José G. Merino

National Institute of Neurological Disorders and Stroke–Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards

Background and Purpose— One in 3 individuals will experience a stroke, dementia or both. Moreover, twice as many individuals will have cognitive impairment short of dementia as either stroke or dementia. The commonly used stroke scales do not measure cognition, while dementia criteria focus on the late stages of cognitive impairment, and are heavily biased toward the diagnosis of Alzheimer disease. No commonly agreed standards exist for identifying and describing individuals with cognitive impairment, particularly in the early stages, and especially with cognitive impairment related to vascular factors, or vascular cognitive impairment. Methods— The National Institute for Neurological Disorders and Stroke (NINDS) and the Canadian Stroke Network (CSN) convened researchers in clinical diagnosis, epidemiology, neuropsychology, brain imaging, neuropathology, experimental models, biomarkers, genetics, and clinical trials to recommend minimum, common, clinical and research standards for the description and study of vascular cognitive impairment. Results— The results of these discussions are reported herein. Conclusions— The development of common standards represents a first step in a process of use, validation and refinement. Using the same standards will help identify individuals in the early stages of cognitive impairment, will make studies comparable, and by integrating knowledge, will accelerate the pace of progress.

Use of a Field-to-Stroke Center Helicopter Transport Program to Extend Thrombolytic Therapy to Rural Residents

Background and Purpose— Giving stroke victims who reside outside communities with hospitals that can administer tissue plasminogen activator (rtPA) access to thrombolytic therapy is a challenge. Helicopter transport to a stroke center is a potential way to make rtPA available to these communities. We examined the experience of the Shands-Jacksonville Acute Stroke Transport Program, a field-to-stroke center helicopter transport program that serves rural counties in the northeastern Florida/southeastern Georgia region. Methods— Prospectively collected data of 111 consecutive helicopter transports to Shands-Jacksonville, from an 11-county region, over a 3-year period were reviewed. Results— Eighty-five patients (76%) had a cerebrovascular event. Forty-seven patients (42%) had an ischemic stroke, 19 (17%) had a transient ischemic attack, and 19 (17%) had a hemorrhagic stroke. Thrombolytic therapy was administered to 18 ischemic stroke patients (38%), with 15 being treated intravenously. Three patients who arrived beyond the 3-hour window were treated intra-arterially. Average field-to-hospital distance for all patients was 29.4 miles (range, 11 to 90 miles). Most patients (n=65) arrived within 135 minutes from symptom onset. Conclusions— A helicopter-based transport system can link a rural region to a stroke center and promote access to thrombolytic therapy.

Distal hyperintense vessels on FLAIR: An MRI marker for collateral circulation in acute stroke?

Background: Hyperintense vessels (HV) on fluid-attenuated inversion recovery imaging are frequently observed in acute ischemic stroke patients. However, the exact mechanism and clinical implications of this sign have not yet been clearly defined. The features of HV and its relevance to other imaging factors are presented here. Methods: Prominence and location of HV were documented in 52 consecutive patients with middle cerebral artery (MCA) territory infarction, before treatment with IV recombinant tissue plasminogen activator. Pretreatment ischemic lesion volume, perfusion lesion volume, and vessel occlusion were determined in addition to recanalization status and ischemic lesion volume on follow-up imaging. NIH Stroke Scale (NIHSS) was used as a measure of clinical severity. Results: HV distal to arterial occlusion was observed in 73% of patients; more frequent in proximal than distal MCA occlusion patients. Among the 38 patients with proximal MCA occlusion, initial perfusion lesion volume was comparable among patients with different grade distal HV. However, patients with more prominent distal HV had smaller initial, 24-hour, and subacute ischemic lesion volumes and lower initial NIHSS scores. Conclusions: The presence of distal hyperintense vessels before thrombolytic treatment is associated with large diffusion–perfusion mismatch and smaller subacute ischemic lesion volumes in patients with proximal middle cerebral artery occlusion. DWI = diffusion-weighted imaging; FLAIR = fluid-attenuated inversion recovery; GRE = gradient recalled echo; HV = hyperintense vessels; MCA = middle cerebral artery; MRA = magnetic resonance angiography; MTT = mean transit time; NIHSS = NIH Stroke Scale; PWI = perfusion-weighted imaging; rt-PA = recombinant tissue plasminogen activator; TE = echo time; TI = inversion time; TIMI = thrombolysis in myocardial infarction; TR = repetition time.

Imaging of acute stroke

Brain imaging provides an objective basis for the clinical inferences that direct individual patient management in the acute stroke setting. A brain CT or MRI scan is required for all patients with suspected stroke or transient ischemic attack. Thrombolytic therapy is arguably the most important aspect of acute stroke management; however, most decisions in acute stroke do not relate to this treatment. Stroke imaging must, therefore, provide information beyond the presence or absence of intracranial hemorrhage (ICH) and early evidence of a large infarct. Noncontrast CT and gradient-recalled echo MRI show comparable accuracy in the diagnosis of acute ICH. Diffusion-weighted MRI is more sensitive than noncontrast CT for differentiation of acute ischemic stroke from nonstroke conditions. Combined multimodal parenchymal, perfusion and vascular imaging with CT or MRI has the potential to identify patients with an ischemic penumbra that might be appropriate for acute reperfusion therapies. MRI identifies a broader range of acute and chronic cerebrovascular pathologies than does CT and, hence, could aid decisions about acute intervention, in-hospital management, and secondary prevention. Here, we present an overview of the diagnostic information that clinicians might gain from CT and MRI in the setting of acute stroke, along with the advantages and disadvantages of these techniques.

Intra- and Interrater Reliability of Ischemic Lesion Volume Measurements on Diffusion-Weighted, Mean Transit Time and Fluid-Attenuated Inversion Recovery MRI

Background and Purpose— We investigated the intra- and interrater reliability of ischemic lesion volumes measurements assessed by different MRI sequences at various times from onset. Methods— Ischemic lesion volumes were measured for intrarater reliability using diffusion-weighted (DWI), mean transit time (MTT) perfusion and fluid-attenuated inversion recovery (FLAIR) MRI at chronic (>3 days from stroke onset) time points. A single intrarater reader, blind to clinical information and time point, repeated the volume measurements on two occasions separated by at least 1 week. Interrater reliability was also obtained in the second set of patients using acute DWI, MTT and chronic FLAIR MRI. Four blinded readers performed these volume measurements. Average deviations across repeat measurements per lesion and differences between sample means between the two measurements were calculated globally, ie, across all sequences and time points, and per reader type for each sequence at each time point. Results— There was good concordance of the mean sample volumes of the 2 intrarater readings (deviations were <4% and 2 mL globally, <2% and 2 mL for DWI, <6% and 7 mL for MTT, and <2% and 1 mL for FLAIR). There was also good concordance of the interrater readings (<5% and 2 mL globally). Conclusions— Repeat measurements of stroke lesion volumes show excellent intra- and interrater concordance for DWI, MTT and FLAIR at acute through chronic time points.

Whole-Brain Arterial Spin Labeling Perfusion MRI in Patients With Acute Stroke

Background and Purpose— Perfusion MRI can be used to identify patients with acute ischemic stroke who may benefit from reperfusion therapies. The risk of nephrogenic systemic fibrosis, however, limits the use of contrast agents. Our objective was to evaluate the ability of arterial spin labeling (ASL), an alternative noninvasive perfusion technique, to detect perfusion deficits compared with dynamic susceptibility contrast (DSC) perfusion imaging. Methods— Consecutive patients referred for emergency assessment of suspected acute stroke within a 7-month period were imaged with both ASL and DSC perfusion MRI. Images were interpreted in a random order by 2 experts blinded to clinical information for image quality, presence of perfusion deficits, and diffusion–perfusion mismatches. Results— One hundred fifty-six patients were scanned with a median time of 5.6 hours (range, 3.0–17.7 hours) from last seen normal. Stroke diagnosis was clinically confirmed in 78 patients. ASL and DSC imaging were available in 64 of these patients. A perfusion deficit was detected with DSC in 39 of these patients; ASL detected 32 of these index perfusion deficits, missing 7 lesions. The median volume of the perfusion deficits as determined with DSC was smaller in patients who were evaluated as normal with ASL than in those with a deficit (median [interquartile range], 56 [10–116] versus 114 [41–225] mL; P=0.01). Conclusions— ASL can depict large perfusion deficits and perfusion–diffusion mismatches in correspondence with DSC. Our findings show that a fast 2½-minute ASL perfusion scan may be adequate for screening patients with acute stroke with contraindications to gadolinium-based contrast agents.

The Ischemic Stroke Genetics Study (ISGS) Protocol

BackgroundThe molecular basis for the genetic risk of ischemic stroke is likely to be multigenic and influenced by environmental factors. Several small case-control studies have suggested associations between ischemic stroke and polymorphisms of genes that code for coagulation cascade proteins and platelet receptors. Our aim is to investigate potential associations between hemostatic gene polymorphisms and ischemic stroke, with particular emphasis on detailed characterization of the phenotype.Methods/DesignThe Ischemic Stroke Genetic Study is a prospective, multicenter genetic association study in adults with recent first-ever ischemic stroke confirmed with computed tomography or magnetic resonance imaging. Patients are evaluated at academic medical centers in the United States and compared with sex- and age-matched controls. Stroke subtypes are determined by central blinded adjudication using standardized, validated mechanistic and syndromic classification systems. The panel of genes to be tested for polymorphisms includes β-fibrinogen and platelet glycoprotein Ia, Iba, and IIb/IIIa. Immortalized cell lines are created to allow for time- and cost-efficient testing of additional candidate genes in the future.DiscussionThe study is designed to minimize survival bias and to allow for exploring associations between specific polymorphisms and individual subtypes of ischemic stroke. The data set will also permit the study of genetic determinants of stroke outcome. Having cell lines will permit testing of future candidate risk factor genes.

Interleukin-6 −174G/C Polymorphism and Ischemic Stroke A Systematic Review

Background and Purpose— Interleukin-6 (IL-6) is associated with atherosclerotic disease and is also a key mediator in the inflammatory response to cerebral ischemia. Although the IL-6 −174G/C promoter polymorphism has been associated with carotid artery atherosclerosis and coronary heart disease, its relation to ischemic stroke is unclear. This review summarizes the current literature and discusses methodological considerations for future studies. Methods— Electronic searches were conducted in the PubMed MEDLINE, Scopus, and ISI Web of Science databases. Two investigators independently reviewed all abstracts to identify studies examining the association between the IL-6 −174G/C polymorphism and ischemic cerebrovascular events. Results— Twelve relevant publications were identified. Three reported on a subset of patients from a later publication, leaving 9 independent studies. Two studies found an association between ischemic stroke and the G allele or GG genotype, whereas 4 found an association with the C allele or CC genotype. One study found the CC genotype to be significantly less frequent in retinal artery occlusion patients. Two studies found no association between the −174G/C polymorphism and stroke. Conclusions— Studies investigating stroke and the −174G/C polymorphism report conflicting results, which may reflect the complex physiology of IL-6 and true differences between stroke subtypes and populations. However, interpretation of published results is hindered by methodological limitations, and greater rigor and consistency in future studies will help unravel the relationship between the −174G/C polymorphism and stroke.

Racial differences in microbleed prevalence in primary intracerebral hemorrhage

Background: Primary intracerebral hemorrhage is two to three times more common in many racial populations, including black patients. Previous studies have shown that microbleeds, identified on gradient echo MRI (GRE), are present in 50–80% of patients with primary ICH. The objective of this study was to compare, by race, the rates, risk factors, and topography of microbleeds in patients hospitalized for primary ICH. Methods: Patients diagnosed with primary ICH at two metropolitan stroke centers were included. Clinical and neuroimaging data were recorded for each patient. Analyses were performed to compare baseline characteristics as well as imaging findings by race. Results: A total of 87 patients met inclusion criteria (42 black subjects, 45 white subjects). The black cohort was younger (p < 0.001), and had a greater rate of hypertension (p = 0.001), but not other vascular risk factors. Microbleeds were more prevalent in the black population, with 74% of blacks having one or more microbleeds compared to 42% of whites (p = 0.005). The black population also tended to have a greater frequency of microbleeds in multiple territories than the white population (38% vs 22%, p = 0.106). When adjusting for age, hypertension, and alcohol use, race was an independent predictor of microbleeds (OR 3.308, 95% CI 1.144–9.571, p = 0.027). Conclusions: These pilot data suggest that significant racial differences exist in the frequency and topography of microbleeds in patients with primary ICH. Microbleeds may be an important emerging imaging biomarker with the potential to provide insights into ICH pathophysiology, prognosis, and disease progression, as well as possible therapeutic strategies, particularly in medically underserved populations.

IDEAL-D: a rational framework for evaluating and regulating the use of medical devices.

High profile device failures have highlighted the inadequacies of current regulation. Art Sedrakyan and colleagues call for a move to a graduated model of approval and suggest a framework to achieve this goal