Neutrophil-to-Lymphocyte Ratio and Response to Intravenous Thrombolysis in Patients with Acute Ischemic Stroke.

BACKGROUND AND AIMS: The Neutrophil-to-Lymphocyte Ratio (NLR) is suggested as a readily available and inexpensive biomarker to predict prognosis of acute stroke. Experience with intravenous (IV) tissue plasminogen activator (tPA) treatment is limited. METHODS: Total 142 (80 female, age: 69 ± 13 yearr) consecutive acute stroke patients treated with IV tPA were evaluated. Admission and 24th hour lymphocyte, neutrophil, and monocyte counts were measured and the NLR was calculated. RESULTS: Average NLR elevated (by 3.47 ± 6.75) significantly from admission to 24th hour (P< .001). Total 52% of patients exerted good response to IV tPA (NIHSS ≤1 or decrease in NIHSS ≥4 at end of 24 hour), while 27% showed dramatic response (decrease in NIHSS ≥8 at end of 24 hour). The patients with "thrombolysis resistance" had significantly higher 24 hour Neutrophil-to-Lymphocyte Ratio (24h NLR) (P= .001). At the end of 3rd month, 46.5% of patients had favorable (modified Rankin's score, mRS 0-2) and 32.4% had excellent (mRS 0-1) outcome. Patients without favorable/excellent outcome had significantly higher 24h NLRs. Regression analysis indicated that post-tPA, but not admission NLR, was an independent negative predictor of excellent (ß =-.216, P= .006) and favorable (ß = -.179, P= .034) outcome after adjustment for age, hypertension, and admission NIHSS. Nine patients who developed symptomatic intracerebral hemorrhage had elevated pre-tPA (7.6 ± 7.39 versus 3.33 ± 3.07, P< .001) and 24h NLR (26.2 ± 18.6 versus 5.78 ± 4.47, P< .001). Of note, receiver operating characteristics analysis failed to detect any reliable NLR threshold for absence of tPA effectiveness/dramatic response, 3rd month good/excellent outcome or any type tPA-induced hemorrhage. CONCLUSIONS: As a marker of stroke-associated acute stress response, the NLR, which increases during the first 24 hours, is an epiphenomenon of poor prognosis. However, pretreatment NLR values have no importance in predicting IV tPA response.

The utility of middle cerebral artery clot density and burden assessment by noncontrast computed tomography in acute ischemic stroke patients treated with thrombolysis.

BACKGROUND: Quantitative and qualitative evaluation of middle cerebral artery (MCA) density, together with extent of thrombi, was assessed on plain computerized tomography (CT) to delineate better the prognostic value of the hyperdense MCA sign (HMCAS) in a cohort of patients who underwent intravenous or intra-arterial thrombolysis. METHODS: Density of MCA was quantified by maximum pixel-sized measurement of Hounsfield unit (HU) in 105 patients with acute MCA proximal segment occlusion, 15 patients with vertebrobasilar circulation stroke (VBS) and 44 nonstroke control subjects. Predictive value of HMCAS, absolute HU value of within MCA, side-to-side HU ratio, and difference along with a newly introduced hyperdense MCA burden score in early dramatic recovery (EDR) and third-month favorable prognosis were determined with multivariate adjustment for age, baseline stroke severity, and thrombus length as measured on CT angiography. Receiver operator characteristics (ROC) curves were used to determine the cutoffs of quantitative indices to determine HMCAS and their prognostic significance. RESULTS: Higher HU was present in the ipsilateral MCA of the patients compared with their contralateral side and basilar tip and any MCA of VBS stroke and control subjects (area under the curve [AUC] of ROC curves was .753). Symptomatic-to-asymptomatic HU difference and ratio of MCA stroke were also significantly higher than side-to-side difference calculated in VBS stroke and control groups (AUC of ROC curves: .770 and .764, respectively). Optimal thresholds of absolute HU (44), side-to-side HU difference (2), and ratio (1.0588) showed borderline sensitivity and specificity. HMCAS and its quantitative indices were not significantly associated with EDR and favorable third-month outcome. Furthermore, there was no difference in terms of cardioembolic and atherothrombotic thrombi HU. CONCLUSIONS: Utility of the HMCAS as a prognostic marker in stroke thrombolysis is not high in the CT angiography era. Previous observation regarding its positive prognostic role can be attributed to its association with proximal location and extent of clot burden, which are detectable reliably with current CT angiography techniques. Neither quantification nor extent of increased density seems to have clinical utility for treatment decision making in MCA strokes and prediction of emboli composition and response to recanalization attempt.

Concurrent acute brain infarcts in patients with monocular visual loss.

OBJECTIVE: Embolism from a proximal source to the retinal circulation could be a sign of embolism from the same source to the hemispheric circulation. We sought to determine the frequency of acute brain infarcts on diffusion-weighted imaging (DWI) in patients with monocular visual loss of presumed ischemic origin (MVL). METHODS: We retrospectively studied 129 consecutive patients with MVL secondary to retinal ischemia. All patients underwent DWI, comprehensive ophthalmologic and neurologic examination, and diagnostic evaluations for the underlying etiology. Statistical analyses explored univariate and multivariate predictors of DWI evidence of acute brain infarcts. RESULTS: DWI revealed concurrent acute brain infarct(s) in 31 of the 129 patients (24%). The probability of positive DWI was higher in embolic versus nonembolic MVL (28 vs 8%, p = 0.04), in MVL characterized by permanent visual loss versus transient symptoms (33 vs 18%, p = 0.04), and in MVL associated with concurrent hemispheric symptoms versus isolated MVL (53 vs 20%, p < 0.01). Patients with positive DWI were more likely to harbor a major underlying etiology as compared to those with normal DWI (odds ratio, 3.7; 95% confidence interval, 1.5-9.4). INTERPRETATION: This study demonstrates that MVL does not always represent an isolated disease of the retina; approximately 1 of every 4 patients with MVL demonstrates acute brain infarcts on DWI. Because patients with concurrent brain infarcts are more likely to exhibit a cardiac or vascular source of embolism, imaging evidence of brain injury in patients with MVL may be a useful marker to guide the timing and extent of diagnostic examinations.

Association of Stroke Lesion Pattern and White Matter Hyperintensity Burden With Stroke Severity and Outcome.

BACKGROUND AND OBJECTIVES: To examine whether high white matter hyperintensity (WMH) burden is associated with greater stroke severity and worse functional outcomes in lesion pattern-specific ways. METHODS: MR neuroimaging and NIH Stroke Scale data at index stroke and the modified Rankin Scale (mRS) score at 3-6 months after stroke were obtained from the MRI-Genetics Interface Exploration study of patients with acute ischemic stroke (AIS). Individual WMH volume was automatically derived from fluid-attenuated inversion recovery images. Stroke lesions were automatically segmented from diffusion-weighted imaging (DWI) images, parcellated into atlas-defined brain regions and further condensed to 10 lesion patterns via machine learning-based dimensionality reduction. Stroke lesion effects on AIS severity and unfavorable outcomes (mRS score >2) were modeled within purpose-built Bayesian linear and logistic regression frameworks. Interaction effects between stroke lesions and a high vs low WMH burden were integrated via hierarchical model structures. Models were adjusted for age, age2, sex, total DWI lesion and WMH volumes, and comorbidities. Data were split into derivation and validation cohorts. RESULTS: A total of 928 patients with AIS contributed to acute stroke severity analyses (age: 64.8 [14.5] years, 40% women) and 698 patients to long-term functional outcome analyses (age: 65.9 [14.7] years, 41% women). Stroke severity was mainly explained by lesions focused on bilateral subcortical and left hemispherically pronounced cortical regions across patients with both a high and low WMH burden. Lesions centered on left-hemispheric insular, opercular, and inferior frontal regions and lesions affecting right-hemispheric temporoparietal regions had more pronounced effects on stroke severity in case of high compared with low WMH burden. Unfavorable outcomes were predominantly explained by lesions in bilateral subcortical regions. In difference to the lesion location-specific WMH effects on stroke severity, higher WMH burden increased the odds of unfavorable outcomes independent of lesion location. DISCUSSION: Higher WMH burden may be associated with an increased stroke severity in case of stroke lesions involving left-hemispheric insular, opercular, and inferior frontal regions (potentially linked to language functions) and right-hemispheric temporoparietal regions (potentially linked to attention). Our findings suggest that patients with specific constellations of WMH burden and lesion locations may have greater benefits from acute recanalization treatments. Future clinical studies are warranted to systematically assess this assumption and guide more tailored treatment decisions.

Prediction of early stroke risk in transient symptoms with infarction: relevance to the new tissue-based definition.

BACKGROUND AND PURPOSE: The risk of stroke shortly after transient ischemic attack with infarction on diffusion-weighted images, also known as transient symptoms with infarction (TSI), is substantially higher than is the risk after imaging-normal transient ischemic attack. We sought to assess the utility of a Web-based recurrence risk estimator (RRE; http://www.nmr.mgh.harvard.edu/RRE/) originally developed for use in patients with ischemic stroke for predicting 7-day risk of stroke in patients with TSI. METHODS: We calculated RRE and ABCD² scores in a retrospective series of 257 consecutive patients with TSI diagnosed by diffusion-weighted images within 24 hours of symptom onset. We defined subsequent stroke as clinical deterioration associated with new infarction spatially distinct from the index lesion. We assessed the predictive performance of each model by computing the area under receiver-operating characteristics curve. RESULTS: Over 7-day follow-up, 16 patients developed a recurrent stroke (6.2%). The sensitivity and specificity of an RRE score of ≥ 2 for predicting 7-day stroke risk were 87% and 73%, respectively. The area under the receiver-operating characteristics curve was 0.85 (95% CI, 0.78-0.92) for RRE and 0.57 (95% CI, 0.45-0.69) for ABCD² score (z-test; P<0.001). CONCLUSIONS: The RRE score seems to predict 7-day risk of stroke after a TSI. If further validated in larger data sets, the RRE score could be useful in identifying high-risk patients with TSI who may benefit from early intervention with targeted stroke prevention strategies.

Clinical challenges associated with the endovascular treatment of acute stroke in a patient with infective endocarditis.

Although stroke is common in infective endocarditis (IE), only 26 cases of thrombectomy have been reported to date for IE-related acute stroke. We report a 40-year-old man who presented with left middle cerebral artery occlusion of unknown cause. Multiple attempts of mechanical aspiration thrombectomy and stentrievers failed to recanalize the artery. Effective revascularization was eventually achieved by placing a self-expanding intracranial stent. Post-procedurally the patient was diagnosed with IE with mitral valve insufficiency, mandating emergent valvular replacement while the patient was still on tirofiban infusion. On follow-up, the patient had a modified Rankin's score of 0, had no recurrent stroke, and the intracranial stent remained patent yet stenosed. Based on the use of a self-expanding intracranial stent in the setting of IE, we discuss the consequences of the fibrotic and inflammatory content of the embolus and the associated high risk of intracranial hemorrhage which complicates clinical decision making.

Clinical- and imaging-based prediction of stroke risk after transient ischemic attack: the CIP model.

BACKGROUND AND PURPOSE: Predictive instruments based on clinical features for early stroke risk after transient ischemic attack suffer from limited specificity. We sought to combine imaging and clinical features to improve predictions for 7-day stroke risk after transient ischemic attack. METHODS: We studied 601 consecutive patients with transient ischemic attack who had MRI within 24 hours of symptom onset. A logistic regression model was developed using stroke within 7 days as the response criterion and diffusion-weighted imaging findings and dichotomized ABCD(2) score (ABCD(2) >/=4) as covariates. RESULTS: Subsequent stroke occurred in 25 patients (5.2%). Dichotomized ABCD(2) score and acute infarct on diffusion-weighted imaging were each independent predictors of stroke risk. The 7-day risk was 0.0% with no predictor, 2.0% with ABCD(2) score >/=4 alone, 4.9% with acute infarct on diffusion-weighted imaging alone, and 14.9% with both predictors (an automated calculator is available at http://cip.martinos.org). Adding imaging increased the area under the receiver operating characteristic curve from 0.66 (95% CI, 0.57 to 0.76) using the ABCD(2) score to 0.81 (95% CI, 0.74 to 0.88; P=0.003). The sensitivity of 80% on the receiver operating characteristic curve corresponded to a specificity of 73% for the CIP model and 47% for the ABCD(2) score. CONCLUSIONS: Combining acute imaging findings with clinical transient ischemic attack features causes a dramatic boost in the accuracy of predictions with clinical features alone for early risk of stroke after transient ischemic attack. If validated in relevant clinical settings, risk stratification by the CIP model may assist in early implementation of therapeutic measures and effective use of hospital resources.

Middle cerebral artery infarcts encompassing the insula are more prone to growth.

BACKGROUND AND PURPOSE: Based on previous observations that infarcts encompassing the insula were linked to unfavorable clinical outcome, we hypothesized that insular damage was directly associated with worsened infarction in ischemic but potentially viable neighboring brain tissue. METHODS: Using acute diffusion- and perfusion-weighted MRI within the first 12 hours of symptom onset and a follow-up MRI on day 5 or later, we calculated the percentage of mismatch lost (PML) in 61 consecutive patients with ischemic stroke within the middle cerebral artery territory. PML denoted the percentage of mismatch tissue between diffusion-weighted imaging and mean transit time maps that eventually underwent infarction. We explored the relationship between PML and insular location using a regression model. RESULTS: The median PML was 17.7% (interquartile range, 3.5% to 54.2%) in insular and 2.5% (0.0% to 12.7%) in noninsular infarcts (P<0.01). The PML correlated with the volume of abnormal regions on diffusion-weighted imaging (P<0.01), mean transit time (P<0.01), cerebral blood flow maps (P<0.01), and cerebral blood volume maps (P<0.01). A linear regression model with PML as response and with acute MRI volumes, age, and the site of vascular occlusion as covariates showed that insular involvement was an independent predictor of PML (P=0.01). The regression model predicted an approximately 3.2-fold increase in PML with insular involvement. CONCLUSIONS: Infarction of the insula is associated with increased conversion of ischemic but potentially viable neighboring tissues into infarction. The unfavorable tissue outcome in insular infarcts may not be a mere bystander effect from proximal middle cerebral artery occlusions.

Severity of leukoaraiosis and susceptibility to infarct growth in acute stroke.

BACKGROUND AND PURPOSE: Leukoaraiosis (LA) is associated with structural and functional vascular changes that may compromise tissue perfusion at the microvascular level. We hypothesized that the volume of LA correlated with the proportion of initially ischemic but eventually infarcted tissue in acute human stroke. METHODS: We studied 61 consecutive patients with diffusion-weighted imaging-mean transit time mismatch. All patients were scanned twice within 12 hours of symptom onset and between days 4 and 30. We explored the relationship between the volume of white matter regions with LA on acute images and the proportion of diffusion-weighted imaging-mean transit time mismatch tissue that progressed to infarction (percentage mismatch lost). RESULTS: Bivariate analyses showed a statistically significant correlation between percentage mismatch lost and LA volume (r=0.33, P<0.01). A linear regression model with percentage mismatch lost as response and LA volume, acute diffusion-weighted imaging and mean transit time volumes, age, admission blood glucose level, admission mean arterial blood pressure, etiologic stroke subtype, time to acute MRI, and time between acute and follow-up imaging as covariates revealed that LA volume was an independent predictor of infarct growth (P=0.04). The adjusted percentage mismatch lost in the highest quartile of LA volume was 1.9-fold (95% CI: 1.2 to 3.1) greater than the percentage mismatch lost in the lowest quartile. CONCLUSIONS: LA volume at the time of acute ischemic stroke is a predictor infarct growth. Because LA is associated with factors that modulate tissue perfusion as well as tissue capacity for handling of ischemia, LA volume appears to be a composite predictive marker for the fate of acutely ischemic tissue.

Interexaminer difference in infarct volume measurements on MRI: a source of variance in stroke research.

BACKGROUND AND PURPOSE: The measurement of ischemic lesion volume on diffusion- (DWI) and perfusion-weighted MRI (PWI) is examiner dependent. We sought to quantify the variance imposed by measurement error in DWI and PWI lesion volume measurements in ischemic stroke. METHODS: Fifty-eight consecutive patients with DWI and PWI within 12 hours of symptom onset and follow-up MRI on >or= day-5 were studied. Two radiologists blinded to each other measured lesion volumes by manual outlining on each image. Interexaminer reliability was evaluated by intraclass correlation coefficients (ICC) and relative paired difference or RPD (ratio of difference between 2 measurements to their mean). The ratio of between-examiner variability to between-subject variability (variance ratio) was calculated for each imaging parameter. RESULTS: The correlation (ICC) between examiners ranged from 0.93 to 0.99. The median RPD was 10.0% for DWI, 14.1% for mean transit time, 18.9% for cerebral blood flow, 21.0% for cerebral blood volume, 16.8% for DWI/MTT mismatch, and 6.3% for chronic T2-weighted images. There was negative correlation between RPD and lesion volume in all but chronic T2-weighted images. The variance ratio ranged between 0.02 and 0.10. CONCLUSIONS: Despite high correlation between volume measurements of abnormal regions on DWI and PWI by different examiners, substantial differences in individual measurements can still occur. The magnitude of variance from measurement error is primarily determined by the type of imaging and lesion volume. Minimizing this source of variance will better enable imaging to deliver on its promise of smaller sample size.

Frontal Intermittent Rhythmic Delta Activity (FIRDA) in the Neurological Intensive Care: Prevalence, Determinants, and Clinical Significance.

INTRODUCTION: Frontal intermittent rhythmic delta activity (FIRDA), a transient rhythmic slow wave pattern over the anterior EEG leads, has been reported in a wide variety of cerebral lesions and different metabolic disturbances. Few authors have analyzed the frequency and clinical significance of FIRDA in the critical care setting. We aimed to better understand these issues in our intensive care cohort and if possible, try to delineate its underlying mechanisms. METHODS: Video-EEG reports of consecutive adult patients in the neurological intensive care unit (NICU) since 2009 were retrospectively reviewed to identify cases with FIRDA. Demographic, clinical, and laboratory data were obtained from EEG reports and patient charts. Age- and sex-matched patients with acute stroke, hospitalized in NICU and no FIRDA on video-EEG monitoring served as the control group. RESULTS: Among 162 patients who underwent video-EEG monitoring, FIRDA was documented in 17%. Female prevalence was 50% and age ranged from 23 to 82 years. Twenty-three (82%) of patients with FIRDA had a diagnosis of stroke. Comparison of demographic characteristics, EEG findings, metabolic disturbances and prognoses revealed no differences between stroke cases with and without FIRDA, except for higher frequency of acute and chronic isolated posterior circulation infarcts in patients with FIRDA. CONCLUSION: FIRDA is more commonly encountered in the neurocritical care setting as compared with outpatient EEG clinics. Our findings in stroke patients indicate that involved vascular territories may be related to the generation of FIRDA.

A computerized algorithm for etiologic classification of ischemic stroke: the Causative Classification of Stroke System.

BACKGROUND AND PURPOSE: The SSS-TOAST is an evidence-based classification algorithm for acute ischemic stroke designed to determine the most likely etiology in the presence of multiple competing mechanisms. In this article, we present an automated version of the SSS-TOAST, the Causative Classification System (CCS), to facilitate its utility in multicenter settings. METHODS: The CCS is a web-based system that consists of questionnaire-style classification scheme for ischemic stroke (http://ccs.martinos.org). Data entry is provided via checkboxes indicating results of clinical and diagnostic evaluations. The automated algorithm reports the stroke subtype and a description of the classification rationale. We evaluated the reliability of the system via assessment of 50 consecutive patients with ischemic stroke by 5 neurologists from 4 academic stroke centers. RESULTS: The kappa value for inter-examiner agreement was 0.86 (95% CI, 0.81 to 0.91) for the 5-item CCS (large artery atherosclerosis, cardio-aortic embolism, small artery occlusion, other causes, and undetermined causes), 0.85 (95% CI, 0.80 to 0.89) with the undetermined group broken into cryptogenic embolism, other cryptogenic, incomplete evaluation, and unclassified groups (8-item CCS), and 0.80 (95% CI, 0.76 to 0.83) for a 16-item breakdown in which diagnoses were stratified by the level of confidence. The intra-examiner reliability was 0.90 (0.75-1.00) for 5-item, 0.87 (0.73-1.00) for 8-item, and 0.86 (0.75-0.97) for 16-item CCS subtypes. CONCLUSIONS: The web-based CCS allows rapid analysis of patient data with excellent intra- and inter-examiner reliability, suggesting a potential utility in improving the fidelity of stroke classification in multicenter trials or research databases in which accurate subtyping is critical.

Assessment of the Predictive Validity of Etiologic Stroke Classification.

Importance: The ability of present-day etiologic stroke classification systems to generate subtypes with discrete stroke characteristics is not known. Objective: To test the hypothesis that etiologic stroke subtyping identifies different disease processes that can be recognized through their different clinical courses. Design, Setting, and Participants: We performed a head-to-head evaluation of the ability of the Causative Classification of Stroke (CCS), Trial of Org 10172 in Acute Stroke Treatment (TOAST), and ASCO (A for atherosclerosis, S for small-vessel disease, C for cardiac source, and O for other cause) classification systems to generate etiologic subtypes with different clinical, imaging, and prognostic characteristics in 1816 patients with ischemic stroke. This study included 2 cohorts recruited at separate periods; the first cohort was recruited between April 2003 and June 2006 and the second between June 2009 and December 2011. Data analysis was performed between June 2014 and May 2016. Main Outcomes and Measures: Separate teams of stroke-trained neurologists performed CCS, TOAST, and ASCO classifications based on information available at the time of hospital discharge. We assessed the association between etiologic subtypes and stroke characteristics by computing receiver operating characteristic curves for binary variables (90-day stroke recurrence and 90-day mortality) and by calculating the ratio of between-category to within-category variability from the analysis of variance for continuous variables (admission National Institutes of Health Stroke Scale score and acute infarct volume). Results: Among the 1816 patients included, the median age was 70 years (interquartile range, 58-80 years) (830 women [46%]). The classification systems differed in their ability to assign stroke etiologies into known subtypes; the size of the undetermined category was 33% by CCS, 53% by TOAST, and 42% by ASCO (P < .001 for all binary comparisons). All systems provided significant discrimination for the validation variables tested. For the primary validation variable (90-day recurrence), the area under the receiver operating characteristic curve was 0.71 (95% CI, 0.66-0.75) for CCS, 0.61 (95% CI, 0.56-0.67) for TOAST, and 0.66 (95% CI, 0.60-0.71) for ASCO (P = .01 for CCS vs ASCO; P < .001 for CCS vs TOAST; P = .13 for ASCO vs TOAST). The classification systems exhibited similar discrimination for 90-day mortality. For admission National Institutes of Health Stroke Scale score and acute infarct volume, CCS generated more distinct subtypes with higher between-category to within-category variability than TOAST and ASCO. Conclusions and Relevance: Our findings suggest that the major etiologic stroke subtypes are distinct categories with different stroke characteristics irrespective of the classification system used to identify them. We further show that CCS generates discrete etiologic categories with more diverse clinical, imaging, and prognostic characteristics than either TOAST or ASCO.

Prediction of Early Recurrence After Acute Ischemic Stroke.

IMPORTANCE: Approximately half of recurrent strokes occur within days and weeks of an ischemic stroke. It is imperative to identify patients at imminent risk of recurrent stroke because recurrent events lead to prolonged hospitalization, worsened functional outcome, and increased mortality. OBJECTIVE: To test the validity of a prognostic score that was exclusively developed to predict early risk of stroke recurrence in a multicenter setting. DESIGN, SETTING, AND PARTICIPANTS: This hospital-based cohort study examined patients with and without magnetic resonance imaging-confirmed recurrent stroke within 90 days after an ischemic stroke. The study was performed at 3 teaching hospitals in the United States, Brazil, and South Korea and comprised adult patients admitted within 72 hours of symptom onset with a magnetic resonance imaging-confirmed diagnosis of acute ischemic stroke. Recruitment to the US cohort was performed from June 1, 2009, through April 30, 2011. Recruitment to the Korean and Brazilian cohorts was performed from January 1, 2007, through December 31, 2011. Data analysis was performed from June 1, 2013, to December 31, 2014. MAIN OUTCOMES AND MEASURES: The primary outcome was recurrent ischemic stroke as defined by a clinical incident that was clearly attributable to a new area of brain infarction occurring within the 90 days of index infarction. An investigator who was masked to the patient's recurrence status calculated the Recurrence Risk Estimator (RRE) score for each patient based on information available after initial line of testing in the emergency department. We assessed the predictive performance of the RRE by computing the area under the receiver operating characteristic curve. RESULTS: The study included 1468 consecutive patients with 59 recurrent ischemic stroke events. The median age of the patients was 69 (interquartile range, 58-79) years, and 633 (43.1%) were female. The cumulative 90-day recurrence rate was 4.2% (95% CI, 3.2%-5.2%). The mean RRE score was 2.2 (95% CI, 1.9-2.5) in patients with recurrence and 1.0 (95% CI, 1.0-1.1) in patients without. The risk of recurrence increased with a higher RRE score (log-rank test, P < .001). The area under the receiver operating characteristic curve for discrimination was 0.76 (95% CI, 0.70-0.82). The RRE identified 710 patients (48.4%) in the study population as high risk (>10%) or low risk (<1%). The sensitivity and specificity were 38% and 93% for identifying low-risk subsets and 41% and 90% for identifying high-risk subsets, respectively. CONCLUSIONS AND RELEVANCE: This study confirms the validity of the RRE score in a multicenter cohort of patients with diverse characteristics. Our findings suggest that the RRE could be useful in identifying high- and low-risk patients for targeted stroke prevention.

Transorbital Ultrasonographic Measurement of Optic Nerve Sheath Diameter in Brain Death.

BACKGROUND: Ultrasonographic measurement of optic nerve sheath diameter (ONSD) can successfully be used to estimate intracranial pressure (ICP) elevation. Its utility in corroboration of brain death (BD) was herein studied. METHODS: ONSD was measured in 29 subjects with BD; in 19 comatose patients (with raised ICP in 11), 20 patients with various neurological diseases, and 40 healthy control subjects. The distance between the inner and outer edges of the echolucent lines around hyperechoic area surrounding the optic nerve (ON) was identified as ONSD external (ONSDe) and ONSD internal (ONSDi). RESULTS: Compared to patients with neurological diseases (5.75 ± .79 mm) or healthy controls (5.98 ± .63 mm), ONSDe was significantly higher in comatose patients (7.61 ± .97 and 6.71 ± 1.07 mm in those with and without raised ICP) and BD subjects (8.34 ± .66 mm). ONSDi showed similar trends across the groups: 6.09 ± .71 mm in BD; 5.89 ± .37 mm in comatose control with elevated ICP; 5.16 ± .49 mm in comatose control with normal ICP; 4.36 ± .68 mm in neurological control; 4.69 ± .67 mm in healthy control. The accuracy of ONSDe measurements in differentiating patients with ICP elevation (n = 40) was .965 as determined by area under the curve (AUC) of receiver-operator characteristics curves. Similarly, accuracy in discrimination of BD was .952. However, ONSDe showed limited yield to identify BD cases among comatose patients with Glasgow coma scale score of 3, where accuracy was .803 (95% CI: .709-.816) and decreased further to .722 (95% CI: .610-.816) when analyses were restricted to comatose patients with ICP elevation. AUC values for ONSDi was similar or lower. CONCLUSION: ONSD is significantly greater in subjects with BD. However, quantification of ONSD cannot discriminate BD subjects from comatose ones with raised ICP with 100% certainty.

Hyperhomocysteinemia is associated with the presence of left atrial thrombus in stroke patients with nonvalvular atrial fibrillation.

BACKGROUND AND PURPOSE: Blood stasis is the fundamental mechanism leading to thrombus formation in the venous system. Homocysteine also poses a significant risk for venous thrombosis through its endothelial toxic and prothrombotic properties. In the present study, we hypothesized that high homocysteine might be associated with thrombus formation in another stasis-related condition, atrial fibrillation. METHODS: Forty-two consecutive patients with ischemic stroke caused by nonvalvular atrial fibrillation and admitted within the first day of symptom onset were included. Total fasting plasma homocysteine, serum folic acid, and vitamin B12 levels were measured. All patients were evaluated by transesophageal echocardiography for the presence of a left atrial (LA) thrombus. Homocysteine and vitamin levels were compared between groups with or without LA thrombus. RESULTS: Transesophageal echocardiography revealed LA thrombus in 20 patients. Mean homocysteine levels were significantly higher in patients with LA thrombus (20.75 versus 13.34 micromol/L, P<0.001). Multivariate logistic regression analysis showed that the effect of high homocysteine was independent of other clinical or echocardiographic variables known to increase LA thrombus (P=0.017). There was no difference in vitamin B12 levels between groups (P=0.118), whereas the mean folic acid level was significantly lower in patients with LA thrombus (P=0.004). CONCLUSIONS: High plasma homocysteine conveys an independent risk for LA thrombus formation in patients with stroke caused by nonvalvular atrial fibrillation. This finding further supports the thrombogenic role of high homocysteine in conditions associated with blood stasis.

Lower hemoglobin correlates with larger stroke volumes in acute ischemic stroke.

BACKGROUND: Hemoglobin tetramers are the major oxygen-carrying molecules within the blood. We hypothesized that a lower hemoglobin level and its reduced oxygen-carrying capacity would associate with larger infarction in acute ischemic stroke patients. METHODS: We studied 135 consecutive patients with acute ischemic stroke and perfusion brain MRI. We explored the association of admission hemoglobin with initial infarct volumes on acute images and the volume of infarct expansion on follow-up images. Multivariable linear regression was performed to analyze the independent effect of hemoglobin on imaging outcomes. RESULTS: Bivariate analyses showed a significant inverse correlation between hemoglobin and initial volume in diffusion-weighted imaging (r = -0.20, p = 0.02) and absolute infarct growth (r = -0.20, p = 0.02). Multivariable linear regression modeling revealed that hemoglobin remained independently predictive of larger infarct volumes acutely (p < 0.005) and with greater infarct expansion (p < 0.01) after adjusting for known covariates. CONCLUSIONS: Hemoglobin level at the time of acute ischemic stroke associates with larger infarcts and increased infarct growth. Clarification of the mechanism of this effect may yield novel insights for therapy.