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.

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.

Results of the ICTuS 2 Trial (Intravascular Cooling in the Treatment of Stroke 2).

BACKGROUND AND PURPOSE: Therapeutic hypothermia is a potent neuroprotectant approved for cerebral protection after neonatal hypoxia-ischemia and cardiac arrest. Therapeutic hypothermia for acute ischemic stroke is safe and feasible in pilot trials. We designed a study protocol to provide safer, faster therapeutic hypothermia in stroke patients. METHODS: Safety procedures and 4°C saline infusions for faster cooling were added to the ICTuS trial (Intravascular Cooling in the Treatment of Stroke) protocol. A femoral venous intravascular cooling catheter after intravenous recombinant tissue-type plasminogen activator in eligible patients provided 24 hours cooling followed by a 12-hour rewarm. Serial safety assessments and imaging were performed. The primary end point was 3-month modified Rankin score 0,1. RESULTS: Of the intended 1600 subjects, 120 were enrolled before the study was stopped. Randomly, 63 were to receive hypothermia plus antishivering treatment and 57 normothermia. Compared with previous studies, cooling rates were improved with a cold saline bolus, without fluid overload. The intention-to-treat primary outcome of 90-day modified Rankin Score 0,1 occurred in 33% hypothermia and 38% normothermia subjects, odds ratio (95% confidence interval) of 0.81 (0.36-1.85). Serious adverse events occurred equally. Mortality was 15.9% hypothermia and 8.8% normothermia subjects, odds ratio (95% confidence interval) of 1.95 (0.56-7.79). Pneumonia occurred in 19% hypothermia versus 10.5% in normothermia subjects, odds ratio (95% confidence interval) of 1.99 (0.63-6.98). CONCLUSIONS: Intravascular therapeutic hypothermia was confirmed to be safe and feasible in recombinant tissue-type plasminogen activator-treated acute ischemic stroke patients. Protocol changes designed to reduce pneumonia risk appeared to fail, although the sample is small. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01123161.

Accuracy of Stroke Diagnosis in Telestroke-Guided Tissue Plasminogen Activator Patients.

OBJECTIVES: The objective of the study is to assess the accuracy of final diagnosis in telestroke-guided tissue plasminogen activator (rt-PA) patients compared with bedside evaluation using computed tomography (CT) or magnetic resonance imaging (MRI) as a surrogate for final stroke diagnosis. The overall goal was to determine if telestroke had similar diagnostic accuracy as bedside evaluations in diagnosing rt-PA-treated patients. MATERIALS AND METHODS: We analyzed all acute stroke code calls who received intravenous rt-PA at our center from October 2013 to June 2015. Calls were grouped into patients who were initially evaluated by telestroke at a spoke partner site (spoke) and patients evaluated in person at the hub. Patients receiving additional neurointervention were excluded to avoid confounding. Relevant variables included severity of stroke (National Institutes of Health Stroke Scale [NIHSS]), rt-PA times, presence of intracranial hemorrhage (ICH), and primary outcome of CT or MRI evidence of stroke after rt-PA administration. Post-rt-PA imaging used included CT or MRI within 72 hours after treatment. RESULTS: Overall, 80 patients received intravenous rt-PA (spoke [n = 23] and hub [n = 57]). There was no difference in mean NIHSS score prior to treatment (10.3 ± 9.2 and 9.8 ± 8.4; P = .936), "onset-to-treatment" time (143.6 ± 53.5 minutes and 141.0 ± 54.1 minutes; P = .915), and ICH rate (13% and 8.8%; adjusted P = .898). The presence of radiographic evidence of stroke at spoke versus hub was not different (78.3% and 66.7%; adjusted P = .338). The most commonly used radiographic modality was MRI (MRI: 80%, CT: 20%). CONCLUSIONS: Using imaging as a surrogate for final diagnosis resulted in no difference in final stroke diagnosis rate between the groups, reinforcing that telestroke evaluations are as accurate as bedside evaluations in diagnosing acute stroke.

Association of Hispanic ethnicity with acute ischemic stroke care processes and outcomes.

BACKGROUND: Few studies have examined the actual hospital arrival mode, emergency department (ED) care processes, and early outcomes in Hispanic vs non-Hispanic acute ischemic stroke (AIS) patients. We evaluated processes and prognosis by Hispanic ethnicity among AIS patients encountered in urban setting. METHODS: We retrospectively reviewed prospectively-collected data on 1,117 AIS patients presenting within 12 hours of ictus to five hospitals in a tertiary-level stroke center network in San Diego, California. Variables of interest included pre-hospital factors, ED care processes, and favorable outcome (day-90 modified Rankin Scale [mRS] score of 0-1); all of which were adjusted for pre-specified covariates in a multivariable logistic regression model. RESULTS: There were 192 Hispanic AIS patients (17.2% of cohort) encountered from June 2004 to March 2011. Hispanic patients were significantly more likely to be younger, female, and diabetic. Hispanic patients arrived by ambulance (vs other arrival modes) less frequently (adjusted OR .56; 95% CI: .38-.81), trended toward a longer time of stroke onset to treatment decision (351.6 vs. 320.02 minutes, P=.07), and experienced a favorable day-90 outcome less often (adjusted OR .52, CI: .28-.96). However, for the day-90 outcome, there was no interaction between ambulance arrival and Hispanic ethnicity (P=.5614). DISCUSSION: Hispanic AIS patients in this study were less likely to arrive at the hospital by ambulance, and experienced half the odds of a favorable outcome compared to others. Strategies to boost ambulance utilization among Hispanic AIS patients and identify contributors to this worrisome outcome disparity are needed.

Defining mild stroke: outcomes analysis of treated and untreated mild stroke patients.

BACKGROUND: Mild deficit is a relative contraindication to administration of intravenous recombinant tissue plasminogen activator (IV rtPA) for acute ischemic stroke. However, what constitutes "mild" deficit is vague. Prior studies showed patients with mild strokes have substantial disability rates at hospital discharge and at 90 days. We investigated whether the application of a new definition altered the rates of disability overall and assessed the effects of thrombolysis. METHODS: This analysis included all adult acute ischemic stroke patients from a prospective registry of consecutive patients (University of California San Diego Specialized Programs of Translational Research in Acute Stroke (SPOTRIAS) database, 2003-2014) with 90-day modified Rankin Scale (mRS) score available who were defined as "mild" using either: National Institutes of Health Stroke Scale (NIHSS) 0-5 or a "Re-examining Acute Eligibility for Thrombolysis" (TREAT) Task Force definition (NIHSS 0-5 and nondisabling based on prespecified syndromes). Dichotomized 90-day mRS were compared between treated and untreated patients using the 2 definitions. RESULTS: Of 802 ischemic stroke patients with mRS scores available, 184 had baseline mRS (0) and met TREAT criteria; 45 (24.5%) were rtPA treated. Among the treated patients, 35.6% had 90-day mRS (2-6), versus 28.8% in the untreated group, a nonsignificant difference after adjusting for baseline NIHSS (P = .47). None of the 45 treated patients had symptomatic hemorrhage. Outcomes were similar using the simpler NIHSS 0-5 definition. CONCLUSIONS: About one third of mild stroke patients were not functionally independent at 90 days, irrespective of treatment or mild definition applied, calling into question the treatment efficacy of IV rtPA for mild strokes and what constitutes an appropriate definition of "mild." Randomized studies are necessary to determine rtPA treatment efficacy in mild stroke patients.

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.

The "DeyeCOM Sign": Predictive Value in Acute Stroke Code Evaluations.

BACKGROUND: Rapid diagnosis in stroke is critical. Computed tomography is often performed initially, even before a neurologic examination. Gaze deviation has been correlated with stroke diagnosis in some cohorts. Conjugate gaze deviation on stroke code imaging, the "DeyeCOM sign," may have emergency stroke care implications. METHODS: We evaluated stroke code imaging from the University of California, San Diego database (2007-2013) for "DeyeCOM sign" diagnostic and predictive utility. Patients were grouped as DeyeCOM+ if conjugate gaze deviation was noted. The differences were assessed using the Fisher exact test for categorical and the Wilcoxon rank-sum test for continuous variables. RESULTS: We evaluated 342 patients; 106 (31%) were DeyeCOM+. Mean age was 63. The most common diagnoses in the DeyeCOM+ group were ischemic stroke (50.94%), transient ischemic attack (8.49%), other (8.49%), somatization (6.6%), and hemorrhage (5.66%). The National Institutes of Health Stroke Scale was greater in stroke patients than that in nonstroke (8.2 versus 3.8; P < .0001), and in DeyeCOM+ compared with DeyeCOM- (6.8 versus 5.6; P = .03). DeyeCOM+ patients were more likely to have a +gaze score (26.4% versus 9.8%; P < .0001), and +gaze patients were more likely to have final stroke diagnosis (26.0% versus 3.6%; P < .0001). There was no overall difference between groups in final stroke diagnosis; however, patients with deviation of 15° or more were more likely to have final diagnosis stroke (63.9% versus 47.9%; P = .03). CONCLUSIONS: DeyeCOM+ patients scored higher and were more likely to have +gaze on the stroke scale, and deviation of 15° or more was correlated with final diagnosis stroke. In current environments, there is pressure to complete stroke evaluations rapidly. Reliable imaging information obtained early (such as gaze deviation on scan correlating with scale score and final stroke diagnosis) could augment decision making even with negative imaging.

Imaging negative stroke: diagnoses and outcomes in intravenous tissue plasminogen activator-treated patients.

BACKGROUND: Intravenous (IV) Alteplase (tissue plasminogen activator [t-PA]) improves outcome in patients with acute ischemic stroke. Of those with full recovery, some may not have had ischemia. We analyzed the frequency and post-treatment outcomes of stroke code patients with no imaging evidence of stroke to establish the incidence of neuroimaging negative cerebral ischemia (NNCI) and stroke mimics treated with t-PA. In addition, we compared these patients with the group of stroke patients with imaging evidence of acute stroke to determine whether there was a difference in adverse events and functional outcomes. METHODS: We included all adult stroke patients treated with IV t-PA within 3 hours of stroke onset from the University of California, San Diego, Specialized Programs of Translational Research in Acute Stroke database through January 2013. The imaging positive stroke (IPS) code group comprised patients with neuroimaging evidence of acute ischemic stroke, whereas the imaging negative stroke code (INS) group included those patients without neuroimaging evidence of acute cerebral ischemia. All final diagnoses were reviewed by an adjudicating body. We reviewed medical records and neuroimaging; compared discharge diagnosis, 90-day modified Rankin Scale (mRS) score, and incidence of intracranial hemorrhage; and adjusted for age, admission National Institutes of Health Stroke Scale (NIHSS), prestroke mRS, and diabetes in multivariable models. RESULTS: We identified 106 patients, 74 IPS patients and 32 INS patients, who had similar baseline characteristics, except for baseline NIHSS (IPS 12.9 ± 8.2, INS 8.0 ± 5.6, P = .002) and incidence of cardiac arrhythmias (IPS 32.4%, INS 12.5%, P = .034). The diagnoses in the INS group were stroke (23, 72%)-representing NNCI, somatization (6, 19%), tumor (1, 3%), seizure (1, 3%), and migraine (1, 3%). All IPS patients were diagnosed with acute ischemic stroke. Adjusted for age, baseline NIHSS, prestroke mRS, and diabetes, the INS patients had significantly higher rates (odds ratio 3.04, P = .036) of good functional outcome (90-day mRS score 0-1). Intracerebral hemorrhage (ICH) was found in 24% of the IPS patients and was symptomatic in 6.8%. None of the INS patients had ICH. CONCLUSIONS: Because most INS patients were found to have NNCI, which may represent either transient ischemic attack or aborted stroke, and there were no intracerebral hemorrhages in the INS group, our data support the safety of administering IV t-PA to all patients in whom acute ischemic stroke is clinically suspected. We have demonstrated that NNCI patients and stroke mimics are common, and future larger scale prospective studies are required to delineate the true frequencies of each and to evaluate differences in outcomes.

Pooled assessment of computed tomography interpretation by vascular neurologists in the STRokE DOC telestroke network.

BACKGROUND AND PURPOSE: The objective of this pooled analysis was to determine the level of agreement between central read and each of 2 groups (spoke radiologists and hub vascular neurologists) in interpreting head computed tomography (CT) scans of stroke patients presenting to telestroke network hospitals. METHODS: The Stroke Team Remote Evaluation Using a Digital Observation Camera (STRokE DOC and STRokE DOC-AZ TIME) trials were prospective, randomized, and outcome blinded comparing telemedicine and teleradiology with telephone-only consultations. In each trial, the CT scans of the subjects were interpreted by the hub vascular neurologist in the telemedicine arm and by the spoke radiologist in the telephone arm. We obtained a central read for each CT using adjudicating committees blinded to treatment arm and outcome. The data were pooled and the results reported for the entire population. Kappa statistics and exact agreement rates were used to assess interobserver agreement for radiographic contraindication to recombinant tissue plasminogen activator (rt-PA), presence of hemorrhage, tumor, hyperdense artery, acute stroke, prior stroke, and early ischemic changes. RESULTS: Among 261 analyzed cases, the agreement with central read for the presence of radiological rt-PA contraindication was excellent for hub vascular neurologist (96.2%, κ = .81, 95% CI .64-.97), spoke radiologist report (94.7%, κ = .64, 95% CI .39-.88), and overall (95.4%, κ = .74, 95% CI .59-.88). For rt-PA-treated patients (N = 65), overall agreement was 98.5%, and vascular neurologist agreement with central read was 100%. CONCLUSIONS: Both vascular neurologists and reports from spoke radiologists had excellent reliability in identifying radiologic rt-PA contraindications. These pooled findings demonstrate that telestroke evaluation of head CT scans for acute rt-PA assessments is reliable.

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.

Statin treatment intensity and cerebral vasomotor reactivity response in patients with ischemic stroke.

BACKGROUND AND PURPOSE: Cerebral vasomotor reactivity (VMR) is vital for regulating brain blood flow and maintaining neurological function. Impaired cerebral VMR is linked to a higher risk of stroke and poor post-stroke outcomes. This study explores the relationship between statin treatment intensity and VMR in patients with ischemic stroke. METHODS: Seventy-four consecutive patients (mean age 69.3 years, 59.4% male) with recent ischemic stroke were included. VMR levels were assessed 4 weeks after the index stroke using transcranial Doppler, measuring the breath-holding index (BHI) as an indicator of the percentage increase in middle cerebral artery blood flow (higher BHI signifies higher VMR). Multistep multivariable regression models, adjusted for demographic and cerebrovascular risk factors, were employed to examine the association between statin intensity treatment and BHI levels. RESULTS: Forty-one patients (55%) received high-intensity statins. Patients receiving high-intensity statins exhibited a mean BHI of 0.85, whereas those on low-intensity statins had a mean BHI of 0.67 (mean difference 0.18, 95% confidence interval: 0.13-0.22, p-value<.001). This significant difference persisted in the fully adjusted model (adjusted mean values: 0.84 vs. 0.68, p-value: .008). No significant differences were observed in BHI values within patient groups on high-intensity or low-intensity statin therapy (all p-values>.05). Furthermore, no significant association was found between baseline low-density lipoprotein (LDL) levels and BHI. CONCLUSIONS: High-intensity statin treatment post-ischemic stroke is linked to elevated VMR independent of demographic and clinical characteristics, including baseline LDL level. Further research is needed to explore statin therapy's impact on preserving brain vascular function beyond lipid-lowering effects.

Transcranial doppler (TCD) in predicting outcomes following successful mechanical thrombectomy of large vessel occlusions in anterior circulation: a systematic review and meta-analysis.

BACKGROUND: Transcranial Doppler (TCD) is a non-invasive, bedside tool that allows for real-time monitoring of the patient's hemodynamic status following mechanical thrombectomy (MT). This systematic review and meta-analysis aims to evaluate the predictive value of TCD parameters following successful MT (Thrombolysis in Cerebral Infarction 2b-3). METHODS: In July 2024, we searched PubMed, Embase, and Scopus, to identify observational studies in which TCD parameters were measured within 48 hours of MT. Using random-effects models, we compared four TCD parameters (mean flow velocity (MFV), MFV index, pulsatility index (PI), and peak systolic velocity (PSV) among groups with vs without hemorrhagic transformation (HT) and favorable vs poor functional recovery (modified Rankin Scale 0-2 vs 3-6). RESULTS: Eleven studies comprising 1432 patients (59% male; mean age range: 63-73 years) were included. The MFV and MFV index were higher in patients with HT (Hedges' g=0.42 and 0.54, P=0.015 and 0.005, respectively). Patients with MFV index ≥1.3 showed a higher risk of all HT (RR 1.97; 95% confidence interval (CI) 1.28 to 3.03, P=0.002), symptomatic HT (RR 4.68; 95% CI 1.49 to 14.65, P=0.008), and poor functional status at 90 days (RR 1.65; 95% CI 1.27 to 2.14, P=0.029), respectively. There was no difference in mean PSV (P=0.1) and PI (P=0.3) among groups with and without HT. CONCLUSION: This study underscores the prognostic value of the MFV index in predicting HT, symptomatic HT, and poor functional recovery after successful MT in the anterior circulation. Large-scale, multi-center studies are necessary to confirm these findings and to validate the MFV index as a reliable predictor for improving post-thrombectomy care.

Combined approach to lysis utilizing eptifibatide and recombinant tissue plasminogen activator in acute ischemic stroke-enhanced regimen stroke trial.

BACKGROUND AND PURPOSE: In a previous study, 0.3 and 0.45 mg/kg of intravenous recombinant tissue plasminogen activator (rt-PA) were safe when combined with eptifibatide 75 mcg/kg bolus and a 2-hour infusion (0.75 mcg/kg per minute). The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke-Enhanced Regimen (CLEAR-ER) trial sought to determine the safety of a higher-dose regimen and to establish evidence for a phase III trial. METHODS: CLEAR-ER was a multicenter, double-blind, randomized safety study. Ischemic stroke patients were randomized to 0.6 mg/kg rt-PA plus eptifibatide (135 mcg/kg bolus and a 2-hour infusion at 0.75 mcg/kg per minute) versus standard rt-PA (0.9 mg/kg). The primary safety end point was the incidence of symptomatic intracranial hemorrhage within 36 hours. The primary efficacy outcome measure was the modified Rankin Scale (mRS) score ≤1 or return to baseline mRS at 90 days. Analysis of the safety and efficacy outcomes was done with multiple logistic regression. RESULTS: Of 126 subjects, 101 received combination therapy, and 25 received standard rt-PA. Two (2%) patients in the combination group and 3 (12%) in the standard group had symptomatic intracranial hemorrhage (odds ratio, 0.15; 95% confidence interval, 0.01-1.40; P=0.053). At 90 days, 49.5% of the combination group had mRS ≤1 or return to baseline mRS versus 36.0% in the standard group (odds ratio, 1.74; 95% confidence interval, 0.70-4.31; P=0.23). After adjusting for age, baseline National Institutes of Health Stroke Scale, time to intravenous rt-PA, and baseline mRS, the odds ratio was 1.38 (95% confidence interval, 0.51-3.76; P=0.52). CONCLUSIONS: The combined regimen of intravenous rt-PA and eptifibatide studied in this trial was safe and provides evidence that a phase III trial is warranted to determine efficacy of the regimen. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00894803.

Prehospital stroke diagnosis and treatment in ambulances and helicopters-a concept paper.

Stroke is the second common cause of death and the primary cause of early invalidity worldwide. Different from other diseases is the time sensitivity related to stroke. In case of an ischemic event occluding a brain artery, 2000000 neurons die every minute. Stroke diagnosis and treatment should be initiated at the earliest time point possible, preferably at the site or during patient transport. Portable ultrasound has been used for prehospital diagnosis for applications other than stroke, and its acceptance as a valuable diagnostic tool "in the field" is growing. The intrahospital use of transcranial ultrasound for stroke diagnosis has been described extensively in the literature. Beyond its diagnostic use, first clinical trials as well as numerous preclinical work demonstrate that ultrasound can be used to accelerate clot lysis (sonothrombolysis) in presence as well as in absence of tissue plasminogen activator. Hence, the use of transcranial ultrasound for diagnosis and possibly treatment of stroke bares the potential to add to current stroke care paradigms significantly. The purpose of this concept article is to describe the opportunities presented by recent advances in transcranial ultrasound to diagnose and potentially treat large vessel embolic stroke in the prehospital environment.

Diffusion-weighted imaging-fluid attenuated inversion recovery mismatch in nocturnal stroke patients with unknown time of onset.

BACKGROUND: More than a quarter of patients with ischemic stroke (IS) are excluded from thrombolysis because of an unknown time of symptom onset. Recent evidence suggests that a mismatch between diffusion-weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR) imaging could be used as a surrogate for the time of stroke onset. We compared used the DWI-FLAIR mismatch and the FLAIR/DWI ratio to estimate the time of onset in a group of patients with nocturnal strokes and unknown time of onset. METHODS: We used a prospectively collected acute IS patient database with MRI as the initial imaging modality. Nineteen selected nocturnal stroke patients with unknown time of onset were compared with 22 patients who had an MRI scan within 6 hours from stroke onset (control A) and 19 patients who had an MRI scan between 6 and 12 hours (control B). DWI and FLAIR signal was rated as normal or abnormal. FLAIR/DWI ratio was calculated from independent DWI and FLAIR ischemic lesion volumes using semiautomatic software. RESULTS: The DWI-FLAIR mismatch was different among groups (unknown 43.7%; control A 63.6%; control B 10.5%; Fisher-Freeman-Halton test; P = .001). There were significant differences in FLAIR/DWI ratio among the 3 groups (unknown 0.05 ± 0.12; control A 0.17 ± 0.15; control B 0.04 ± 0.06; Kruskal-Wallis test; P < .0001). Post-hoc pairwise comparisons revealed that FLAIR/DWI ratio from the unknown group was significantly different from the control B group (P = .0045) but not different from the control A group. DWI volumes were not different among the 3 groups. CONCLUSIONS: A large proportion of patients with nocturnal IS and an unknown time of stroke initiation have a DWI-FLAIR mismatch, suggesting a recent onset of stroke.

Ransomware Attack Associated With Disruptions at Adjacent Emergency Departments in the US.

Importance: Cyberattacks on health care delivery organizations are increasing in frequency and sophistication. Ransomware infections have been associated with significant operational disruption, but data describing regional associations of these cyberattacks with neighboring hospitals have not been previously reported, to our knowledge. Objective: To examine an institution's emergency department (ED) patient volume and stroke care metrics during a month-long ransomware attack on a geographically proximal but separate health care delivery organization. Design, Setting, and Participants: This before and after cohort study compares adult and pediatric patient volume and stroke care metrics of 2 US urban academic EDs in the 4 weeks prior to the ransomware attack on May 1, 2021 (April 3-30, 2021), as well as during the attack and recovery (May 1-28, 2021) and 4 weeks after the attack and recovery (May 29 to June 25, 2021). The 2 EDs had a combined mean annual census of more than 70 000 care encounters and 11% of San Diego County's total acute inpatient discharges. The health care delivery organization targeted by the ransomware constitutes approximately 25% of the regional inpatient discharges. Exposure: A month-long ransomware cyberattack on 4 adjacent hospitals. Main Outcomes and Measures: Emergency department encounter volumes (census), temporal throughput, regional diversion of emergency medical services (EMS), and stroke care metrics. Results: This study evaluated 19 857 ED visits at the unaffected ED: 6114 (mean [SD] age, 49.6 [19.3] years; 2931 [47.9%] female patients; 1663 [27.2%] Hispanic, 677 [11.1%] non-Hispanic Black, and 2678 [43.8%] non-Hispanic White patients) in the preattack phase, 7039 (mean [SD] age, 49.8 [19.5] years; 3377 [48.0%] female patients; 1840 [26.1%] Hispanic, 778 [11.1%] non-Hispanic Black, and 3168 [45.0%] non-Hispanic White patients) in the attack and recovery phase, and 6704 (mean [SD] age, 48.8 [19.6] years; 3326 [49.5%] female patients; 1753 [26.1%] Hispanic, 725 [10.8%] non-Hispanic Black, and 3012 [44.9%] non-Hispanic White patients) in the postattack phase. Compared with the preattack phase, during the attack phase, there were significant associated increases in the daily mean (SD) ED census (218.4 [18.9] vs 251.4 [35.2]; P < .001), EMS arrivals (1741 [28.8] vs 2354 [33.7]; P < .001), admissions (1614 [26.4] vs 1722 [24.5]; P = .01), patients leaving without being seen (158 [2.6] vs 360 [5.1]; P < .001), and patients leaving against medical advice (107 [1.8] vs 161 [2.3]; P = .03). There were also significant associated increases during the attack phase compared with the preattack phase in median waiting room times (21 minutes [IQR, 7-62 minutes] vs 31 minutes [IQR, 9-89 minutes]; P < .001) and total ED length of stay for admitted patients (614 minutes [IQR, 424-1093 minutes] vs 822 minutes [IQR, 497-1524 minutes]; P < .001). There was also a significant increase in stroke code activations during the attack phase compared with the preattack phase (59 vs 102; P = .01) as well as confirmed strokes (22 vs 47; P = .02). Conclusions and Relevance: This study found that hospitals adjacent to health care delivery organizations affected by ransomware attacks may see increases in patient census and may experience resource constraints affecting time-sensitive care for conditions such as acute stroke. These findings suggest that targeted hospital cyberattacks may be associated with disruptions of health care delivery at nontargeted hospitals within a community and should be considered a regional disaster.

Determinants of effective cooling during endovascular hypothermia.

BACKGROUND: Therapeutic hypothermia is a promising neuroprotective therapy with multiple mechanisms of action. We demonstrated the feasibility of thrombolysis combined with endovascular hypothermia, but not all patients achieved effective cooling. We sought to identify the factors that determined effective cooling. METHODS: In 26 patients who underwent endovascular hypothermia, we computed four measures of effective cooling: time to reach target; Area-Under-the-Curve (AUC) 34 ratio; AUC-34; and AUC-35. By multivariate regression, we examined the effects of age, weight, starting temperature, body mass index, body surface area (BSA), gender, shivering, and total meperidine dose on the four outcome measures. RESULTS: In univariate analyses, all four outcome measures were significantly influenced by BSA (p < 0.01 in all univariate analyses). Time to reach target temperature was quicker in older patients (p < 0.01). Shivering and meperidine dose were highly intercorrelated (r = 0.6, p < 0.01) and both marginally influenced all four outcome measures. In multivariate analysis, AUC ratio and time to reach target temperature were significantly influenced by BSA (p < 0.01) and meperidine (p < 0.05); AUC-34 was influenced only by BSA (p < 0.01). The AUC-35 was influenced by BSA (p < 0.01), shivering, and total meperidine dose (p < 0.05). CONCLUSIONS: The most important determinant of effective cooling during endovascular hypothermia is BSA; larger patients are more difficult to cool and maintain in therapeutic range. Older patients cool more quickly. Shivering was well controlled by the combination of meperidine, buspirone, and surface counter-warming and only minimally influenced cooling effectiveness. Future trials of therapeutic hypothermia may include added measures to cool larger patients more effectively.