Novel Treatments for Transient Ischemic Attack and Acute Ischemic Stroke.

The treatment of acute ischemic stroke is one of the most rapidly evolving areas in medicine. Like all ischemic vascular emergencies, the priority is reperfusion before irreversible infarction. The central nervous system is sensitive to brief periods of hypoperfusion, making stroke a golden hour diagnosis. Although the phrase "time is brain" is relevant today, emerging treatment strategies use more specific markers for consideration of reperfusion than time alone. Innovations in early stroke detection and individualized patient selection for reperfusion therapies have equipped the emergency medicine clinician with more opportunities to help stroke patients and minimize the impact of this disease.

High-Risk Chief Complaints III: Neurologic Emergencies.

A careful history and thorough physical examination are necessary in patients presenting with acute neurologic dysfunction. Patients presenting with headache should be screened for red-flag criteria that suggest a dangerous secondary cause warranting imaging and further diagnostic workup. Dizziness is a vague complaint; focusing on timing, triggers, and examination findings can help reduce diagnostic error. Most patients presenting with back pain do not require emergent imaging, but those with new neurologic deficits or signs/symptoms concerning for acute infection or cord compression warrant MRI. Delay to diagnosis and treatment of acute ischemic stroke is a frequent reason for medical malpractice claims.

Sex differences in 90-day outcomes after mechanical thrombectomy for acute ischemic stroke.

BACKGROUND: It is largely unknown whether functional outcomes after mechanical thrombectomy for large vessel occlusion (LVO) ischemic strokes differ by sex in non-clinical trial populations. We investigated sex differences in 90-day outcomes among ischemic stroke patients receiving mechanical thrombectomy. METHODS: This was a prospective cohort of adults treated with mechanical thrombectomy for LVO at a single academic comprehensive stroke center from July 2015 to April 2017. Data on independence (mRS ≤2) at hospital discharge and 90 days were collected prospectively. Multiple logistic regression was used to determine the association between sex and 90-day independence, first adjusting for demographics, pre-stroke mRS, and NIHSS, then by co-morbidities and time to thrombectomy, and finally by vessel recanalization and use of intravenous thrombolysis. RESULTS: We included 279 patients, 52% of whom were female. Compared with males, females were older (median years (IQR) 81 (75-88) vs. 71.5 (60-81), P<0.001) and had higher baseline NIHSS (mean SD 18.2±7.5 vs . 16.0±7.1, P=0.02). Similar proportions of males and females had pre-stroke mRS ≤2 (73.3% vs.67.1%, P=0.27). In multivariate analyses, males and females had a similar likelihood of being independent at discharge (aOR 0.71 (95%CI 0.32 to 1.58)), but females were less likely to be independent at 90 days (aOR 0.37 95% CI 0.16 to 0.87). CONCLUSIONS: In patients treated with mechanical thrombectomy for LVOs at a large comprehensive stroke center, females were less likely to be independent at 90 days. Future research should investigate contributors to poor outcomes post-discharge in females with LVOs, along with potential interventions to improve outcomes.

Troponin Improves the Yield of Transthoracic Echocardiography in Ischemic Stroke Patients of Determined Stroke Subtype.

Background and Purpose- Transthoracic echocardiography (TTE) is widely used in the ischemic stroke setting. In this study, we aim to investigate the yield of TTE in patients with ischemic stroke and known subtype and whether the admission troponin level improves the yield of TTE. Methods- Data were abstracted from a single-center prospective ischemic stroke database for 18 months and included all patients with ischemic stroke whose etiologic subtype could be obtained without the need of TTE. Unadjusted and adjusted regression models were built to determine whether positive cardiac troponin levels (≥0.1 ng/mL) improve the yield of TTE, adjusting for demographic and clinical characteristics. Results- We identified 578 patients who met the inclusion criteria. TTE changed clinical management in 64 patients (11.1%), but intracardiac thrombus was detected in only 4 patients (0.7%). In multivariable models, there was an association between TTE changing management and positive serum troponin level (adjusted odds ratio, 4.26; 95% CI, 2.17-8.34; P<0.001). Conclusions- In patients with ischemic stroke, TTE might lead to a change in clinical management in ≈1 of 10 patients with known stroke subtype before TTE but changed acute treatment decisions in <1 percent of patients. Serum troponin levels improved the yield of TTE in these patients.

Baseline NIH Stroke Scale is an inferior predictor of functional outcome in the era of acute stroke intervention.

Background and aims Baseline National Institutes of Health Stroke Scale (NIHSS) scores have frequently been used for prognostication after ischemic stroke. With the increasing utilization of acute stroke interventions, we aimed to determine whether baseline NIHSS scores are still able to reliably predict post-stroke functional outcome. Methods We retrospectively analyzed prospectively collected data from a high-volume tertiary-care center. We tested strength of association between NIHSS scores at baseline and 24 h with discharge NIHSS using Spearman correlation, and diagnostic accuracy of NIHSS scores in predicting favorable outcome at three months (defined as modified Rankin Scale 0-2) using receiver operating characteristic curve analysis with area under the curve. Results There were 1183 patients in our cohort, with median baseline NIHSS 8 (IQR 3-17), 24-h NIHSS 4 (IQR 1-11), and discharge NIHSS 2 (IQR 1-8). Correlation with discharge NIHSS was r = 0.60 for baseline NIHSS and r = 0.88 for 24-h NIHSS. Of all patients with follow-up data, 425/1037 (41%) had favorable functional outcome at three months. Receiver operating characteristic curve analysis for predicting favorable outcome showed area under the curve 0.698 (95% CI 0.664-0.732) for baseline NIHSS, 0.800 (95% CI 0.772-0.827) for 24-h NIHSS, and 0.819 (95% CI 0.793-0.845) for discharge NIHSS; 24 h and discharge NIHSS maintained robust predictive accuracy for patients receiving mechanical thrombectomy (AUC 0.846, 95% CI 0.798-0.895; AUC 0.873, 95% CI 0.832-0.914, respectively), while accuracy for baseline NIHSS decreased (AUC 0.635, 95% CI 0.566-0.704). Conclusion Baseline NIHSS scores are inferior to 24 h and discharge scores in predicting post-stroke functional outcomes, especially in patients receiving mechanical thrombectomy.

Predictors of symptomatic intracranial haemorrhage in patients with an ischaemic stroke with neurological deterioration after intravenous thrombolysis.

OBJECTIVES: Early neurological deterioration prompting urgent brain imaging occurs in nearly 15% of patients with ischaemic stroke receiving intravenous tissue plasminogen activator (tPA). We aim to determine risk factors associated with symptomatic intracranial haemorrhage (sICH) in patients with ischaemic stroke undergoing emergent brain imaging for early neurological deterioration after receiving tPA. METHODS: We abstracted data from our prospective stroke database and included all patients receiving tPA for ischaemic stroke between 1 March 2015 and 1 March 2017. We then identified patients with neurological deterioration who underwent urgent brain imaging prior to their per-protocol surveillance imaging and divided patients into two groups: those with and without sICH. We compared baseline demographics, clinical variables, in-hospital treatments and functional outcomes at 90 days between the two groups. RESULTS: We identified 511 patients who received tPA, of whom 108 (21.1%) had an emergent brain CT. Of these patients, 17.5% (19/108) had sICH; 21.3% (23/108) of emergent scans occurred while tPA was infusing, though only 4.3% of these scans (1/23) revealed sICH. On multivariable analyses, the only predictor of sICH was a change in level of consciousness (OR 6.62, 95% CI 1.64 to 26.70, P=0.008). CONCLUSION: Change in level of consciousness is associated with sICH among patients undergoing emergent brain imaging after receiving tPA. In this group of patients, preparation of tPA reversal agents while awaiting brain imaging may reduce reversal times. Future studies are needed to study the cost-effectiveness of this approach.

Perfusion imaging and recurrent cerebrovascular events in intracranial atherosclerotic disease or carotid occlusion.

Background Large vessel disease stroke subtype carries the highest risk of early recurrent stroke. In this study we aim to look at the association between impaired perfusion and early stroke recurrence in patients with intracranial atherosclerotic disease or total cervical carotid occlusion. Methods This is a retrospective study from a comprehensive stroke center where we included consecutive patients 18 years or older with intracranial atherosclerotic disease or total cervical carotid occlusion admitted with a diagnosis of ischemic stroke within 24 h from symptom onset with National Institute Health Stroke Scale < 15, between 1 December 2016 and 30 June 2017. Patients with (1) evidence of ≥ 50% stenosis of a large intracranial artery or total carotid artery occlusion, (2) symptoms referable to the territory of the affected artery, and (3) perfusion imaging data using the RAPID processing software were included. The primary predictor was unfavorable perfusion imaging defined as Tmax > 6 s mismatch volume (penumbra volume-infarct volume) of 15 ml or more. The outcome was recurrent cerebrovascular events at 90 days defined as worsening or new neurological symptoms in the absence of a nonvascular cause attributable to the decline, or new infarct or infarct extension in the territory of the affected artery. We used Cox proportional hazards models to determine the association between impaired perfusion and recurrent cerebrovascular events. Results Sixty-two patients met our inclusion criteria; mean age 66.4 ± 13.1 years, 64.5% male (40/62) and 50.0% (31/62) with intracranial atherosclerotic disease. When compared to patients with favorable perfusion pattern, patients with unfavorable perfusion pattern were more likely to have recurrent cerebrovascular events (55.6% (10/18) versus 9.1% (4/44), p < 0.001). This association persisted after adjusting for potential confounders (adjusted hazard ratio 10.44, 95% confidence interval 2.30-47.42, p = 0.002). Conclusion Perfusion mismatch predicts recurrent cerebrovascular events in patients with ischemic stroke due to intracranial atherosclerotic disease or total cervical carotid occlusion. Studies are needed to determine the utility of revascularization strategies in this patient population.

Is There a Neurologist in the House? A Summary of the Current State of Neurovascular Rotations for Emergency Medicine Residents.

OBJECTIVES: Neurovascular and neurocritical care emergencies constitute a leading cause of morbidity/mortality. There has been great evolution in this field, including but not limited to extended time-window therapeutic interventions for acute ischemic stroke. The intent of this article is to evaluate the goals and future direction of clinical rotations in neurovascular and neurocritical care for emergency medicine (EM) residents. METHODS: A panel of 13 board-certified emergency physicians from the Society for Academic Emergency Medicine (SAEM) neurologic emergencies interest group (IG) convened in response to a call for publications-three with fellowship training/board certification in stroke and/or neurocritical care; five with advanced research degrees; three who have been authors on national practice guidelines; and six who have held clinical duties within neurology, neurosurgery, or neurocritical care. A mixed-methods analysis was performed including a review of the literature, a survey of Council of Emergency Medicine Residency Directors (CORD) residency leaders/faculty and SAEM neuro-IG members, and a consensus review by this panel of select neurology rotations provided by IG faculty. RESULTS: Thirteen articles for residency neurovascular education were identified: three studies on curriculum, three studies evaluating knowledge, and seven studies evaluating knowledge after an educational intervention. Intervention outcomes included the ability to recognize and manage acute strokes, manage intracerebral hemorrhage, calculate National Institutes of Health Stroke Scale (NIHSS), and interpret images. In the survey sent to CORD residency leaders and neuro-IG faculty, response was obtained from 48 programs. A total of 52.1% indicated having a required rotation (6.2% general neurology, 2% stroke service, 18.8% neurologic intensive care unit, 2% neurosurgery, 22.9% on a combination of services). The majority of programs with required rotations have a combination rotation (residents rotate through multiple services) and evaluations were positive. CONCLUSIONS: Variability exists in the availability of neurovascular/neurocritical care rotations for EM trainees. Dedicated clinical time in neurologic education was beneficial to participants. Given recent advancements in the field, augmentation of EM residency training in this area merits strong consideration.

Early Elevated Troponin Levels After Ischemic Stroke Suggests a Cardioembolic Source.

BACKGROUND AND PURPOSE: Elevated cardiac troponin is a marker of cardiac disease and has been recently shown to be associated with embolic stroke risk. We hypothesize that early elevated troponin levels in the acute stroke setting are more prevalent in patients with embolic stroke subtypes (cardioembolic and embolic stroke of unknown source) as opposed to noncardioembolic subtypes (large-vessel disease, small-vessel disease, and other). METHODS: We abstracted data from our prospective ischemic stroke database and included all patients with ischemic stroke during an 18-month period. Per our laboratory, we defined positive troponin as ≥0.1 ng/mL and intermediate as ≥0.06 ng/mL and <0.1 ng/mL. Unadjusted and adjusted regression models were built to determine the association between stroke subtype (embolic stroke of unknown source and cardioembolic subtypes) and positive and intermediate troponin levels, adjusting for key confounders, including demographics (age and sex), clinical characteristics (hypertension, hyperlipidemia, diabetes mellitus, renal function, coronary heart disease, congestive heart failure, current smoking, and National Institutes of Health Stroke Scale score), cardiac variables (left atrial diameter, wall-motion abnormalities, ejection fraction, and PR interval on ECG), and insular involvement of infarct. RESULTS: We identified 1234 patients, of whom 1129 had admission troponin levels available; 10.0% (113/1129) of these had a positive troponin. In fully adjusted models, there was an association between troponin positivity and embolic stroke of unknown source subtype (adjusted odds ratio, 4.46; 95% confidence interval, 1.03-7.97; P=0.003) and cardioembolic stroke subtype (odds ratio, 5.00; 95% confidence interval, 1.83-13.63; P=0.002). CONCLUSIONS: We found that early positive troponin after ischemic stroke may be independently associated with a cardiac embolic source. Future studies are needed to confirm our findings using high-sensitivity troponin assays and to test optimal secondary prevention strategies in patients with embolic stroke of unknown source and positive troponin.

New biomarker for acute ischaemic stroke: plasma glycogen phosphorylase isoenzyme BB.

BACKGROUND: Glycogen phosphorylase is the key enzyme that breaks down glycogen to yield glucose-1-phosphate in order to restore depleted energy stores during cerebral ischaemia. We sought to determine whether plasma levels of glycogen phosphorylase BB (GPBB) isoform increased in patients with acute ischaemic stroke (AIS). METHODS: We studied plasma GPBB levels within 12 hours and again at 48±24 hours of symptom onset in 172 patients with imaging-confirmed AIS and 133 stroke-free individuals. We determined the ability of plasma GPBB to discriminate between cases and controls and examined the predictive value of plasma GPBB for 90-day functional outcome, 90-day survival and acute lesion volumes on neuroimaging. RESULTS: The mean (SD) GPBB levels were higher in cases (46.3±38.6 ng/mL at first measurement and 38.6±36.5 ng/mL at second measurement) than in controls (4.1±7.6 ng/mL, p<0.01 for both). The area under the receiver operating characteristic (ROC) curve for case-control discrimination based on first GPBB measurement was 0.96 (95% CI 0.93 to 0.98). The sensitivity and specificity based on optimal operating point on the ROC curve (7.0 ng/mL) were both 93%. GPBB levels increased in 90% of patients with punctate infarcts (<1.5 mL) and in all patients admitted within the first 4.5 hours of onset. There was no correlation between GPBB concentration and either clinical outcome or acute infarct volume. CONCLUSION: GPBB demonstrates robust response to acute ischaemia and high sensitivity for small infarcts. If confirmed in more diverse populations that also include stroke mimics, GPBB could find utility as a stand-alone marker for acute brain ischaemia.

The Association between Diffusion MRI-Defined Infarct Volume and NIHSS Score in Patients with Minor Acute Stroke.

BACKGROUND: Prior studies have shown a correlation between the National Institutes of Health Stroke Scale (NIHSS) and stroke volume on diffusion weighted imaging (DWI); data are more limited in patients with minor stroke. We sought to determine the association between DWI lesion(s) volume and the (1) total NIHSS score and (2) NIHSS component scores in patients with minor stroke. METHODS: We included all patients with minor stroke (NIHSS 0-5) enrolled in the Stroke Warning Information and Faster Treatment study. We calculated lesion(s) volume (cm3 ) on the DWI sequence using Medical Image Processing, Analysis, and Visualization (MIPAV, NIH, Version 7.1.1). We used nonparametric tests to study the association between the primary outcome, DWI lesion(s) volume, and the predictors (NIHSS score and its components). RESULTS: We identified 894 patients with a discharge diagnosis of minor stroke; 709 underwent magnetic resonance imaging and 510 were DWI positive. There was a graded relationship between the NIHSS score and median DWI lesion volume in cm3 : (NIHSS 0: 7.1, NIHSS 1: 8.0, NIHSS 2: 17.1, NIHSS 3: 11.6, NIHSS 4: 19.0, and NIHSS 5: 23.6, P < .01). The median lesion volume was significantly higher in patients with neglect (105.6 vs. 12.5, P = .025), language disorder (34.6 vs. 11.9, P < .001), and visual field impairment (185.6 vs. 11.6, P < .001). Other components of the NIHSS were not associated with lesion volume. CONCLUSION: In patients with minor stroke, the nature of deficit when used with the NIHSS score can improve prediction of infarct volume. This may have clinical and therapeutic implications.

Developing a statewide protocol to ensure patients with suspected emergent large vessel occlusion are directly triaged in the field to a comprehensive stroke center: how we did it.

We describe the process by which we developed a statewide field destination protocol to transport patients with suspected emergent large vessel occlusion to a comprehensive stroke center.

The Advanced Reperfusion Era: Implications for Emergency Systems of Ischemic Stroke Care.

Large vessel ischemic stroke is a leading cause of morbidity and mortality throughout the world. Recent advances in endovascular stroke treatment are changing the treatment paradigm for these patients. This concepts article summarizes the time-dependent nature of stroke care and evaluates the recent advancements in endovascular treatment. These advancements have significant implications for out-of-hospital, hospital, and regional systems of stroke care. Emergency medicine clinicians have a central role in implementing these systems that will ensure timely treatment of patients and selection of those who may benefit from endovascular care.

Treatment of Acute Ischemic Stroke.

Although stroke declined from the third to fifth most common cause of death in the United States, the annual incidence and overall prevalence continue to increase. Since the available US Food and Drug Administration-approved treatment options are time dependent, improving early stroke care may have more of a public health impact than any other phase of care. Timely and efficient stroke treatment should be a priority for emergency department and prehospital providers. This article discusses currently available and emerging treatment options in acute ischemic stroke focusing on the preservation of salvageable brain tissue, minimizing complications, and secondary prevention.

Minor Stroke and Transient Ischemic Attack: Research and Practice.

A majority of patients with ischemic stroke present with mild deficits for which aggressive management is not often pursued. Comprehensive work-up and appropriate intervention for minor strokes and transient ischemic attacks (TIAs) point toward better patient outcomes, lower costs, and fewer cases of disability. Imaging is a key modality to guide treatment and predict stroke recurrence. Patients with large vessel occlusions have been found to suffer worse outcomes and could benefit from intervention. Whether intravenous thrombolytic therapy decreases disability in minor stroke patients and whether acute endovascular intervention improves functional outcomes in patients with minor stroke and known large vessel occlusion remain controversial. Studies are ongoing to determine ideal antiplatelet therapy for stroke and TIA, while ongoing statin therapy, surgical management for patients with carotid stenosis, and anticoagulation for patients with atrial fibrillation have all been proven to decrease the rate of stroke recurrence and improve outcomes. This review summarizes the current evidence and discusses the standard of care for patients with minor stroke and TIA.

Imaging Parameters and Recurrent Cerebrovascular Events in Patients With Minor Stroke or Transient Ischemic Attack.

IMPORTANCE: Neurological worsening and recurrent stroke contribute substantially to morbidity associated with transient ischemic attacks and strokes (TIA-S). OBJECTIVE: To determine predictors of early recurrent cerebrovascular events (RCVEs) among patients with TIA-S and National Institutes of Health Stroke Scale scores of 0 to 3. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted at 2 tertiary care centers (Columbia University Medical Center, New York, New York, and Tulane University Medical Center, New Orleans, Louisiana) between January 1, 2010, and December 31, 2014. All patients with neurologist-diagnosed TIA-S with a National Institutes of Health Stroke Scale score of 0 to 3 who presented to the emergency department were included. MAIN OUTCOMES AND MEASURES: The primary outcome (adjudicated by 3 vascular neurologists) was RCVE: neurological deterioration in the absence of a medical explanation or recurrent TIA-S during hospitalization. RESULTS: Of the 1258 total patients, 1187 had no RCVEs and 71 had RCVEs; of this group, 750 patients (63.2%) and 39 patients (54.9%), respectively, were aged 60 years or older. There were 505 patients with TIA-S at Columbia University; 31 (6.1%) had RCVEs (15 patients had neurological deterioration only, 11 had recurrent TIA-S only, and 5 had both). The validation cohort at Tulane University consisted of 753 patients; 40 (5.3%) had RCVEs (24 patients had neurological deterioration only and 16 had both). Predictors of RCVE in multivariate models in both cohorts were infarct on neuroimaging (computed tomographic scan or diffusion-weighted imaging sequences on magnetic resonance imaging) (Columbia University: not applicable and Tulane University: odds ratio, 1.75; 95% CI, 0.82-3.74; P = .15) and large-vessel disease etiology (Columbia University: odds ratio, 6.69; 95% CI, 3.10-14.50 and Tulane University: odds ratio, 8.13; 95% CI, 3.86-17.12; P < .001). There was an increase in the percentage of patients with RCVEs when both predictors were present. When neither predictor was present, the rate of RCVE was extremely low (up to 2%). Patients with RCVEs were less likely to be discharged home in both cohorts. CONCLUSIONS AND RELEVANCE: In patients with minor stroke, vessel imaging and perhaps neuroimaging parameters, but not clinical scores, were associated with RCVEs in 2 independent data sets. Prospective studies are needed to validate these predictors.