José Biller

2015 American Heart Association/American Stroke Association Focused Update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

Purpose— The aim of this guideline is to provide a focused update of the current recommendations for the endovascular treatment of acute ischemic stroke. When there is overlap, the recommendations made here supersede those of previous guidelines. Methods— This focused update analyzes results from 8 randomized, clinical trials of endovascular treatment and other relevant data published since 2013. It is not intended to be a complete literature review from the date of the previous guideline publication but rather to include pivotal new evidence that justifies changes in current recommendations. Members of the writing committee were appointed by the American Heart Association/American Stroke Association Stroke Council’s Scientific Statement Oversight Committee and the American Heart Association/American Stroke Association Manuscript Oversight Committee. Strict adherence to the American Heart Association conflict of interest policy was maintained throughout the consensus process. Recommendations follow the American Heart Association/American Stroke Association methods of classifying the level of certainty of the treatment effect and the class of evidence. Prerelease review of the draft guideline was performed by 6 expert peer reviewers and by the members of the Stroke Council Scientific Statement Oversight Committee and Stroke Council Leadership Committee. Results— Evidence-based guidelines are presented for the selection of patients with acute ischemic stroke for endovascular treatment, for the endovascular procedure, and for systems of care to facilitate endovascular treatment. Conclusions— Certain endovascular procedures have been demonstrated to provide clinical benefit in selected patients with acute ischemic stroke. Systems of care should be organized to facilitate the delivery of this care.Purpose— The aim of this guideline is to provide a focused update of the current recommendations for the endovascular treatment of acute ischemic stroke. Where there is overlap, the recommendations made here supersede those of previous guidelines. Methods— This focused update analyzes results from 8 randomized clinical trials of endovascular treatment and other relevant data published since 2013. It is not intended to be a complete literature review from the date of the previous guideline publication but rather to include pivotal new evidence that justifies changes in current recommendations. Members of the writing committee were appointed by the American Heart Association/American Stroke Association Stroke Council’s Scientific Statement Oversight Committee and the American Heart Association/American Stroke Association Manuscript Oversight Committee (MOC). Strict adherence to the American Heart Association conflict of interest policy was maintained throughout the consensus process. Recommendations follow the American Heart Association/American Stroke Association methods of classifying the level of certainty of the treatment effect and the class of evidence. Prerelease review of the draft guideline was performed by 6 expert peer reviewers and by the members of the Stroke Council Scientific Statement Oversight Committee and Stroke Council Leadership Committee. Results— Evidence-based guidelines are presented for the selection of patients with acute ischemic stroke for endovascular treatment, the endovascular procedure and for systems of care to facilitate endovascular treatment. Conclusions— Certain endovascular procedures have been demonstrated to provide clinical benefit in selected patients with acute ischemic stroke. Systems of care should be organized to facilitate the delivery of this care.

Management of Stroke in Infants and Children: A Scientific Statement From a Special Writing Group of the American Heart Association Stroke Council and the Council on Cardiovascular Disease in the Young

PURPOSE The purpose of this statement is to review the literature on childhood stroke and to provide recommendations for optimal diagnosis and treatment. This statement is intended for physicians who are responsible for diagnosing and treating infants, children, and adolescents with cerebrovascular disease. METHODS The Writing Group members were appointed by the American Heart Association Stroke Councils Scientific Statement Oversight Committee. The panel included members with several different areas of expertise. Each of the panels recommendations was weighted by applying the American Heart Association Stroke Councils Levels of Evidence grading algorithm. After being reviewed by panel members, the manuscript was reviewed by 4 expert peer reviewers and by members of the Stroke Council Leadership Committee and was approved by the American Heart Association Science Advisory and Coordinating Committee. We anticipate that this statement will need to be updated in 4 years. RESULTS Evidence-based recommendations are provided for the prevention of ischemic stroke caused by sickle cell disease, moyamoya disease, cervicocephalic arterial dissection, and cardiogenic embolism. Recommendations on the evaluation and management of hemorrhagic stroke also are provided. Protocols for dosing of heparin and warfarin in children are suggested. Also included are recommendations on the evaluation and management of perinatal stroke and cerebral sinovenous thrombosis in children.

Acute blood glucose level and outcome from ischemic stroke

Objective: To study the relation between acute blood glucose level and outcome from ischemic stroke. Background: Hyperglycemia may augment acute ischemic brain injury and increase the risk of hemorrhagic transformation of the infarct. Methods: The authors analyzed the relation between admission blood glucose level (within 24 hours from ischemic stroke onset) and clinical outcome in 1,259 patients enrolled in the Trial of ORG 10172 in Acute Stroke Treatment (TOAST)—a placebo-controlled, randomized, double-blind trial to test the efficacy of a low-molecular weight heparinoid in acute ischemic stroke. Very favorable outcome was defined as a Glasgow Outcome Scale score of 1 and a modified Barthel index of 19 or 20. Neurologic improvement at 3 months was defined as a decrease by ≥4 points on the NIH Stroke Scale compared with baseline or a final score of 0. Hemorrhagic transformation of infarct was assessed within 10 days after onset of stroke with repeat cerebral CT. Stroke subtype as lacunar or nonlacunar (atherothromboembolic, cardioembolic, and other or undetermined etiology) was classified by one investigator after completion of stroke evaluation according to study protocol. Results: In all strokes combined (p = 0.03) and in nonlacunar strokes (p = 0.02), higher admission blood glucose levels were associated with worse outcome at 3 months according to multivariate logistic regression analysis adjusted for stroke severity, diabetes mellitus, and other vascular risks. In lacunar strokes, the relationship between acute blood glucose level and outcome was related to treatment. In the placebo group, higher admission blood glucose levels were associated with better outcome at 3 months. However, in the active drug group, as the glucose level increased from 50 to 150 mg/dL, the probability of a very favorable outcome decreased sharply and remained relatively unchanged as the glucose level increased further (p = 0.002, for overall effect of glucose on outcome). Acute blood glucose level was not associated with symptomatic hemorrhagic transformation of infarcts or with neurologic improvement at 3 months. Conclusions: During acute ischemic stroke hyperglycemia may worsen the clinical outcome in nonlacunar stroke, but not in lacunar stroke, and is not associated with an increased risk of hemorrhagic transformation of the infarct.

Guidelines and Recommendations for Perfusion Imaging in Cerebral Ischemia A Scientific Statement for Healthcare Professionals by the Writing Group on Perfusion Imaging, From the Council on Cardiovascular Radiology of the American Heart Association

A number of techniques have been developed during the past four decades to evaluate cerebral perfusion. The oldest used 133Xe, a lipophilic radioactive tracer that easily diffuses through the blood-brain barrier (BBB). It was either injected or inhaled, and probes placed over the scalp were used to measure perfusion to the cerebral cortex.1,2 In the mid-1970s, the development of a scanner to detect the emission of positrons led to positron emission tomography (PET) in humans.3 Using a number of radioisotopes, this technology can measure cerebral blood flow (CBF) and various metabolic processes, but until recently it has been primarily used as a research tool. Stable (“cold”) xenon was found to attenuate x-rays in a manner similar to iodine, and there were a number of projects in the 1970s to use this gas as a contrast agent for the rapidly emerging technology of computed tomography (CT), particularly as a perfusion tracer.4 This resulted in the development of the xenon-enhanced CT (XeCT) technique to calculate CBF in patients.5 With improvements in single photon emission CT (SPECT) during the 1980s, a number of compounds that are metabolized in the central nervous system (CNS) were found to be appropriate for perfusion imaging.6,7 Perfusion-weighted and diffusion-weighted magnetic resonance (MR) imaging (PWI and DWI) were developed in the late 1980s,8,9 and that technology has continued to improve. Finally, with the evolution of helical and spiral multislice CT technology, CT perfusion (CTP) imaging is becoming a potentially important clinical technique.10 Although the development of these technologies has been fascinating, their role in evaluating a variety of diseases of the CNS is controversial. It might seem obvious that a disorder of blood flow, such as acute stroke or chronic vascular occlusive disease, should be studied with a perfusion imaging technique. …

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.

National Stroke Association guidelines for the management of transient ischemic attacks

Transient ischemic attacks are common and important harbingers of subsequent stroke. Management varies widely, and most published guidelines have not been updated in several years. We sought to create comprehensive, unbiased, evidence‐based guidelines for the management of patients with transient ischemic attacks.

Fibromuscular Dysplasia: State of the Science and Critical Unanswered Questions A Scientific Statement From the American Heart Association

Fibromuscular dysplasia (FMD) is nonatherosclerotic, noninflammatory vascular disease that may result in arterial stenosis, occlusion, aneurysm, or dissection.1–3 The cause of FMD and its prevalence in the general population are not known.4 FMD has been reported in virtually every arterial bed but most commonly affects the renal and extracranial carotid and vertebral arteries (in ≈65% of cases).5 The clinical manifestations of FMD are determined primarily by the vessels that are involved. When the renal artery is involved, the most frequent finding is hypertension, whereas carotid or vertebral artery FMD may lead to dizziness, pulsatile tinnitus, transient ischemic attack (TIA), or stroke. There is an average delay from the time of the first symptom or sign to diagnosis of FMD of 4 to 9 years.5,6 This is likely because of a multitude of factors: the perception that this is a rare disease and thus FMD is not considered in the differential diagnosis, the reality that FMD is poorly understood by many healthcare providers, and the fact that many of the signs and symptoms of FMD are nonspecific, thus leading the clinician down the wrong diagnostic pathway. A delay in diagnosis can lead to impaired quality of life and poor outcomes such as poorly controlled hypertension and its sequelae, TIA, stroke, dissection, or aneurysm rupture. It should also be noted that FMD may be discovered incidentally while imaging is performed for other reasons or when a bruit is heard in the neck or abdomen in an asymptomatic patient without the classic risk factors for atherosclerosis. The first description of FMD is attributed to Leadbetter and Burkland7 in a 5½-year-old boy with severe hypertension and a renal artery partially occluded by an intra-arterial mass of smooth muscle. He underwent a unilateral nephrectomy of an …

Protocol Violations in Community-Based rTPA Stroke Treatment Are Associated With Symptomatic Intracerebral Hemorrhage

Background— Recombinant tissue plasminogen activator (rTPA) is an established treatment for acute ischemic stroke. The rate and type of protocol violations in rTPA use and their effect on patient outcomes in this setting are not well understood. Objective— The objective of this study was to examine associations between protocol violations and outcomes in community-based rTPA use. Methods— We reviewed medical records of stroke patients treated with rTPA in 10 acute-care hospitals in Indianapolis from July 1996 to February 1998 and assessed complications and outcome. Retrospective National Institute of Health Stroke Scale (on admission and discharge), Canadian Neurological Scale, and length of hospital stay were calculated. Appropriate use of rTPA was determined by the National Institute of Neurological Disorders and Stroke (NINDS) protocol. Results— Fifty patients (mean age, 66 years; 76% white; 56% men) were treated by general neurologists (70%), stroke neurologists (24%), or emergency physicians (6%). Mean times to hospital arrival, brain CT, and start of rTPA infusion were 44, 86, and 141 minutes, respectively. In-hospital mortality rate was 10% (4 intracerebral hemorrhage [ICH], 1 cardiogenic shock). Complications were more frequent among patients with protocol violations (n=8) compared with those without all hemorrhages (75% versus 10%, P <0.001), symptomatic ICH (38% versus 5%, P <0.02), and ICH attributable to rTPA, occurring within 36 hours (38% versus 2.4%, P <0.01), respectively. Conclusions— NINDS protocol violations are relatively common and are associated with symptomatic cerebral and systemic hemorrhages. When the NINDS protocol is strictly followed, hemorrhage rates in community-based rTPA use are similar to those in the NINDS trial.

Subtypes of ischemic stroke in children and young adults

Specific strategies for primary and secondary stroke prevention in children and young adults can only be recommended once the causes of stroke in these age groups are well described. ICD-9 codes were used to identify children aged 1 to 18 years with acute ischemic stroke. Young adults aged>18 to 45 years were identified from the Indiana University and Northwestern University Young Adults Stroke Registries. Validated criteria were used to subtype ischemic stroke as atherothrombotic (AT), cardioembolic(CE), small-vessel (SV), other determined cause, or unknown cause. Ninety-two children and 116 young adults were identified. Stroke subtypes in children/young adults (percentages) were as follows: AT 0/16 (p< 0.001), CE 15/14 (p = 10), SV 0/3 (p = 0.26), other 49/44 (p = 0.40), and unknown 36/23 (p = 0.04). Children had more prothrombotic causes (25% versus 14%, p = 0.03), and young adults had more dissections (3% versus 15%, p = 0.005). Children aged 15 to 18 years had causes of ischemic stroke more similar to those in young adults. The cause of ischemic stroke is less often identified in children than it is in young adults. Children have more prothrombotic causes of stroke, and adults have more atherothrombotic causes and dissections. Lacunar strokes are rare in both children and young adults. The age of 15 years should be used to separate childhood from young-adult ischemic stroke.

Reduced cerebrovascular blood flow velocities and vasoreactivity in open-angle glaucoma

PURPOSE To compare cerebral blood flow velocities between open-angle glaucoma (OAG) patients and controls, at baseline and during hyperoxia. DESIGN Observational cohort study. METHODS A prospective study was conducted in a single institution. Sixteen OAG patients and 15 normal subjects, matched for age, were enrolled. Patients and controls were studied at baseline, while breathing room air, and during 100% oxygen breathing. The eye with the more severe visual field defect was chosen in glaucoma patients, while in controls, the study eye was chosen randomly. Subjects with history of diabetes, cardiovascular, or respiratory disease were excluded. Measurements included brachial arterial pressure, heart rate, intraocular pressure and transcranial Doppler (TCD). Mean and peak velocity and pulsatility index of the ipsilateral middle cerebral artery (MCA) were measured by TCD. RESULTS At baseline, MCA mean and peak systolic blood flow velocities were significantly lower in glaucoma patients compared with controls velocities were significantly lower in glaucoma patients compared with controls (mean velocity: 50.2 vs 65.3 cm/s, P <.05; peak velocity: 74.2 vs 96.8 cm/s, P <.05). Additionally, while hyperoxia significantly decreased both mean and peak systolic velocities in MCA of controls (mean velocity: 65.3 vs 57.7 cm/s, P <.05; peak velocity 96.8 vs 87.9 cm/s, P <.05), it did not cause any significant change in OAG patients. CONCLUSIONS Glaucoma patients were found to have lower MCA blood flow velocities and an absence of vasoreactivity to hyperoxia, compared with controls. The relationship of these cerebral hemodynamic abnormalities to glaucoma pathogenesis and progression remains to be explored.