Prior Infarction Research Articles

Abstract 24: Predictors of Occult Atrial Fibrillation in Cryptogenic Stroke

Background and Purpose: Prolonged cardiac monitoring may identify paroxysmal atrial fibrillation (AF) in patients with cryptogenic stroke. We aimed to identify clinical, echocardiographic, and neuroimaging features which may increase the efficiency of detecting AF on cardiac monitoring. Methods: We studied a retrospective cohort of 227 subjects with cryptogenic ischemic stroke referred for 28 day mobile cardiac outpatient telemetry (MCOT). Patients with large artery disease or high risk sources of cardioembolism were excluded. We reviewed medical records, brain images, and echocardiograms, blinded to MCOT results. Acute and/or chronic infarctions were characterized by size, location, and as cortical, subcortical, or both; wedge-shaped; lacunar; borderzone; and/or multiple territories. Cardiac features included left atrial (LA) size, ejection fraction, aortic arch atheroma, and PFO. Variables were tested in univariate analyses and further incorporated in a multivariate logistic regression model to determine independent predictors of detecting AF. Results: The cohort age was 62.9±2.9 years, 42% were men, and 53% were white. Median CHADS was 3 and CHADS2Vasc was 5. Infarcts were >1.5 cm in 62% of subjects, predominantly cortical in 47%, subcortical in 39%. Only 9% were single, deep, and <1.5 cm. LA size was 3.6±0.7 cm and ejection fraction was 61±9%. MCOT detected AF in 30 (13%) patients. In multivariate analysis, AF was only associated with age>60 (OR 3.6 [1.2-10.4], p=0.02) and prior (chronic) cortical or cerebellar infarction (OR 3.3 [1.3-8.6], p=0.013) (C-statistic 0.72). There was no association with any other clinical, echocardiographic, or radiographic parameter. AF was detected in 32% of patients with age >60 and the presence of prior cortical or cerebellar infarction, compared to 4% with neither of these factors. Conclusion: Atrial fibrillation is detected on MCOT in a substantial minority of cryptogenic stroke patients. Age>60 and the presence of prior cortical or cerebellar strokes are predictive of detecting AF in these patients. Other brain and cardiac characteristics were not found to be helpful. These data may aid in the selection of patients for prolonged arrhythmia monitoring.

Abstract T P43: Detection of Advanced Leukoaraiosis Does Not Augment Imaging-Enhanced Prediction of Early Stroke Risk in Transient Ischemic Attack

Background: The risk of stroke following transient ischemic attack (TIA) is high in patients with evidence of transient symptoms with infarction (TSI) on CT or diffusion-weighted imaging (DWI). The extent to which leukoaraiosis augments imaging-based risk prediction is unresolved. We sought to determine whether the presence of advanced leukoaraiosis improves the predictive performance of early CT and MR-based neuroimaging modalities in patients diagnosed with clinical TIA. Methods: We retrospectively identified 37 cases of 30-day recurrent stroke that had MRI performed within 1 day of presentation, and compared to 43 patients without recurrence from a larger cohort of 1250 patients admitted to the hospital from a single emergency department with suspected TIA between 1/1/2000 and 7/16/2011. In all subjects (n=80), CT and MR (DWI and T2Flair)images were reviewed by a physician reader blinded to outcome and graded for the presence of abnormalities such as acute infarction, prior infarction, and advanced leukoaraiosis as defined by a Van Sweiten scale of 2 in either the anterior or posterior regions. We assessed the predictive performance of DWI alone, CT for infarction, CT for any abnormality and MRI for any abnormality by computing the area under the receiver-operating characteristics curve. Results: The sensitivity of CT increased from 14% to 71% and MR from 68% to 93% in predicting 30-day stroke recurrence upon inclusion of acute or old infarction or advanced leukoaraiosis. Specificity decreased from 100% to 44% and 67% to 30% respectively. The area under the receiver-operating characteristic curve was 0.57 for CT for infarction alone and 0.58 for CT including leukoaraiosis; 0.68 for DWI alone and 0.61 for DWI or T2Flair evidence of old infarction or advanced leukoaraiosis. Conclusions: The addition of advanced leukoaraiosis does not appear to add to the predictive ability of CT or MRI-based neuroimaging in the early risk stratification of patients with TIA.

Abstract T P79: Molecular Disorganization of Axons Adjacent to Subcortical Stroke in Hereditary Endotheliopathy With Retinopathy, Nephropathy, and Stroke; an Imaging to Molecular Neuropathology Correlation

White matter stroke secondary to microvascular injury is common yet the molecular changes that accompany ischemic damage to white matter are poorly understood. MRI imaging studies suggest that abnormalities exist within the white matter adjacent to lacunar infarcts and this may lead to infarct progression through a functional disruption of adjacent axons. Hereditary subcortical stroke syndromes provide a unique opportunity to study the molecular mechanisms of cerebral microvascular disease and its effect on white matter. Here, we examined two autopsy cases of hereditary endotheliopathy with retinopathy, nephropathy and stroke (HERNS) syndrome with severe microvascular ischemic disease in the cerebral white matter to determine the molecular organization of myelin and axons within the cerebral white matter adjacent to lacunar infarcts in these patients. MRI imaging was used to identify regions of prior lacunar infarction or FLAIR hyperintensity. Serial paraffin-embedded sections within these regions were immunolabeled for markers of nodes of Ranvier and paranodes as well as neurofilaments and myelin basic protein and compared to normal-appearing white matter and non-diseased controls. Compared to controls, HERNS cases demonstrate lengthening of paranodes and disrupted nodal staining patterns consistent with a loss of normal axon-oligodendrocyte molecular interactions. These abnormalities of axonal microdomains are present beyond the region of infarction suggested by MRI and H&E sections and occur in areas of FLAIR hyperintensity without frank lacunar infarction. These results indicate there is a peri-infarct in white matter stroke marked by molecular disruption of axons surrounding the infarct that may serve as a new therapeutic target for this currently untreatable form of ischemic stroke.

Abstract W P151: Aging is Associated With Progressive Insufficiency of Circle of Willis Collaterals in Humans

Introduction: Increasing age is the single largest non-modifiable risk factor for ischemic stroke. Recent studies have shown that increasing age is associated with inadequacy of leptomeningeal collaterals, and aging has been shown to cause a progressive decline in the number and diameter of collateral vessels in experimental mice, resulting in an increased collateral resistance and an enhanced stroke severity. Hypothesis: Aging leads to progressive loss of Circle of Willis collateral vessels in humans. Method: We studied a retrospective, consecutive series of 167 women and 112 men undergoing cerebral angiography for any reason. A blinded investigator scored the Circle of Willis collaterals for each angiogram using a scoring system of 0 - 2 for each collateral (0 = absent, 1 = hypo-plastic, 2 = robust) for a total score of 0 - 14. Collaterals scored included the bilateral A1 segments of the anterior cerebral arteries, bilateral P1 segments of the posterior cerebral arteries, bilateral posterior communicating arteries, and the anterior communicating artery. We compared the number of collaterals based on age, gender, and race as well as history of prior infarct, aneurysm, smoking, hypertension, diabetes, and obesity. Results: Females had significantly more collaterals than men (p = 0.04) . The average collateral score for males and females was 10.77 and 11.14, respectively. Patients younger than 60 years of age had a significantly higher number of collaterals (average collateral score, 11.54) compared with patients older than 60 (average collateral score, 10.47; p = 1.59 x 10 -9 ). Females exhibited a greater loss of collaterals with advancing age (p = 3.53 x 10 -5 ) than men (p = 0.00016). Data was subjected to the Dunn-Bonferroni corrected t-test for preplanned comparisons or the Student t-test. Conclusion: Based on our study, patients younger than 60 years are significantly more likely to have an angiographically-complete Circle of Willis. The underlying mechanism for this effect in humans is uncertain and the subject of a future study.

Low Pre-Existing Gray Matter Volume in the Medial Temporal Lobe and White Matter Lesions Are Associated with Postoperative Cognitive Dysfunction after Cardiac Surgery

ObjectivesPostoperative cognitive dysfunction (POCD) is recognized as a complication in the elderly after cardiac surgery. Imaging of the brain provides evidence of neurodegeneration in elderly patients; however, abnormalities in brain structure and their relation to POCD are uncertain. This pilot study investigated whether loss of gray matter in the bilateral medial temporal lobe (MTL), seen in preoperative MRI, was associated with POCD.MethodsData were collected prospectively on 28 elderly patients scheduled for elective cardiac surgery. MRI of the brains of all patients were assessed for prior cerebral infarctions, and carotid and intracranial arterial stenosis. Patients also completed six neuropsychological tests of memory, attention and executive function before and after surgery. POCD was defined as an individual decrease in more than two tests of at least 1 standard deviation from the group baseline mean for that test. The degree of gray matter loss in the MTL of each patient was calculated using voxel-based morphometry with three-dimensional, T1-weighted MRI. This represented the degree of gray matter change as a Z score.ResultsPostoperative cognitive dysfunction was identified in 8 of the 28 patients (29%). Patients with POCD had significantly more white matter lesions on MRI, and greater loss of gray matter in the bilateral MTL (average Z score 2.0±0.9) than patients without POCD. An analysis by stepwise logistic regression identified gray matter loss in the MTL and cerebral infarctions on MRI as independent predictors of POCD.ConclusionsThese preliminary findings suggested that reduced gray matter in the bilateral MTL and white matter lesions existed in brains of elderly cardiac surgery patients who experienced POCD. Additional studies with larger sample sizes are needed to confirm these findings.

Incidence and Outcome of Pediatric Patients With Intracranial Hemorrhage While Supported on Ventricular Assist Devices

Pediatric patients supported on ventricular assist devices (VADs) require systemic anticoagulation and are at risk for intracranial hemorrhage (ICH). Little is known about the incidence or outcomes of pediatric patients with ICH while supported on a VAD. A retrospective chart review of all patients receiving VAD support was completed. Patients diagnosed with ICH while supported on a VAD were identified. Significant factors prior to diagnosis of ICH, medical/surgical treatment of ICH, and patient outcomes were assessed. Five of 30 (17%) patients supported on a VAD from January 2000 to November 2012 were diagnosed with an ICH. Four patients had an identified cerebral thromboembolic injury prior to the ICH. Four patients required interruption in their anticoagulation regimen due to other bleeding concerns prior to ICH. Neurosurgical intervention consisted of evacuation of hemorrhage in one, whereas two others required management of hydrocephalus with external ventricular drainage. Three of the five patients died on VAD support. Two deaths were directly related to ICH, whereas the third was unrelated. Two patients were successfully transplanted; one remains with a significant neurological impairment, and the other has recovered with minimal residual impairment following neurosurgical evacuation of a large subdural hematoma. ICH is a devastating complication of VAD support. Prior ischemic infarcts and interruptions to anticoagulation may put a patient at risk for ICH. Prompt neurosurgical evaluation/intervention can result in positive outcomes.

Epicardial Ablation of Ventricular Tachycardia in Ischemic Heart Disease

Epicardial approaches have increased ablation success in nonischemic cardiomyopathy, but the use for postinfarction ventricular tachycardias (VT) is less clear. We report the findings for epicardial VT ablation in postinfarct patients. Records of 444 consecutive patients with VT because of prior infarction referred for 600 catheter ablation procedures were reviewed. Epicardial procedures were performed in the electrophysiology laboratory in 56 (13%) patients using percutaneous (43 patients) or surgical (13 patients) epicardial access. In 7 patients, epicardial ablation was performed surgically in the operating room. In the electrophysiology laboratory epicardial VT targets were identified in 38 (68%) patients and epicardial ablation abolished ≥1 VT in 27 patients (6% of the total study population); inducibility was not tested after ablation in 4, and VT remained inducible in 7 patients. No ablation was performed in 18 (32%) patients because of no accessible epicardial target or a complication. Major complications occurred in 8 (14%) of the 57 electrophysiology laboratory procedures. After the first procedure any VT recurred in 21 (54%) of 39 patients who had epicardial ablation compared with 164 (47%) of 347 endocardial-only ablation patients (P=0.35). Epicardial ablation is potentially useful in ≥6% of the postinfarction VT population, but the number could be substantially greater because more than two thirds of patients selected for epicardial mapping after failed ablation had an epicardial VT target. Successful epicardial ablation of a VT was not predictable from infarct location or other patient characteristics.

Letter by Gaillard et al Regarding Article, “Thrombolysis Despite Recent Stroke: A Case Series”

To the Editor: We read with great interest the article by Alhazzaa et al,1 reporting a retrospective analysis of a case series of 6 patients with previous ischemic stroke within the previous 3 months treated with recombinant tissue-type plasminogen activator (rtPA) for acute ischemic stroke beyond current guidelines. They found a 50% (3/6) post-thrombolysis hemorrhagic transformation rate among remote prior infarction, asymptomatic in all cases and without any parenchymal hemorrhage according to European Cooperative Acute Stroke Study trial definition. These results, as underlined by the authors, are encouraging and provide further evidence that thrombolysis beyond guidelines in this particular subgroup of patients could be safe and useful, given a low presumed hemorrhagic risk. This is in agreement with 2 other published retrospective consecutive case series, which lead to same conclusions in the setting of subacute recent silent …

Pre-existing cerebral infarcts as a risk factor for delirium after coronary artery bypass graft surgery

Delirium is a common and critical clinical syndrome in older patients. We examined whether abnormalities in the brain that could be assessed by magnetic resonance imaging predisposed patients to develop delirium after coronary artery bypass graft surgery. We also analysed the association between delirium and cognitive dysfunction after coronary artery bypass graft surgery. Data were collected prospectively on 153 patients aged 60 years or older who consecutively underwent elective isolated coronary artery bypass graft surgery. All patients were assessed for prior cerebral infarctions and craniocervical artery stenosis by magnetic resonance imaging (MRI) and angiography of their brains. Atherosclerosis of the ascending aorta was examined by epiaortic ultrasound at the time of surgery. Individual cognitive status was measured using four tests in all the patients before surgery and on the seventh postoperative day. A single psychiatrist diagnosed delirium using the Diagnostic and Statistical Manual of Mental Disorders 4th edition IV criteria. Postoperative delirium occurred in 16 patients (10.5%). Compared with patients who did not develop postoperative delirium, delirious patients had significantly higher rates of peripheral artery disease, preoperative decline in global cognitive function and pre-existing multiple cerebral infarctions on MRI. In addition, 9 (56%) of the delirious patients suffered postoperative cognitive dysfunction. Stepwise logistic regression analysis found significant independent predictors of postoperative delirium to be preoperative cerebral infarcts on MRI (odds ratio [OR], 2.26; 95% confidence interval [CI] 1.10-4.78), preoperative decline in global cognitive function (OR 4.54; 95% CI 1.21-16.51) and atherosclerosis of the ascending aorta (OR 2.44; 95% CI 1.03-5.62). Our findings suggested that postoperative delirium was associated with pre-existing multiple cerebral infarctions on MRI, preoperative decline in global cognitive function and ascending aortic atherosclerosis in elderly patients undergoing coronary artery bypass graft surgery and increased risk of postoperative cognitive dysfunction.

Akinetic Mutism Without a Structural Prefrontal Lesion

Akinetic mutism is characterized by profound apathy and a lack of verbal and motor output for action, despite preserved alertness. The condition usually follows bilateral damage to the medial frontal subcortical circuits. We report a 59-year-old right-handed woman who was admitted to the neurology ward with sudden-onset akinetic mutism. Her medical history included an ischemic stroke 3 years earlier, with residual anomia and mild agraphia but no motor dysfunction. On this admission, a cranial computed tomography scan disclosed an acute left superior cerebellar infarction embracing the vermis, and a prior left inferior parietal infarct. Electroencephalogram showed bilateral frontal delta-wave activity. Four weeks later, we performed a technetium-99m hexamethylpropyleneamine oxime single-photon emission computed tomography (Tc-HMPAO SPECT) scan to study the patient's frontal lobe function. The SPECT scan revealed the causative bifrontal hypoperfusion, more prominent on the right, while the structurally evident cerebellar infarction was predictably masked by subacute hyperperfusion phenomenon. Contralateral frontal diaschisis is an established sequela of cerebellar infarction. Because this patient also had lesions in the left parietal region, her left prefrontal area was critically deprived of its major reciprocally connected cortical counterparts (right prefrontal and left parietal), and also became dysfunctional. Her resulting bilateral frontal dysfunction is a common cause of akinetic mutism.

Sleeping altitude and sudden cardiac death

Mountain activities characterized by strenuous exercise in a hypoxic setting place unique demands on the body. The mortality rate associated with mountain activities is high, with sudden cardiac death (SCD) representing the most frequent of all nontraumatic deaths. We evaluated the possible effect of acclimatization in reduction of SCD during high-altitude sojourns. This was a retrospective cohort study involving all deaths (N = 559) that occurred during mountain activities in Austria from 1985 through 1993. Baseline patient demographics, cardiovascular comorbidities, smoking history, family history of SCD, sleeping altitude, annual mountaineering frequency, and physical activity on the day of SCD were included in a questionnaire previously used in a pilot study. Data from 301 of 599 individuals without prespecified exclusions were available for analysis (79% of eligible cohort). Sudden cardiac deaths happened mostly around noon (29%), and mean altitude at which SCDs occurred was 1,710 ± 501 m. When sleeping altitude was divided into quartiles (<700 m, 700-999 m, 1,000-1,299 m, and >1,299 m), the odds ratio for SCD on the first day at altitude when sleeping below 700 m was 5.7 (95% CI 2.8-11.6) as compared with sleeping above 1,299 m. For males >34 years, those with history of coronary artery disease and/or prior infarction, and those unaccustomed to physical activity at altitude, sleeping at moderate altitude before exercising at altitude may reduce the risk of SCD.

Abstract TP70: Safety of IV tPA Administration with CT Evidence of Prior Infarction

Background: Prior stroke within 3 months excludes patients from thrombolysis, however patients may have CT evidence of prior infarct often of unknown time of origin. We aimed to determine if the presence of a previous infarct on pre-treatment head CT is a predictor of hemorrhagic complications following administration of IV tPA. Methods: We retrospectively analyzed the database of consecutive patients treated with IV tPA at our institution from 2009-2011. Pre-treatment CTs were reviewed without knowledge of subsequent hemorrhagic transformation (HT) for evidence of any prior infarct. Further independent review determined if any HT was present on repeat CT or MRI. Symptomatic ICH (sICH) was defined as the presence of parenchymal hematoma (PH-1 or PH-2) and neurological deterioration by ≥ 4 points within 36 hours. Results: Of 212 IV tPA treated patients, 72 (34%) had evidence of prior infarct on pre-treatment CT. Any HT was found in 16%, sICH occurred in 2.4% of the total population, and both events never occurred in the areas of prior infarcts. Patients with prior infarcts on CT were older (median age 72 vs 65; p=0.001), were more likely to have a history of hypertension (85% vs 71%; p=0.024), were on antiplatelet agents prior to admission (49% vs 31%; p=0.007) and had higher pre-treatment NIHSS scores (median 10 vs 7; p=0.023). Patients with prior infarcts on CT did not experience more HT (p=0.3956) nor sICH (p=0.2207), even after stratifying for prior lacunar or cortical stroke appearances (p=0.301). More patients with prior infarcts on CT had microbleeds on follow-up MRI (25% vs 11%; p=0.033), and patients with prior infarcts and microbleeds experienced more HT (63% vs. 10%; p&lt;0.0001) but did not have more sICH (p=0.4784). Conclusions: Visualization of prior infarcts on pre-treatment CT does not predict an increased risk of sICH and should not be viewed as a contraindication for systemic tPA treatment after clinically evident strokes within 3 months were excluded. A subgroup of patients with prior infarcts and subsequently discovered cerebral microbleeds show a propensity to develop asymptomatic HT.

Abstract 104: The Impact of Ischemic and Structural Brain Tissue Changes on Response to rt-PA: An Analysis of Imaging from 3035 Patients in The Third International Stroke Trial

Aim: Early infarct signs predict symptomatic intracranial haemorrhage (SICH) and poor outcome after stroke. Structural brain features increase with age. It is unclear if, or when, any of these imaging signs should influence decisions to use rt-PA. We assessed imaging, SICH, 6-month outcome and rt-PA effects in 3035 patients randomised in IST-3. Methods: IST-3 was a randomised trial of iv rt-PA (0.9mg/kg) &lt;6 hours of ischaemic stroke ( ISRCTN25765518 ). All pre- and post-randomisation imaging was read centrally, masked, by international experts for early infarct signs (tissue hypodensity site/size, swelling, hyperdense artery) and structural brain changes (atrophy, leukoaraiosis, prior infarct) using validated scales. We tested associations between pre-treatment imaging, SICH, 6-month outcome and rt-PA effects, adjusted for time, NIHSS, age, with logistic regression. Results: Of 3035 patients, (1515 rt-PA, 1520 control; baseline imaging CT 2848, 98%, MR 54, 2%), 1616 aged &gt;80; 851 treated &lt;3hr, 1177 3-4.5 and 1007 4.5-6hr; 40% had tissue hypodensity/swelling (ASPECTS &lt;7 in 25%, 8-10 in 75%); 24% had hyperdense artery; 50% had leukoaraiosis, atrophy or prior infarct; 9% were totally normal. On adjusted analyses, no imaging feature alone modified rt-PA effects. SICH increased with prior infarct (OR 1.66, p=0.009), tissue hypodensity (1.51, p=0.04), hyperdense artery (1.51, p=0.04). 6-month independent survival decreased with hypodensity (0.66, p=0.000), swelling (0.59, p=0.000), hyperdense artery (0.59, p=0.000), leukoaraiosis (0.72, p=0.0008) and atrophy (0.74, p=0.01). On elimination modelling, prior infarct predicted 54% of SICH risk; swelling, hyperdense artery, leukoaraiosis each predicted 33% of poor outcome risk. Conclusion: Amongst these 3035 patients, neither structural nor early ischaemic imaging features alone modify rt-PA effects, but can inform rt-PA treatment decisions where benefits are likely to be marginal by predicting risk of rt-PA-associated SICH and poor functional outcome. The results are also relevant to older as well as younger patients and to rt-PA given &lt;3 as well as up to 6 hours after stroke.

Abstract 67: Importance Of Previous Brain Infarcts In Patients With Asymptomatic Carotid Stenosis And The Impact Of Surgery From The Asymptomatic Carotid Surgery Trial-1

Background and aims: Silent brain infarcts are common in patients at increased risk of stroke and are associated with a poor prognosis. Similar adverse associations were claimed in asymptomatic carotid stenosis (ASCS) patients but the impact of previous infarction or symptoms on the beneficial effects of carotid endarterectomy (CEA) is not clear. Our aim was to evaluate the importance of prior brain infarcts (PBI) in ASCS patients enrolled in ACST-1 - a large trial with 10-year follow-up. Methods: Of 3120 patients included in ACST-1, 787 patients without baseline imaging were excluded. Trial patients (2333) with brain imaging at trial entry were identified &amp; divided into those with PBI (i.e. radiological evidence of an asymptomatic infarct or prior ischaemic symptoms [PIS] &gt;6 months prior to randomization) (group 1, 1331 patients) &amp; those with normal imaging and no PIS (group 2, 1002 patients). The trial allocated immediate CEA treatment to about half of the patients in both groups. First stroke and vascular death in these groups were compared during follow-up irrespective of treatment assignment and, for both groups, the impact of CEA was analyzed. Results: Baseline characteristics of excluded &amp; analyzed patients were similar, male gender and hypertension being commoner in group 1 with slightly tighter ipsilateral stenosis in group 2. After 10 years stroke was significantly commoner in group 1 (absolute risk increase [ARI] 5.8% [1.8-9.8], p=0.004) as was risk of stroke and vascular death (6.9% [1.9-12.0] ARI, p=0.007). Multivariate analysis confirmed that PBI was associated with greater risk of stroke (HR=1.51 95%CI:1.17-1.95) and of any stroke or other vascular death (HR=1.30 95%CI:1.11-1.52). Benefits of CEA at 5 years appeared greater for group 1 patients (gain 4.9% p=0.005%) than for group 2 (gain at 5 years, 3.9% p=0.02%) though it must be emphasized that the trial was not designed to test this comparison. Conclusions: ASCS patients with prior brain infarcts have higher stroke risk during long-term follow-up than those without PBI and may benefit more from CEA.

Abstract 10: Perfusion Imaging In Patients Randomised To rt-PA or Control In The Third International Stroke Trial (IST-3): Baseline Characteristics And Association With Outcome.

Aim: Perfusion imaging (PI) may help identify patients with brain at risk of infarction who may benefit most from rt-PA. It remains unclear which perfusion parameter is most specific or if PI should influence decisions for use of rt-PA. IST-3 aimed to improve use of rt-PA. Methods: IST-3 was a randomised trial of iv rt-PA (0.9mg/kg) &lt;6 hours of acute ischaemic stroke (registration ISRCTN25765518 ). Pre-randomisation CT or MR PI was performed in some centres. PI data were processed centrally to produce maps of relative (r) CBF; quantitative (q) CBF, CBV, MTT, Tmax. PI images were read centrally, blind, scoring PI lesion extent by ASPECTS and relative to plain CT/MR lesion size (&lt;80%/100%/&gt;120%). All plain CT or MR imaging was assessed, blind, by an expert panel for early infarct signs (site/size of tissue hypodensity, swelling; hyperdense artery; haemorrhage) and background brain changes (atrophy, leukoaraiosis, prior infarct) with validated scales. We assessed baseline characteristics of patients randomised with/without PI in IST-3 and associations with outcome. Results: 28 IST-3 centres performed PI on 152 patients: 129 were pre-randomisation, 113 were analysable (97 CT, 16 MR). Baseline features were the same in those with as without PI, respectively: 55% v 53% were aged &gt;80; 52% vs 50% had NIHSS ≥11; 35% v 41% with visible infarct signs. PI lesions were smallest for qCBV, largest for qMTT. PI lesions were larger (all parameters) in patients scanned &lt;3 vs 3-6 hours (with more &gt;120% plain scan lesion), aged &gt;80 vs &lt;80, and with higher NIHSS scores. Large qCBV lesions were associated with SICH, early and late death and poor functional outcome. Large lesions on other PI parameters were associated with poor functional outcome. Conclusion: IST-3 is the largest randomised trial of rt-PA in patients with PI. Results will be generalisable to the types of patients included in IST-3. Patients presenting &lt;3 hours have larger PI lesions with more mismatch. Large CBV lesions may predict SICH and poor outcome. Results by rt-PA allocation are awaited.

Adverse event rates following primary PCI for STEMI at US and non-US hospitals: three-year analysis from the HORIZONS-AMI trial

To examine outcomes in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) at US sites versus sites outside the US (OUS). In the HORIZONS-AMI trial 3,602 STEMI patients in 11 countries were randomised to primary PCI with bivalirudin versus heparin + glycoprotein IIb/IIIa inhibitors. US patients (n=814) had more diabetes, prior infarction, prior bypass surgery, and renal insufficiency. OUS patients (n=2,788) had longer door-to-balloon times, more radial access, fewer bypass surgeries, and were discharged more often on beta-blockers and statins. At three years US patients had higher mortality (9.7% vs. 6.0%, p=0.0003), reinfarction (10.2% vs. 6.4%, p=0.001), major adverse cardiac events (MACE; 28.2% vs. 20.1%, p<0.0001), major bleeding (16.9% vs. 6.4%, p<0.0001) and net adverse clinical events (NACE; 36.6% vs. 23.8%, p<0.0001), which persisted after adjusting for baseline risk. In the HORIZONS-AMI trial, STEMI patients undergoing primary PCI at US versus OUS sites had higher rates of adverse events, which persisted after adjusting for baseline risk. The reasons for these differences are not clear but may be due to unmeasured confounders, different thresholds for event reporting, or valid differences in systems of care and treatments.

Neuroimaging Findings in Cryptogenic Stroke Patients With and Without Patent Foramen Ovale

Patent foramen ovale (PFO) and cryptogenic stroke are commonly associated but some PFOs are incidental. Specific radiological findings associated with PFO may be more likely to indicate a PFO-related cause. We examined whether specific radiological findings are associated with PFO among subjects with cryptogenic stroke and known PFO status. We analyzed the Risk of Paradoxical Embolism(RoPE) Study database of subjects with cryptogenic stroke and known PFO status, for associations between PFO and: (1) index stroke seen on imaging, (2) index stroke size, (3) index stroke location, (4) multiple index strokes, and (5) prior stroke on baseline imaging. We also compared imaging with purported high-risk echocardiographic features. Subjects (N=2680) were significantly more likely to have a PFO if their index stroke was large (odds ratio [OR], 1.36; P=0.0025), seen on index imaging (OR, 1.53; P=0.003), and superficially located (OR, 1.54; P<0.0001). A prior stroke on baseline imaging was associated with not having a PFO (OR, 0.66; P<0.0001). Finding multiple index strokes was unrelated to PFO status (OR, 1.21; P=0.161). No echocardiographic variables were related to PFO status. This is the largest study to report the radiological characteristics of patients with cryptogenic stroke and known PFO status. Strokes that were large, radiologically apparent, superficially located, or unassociated with prior radiological infarcts were more likely to be PFO-associated than were unapparent, smaller, or deep strokes, and those accompanied by chronic infarcts. There was no association between PFO and multiple acute strokes nor between specific echocardiographic PFO features with neuroimaging findings.

Does Motor Dysfunction After Cerebral Infarction Impede the Development of Angina Symptoms?

Previous studies based on coronary angiography or computed tomography coronary angiography have demonstrated a high prevalence of coronary stenosis in patients with cerebral infarction and no prior history of coronary artery disease (CAD). The purpose of the present study was to compare the coronary angiographic findings of patients with prior cerebral infarction with those of patients with no prior cerebral infarction. Consecutive patients (n = 126) who underwent a first coronary angiography for suspected CAD but had no prior history of CAD were classified into 2 groups, those with a clinical history of cerebral infarction (cerebral infarction group) and those without a clinical history of cerebral infarction (noncerebral infarction group). The incidences of diabetes mellitus, peripheral artery disease, coronary stenosis, and multivessel disease were significantly higher in the cerebral infarction group than in the noncerebral infarction group. Multiple logistic regression analysis relating to coronary stenosis identifi ed prior cerebral infarction (P = 0.0027, odds ratio = 4.414) and diabetes mellitus (P = 0.0446, odds ratio = 2.619) as explanatory factors. Thirty-four of 78 patients (44%) with coronary stenosis did not have angina symptoms. Multiple logistic regression analysis regarding the lack of angina symptoms identified motor dysfunction (modified Rankin scale ≥ 2) (P = 0.0028, odds ratio = 8.323) as an explanatory factor. The results of the present study suggest that compared with patients without cerebral infarction those with the disorder have a high prevalence of coronary stenosis, and indicate that the development of angina symptoms is influenced by the severity of motor dysfunction.

Hemorrhagic Transformation of Ischemic Stroke in Patient Treated With Rivaroxaban

Rivaroxaban (BAY 59-7939) is an oral factor Xa inhibitor used for stroke prevention in atrial fibrillation. There are currently no evidence based guidelines for treatment of hemorrhagic side effects of factor Xa inhibitors. We report a case of delayed hemorrhagic conversion of an ischemic infarct in a 60-year-old male treated with rivaroxaban for stroke prevention in a setting of paroxysmal atrial fibrillation. The patient presented with generalized discomfort and malaise as well as worsening of expressive aphasia from a prior infarct. In addition, right superior quadrantanopsia was present. CT head at 140 minutes and 8 hours following symptom onset revealed confluent petechiae and linear gyral hyperintensities of the left temporal lobe without mass effect, classified as type 2 Hemorrhagic Transformation (HI2). The patient received a single unit of fresh frozen plasma (FFP) and three doses of Vitamin K. He remained clinically stable without need for neurosurgical intervention, and was subsequently discharged with a plan to commence aspirin therapy five days after onset and switch to dabigatran two weeks later for management of paroxysmal atrial fibrillation. Hemorrhagic transformation in this case remained clinically stable following conservative therapy, likely due to pharmacological clearance of rivaroxaban. Prothrombin complex concentrates may be considered for emergent reversal of rivaroxaban. doi: http://dx.doi.org/10.4021/jh78w

De Novo Glioblastoma in the Territory of a Prior Middle Cerebral Artery Infarct

We report a case of a patient who developed glioblastoma in the territory of a previous infarction. Two years after an ischemic stroke, the patient presented with a cystic, necrotic, and heterogeneously enhancing mass. Open biopsy and debulking of the mass with histological analysis revealed the mass to be glioblastoma. Though several cases of posttraumatic GBM have been reported, this is the first proposed case of GBM after an ischemic stroke. From this case, we suggest that the ischemic stroke, like other forms of cortical injury, may predispose to glioblastoma formation.