Strokes Averted by Intravenous Thrombolysis: A Secondary Analysis of a Prospective, Multicenter, Controlled Trial of Mobile Stroke Units.

OBJECTIVE: This study was undertaken to examine averted stroke in optimized stroke systems. METHODS: This secondary analysis of a multicenter trial from 2014 to 2020 compared patients treated by mobile stroke unit (MSU) versus standard management. The analytical cohort consisted of participants with suspected stroke treated with intravenous thrombolysis. The main outcome was a tissue-defined averted stroke, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours attributed to thrombolysis and no acute infarction/hemorrhage on imaging. An additional outcome was stroke with early symptom resolution, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours attributed to thrombolysis. RESULTS: Among 1,009 patients with a median last known well to thrombolysis time of 87 minutes, 159 (16%) had tissue-defined averted stroke and 276 (27%) had stroke with early symptom resolution. Compared with standard management, MSU care was associated with more tissue-defined averted stroke (18% vs 11%, adjusted odds ratio [aOR] = 1.82, 95% confidence interval [CI] = 1.13-2.98) and stroke with early symptom resolution (31% vs 21%, aOR = 1.74, 95% CI = 1.12-2.61). The relationships between thrombolysis treatment time and averted/early recovered stroke appeared nonlinear. Most models indicated increased odds for stroke with early symptom resolution but not tissue-defined averted stroke with earlier treatment. Additionally, younger age, female gender, hyperlipidemia, lower National Institutes of Health Stroke Scale, lower blood pressure, and no large vessel occlusion were associated with both tissue-defined averted stroke and stroke with early symptom resolution. INTERPRETATION: In optimized stroke systems, 1 in 4 patients treated with thrombolysis recovered within 24 hours and 1 in 6 had no demonstrable brain injury on imaging. ANN NEUROL 2024;95:347-361.

Prospective, Multicenter, Controlled Trial of Mobile Stroke Units.

BACKGROUND: Mobile stroke units (MSUs) are ambulances with staff and a computed tomographic scanner that may enable faster treatment with tissue plasminogen activator (t-PA) than standard management by emergency medical services (EMS). Whether and how much MSUs alter outcomes has not been extensively studied. METHODS: In an observational, prospective, multicenter, alternating-week trial, we assessed outcomes from MSU or EMS management within 4.5 hours after onset of acute stroke symptoms. The primary outcome was the score on the utility-weighted modified Rankin scale (range, 0 to 1, with higher scores indicating better outcomes according to a patient value system, derived from scores on the modified Rankin scale of 0 to 6, with higher scores indicating more disability). The main analysis involved dichotomized scores on the utility-weighted modified Rankin scale (≥0.91 or <0.91, approximating scores on the modified Rankin scale of ≤1 or >1) at 90 days in patients eligible for t-PA. Analyses were also performed in all enrolled patients. RESULTS: We enrolled 1515 patients, of whom 1047 were eligible to receive t-PA; 617 received care by MSU and 430 by EMS. The median time from onset of stroke to administration of t-PA was 72 minutes in the MSU group and 108 minutes in the EMS group. Of patients eligible for t-PA, 97.1% in the MSU group received t-PA, as compared with 79.5% in the EMS group. The mean score on the utility-weighted modified Rankin scale at 90 days in patients eligible for t-PA was 0.72 in the MSU group and 0.66 in the EMS group (adjusted odds ratio for a score of ≥0.91, 2.43; 95% confidence interval [CI], 1.75 to 3.36; P<0.001). Among the patients eligible for t-PA, 55.0% in the MSU group and 44.4% in the EMS group had a score of 0 or 1 on the modified Rankin scale at 90 days. Among all enrolled patients, the mean score on the utility-weighted modified Rankin scale at discharge was 0.57 in the MSU group and 0.51 in the EMS group (adjusted odds ratio for a score of ≥0.91, 1.82; 95% CI, 1.39 to 2.37; P<0.001). Secondary clinical outcomes generally favored MSUs. Mortality at 90 days was 8.9% in the MSU group and 11.9% in the EMS group. CONCLUSIONS: In patients with acute stroke who were eligible for t-PA, utility-weighted disability outcomes at 90 days were better with MSUs than with EMS. (Funded by the Patient-Centered Outcomes Research Institute; BEST-MSU ClinicalTrials.gov number, NCT02190500.).

ICU Interventions in Ischemic Stroke Patients Treated Using Liberalized IV-tPA Criteria.

BACKGROUND AND OBJECTIVE: Current standard practice guidelines recommend ICU admission for ischemic stroke patients treated with intravenous tissue plasminogen activator (IV-tPA). More recently, the trend in stroke care is to broaden eligibility for IV thrombolysis. Two examples are a more liberal inclusion criteria known as SMART criteria (sIV-tPA), and the transfer of patients to comprehensive stroke centers (CSC). The present study characterizes ICU interventions in these patients. Understanding which stroke patients that require ICU-level care may allow for placement of patients in the appropriate level of care at hospital admission. METHODS: We performed a retrospective review of consecutive transfer and nontransfer sIV-tPA-treated patients admitted to the ICU at a CSC. We evaluated the frequency, timing, and nature of ICU interventions. RESULTS: Three hundred and thirty one patients were treated with sIV-tPA and 42% required ICU interventions during ICU admission. Of patients requiring ICU interventions, 98% had an ICU intervention performed in triage, prior to admission. National Institute of Health Stroke Scale score only had a moderate association to requirement of ICU interventions. Neither transferring patients to a CSC nor the number of standard IV-tPA contraindications increased ICU interventions. CONCLUSIONS: Liberalized IV-tPA administration did not increase ICU interventions. Nearly all patients that required ICU interventions declared this need in triage, prior to ICU admission. This timing of ICU intervention use during triage is highly sensitive for whether a patient will require ongoing ICU-level care during hospital admission. Identifying ICU intervention use in triage may allow for more effective placement of post-IV-tPA patients in the appropriate inpatient care setting, leading to better utilization of scarce ICU resources.

Generalized Safety and Efficacy of Simplified Intravenous Thrombolysis Treatment (SMART) Criteria in Acute Ischemic Stroke: The MULTI SMART Study.

BACKGROUND: Common intravenous recombinant tissue plasminogen activator (IV rt-PA) exclusion criteria may substantially limit the use of thrombolysis. Preliminary data have shown that the SMART (Simplified Management of Acute stroke using Revised Treatment) criteria greatly expand patient eligibility by reducing thrombolysis exclusions, but they have not been assessed on a large scale. We evaluated the safety and efficacy of general adoption of SMART thrombolysis criteria to a large regional stroke network. METHODS: Retrospective analysis of consecutive patients who received IV thrombolysis within a regional stroke network was performed. Patients were divided into those receiving thrombolysis locally versus at an outside hospital. The primary outcome was modified Rankin Scale score (≤1) at discharge and the main safety outcome was symptomatic intracranial hemorrhage (sICH) rate. RESULTS: There were 539 consecutive patients, and 50.5% received thrombolysis at an outside facility. Ninety percent of the patients possessed common conventional IV rt-PA contraindications. There were no significant differences between local and network treated patients in favorable outcome (45.4% versus 37.4%; odds ratio [OR], .72; P > .09), mortality (9% versus 14%; OR, 1.6; P > .07), or sICH rate (2.6% versus 5.1%; OR, 2.0; P = .13). Multivariate analysis showed no association between receiving IV rt-PA at an outlying spoke hospital and higher rate of sICH or worse outcome at discharge. CONCLUSIONS: Generalized application of SMART criteria is safe and effective. Widespread application of these criteria could substantially increase the proportion of patients who might qualify for treatment.

Reduced clopidogrel metabolism in a multiethnic population: prevalence and rates of recurrent cerebrovascular events.

BACKGROUND: Concern has recently been raised over the possibility of a reduced efficacy of clopidogrel because of genetic variations in cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19) metabolism. A black box warning from the US Food and Drug Administration recommends that all patients be tested. It has been estimated that approximately 3% (range 2-14%) of the population are poor metabolizers, but few data are available for cerebrovascular patients. The objective of this study is to evaluate the frequency and effects of variability in CYP2C19 metabolism in patients with cerebrovascular disease. METHODS: A retrospective review of all patients with stroke and transient ischemic attack (TIA) tested for the clopidogrel CYP2C19 genotype was performed, with a collection of data including race/ethnicity, CYP2C19 status, and the presence of recurrent vascular events. RESULTS: A total of 53 cerebrovascular patients were tested, consisting of 5.7% poor (n = 3), 26.4% intermediate (n = 14), 62.3% extensive (n = 33), 3.8% indeterminate (n = 2), and 1.9% "mixed ultra rapid and poor" (n = 1) metabolizers. Only 10 of 38 white patients (26.3%; 95% confidence interval [CI] 0.14-0.42) were intermediate or poor metabolizers, compared with 7 of 15 (46.7%; 95% CI 0.25-0.70) nonwhites. Of 43 patients treated with clopidogrel, 3 of 27 extensive metabolizers (11.1%; 95% CI 0.04-0.28) had recurrent cerebrovascular events compared with 33.3% of intermediate metabolizers (4/12; 95% CI 0.14-0.61) and 50% of poor metabolizers (1/2; 95% CI 0.09-0.90). CONCLUSIONS: These data suggest that the proportion of poor/intermediate clopidogrel metabolizers in cerebrovascular patients is comparable to cardiovascular studies and these patients may have an increased risk of recurrent cerebrovascular events. Routine CYP2C19 testing may be warranted.

Headpulse measurement can reliably identify large-vessel occlusion stroke in prehospital suspected stroke patients: Results from the EPISODE-PS-COVID study.

BACKGROUND: Large-vessel occlusion (LVO) stroke represents one-third of acute ischemic stroke (AIS) in the United States but causes two-thirds of poststroke dependence and >90% of poststroke mortality. Prehospital LVO stroke detection permits efficient emergency medical systems (EMS) transport to an endovascular thrombectomy (EVT)-capable center. Our primary objective was to determine the feasibility of using a cranial accelerometry (CA) headset device for prehospital LVO stroke detection. Our secondary objective was development of an algorithm capable of distinguishing LVO stroke from other conditions. METHODS: We prospectively enrolled consecutive adult patients suspected of acute stroke from 11 study hospitals in four different U.S. geographical regions over a 21-month period. Patients received device placement by prehospital EMS personnel. Headset data were matched with clinical data following informed consent. LVO stroke diagnosis was determined by medical chart review. The device was trained using device data and Los Angeles Motor Scale (LAMS) examination components. A binary threshold was selected for comparison of device performance to LAMS scores. RESULTS: A total of 594 subjects were enrolled, including 183 subjects who received the second-generation device. Usable data were captured in 158 patients (86.3%). Study subjects were 53% female and 56% Black/African American, with median age 69 years. Twenty-six (16.4%) patients had LVO and 132 (83.6%) were not LVO (not-LVO AIS, 33; intracerebral hemorrhage, nine; stroke mimics, 90). COVID-19 testing and positivity rates (10.6%) were not different between groups. We found a sensitivity of 38.5% and specificity of 82.7% for LAMS ≥ 4 in detecting LVO stroke versus a sensitivity of 84.6% (p < 0.0015 for superiority) and specificity of 82.6% (p = 0.81 for superiority) for the device algorithm (CA + LAMS). CONCLUSIONS: Obtaining adequate recordings with a CA headset is highly feasible in the prehospital environment. Use of the device algorithm incorporating both CA and LAMS data for LVO detection resulted in significantly higher sensitivity without reduced specificity when compared to the use of LAMS alone.

Outcomes of patients with pre-existing disability managed by mobile stroke units: A sub-analysis of the BEST-MSU study.

BACKGROUND: Few data exist on acute stroke treatment in patients with pre-existing disability (PD) since they are usually excluded from clinical trials. A recent trial of mobile stroke units (MSUs) demonstrated faster treatment and improved outcomes, and included PD patients. AIM: To determine outcomes with tissue plasminogen activator (tPA), and benefit of MSU versus management by emergency medical services (EMS), for PD patients. METHODS: Primary outcomes were utility-weighted modified Rankin Scale (uw-mRS). Linear and logistic regression models compared outcomes in patients with versus without PD, and PD patients treated by MSU versus standard management by EMS. Time metrics, safety, quality of life, and health-care utilization were compared. RESULTS: Of the 1047 tPA-eligible ischemic stroke patients, 254 were with PD (baseline mRS 2-5) and 793 were without PD (baseline mRS 0-1). Although PD patients had worse 90-day uw-mRS, higher mortality, more health-care utilization, and worse quality of life than non-disabled patients, 53% returned to at least their baseline mRS, those treated faster had better outcome, and there was no increased bleeding risk. Comparing PD patients treated by MSU versus EMS, 90-day uw-mRS was 0.42 versus 0.36 (p = 0.07) and 57% versus 46% returned to at least their baseline mRS. There was no interaction between disability status and MSU versus EMS group assignment (p = 0.67) for 90-day uw-mRS. CONCLUSION: PD did not prevent the benefit of faster treatment with tPA in the BEST-MSU study. Our data support inclusion of PD patients in the MSU management paradigm.

Comparison of computed tomography angiography and transesophageal echocardiography for evaluating aortic arch disease.

Aortic arch (AA) atheroma is a common source of artery-to-artery embolism. Identification of AA atherosclerotic disease is an important component of the embolic stroke workup. Transesophageal echocardiography (TEE) is the gold standard for AA evaluation, but it has associated risks and is not always readily available. Computed tomography angiography (CTA) is a rapid and noninvasive alternative. This study was conducted to compare the sensitivity and specificity of CTA and TEE for detecting AA disease. We performed a retrospective review of 250 consecutive patients at a tertiary stroke center who underwent both TEE and CTA within a 90-day period. We compared the presence and characteristics of AA plaques using a predetermined grading system for plaques in the ascending, transverse, and descending arch for both modalities (grades 1-4). Out of 750 AA segments (ascending, transverse, and descending AA in 250 patients), 494 were adequately imaged by CTA and TEE. The sensitivity of CTA in detecting grade 1-4 AA atheromas was 53%, and the specificity was 89%. For only high-grade atheromas, the specificity improved to 99%, but the sensitivity decreased to 23%. The negative predictive value of CTA for detection of AA atheromas was 60% (range 54%-65%) for all grades and 95% (range 92%-96%) for high-grade atheromas. CTA has a high negative predictive value for AA atheromas, especially for higher-grade atheromas, and thus may be a useful screening tool to exclude high-grade plaques, indicating a possible complementary role for CTA in detecting AA atheromas.

Advanced cerebral monitoring in neurocritical care.

New cerebral monitoring techniques allow direct measurement of brain oxygenation and metabolism. Investigation using these new tools has provided additional insight into the understanding of the pathophysiology of acute brain injury and suggested new ways to guide management of secondary brain injury. Studies of focal brain tissue oxygen monitoring have suggested ischemic thresholds in focal regions of brain injury and demonstrated the interrelationship between brain tissue oxygen tension (P bt O 2 ) and other cerebral physiologic and metabolic parameters. Jugular venous oxygen saturation (SjVO 2 ) monitoring may evaluate global brain oxygen delivery and consumption, providing thresholds for detecting brain hypoperfusion and hyperperfusion. Furthermore, critically low values of P bt O 2 and SjVO 2 have also been predictive of mortality and worsened functional outcome, especially after head trauma. Cerebral microdialysis measures the concentrations of extracellular metabolites which may be relevant to cerebral metabolism or ischemia in focal areas of injury. Cerebral blood flow may be measured in the neurointensive care unit using continuous methods such as thermal diffusion and laser Doppler flowmetry. Initial studies have also attempted to correlate findings from advanced neuromonitoring with neuroimaging using dynamic perfusion computed tomography, positron emission tomography, and Xenon computed tomography. Additionally, new methods of data acquisition, storage, and analysis are being developed to address the increasing burden of patient data from neuromonitoring. Advanced informatics techniques such as hierarchical data clustering, generalized linear models, and heat map dendrograms are now being applied to multivariable patient data in order to better develop physiologic patient profiles to improve diagnosis and treatment.