A Stroke Care Model at an Academic, Comprehensive Stroke Center During the 2020 COVID-19 Pandemic.

BACKGROUND AND PURPOSE: The COVID-19 pandemic has required the adaptation of hyperacute stroke care (including stroke code pathways) and hospital stroke management. There remains a need to provide rapid and comprehensive assessment to acute stroke patients while reducing the risk of COVID-19 exposure, protecting healthcare providers, and preserving personal protective equipment (PPE) supplies. While the COVID infection is typically not a primary cerebrovascular condition, the downstream effects of this pandemic force adjustments to stroke care pathways to maintain optimal stroke patient outcomes. METHODS: The University of California San Diego (UCSD) Health System encompasses two academic, Comprehensive Stroke Centers (CSCs). The UCSD Stroke Center reviewed the national COVID-19 crisis and implications on stroke care. All current resources for stroke care were identified and adapted to include COVID-19 screening. The adjusted model focused on comprehensive and rapid acute stroke treatment, reduction of exposure to the healthcare team, and preservation of PPE. AIMS: The adjusted pathways implement telestroke assessments as a specific option for all inpatient and outpatient encounters and accounts for when telemedicine systems are not available or functional. COVID screening is done on all stroke patients. We outline a model of hyperacute stroke evaluation in an adapted stroke code protocol and novel methods of stroke patient management. CONCLUSIONS: The overall goal of the model is to preserve patient access and outcomes while decreasing potential COVID-19 exposure to patients and healthcare providers. This model also serves to reduce the use of vital PPE. It is critical that stroke providers share best practices via academic and vetted social media platforms for rapid dissemination of tools and care models during the COVID-19 crisis.

PREMISE: Posterior Circulation Results Comparing Embolectomy to Medical Intervention in Stroke Emergencies.

Background Intravenous (IV) tissue plasminogen activator (rt-PA) is a proven therapy for stroke in the acute treatment window. Recent published data has shown efficacy for embolectomy for acute ischemic strokes within up to six, 16 and 24 hours in the anterior circulation but there is no guideline for optimal therapy for patients with posterior circulation stroke, specifically basilar artery occlusion (BAO) outside the standard IV rt-PA treatment window. Aim To evaluate differences in outcomes between maximal medical treatment versus thrombectomy in BAO. Method We retrospectively evaluated prospectively collected acute stroke code patients from our stroke registry from 7/2004 to 7/2016. Patients who received IV rt-PA were excluded. Patients with evidence of posterior circulation ischemia and a hyper dense artery sign on initial non-contrast CT were included as a surrogate for direct vessel data before 2014. Patients after 9/2014 were selected by evidence of BAO on vessel imaging. All patients were categorized either as endovascular therapy or standard medical treatment alone. Demographics, hospital discharge location and Modified Rankin Scale (mRS) at 90 days were compared. Two-sample t-test and Fisher's exact test compared continuous and categorical variables across groups respectively. Results A total of 18 patients were included (three embolectomy and 15 medical therapy only). There were no significant differences in demographic data (age, gender, race, ethnicity, blood pressure, diabetes mellitus, hypertension, atrial fibrillation, tobacco use, alcohol use and initial NIHSS). Results for outcome and efficacies showed no statistical difference between medical management and endovascular intervention for functional outcome mRS (0-3) at 90 days (p = 0.2) and discharge location of home/inpatient rehabilitation vs other locations (p = 0.52). Conclusions Our single-center review showed the expected transition from predominantly medically treated posterior circulation BAOs, to a mixed pattern including embolectomy. Although the sample size was small, this study also illustrates the lack of clear efficacy data for optimal treatment strategies, and the ongoing treatment challenges in posterior circulation stroke population in a population of patients outside the rt-PA window.

The Sustained DeyeCOM Sign as a Predictor of Large Vessel Occlusions and Stroke Mimics.

INTRODUCTION: Rapid imaging in acute stroke is critical and often occurs before full examination. Early, reliable examination findings clarify diagnosis and improve treatment times. The DeyeCOM sign has been described as a predictor of ischemic stroke. In this study, we evaluate a sustained DeyeCOM sign on serial computed tomography scans in prediction of large vessel occlusion. METHODS: Between April and June 2017, we retrospectively reviewed 46 patients with acute stroke from the University of California, San Diego Stroke Registry, who had both computed tomography and computed tomography angiography as part of their acute work-up. A DeyeCOM(+) sign was defined as a conjugate gaze deviation on imaging of at least 15°. DeyeCOM(++) was defined as sustained gaze deviation on both scans. RESULTS: Three groups of patients were observed: DeyeCOM(++), nonsustained gaze deviation, and no gaze deviation (DeyeCOM(--)). All patients in the DeyeCOM(++) (8 of 8, 100%) had large vessel occlusion. Of those with nonsustained gaze deviation, 2 of 7 (29%) had large vessel occlusion. No patients in the DeyeCOM(--) (0 of 31, 100%) had large vessel occlusion. The specificity and sensitivity of DeyeCOM(++) for large vessel occlusion was 100% (confidence interval [CI] .90-1.0) and 80% (CI .44-.97). The specificity and sensitivity of DeyeCOM(--) for absence of large vessel occlusion was 100% (CI .69-1.0) and 86% (CI .70-.95). CONCLUSIONS: DeyeCOM(++) had 100% specificity for large vessel occlusion, whereas DeyeCOM(--) had a 100% specificity for absence of large vessel occlusion. Sustained DeyeCOM, whether positive or negative, is a strong predictor of ultimate diagnosis that could lead to quicker endovascular treatment times.

Feasibility and Safety of Using External Counterpulsation to Augment Cerebral Blood Flow in Acute Ischemic Stroke-The Counterpulsation to Upgrade Forward Flow in Stroke (CUFFS) Trial.

BACKGROUND: External counterpulsation (ECP) increases perfusion to a variety of organs and may be helpful for acute stroke. METHODS: We conducted a single-blinded, prospective, randomized controlled feasibility and safety trial of ECP for acute middle cerebral artery (MCA) ischemic stroke. Twenty-three patients presenting within 48 hours of symptom onset were randomized into one of two groups. One group was treated with ECP for 1 hour at a pressure of up to 300 mmHg ("full pressure"). During the procedure, we also determined the highest possible pressure that would augment MCA mean flow velocity (MFV) by 15%. The other group was treated with ECP at 75 mmHg ("sham pressure"). Transcranial Doppler MCA flow velocities and National Institutes of Health Stroke Scale (NIHSS) scores of both groups were checked before, during, and after ECP. Outcomes were assessed at 30 days after randomization. RESULTS: Although the procedures were feasible to implement, there was a frequent inability to augment MFV by 15% despite maximal pressures in full-pressure patients. In sham-pressure patients, however, MFV frequently increased as shown by increases in peak systolic velocity and end diastolic velocity. In both groups, starting ECP was often associated with contemporaneous improvements in NIHSS stroke scores. There were no between-group differences in NIHSS, modified Rankin Scale Scores, and Barthel Indices, and no device or treatment-related serious adverse events, deaths, intracerebral hemorrhages, or episodes of acute neuro-worsening. CONCLUSIONS: ECP was safe and feasible to use in patients with acute ischemic stroke. It was associated with unexpected effects on flow velocity, and contemporaneous improvements in NIHSS score regardless of pressure used, with a possibility that even very low ECP pressures had an effect. Further study is warranted.

Does symptom onset to primary stroke center time goals affect stroke outcome?

BACKGROUND: Treating acute ischemic stroke (AIS) within 4.5 hours and door-to-needle time of less than 60 minutes may optimize recovery. It is unknown if onset to Primary Stroke Center (PSC) time goals affect outcome. The purpose of this study was to examine effects of symptom onset to PSC time goals on outcome. METHODS: Analysis included prospectively collected data from the University of California San Diego Specialized Program of Treatment Research in Acute Stroke. All AIS patients treated with intravenous recombinant tissue plasminogen activator were included if treated within 270 minutes, and 90-day modified Rankin Scale (mRS) score was known. Primary outcome of the 90-day mRS was analyzed using multivariable logistic regression. Good outcome was defined as a 90-day mRS score of 0-2. Variables assessed were time from onset to arrival, stroke code, neurologic exam, imaging, laboratories, treatment decision, and treatment (by quartiles). RESULTS: Two hundred ninety-one patients were included (49.8% female, mean age 70.6 ± 16.1, median National Institutes of Health Stroke Scale 10, SD = 8.5). Good outcome occurred in 45% of patients. Significant baseline differences included HTN (P ≤ .001), A fib (P ≤ .001), prestroke mRS (P < .001), and Hispanic ethnicity (P = .011). Comparing good with poor outcome groups: mean onset to arrival was 70.6 min versus 62.5 min (P = .129) and mean onset to treatment was 140.1 min versus 134.9 min (P = .118). Controlling for prespecified covariates, no PSC time goals were significant predictors of the 90-day outcome. CONCLUSIONS: In our Comprehensive Stroke Center (CSC), onset to PSC time goals were not significant predictors of the 90-day outcome. Expedited care processes in CSC may compensate for differences in outcome. These results should be validated in a larger cohort and in PSCs versus CSCs.

Therapeutic hypothermia is associated with a decrease in urine output in acute stroke patients.

AIMS: It is unclear what effect therapeutic hypothermia may have on renal function, because its effect has so far been primarily evaluated in settings in which there may be possible confounding perturbations in cardiovascular and renal physiology, such deep intraoperative hypothermia, general anesthesia, and post-cardiac arrest. We sought to determine if therapeutic hypothermia affects renal function in awake patients with normal renal function who were enrolled into a clinical trial of hypothermia plus intravenous thrombolysis for acute ischemic stroke. METHODS: Eleven patients with normal renal function were cooled to 33°C for 24 h using an endovascular catheter, and then re-warmed over 12 h to 36.5°C, while hourly temperature, blood pressure, and fluid status data was recorded. Blood samples for blood urea nitrogen (BUN), creatinine, and hematocrit were drawn prior to treatment (baseline), immediately after hypothermia and re-warming (day 2), and again at day 7 or discharge, and values compared. RESULTS: On initiation of cooling, temperatures dropped from a median pre-treatment value of 36.1°C (IQR: 35.8-36.4°C) to 33.1°C (IQR: 33.1-33.4°C). Urine output decreased 5.1 ml/h for every 1°C decrease in body temperature (p-value=0.001), with no associated serious adverse events. There were no statistically significant changes in BUN, creatinine, or hematocrit in the hypothermia patients. CONCLUSION: Inducing hypothermia in patients with relatively unperturbed renal physiology results in a decrease in urine output that is linearly correlated with the decrease in core temperature. This has important implications for fluid management in patients undergoing therapeutic hypothermia.

Intravenous thrombolysis plus hypothermia for acute treatment of ischemic stroke (ICTuS-L): final results.

BACKGROUND AND PURPOSE: Induced hypothermia is a promising neuroprotective therapy. We studied the feasibility and safety of hypothermia and thrombolysis after acute ischemic stroke. METHODS: Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke (ICTuS-L) was a randomized, multicenter trial of hypothermia and intravenous tissue plasminogen activator in patients treated within 6 hours after ischemic stroke. Enrollment was stratified to the treatment time windows 0 to 3 and 3 to 6 hours. Patients presenting within 3 hours of symptom onset received standard dose intravenous alteplase and were randomized to undergo 24 hours of endovascular cooling to 33°C followed by 12 hours of controlled rewarming or normothermia treatment. Patients presenting between 3 and 6 hours were randomized twice: to receive tissue plasminogen activator or not and to receive hypothermia or not. Results- In total, 59 patients were enrolled. One patient was enrolled but not treated when pneumonia was discovered just before treatment. All 44 patients enrolled within 3 hours and 4 of 14 patients enrolled between 3 to 6 hours received tissue plasminogen activator. Overall, 28 patients randomized to receive hypothermia (HY) and 30 to normothermia (NT). Baseline demographics and risk factors were similar between groups. Mean age was 65.5±12.1 years and baseline National Institutes of Health Stroke Scale score was 14.0±5.0; 32 (55%) were male. Cooling was achieved in all patients except 2 in whom there were technical difficulties. The median time to target temperature after catheter placement was 67 minutes (Quartile 1 57.3 to Quartile 3 99.4). At 3 months, 18% of patients treated with hypothermia had a modified Rankin Scale score of 0 or 1 versus 24% in the normothermia groups (nonsignificant). Symptomatic intracranial hemorrhage occurred in 4 patients (68); all were treated with tissue plasminogen activator <3 hours (1 received hypothermia). Six patients in the hypothermia and 5 in the normothermia groups died within 90 days (nonsignificant). Pneumonia occurred in 14 patients in the hypothermia and in 3 of the normothermia groups (P=0.001). The pneumonia rate did not significantly adversely affect 3 month modified Rankin Scale score (P=0.32). CONCLUSIONS: This study demonstrates the feasibility and preliminary safety of combining endovascular hypothermia after stroke with intravenous thrombolysis. Pneumonia was more frequent after hypothermia, but further studies are needed to determine its effect on patient outcome and whether it can be prevented. A definitive efficacy trial is necessary to evaluate the efficacy of therapeutic hypothermia for acute stroke.

An ethical hierarchy for decision making during medical emergencies.

Evidence from well-designed clinical trials may guide clinicians, reduce regional variation, and lead to improved outcomes. Many physicians choose to ignore evidence-based practice guidelines. Using unproven therapies outside of a randomized trial slows recruitment in clinical trials that could yield information on clinical and economic efficacy. Using acute stroke therapy as an illustration, we present an ethical hierarchy for therapeutic decision making during medical emergencies. First, physicians should offer standard care. If no standard care option exists, the physician should consider enrollment in a randomized clinical trial. If no trial is appropriate, the physician should consider a nonrandomized registry, or consensus-based guidelines. Finally, only after considering the first 3 options, the physician should use best judgment based on previous personal experience and any published case series or anecdotes. Given the paucity of quality randomized clinical trial data for most medical decisions, the "best judgment" option will be used most frequently. Nevertheless, such a hierarchy is needed because of the limited time during medical emergencies for consideration of general principles of clinical decision making. There should be general agreement in advance as to the hierarchy to follow in selecting treatment for critically ill patients. Were more clinicians to follow this hierarchy, and choose to participate in clinical trials, the generation of new knowledge would accelerate, yielding rigorous data supporting or refuting the efficacy and safety of new interventions more quickly, thus benefiting far more patients over time.

Analysis of the National Institute of Neurological Disorders and Stroke tissue plasminogen activator studies following European Cooperative Acute Stroke Study III patient selection criteria.

BACKGROUND: In 1995 two studies by the National Institute of Neurological Disorders and Stroke (NINDS) proved that intravenous tissue plasminogen activator (t-PA) was superior to placebo in patients with stroke of less than 3 hours' duration. The recently published European Cooperative Acute Stroke Study (ECASS) III introduced new patient selection criteria and treatment between 3 and 4.5 hours. Using these criteria, t-PA was shown effective at the later time window. Both analyses used the 3-month modified Rankin scale (mRS) score as main primary outcome. We sought to study the effect of applying the ECASS III selection criteria to the original NINDS cohort. METHODS: We analyzed the subgroup of patients from NINDS sample who matched the ECASSS III criteria. We examined 3-month outcomes adjusted and unadjusted for confounding factors. RESULTS: The NINDS t-PA study included 624 patients. A total of 200 in the t-PA-treated group and 199 in the placebo group were selected after applying ECASS III criteria. Of these selected patients, 52% in the t-PA group versus 31% had mRS score of 0 or 1 at 3 months (P < .001). The unadjusted odds ratio for t-PA treatment versus placebo on day-90 mRS score 0 to 1 versus 2 to 6 was 2.45 (95% confidence interval: 1.63-3.69). When adjusted for baseline National Institutes of Health Stroke Scale score, smoking status, time to treatment, and history of hypertension, the odds ratio was 2.14 (95% confidence interval: 1.34-3.41) (P < .001). CONCLUSION: Using the ECASS III criteria in patients treated in less than 3 hours, 52% of t-PA-treated patients had a favorable outcome at 3 months.

A trial of therapeutic hypothermia via endovascular approach in awake patients with acute ischemic stroke: methodology.

BACKGROUND: Therapeutic hypothermia has been shown to be of benefit in improving neurological outcome in cardiac arrest. It now is being investigated in acute stroke and myocardial infarction. The majority of the literature describes its use in intubated, pharmacologically paralyzed patients, using surface cooling techniques that are susceptible to patient shivering, imprecise temperature control, time lag to target-temperature acquisition, and rebound hyperthermia. OBJECTIVES: To develop a method of inducing therapeutic hypothermia in a rapid, precise, and tolerable fashion in awake, nonintubated patients. METHODS: This method was developed for an ongoing clinical trial investigating a combination of therapeutic hypothermia and intravenous thrombolysis for acute ischemic stroke. In the protocol, an endovascular cooling device is placed in the inferior vena cava of a patient, and a combination of buspirone, meperidine, and cutaneous warming with a heating blanket is used to suppress shivering as the patient is cooled to a target temperature of 33 degrees C, kept there for a total of 24 hours from hypothermia initiation, and then rewarmed in a controlled fashion during the next 12 hours. RESULTS: Ten patients underwent the therapeutic hypothermia protocol. The median pretreatment core temperature was 36.1 degrees C (interquartile range [IQR]: 35.8 degrees C-36.4 degrees C). On initiation of cooling, the core temperatures dropped rapidly and then leveled off, approaching a median plateau value of 33.4 degrees C (IQR: 33.2 degrees C-33.9 degrees C) in a mean time of 1.7 (+/- 0.7) hours from cooling initiation, with a median average postplateau temperature during the cooling phase of 33.8 degrees C (IQR: 33.3 degrees C-34.6 degrees C), and a median lowest temperature of 33.1 degrees C (IQR: 33.0 degrees C-33.3 degrees C). The procedure was well tolerated, with minimal shivering and no rebound hyperthermia. CONCLUSIONS: This is a method by which a rapid and precise therapeutic decrease in core temperature can be achieved without the necessity for intubation or neuromuscular blockade and with minimal patient discomfort or shivering.