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The incidence of early seizures (ES) in traumatic brain injury (TBI) ranges between 1 and 7%. However, the incidence of ES after a non-severe TBI (NSTBI) with traumatic hemorrhage (TH) is unknown. Moreover, the data about seizure prophylaxis (SP) in this population remains inconclusive. We aim to determine the incidence of ES in NSTBI and the efficacy of SP. We retrospectively reviewed all adult patients with NSTBI with evidence of a TH on presentation from 2015 to 2018 at Methodist University Hospital in Memphis TN. Patients with history of epilepsy or receiving antiseizure medications (ASM) were excluded. We collected demographic data, the type, severity, and mechanism of injury; the need for neurosurgical intervention (NSI); ES; and SP use. A total of 633 patients met our inclusion criteria; 94.4% had mild TBI; mean age was 70.5 years (SD 16.9); 55.0% were males; and 49.1% had subdural hematoma (SDH). Same level fall was the most common mechanism of injury in 79%. Forty patients (6.3%) had ES. After excluding seizures on presentation, 22 of 310 (7.1%) patients had an ES in the SP group (16 clinical) vs 5 of 310 (1.6%) in the non-prophylaxis group (all clinical) (P = 0.001). Levetiracetam as SP was used in 83.5%. Patients with combined SDH and traumatic subarachnoid hemorrhage or with multicompartment hemorrhage were more likely to have ES than SDH alone (p = 0.02 and 0.001, respectively). NSI was not a predictor for ES in our cohort. The incidence of ES (clinical and electrographic) in NSTBI with TH patients in our cohort is higher than previously reported in those with non-severe TBI. ES were reported more in the SP group, which might indicate a clinical selection bias giving more moderate TBI and multicompartmental hemorrhage patients receiving ASM for SP. However, prospective studies are required to further determine the predictors of ES in non-severe TBI and the effect of ASM for SP on outcomes and reducing ES in NSTBI patients.

Key Points Question Does the prevalence and burden of risk factors for lobar and nonlobar intracerebral hemorrhage (ICH) differ among Black, Hispanic, and White populations? Findings In this case-control study of 3000 cases of ICH among Black, Hispanic, and White patients, the ɛ2 and ɛ4 alleles of APOE, the gene encoding apolipoprotein E, were associated with lobar ICH in White but not Black and Hispanic patients; hypertension was a risk factor for both lobar and nonlobar ICH in all groups; and the mean age for ICH among Black and Hispanic patients was more than 10 years younger than that of their White counterparts. Black and Hispanic patients had a higher attributable risk percentage for treated or untreated hypertension and lack of health insurance than White patients. Meaning These findings suggest that potentially modifiable risk factors and social determinants of health are important contributors to the disproportionate ICH burden experienced by Black and Hispanic populations., This case-control study examines the prevalence, odds, and population attributable risk for established and novel risk factors for intracerebral hemorrhage, stratified by intracerebral hemorrhage location and racial/ethnic group., Importance Black and Hispanic individuals have an increased risk of intracerebral hemorrhage (ICH) compared with their White counterparts, but no large studies of ICH have been conducted in these disproportionately affected populations. Objective To examine the prevalence, odds, and population attributable risk (PAR) percentage for established and novel risk factors for ICH, stratified by ICH location and racial/ethnic group. Design, Setting, and Participants The Ethnic/Racial Variations of Intracerebral Hemorrhage Study was a case-control study of ICH among 3000 Black, Hispanic, and White individuals who experienced spontaneous ICH (1000 cases in each group). Recruitment was conducted between September 2009 and July 2016 at 19 US sites comprising 42 hospitals. Control participants were identified through random digit dialing and were matched to case participants by age (±5 years), sex, race/ethnicity, and geographic area. Data analyses were conducted from January 2019 to May 2020. Main Outcomes and Measures Case and control participants underwent a standardized interview, physical measurement for body mass index, and genotyping for the ɛ2 and ɛ4 alleles of APOE, the gene encoding apolipoprotein E. Prevalence, multivariable adjusted odds ratio (OR), and PAR percentage were calculated for each risk factor in the entire ICH population and stratified by racial/ethnic group and by lobar or nonlobar location. Results There were 1000 Black patients (median [interquartile range (IQR)] age, 57 [50-65] years, 425 [42.5%] women), 1000 Hispanic patients (median [IQR] age, 58 [49-69] years; 373 [37.3%] women), and 1000 White patients (median [IQR] age, 71 [59-80] years; 437 [43.7%] women). The mean (SD) age of patients with ICH was significantly lower among Black and Hispanic patients compared with White patients (eg, lobar ICH: Black, 62.2 [15.2] years; Hispanic, 62.5 [15.7] years; White, 71.0 [13.3] years). More than half of all ICH in Black and Hispanic patients was associated with treated or untreated hypertension (PAR for treated hypertension, Black patients: 53.6%; 95% CI, 46.4%-59.8%; Hispanic patients: 46.5%; 95% CI, 40.6%-51.8%; untreated hypertension, Black patients: 45.5%; 95% CI, 39.%-51.1%; Hispanic patients: 42.7%; 95% CI, 37.6%-47.3%). Lack of health insurance also had a disproportionate association with the PAR percentage for ICH in Black and Hispanic patients (Black patients: 21.7%; 95% CI, 17.5%-25.7%; Hispanic patients: 30.2%; 95% CI, 26.1%-34.1%; White patients: 5.8%; 95% CI, 3.3%-8.2%). A high sleep apnea risk score was associated with both lobar (OR, 1.68; 95% CI, 1.36-2.06) and nonlobar (OR, 1.62; 95% CI, 1.37-1.91) ICH, and high cholesterol was inversely associated only with nonlobar ICH (OR, 0.60; 95% CI, 0.52-0.70); both had no interactions with race and ethnicity. In contrast to the association between the ɛ2 and ɛ4 alleles of APOE and ICH in White individuals (eg, presence of APOE ɛ2 allele: OR, 1.84; 95% CI, 1.34-2.52), APOE alleles were not associated with lobar ICH among Black or Hispanic individuals. Conclusions and Relevance This study found sleep apnea as a novel risk factor for ICH. The results suggest a strong contribution from inadequately treated hypertension and lack of health insurance to the disproportionate burden and earlier onset of ICH in Black and Hispanic populations. These findings emphasize the importance of addressing modifiable risk factors and the social determinants of health to reduce health disparities.

Background Minimally invasive surgery procedures, including stereotactic catheter aspiration and clearance of intracerebral hemorrhage (ICH) with recombinant tissue plasminogen activator hold a promise to improve outcome of supratentorial brain hemorrhage, a morbid and disabling type of stroke. A recently completed Phase III randomized trial showed improved mortality but was neutral on the primary outcome (modified Rankin scale score 0 to 3 at 1 yr). Objective To assess surgical performance and its impact on the extent of ICH evacuation and functional outcomes. Methods Univariate and multivariate models were used to assess the extent of hematoma evacuation efficacy in relation to mRS 0 to 3 outcome and postulated factors related to patient, disease, and protocol adherence in the surgical arm (n = 242) of the MISTIE trial. Results Greater ICH reduction has a higher likelihood of achieving mRS of 0 to 3 with a minimum evacuation threshold of ≤15 mL end of treatment ICH volume or ≥70% volume reduction when controlling for disease severity factors. Mortality benefit was achieved at ≤30 mL end of treatment ICH volume, or >53% volume reduction. Initial hematoma volume, history of hypertension, irregular-shaped hematoma, number of alteplase doses given, surgical protocol deviations, and catheter manipulation problems were significant factors in failing to achieve ≤15 mL goal evacuation. Greater surgeon/site experiences were associated with avoiding poor hematoma evacuation. Conclusion This is the first surgical trial reporting thresholds for reduction of ICH volume correlating with improved mortality and functional outcomes. To realize the benefit of surgery, protocol objectives, surgeon education, technical enhancements, and case selection should be focused on this goal.

BackgroundMobile stroke units (MSUs) performance dependability and diagnostic yield of 16-slice, ultra-fast CT with auto-injection angiography (CTA) of the aortic arch/neck/circle of Willis has not been previously reported.MethodsWe performed a prospective observational study of the first-of-its kind MSU equipped with high resolution, 16-slice CT with multiphasic CTA. Field CT/CTA was performed on all suspected stroke patients regardless of symptom severity or resolution. Performance dependability, efficiency and diagnostic yield over 365 days was quantified.Results1031 MSU emergency activations occurred; of these, 629 (61%) were disregarded with unrelated diagnoses, and 402 patients transported: 245 (61%) ischemic or hemorrhagic stroke, 17 (4%) transient ischemic attack, 140 (35%) other neurologic emergencies. Total time from non-contrast CT/CTA start to images ready for viewing was 4.0 (IQR 3.5–4.5) min. Hemorrhagic stroke totaled 24 (10%): aneurysmal subarachnoid hemorrhage 3, hemorrhagic infarct 1, and 20 intraparenchymal hemorrhages (median intracerebral hemorrhage score was 2 (IQR 1–3), 4 (20%) spot sign positive). In 221 patients with ischemic stroke, 73 (33%) received alteplase with 31.5% treated within 60 min of onset. CTA revealed large vessel occlusion in 66 patients (30%) of which 9 (14%) were extracranial; 27 (41%) underwent thrombectomy with onset to puncture time averaging 141±90 min (median 112 (IQR 90–139) min) with full emergency department (ED) bypass. No imaging needed to be repeated for image quality; all patients were triaged correctly with no inter-hospital transfer required.ConclusionsMSU use of advanced imaging including multiphasic head/neck CTA is feasible, offers high LVO yield and enables full ED bypass.

Background: Hypercholesterolemia is associated with increased risk of ischemic strokes. Statin therapy has been shown to reduce risk of cardiovascular mortality including ischemic strokes. Despite these benefits there still exists a debatable effect of statin use in outcome of patients with intracerebral hemorrhage. Methods: Retrospective analysis was performed using data from the Antihypertensive treatment of acute cerebral hemorrhage II (ATACH-2) trial to determine effect of baseline compliant statin use on occurrence of adverse events, mortality and death and disability at 90 days. We compared demographic, clinical characteristics and outcomes of subjects dichotomized into those on statin therapy at baseline versus those who were not. We performed a multivariate analysis using binary logistic regression model after adjusting for all potential confounders for binary variables as well as linear regression model for continuous variables. Results: Of the total 1000 participants in the ATACH-2 trial total of 931 responded and were included. Of the 931 there were 271 (29.1%) who were complaint with baseline statin use, with mean age 61.6 SD± 13.0 and 60.9% were males. Those were complaint with statin use had significantly higher rates of previous stroke (13.9% vs 19.7%), coronary artery disease (2.3% vs 7.7%), hyperlipidemia (15.7% vs 42.0%), and type 2 diabetes mellitus (14.2% vs 25.2%). In the multivariate analysis after adjusting for age, race, hypertension, and smoking those who were compliant with baseline statin use had significant lower odds of recurrent hemorrhagic adverse events (OR 0.4, 95% CI 0.21- 0.89; p-value .023) and lower odds of requiring surgical evacuation (OR 0.3, 95% CI 0.12 - 0.91; p-value .032). In a linear regression model those who were compliant with statin use had lower 24hr NIHSS score ( β -1.2, S.E 0.5; p-value .031) and higher baseline GCS score ( β 0.3, S.E 0.1; p-value .02). There was no difference in favorable outcome mRS 0-2 or death in the multivariate analysis. Conclusion: Patient who are compliant with statin use seem to have higher GCS score at baseline and improved NIHSS scores at 24hrs. They were at lower odds of having recurrent hemorrhagic bleeds after discharge and required less surgical evacuations.

Ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) patients often require endotracheal intubation (EI) and mechanical ventilation (MV). Predicting the need for prolonged EI and timing of tracheostomy (TR) is challenging. While TR is performed for about 10–15% of patients in the general intensive care unit (ICU), the rate in the neurological ICU and for stroke patients ranges between 15 and 35%. Thus, we performed an external validation of the recently published SETscore. This is a retrospective review for all patients with IS, non-traumatic ICH, and SAH who required intubation within 48 h of admission to the neurological ICU. We compared the SETscore between tracheostomized versus successfully extubated patients, and early TR (within 7 days) versus late TR (after 7 days). Out of 511 intubated patients, 140 tracheostomized and 105 extubated were included. The sensitivity for a SETscore > 10 to predict the need for TR was 81% (95% CI 74–87%) with a specificity of 57% (95% CI 48–67%). The score had moderate accuracy in correctly identifying those requiring TR and those successfully extubated: 71% (95% CI 65–76%). The AUC of the score was 0.74 (95% CI 0.68–0.81). Multivariable logistic regression models were used to identify other independent predictors of TR. After including body mass index (BMI), African American (AA) race, ICH and a positive sputum culture in the SETscore, sensitivity, specificity, overall accuracy, and AUC improved to 90%, 78%, 85%, and 0.89 (95% CI 0.85–0.93), respectively. In our cohort, performing early TR was associated with improvement in the ICU median length of stay (LOS) (15 vs 20.5 days; p = 0.002) and mean ventilator duration (VD) (13.4 vs 18.2 days; p = 0.005) in comparison to late TR. SETscore is a simple score with a moderate accuracy and with a fair AUC used to predict the need for TR after MV for IS, ICH, and SAH patients. Our study also demonstrates that early TR was associated with a lower ICU LOS and VD in our cohort. The utility of this score may be improved when including additional variables such as BMI, AA race, ICH, and positive sputum cultures.

Background We evaluated computed tomography head (CTH) imaging obtained prior to targeted temperature management (TTM) in patients after cardiac arrest, and its role in prognostication. Methods In this retrospective cohort study in a tertiary-care hospital, 341 adults presenting with out-of-hospital cardiac arrest received a CTH prior to TTM. Associations between outcomes and neuroimaging variables were evaluated with Chi-square analysis for significant associations that yielded a composite neuroimaging score—Tennessee Early Neuroimaging Score (TENS). Univariable and multivariable logistic regression analysis including TENS as an independent variable and the four outcome dependent variables were analyzed. Results Four of the neuroimaging variables—sulcal effacement, partial gray-white matter effacement, total gray-white matter effacement, deep nuclei effacement—had significant associations with each of the four outcome variables and yielded TENS. In multivariable logistic regression models adjusted for potential confounders, TENS was associated with poor discharge CPC (OR 2.15, 95%CI 1.16–3.98, p = .015), poor disposition (OR 2.62, 95%CI 1.37–5.02, p = .004), in-hospital mortality (OR 1.99, 95%CI 1.09–3.62, p = .024), and ICU mortality (OR 1.89, 95%CI 1.12–3.20, p = .018). Conclusion Imaging prior to TTM may help identify post-cardiac arrest patients with severe anoxic brain injury and poor outcomes.

Introduction: Intracerebral hemorrhage (ICH) is the most severe subtype of stroke with a high mortality rate and majority of survivors suffering significant disability. The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study prospectively recruited 1000 white, 1000 black and 1000 Hispanic spontaneous ICH cases. Herein, we report the main results of the predictors of 3 month outcome after ICH. Hypothesis: We hypothesized that ICH Score variables of age, ICH volume, ICH location, presence of intraventricular hemorrhage (IVH), and presenting Glasgow Coma Scale would predict long-term disability in addition to prior validation of mortality. Methods: Between 2010-2015, cases were prospectively recruited with uniform phenotype definitions, centralized neuroimaging review and with telephone follow-up at 3 months. Apolipoprotein E genotyping was performed centrally. Individual characteristics were screened for association under a logistic regression model, 90-day mRS ≥ 4 versus 0-3, and those meeting P Results: The Table presents the prevalence/average of each variable entering the final multivariate model for association with poor (mRS 4-6) compared to good (mRS 0-3) outcome at 3 months. When analyses were repeated excluding withdrawal of care, overall Graeb (IVH) score fell out of the model (with presence of IVH replacing it) but the remaining variables were retained and in the same direction of effect. C-statistic for the multivariate model = 0.884 compared to 0.763 for ICH score alone (p=1.7E-22). Conclusion: ICH score elements were validated as predictive of 3 month outcome. Novel baseline characteristics such as white matter hyperintensity as well as subsequent clinical events that may affect outcomes were identified. Location specific results to be presented.

Introduction: Intracerebral hemorrhage (ICH) is the most severe subtype of stroke. Its mortality rate is high, and the majority of survivors suffer significant disability. The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study prospectively recruited 1000 non-Hispanic white, 1000 non-Hispanic black, and 1000 Hispanic spontaneous ICH cases to study the epidemiology and genomics of ICH. Herein, we report the primary determinants of 3-month outcome after ICH in a large, multi-ethnic cohort. Methods: Between 2010 and 2015, cases were prospectively recruited with uniform data collection and phenotype definitions, centralized neuroimaging review, and telephone follow-up at 3 months. Individual characteristics were screened for association with 3-month outcome of modified Rankin Scale (mRS) ≥4 versus ≤3 under a logistic regression model, and those meeting P

Background: MSU’s are capable of ultra-early treatment of acute stroke patients in the field. We tested field use of a high-resolution CT and CT-angiography on our MSU. Methods: We designed and implemented the first of its kind MSU equipped with a 16 slice CT scanner (24-row adaptive detector array, fixed 70 cm gantry, auto-injection system, Somatom Scope, Siemens), led by stroke fellowship trained MDs or ANVP-board certified nurse practitioners without telemedicine support. Head/neck CTA was performed on all suspected stroke patients immediately following noncontrast CT. The MSU is embedded within local Fire/EMS and is activated by 911, or by on-scene medics 14 days/month. Transport and drug re-stock agreements were developed with Comprehensive, Primary, and CSC-Capable (CSC-cap) competing stroke centers. Results: Of 420 activations in the first year, our MSU transported a total 206 patients: 127 (62%) strokes and 79 (38%) stroke mimics. In all 127 acute stroke patients (68±16 years, 58% women, 65% African American, 34% White, 1% Hispanic), median CT/CTA completion time, from start of scan, to images ready for diagnostic viewing, was 3.5 minutes (IQR 3-4). Diagnosis was 15 (12%) hemorrhages, 12 (9%) suspected TIA, 100 (79%) acute ischemic stroke (AIS). AIS median NIHSS was 9, IQR 7-17. IV-tPA treatment rate was 38% with median scene arrival to bolus time of 13 min, IQR 11-16. Large vessel occlusion (LVO) was found in 30% of ischemic strokes. No patients required repeat imaging on arrival due to image quality, and 100% were accurately triaged to CSC, PSC, or CSC-cap hospitals without the need for subsequent transfer. Conclusions: MSUs can effectively operate a high-resolution automated CT similar to in-hospital radiology settings. The addition of head/neck CTA in the field yields a high rate of LVO detection supporting definitive prehospital triage to Comprehensive Stroke Centers.

Background: Lowering of blood pressure (BP) is discouraged in current ASA guidelines for emergency medical service (EMS) personnel. However, ultra-early treatment with IVtPA and BP lowering in ICH are possible on mobile stroke units (MSU). We examined the effectiveness and safety of two antihypertensive agents for MSU treatment. Methods: Consecutive MSU patients were treated with target ICH BP parameters less than 140/90, and IVtPA BP parameters by current guidelines. BP was measured by noninvasive oscillometric cuff, and cycled every 5 minutes per EMS MSU protocol. Available agents were labetalol IV 10-20mg and/or nicardipine double-strength premix infusion started at 5mg/hour and titrated. Preference in usage, and effect were recorded and analyzed for the first year of MSU operation. Results: During 168 service days, 127 acute stroke patients were transported (68±16, range 23-96 years; 58% women; 65% African American, 34% White; 1% Hispanic). Fifteen (12%) had hemorrhage on CT (1 aneurysmal SAH, 1 SDH, 1 subacute AIS with HT-2; 12 HTN ICH [median ICH score 2, IQR 1-3] of which 1 had a positive spot sign on CTA). AIS cases (n=100) had median NIHSS 9 (IQR 7-17); 38% were treated with IVtPA at a median 13 (IQR 11-16) minutes from scene arrival, one of these by IO route, with 1 angioedema and 0 sICH. Labetalol was used for 9 patients, with all but one (89%) requiring the addition of nicardipine infusion. In 24 patients nicardipine was the first agent selected, with 100% achieving target BP control prior to hospital arrival. Conclusions: MSU use of nicardipine double-strength premix infusions provides rapid, reliable, and safe BP control. When time is of the essence, elimination of labetalol, in favor of a dihydropyridine calcium channel blocker infusion may provide the most rapid achievement of prescribed BP parameters.

Background and Purpose: Despite recent landmark randomized controlled trials showing significant benefits for hemicraniectomy (HCT) compared with medical therapy (MT) in patients with malignant middle cerebral artery infarction (MMCAI), HCT rates have not substantially increased in the United States. We sought to evaluate early outcomes in patients with MMCAI who were treated with HCT (cases) in comparison to patients treated with MT due to the perception of procedural futility by families (controls). Methods: We retrospectively evaluated consecutive patients with acute MMCAI treated in 2 tertiary care centers during a 7-year period. Pretreatment National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) at 3 months were documented. Functional independence (FI) and survival without severe disability (SWSD) were defined as mRS of 0-2 and 0-4, respectively. Results: A total of 66 patients (37 cases and 29 controls) fulfilled the study inclusion criteria (mean age 59 ± 15 years, 52% men, median admission NIHSS score: 19 points [interquartile range {IQR}: 16-22]). Cases were younger (51 ± 11 versus 68 ± 13 years; P

Intracerebral hemorrhage (ICH) is the second most common subtype of stroke and a critical disease usually leading to severe disability or death. Around 20% of patients with ICH will experience a decrease in the Glasgow Coma Scale of two or more points between the prehospital assessment and the initial evaluation in the emergency department (ED). Therefore, aggressive prehospital and ED treatment is cornerstone for effective management of patients with ICH. Initial management should focus on urgent stabilization of cardiorespiratory variables and treatment of intracranial complications. Recent technological innovations have opened new perspectives for stroke diagnosis and treatment before the patient arrives at the hospital. These prehospital measures include presumed stroke diagnosis by paramedics, mobile telemedicine for remote clinical examination and imaging, mobile stroke units with integrated computerized tomography (CT) scanners, point-of-care laboratories in ambulances, and prehospital notification provided by emergency medical staff (EMS). Primary management of ICH in ED includes rapid clinical evaluation, laboratory studies including blood glucose and coagulation defects, diagnostic imaging studies, management of blood pressure and early intracranial complications such as hydrocephalus or impending herniation, and admission to stroke unit or neuroscience intensive care unit (NICU). In this book chapter, we will discuss in detail about various prehospital and ED management strategies for management of patients with ICH.

The safety and efficacy of intravenous thrombolysis (IVT) in dissection-related ischemic stroke (DRIS) has not been established. We sought to determine safety and recovery rates of IVT in DRIS using prospective, international, multicenter data and by conducting a comprehensive meta-analysis of reported case series. We analyzed consecutive DRIS patients treated with IVT according to national guidelines during a 5-year period at six tertiary-care stroke centers, and also conducted a comprehensive review and meta-analysis of all available case series reporting safety outcomes in DRIS treated with IVT according to PRISMA guidelines. A total of 39 DRIS patients (mean age 60 ± 18 years; 59% men; median NIHSS 13 points, IQR 9-17) received IVT in our multicenter study. Symptomatic intracranial hemorrhage (sICH), in-hospital mortality, complete recanalization, favorable functional outcome (FFO; mRS-score of 0-1) and functional independence (FI; mRS-score of 0-2) were 0% (adjusted Wald 95% CI 0-8%), 10% (3-24%), 55% (40-70%), 61% (45-74%) and 68% (52-81%). The pooled sICH and mortality rates in meta-analysis including 10 case series (234 IVT-DRIS patients) were 2% (0-5%) and 4% (0-8%). The pooled recanalization, FFO and FI rates were 45% (26-67%), 41% (29-54%) and 61% (48-72%), respectively. Substantial heterogeneity was only found for FFO (I(2) = 61%; p = 0.006). Subsequent meta-regression analysis identified baseline NIHSS and dissection in the posterior circulation as independent predictors of FFO (p < 0.05), accounting for FFO variance across different studies. Our prospective, international data coupled with comprehensive meta-analysis results underscore IVT safety in DRIS, while further independent validation is required in larger observational registries or RCTs.

Background and Purpose— Shortening door-to-needle time may lead to inadvertent intravenous thrombolysis (IVT) administration in stroke mimics (SMs). We sought to determine the safety of IVT in SMs using prospective, single-center data and by conducting a comprehensive meta-analysis of reported case-series. Methods— We prospectively analyzed consecutive IVT-treated patients during a 5-year period at a tertiary care stroke center. A systematic review and meta-analysis of case-series reporting safety of IVT in SMs and confirmed acute ischemic stroke were conducted. Symptomatic intracerebral hemorrhage was defined as imaging evidence of ICH with an National Institutes of Health Stroke scale increase of ≥4 points. Favorable functional outcome at hospital discharge was defined as a modified Rankin Scale score of 0 to 1. Results— Of 516 consecutive IVT patients at our tertiary care center (50% men; mean age, 60±14 years; median National Institutes of Health Stroke scale, 11; range, 3–22), SMs comprised 75 cases. Symptomatic intracerebral hemorrhage occurred in 1 patient, whereas we documented no cases of orolingual edema or major extracranial hemorrhagic complications. In meta-analysis of 9 studies (8942 IVT-treated patients), the pooled rates of symptomatic intracerebral hemorrhage and orolingual edema among 392 patients with SM treated with IVT were 0.5% (95% confidence interval, 0%–2%) and 0.3% (95% confidence interval, 0%–2%), respectively. Patients with SM were found to have a significantly lower risk for symptomatic intracerebral hemorrhage compared with patients with acute ischemic stroke (risk ratio=0.33; 95% confidence interval, 0.14–0.77; P =0.010), with no evidence of heterogeneity or publication bias. Favorable functional outcome was almost 3-fold higher in patients with SM in comparison with patients with acute ischemic stroke (risk ratio=2.78; 95% confidence interval, 2.07–3.73; P Conclusions— Our prospective, single-center experience coupled with the findings of the comprehensive meta-analysis underscores the safety of IVT in SM.

Background: Mobile Stroke Units (MSU) are growing in numbers throughout the U.S. and abroad, with numerous staffing configurations, telemedicine, and differing imaging capabilities. We aimed to test the diagnostic accuracy and treatment safety, alongside time to diagnosis and treatment delivery of a novel advanced practice provider (APP) led MSU team. Methods: We launched an MSU housing a hospital-grade Siemens Somatom CT with CTA capabilities, and hired APPs with advanced neurovascular practitioner board certification to lead field medical diagnosis and order/initiate treatment for encountered stroke patients. Consecutive MSU patients were evaluated for differences between APPs and Vascular Neurologists (VNs) diagnosis and management, and scene diagnosis and treatment times were collected. Results: Agreement between APP field medical diagnosis and MD hospital diagnosis was 100%; stroke mimic diagnosis agreement was 98%. Overall agreement for field interpretation of CT/CTA was 97%, with discrepancies not associated with stroke treatment decisions. MDs’ agreement with APPs’ identification/treatment of ICH was 100%, and IVtPA treatment decisions 98% (APPs more conservative). Scene arrival to medical diagnosis (including clinical exam and imaging completion/interpretation) ranged from 7-10 minutes, of which 4 minutes were CT/CTA start to finish times. Scene arrival to IVtPA bolus ranged from 16 minutes to 33 minutes and was driven primarily by need for control of excessive hypertension, with scene arrival to start of nicardipine premix infusion ranging from 10-14 minutes. Conclusions: Use of an APP-led MSU is safe and non-inferior to VN diagnosis/management, and may be faster than telemedicine guided MSU treatment.

Background: An increasing shortage of vascular neurologists forced an academic provider to find a city-wide solution to offer 24x7 access to intravenous thrombolysis (IVT) across independent and competing health care systems in the area. We sought to prospectively evaluate the annual IVT treatment delivery in our population and compare it to leading stroke centers worldwide. Methods: The largest single ER system and 3 other independent hospital providers in the area agreed to work with a single practice plan vascular neurology team (catchment area of 1,344,127 individuals). All acute ischemic stroke patients that were treated with IVT across all primary or tertiary care centers in our area were prospectively documented over a 12-month period (January-December 2015). A literature search was performed using narrative review methodology to document similar population-based treatment rates across leading stroke centers in North America, Europe and Australasia. Results: A total of 552 patients received IVT with tissue plasminogen activator (tPA) in 2015. Single ER system delivered 433 IV tPA treatments and 119 more patients were treated in the remaining hospitals. The annual tPA treatment rate was 41 per 100.000 individuals (95%CI: 38-44) favorably comparable to published annual treatment rates from leading international stroke centers (Table, 1998 thru 2015). Conclusions: A city-wide vascular neurology team can attend to patient populations across competing health care systems in the U.S. and deliver IVT at volumes and rates above those reported by leading treatment centers worldwide. Communities with competing systems can improve tPA delivery by sharing vascular neurology resources.

Objective: To evaluate if a family presence educational intervention during brain death evaluation improves understanding of brain death without affecting psychological distress. Design: Randomized controlled trial. Setting: Four ICUs at an academic tertiary care center. Subjects: Immediate family members of patients suspected to have suffered brain death. Interventions: Subjects were group randomized to presence or absence at bedside throughout the brain death evaluation with a trained chaperone. All randomized subjects were administered a validated understanding brain death survey before and after the intervention. Subjects were assessed for psychological well-being between 30 and 90 days after the intervention. Measurements and Main Results: Follow-up assessment of psychological well-being was performed using the Impact of Event Scale and General Health Questionnaire. Brain death understanding, Impact of Event Scale, and General Health Questionnaire scores were analyzed using Wilcoxon nonparametric tests. Analyses were adjusted for within family correlation. Fifty-eight family members of 17 patients undergoing brain death evaluation were enrolled: 38 family members were present for 11 brain death evaluations and 20 family members were absent for six brain death evaluations. Baseline understanding scores were similar between groups (median 3.0 [presence group] vs 2.5 [control], p = 0.482). Scores increased by a median of 2 (interquartile range, 1-2) if present versus 0 (interquartile range, 0-0) if absent (p < 0.001). Sixty-six percent of those in the intervention group achieved perfect postintervention understanding scores, compared with 20% of subjects who were not present (p = 0.02). Median Impact of Event Scale and General Health Questionnaire scores were similar between groups at follow-up (Impact of Event Scale: present = 20.5, absent = 23.5, p = 0.211; General Health Questionnaire: present = 13.5, absent = 13.0, p = 0.250). Conclusions: Family presence during brain death evaluation improves understanding of brain death with no apparent adverse impact on psychological well-being. Family presence during brain death evaluation is feasible and safe.

Background and Purpose Preliminary studies have indicated that sulfonylurea drugs (SUD) may confer protection against cerebral swelling and hemorrhagic transformation in severe acute ischemic stroke (AIS). We sought to determine whether pretreatment and in-hospital use of SUD may be associated with better outcomes in diabetic AIS patients treated with intravenous thrombolysis (IVT). Subjects and Methods We analyzed consecutive diabetic AIS patients treated with IVT during a 3-year period. Pretreatment with SUD, admission NIHSS (National Institutes of Health Stroke Scale) score, NIHSS at 48 hours, and modified Rankin Scale (mRS) at discharge were documented. Patients who discontinued SUD during hospitalization were excluded. Symptomatic intracranial hemorrhage (sICH) was defined as imaging evidence of ICH with NIHSS score increase of greater than or equal to 4 points within 72 hours. Early neurological improvement was defined as an NIHSS score decrease of greater than or equal to 4 points or NIHSS score of 0 at 48 hours. Cerebral edema was documented by neuroradiology reports. Favorable functional outcome (FFO) was defined as discharge mRS of 0-1. Results A total of 148 diabetic AIS patients were evaluated (mean age 64 ± 11 years, 49% men, median admission NIHSS score: 8 points). We identified 42 (28%) cases pretreated with SUD. The prevalence of complications and favorable outcomes did not differ ( P > .1) between patients pretreated and nonpretreated with SUD: sICH (2% versus 5%), cerebral edema (5% versus 4%), early neurological improvement (42% versus 43%), in-hospital mortality (12% versus 5%), and FFO (22% versus 32%). Conclusions Pretreatment and in-hospital use of SUD appears not to be associated with early favorable outcomes and lower likelihood of potential complications in diabetic AIS patients treated with IVT.

BACKGROUND AND PURPOSE: Transcranial Doppler is a useful ancillary test for brain death confirmation because it is safe, noninvasive, and done at the bedside. Transcranial Doppler confirms brain death by evaluating cerebral circulatory arrest. Case series studies have generally reported good correlations between transcranial Doppler confirmation of cerebral circulatory arrest and clinical confirmation of brain death. The purpose of this study is to evaluate the utility of transcranial Doppler as an ancillary test in brain death confirmation. MATERIALS AND METHODS: We conducted a systematic review of the literature and a diagnostic test accuracy meta-analysis to compare the sensitivity and specificity of transcranial Doppler confirmation of cerebral circulatory arrest, by using clinical confirmation of brain death as the criterion standard. RESULTS: We identified 22 eligible studies (1671 patients total), dating from 1987 to 2014. Pooled sensitivity and specificity estimates from 12 study protocols that reported data for the calculation of both values were 0.90 (95% CI, 0.87–0.92) and 0.98 (95% CI, 0.96–0.99), respectively. Between-study differences in the diagnostic performance of transcranial Doppler were found for both sensitivity (I(2) = 76%; P < .001) and specificity (I(2) = 74.3%; P < .001). The threshold effect was not significant (Spearman r = −0.173; P = .612). The area under the curve with the corresponding standard error (SE) was 0.964 ± 0.018, while index Q test ± SE was estimated at 0.910 ± 0.028. CONCLUSIONS: The results of this meta-analysis suggest that transcranial Doppler is a highly accurate ancillary test for brain death confirmation. However, transcranial Doppler evaluates cerebral circulatory arrest rather than brain stem function, and this limitation needs to be taken into account when interpreting the results of this meta-analysis.

Objective: Our aim was to evaluate the diagnostic yield of transesophageal echocardiography (TEE) in consecutive patients with ischemic stroke (IS) fulfilling the diagnostic criteria of embolic strokes of undetermined source (ESUS). Methods: We prospectively evaluated consecutive patients with acute IS satisfying ESUS criteria who underwent in-hospital TEE examination in 3 tertiary care stroke centers during a 12-month period. We also performed a systematic review and meta-analysis estimating the cumulative effect of TEE findings on therapeutic management for secondary stroke prevention among different IS subgroups. Results: We identified 61 patients with ESUS who underwent investigation with TEE (mean age 44 ± 12 years, 49% men, median NIH Stroke Scale score = 5 points [interquartile range: 3–8]). TEE revealed additional findings in 52% (95% confidence interval [CI]: 40%–65%) of the study population. TEE findings changed management (initiation of anticoagulation therapy, administration of IV antibiotic therapy, and patent foramen ovale closure) in 10 (16% [95% CI: 9%–28%]) patients. The pooled rate of reported anticoagulation therapy attributed to abnormal TEE findings among 3,562 acute IS patients included in the meta-analysis (12 studies) was 8.7% (95% CI: 7.3%–10.4%). In subgroup analysis, the rates of initiation of anticoagulation therapy on the basis of TEE investigation did not differ ( p = 0.315) among patients with cryptogenic stroke (6.9% [95% CI: 4.9%–9.6%]), ESUS (8.1% [95% CI: 3.4%–18.1%]), and IS (9.4% [95% CI: 7.5%–11.8%]). Conclusions: Abnormal TEE findings may decisively affect the selection of appropriate therapeutic strategy in approximately 1 of 7 patients with ESUS.

Background&Purpose: Despite recent landmark RCTs showing significant survival and functional outcome benefits with HCT compared with medical therapy (MT) in patients with malignant MCA infarction (MMCAI), HCT rates have not substantially increased in the US. It is difficult for patients’ families to reconcile the wishes of the patient with the possibility of poor functional outcome. We sought to evaluate early outcomes in patients with MMCAI who were treated with HCT (cases) in comparison to patients treated with MT due to the perception of procedural futility by families (controls). Subjects&Methods: We evaluated in a retrospective cohort study design consecutive patients with acute MMCAI treated in two tertiary care centers during a seven-year period. Pre-treatment NIHSS, NIHSS at discharge and modified Rankin Scale (mRS) at three months were documented. Functional independence (FI) and survival without severe disability (SWSD) were defined as mRS of 0-2 and 0-4 respectively. Results: A total of 66 patients (37 cases and 29 controls) fulfilled the study inclusion criteria [mean age 59±15 years, 52% men, median admission NIHSS-score: 19 points (IQR: 16-22]. Cases were younger (51±11 vs 68±13 years; p0.05) in terms of other baseline characteristics. The rates of FI and SWSD at three months were higher in cases than controls [16% vs 0% (p=0.031) & 62% vs 0% (p Conclusions: HCT is a critical and effective therapy for patients with MMCAI but cannot provide a gurantee of functional recovery. Refusal of HCT by medical decision makers is common and reflects the complexity of issues under consideration in terms of patient outlook beyond the reduction of mortality following acute MMCAI.

Background&Purpose: Experimental and retrospective clinical data have indicated that sulfonylurea drugs (SUD) may confer protection against cerebral swelling and hemorrhagic transformation in AIS. We sought to determine whether pretreatment and in-hospital use of SUD may be associated with better outcomes in diabetic AIS patients treated with IVT. Subjects&Methods: We retrospectively analyzed prospectively collected data of consecutive AIS treated with IVT during a three-year period. Pre-treatment NIHSS, NIHSS at 48 hours and modified Rankin Scale (mRS) at discharge were documented. Symptomatic intracerebral hemorrhage (sICH) was defined as imaging evidence of ICH with NIHSS increase of 4 points within 72 hours. Early neurological improvement was defined as a NIHSS-score decrease of ≥4 points or a NIHSS-score of 0 at 48 hours. Cerebral edema was documented by neuroradiology reports. Favorable functional outcome (FFO) was defined as mRS of 0-1. Results: A total of 148 diabetic AIS patients fulfilled the study inclusion criteria (mean age 64±11 years, 49% men, median admission NIHSS-score: 8 points). We identified 42 patients pre-treated with SUD (mean age 65±11 years, 50% men, median admission NIHSS-score: 8 points) all of whom continued to receive these medications during hospitalization. Demographic characteristics, vascular risk factors and admission NIHSS-scores did not differ (p>0.1) between patients pretreated (cases) and non-pretreated with SUD (controls). The prevalence of complications and favorable outcomes did not differ (p>0.1) between cases and controls: sICH (2% vs. 5%), cerebral edema (5% vs 4%), early neurological improvement (42% vs 43%), in-hospital mortality (12% vs 5%) and FFO (22% vs 32%). Conclusions: Pretreatment and in-hospital use of SUD appears not to be associated with early favorable outcomes and lower likelihood of potential complications in diabetic AIS patients treated with IVT.

Background&Purpose: The currently proposed criteria for the definition of embolic strokes of undetermined source (ESUS) do not include investigation with transesophageal echocardiography (TEE) among the mandatory diagnostic work-up. We sought to evaluate the diagnostic yield of TEE in consecutive patients fulfilling ESUS criteria. Methods: We prospectively evaluated ischemic stroke (IS) patients fulfilling ESUS criteria from three tertiary care stroke centers during a twelve month period. All patients underwent additional diagnostic work-up with TEE to estimate both the diagnostic yield and the impact of TEE findings in the therapeutic management of patients with ESUS. Results: We identified 61 patients with ESUS who underwent investigation with TEE [mean age 44.3±11.5 years; 49.2% males; median NIHSS=5 (IQR, 3-8)]. TEE revealed additional findings in 52.4% (95%CI by the adjusted Wald method: 40.2%-64.5%) of the patients. Patent foramen ovale (PFO) and atrial septal aneurysm (ASA) were reported in 27.8% (95%CI: 18.1%-40.2%) and 13.1% (95%CI: 6.5%-24.1%) of the study population respectively. The concurrence of PFO and ASA was reported in 4 patients (6.5%, 95%CI: 2.1%-16.1%). The presence of valvular vegetations was documented in 2 patients (3.2%; 95%CI: 0%-11.8%), while thrombus was found in the left atrium of one patient (1.6%, 95%CI: 0%-9.5%). Complex aortic arch atheromatosis was reported in 6.5% (95%CI: 2.1%-16.1%) of the patients. Neither myxomas, nor ventricular septal defects were found in TEE examinations. TEE findings changed the management in 16.4% (95%CI: 8.9%-27.8%) of the patients. Anticoagulants were initiated in 5 patients, while the other 2 patients with endocarditis received treatment with intravenous antibiotics. Finally, 3 of the 61 patients underwent a PFO-closure procedure due to the large size of the shunt and the previous history of recurrent cryptogenic IS. Conclusions: Our findings suggest that ESUS patients should undergo investigation with TEE in search of potential cardioembolic or aortogenic sources. TEE findings may have a decisive impact on the selection of the appropriate therapeutic approach for these patients.

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 Conclusions— Our single-center data indicate favorable safety and outcomes of intravenous thrombolysis administered to SM.

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.

Background and Purpose— Characteristics of ultrasound-activated gaseous microspheres (μS) reflective of their size and quantities are needed for future dose-escalation and drug delivery trials. Methods— A double-blind, interobserver-validated analysis of multi-gate power-motion Doppler μS traces included large (>8μ) μS from agitated saline injections in the right-to-left shunt (RLS) positive stroke patients and small ( Results— In 101 μS traces from 50 RLS-positive and 10 thrombolysis+μS treated patients, a large μS passage had median maximum duration 30.8 ms (interquartile range [IQR] 22.0ms), multi-gate travel time (MGTT) 58.6±19.3 ms versus small μS: duration 8.3ms (IQR 4.3ms), MGTT 43.2±13.9ms, P P P P =0.719) and higher than surrounding red blood cell velocities (28.8±13.8 cm/s, P Conclusions— With normal or reduced flow, activated μS passage duration through a small power motion Doppler gate can quantify the dose of delivered μS. Ultrasound can determine a minimum number of μS needed to achieve constant flow enhancement and targeted drug delivery. Propagation speed of μS smaller than red blood cells may reflect plasma flow velocities around acute occlusions.

Background and Purpose— Intracranial arterial stenosis increases flow velocities on the upslope of the Spencer’s curve of cerebral hemodynamics. However, the velocity can decrease with long and severely narrowed vessels. We assessed the frequency and accuracy for detection of focal and diffuse intracranial stenoses using novel diagnostic criteria that take into account increased resistance to flow with widespread lesions. Methods— We evaluated consecutive patients referred to a neurovascular ultrasound laboratory with symptoms of cerebral ischemia. Transcranial Doppler mean flow velocities were classified as normal (30 to 99 cm/s), high and low. Pulsatility index ≥1.2 was considered high. Focal intracranial disease was defined as ≥50% diameter reduction by the Warfarin Aspirin in Symptomatic Intracranial Disease criteria. Diffuse disease was defined as stenoses in multiple intracranial arteries, multiple segments of one artery, or a long (>1 cm) stenosis in one major artery on contrast angiography (CT angiography or digital subtraction angiography) as the gold standard. Results— One hundred fifty-three patients (96 men, 76% white, age 62±15 years) had previous strokes (n=135) or transient ischemic attack (n=18). Transcranial Doppler detection of focal and diffuse intracranial disease had sensitivity 79.4% (95% CI: 65.8% to 93%), specificity 92.4% (95% CI: 87.7% to 97.2%), positive predictive value 75.0% (95% CI: 60.9% to 89.2%), negative predictive value 94.0% (95% CI: 89.7% to 98.3%), and overall accuracy 89.5% (95% CI: 84.5% to 94.4%). After adjustment for stroke risk factors, transcranial Doppler findings of low mean flow velocities and high pulsatility index in a single vessel were independently associated with angiographically demonstrated diffuse single vessel intracranial disease, whereas low mean flow velocities/high pulsatility index in multiple vessels were related to multivessel intracranial disease (OR: 19.7, 95% CI: 4.8 to 81.2, P Conclusions— Diffuse intracranial disease may have a higher than expected frequency in a select stroke population and can be detected with noninvasive screening.

Background— Early recovery after intravenous thrombolysis can be observed in stroke; however, the utility of measuring clinical improvement to assess artery status has not been established. We sought to determine the accuracy of serial National Institutes of Health Stroke Scale (NIHSS) scores to detect complete early recanalization of the middle cerebral artery. Methods and Results— Data from the CLOTBUST trial (Combined Lysis of Thrombus in Brain Ischemia Using Transcranial Ultrasound and Systemic tPA) were used to determine the most sensitive and specific NIHSS-derived parameter to identify complete recanalization. Then, reproducibility was tested against a separate patient population (Barcelona data set). NIHSS scores were determined before tissue plasminogen activator bolus and at 60 and 120 minutes in both data sets. Receiver operating characteristic curves were used to compare test performance. The accuracy of individual cutoffs was demonstrated by sensitivity, specificity, and positive and negative predictive values. A total of 122 patients in the CLOTBUST data set and 98 in the Barcelona data set received 0.9 mg/kg intravenous tissue plasminogen activator [mean age 69±12 versus 72±12 years, 57% male versus 51% male, median NIHSS 16 versus 17 points, mean time from onset to treatment 140±32 versus 177±59 minutes, and complete recanalization of the middle cerebral artery in 19% versus 17%). For identification of recanalization, an NIHSS score reduction of ≥40% offered the best tradeoff, with sensitivity, specificity, positive predictive value, and negative predictive value of 65%, 85%, 50%, and 91% at 60 minutes and 74%, 80%, 58%, and 89% at 120 minutes, respectively. Test performance was equal in the Barcelona data set. Conclusions— Relative changes in serial NIHSS scores can serve as a simple clinical indicator of arterial status after intravenous thrombolysis. Accuracy parameters are affected by the process of recanalization and its varying clinical significance.

Although common carotid artery (CCA) occlusions are rare, acute clinical presentations vary from mild to devastating strokes primarily due to tandem occlusions in the intracranial arteries. Three patients with acute CCA occlusions were treated with systemic tissue plasminogen activator (TPA). Blood pressures were kept at the upper limits allowed with TPA therapy with fluid balance and the 'head-down' position. Recanalization occurred in intracranial vessels only. Marked early neurological improvement occurred in two of three patients. CCA occlusions should not be considered contra-indication to systemic thrombolysis.

The evaluation of victims of ischemic stroke has evolved over the last few years, primarily as a result of the introduction of innovative, sensitive, and informative diagnostic procedures. The role of the neurologist appears to have been redefined as one in which the identification of the presumptive cause and mechanism of the stroke is one of the primary responsibilities. We compared the etiologic stroke subtypes of patients entered into the Saint Louis University Stroke Registry for the period January to June, 1986 (Group A), with analogous data collected in patients entered from January to June, 1992 (Group B). Group A included 57 patients whose stroke subtype distribution was as follows: 19% due to athero-thromboembolism, 18% cardiogenic, 5% lacunar, and 4% due to other causes. In addition, 54% of patients had strokes of unknown etiology. Group B comprised 137 patients with the following etiologic distribution: 35% cardiogenic, 26% atherothrombolic, 3% lacunar, and 6% from other causes. Only 29% had strokes of unknown etiology. The apparent increase in the proportion of cardiogenic strokes may be related to wider utilization of transesophageal echocardiography. There was also a significant drop in the proportion of strokes of unknown etiology. Finally, in comparison with other stroke registries, our data suggest that many small strokes may also result from cardiogenic embolism. These apparent changes in the proportion of stroke subtypes should be considered when patients are being evaluated for risk stratification.

Although shown to be more effective than aspirin for secondary stroke prevention, the guidelines for utilizing ticlopidine in daily clinical practice are as yet undefined. We reviewed all entries into the Saint Louis University Stroke Registry for the period of January to December 1992 and identified individuals admitted with diagnosis of cerebral infarction or transient ischemic attack (TIA) and who, upon discharge, were prescribed ticlopidine. The etiologic diagnosis, event recurrence during follow-up, compliance with medication, and side effects of all these patients were documented following review of inpatient and outpatient records. A total of 32 patients, 19 (69%) with cerebral infarction and 10 (31%) with TIA were identified. The etiologic diagnoses included: 11 patients with atherothrom-boembolic events, three with lacunar strokes, seven with cardioembolic events, and 11 with stroke of uncertain etiology. None of the patients reported recurrent cerebrovascular events. Sixteen (50%) patients continued to take the drug up to their last visit, whereas 9 (28%) had it discontinued. Five patients were lost to follow-up, and two died from cardiac arrest. The reasons for drug discontinuation included high cost in two patients, allergic reactions in two, and gastrointestinal side effects in three. Two additional patients stopped taking ticlopidine on their own due to uncertain reasons. In spite of its potential usefulness, intolerance to ticlopidine and its high cost result in treatment discontinuation in a significant proportion of patients. These factors and their effect on patients' compliance must be taken into account when prescribing this medication.

Background&Purpose: There are contradictory data on the potential association between size of patent foramen ovale (PFO) or coexisting atrial septal aneurysm (ASA) and risk of recurrent stroke. We performed a meta-analysis to evaluate the relationship of PFO size and concomitant ASA with recurrent stroke in medically-treated stroke patients with PFO. Subjects&Methods: We conducted a systematic review and meta-analysis according to PRISMA guidelines of all available prospective studies reporting recurrent cerebrovascular events defined as stroke and/or transient ischemic attacks (TIA) in medically treated patients with PFO diagnosed by echocardiography and/or transcranial Doppler (TCD). Shunt size was stratified according to validated transeosophageal (TEE) or TCD criteria as “small”, “moderate” or “large”. Coexisting ASA was diagnosed using TEE criteria. Results: We identified 6 eligible studies including a total of 1,727 patients. PFO size (large vs. moderate-small PFO) was not associated with a combined higher risk of recurrent stroke/TIA (RR=1.27; 95%CI= 0.52-3.08; p=0.60; Figure, Panel A) or a higher risk of recurrent stroke alone (RR=1.14; 95%CI= 0.56-2.32; p=0.72; Figure, Panel B). Coexisting ASA was not associated with a combiner higher risk of recurrent stroke/TIA (RR=1.63; 95%CI= 0.89-2.98; p=0.11; Figure, Panel C). There was no evidence of heterogeneity for all analyses (I squared statistic < 50%, p > 0.1 Cohran Q test) across the included studies. Conclusions: Our meta-analysis failed to detect any association between PFO-size and risk of recurrent cerebrovascular events in medically-treated stroke patients with PFO. Similarly, the presence of ASA was not related to risk of recurrent cerebral ischemia.

Background&Purpose: Shortening door-to-needle time may lead to intravenous thrombolysis (IVT) administration in stroke mimics (SM). We sought to determine safety of IVT in SM using prospective, single-center data and by conducting a comprehensive meta-analysis of reported case series. Subjects&Methods: We analyzed consecutive IVT-treated patients during a 5-year period (2009-2013) at a tertiary care stroke center. Non-contrast head CT, NIHSS pre-treatment and modified Rankin scores (mRS) at discharge were obtained as standard of care. SM was defined as no acute ischemic lesions on MRI and the final non-stroke diagnosis established by radiologists and treating physicians unaware of the purposes of this study. Symptomatic intracerebral hemorrhage (sICH) was defined as imaging evidence of ICH with NIHSS increase of 4 or more points. Functional independence (FI) was defined as mRS 0-1. We also conducted a comprehensive meta-analysis of all available case-series reporting safety of IVT in SM using PRISMA guidelines. Results: Of 516 consecutive IVT patients at our tertiary care center (50% men; mean age 60±14years; median NIHSS 11, range 3-22), SM comprised 75 cases (14.5%, 95%CI by adjusted wald method: 11.7%-17.9%). sICH occurred in one patient (1.3%; 95%CI:0%-7.9%), while we documented no cases of orolingual edema (OE) or major extracranial hemorrhagic complications (0%; 95%CI:0%-4.2%). Two patients experienced minor extra-cranial hemorrhagic complications (1 case of gingival & 1 case of nose bleeding). Meta-analysis of 9 studies including 8,942 patients treated with IVT and reporting safety outcomes in 392 SM showed pooled rates of sICH and OE 0.5% (95%CI: 0%-2%) and 0.3% (95%CI: 0%-2%) respectively. We documented no heterogeneity between estimates of sICH (I squared statistic=0%; p=0.941 Cohran Q test), and OE (I squared statistic=0%; p=0.913 Cohran Q test). Conclusions: Our prospectively collected data coupled with the findings of the comprehensive meta-analysis underscore the safety of IVT in SM given the low prevalence of hemorrhagic and systemic complications and the lack of heterogeneity across reported case-series.

Background&Purpose: Current data is limited regarding the comparative utility of Transthoracic echocardiography (TTE) vs. TEE in diagnosing potential sources of cardioembolism (PSOC) in patients with cryptogenic stroke, particularly in young stroke patients. We sought to evaluate the comparative diagnostic yield of these two echocardiographic modalities in young IS patients. Methods: We conducted a retrospective chart review of consecutive young (18-45 yrs) IS patients admitted to a tertiary care stroke center over a study period of 42 months. All patients underwent both TTE and TEE during their standard diagnostic work-up. Stroke classification at discharge was performed according to TOAST criteria by treating physicians. Results: The study population consisted of 83 IS patients (mean age 38±5years, 40% men, 86% blacks, median admission NIHSS-score 3 points, IQR 1-8) who underwent both echocardiographic examinations. Cardioembolic stroke (CS) was the discharge diagnosis in 22 cases (27%). EF calculated by TEE strongly correlated to EF calculated by TTE (r=0.846; p Conclusions: Our study showed that the yield of TEE for detecting PSOC was higher than that of TTE, while abnormal TEE findings were independently associated with a higher likelihood of CS diagnosis. TEE should be considered as the initial echocardiographic modality for evaluating young IS patients, since it may expedite workup and early detection of stroke etiopathogenic mechanism.

Background:We hypothesized that patients with clinically severe strokes but less severe early ischemic changes on brain CT (i.e., clinical-CT mismatch) may respond better to intravenous recombinant tissue plasminogen activator (i.v. rt-PA) within 3 h of symptom onset. Methods: In this secondary analysis of the CLOTBUST data, patients with middle cerebral artery occlusions on transcranial Doppler (TCD) were treated with i.v. rt-PA. Alberta Stroke Program Early CT Scores were obtained with raters blinded to the NIH Stroke Scale and TCD results. Two mismatch criteria and three criteria of response to therapy were explored. Results: Of 126 patients, 67% had a mismatch type 1 and 74% had a mismatch type 2. The presence of clinical-CT mismatch by either definition did not correlate with any of the three criteria of response to rt-PA. Recanalization was a strong determinant of response, whether or not mismatch was present. Conclusions: Mismatch between severity of neurological deficit and CT findings is common but does not predict response to rt-PA therapy given within 3 h.

INTRODUCTION Vasospasm after subarachnoid hemorrhage remains a management challenge. The accepted treatment involves hypertensive, hypervolemic, hemodilution therapy. However, there is variation in the application of this treatment. Most authors increase mean arterial pressure (MAP), which can be associated with significant morbidity. Others increase cardiac output (CO). In this study, we examined the relationship between volume status, CO, and MAP and cerebral blood flow (CBF) in the setting of vasospasm. METHODS A xenon blood flow tomography-based system was used to quantitate CBF. Sixteen patients with vasospasm after subarachnoid hemorrhage were treated with hypervolemia, phenylephrine to increase MAP, or dobutamine to increase CO. Direct CBF measurements were obtained before and after treatment. A strength of this study is that only one variable (central venous pressure, MAP, or CO) was manipulated in each patient, and the effect of this change was measured immediately. RESULTS With phenylephrine, mean MAP increased from 102.4 to 132.1 mm Hg. In regions of diminished CBF due to vasospasm, mean CBF increased from 19.2 to 33.7 ml/100 g/min. Similarly, dobutamine increased the cardiac index from a mean of 4.1 to 6.0 L/min/m2 and slightly decreased MAP. CBF increased from a mean of 24.8 to 35.4 ml/100 g/min. Both were statistically significant changes. With hypervolemia, the average central venous pressure increased from a mean of 5.4 to 7.3 cm H2O; no changes in mean CBF were noted. CONCLUSION This article reports the first human study that shows with direct measurements the independent influence of CO in the setting of vasospasm. Increases in CO without changes in MAP can elevate CBF. This finding has immediate clinical application because CO manipulation is much safer than increasing MAP. Because both interventions were equally efficacious, our protocol has been changed to augment CO as a first measure. Induced hypertension is reserved for patients in whom this initial treatment fails.

Background Residual blood flow around thrombus prior to treatment predicts success of coronary thrombolysis. The authors aimed to correlate the presence of residual flow signals in the middle cerebral artery (MCA) with completeness of recanalization after intravenous tissue plasminogen activator (TPA). Methods The authors studied consecutive patients treated with intravenous TPA therapy who had a proximal MCA occlusion on pretreatment transcranial Doppler (TCD). Patients were continuously monitored for 2 hours after TPA bolus. Absent residual flow signals correspond to the thrombolysis in brain ischemia (TIBI) 0 grade, and the presence of residual flow signals was determined as TIBI 1-3 flow grades. Complete recanalization was defined as flow improvement to TIBI grades 4-5. Results Seventy-five patients with a proximal MCA occlusion had median pre-bolus NIHSS 16 (85% with > or = 10 points). TPA bolus was given at 141 +/- 56 minutes (median 120 minutes). Complete recanalization was observed in 25 (33%), partial in 23 (31%), and no early recanalization was seen in 27 (36%) patients within 2 hours after TPA bolus. Only 19% with absent residual flow signals (TIBI grade 0, n = 26) on pretreatment TCD had complete early recanalization. If pretreatment TCD showed the presence of any residual flow (TIBI 1-3, n = 49), 41% had complete recanalization within 2 hours of TPA bolus (P = .03). Conclusions Patients with detectable residual flow signals before IV TPA bolus are twice as likely to have early complete recanalization. Those with no detectable residual flow signals have less than 20% chance for complete early recanalization with intravenous TPA and may be candidates for intra-arterial therapies.

Background and Purpose —Inhospital placement of patients with mild (National Institutes of Health Stroke Scale [NIHSS] score Methods —We reviewed 138 consecutive patients admitted within 24 hours of stroke onset to 2 physically adjacent hospitals with different admitting practices. Outcome measures included complication rates, discharge Rankin scale score, hospital discharge placement, costs, and length of stay (LOS). Results —Hospital A, a 626-bed university-affiliated hospital, admitted 43% of mild and moderate strokes (MMS) to an ICU (26% of mild, 74% of moderate), whereas hospital B, a 618-bed community facility, admitted 18% of MMS to an ICU (3% of mild, 45% of moderate; P Conclusions —While limited by the retrospective nature of our study, routinely admitting acute MMS patients to an ICU provides no cost or outcomes benefits.

Carotid artery stenosis is a common and potentially treatable cause of stroke. Stroke risk is increased as the degree of carotid stenosis increases, as well as in patients with neurological symptoms referable to the stenosed carotid artery. Carotid stenosis can be quantified by ultrasound imaging, magnetic resonance angiography, or conventional angiography. Medical treatment with platelet antiaggregants reduces stroke risk in some patients; other patients are best treated with carotid endarterectomy. Experimental treatments for carotid stenosis, including carotid angioplasty with or without stenting, are under investigation. We summarize the current literature and provide treatment recommendations for patients with atherosclerotic carotid artery disease.

Background and Purpose— Epidemiological studies of intracerebral hemorrhage (ICH) have consistently demonstrated variation in incidence, location, age at presentation, and outcomes among non-Hispanic white, black, and Hispanic populations. We report here the design and methods for this large, prospective, multi-center case–control study of ICH. Methods— The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study is a multi-center, prospective case–control study of ICH. Cases are identified by hot-pursuit and enrolled using standard phenotype and risk factor information and include neuroimaging and blood sample collection. Controls are centrally identified by random digit dialing to match cases by age (±5 years), race, ethnicity, sex, and metropolitan region. Results— As of March 22, 2013, 1655 cases of ICH had been recruited into the study, which is 101.5% of the target for that date, and 851 controls had been recruited, which is 67.2% of the target for that date (1267 controls) for a total of 2506 subjects, which is 86.5% of the target for that date (2897 subjects). Of the 1655 cases enrolled, 1640 cases had the case interview entered into the database, of which 628 (38%) were non-Hispanic black, 458 (28%) were non-Hispanic white, and 554 (34%) were Hispanic. Of the 1197 cases with imaging submitted, 876 (73.2%) had a 24 hour follow-up CT available. In addition to CT imaging, 607 cases have had MRI evaluation. Conclusions— The ERICH study is a large, case–control study of ICH with particular emphasis on recruitment of minority populations for the identification of genetic and epidemiological risk factors for ICH and outcomes after ICH.

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 ≥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.

PURPOSE: To report ocular findings in the mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome) in a family with the A to G 3243 mitochondrial (mt) DNA point mutation. METHODS: Case reports. Ocular findings are described from four family members with the MELAS associated A to G 3243 mt DNA point mutation. RESULTS: Findings included ophthalmoplegia, neurosensory deafness, reduction of photopic and scotopic electroretinogram b-wave amplitudes, and myopathy, as well as macular retinal pigment epithelial atrophy. No family members had nyctalopia, attenuation of retinal blood vessels, or retinal bone spicule pigmentation. CONCLUSION: The finding of slowly progressive macular retinal pigment epithelial atrophy expands the reported phenotypic diversity of patients with A3243G mt DNA mutations. MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) is a maternally inherited disorder associated with abnormal mitochondria, manifesting in tissues highly dependent on oxidative metabolism. Ocular changes in MELAS syndrome have included reversible scotomata, ophthalmoplegia, pigmentary retinopathy, marked attenuation of the scotopic electroretinogram, myopia, and nuclear cataract. 1 , 2 We highlight some of these ocular manifestations in a family with MELAS syndrome and describe a distinct maculopathy. A 48-year-old woman was referred for evaluation of an asymptomatic maculopathy. Her medical history included mild sensorineural hearing loss; her family history included a mother with congestive heart failure, diabetes mellitus, ophthalmoplegia, and parafoveal atrophy as well as a deceased brother who had an unknown ocular disease, deafness, diabetes, and heart failure. Ocular examination disclosed best-corrected visual acuities of RE: 20/25 and LE: 20/30, normal results from Ishihara color plate testing, significant limitation of gaze in all fields (as much as 70% of expected), and several patches of macular retinal pigment epithelial atrophy bilaterally, which were noted to have become slightly larger compared with fundus photographs taken 8 years earlier. These regions of atrophy correlated with scotomata on Amsler grid and visual field testing Figure 1 , Figure 2 . Download : Download high-res image (393KB) Download : Download full-size image Figure 1 . Retinal pigment epithelial atrophy (arrows) of the right eye in a patient with heteroplasmy for wild-type and A to G 3243 mt DNA mutation. Download : Download high-res image (255KB) Download : Download full-size image Figure 2 . Retinal epithelial atrophy (arrow) of the left eye of the patient in Figure 1 . Her electroretinogram disclosed reduction of photopic and scotopic b-wave amplitudes with normal implicit times. Screening for mitochondrial disorders was suggested but refused by the patient. Several months later, the patient’s sister was diagnosed with MELAS syndrome after presenting with stroke; she was found to have bilateral neurosensory deafness, bicuspid aortic valve, and diabetes mellitus, and a muscle biopsy was positive for ragged red muscle fibers. She was noted to have ophthalmoplegia but did not have ophthalmic complaints. No family members had nyctalopia, waxy pallor of the optic nerve, or attenuation of the retinal vessels. The four tested members of the family, including the sister with MELAS syndrome as well as the original patient and her daughter and son, were found to have the A to G 3243 mt DNA mutation heteroplasmic with wild-type mt DNA. This report amplifies and corroborates some of the ophthalmic features of MELAS syndrome by describing geographic atrophy of the macula in families with the syndrome. The symptoms associated with MELAS syndrome typically appear in childhood and often cause death by the fourth decade. 3 Two mt DNA mutations have been associated with this syndrome and are both located in the tRNAleu (UUR) gene. In 80% of cases, the mutation is an A to G transition at mt-3243, and in 10% of cases, the mutation is an A to G transition at mt-3271. 4 Many maternal relatives of patients with MELAS syndrome exhibit a scarcity of symptoms secondary to the presence of “heteroplasmy,” a mixture of mutant and wild-type intracellular mitochondria. The mutant phenotype is expressed only when an intracellular threshold of mt DNA has been reached. Mitochondrial mutation is uncommon in the general population; however, patients with the mutation were recently shown to have a wider range of phenotypic diversity than previously reported. 5 Nutritional supplementation should be considered, although no large, well-designed trial has studied its efficacy. 1 Atrophic macular pigment epithelial atrophy associated with motility disorders and deafness should precipitate an evaluation for mitochondrial disorders.

The objective of this study was to describe the clinical features of cases hospitalized with West Nile virus (WNV) infections and identify clinical parameters that could potentially predict poor outcome (death). Retrospective medical chart reviews were completed for 172 confirmed cases of WNV infection hospitalized in the Houston, Texas, metropolitan area between 2002 and 2004. Of the 172 patients, 113 had encephalitis which resulted in 17 deaths, 47 had meningitis, and 12 had uncomplicated fever. Risk factors associated with progression from encephalitis to death were absence of pleocytosis in the cerebrospinal fluid, renal insufficiency, requiring intubation and mechanical ventilation, presence of myoclonus or tremors, and loss of consciousness. These findings can aid physicians in evaluating their patients suspected of WNV infection and determining outcomes in their patients with confirmed WNV neuroinvasive disease.

Background and Purpose— Ultrasound transiently expands perflutren-lipid microspheres (μS), transmitting energy momentum to surrounding fluids. We report a pilot safety/feasibility study of ultrasound-activated μS with systemic tissue plasminogen activator (tPA). Methods— Stroke subjects treated within 3 hours had abnormal Thrombolysis in Brain Ischemia (TIBI) residual flow grades 0 to 3 before tPA on transcranial Doppler (TCD). Randomization included Controls (tPA+TCD) or Target (tPA+TCD+2.8 mL μS). The primary safety end point was symptomatic intracranial hemorrhage (sICH) with worsening by ≥4 NIHSS points within 72 hours. Results— Fifteen subjects were randomized 3:1 to Target, n=12 or Control, n=3. After treatment, asymptomatic ICH occurred in 3 Target and 1 Control, and sICH was not seen in any study subject. μS reached MCA occlusions in all Target subjects at velocities higher than surrounding residual red blood cell flow: 39.8±11.3 vs 28.8±13.8 cm/s, PP =0.028. At 2 hours, sustained complete recanalization was 42% versus 13%, P =0.003, and NIHSS scores 0 to 3 were reached by 17% versus 8%, P =0.456. Conclusions— Perflutren μS reached and permeated beyond intracranial occlusions with no increase in sICH after systemic thrombolysis suggesting feasibility of further μS dose-escalation studies and development of drug delivery to tissues with compromised perfusion.

Background and Purpose— Evaluation of posterior circulation with single-gate transcranial Doppler (TCD) is technically challenging and yields lower accuracy parameters in comparison to anterior circulation vessels. Transcranial power motion-mode Doppler (PMD-TCD), in addition to spectral information, simultaneously displays in real-time flow signal intensity and direction over 6 cm of intracranial space. We aimed to evaluate the diagnostic accuracy of PMD-TCD against angiography in detection of acute posterior circulation stenoocclusive disease. Methods— Consecutive patients presenting to the emergency room with symptoms of acute ( Results— A total of 213 patients (119 men; mean age 65±16 years; ischemic stroke 71%, transient ischemic attack 29%) underwent emergent neurovascular assessment. Compared with angiography, PMD-TCD showed 17 true-positive, 8 false-negative, 6 false-positive, and 182 true-negative studies in posterior circulation vessels (sensitivity 73% [55% to 91%], specificity 96% [93% to 99%], positive predictive value 68% [50% to 86%], negative predictive value 95% [92% to 98%], accuracy 93% [90% to 96%]). In 14 patients (82% of true-positive cases), PMD display showed diagnostic flow signatures complementary to the information provided by the spectral display: reverberating or alternating flow, distal basilar artery flow reversal, high-resistance flow, emboli tracks and, bruit flow signatures. Conclusions— PMD-TCD yields a satisfactory agreement with urgent brain angiography in the evaluation of patients with acute posterior circulation cerebral ischemia. PMD display can depict flow signatures that are complimentary to and can increase confidence in standard single-gate TCD spectral findings.