FABS: An Intuitive Tool for Screening of Stroke Mimics in the Emergency Department.

BACKGROUND AND PURPOSE: A large number of patients with symptoms of acute cerebral ischemia are stroke mimics (SMs). In this study, we sought to develop a scoring system (FABS) for screening and stratifying SM from acute cerebral ischemia and to identify patients who may require magnetic resonance imaging to confirm or refute a diagnosis of stroke in the emergency setting. METHODS: We designed a scoring system: FABS (6 variables with 1 point for each variable present): absence of Facial droop, negative history of Atrial fibrillation, Age <50 years, systolic Blood pressure <150 mm Hg at presentation, history of Seizures, and isolated Sensory symptoms without weakness at presentation. We evaluated consecutive patients with symptoms of acute cerebral ischemia and a negative head computed tomography for any acute finding within 4.5 hours after symptom onset in 2 tertiary care stroke centers for validation of FABS. RESULTS: A total of 784 patients (41% SMs) were evaluated. Receiver operating characteristic curve (C statistic, 0.95; 95% confidence interval [CI], 0.93-0.98) indicated that FABS≥3 could identify patients with SM with 90% sensitivity (95% CI, 86%-93%) and 91% specificity (95% CI, 88%-93%). The negative predictive value and positive predictive value were 93% (95% CI, 90%-95%) and 87% (95% CI, 83%-91%), respectively. CONCLUSIONS: FABS seems to be reliable in stratifying SM from acute cerebral ischemia cases among patients in whom the head computed tomography was negative for any acute findings. It can help clinicians consider advanced imaging for further diagnosis.

Characterization of a Thermoacoustic-based Pulsed High Power Microwave Detector Chain.

ABSTRACT: Detection of microwave-induced thermoacoustic (TA) wave generation was evaluated as a potential technique for detection of high power microwave (HPM) directed energy exposure. Even when HPM is employed for counter-materiel effects, incidental but still potentially harmful personnel exposure is possible. Real-time detection of ongoing exposure with potentially unknown time and frequency domain characteristics is a critical first step in preventing acute health effects by alerting and then enabling the timely use of electromagnetic frequency energy shielding, such as structures and vehicles. Leveraging the TA effect as a field interaction mechanism, a lossy dielectric polymer subjected to pulsed HPM was tested using a planar sample geometry with thin film piezoelectric sensors used to capture the resulting TA output. The piezoelectric signal was analyzed in both the time and frequency domain to determine empirical relationships between incident microwave beam properties and signal components. This analysis was coupled with an empirically-based single term Cole-Cole model approximation fit for the complex permittivity. The results were used to identify appropriate signal conditioning and processing techniques needed to convert the TA response into a useful form for personnel exposure applications. These results also served as a comparison point for multi-physics finite element method computational modeling of the electromagnetic response of a simplified three-layer tissue model.

A model to prevent fibrinolysis in patients with stroke mimics.

BACKGROUND: Many patients with stroke-mimicking conditions receive treatment with intravenous fibrinolysis (IVF), a treatment associated with potentially serious complications. We sought to determine if any clinical or radiographic characteristics can help predict stroke mimics among IVF candidates. METHODS: This retrospective study was carried out at a single institution. Patients treated with intravenous recombinant tissue plasminogen activator (rt-PA; n = 193) were divided into 3 categories: acute ischemic stroke (n = 142), aborted stroke (n = 21), and stroke mimics (n = 30). Analysis of variance and the chi-square test were used to assess differences, while logistic regression models were computed to predict groups. RESULTS: Mimics treated with rt-PA did not experience complications (intracranial bleeding, systemic hemorrhage, or angioedema), and had better neurologic and functional outcomes than stroke patients (P < .05). Several variables helped differentiate strokes from mimics, including atherosclerosis on computed tomographic angiography (odds ratio [OR] 23.6; 95% confidence interval [CI] 8.4-66.2), atrial fibrillation (OR 11.4; 95% CI 1.5-86.3), age >50 years (OR 7.2; 95% CI 2.8-18.5), and focal weakness (OR 4.15; 95% CI 1.75-9.8). Other variables decreased chances of stroke: migraine history (OR 0.05; 95% CI 0.01-0.4), epilepsy (OR 0.13; 95% CI 0.02-0.8), paresthesia (OR 0.1; 95% CI 0.04-0.3), and precordialgia (OR 0.045; 95% CI 0.002-0.9). A regression model using focal weakness, computed tomographic angiography findings, and precordialgia had a 90.2% predictive accuracy. CONCLUSIONS: IVF has low complication rates in stroke mimics. Certain clinical characteristics appear predictive of stroke mimics, particularly normal computed tomographic angiography. If confirmed, this may help prevent giving IVF to patients without stroke.

Modeling a Lossy Dieletric Polymer-based Thermoacoustic High Power Microwave Directed Energy Exposure Detection System.

ABSTRACT: Presented are design considerations for a potential detection and measurement technique that could provide operational awareness of high power microwave (HPM) directed energy weapon exposure for force health protection applications, leveraging thermoacoustic (TA) wave generation as the field interaction mechanism. The HPM electromagnetic frequency (EMF) regime, used in applications in both the counter-materiel and non-lethal counter-personnel design space, presents real-time personnel exposure warning challenges due to the potentially wide variation in time and frequency domain characteristics of the incident beam. As with other EM-thermal interactions, the thermoacoustic wave effect provides the potential to determine EM energy and power deposition without the need to measure ambient field intensity values or overload-sensitive EMF survey equipment. Following measurement of relevant EM, thermal, and elastic material property values, a carbon-filled polytetrafluoroethylene (CF-PTFE) lossy dielectric medium subject to pulsed HPM was computationally modeled using the commercial finite element method multi-physics simulation software package COMSOL. The simulation was used to explore the impacts of various material properties on TA signal output as a function of simulated incident field power density, EM frequency, and pulse length, thereby informing the selection of system components for the further development of a full TA-based HPM detection chain.

Safety and outcomes of intravenous thrombolysis in stroke mimics: a 6-year, single-care center study and a pooled analysis of reported series.

BACKGROUND AND PURPOSE: Efforts to increase the availability and shorten the time delivery of intravenous thrombolysis in patients with acute ischemic stroke carry the potential for tissue plasminogen activator administration in patients with diseases other than stroke, that is, stroke mimics (SMs). We aimed to determine safety and to describe outcomes of intravenous thrombolysis in SM. METHODS: We retrospectively analyzed stroke registry data of consecutive acute ischemic stroke admissions treated with intravenous thrombolysis over a 6-year-period. The admission National Institutes of Health Stroke Scale score, vascular risk factors, ischemic lesions on brain MRI (routinely performed as part of diagnostic work-up), and discharge modified Rankin Scale scores were documented. Initial stroke diagnosis in the emergency department was compared with final discharge diagnosis. SM diagnosis was based on the absence of ischemic lesions on diffusion-weighted imaging sequences in addition to an alternate discharge diagnosis. Symptomatic intracranial hemorrhage was defined as brain imaging evidence of intracranial hemorrhage with clinical worsening by National Institutes of Health Stroke Scale score increase of ≥4 points. RESULTS: Intravenous thrombolysis was administered in 539 patients with acute ischemic stroke (55% men; mean age, 66 ± 15 years). Misdiagnosis of acute ischemic stroke was documented in 56 cases (10.4%; 95% CI, 7.9% to 13.3%). Conversion disorder (26.8%), complicated migraine (19.6%), and seizures (19.6%) were the 3 most common final diagnoses in SM. SMs were younger (mean age, 56 ± 13 years) and had milder baseline stroke severity (median National Institutes of Health Stroke Scale, 6; interquartile range, 4) compared with patients with confirmed acute ischemic stroke (mean age, 67 ± 14 years; median National Institutes of Health Stroke Scale, 8; interquartile range, 10; P<0.001). There was no case of symptomatic intracranial hemorrhage in SMs (0%; 95% CI, 0% to 5.5%); 96% of SMs were functionally independent at hospital discharge (modified Rankin Scale, 0 to 1). CONCLUSIONS: Our single-center data indicate favorable safety and outcomes of intravenous thrombolysis administered to SM.

Cerebral ischemic events associated with 'bubble study' for identification of right to left shunts.

BACKGROUND AND PURPOSE: Detection of an intracardiac shunt is frequently sought during the evaluation of patients with cryptogenic ischemic stroke and agitated saline intravenous injection, or "bubble study" (BS), is performed in most cases. We present the first attempt to identify the clinical features in patients who had cerebral ischemic events with BS. METHODS: Using a list serve established by the American Academy of Neurology, a member posted a question regarding the safety of BS in patients with patent foramen ovale. A standardized questionnaire was used to gather data about patients with cerebral ischemic events, details of each case were reviewed, and the findings pooled. RESULTS: Five patients with ischemic complications of BS (all female, aged 42 to 90 years) were identified from 4 institutions, 3 ischemic strokes and 2 transient ischemic attacks. Events occurred either during or within 5 minutes of BS. Early brain MRIs confirmed acute infarction in 3, including one who had transient symptoms. MRI infarct volumes were small, and deficits were mild in those who developed stroke. Diagnostic evaluation revealed a patent foramen ovale alone in one case, a pulmonary arteriovenous malformation in one case, and a patent foramen ovale and/or pulmonary shunt in 3 cases. CONCLUSIONS: Ischemic cerebrovascular complications can occur in patients who undergo BS and are associated with the presence of cardiac or pulmonary shunts. The true incidence and degree of disability remains unknown, and further study is indicated to assess the impact of technical differences in BS methodology. Novel methods to promote physician communication such as the use of electronic list serves may reduce barriers to reporting of drug, technique, or device complications and should be explored to identify rare complications that otherwise will likely go unappreciated.

Pre-tissue plasminogen activator blood pressure levels and risk of symptomatic intracerebral hemorrhage.

BACKGROUND AND PURPOSE: From small pilot studies, uncontrolled pretreatment systolic blood pressure >185 mm Hg and diastolic blood pressure >110 mm Hg in patients with acute ischemic stroke were introduced in the National Institute of Neurological Diseases and Stroke rtPA Stroke Study as a contraindication for thrombolysis. We sought to determine if pretreatment blood pressure protocol violations in patients with acute ischemic stroke receiving intravenous tissue plasminogen activator are related to the subsequent risk of symptomatic intracranial hemorrhage (sICH). METHODS: We reviewed medical records of consecutive ischemic stroke admissions treated with intravenous thrombolysis over a 10-year period at our tertiary care hospital. The National Institutes of Health Stroke Scale score on admission was used to determine baseline stroke severity. The closest documented blood pressure values to the time of tissue plasminogen activator bolus (range, 0 to 10 minutes) were considered as pretreatment blood pressure. Pretreatment blood pressure protocol violations were identified as systolic blood pressure >185 or diastolic blood pressure >110 mm Hg prebolus. sICH was defined as brain imaging evidence of intracranial hemorrhage with clinical worsening by the National Institutes of Health Stroke Scale score increase of >or=4 points. RESULTS: Among 510 patients with ischemic stroke treated with intravenous tissue plasminogen activator (282 men; mean age, 65+/-15 years), sICH occurred in 31 patients (6.1%). Blood pressure protocol violations were present in 63 patients (12.4%) and they were more frequent in patients with sICH (26% versus 12%; P=0.019). After adjusting for demographic characteristics, onset-to-treatment time, baseline National Institutes of Health Stroke Scale, stroke risk factors and medications, pretreatment blood pressure protocol violations were independently associated with a higher likelihood of sICH (OR, 2.59; 95% CI, 1.07 to 6.25; P=0.034). CONCLUSIONS: These data support current guidelines advising not to use intravenous tissue plasminogen activator when pretreatment blood pressure exceeds the prespecified thresholds by showing that blood pressure protocol violations are independently associated with a higher likelihood of sICH.

The combined approach to lysis utilizing eptifibatide and rt-PA in acute ischemic stroke: the CLEAR stroke trial.

BACKGROUND AND PURPOSE: Multiple approaches are being studied to enhance the rate of thrombolysis for acute ischemic stroke. Treatment of myocardial infarction with a combination of a reduced-dose fibrinolytic agent and a glycoprotein (GP) IIb/IIIa receptor antagonist has been shown to improve the rate of recanalization versus fibrinolysis alone. The combined approach to lysis utilizing eptifibatide and recombinant tissue-type plasminogen activator (rt-PA) (CLEAR) stroke trial assessed the safety of treating acute ischemic stroke patients within 3 hours of symptom onset with this combination. METHODS: The CLEAR trial was a National Institutes of Health/National Institute of Neurological Disorders and Stroke-funded multicenter, double-blind, randomized, dose-escalation and safety study. Patients were randomized 3:1 to either low-dose rt-PA (tier 1=0.3 mg/kg, tier 2=0.45 mg/kg) plus eptifibatide (75 microg/kg bolus followed by 0.75 microg/kg per min infusion for 2 hours) or standard-dose rt-PA (0.9 mg/kg). The primary safety end point was the incidence of symptomatic intracerebral hemorrhage within 36 hours. Secondary analyses were performed regarding clinical efficacy. RESULTS: Ninety-four patients (40 in tier 1 and 54 in tier 2) were enrolled. The combination group of the 2 dose tiers (n=69) had a median age of 71 years and a median baseline National Institutes of Health Stroke Scale (NIHSS) score of 14, and the standard-dose rt-PA group (n=25) had a median age of 61 years and a median baseline NIHSS score of 10 (P=0.01 for NIHSS score). Fifty-two (75%) of the combination treatment group and 24 (96%) of the standard treatment group had a baseline modified Rankin scale score of 0 (P=0.04). There was 1 (1.4%; 95% CI, 0% to 4.3%) symptomatic intracranial hemorrhage in the combination group and 2 (8.0%; 95% CI, 0% to 19.2%) in the rt-PA-only arm (P=0.17). During randomization in tier 2, a review by the independent data safety monitoring board demonstrated that the safety profile of combination therapy at the tier 2 doses was such that further enrollment was statistically unlikely to indicate inadequate safety for the combination treatment group, the ultimate outcome of the study. Thus, the study was halted. There was a trend toward increased clinical efficacy of standard-dose rt-PA compared with the combination treatment group. CONCLUSIONS: The safety of the combination of reduced-dose rt-PA plus eptifibatide justifies further dose-ranging trials in acute ischemic stroke.

Study of the propensity for hemorrhage in Hispanic Americans with stroke.

OBJECTIVE: Multiple sources document a higher proportion of intraparenchymal hemorrhage (HEM) in Hispanic (HIS) than white (WHI) patients with stroke. We sought an explanation for this phenomenon through analysis of multiple variables in our hospital-based stroke population. METHODS: We performed univariate and multivariate analysis of risk factors in our HIS and WHI patients with stroke to identify differences that might account for a greater propensity for HEM in HIS patients. RESULTS: Multivariate analysis disclosed that the risk of HEM correlated significantly with untreated hypertension (HTN), HIS ethnicity, and heavy alcohol intake. A negative correlation was found for hyperlipidemia and diabetes. Our HIS patients with stroke had a greater prevalence of untreated HTN and heavy alcohol intake, with HIS men being at greatest risk. CONCLUSIONS: HIS patients with stroke in our hospital-based population appear relatively more prone to HEM than do WHI patients. This risk correlates with a greater likelihood of having untreated HTN and heavy alcohol intake, more so for HIS men. The explanation appears to be a relative lack of health awareness and involvement in our health care system. The possibility that HIS ethnicity itself constitutes a biological risk factor for HEM remains a matter of speculation. Validation of this work with community data should lead to remediation through a community-based effort.

Recombinant tissue plasminogen activator (rtPA) for stroke. The perspective at 8 years.

OBJECTIVE: To review the 8-year experience with recombinant tissue plasminogen activator (rtPA) for stroke, with commentary on ramifications for the approach to stroke treatment, directions in stroke research, and sociological aspects of stroke as a disease of concern in our society. BACKGROUND: Approved in 1996, rtPA remains the only drug indicated for the treatment of ischemic stroke. Stroke treatment and research have evolved rapidly in response to opportunities and discoveries related to the advent of rtPA. The presence of rtPA has engendered an increased level of awareness about all aspects of stroke. METHODOLOGY: Literature review was performed, focusing on topics that in the author's view are of greatest relevance to the use of rtPA in clinical practice and to the directions in which the presence of rtPA is moving the field of stroke treatment, research, and politics. RESULTS: Challenges have been raised, and met, regarding the validity of the data upon which the approval for rtPA was based. Limitations in the use of rtPA include the brief time available for treatment, the need for rapid imaging and blood-pressure control, and the fact that large-artery occlusions respond poorly. The major risk of treatment is brain hemorrhage, and although predictors of hemorrhage are known, their presence does not constitute an absolute contraindication to treatment. A virtual subindustry has evolved to enhance the benefit and applicability of rtPA through refined imaging technology and the use of rtPA intra-aterially, as well as in combination with other agents and devices. Sociopolitically, rtPA has elevated the level of awareness of stroke and provided impetus for the stroke center movement and federal legislation to stop stroke. CONCLUSION: The development of rtPA has been the most effective advance in the field of stroke. It has generated healthy debate regarding the design, performance, and interpretation of stroke trials, including cost-benefit considerations. rtPA has stimulated research in a multitude of areas, enhanced our understanding of stroke pathophysiology, and defined important limits and risks for urgent intervention. rtPA is the cornerstone of the stroke center movement, as well as legislation in behalf of stroke at the congressional level.

The stroke 8: a daily checklist for inpatient stroke management.

Checklists and disease-specific order sets are increasingly being used in health care to reduce medical errors and improve the quality of patient care. Stroke, which has standardized and well-defined care processes, is an idea/ideal condition for the use of checklists. We describe the Stroke 8 checklist, designed to be part of the daily assessment of patients hospitalized with acute stroke. It consists of 8 items classified into 3 categories as follows: (1) stroke prevention: antithrombotic use, statin use, glucose control, blood pressure control; (2) prevention of complications: deep venous thrombosis prophylaxis, temperature control; and (3) recovery and disposition: fluids and nutrition, mobility and therapy. The Stroke 8 checklist has been implemented in 3 formats over an 8-year period: laminated cards, an electronic documentation template, and an electronic template supplemented with clinical data autopopulated from the electronic health record. We have found the Stroke 8 to be a valuable tool in the daily inpatient management of patients with acute stroke.

Need for performance protocols in TEE and TCD for detection of right to left shunts.

BACKGROUND AND PURPOSE: Although transesophageal echocardiography (TEE) is the gold standard for right to left shunt detection, we observed that transcranial Doppler (TCD) was more sensitive and sought an explanation. METHODS: We retrospectively evaluated results of TCD and TEE in 118 patients with cryptogenic stroke and transient ischemic attacks. TCDs were done as per modification of a published performance protocol and interpreted by a neurologist and radiologist. TEEs were performed and interpreted by five cardiologists without standardized protocol. Statistical methodology included χ(2) tests, Fisher exact tests, and ANOVA. RESULTS: Overall agreement between TCD and TEE was found for 76 of 118 patients. Sensitivities of TCD and TEE were 93.8% and 53.1%. Sensitivities for TCD interpreters were 61.1% and 64.1%. Sensitivities for TEE operators varied from 46.7% to 75.7%. We were unable to find a performance protocol for TEE microbubble studies in either published literature or certification organizations. CONCLUSIONS: TEEs and TCDs are operator dependent and thus subject to false negatives. The lower yield and interoperator variability in TEE results appear to reflect the lack of performance protocols and engender concern about false negatives in community use. Consensus performance protocols and certification criteria for both modalities should have an impact on accuracy of shunt detection.

Detection of right-to-left shunts: comparison between the International Consensus and Spencer Logarithmic Scale criteria.

BACKGROUND: International Consensus Criteria (ICC) consider right-to-left shunt (RLS) present when Transcranial Doppler (TCD) detects even one microbubble (microB). Spencer Logarithmic Scale (SLS) offers more grades of RLS with detection of >30 microB corresponding to a large shunt. We compared the yield of ICC and SLS in detection and quantification of a large RLS. SUBJECTS AND METHODS: We prospectively evaluated paradoxical embolism in consecutive patients with ischemic strokes or transient ischemic attack (TIA) using injections of 9 cc saline agitated with 1 cc of air. Results were classified according to ICC [negative (no microB), grade I (1-20 microB), grade II (>20 microB or "shower" appearance of microB), and grade III ("curtain" appearance of microB)] and SLS criteria [negative (no microB), grade I (1-10 microB), grade II (11-30 microB), grade III (31100 microB), grade IV (101300 microB), grade V (>300 microB)]. The RLS size was defined as large (>4 mm) using diameter measurement of the septal defects on transesophageal echocardiography (TEE). RESULTS: TCD comparison to TEE showed 24 true positive, 48 true negative, 4 false positive, and 2 false negative cases (sensitivity 92.3%, specificity 92.3%, positive predictive value (PPV) 85.7%, negative predictive value (NPV) 96%, and accuracy 92.3%) for any RLS presence. Both ICC and SLS were 100% sensitive for detection of large RLS. ICC and SLS criteria yielded a false positive rate of 24.4% and 7.7%, respectively when compared to TEE. CONCLUSIONS: Although both grading scales provide agreement as to any shunt presence, using the Spencer Scale grade III or higher can decrease by one-half the number of false positive TCD diagnoses to predict large RLS on TEE.

Intra-arterial thrombolysis for acute ischemic stroke: preliminary experience with platelet glycoprotein IIb/IIIa inhibitors as adjunctive therapy.

OBJECTIVE: To evaluate the safety profile of platelet glycoprotein IIb/IIIa inhibitors administered as adjunctive therapy to patients with large-vessel occlusion and acute ischemic stroke refractory to pharmacological thrombolysis with recombinant tissue plasminogen activator (rtPA) and mechanical disruption, balloon angioplasty, or both. METHODS: Twenty-one patients (mean age, 62 yr; range, 29-88 yr) met the following criteria: 1) large-vessel occlusion and acute ischemic stroke syndrome at presentation, 2) failure to recanalize after administration of rtPA (intra-arterial and/or intravenous) with or without mechanical thrombolysis, and 3) subsequent treatment with IIb/IIIa inhibitors (intra-arterial or intravenous). RESULTS: Eleven patients had ischemia in the dominant hemisphere, 8 in the vertebrobasilar system, and 2 in the nondominant hemisphere. Twelve patients received intravenous rtPA without significant improvement; 9 patients were not candidates for intravenous rtPA. All patients received intra-arterial rtPA. The IIb/IIIa inhibitors were administered intravenously in 3 patients, intra-arterially in 16, and both intravenously and intra-arterially in 2. Balloon angioplasty was performed in 18 patients. Complete or partial recanalization was achieved in 17 of the 21 patients. After thrombolysis, 15 improved clinically. Three patients (14%) sustained an asymptomatic intracerebral hemorrhage after thrombolytic therapy. No patient was clinically worse after intervention. At last follow-up (mean, 8.5 mo), 13 patients were functionally independent (modified Rankin score, 0-3) and 8 were disabled or dead. CONCLUSION: IIb/IIIa inhibitors are an alternative for achieving recanalization. The risk of hemorrhage may be low. As part of an escalating protocol that includes pharmacological and mechanical thrombolysis, IIb/IIIa inhibitors may improve clinical outcomes.

Arterial thrombosis induced by IVIg and its treatment with tPA.

IV immunoglobulin therapy can lead to vascular events through increased serum viscosity and possibly other mechanisms. The authors describe the successful use of tissue plasminogen activator in three of four patients who developed cerebral and peripheral arterial thrombosis after treatment with IV immunoglobulin.