Finally, both involved activation of c-Jun N-terminal kinase (JNK) signaling. Nedd-2 expression by sympathetic neurons declined in parallel with the developmental loss of LIF-mediated cell death, suggesting that downregulation of the caspase during development may underlie the loss of cytokine-mediated apoptosis. Treatment of sympathetic neurons with an antibody that blocks the function of the low-affinity neurotrophin receptor (p75(LNTR)) prevented LIF-induced cell death. Similarly genetic deletion of p75(LNTR) prevented apoptosis after LIF treatment. These observations suggest that concurrent p75(LNTR) signaling is necessary for LIF-induced cell death and that cytokine-mediated cell death and growth factor deprivation appear to activate the same intracellular pathways involving JNK signaling.

Enormous interest in cell death in the past several years has moved apoptosis to the forefront of scientific research. Apoptosis has been found to mediate cell deletion in tissue homeostasis, embryological development, and immunological functioning. It also occurs in pathological conditions, including cancer and acquired immunodeficiency syndrome, and is implicated in neurodegenerative diseases. Claims of neuronal apoptosis induced by various agents and conditions are published regularly, but in many instances the data are questionable because they are incomplete. This review presents a brief history of apoptosis and describes the evidence required before claims of apoptosis are made. Summaries and critiques of important investigations concerning the genetic and biochemical regulation of neuronal apoptosis are presented, as are other studies describing connections between apoptosis and neuronal cell death in physiological and pathological situations. There is a realization that apoptosis can be programmed and is distinguishable from necrotic cell death. Combining apoptosis with programmed cell death produces misleading terminology and confusion over these two forms of cell degeneration. Further investigations into neuronal apoptosis should focus on all of the criteria that the original investigators outlined 25 years ago, to clarify whether apoptosis and/or another form of cell death mediates neuronal degeneration in physiological settings and in neurological diseases such as Alzheimer's disease, Parkinson's disease, epilepsy, and ischemia/stroke.

Leonard I. Malis introduced important changes in the antimicrobial regimen for neurosurgical procedures at The Mount Sinai Hospital. Among Dr. Malis' innovations, intraoperative administration of a single dose each of vancomycin and gentamicin or tobramicin and constant irrigation of the surgical site with a bactericidal antibiotic (streptomycin) led to the elimination of primary wound infections during a 20-year period. In a study to locate potential sources of microbial contamination in his operating room, this combination of parenteral antibiotics was justified, because 36% of patients were at risk for exposure to methicillin-resistant Staphylococcus aureus and Gram-negative bacteria. Streptomycin as a topical agent was found to be highly efficacious in preventing intraoperative growth of potential pathogens cultured from the surgical wound and the operating room environment.

An enormous interest in cell death over the past several years has catapulted apoptosis to the forefront of scientific research. Apoptosis has been found to mediate cell deletion in tissue homeostasis, embryological development and immunologic function. It also occurs in pathological situations including cancer and AIDS, and is implicated in a variety of ocular diseases. This review presents a brief history of apoptosis and the proper evidence needed in order to claim that apoptosis is taking place. A summary and critique of important investigations concerning the genetic and biochemical regulation of apoptosis is presented, as well as a focus on other studies drawing a connection between apoptosis and cell death in physiological and pathological situations.