ABSTRACT BACKGROUND AND PURPOSE Cerebral microinfarcts (CMI) are associated with intracerebral hemorrhage due to small vessel disease (SVD) in studies not including an ischemic etiologic workup. We aimed to determine their incidence and potential causes in a large ischemic stroke (IS) cohort. METHODS Consecutive patients with MRI‐confirmed IS within 72 hours of onset were enrolled. Subjects had either single high‐risk embolic source (cardioembolic or large vessel disease) or no embolic source. CMIs were classified by their relationship to the primary infarct as within or outside the same vascular territory. White matter hyperintensities (WMH) and microbleeds were markers SVD severity. Multivariable regression tested the association between CMIs and potential etiologies. RESULTS We analyzed 946 IS patients, mean age 69 ± 15 years, 46% female. We detected CMI (≤5 mm) on diffusion‐weighted imaging in 269 (28%) subjects, 190 (71%) within the vascular territory of the primary infarct. Large‐vessel atherosclerosis ( P <.001), cardioembolic source ( P <.001), higher WMH ( P = .032) and lower systolic blood pressure (SBP, P = .024) were independently associated with the presence of CMI. While SBP was associated with CMI in any location ( P <.05), WMH was only associated with CMI outside the territory of the primary infarct ( P = .033), and large vessel atherosclerosis with CMI within the primary infarct territory ( P = .004). CONCLUSIONS CMIs occurring within the vascular territory of a larger infarct are more likely embolic, but those occurring outside are probably related to SVD. Our findings suggest a role for SVD in pathogenesis of CMIs and emphasize the importance of etiologic workup to identify alternate etiologies.

BackgroundGlycogen phosphorylase is the key enzyme that breaks down glycogen to yield glucose-1-phosphate in order to restore depleted energy stores during cerebral ischaemia. We sought to determine whether plasma levels of glycogen phosphorylase BB (GPBB) isoform increased in patients with acute ischaemic stroke (AIS).MethodsWe studied plasma GPBB levels within 12 hours and again at 48±24 hours of symptom onset in 172 patients with imaging-confirmed AIS and 133 stroke-free individuals. We determined the ability of plasma GPBB to discriminate between cases and controls and examined the predictive value of plasma GPBB for 90-day functional outcome, 90-day survival and acute lesion volumes on neuroimaging.ResultsThe mean (SD) GPBB levels were higher in cases (46.3±38.6 ng/mL at first measurement and 38.6±36.5 ng/mL at second measurement) than in controls (4.1±7.6 ng/mL, p<0.01 for both). The area under the receiver operating characteristic (ROC) curve for case–control discrimination based on first GPBB measurement was 0.96 (95% CI 0.93 to 0.98). The sensitivity and specificity based on optimal operating point on the ROC curve (7.0 ng/mL) were both 93%. GPBB levels increased in 90% of patients with punctate infarcts (<1.5 mL) and in all patients admitted within the first 4.5 hours of onset. There was no correlation between GPBB concentration and either clinical outcome or acute infarct volume.ConclusionGPBB demonstrates robust response to acute ischaemia and high sensitivity for small infarcts. If confirmed in more diverse populations that also include stroke mimics, GPBB could find utility as a stand-alone marker for acute brain ischaemia.

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.

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.

Background and Purpose: The goal of etiologic ischemic stroke classification is to generate determined subtypes with discrete phenotypic, therapeutic, and prognostic characteristics. Although several new etiologic classification systems have been developed in recent years, their ability to unambiguously generate discrete subtypes is not known. We prospectively examined predictive ability of TOAST, Causative Classification of Stroke System (CCS), and ASCO (based on grade-1 definitions) for various hard stroke features in 2284 consecutive patients within the context of an NIH-funded study. Methods: Three raters blinded to each other’s assignments as well as to the study end points performed subtype assignments based on information available at discharge. The primary validation end-point was 90-day stroke recurrence. Secondary validation end-points were admission infarct volume on DWI, admission NIHSS score, and 90-day mortality. We assessed predictive ability of each system by ROC analysis and determined within-category / between-category variance by calculating F values from ANOVA for continuous variables. Results: CCS demonstrated larger area under the ROC curve (AUC, 0.71, 95%CI: 0.66-0.75) for stroke recurrence when compared to ASCO (0.66, 95%CI: 0.61-0.71, p=0.04) and TOAST (0.61, 95%CI: 0.55-0.67, p<0.01). The difference in AUC between ASCO and TOAST for recurrent stroke was borderline (p=0.052). There was no difference in AUC for 90-day mortality among the systems [0.67 (95%CI, 0.63-0.70) for CCS, 0.67 (95%CI, 0.64-0.70) for ASCO, and 0.65 (95%CI, 0.62-0.68) for TOAST]. The size of undetermined category was 33% with CCS, 40% with ASCO, and 52% with TOAST (p<0.01). CCS demonstrated larger F values for admission NIHSS (41.8) and infarct volume on DWI (12.0) than ASCO (38.1, 11.4 respectively) and TOAST (37.7, 9.5 respectively). Conclusion: This study demonstrates that etiologic stroke subtypes confer predictive information for early stroke recurrence regardless of the classification system used to identify them. Our results also indicate that CCS exhibits greater capacity to generate homogenous categories with different features and assigns a larger proportion of strokes into determined subtypes as compared to other systems.

Objective:Migraine, particularly with aura, is a risk factor for ischemic stroke. Recent data in migraine mutant mice suggest that cerebral hyperexcitability associated with migraine accelerates recruitment of ischemic penumbra into the core, resulting in faster infarct growth compared with wild type. We hypothesized that individuals with a history of migraine are more likely to exhibit increased recruitment of ischemic tissue into the infarct in acute stroke.Methods:In this retrospective case-control study, we identified participants with reliably documented migraine history, measured lesion volumes on diffusion-weighted and perfusion-weighted MRI obtained within 72 hours of symptom onset, calculated the proportion of ischemic tissue on perfusion-weighted imaging (PWI) hyperintense on diffusion-weighted imaging (DWI), and compared the proportion of patients with no-mismatch pattern defined as DWI lesion >83% of PWI lesion.Results:Migraineurs (n = 45) were younger, more often female, less likely to have vascular risk factors, and more often had cervical artery dissection, but otherwise did not differ from controls (n = 27). A significantly larger proportion of migraineurs had no-mismatch pattern, indicating that the entire perfusion defect was recruited into the infarct by the time of MRI (22% vs 4% of migraineurs and controls, respectively; p = 0.044). The difference was even more prominent in migraineurs with aura (36% vs 4%, p = 0.019). The association between migraine and no-mismatch pattern persisted after adjustment for time to MRI (p = 0.041).Conclusions:This case-control study supports the hypothesis that a history of migraine, particularly with aura, is associated with a no-mismatch pattern during acute ischemic stroke, consistent with data obtained in migraine mutant mice.

Background/Objective: Punctate infarcts (PI) are increasingly seen on DWI of patients with intracerebral hemorrhage (ICH) due to small vessel disease (SVD). We aimed to determine their incidence and potential causes in a large ischemic stroke (IS) cohort that had thorough etiologic workup. Methods: Consecutive patients with MRI-confirmed IS within 72 hours of onset were enrolled. Subjects had either a single high-risk embolic source (cardioembolic or large vessel disease) or no embolic source. PIs were classified by their relationship to the primary infarct as within or outside the same vascular territory. White matter disease burden (WMDB) and microbleed counts were obtained to be used as markers of severity of SVD. Multivariable regression models were constructed to assess the association between PIs and potential etiologies (embolism vs SVD). Results: We analyzed 946 IS patients, mean age 69 +/- 15 years, 46% female. We detected PI (≤5mm) in 269 (28%) subjects, 190 (71%) within the vascular territory of the primary infarct. Large-vessel atherosclerosis (p<0.001), cardioembolic source (p<0.001), higher WMDB (p=0.032) and lower systolic blood pressure (SBP, p=0.024) were independently associated with the presence of PI. While lower SBP was associated with PI in any location (p<0.05), WMDB was only associated with PI outside the vascular territory of the primary infarct (p=0.033); and large vessel atherosclerosis was only associated with PI within the vascular territory of the primary infarct (p=0.004). Conclusions: PIs occurring within the vascular territory of a larger infarct are more likely to have a proximal embolic source, but those occurring outside are more likely related to SVD. Their relatively high incidence and diverse etiologic associations in a cohort of IS patients emphasize the importance of research into their mechanisms.

Background: Cardioembolic (CE) stroke carries significant morbidity and mortality. Current risk stratification tools such as CHADS2 score do not include any imaging parameters and are based on clinical features, which have limitations. Left atrial (LA) enlargement and remodeling may be associated with CE risk due to predisposition for atrial arrhythmias and thrombus formation. Left atrial cross sectional area (LACSA), a novel echo measure which reflects both LA size and shape, may improve CE stroke risk assessment. Aim: This study examined the value of LACSA in predicting CE stroke risk and the improvement in risk prediction when added to CHADS2 score. Methods: Clinical and echo parameters were examined in a prospective cohort of 1275 consecutive patients with ischemic stroke. Strokes were classified using the Causative Classification of Strokes and 259 (20%) were classified as CE stroke. LACSA was calculated using the formula: π/4*largest measured LA diameter*smallest measured LA diameter where mid LA diameter was measured in the parasternal long axis, 4 chamber and 2 chamber views. Results: Patients with CE stroke had greater LACSA (8.6 ± 2.3 vs 6.4 ± 1.8 cm2/m2; p<0.001) and mean CHADS2 score (2.25 ± 1.28 vs 1.87 ± 1.40; p<0.0001) compared to non-CE stroke patients. LACSA was independently associated with CE strokes (OR 1.21; 95% CI 1.08-1.34; p=0.001) in a multivariable model adjusted for CHADS2, gender, score, BMI, atrial fibrillation, anti-platelet and anti-coagulant use, E/E’ and LVEF. The addition of LACSA to CHADS2 score improved the prediction of CE stroke (c-statistic for predicting CE stroke using CHADS2 alone was 0.59 (95% CI 0.55-0.63) vs CHADS2 and LACSA 0.78 (95% CI 0.72-0.80) (p<0.001). Conclusion: LACSA is a novel measure of LA remodeling and associated with CE stroke. LACSA, an imaging parameter, enhances the risk prediction of the CHADS2 score, a clinical measure of risk, improving risk stratification for CE stroke and impacting therapeutic strategies.

Epidemiological data indicate that migraine is an independent stroke risk factor. Recent data suggest that migraine mutations increase brain vulnerability to ischemia via excitatory mechanisms (Circulation 2012; 125:335). Migraine mutant mice developed higher number of ischemic depolarizations and accelerated infarct growth during hyperacute stroke, with worse tissue and neurological outcomes. Here, we retrospectively assessed acute stroke evolution in patients with a reliably documented migraine history. In a blinded fashion, we analyzed the lesion volume on diffusion-weighted imaging (DWI), and the volume of perfusion defect on perfusion-weighted imaging (PWI) using mean transit time (MTT), from consecutive patients during the years 2003-2012 in the Massachusetts General Hospital stroke database. DWI-PWI mismatch was calculated on spatially co-registered DWI and MTT maps, as a marker for viable tissue at risk for infarction. A total of 155 stroke patients had reliably documented presence or absence of a migraine history. Stroke patients with a history of migraine were younger and more often female, compared to stroke patients who never suffered from migraine. Migraineurs less frequently had coronary artery disease or diabetes. The frequency of posterior circulation lesions was significantly higher in migraineurs. Otherwise, groups were comparable. In migraineurs with aura, a larger proportion of the perfusion defect showed DWI changes, resulting in smaller DWI/PWI mismatches. A significantly larger proportion of migraineurs with aura showed no mismatch (i.e., DWI/PWI>0.9), indicating that the entire perfusion defect was already infarcted (Table). Our data show that a history of migraine, particularly with aura, is associated with accelerated acute infarct growth, consistent with data obtained in migraine mutant mice. [Table. Diffusion-perfusion mismatch. *p=0.011 migraine vs no migraine, † p=0.002 migraine with aura vs no migraine]

BACKGROUND: Sympathetic nervous system activation during acute ischemic stroke (AIS) can lead to a number of undesirable changes such as hyperglycemia, left ventricular stunning, and immunosuppression and thereby could potentially result in worsening of clinical and tissue outcome. We hypothesized that prior beta blocker (BB) use could be beneficial in patients with AIS by opposing increased sympathetic activity. METHODS: This was a consecutive study of patients with AIS conducted as a part of an ongoing prospective NIH-funded study (Heart-Brain Interactions Study). The relationship between BB use within 24 hours prior to stroke onset and outcome measured by modified Rankin Score (mRS) at 3 months was tested using multiple logistic regression. Infarcts including the insula and/or the surrounding opercular cortex were classified “insular”. RESULTS: There were 402 BB-users and 612 BB non-users. BB-users were older and more often had vascular risk factors such as coronary artery disease, atrial fibrillation, and congestive heart failure. Univariate analyses revealed that prior BB use was associated with decreased probability of good outcome (OR 0.72, 95% CI 0.55 - 0.93 for mRS<3). A multivariable analysis adjusting for differences between BB-users and BB non-users showed that BB use was not a predictor of either good or bad outcome (OR 1.33, 95% CI 0.90 - 1.96). However, there was a significant interaction between BB use and insular infarction (p=0.04). A second multivariable model also including the interaction term showed that prior BB use was a significant predictor of favorable outcome in patients with infarcts including the insula (OR 2.21, 95% CI 1.03 - 4.75). CONCLUSIONS: These findings suggest that BB therapy may be beneficial in selected patients with AIS whose infarcts encompass the insula.

Background: Glycogen phosphorylase-BB (GPBB) is the key enzyme that breaks down glycogen to yield glucose-1-phosphate in order to meet the emergent ATP need during cerebral ischemia. GPBB is one of the most sensitive and specific plasma markers for early detection of acute myocardial ischemia. GPBB concentration is about 100 times higher in brain than in heart. We hypothesized that plasma levels of GPBB might elevate following cerebral ischemia. Methods: We measured plasma GPBB levels in 172 patients with imaging-confirmed brain infarction at two time points (within 9 hours of symptom onset and at 48 hours). The control group consisted of 97 age-matched subjects without stroke. GPBB levels were determined blind to case/control assignment using a commercially available ELISA kit (Diagenics, Germany). Results: Baseline mean (±SD) GPBB level was 46.3 ng/ml (± 38.6 ng/ml) in cases and 4.8 ng/ml (±8.0 ng/ml) in controls (p < 0.001, Figure). GPBB levels slightly decreased from baseline to 48 hours in patients with stroke (38.7 ± 36.5 ng/ml, p = 0.02). The discriminative ability of GPBB between cases and controls as measured by the area under the Receiver Operating Characteristic (ROC) curve was high (0.95, 95% CI 0.93-0.98). GPBB level corresponding to optimal operating point on the ROC curve was 6 ng/ml. Based on the 6 ng/dl cut-off, baseline plasma GPBB showed 94% sensitivity and 90% specificity for diagnosis of ischemic stroke. Conclusion: Plasma GPBB appears to be a sensitive and specific marker for early diagnosis of brain ischemia. Its high proportional rise with respect to the discriminator value suggests that GPBB may find utility particularly in the diagnosis of mild ischemic syndromes associated with trace amounts of brain injury.

Background and Purpose— The integrity of white matter tracts connecting different parts of the brain is important for rapid compensation for the lost function from ischemic stroke. Impaired white matter reserve capacity secondary to leukoaraiosis may facilitate detection of new symptomatic ischemic events that would otherwise remain inconspicuous after an initial ischemic stroke. We sought to identify whether the extent of leukoaraiosis was a predictor of risk of early stroke recurrence. Methods— We used Cox regression analysis in consecutive patients with ischemic stroke to determine the relationship between leukoaraiosis burden and symptomatic stroke recurrence within 90 days. We graded total leukoaraiosis, periventricular leukoaraiosis, and subcortical leukoaraiosis using the Fazekas scale as mild (<2) and extensive (≥2) on fluid-attenuated inversion recovery images obtained within 72 hours of stroke onset in the hemisphere contralateral to acute stroke. Results —There were 106 recurrent events in 2378 patients. The cumulative incidence of recurrence was 5.9% at 90 days. Kaplan–Meier estimate of recurrence-free survival rate was lower in patients with extensive leukoaraiosis ( P =0.04) and extensive periventricular leukoaraiosis ( P =0.02) but not in extensive subcortical leukoaraiosis ( P =0.09). Multivariable Cox regression analysis revealed a hazard ratio of 1.50 (95% confidence interval, 1.00–2.25) for extensive leukoaraiosis, 1.67 (95% confidence interval, 1.11–2.51) for extensive periventricular leukoaraiosis, and 1.42 (95% confidence interval, 0.94–2.12) for extensive subcortical leukoaraiosis. Conclusions— The extent of leukoaraiosis independently predicts 90-day recurrent stroke risk after ischemic stroke. This suggests that leukoaraiosis may be used for risk stratification in ischemic stroke.

Background and hypothesis: Patients with diabetes mellitus (DM) are less likely to develop adverse outcomes than are those without DM in response to acute elevations in plasma glucose after stroke. We hypothesized that baseline glycosylated hemoglobin (HbA1c) level, which provides an estimate of long-term plasma glucose concentration, inversely correlated with clinical and tissue outcome in acute ischemic stroke patients presenting with hyperglycemia. Methods: Within the context of an ongoing prospective study (Heart-Brain Interactions Study), we measured plasma glucose and HbA1c levels in 1080 patients with acute ischemic stroke within 72 hours of symptom onset. We classified patients into 3 HbA1c strata based on the American Diabetes Association criteria: group-I (HbA1c <5.7%, n=439), group-II (HbA1c: 5.7 to 6.4%, n=290), group-III (known DM or HbA1c >6.4, n=351). We examined the relationship between admission blood glucose level, acute infarct volume on DWI, and unfavorable outcome (mRS≥3) at 3 months in each HbA1c stratum. Results: The probability of unfavorable outcome decreased by increasing baseline HbA1c level; the OR (95% CI) for unfavorable outcome for every 10 mg/dl increase in glucose level was 1.42 (1.25-1.62) in group-I, 1.19 (1.07-1.33) in group-II, and 1.02 (0.99-1.05) in group-III. When hyperglycemia was defined as ≥144 mg/dl, OR (95% CI) for unfavorable outcome was 6.53 (2.65-16.14) in group-I, 1.56 (0.77-3.15) in group-II, and 1.35 (0.78-2.33) in group-III. Adjusting for age and sex did not change the results. For every 10 ml elevation in plasma glucose, the mean infarct volume increased by 7.45 ml (5.04-9.85) in group-I, 4.96 ml (2.82-7.09) in group-II, and 0.73 ml (-0.24-1.70) in group-III. Conclusions: Chronic hyperglycemia appears to protect from deleterious effects of acute elevations in blood glucose after ischemic stroke. Further research is warranted examining whether baseline HbA1c concentration predicts benefit from interventions for glycemic control in acute stroke.

Objective: To investigate the relationship between acute infarct volume on diffusion-weighted imaging (DWI) and acute stress hyperglycemia (ASH) in a prospectively collected dataset. Background The published evidence on the relationship between ischemic lesion volume and ASH is conflicting. While some studies report higher infarct volumes in patients with ASH, others refute this by claiming that small infarcts such as lacunar infarcts are also associated with ASH. Small sample size, failure to use a consistent definition for ASH, inability to account for differences in timing of infarct volume and glucose measurements, and differences in infarct size determination contribute to the controversy. We sought to investigate the relationship between acute infarct volume and ASH in a prospectively collected dataset within the context of the Heart-Brain Interactions Study (HBS). Design/Methods: HBS is an ongoing study aiming to identify the neuroanatomic correlates of stroke-related cardiac injury and acute stress response. We performed blood glucose measurement within 36 hours and DWI within 72 hours of symptom onset in consecutive patients enrolled to the HBS. ASH was defined as elevated blood glucose (>144 mg/dl) in the absence of elevated Hemoglobin A1c ( Results: We identified 98 consecutive patients with ASH and 217 controls out of 1240. The median infarct volume was higher in patients than controls (11 cc vs. 4 cc, p Conclusions: The study shows that infarct volume is an independent predictor of ASH. The probability of ASH increases by increasing infarct volume. Disclosure: Dr. Helenius has nothing to disclose. Dr. Avery has nothing to disclose. Dr. Polnar has nothing to disclose. Dr. Caceres has nothing to disclose. Dr. Siket has nothing to disclose. Dr. AY has nothing to disclose.