Salvador Cruz-Flores

Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke (ICTuS-L) Final Results

Background and Purpose— Induced hypothermia is a promising neuroprotective therapy. We studied the feasibility and safety of hypothermia and thrombolysis after acute ischemic stroke. Methods— Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke (ICTuS-L) was a randomized, multicenter trial of hypothermia and intravenous tissue plasminogen activator in patients treated within 6 hours after ischemic stroke. Enrollment was stratified to the treatment time windows 0 to 3 and 3 to 6 hours. Patients presenting within 3 hours of symptom onset received standard dose intravenous alteplase and were randomized to undergo 24 hours of endovascular cooling to 33°C followed by 12 hours of controlled rewarming or normothermia treatment. Patients presenting between 3 and 6 hours were randomized twice: to receive tissue plasminogen activator or not and to receive hypothermia or not. Results– In total, 59 patients were enrolled. One patient was enrolled but not treated when pneumonia was discovered just before treatment. All 44 patients enrolled within 3 hours and 4 of 14 patients enrolled between 3 to 6 hours received tissue plasminogen activator. Overall, 28 patients randomized to receive hypothermia (HY) and 30 to normothermia (NT). Baseline demographics and risk factors were similar between groups. Mean age was 65.5±12.1 years and baseline National Institutes of Health Stroke Scale score was 14.0±5.0; 32 (55%) were male. Cooling was achieved in all patients except 2 in whom there were technical difficulties. The median time to target temperature after catheter placement was 67 minutes (Quartile 1 57.3 to Quartile 3 99.4). At 3 months, 18% of patients treated with hypothermia had a modified Rankin Scale score of 0 or 1 versus 24% in the normothermia groups (nonsignificant). Symptomatic intracranial hemorrhage occurred in 4 patients (68); all were treated with tissue plasminogen activator <3 hours (1 received hypothermia). Six patients in the hypothermia and 5 in the normothermia groups died within 90 days (nonsignificant). Pneumonia occurred in 14 patients in the hypothermia and in 3 of the normothermia groups (P=0.001). The pneumonia rate did not significantly adversely affect 3 month modified Rankin Scale score (P=0.32). Conclusion— This study demonstrates the feasibility and preliminary safety of combining endovascular hypothermia after stroke with intravenous thrombolysis. Pneumonia was more frequent after hypothermia, but further studies are needed to determine its effect on patient outcome and whether it can be prevented. A definitive efficacy trial is necessary to evaluate the efficacy of therapeutic hypothermia for acute stroke.

Racial-Ethnic Disparities in Stroke Care: The American Experience: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

Purpose— Our goal is to describe the effect of race and ethnicity on stroke epidemiology, personal beliefs, access to care, response to treatment, and participation in clinical research. In addition, we seek to determine the state of knowledge on the main factors that may explain disparities in stroke care, with the goal of identifying gaps in knowledge to guide future research. The intended audience includes physicians, nurses, other healthcare professionals, and policy makers. Methods— Members of the writing group were appointed by the American Heart Association Stroke Council Scientific Statement Oversight Committee and represent different areas of expertise in relation to racial-ethnic disparities in stroke care. The writing group reviewed the relevant literature, with an emphasis on reports published since 1972. The statement was approved by the writing group; the statement underwent peer review, then was approved by the American Heart Association Science Advisory and Coordinating Committee. Results— There are limitations in the definitions of racial and ethnic categories currently in use. For the purpose of this statement, we used the racial categories defined by the US federal government: white, black or African American, Asian, American Indian/Alaskan Native, and Native Hawaiian/other Pacific Islander. There are 2 ethnic categories: people of Hispanic/Latino origin or not of Hispanic/Latino origin. There are differences in the distribution of the burden of risk factors, stroke incidence and prevalence, and stroke mortality among different racial and ethnic groups. In addition, there are disparities in stroke care between minority groups compared with whites. These disparities include lack of awareness of stroke symptoms and signs and lack of knowledge about the need for urgent treatment and the causal role of risk factors. There are also differences in attitudes, beliefs, and compliance among minorities compared with whites. Differences in socioeconomic status and insurance coverage, mistrust of the healthcare system, the relatively limited number of providers who are members of minority groups, and system limitations may contribute to disparities in access to or quality of care, which in turn might result in different rates of stroke morbidity and mortality. Cultural and language barriers probably also contribute to some of these disparities. Minorities use emergency medical services systems less, are often delayed in arriving at the emergency department, have longer waiting times in the emergency department, and are less likely to receive thrombolysis for acute ischemic stroke. Although unmeasured factors may play a role in these delays, the presence of bias in the delivery of care cannot be excluded. Minorities have equal access to rehabilitation services, although they experience longer stays and have poorer functional status than whites. Minorities are inadequately treated with both primary and secondary stroke prevention strategies compared with whites. Sparse data exist on racial-ethnic disparities in access to surgical care after intracerebral hemorrhage and subarachnoid hemorrhage. Participation of minorities in clinical research is limited. Barriers to participation in clinical research include beliefs, lack of trust, and limited awareness. Race is a contentious topic in biomedical research because race is not proven to be a surrogate for genetic constitution. Conclusions— There are limitations in the current definitions of race and ethnicity. Nevertheless, racial and ethnic disparities in stroke exist and include differences in the biological determinants of disease and disparities throughout the continuum of care, including access to and quality of care. Access to and participation in research is also limited among minority groups. Acknowledging the presence of disparities and understanding the factors that contribute to them are necessary first steps. More research is required to understand these differences and find solutions.

Effect of Systolic Blood Pressure Reduction on Hematoma Expansion, Perihematomal Edema, and 3-Month Outcome Among Patients With Intracerebral Hemorrhage: Results From the Antihypertensive Treatment of Acute Cerebral Hemorrhage Study

BACKGROUND Evidence indicates that systolic blood pressure (SBP) reduction may reduce hematoma expansion in patients with intracerebral hemorrhage (ICH) who are initially seen with acute hypertensive response. OBJECTIVE To explore the relationship between different variables of SBP reduction and hematoma expansion, perihematomal edema, and 3-month outcome among patients with ICH. DESIGN Post hoc analysis of a traditional phase 1 dose-escalation multicenter prospective study. SETTING Emergency departments and intensive care units. PATIENTS Patients having ICH with an elevated SBP of at least 170 mm Hg who were seen within 6 hours of symptom onset. INTERVENTION Systolic blood pressure reduction using intravenous nicardipine hydrochloride targeting 3 tiers of sequentially escalating SBP reduction goals (170-199, 140-169, or 110-139 mm Hg). MAIN OUTCOME MEASURES We evaluated the effect of SBP reduction (relative to initial SBP) on the following: hematoma expansion (defined as an increased intraparenchymal hemorrhage volume >33% on 24-hour vs baseline computed tomographic [CT] images), higher perihematomal edema ratio (defined as a >40% increased ratio of edema volume to hematoma volume on 24-hour vs baseline CT images), and poor 3-month outcome (defined as a modified Rankin scale score of 4-6). RESULTS Sixty patients (mean [SD] age, 62.0 [15.1] years; 34 men) were recruited (18, 20, and 22 patients in each of the 3 SBP reduction goal tiers). The median area under the curve (AUC) (calculated as the area between the hourly SBP measurements over 24 hours and the baseline SBP) was 1360 (minimum, 3643; maximum, 45) U. Comparing patients having less vs more aggressive SBP reduction based on 24-hour AUC analysis, frequencies were 32% vs 17% for hematoma expansion, 61% vs 40% for higher perihematomal edema ratio, and 46% vs 38% for poor 3-month outcome (P > .05 for all). The median SBP reductions were 54 mm Hg at 6 hours and 62 mm Hg at 6 hours from treatment initiation. Comparing patients having equal to or less vs more than the median SBP reduction at 2 hours, frequencies were 21% vs 31% for hematoma expansion, 42% vs 57% for higher perihematomal edema ratio, and 35% vs 48% for poor 3-month outcome (P > .05 for all). CONCLUSIONS We found no significant relationship between SBP reduction and any of the outcomes measured herein; however, the Antihypertensive Treatment of Acute Cerebral Hemorrhage study was primarily a safety study and was not powered for such end points. The consistent favorable direction of these associations supports further studies with an adequately powered randomized controlled design to evaluate the efficacy of aggressive pharmacologic SBP reduction.

Hospital Mortality and Complications of Electively Clipped or Coiled Unruptured Intracranial Aneurysm

Background and Purpose— To determine the hospital mortality rates associated with elective surgical clipping and endovascular coiling of unruptured intracranial aneurysms. Methods— We identified a cohort of patients electively admitted to US hospitals with the diagnosis of unruptured intracranial aneurysm from the National Inpatient Sample database for the years 2000 through 2006. Patient demographics, hospital-associated complications, and in-hospital mortality were compared among the treatment groups. A multivariate logistic regression analysis was used to identify independent variables associated with hospital mortality. Cochrane–Armitage test was used to assess the trend of hospital use of these procedures. Results— After data cleansing, 3738 (34.3%) patients had aneurysm clipping and 3498 (32.1%) had endovascular coiling. The basic demographics including age, race, and comorbidity indices were similar between the groups. The length of hospital stay was longer in the clipped population (median 4 versus 1 day; P<0.0001), incurring a higher hospital charge in the coiled population (median

Low-Dose Recombinant Tissue-Type Plasminogen Activator Enhances Clot Resolution in Brain Hemorrhage: The Intraventricular Hemorrhage Thrombolysis Trial

42 070 versus

Isolated vertigo as a manifestation of vertebrobasilar ischemia

38 166; P<0.0001). Hospital mortality was higher in the clipped population: 60 (1.6%) versus 20 (0.57%; adjusted odds ratio 3.63; 95% CI, 1.57, 8.42). Perioperative intracerebral hemorrhage and acute ischemic stroke were higher in the clipped population. The rate of hospital use of the endovascular coiling has increased over the years included in this study (<0.0001). Conclusions— Elective coiling of unruptured intracranial aneurysms is associated with fewer deaths and perioperative complications compared with elective clipping. The trend of hospital use of the coiling procedures has increased during recent years.

Brainstem involvement in hypertensive encephalopathy: Clinical and radiological findings

Background and Purpose— Patients with intracerebral hemorrhage and intraventricular hemorrhage have a reported mortality of 50% to 80%. We evaluated a clot lytic treatment strategy for these patients in terms of mortality, ventricular infection, and bleeding safety events, and for its effect on the rate of intraventricular clot lysis. Methods— Forty-eight patients were enrolled at 14 centers and randomized to treatment with 3 mg recombinant tissue-type plasminogen activator (rtPA) or placebo. Demographic characteristics, severity factors, safety outcomes (mortality, infection, bleeding), and clot resolution rates were compared in the 2 groups. Results— Severity factors, including admission Glasgow Coma Scale, intracerebral hemorrhage volume, intraventricular hemorrhage volume, and blood pressure were evenly distributed, as were adverse events, except for an increased frequency of respiratory system events in the placebo-treated group. Neither intracranial pressure nor cerebral perfusion pressure differed substantially between treatment groups on presentation, with external ventricular device closure, or during the active treatment phase. Frequency of death and ventriculitis was substantially lower than expected and bleeding events remained below the prespecified threshold for mortality (18% rtPA; 23% placebo), ventriculitis (8% rtPA; 9% placebo), symptomatic bleeding (23% rtPA; 5% placebo, which approached statistical significance; P=0.1). The median duration of dosing was 7.5 days for rtPA and 12 days for placebo. There was a significant beneficial effect of rtPA on rate of clot resolution. Conclusions— Low-dose rtPA for the treatment of intracerebral hemorrhage with intraventricular hemorrhage has an acceptable safety profile compared to placebo and historical controls. Data from a well-designed phase III clinical trial, such as CLEAR III, will be needed to fully evaluate this treatment. Clinical Trial Registration— Participant enrollment began before July 1, 2005.

Mortality of Cerebral Venous–Sinus Thrombosis in a Large National Sample

Objective: We sought to demonstrate that isolated episodes of vertigo can be the only manifestation of vertebrobasilar ischemia. Background: Isolated persistent vertigo is classically ascribed to labyrinthine disorders and is only rarely considered to reflect vertebrobasilar ischemia. Methods: We retrospectively analyzed all of the records of the Saint Louis University Stroke Registry between January 1, 1992 and September 1, 1993. We set out to identify those patients discharged with a diagnosis of transient ischemic attack (TIA) in the vertebrobasilar system. We reviewed their clinical records and the results of their diagnostic studies. Results: We screened 600 admissions and found 29 patients with vertebrobasilar circulation TIAs. Of these, five men and one woman had episodic vertigo for at least 4 weeks as their only presenting symptom. All six patients had one of two abnormal patterns on magnetic resonance angiography (MRA): focal basilar stenosis or widespread vertebrobasilar slow flow. In three patients, the MRA findings were confirmed by cerebral angiography. Five patients were treated with warfarin and one with aspirin. Two patients developed brainstem infarctions, one of them fatal. Conclusions: Isolated vertigo can be the only manifestation of vertebrobasilar ischemia. Its frequency may be underestimated in clinical practice. Noninvasive testing is helpful both for diagnosis and follow-up. NEUROLOGY 1996;47: 94-97

Cannabis-Related Stroke: Case Series and Review of Literature

Abstract—Predominant brainstem or cerebellar edema is rare in hypertensive encephalopathy and usually affects patients with secondary hypertension. Despite the severity of the radiologic findings, clinical features of brainstem involvement are uncommon. The authors report the clinical and radiologic features of two patients.To the Editor: In their article, Cruz-Flores et al.1 described two original cases and reviewed the literature. In their methods, the authors stated that they excluded most of previously published articles because of lack of adequate data. Only 15 reports met their inclusion criteria. Because of the limitation of the number of allowed references to 10 for a “Brief Communication” in Neurology, the authors referenced only nine articles, none of which included selected patients with brainstem hypertensive encephalopathy (HTE). The readers have to logon to the Neurology Web site to consult the appendix in order to see which studies have been selected. Although it may be convenient to post additional material such as large tables on the Neurology Web site, the list of references used in a review of the literature should be immediately available to the reader of printed articles. Indeed a quick review of this article is misleading and would suggest that these two cases are unique and that brainstem involvement of HTE was never well documented in the past. As detailed by the authors in Appendix E-1, at least 15 good studies (usually with more than two cases) have reported similar clinical and radiological findings, most of which were published with in the past few years, including in Neurology.

Hemicraniectomy and Durotomy Upon Deterioration From Infarction-Related Swelling Trial: Randomized Pilot Clinical Trial

Background and Purpose— The purpose of this study was to evaluate the mortality rates associated with cerebral venous–sinus thrombosis in a large national sample. Methods— A cohort of patients with cerebral venous–sinus thrombosis was identified from the National Inpatient Sample database for the years 2000 to 2007. According to the International Classification of Diseases, 9th Revision, Clinical Modification codes, cerebral venous–sinus thrombosis is categorized into pyogenic and nonpyogenic groups. Multivariate logistic regression analysis was used to assess covariates associated with hospital mortality. Results— Among 3488 patients, the overall mortality rate was 4.39%, which was nonsignificantly higher among the pyogenic group (4.55% versus 3.52%; OR, 0.76; 95% CI, 0.47–1.23). In the pyogenic cerebral venous–sinus thrombosis group, hematologic disorders were the most frequent predisposing condition (16.2%); whereas systemic malignancy followed by hematologic disorders were most common in the nonpyogenic group (14.08% and 10.04%, respectively). Predictors of mortality included age, intracerebral hemorrhage as well as the predisposing conditions of hematologic disorders, systemic malignancy, and central nervous system infection. Conclusions— Compared with arterial stroke, CVST harbors a relatively low mortality rate. Death is determined by age, the presence of intracerebral hemorrhage, and certain predisposing conditions.