Brian Buck

Atrial Fibrillation in Patients with Cryptogenic Stroke

BACKGROUND Atrial fibrillation is a leading preventable cause of recurrent stroke for which early detection and treatment are critical. However, paroxysmal atrial fibrillation is often asymptomatic and likely to go undetected and untreated in the routine care of patients with ischemic stroke or transient ischemic attack (TIA). METHODS We randomly assigned 572 patients 55 years of age or older, without known atrial fibrillation, who had had a cryptogenic ischemic stroke or TIA within the previous 6 months (cause undetermined after standard tests, including 24-hour electrocardiography [ECG]), to undergo additional noninvasive ambulatory ECG monitoring with either a 30-day event-triggered recorder (intervention group) or a conventional 24-hour monitor (control group). The primary outcome was newly detected atrial fibrillation lasting 30 seconds or longer within 90 days after randomization. Secondary outcomes included episodes of atrial fibrillation lasting 2.5 minutes or longer and anticoagulation status at 90 days. RESULTS Atrial fibrillation lasting 30 seconds or longer was detected in 45 of 280 patients (16.1%) in the intervention group, as compared with 9 of 277 (3.2%) in the control group (absolute difference, 12.9 percentage points; 95% confidence interval [CI], 8.0 to 17.6; P<0.001; number needed to screen, 8). Atrial fibrillation lasting 2.5 minutes or longer was present in 28 of 284 patients (9.9%) in the intervention group, as compared with 7 of 277 (2.5%) in the control group (absolute difference, 7.4 percentage points; 95% CI, 3.4 to 11.3; P<0.001). By 90 days, oral anticoagulant therapy had been prescribed for more patients in the intervention group than in the control group (52 of 280 patients [18.6%] vs. 31 of 279 [11.1%]; absolute difference, 7.5 percentage points; 95% CI, 1.6 to 13.3; P=0.01). CONCLUSIONS Among patients with a recent cryptogenic stroke or TIA who were 55 years of age or older, paroxysmal atrial fibrillation was common. Noninvasive ambulatory ECG monitoring for a target of 30 days significantly improved the detection of atrial fibrillation by a factor of more than five and nearly doubled the rate of anticoagulant treatment, as compared with the standard practice of short-duration ECG monitoring. (Funded by the Canadian Stroke Network and others; EMBRACE ClinicalTrials.gov number, NCT00846924.).

Impact of collateral flow on tissue fate in acute ischaemic stroke

Background: Collaterals may sustain penumbra prior to recanalisation yet the influence of baseline collateral flow on infarct growth following endovascular therapy remains unknown. Methods: Consecutive patients underwent serial diffusion and perfusion MRI before and after endovascular therapy for acute cerebral ischaemia. We assessed the relationship between MRI diffusion and perfusion lesion indices, angiographic collateral grade and infarct growth. Tmax perfusion lesion maps were generated and diffusion–perfusion mismatch regions were divided into Tmax ⩾4 s (severe delay) and Tmax ⩾2 but <4 s (mild delay). Results: Among 44 patients, collateral grade was poor in 7 (15.9%), intermediate in 20 (45.5%) and good in 17 (38.6%) patients. Although diffusion–perfusion mismatch volume was not different depending on the collateral grade, patients with good collaterals had larger areas of milder perfusion delay than those with poor collaterals (p = 0.005). Among 32 patients who underwent day 3–5 post-treatment MRIs, the degree of pretreatment collateral circulation (r = −0.476, p = 0.006) and volume of diffusion–perfusion mismatch (r = 0.371, p = 0.037) were correlated with infarct growth. Greatest infarct growth occurred in patients with both non-recanalisation and poor collaterals. Multiple regression analysis revealed that pretreatment collateral grade was independently associated with infarct growth. Conclusion: Our data suggest that angiographic collateral grade and penumbral volume interactively shape tissue fate in patients undergoing endovascular recanalisation therapy. These angiographic and MRI parameters provide complementary information about residual blood flow that may help guide treatment decision making in acute cerebral ischaemia.

A Brief Prehospital Stroke Severity Scale Identifies Ischemic Stroke Patients Harboring Persisting Large Arterial Occlusions

Background and Purpose— The Los Angeles Motor Scale (LAMS) is a brief 3-item stroke severity assessment measure designed for prehospital and Emergency Department use. Methods— The LAMS and NIHSS were scored in under-12-hour acute anterior circulation ischemic stroke patients. Stroke severity ratings were correlated with cervicocerebral vascular occlusion on CTA, MRA, and catheter angiography. Receiver operating curves, c statistics, and likelihood ratios were used to evaluate the predictive value for vascular occlusion of stroke severity ratings. Results— Among 119 patients, mean age was 67 (±18), 45% were male. Time from onset to ED arrival was mean 190 minutes (range 10 to 660). Persisting large vessel occlusions (PLVOs) were present in 62% of patients. LAMS stroke severity scores were higher in patients harboring a vascular occlusion, median 5 (IQR 4 to 5) versus 2 (IQR 1 to 3). Similarly, NIHSS stroke severity scores were higher in PLVO patients, 19 (14 to 24) versus 5 (3 to 7). ROC curves demonstrated that the LAMS was highly effective in identifying patients with PLVOs, c statistic 0.854. At the optimal threshold of 4 or higher, LAMS scores showed sensitivity 0.81, specificity 0.89, and overall accuracy 0.85. LAMS performance was comparable to NIHSS performance (c statistic 0.933). The positive likelihood ratio associated with a LAMS score ≥4 was 7.36 and the negative likelihood ratio 0.21. Conclusions— Stroke severity assessed by the LAMS predicts presence of large artery anterior circulation occlusion with high sensitivity and specificity. The LAMS is a promising instrument for use by prehospital personnel to identify select stroke patients for direct transport to Comprehensive Stroke Centers capable of endovascular interventions.

Hemorrhagic Transformation of Ischemic Stroke: Prediction with CT Perfusion

PURPOSE To determine whether admission computed tomography (CT) perfusion-derived permeability-surface area product (PS) maps differ between patients with hemorrhagic acute stroke and those with nonhemorrhagic acute stroke. MATERIALS AND METHODS This prospective study was institutional review board approved, and all participants gave written informed consent. Forty-one patients who presented with acute stroke within 3 hours after stroke symptom onset underwent two-phase CT perfusion imaging, which enabled PS measurement. Patients were assigned to groups according to whether they had hemorrhage transformation (HT) at follow-up magnetic resonance (MR) imaging and CT and/or whether they received tissue plasminogen activator (TPA) treatment. Clinical, demographic, and CT perfusion variables were compared between the HT and non-HT patient groups. Associations between PS and HT were tested at univariate and multivariate logistic regression analyses and receiver operating characteristic (ROC) analysis. RESULTS HT developed in 23 (56%) patients. Patients with HT had higher National Institutes of Health Stroke Scale (NIHSS) scores (P = .005), poorer outcomes (P = .001), and a higher likelihood of having received TPA (P = .005) compared with patients without HT. Baseline blood flow (P = .17) and blood volume (P = .11) defects and extent of flow reduction (P = .27) were comparable between the two groups. The mean PS for the HT group, 0.49 mL x min(-1) x (100 g)(-1), was significantly higher than that for the non-HT group, 0.09 mL x min(-1) x (100 g)(-1) (P < .0001). PS (odds ratio, 3.5; 95% confidence interval [CI]: 1.69, 7.06; P = .0007) and size of hypoattenuating area at nonenhanced admission CT (odds ratio, 0.4; 95% CI: 0.2, 0.7; P = .002) were the only independent variables associated with HT at stepwise multivariate analysis. The mean area under the ROC curve was 0.918 (95% CI: 0.828, 1.00). The PS threshold of 0.23 mL x min(-1) x (100 g)(-1) had 77% sensitivity and 94% specificity for detection of HT. CONCLUSION Admission PS measurement appears promising for distinguishing patients with acute stroke who are likely from those who are not likely to develop HT. SUPPLEMENTAL MATERIAL http://radiology.rsnajnls.org/cgi/content/full/250/3/867/DC1.

Early Neutrophilia Is Associated With Volume of Ischemic Tissue in Acute Stroke

Background and Purpose— Few data exist on the relationship between differential subpopulations of peripheral leukocytes and early cerebral infarct size in ischemic stroke. Using diffusion-weighted MR imaging (DWI), we assessed the relationship of early total and differential peripheral leukocyte counts and volume of ischemic tissue in acute stroke. Methods— All included patents had laboratory investigations and neuroimaging collected within 24 hours of stroke onset. Total peripheral leukocyte counts and differential counts were analyzed individually and by quartiles. DWI lesions were outlined using a semiautomated threshold technique. The relationship between leukocyte quartiles and DWI infarct volumes was examined using multivariate quartile regression. Results— 173 patients met study inclusion criteria. Median age was 73 years. Total leukocyte counts and DWI volumes showed a strong correlation (Spearman rho=0.371, P<000.1). Median DWI volumes (mL) for successive neutrophil quartiles were: 1.3, 1.3, 3.2, and 20.4 (P for trend <0.001). Median DWI volumes (mL) for successive lymphocyte quartiles were: 3.2, 8.1, 1.3, and 1.5 (P=0.004). After multivariate analysis, larger DWI volume remained strongly associated with higher total leukocyte and neutrophil counts (both probability values <0.001), but not with lymphocyte count (P=0.4971). Compared with the lowest quartiles, DWI volumes were 8.7 mL and 12.9 mL larger in the highest quartiles of leukocyte and neutrophil counts, respectively. Conclusions— Higher peripheral leukocyte and neutrophil counts, but not lymphocyte counts, are associated with larger infarct volumes in acute ischemic stroke. Attenuating neutrophilic response early after ischemic stroke may be a viable therapeutic strategy and warrants further study.

Prediction of hemorrhagic transformation after recanalization therapy using T2*-permeability magnetic resonance imaging

Predicting hemorrhagic transformation (HT) is critical in the setting of recanalization therapy for acute stroke. Dedicated magnetic resonance imaging (MRI) sequences for detection of increased blood–brain barrier (BBB) permeability recently have been developed. We evaluated the ability of a novel MRI permeability technique to detect baseline derangements predictive of various forms of HT after recanalization therapy.

Cholesterol level and symptomatic hemorrhagic transformation after ischemic stroke thrombolysis

Background: Prestroke statin use may improve ischemic stroke outcomes, yet there is also evidence that statins and extremely low cholesterol levels may increase the risk of intracranial hemorrhage. We evaluated the independent effect of statin use and admission cholesterol level on risk of symptomatic hemorrhagic transformation (sHT) after recanalization therapy for acute ischemic stroke. Methods: We analyzed ischemic stroke patients recorded in a prospectively maintained registry that received recanalization therapies (IV or intra-arterial fibrinolysis or endovascular embolectomy) at a university medical center from September 2002 to May 2006. The independent effect of premorbid statin use on sHT post intervention was evaluated by logistic regression, adjusting for prognostic and treatment variables known to predict increased HT risk after ischemic stroke. Results: Among 104 patients, mean age was 70 years, and 49% were men. Male sex, hypertension, statin use, low total cholesterol and low-density lipoprotein (LDL) cholesterol, current smoking, elevated glucose levels, and higher admission NIH Stroke Scale (NIHSS) score were all associated with a greater risk of sHT in univariate analysis. After adjusting for covariates, low LDL cholesterol (odds ratio [OR], 0.968 per 1-mg/dL increase; 95% CI, 0.941 to 0.995), current smoking (OR, 14.568; 95% CI, 1.590 to 133.493), and higher NIHSS score (OR, 1.265 per 1-point increase; 95% CI, 1.047 to 1.529) were independently associated with sHT risk. Conclusions: Lower admission low-density lipoprotein cholesterol level with or without statin use, current smoking, and greater stroke severity are associated with greater risk for symptomatic hemorrhagic transformation after recanalization therapy for ischemic stroke.

Dispatcher Recognition of Stroke Using the National Academy Medical Priority Dispatch System

Background and Purpose— Emergency medical dispatchers play an important role in optimizing stroke care if they are able to accurately identify calls regarding acute cerebrovascular disease. This study was undertaken to assess the diagnostic accuracy of the current national protocol guiding dispatcher questioning of 911 callers to identify stroke (QA Guide version 11.1 of the National Academy Medical Priority Dispatch System). Methods— We identified all Los Angeles Fire Department paramedic transports of patients to University of California Los Angeles Medical Center during the 12-month period from January to December 2005 in a prospectively maintained database. Dispatcher-assigned Medical Priority Dispatch System codes for each of these patient transports were abstracted from the paramedic run sheets and compared to final hospital discharge diagnosis. Results— Among 3474 transported patients, 96 (2.8%) had a final diagnosis of stroke or transient ischemic attack. Dispatchers assigned a code of potential stroke to 44.8% of patients with a final discharge diagnosis of stroke or TIA. Dispatcher identification of stroke showed a sensitivity of 0.41, specificity of 0.96, positive predictive value of 0.45, and negative predictive value of 0.95. Conclusions— Dispatcher recognition of stroke calls using the widely employed Medical Priority Dispatch System algorithm is suboptimal, with failure to identify more than half of stroke patients as likely stroke. Revisions to the current national dispatcher structured interview and symptom identification algorithm for stroke may facilitate more accurate recognition of stroke by emergency medical dispatchers.

Renal safety of CT angiography and perfusion imaging in the emergency evaluation of acute stroke.

BACKGROUND AND PURPOSE: Multimodal CT imaging with contrast-enhanced CT angiography (CTA) and CT perfusion (CTP) is increasingly being used to guide emergency management of acute stroke. However, little has been reported about the safety of intravenous contrast administration associated with these studies in the acute stroke population, including cases in which baseline creatinine values are unknown. We investigated the incidence of contrast-induced nephropathy (CIN), defined as a 25% or more increase in baseline creatinine levels within 72 hours of contrast administration and chronic kidney disease in patients receiving CTA±CTP at our regional stroke center. MATERIALS AND METHODS: We analyzed 198 patients who underwent contrast CT studies for evaluation of acute ischemic or hemorrhagic stroke at our center (2003–2007). Through retrospective chart abstraction, we analyzed serial creatinine levels (baseline to day 3) and later values (≥day 4) where available. The incidences of CIN and/or chronic kidney disease were documented. After power analysis, CIN and non-CIN groups were compared by using the unpaired t test, Wilcoxon rank sum test, or Fisher exact test. RESULTS: None of the 198 patients developed chronic kidney disease or required dialysis. Of 175 patients with serial creatinine measurements between baseline and day 3, 5 (2.9%) developed CIN. The incidence of CIN was 2% in patients who were scanned before a baseline creatinine level was available. CONCLUSION: The incidence of renal sequelae is relatively low in acute stroke patients undergoing emergent multimodal CT scanning. Prompt CTA/CTP imaging of acute stroke, if indicated, need not be delayed in those with no history of renal impairment.

Patterns and Predictors of Blood–Brain Barrier Permeability Derangements in Acute Ischemic Stroke

Background and Purpose— MRI permeability imaging is a promising approach to identify patients with acute ischemic stroke with an increased propensity for hemorrhagic transformation (HT). Permeability imaging provides direct visualization of blood–brain barrier derangements in ischemic fields. Methods— We retrospectively analyzed clinical and MRI data on patients with acute cerebral ischemia within the middle cerebral artery territory to identify the frequency, patterns, and predictors of permeability derangements and their association with HT types. Results— A total of 179 permeability scans was obtained in 127 patients (59 men; mean age, 66.8 years). Among 179 image sets (82 pre-/no treatment and 97 posttreatment), permeability derangements were present in 29 images, frequently at the basal ganglia (n=23) and rarely at the juxta-cortical area (n=6). After adjusting for covariates, diastolic pressure (OR, 1.12, per 1-mm Hg increase; 95% CI, 1.02 to 1.22) and s-glucose (OR, 1.04, per 1-mg/dL increase; 95% CI, 1.01 to 1.07) were independently associated with pretreatment permeability derangements, whereas low-density lipoprotein cholesterol (OR, 0.97, per 1-mg/dL increase; 95% CI, 0.94 to 0.99), malignant MRI profile (OR, 24.84; 95% CI, 1.50 to 412.93), and time from onset to recanalization therapy (OR, 1.47, per 1-hour increase; 95% CI, 1.10 to 1.96) were independently associated with permeability derangements after recanalization therapy. Types of HT varied among the patients with permeability derangements (no HT, 4; hemorrhagic infarct type, 12; and parenchymal hematoma, 13) and transient derangements (without subsequent HT) and normalization of derangements (in the presence of HT) on permeability images was observed in several cases. Conclusions— Permeability derangements, a dynamic process associated with ischemic stroke pathophysiology and recanalization therapy, vary in pattern and evolution toward HT. Several prognostic and therapeutic predictors for HT are independently associated with pre- and posttreatment permeability derangements.