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 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.

The 10-second stroke: a case report.

BACKGROUND: Acute infarction is detected in a third of patients undergoing diffusion-weighted magnetic resonance imaging (DW-MRI) with clinically suspected transient ischemic attack. The longer symptoms are present, the more likely an infarct will be identified on DW-MRI. Events as short as 10 minutes have been reported in association with a DW-MRI lesion. METHODS: We present a case of an otherwise healthy man with a 10-second episode of neurologic dysfunction associated with DW-MRI lesions from a cardioembolic source. RESULTS: The atypical symptoms and lack of risk factors for cerebrovascular disease made his diagnosis easy to miss. CONCLUSIONS: Early DW-MRI may be of benefit beyond clinical judgment in patients with fleeting symptoms of neurologic dysfunction.

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.

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.

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.

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.

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.

Transient ischemic attack: an evidence-based update.

Transient ischemic attack represents a medical emergency and warns of an impending stroke in roughly one-third of patients who experience it. The risk of stroke is highest in the first 48 hours following a transient ischemic attack, and the initial evaluation in the emergency department is the best opportunity to identify those at highest risk of stroke recurrence. The focus should be on differentiating transient ischemic attack from stroke and common mimics. Accurate diagnosis is achieved by obtaining a history of abrupt onset of negative symptoms of ischemic origin fitting a vascular territory, accompanied by a normal examination and the absence of neuroimaging evidence of infarction. Transient ischemic attacks rarely last longer than 1 hour, and the classic 24-hour time-based definition is no longer relevant. Once the diagnosis has been made, clinical risk criteria may augment imaging findings to identify patients at highest and lowest risk of early recurrence. Early etiologic evaluation, including neurovascular and cardiac investigations, allows for catered secondary prevention strategies. Specialized transient ischemic attack clinics and emergency department observation units are safe and efficient alternatives to hospital admission for many transient ischemic attack patients.

Transient ischemic attack: reviewing the evolution of the definition, diagnosis, risk stratification, and management for the emergency physician.

A transient ischemic attack (TIA) is an episode of reversible neurologic deficit caused by temporary focal central nervous system hypoperfusion. TIA is a medical emergency. Because patients with TIA in the emergency department (ED) have a high risk for stroke within the next 48 hours, it is imperative for the clinician to recognize this golden opportunity to prevent a disabling stroke. This article reviews our conceptual understanding of TIA, its definition, diagnosis, ways to stratify stroke risk, the acute management and disposition in the ED, and the potential future role of diagnostic biomarkers.

Physician discretion is safe and may lower stress test utilization in emergency department chest pain unit patients.

INTRODUCTION: Chest pain unit (CPU) observation with defined stress utilization protocols is a common management option for low-risk emergency department patients. We sought to evaluate the safety of a joint emergency medicine and cardiology staffed CPU. METHODS: Prospective observational trial of consecutive patients admitted to an emergency department CPU was conducted. A standard 6-hour observation protocol was followed by cardiology consultation and stress utilization largely at their discretion. Included patients were at low/intermediate risk by the American Heart Association, had nondiagnostic electrocardiograms, and a normal initial troponin. Excluded patients were those with an acute comorbidity, age >75, and a history of coronary artery disease, or had a coexistent problem restricting 24-hour observation. Primary outcome was 30-day major adverse cardiovascular events-defined as death, nonfatal acute myocardial infarction, revascularization, or out-of-hospital cardiac arrest. RESULTS: A total of 1063 patients were enrolled over 8 months. The mean age of the patients was 52.8 ± 11.8 years, and 51% (95% confidence interval [CI], 48-54) were female. The mean thrombolysis in myocardial infarction and Diamond & Forrester scores were 0.6% (95% CI, 0.51-0.62) and 33% (95% CI, 31-35), respectively. In all, 51% (95% CI, 48-54) received stress testing (52% nuclear stress, 39% stress echocardiogram, 5% exercise, 4% other). In all, 0.9% patients (n = 10, 95% CI, 0.4-1.5) were diagnosed with a non-ST elevation myocardial infarction and 2.2% (n = 23, 95% CI, 1.3-3) with acute coronary syndrome. There was 1 (95% CI, 0%-0.3%) case of a 30-day major adverse cardiovascular events. The 51% stress test utilization rate was less than the range reported in previous CPU studies (P < 0.05). CONCLUSIONS: Joint emergency medicine and cardiology management of patients within a CPU protocol is safe, efficacious, and may safely reduce stress testing rates.

Psychogenic seizures: A review and description of pitfalls in their acute diagnosis and management in the emergency department.

Patients with psychogenic (nonepileptic) seizures (PS) are frequently encountered by clinicians in the emergency medicine setting. Despite the tendency for these patients to seek frequent medical attention, the time between onset of symptoms and diagnosis is often more than 7 years. The cause of PS is multifactorial, but most patients are thought to have an underlying dissociative condition. The diagnostic evaluation in the emergency department is challenging and relies heavily on clinical suspicion, based on historical and physical features. Laboratory testing and therapeutic maneuvers are of limited utility; prolonged video electroencephalography is the diagnostic gold standard. Once the diagnosis has been secured, the mainstay of treatment involves addressing the underlying psychological distress.