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Background We hypothesized that stroke outcome is related to multiple baseline hydration‐related factors including volume contracted state (VCS) and diuretic use. Methods and Results We analyzed a prospective cohort of subjects with ischemic stroke Conclusions A VCS at the time of hospitalization was associated with more severe stroke and odds of death but not associated with worse functional outcome when accounting for relevant characteristics. Diuretic use and low serum potassium at the time of stroke onset were associated with worse outcome and may be worthy of further investigation.

Delayed cerebral ischemia (DCI) continues to be a sequela of aneurysmal subarachnoid hemorrhage (aSAH) that carries significant morbidity and mortality. Aside from nimodipine, no therapeutic agents are available to reduce the incidence of DCI. Pathophysiologic mechanisms contributing to DCI are poorly understood, but accumulating evidence over the years implicates several factors. Those have included microvessel vasoconstriction, microthrombosis, oxidative tissue damage, and cortical spreading depolarization as well as large vessel vasospasm. Common to these processes is red blood cell leakage into the cerebrospinal fluids (CSF) and subsequent lysis which releases hemoglobin, a central instigator in these events. This has led to the hypothesis that early blood removal may improve clinical outcome and reduce DCI. This paper will provide a narrative review of the evidence of hemoglobin as an instigator of DCI. It will also elaborate on available human data that discuss blood clearance and CSF drainage as a treatment of DCI. Finally, we will address a recent novel device that is currently being tested, the Neurapheresis CSF Management System™. This is an automated dual-lumen lumbar drainage system that has an option to filter CSF and return it to the patient.

ObjectiveThe widespread adoption of endovascular therapy (EVT) for emergent large vessel occlusion has led to increased nationwide demand for neurointerventionalists, heightened interest among neurology residents to pursue neurointervention as a career, and increased importance of neurointervention exposure for all neurologists who care for patients with acute ischemic stroke. Exposure to neurointervention and its career path are not well-defined for neurology trainees.MethodsThe Society for Vascular and Interventional Neurology (SVIN) Education Committee conducted a multicenter electronic survey directed towards neurology residents and vascular neurology (VN), neurocritical care (NCC), and neurointervention fellows in June 2018. A total of 250 programs were invited to participate; 76 trainees completed the survey.ResultsRespondents self-identified as 22% postgraduate year (PGY)2, 40% PGY3/4, 30% VN fellows, and 8% neurointervention or NCC fellows. Eighty-seven percent of trainees had more than 2 months exposure to VN during residency, 41% to NCC, and only 3% to neurointervention. Sixty-eight percent of respondents had no exposure to neurointervention during residency. Whereas 72% believed that a background in neurology was good preparation for neurointervention, only 41% agreed that fellowship training pathway in neurointervention is well-structured for neurology residents when compared to other subspecialties.ConclusionIn this survey, respondents identified lack of exposure to neurointervention and a well-defined training pathway as obstacles towards pursuing neurointervention as a career. These obstacles must be addressed for the continued development of neurointervention as a subspecialty of neurology.

Background Inter-observer variability in stroke aetiological classification may have an effect on trial power and estimation of treatment effect. We modelled the effect of misclassification on required sample size in a hypothetical cardioembolic (CE) stroke trial. Methods We performed a systematic review to quantify the reliability (inter-observer variability) of various stroke aetiological classification systems. We then modelled the effect of this misclassification in a hypothetical trial of anticoagulant in CE stroke contaminated by patients with non-cardioembolic (non-CE) stroke aetiology. Rates of misclassification were based on the summary reliability estimates from our systematic review. We randomly sampled data from previous acute trials in CE and non-CE participants, using the Virtual International Stroke Trials Archive. We used bootstrapping to model the effect of varying misclassification rates on sample size required to detect a between-group treatment effect across 5000 permutations. We described outcomes in terms of survival and stroke recurrence censored at 90 days. Results From 4655 titles, we found 14 articles describing three stroke classification systems. The inter-observer reliability of the classification systems varied from ‘fair’ to ‘very good’ and suggested misclassification rates of 5% and 20% for our modelling. The hypothetical trial, with 80% power and alpha 0.05, was able to show a difference in survival between anticoagulant and antiplatelet in CE with a sample size of 198 in both trial arms. Contamination of both arms with 5% misclassified participants inflated the required sample size to 237 and with 20% misclassification inflated the required sample size to 352, for equivalent trial power. For an outcome of stroke recurrence using the same data, base-case estimated sample size for 80% power and alpha 0.05 was n = 502 in each arm, increasing to 605 at 5% contamination and 973 at 20% contamination. Conclusions Stroke aetiological classification systems suffer from inter-observer variability, and the resulting misclassification may limit trial power. Trial registration Protocol available at reviewregistry540. Electronic supplementary material The online version of this article (10.1186/s13063-019-3222-x) contains supplementary material, which is available to authorized users.

Background and aim The availability and access of hospital administrative data [coding for Charlson comorbidity index (CCI)] in large data form has resulted in a surge of interest in using this information to predict mortality from stroke. The aims of this study were to determine the minimum clinical data set to be included in models for predicting disability after ischemic stroke adjusting for CCI and clinical variables and to evaluate the impact of CCI on prediction of outcome. Method We leverage anonymized clinical trial data in the Virtual International Stroke Trials Archive. This repository contains prospective data on stroke severity and outcome. The inclusion criteria were patients with available stroke severity score such as National Institutes of Health Stroke Scale (NIHSS), imaging data, and outcome disability score such as 90-day Rankin Scale. We calculate CCI based on comorbidity data in this data set. For logistic regression, we used these calibration statistics: Nagelkerke generalised R2 and Brier score; and for discrimination we used: area under the receiver operating characteristics curve (AUC) and integrated discrimination improvement (IDI). The IDI was used to evaluate improvement in disability prediction above baseline model containing age, sex, and CCI. Results The clinical data among 5,206 patients (55% males) were as follows: mean age 69 ± 13 years, CCI 4.2 ± 0.8, and median NIHSS of 12 (IQR 8, 17) on admission and 9 (IQR 5, 15) at 24 h. In Model 2, adding admission NIHSS to the baseline model improved AUC from 0.67 (95% CI 0.65–0.68) to 0.79 (95% CI 0.78–0.81). In Model 3, adding 24-h NIHSS to the baseline model resulted in substantial improvement in AUC to 0.90 (95% CI 0.89–0.91) and increased IDI by 0.23 (95% CI 0.22–0.24). Adding the variable recombinant tissue plasminogen activator did not result in a further change in AUC or IDI to this regression model. In Model 3, the variable NIHSS at 24 h explains 87.3% of the variance of Model 3, follow by age (8.5%), comorbidity (3.7%), and male sex (0.5%). Conclusion Our results suggest that prediction of disability after ischemic stroke should at least include 24-h NIHSS and age. The variable CCI is less important for prediction of disability in this data set.

Introduction: Hematoma enlargement (HE) in intracerebral hemorrhage (ICH) possibly occurs soon after onset but is not captured due to delays in imaging. The Mobile Stroke Unit (MSU) can identify ICH patients in the prehospital setting and can increase our understanding of ICH patients in the first hour of onset. Methods: This was a prospective, observational study to examine patients within 4 hours of symptom onset and early HE in ICH due to hypertension and/or coagulopathies. A baseline head CT (HCT) was performed on the MSU, followed by a 1-hour HCT at the destination hospital. Patients during MSU control weeks were included but not required to have a 1-hour HCT. Blood pressure was treated to a systolic goal of 6cc or >30% between scans. Patients were categorized by time to first HCT (≤61min, 62-120min, and 120-270min). Overall HE for each group was calculated using the scan nearest to 24 hours. HE on the 1-hour HCT was calculated for the ≤61min group and for the all patients collectively. The additional HE between the 1-hour HCT and scan nearest to 24 hours was also captured. Results: Twenty-three patients (19 MSU) were included. Four of 8 (50%) patients in the ≤61min group, 3/7 (42.9%) in the 62-120min group, and 3/8 (37.5%) in the 120-270min group had HE in the first 24hrs, p=1.0 (Figure 1). Among the patients who had a 1-hour HCT, the incidence of HE over the first hour in the ≤61min group was 0.4 (2/5) and 0.36 (4/11) for all 3 groups. Additional HE beyond the 1-hour HCT occurred in only 1/9 patients (no follow up scan in 2 patients). Conclusion: There was a high incidence of HE 1 to 2 hours after onset in ICH patients. This period may be an optimal window for treatment. Limitations include a small sample size and confounding due to early intervention in the MSU group. A larger study is currently ongoing.

Background Desmoteplase is a novel, highly fibrin-specific thrombolytic agent in phase III of clinical development. In comparison to alteplase, it has high fibrin selectivity, is associated with minimal or no neurotoxicity, and has no apparent negative effect on the blood–brain barrier. The safety and efficacy of desmoteplase is being studied in the Desmoteplase in Acute Ischemic Stroke clinical trial program. Three studies (Dose Escalation Study of Desmoteplase in Acute Ischemic Stroke, Desmoteplase in Acute Ischemic Stroke, and Desmoteplase in Acute Ischemic Stroke-2) have been completed, two large randomized, double-blind, placebo-controlled, phase III trials are ongoing at >200 sites worldwide (Desmoteplase in Acute Ischemic Stroke-3 and Desmoteplase in Acute Ischemic Stroke-4, n = 800; DIAS-3 and DIAS-4), and a randomized, double-blind, placebo-controlled, dose-escalation phase II trial is ongoing in Japan (Desmoteplase in Acute Ischemic Stroke-Japan, n = 48; DIAS-J). Aims The objective of DIAS-3 and DIAS-4 is to evaluate the safety and efficacy of a single IV bolus injection of 90 μg/kg desmoteplase given three- to nine-hours after onset of ischemic stroke (National Institutes of Health Stroke Scale 4–24, age 18–85 years). The objective of DIAS-J is to evaluate the safety and tolerability of desmoteplase 70 and 90 μg/kg three- to nine-hours after ischemic stroke onset in Japanese patients. Methods Patients are included with occlusion or high-grade stenosis (thrombolysis in myocardial infarction 0–1) in proximal cerebral arteries on magnetic resonance or computed tomography angiography but excluded with extended ischemic edema on computed tomography or diffusion-weighted imaging. Conclusion Desmoteplase is the only thrombolytic agent in late-stage development for acute ischemic stroke that is now tested in patients with proven stroke pathology. The results of the Desmoteplase in Acute Ischemic Stroke clinical trial program will show whether patients with major artery occlusions but not extended ischemic brain damage can be safely and effectively treated up to nine-hours after onset.

Background: A Mobile Stroke Unit (MSU) delivers Emergency Department (ED) care in the pre-hospital setting. We describe establishing the first MSU in the U.S. Methods: A full time Medical Director and Project Manager took ownership of the project. A funding plan was developed to build,staff and supply the unit for 3 years. An ambulance company donated a standard ambulance. MSU build-out began after purchase of the CT scanner. A consortium of stakeholders was formed including leaders of the stroke programs and EDs of the city’s 3 Comprehensive Stroke Centers (CSCs) and Houston Emergency Medical Services (EMS). Policies and procedures were developed to obtain both state and city health department licensing and inspection, and an accountability system to maintain the unit to standards. Radiation safety certification was obtained from the state health department. Radiation safety experts inspected the vehicle,obtained rad. measurements and designed safety procedures,confirming minimal risk. Insurance on the vehicle and all equipment was obtained. Staffing was hired,and a secure location to park the MSU with electrical hook-up and an office were located. An EMS education program was carried out and communication pathway developed enabling immediate MSU dispatch within a 5 mile radius following a 911 call, as well as for first-responders to activate the MSU. A study protocol was written to evaluate logistics,cost-effectiveness,telemedicine (TM) vs. on-scene decisions and patient outcomes. A HIPPA-compliant technology grid enabled viewing of CT images by the TM team and receiving hospital radiologist. Results: The MSU effort began in March 2013 and the MSU received Feb 4, 2014. The Houston MSU is a standard 12’ ambulance staffed by a neurologist and registered nurse with stroke expertise, CT tech, and paramedic, with TM connectivity, responding to acute stroke dispatches daily from 8a-6p. All MSU management is standard of care; patient consent is not required except to include patient data. This includes a non-con head CT, point of care labs, blood pressure management and if necessary advanced life support. Conclusion: The Houston MSU treated its first patient on May16,2014, and is carrying out acute stroke treatment within 10-18 minutes of arrival on location.

Introduction: During treatment of patients with acute stroke, practitioners must perform many tasks simultaneously, including diagnosing, treating, and screening/enrolling in clinical trials. These tasks must often be performed in parallel, and in the most timely manner possible. Especially for those unfamiliar with local processes or resources, a smartphone application can aid in these tasks. Description: A smartphone application compatible with iOS and Android operating systems was constructed for the Stroke Team at the University of Texas at Houston. It features a hierarchical structure (Figure 1), with four components. First, a phone dialer function allows access to critical personnel directly from the phone (Figure 2). Second, references for clinical trials and other data such as treatment protocols is available (Figure 3). Next, a timekeeper function allows recording of benchmark times (including symptom onset, arrival time, head CT acquisition time, and tPA administration time); once times are recorded, the application updates time windows in real-time (Figure 4). Finally, a tool allows users to screen patients for eligible clinical trials automatically: by entering basic data such as age, modified Rankin Scale and NIHSS (Figure 5), the application determines whether the patient may be eligible for ongoing clinical trials (Figure 6). The application allows emailing of these data to the user for inclusion in official documentation, or notification of appropriate personnel. Conclusion: A smartphone application that centralizes various disparate resources may allow for more efficient management of the acute stroke patient. Further, such an application may allow easy screening for clinical trials by new practitioners as they learn of the various inclusion criteria for their studies.

Background: Currently, t-PA is the only FDA approved treatment for acute ischemic stroke (AIS). Supplementing t-PA with therapeutic hypothermia is being evaluated, but cooler temperatures may affect the enzymatic activity of t-PA. Thromboelastography (TEG) determines coagulation status in whole blood, and has detected hypercoagulability in AIS patients compared to healthy controls. Using TEG, we evaluated the effect of variable degrees of hypothermia on clot formation and lysis in AIS patients receiving t-PA. Methods: Between June 2012 -July 2013, venous blood from 18 AIS patients receiving t-PA within 4.5 hours of symptom onset was collected prior to and 10 minutes after t-PA bolus. Blood samples were analyzed by TEG at 30°C, 33°C, and 37°C. The variables of interest were R (initiation of clot formation), K (speed of clot strengthening), Angle α (rate of clot formation), and LY30 (percentage of clot lysis over 30 minutes) (see figure). All statistical analyses were performed using SAS 9.3. Results: Baseline R averaged 6.0, 5.6, and 4.6 minutes at 30°C, 33°C, and 37°C (p=0.02),K averaged 2.5, 2.3, and 1.4 (p=0.01),and Angle averaged 59.1, 62.4, and 69.3(p=0.01), indicating slower clotting at lower temperatures. Post t-PA LY30 averaged 93.9, 93.9, 89.8 (p= 0.61, N=18) indicating no effect on t-PA lytic activity at lower temperatures. Conclusions: Our data suggest that hypothermia progressively slows clot formation in AIS patients but has no effect on the lytic effect of t-PA as measured by TEG.

Objective: Pre-hospital evaluation using audio/video telemedicine (TM) might accelerate acute stroke treatment with t-PA. We explored the reliability and feasibility of using TM via a mobile device in ambulances to help identify and evaluate acute stroke patients. Methods: Ten unique, scripted stroke scenarios with various levels of stroke severity were portrayed by trained actors retrieved and transported by EMS to our stroke center. Each scenario was conducted 4 times, for a total of 40 scenarios. Each scenario began when EMS arrived on scene and a vascular neurologist (VN) simultaneously logged on to the TM device remotely, and ended once the ambulance arrived at the emergency department. The VNs performed assessments in real-time, obtaining clinical data points and NIHSS using the In-Touch RP-Xpress TM device with Verizon 4G wireless connectivity. Each scenario was recorded for a subsequent evaluation by a second blinded VN. Study feasibility was defined by the ability to conduct 80% of the sessions without major technological limitations. Reliability was defined by a 90% concordance between the data derived during the live/recorded sessions and the scripted scenarios; intra-class correlation (ICC) for NIHSS gathered during the live and recorded sessions was calculated. Audio/video quality and stability of connection were graded by paramedics and VNs for the live sessions on a scale of 1 to 5 (1=Poor; 2= Fair; 3= Good; 4= Very Good; 5=Excellent). Results: In 34 of 40 (85%) scenarios, the tele-consultation was conducted without major technical complication. The absolute agreement for ICC using the two-way mixed-effects model was 0.991 (95% CI 0.97-0.998) for the NIHSS obtained during the live sessions and 0.97 (95% CI 0.91-0.997) for the recorded sessions. Of the 34 live assessments, 30 (91%) matched the NIHSS by ±2 points, and 96% of the clinical information obtained by the remote neurologist matched those provided from the script. Audio/video quality and stability of connection were rated from good to very good by the EMS and VNs Conclusion: Mobile TM is reliable and feasible in assessing actors simulating acute stroke in the pre-hospital setting.

Background: Intracerebral hemorrhage (ICH) has high morbidity, and hematoma enlargement (HE) causes worse outcome. Thromboelastography (TEG) measures the dynamics of clot formation and dissolution, and might be useful for assessing bleeding risk. Speed of clot formation in minutes is measured by parameters R, K, and delta, and clot strength in dynes of resistance by MA and G. We used TEG to detect changes in clotting in patients with and without HE after ICH. Methods: This prospective study included 64 patients with spontaneous ICH admitted from 2009 to 2013. TEG was performed within 6 hours of symptom onset and after 36 hours. Brain imaging was obtained at baseline and 36 ±12 hours, and HE defined as total volume increase > 6cc or >33%.TEG was also obtained from 57 healthy controls. Comparisons between groups were assessed by t-test or Wilcoxon rank sum tests. Multivariable regression was performed after controlling for potential confounders. Results: Age and gender were not different between ICH patients and controls. Compared to controls, ICH patients demonstrated faster and stronger clot formation; shorter R and delta (p Discussion: TEG may detect important coagulation changes in patients with ICH; clotting may become faster and stronger in immediate response to ICH; a less robust response may be associated with HE. These findings may have relevance to patient management and deserve further investigation. Delta values at baseline for controls, all hemorrhage patients, hemorrhage enlargement (HE) + and (HE) - patients.

It is indisputable that in the first 2 to 3 hours of an acute ischemic, the best strategy to maximize recovery is robustly time-based and depends on getting the artery open as soon as possible. The second law of thermodynamics and the underappreciated effect of clot consistency and size must be accounted for in our efforts to minimize time to recanalization within the first 2 to 3 hours. It is also clear that at later time intervals, beyond 4.5 hours, few patients completely recover even with sustained complete recanalization, and that the ability to recover depends more on physiologic tissue issues than on the duration of the occlusion. Clinical factors as well as imaging should be used to select patients who may benefit from delayed attempts at reperfusion.

Introduction: Aspiration Pneumonia (AsPNA) in acute stroke patients can lead to a three-fold risk in mortality. Treatment of AsPNA requires increased acuity of hospital care for antibiotic therapy and respiratory management. This care is provided at all levels, including Inpatient Rehabilitation (IR), Skilled Nursing Facility (SNF) or Sub-acute Care (Sub). There are limited studies assessing the role of AsPNA as an independent predictor of post-stroke disposition. Hypothesis: Low NIHSS is a predictor of higher functional status. We assessed the hypothesis that absence of AsPNA predicts post-stroke disposition to a functional level similar to low NIHSS. Methods: All patients admitted to the UT Stroke Service between January 2004 and October 2009 were included. Stratification occurred for age>65, NIHSS and stroke risk factors. Using multivariate logistic regression, the data was analyzed for differences in post-stroke disposition among patients without aspiration pneumonia. Results: Home vs. Other Level of Care Of 3390 patients, 1668 were discharged home, 1722 to another level of care. Patients without AsPNA are 5.3 times more likely to be discharged home (P = 15.1 times more likely to be discharged home. IR vs. SNF Of 1547 patients, 983 patients were discharged to IR, 564 to SNF. Patients without AsPNA are 8.6 times more likely to be discharged to IR (P = 3.4 times more likely to be discharged to IR. SNF vs. Sub Of 739 patients, 564 were discharged to SNF, 175 to Sub. Patients without AsPNA are 5.5 times more likely to be discharged to SNF (P = 2.6 times more likely to be discharged to SNF. Conclusions: The absence of AsPNA is an independent predictor of improved post-stroke disposition. Patients with AsPNA have an increased likelihood of post-acute stroke care at a lower functional level, with a correlation stronger than NIHSS. This study is limited by its retrospective nature and unmeasured psychosocial factors related to discharge. Prospective studies on dysphagia screening, dietary modification and respiratory management are needed.

Introduction: Six percent of patients who receive IV rt-PA for cerebral ischemia experience a combination of neurologic worsening (NW) with intraparechymal hemorrhage (PH2). Also known as symptomatic intracerebral hemorrhage (sICH), PH2+NW is a good predictor of stroke mortality. There is growing clinical evidence that NW, defined as a two point increase in NIHSS, should be evaluated independently when predicting clinical metrics and outcomes. Hypothesis: To test the strength of NW as a predictor of clinical metrics in acute ischemic stroke patients receiving rt-PA. Methods: Patients with ischemic stroke who received IV rt-PA admitted to the UT Stroke Service between July 2004 and October 2010 were included (n=1083). No PH2/NW served as the control. We assessed differences in demographics and clinical metrics with respect to PH2, NW, PH2+NW and No PH2/NW using Chi-square or Fisher's Exact test when appropriate. Results: Demographics: There were no differences in age or gender across all groups. PH2+NW had the highest NIHSS (P=0.0005) and mortality (P= Conclusions: Neurologic worsening in patients who received IV rt-PA for acute ischemic stroke is associated with increased days in the ICU and prolonged hospital length of stay. These patients are more likely to be members of minority groups and require treatment in a subacute facility, custodial/hospice care or a medical transfer of care. This study is limited by undetermined psychosocial factors and the size of the PH2 and PH2+NW groups. More research is needed on neurologic worsening in minority populations and the impact of transfer of care on a further increase in length of stay.

Introduction: Dysphagia is one of the most common post-stroke complications. The use of feeding tubes to provide nutrition requires increased acuity of care for management, which affects costs. This care is provided at all levels, including Inpatient Rehabilitation (IR), Skilled Nursing Facility (SNF) or Sub-acute (Sub). There are limited studies of the role of dysphagia as a predictor of post-stroke disposition. Hypothesis: Low NIHSS is a predictor of higher function. We assessed the hypothesis that the absence of tube feeds as an indicator of dysphagia is a predictor of post-stroke disposition to a similar functional level. Methods: All patients admitted to the UT Stroke Service between January 2004 and October 2009 were included. Stratification occurred for age >65, NIHSS and stroke risk factors. Using multivariate logistic regression, the data was analyzed to determine if differences in post-stroke disposition were present among patients not receiving tube feeds as an indicator of dysphagia. Results: Home vs. Other Level of Care Of 3389 patients, 1668 were discharged home, 1721 to another level of care. Patients without tube feeds are 14.6 times more likely to be discharged home (P = 10.9 times more likely to be discharged home. IR vs. SNF Of 1546 patients, 983 were discharged to acute IR, 563 to SNF. Patients without tube feeds are 6.1 times more likely to be discharged to IR (P = 2.5 times more likely to be discharged to IR. SNF vs. Sub Of 738 patients, 563 were discharged to SNF, 175 to Sub. Patients without tube feeds are 3 times more likely to be discharged to SNF (P = 2 times more likely to be discharged to SNF. Conclusions: The absence of tube feeds as an indicator of dysphagia is a predictor of improved post-stroke disposition, with a correlation stronger than NIHSS. This study is limited by its retrospective nature and unmeasured psychosocial factors related to discharge. Prospective studies should focus on early diagnosis, therapeutic intervention and caregiver involvement in dysphagia education to improve outcomes and decrease the cost of post-stroke care.