Severe Hypoperfusion Research Articles

Abstract WMP81: Collaterals and the Severity of Hypoperfusion in Acute Ischemic Stroke are Independent of Dehydration or Volume Status

Background: Systemic hemodynamic factors may affect blood flow to the brain, yet the influence of volume status and the use of fluid administration to improve perfusion in acute ischemic stroke remains unproven. We correlated the presence of dehydration and volume status defined by initial lab values with perfusion MRI and collaterals at angiography in middle cerebral artery (MCA) stroke patients. Methods: Retrospective analysis of a consecutive series of isolated M1 MCA occlusions was conducted at an expert core lab to quantify acute Tmax volumes, Tmax hypoperfusion severity ratios and ASITN collateral grade on digital subtraction angiography (DSA). Blood urea nitrogen (BUN) and creatinine (Cr) measured during triage were correlated with hypoperfusion and ASITN/SIR grade. Statistical methods included correlations and ANOVA. Results: 95 patients (median age 74 (24-101) years; 71 women; median NIHSS 16; median time to MRI, 4h06min) with acute stroke due to M1 occlusion (52 proximal, 43 distal) had contemporaneous BUN/Cr, perfusion MRI and DSA during a 6-year period. Dehydration was noted in 38% (BUN/Cr>20) and 71% (BUN/Cr>15) of patients. Tmax>6sec volumes were median 197 cc (IQR 102-347), with Tmax hypoperfusion severity ratios of 10/6 (median 0.80 (IQR 0.72-0.87)). DSA collateral grade was median 2 (IQR 2-3). Volume status or BUN/Cr was distinct from Tmax hypoperfusion severity at all thresholds, including Tmax>6s (r=0.143, p=0.166), Tmax 10/6 (r=0.114, p=0.271). Direct correlation between BUN/Cr and DSA collateral grade was also unapparent (r=0.034, p=0.744). Conclusions: Dehydration and the degree of volume depletion may be common, but are not associated with the severity of collateral perfusion in acute M1 MCA occlusion. Collateral grade defined by DSA and the associated severity of hypoperfusion in the brain is unrelated to intravascular volume status.

Abstract 158: The Malignant CTP Imaging Profile Predicts Worse Functional Outcomes

Introduction: The Malignant MRI profile, defined as a large lesion on DWI or PWI (Tmax>10s), has been proposed as a marker of poor outcome despite reperfusion. It is not known if a corresponding malignant CT perfusion (CTP) profile can be used to identify stroke patients with a poor prognosis despite timely reperfusion. Hypothesis: The Malignant CTP profile identifies stroke patients with poor clinical outcomes despite endovascular reperfusion. Methods: The NIH-funded CTP to predict Response to recanalization in Ischemic Stroke Project (CRISP) prospectively enrolled acute ischemic stroke patients undergoing intra-arterial thrombectomy. CTP was obtained prior to the procedure and followed by a post-procedural MRI within 36 hours. The CTP Malignant profile was pre-specified as an infarct core (rCBF <30%) ≥70mL or a lesion with severe hypoperfusion (Tmax>10s) ≥100mL. Poor functional outcome was defined as a mRS 5-6 at 90 days. We evaluated performance of the pre-specified Malignant CTP profile for predicting poor functional outcome. We then performed an ROC analysis to optimize the ischemic core and Tmax>10s volumes for predicting poor outcome with high specificity (≥90%). Results: Among 190 patients who underwent endovascular therapy, and had technically adequate CTP and 90-day outcome data, 51 (27%) had the Malignant CTP profile (45 on Tmax10 criteria alone, 6 on both infarct core and Tmax10 criteria). The Malignant CTP profile was associated with an increased rate of poor outcome (26% vs 14%; OR = 2.2; 95% CI 0.98-4.8; p=0.08). In patients with reperfusion (n=170), the percent of poor outcomes was significantly higher among patients with the Malignant CTP profile (27% vs 12%, p=0.02; OR = 3.1; 95% CI 1.3-7.4, adjusted for age). Based on ROC analysis, a CTP infarct core >50 mL or a Tmax>10s lesion >150 mL predicted poor outcome with high specificity (90%), but corresponding sensitivity was low (28%) and PPV was modest (36%, or 9/25). Conclusion: Although presence of the Malignant CTP profile doubled the likelihood of poor outcome, only 1 out of 3 patients with this profile who had endovascular reperfusion experienced a poor outcome. This suggests that a subset of patients with the Malignant CTP profile may benefit from endovascular therapy.

Interferon-β Modulates Inflammatory Response in Cerebral Ischemia.

BackgroundStroke is a leading cause of death in the world. In >80% of strokes, the initial acute phase of ischemic injury is due to the occlusion of a blood vessel resulting in severe focal hypoperfusion, excitotoxicity, and oxidative damage. Interferon‐β (IFNβ), a cytokine with immunomodulatory properties, was approved by the US Food and Drug Administration for the treatment of relapsing‐remitting multiple sclerosis for more than a decade. Its anti‐inflammatory properties and well‐characterized safety profile suggest that IFNβ has therapeutic potential for the treatment of ischemic stroke.Methods and ResultsWe investigated the therapeutic effect of IFNβ in the mouse model of transient middle cerebral artery occlusion/reperfusion. We found that IFNβ not only reduced infarct size in ischemic brains but also lessened neurological deficits in ischemic stroke animals. Further, multiple molecular mechanisms by which IFNβ modulates ischemic brain inflammation were identified. IFNβ reduced central nervous system infiltration of monocytes/macrophages, neutrophils, CD4+ T cells, and γδ T cells; inhibited the production of inflammatory mediators; suppressed the expression of adhesion molecules on brain endothelial cells; and repressed microglia activation in the ischemic brain.ConclusionsOur results demonstrate that IFNβ exerts a protective effect against ischemic stroke through its anti‐inflammatory properties and suggest that IFNβ is a potential therapeutic agent, targeting the reperfusion damage subsequent to the treatment with tissue plasminogen activator.

Large Volumes of Critically Hypoperfused Penumbral Tissue Do Not Preclude Good Outcomes After Complete Endovascular Reperfusion

Acute ischemic stroke patients with large volumes of severe hypoperfusion (Tmax>10 s>100 mL) on magnetic resonance imaging have a higher likelihood of intracranial hemorrhage and poor outcomes after reperfusion. We aim to evaluate the impact of the extent of Tmax>10 s CTP lesions in patients undergoing successful treatment. Retrospective database review of endovascular acute ischemic stroke treatment between September 2010 and March 2015 for patients with anterior circulation occlusions with baseline RAPID CTP and full reperfusion (mTICI 3). The primary outcome was the impact of the Tmax>10 s lesion spectrum on infarct growth. Secondary safety and efficacy outcomes included parenchymal hematomas and good clinical outcomes (90-day modified Rankin Scale score, 0-2). Of 684 treated patients, 113 patients fit the inclusion criteria. Tmax>10 s>100 mL patients (n=37) had significantly higher baseline National Institutes of Health Stroke Scale (20.7±3.8 versus 17.0±5.9; P<0.01), more internal carotid artery terminus occlusions (29% versus 9%; P=0.02), and larger baseline (38.6±29.6 versus 11.7±15.8 mL; P<0.01) and final (60.7±60.0 versus 29.4±33.9 mL; P<0.01) infarct volumes when compared with patients without Tmax>10 s>100 mL (n=76); however, the 2 groups were otherwise well balanced. There were no significant differences in infarct growth (22.1±51.6 versus 17.8±32.4 mL; P=0.78), severe intracranial hemorrhage (PH2: 2% versus 4%; P=0.73), good outcomes (90-day mRS score, 0-2: 56% versus 59%; P=0.83), or 90-day mortality (16% versus 7%; P=0.28). On multivariate analysis, only baseline National Institutes of Health Stroke Scale (odds ratio, 1.19; 95% confidence interval, 1.06-1.34; P<0.01) and baseline infarct core volume (odds ratio, 1.05; 95% confidence interval, 1.02-1.08; P<0.01) were independently associated with Tmax>10 s>100 mL. There was no association between Tmax>10 s>100 mL with any PH, good outcome, or infarct growth. In the setting of limited baseline ischemic cores, large Tmax>10 s lesions on computed tomographic perfusion do not seem to be associated with a higher risk of parenchymal hematomas and do not preclude good outcomes in patients undergoing endovascular reperfusion with contemporary technology.

Microdialysis measurements of equine lamellar perfusion and energy metabolism in response to physical and pharmacological manipulations of blood flow.

A suitable method for evaluating lamellar perfusion changes and their metabolic consequences is currently lacking. To examine perfusion changes in lamellar tissue using serial microdialysis measurements of urea clearance and energy metabolites. Randomised, controlled (within subject) experimental trial. Nine Standardbred horses were instrumented with microdialysis probes in the foot lamellar tissue and skin (over the tail base). Urea (20 mmol/l) was added to the perfusate and its clearance was used to estimate local perfusion. Samples were collected every 15 min for a 1 h control period, then during application of a distal limb tourniquet, during periods when norepinephrine or potassium chloride (KCl) were included in both skin and lamellar perfusates, and after systemic (intravenous) acetylpromazine. Dialysate concentrations of glucose, lactate, pyruvate and urea were measured and lactate:glucose (L:G) and lactate:pyruvate (L:P) ratios calculated. Values were compared with pre-intervention baseline and also between simultaneous skin and lamellar samples using nonparametric statistical methods. Lamellar glucose decreased and lactate, urea, L:G and L:P increased significantly with tourniquet application, without significant changes in skin dialysate values. Lamellar and skin glucose decreased and L:G increased significantly during norepinephrine infusion, but mild increases in urea were not significant at either site. KCl caused significant decreases in lamellar and skin L:G, and an increase in skin glucose, but did not affect urea clearance. Acetylpromazine caused profound decreases in lamellar glucose and L:P, with increased L:G and pyruvate, but did not affect urea clearance or any skin dialysate values. Significant changes in microdialysis urea clearance only occurred with severe lamellar hypoperfusion. However, changes in dialysate metabolite concentrations reflected less profound fluctuations in perfusion. This method may be useful for examining lamellar perfusion and energy balance during laminitis development and for the evaluation of vasoactive therapeutics.

Anomalous Origins of Coronary Arteries From the Pulmonary Artery: A Comprehensive Review of Literature and Surgical Options.

Anomalous origins of coronary arteries from the pulmonary artery are rare malformations in which the coronary arteries originate from pulmonary artery sinuses or branches. The consequences are variable although, in most cases, these anomalies lead to severe coronary hypoperfusion and ventricular dysfunction. Surgical correction is indicated once the diagnosis is established due to high early mortality associated with the disease. In nearly all cases, the anomalous artery can be excised from its pulmonary origin, mobilized, and reimplanted directly into the ascending aorta using different surgical techniques. In rare circumstances, technical modifications must be used to restore a normal dual coronary perfusion. The emphasis of this article is to provide a collective review of surgical options published in the literature.

Predicting Collateral Status With Magnetic Resonance Perfusion Parameters: Probabilistic Approach With a Tmax-Derived Prediction Model.

Good collateral flow is an important predictor for favorable responses to recanalization therapy and successful outcomes after acute ischemic stroke. Magnetic resonance perfusion-weighted imaging (MRP) is widely used in patients with stroke. However, it is unclear whether the perfusion parameters and thresholds would predict collateral status. The present study evaluated the relationship between hypoperfusion severity and collateral status to develop a predictive model for good collaterals using MRP parameters. Patients who were eligible for recanalization therapy that underwent both serial diffusion-weighted imaging and serial MRP were enrolled into the study. A collateral flow map derived from MRP source data was generated through automatic postprocessing. Hypoperfusion severity, presented as proportions of every 2-s Tmax strata to the entire hypoperfusion volume (Tmax≥2 s), was compared between patients with good and poor collaterals. Prediction models for good collaterals were developed with each Tmax strata proportion and cerebral blood volumes. Among 66 patients, 53 showed good collaterals based on MRP-based collateral grading. Although no difference was noted in delays within 16 s, more severe Tmax delays (Tmax16-18 s, Tmax18-22 s, Tmax22-24 s, and Tmax>24 s) were associated with poor collaterals. The probability equation model using Tmax strata proportion demonstrated high predictive power in a receiver operating characteristic analysis (area under the curve=0.9303; 95% confidence interval, 0.8682-0.9924). The probability score was negatively correlated with the volume of infarct growth (P=0.030). Collateral status is associated with more severe Tmax delays than previously defined. The present Tmax severity-weighted model can determine good collaterals and subsequent infarct growth.

Natural course of total mismatch and predictors for tissue infarction.

We longitudinally assessed patients presenting with total mismatch and hypothesized that hypoperfusion intensity ratio (HIR), severity of stroke, and occlusion of blood vessel are predictors of tissue fate. Patients with suspected stroke or TIA admitted to our emergency department between September 2008 and October 2012 with suspected stroke or TIA were eligible to participate in the ongoing stroke imaging study 1000Plus. Patients received acute and follow-up stroke MRI, basic demographics were collected, and stroke severity was rated according to the NIH Stroke Scale (NIHSS). Inclusion criteria for the substudy were total mismatch on admission examination and available follow-up. We identified 23 patients with total mismatch: median age 70 years (interquartile range 66-78), 10 female (43.5%). Infarction was found on follow-up diffusion-weighted imaging (median lesion size 1.3 mL) in 9 patients (39.1%). Infarction was correlated with NIHSS at admission (p = 0.026) and HIR (p = 0.015) but not with vessel occlusion. Clinical outcome as measured by last recorded NIHSS score and modified Rankin Scale score at discharge was significantly worse in patients with infarction on follow-up. Final infarction is frequently seen in patients with total mismatch. Clinical presentation at admission and severity of hypoperfusion measured by HIR, but not occlusion of the supplying vessel, predict tissue fate.

Locked-in syndrome caused by bilateral midbrain infarctions with occlusion of the intracranial vertebral artery

Bilateral cerebral peduncles are rarely simultaneously infarcted unless the basilar artery is involved. A 60-year-old man developed locked-in syndrome because of bilateral cerebral peduncle infarctions with right intracranial vertebral artery occlusion. Dysarthria occurred a day before admission. His neurological condition rapidly deteriorated, and he subsequently became quadriplegic. His left vertebral artery showed a posterior inferior cerebellar artery end pattern, and anastomosis between the anterior and posterior circulations through the hypoplastic right P1 and fine left posterior communicating artery was insufficient; therefore, severe hypoperfusion and multiple infarctions in the distribution of the posterior circulation were induced by right intracranial vertebral artery occlusion. These findings highlight the fact that large-artery atherosclerosis represents an important cause of mesencephalic infarctions. Several neurological manifestations are caused by intracranial vertebral artery occlusion, and when collateral flow to the posterior circulation is insufficient, intracranial vertebral artery occlusion results in bilateral cerebral peduncle infarctions and locked-in syndrome without basilar artery occlusion.

Cerebral Hypoperfusion and Hypometabolism Detected by Arterial Spin Labeling MRI and FDG-PET in Early-Onset Alzheimer's Disease.

Early-onset Alzheimer's disease (EOAD) is frequently associated with atypical clinical presentations and its early detection remains a challenging issue. In this study, we used arterial spin labeling (ASL), a noninvasive perfusion MRI sequence, and [(18)F]-FDG-PET to detect the perfusion and metabolic features in patients with EOAD. All patients were investigated in the French reference center for young-onset dementia and were assessed by MRI, including a pseudo-continuous ASL (pCASL) sequence, and [(18)F]-FDG-PET. Quantitative analyses and intermodality comparison with correlation analysis were made after data processing including correction of partial volume effects, cortical projection, and specific intensity normalization. We prospectively included 37 patients with EOAD with a mean age of 58.3 years. The areas of most severe hypoperfusion detected with ASL were located in the parietal lobes, the precuneus, the right posterior cingulate cortex, and the frontal lobes (P < .05). The areas of lowest glucose metabolism detected by [(18)F]-FDG-PET were identified in the temporoparietal cortex and the precuneus (P < .05). Hypometabolic regions were more extensive than hypoperfused regions on ASL maps whereas ASL highlighted alterations in the frontal lobes without apparent hypometabolism on [(18)F]-FDG-PET maps. ASL and [(18)F]-FDG-PET detected pathological areas of similar distribution mainly located in the inferior parietal lobules and local zones in the temporal cortex in patients with EOAD. Our preliminary study showed that ASL and [(18)F]-FDG-PET may have a complementary role in combination with structural MRI for the assessment of suspected EOAD.

Hyperintense Vessels on FLAIR: Hemodynamic Correlates and Response to Thrombolysis

Hyperintense vessels on baseline FLAIR MR imaging of patients with ischemic stroke have been linked to leptomeningeal collateralization, yet the ability of these to maintain viable ischemic tissue remains unclear. We investigated whether hyperintense vessels on FLAIR are associated with the severity of hypoperfusion and response to thrombolysis in patients treated with intravenous tissue-plasminogen activator. Consecutive patients with ischemic stroke with an MR imaging before and within 24 hours of treatment, with proved vessel occlusion and available time-to-maximum maps were included (n = 62). The severity of hypoperfusion was characterized on the basis of the hypoperfusion intensity ratio (volume with severe/mild hypoperfusion [time-to-maximum ≥ 8 seconds / time-to-maximum ≥ 2 seconds]). The hypoperfusion intensity ratio was dichotomized at the median to differentiate moderate (hypoperfusion intensity ratio ≤ 0.447) and severe (hypoperfusion intensity ratio > 0.447) hypoperfusion. Good outcome was defined as a modified Rankin Scale score of ≤2. Hyperintense vessels on FLAIR were identified in 54 patients (87%). Patients with extensive hyperintense vessels on FLAIR (>4 sections) had higher NIHSS scores, larger baseline lesion volumes, higher rates of perfusion-diffusion mismatch, and more severe hypoperfusion (hypoperfusion intensity ratio). In stepwise backward multivariate regression analysis for the dichotomized hypoperfusion intensity ratio (including stroke etiology, age, perfusion deficit, baseline lesion volume, smoking, and extent of hyperintense vessels on FLAIR), extensive hyperintense vessels on FLAIR were independently associated with severe hypoperfusion (OR, 6.8; 95% CI, 1.1-42.7; P = .04). The hypoperfusion intensity ratio was an independent predictor of a worse functional outcome at 3 months poststroke (OR, 0.2; 95% CI, 0.5-0.6; P < .01). Hyperintense vessels on FLAIR are associated with larger perfusion deficits, larger infarct growth, and more severe hypoperfusion, suggesting that hyperintense vessels on FLAIR most likely indicate severe ischemia as a result of insufficient collateralization.

Global Coronary Artery Plaque Area is Associated with Myocardial Hypoperfusion in Women with Non-ST Elevation Myocardial Infarction.

Background: Women with non-ST elevation myocardial infarction (NSTEMI) have similar extent of myocardial ischemia but less obstructive coronary artery disease (CAD) than their male counterparts. We tested the impact of global coronary artery plaque area and artery tortuosity on myocardial perfusion in NSTEMI patients.Methods: Coronary artery plaque area was determined by quantitative angiography in 108 patients (32% women) with NSTEMI. Myocardial perfusion was assessed by contrast echocardiography in the 17 individual left ventricular segments. Artery tortuosity was defined as ≥3 curves >45° in a main coronary artery.Results: Age, prevalence of hypertension, and diabetes did not differ between sexes (all nonsignificant). Women had lower prevalence of ≥50% coronary artery stenosis (74% vs. 91%, p<0.05), while global coronary plaque area (35±22 vs. 43±21mm2) and the number of segments with hypoperfusion (6.9±3.7 vs. 7.2±3.4) did not differ between sexes (both p>0.07). In multivariate analysis, larger coronary artery plaque area was associated with a 35% higher risk for having severe myocardial hypoperfusion (odds ratio 1.35 [95% confidence interval 1.01–1.80], p<0.05) in the total study population, while no association between artery tortuosity and myocardial ischemia was found. Similar results were obtained in separate analysis among women and men.Conclusion: In women and men with NSTEMI, the global coronary artery plaque area was an important determinant of the severity of myocardial hypoperfusion at rest independent of presence of significant coronary stenoses. These findings may expand current understanding of NSTEMI in patients with nonobstructive CAD.

Fusion Image of Coronary Artery and Myocardial Perfusion Using Computed Tomography

Coronary angiography of 64-year-old man with chest pain shows the total occlusion (Fig 1, arrows) in the proximal portion of the left ascending coronary artery (LAD). Stress perfusion cardiac magnetic resonance image (MRI) depicts endocardium hypoperfusion area in the LAD territory and late gadolinium enhancement MRI showed subendocardial infarction. In this case, fusion image of coronary computed tomography (CT) and perfusion CT can present coronary lesions and following myocardial ischemia precisely. Pre-coronary artery bypass grafting (CABG) epicardial image shows the hypoperfusion area in LAD territory (Fig 2A, arrows), and subendocardial image shows the severe hypoperfusion lesion (Fig 2B, arrows). Transmural ischemic changes that were mainly seen in the anteroseptal wall were improved in the epicardium (Fig 2C) after CABG. However, subendocardial image shows residual ischemia in the subendocardium (Fig 2D, arrows), which suggests that blood flow could not be improved sufficiently with subendocardial infarction. Combined technique with perfusion CT using a 256-slice multidetector CT and a time axis interpolation technique [1Wai B. Thai W.E. Brown H. Truong Q.A. Novel phase-based noise reduction strategy for quantification of left ventricular function and mass assessment by cardiac CT: comparison with cardiac magnetic resonance.Eur J Radiol. 2013; 82: e337-e341Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar] allowed us to assess CT attenuation independent stratified myocardial ischemia.

Maternal Serum S100-B, PAPP-A and IL-6 levels in severe preeclampsia.

We aimed to investigate the relationship of maternal serum levels of S100-B, PAPP-A and IL-6 with severe preeclampsia. This prospective case-control study consisted of 27 severe preeclamptic and 36 healthy singleton pregnancies. The groups were matched for parity, maternal age and body mass index. Maternal blood sampling for S100B, PAPP-A and IL-6 was performed at the morning after an overnight fasting. S100-B concentrations were significantly higher in severe preeclampsia group (0.09 ± 0.05 vs. 0.13 ± 0.01 µg/L; p = 0.025). PAPP-A levels were higher (196.54 ± 21.56 vs. 208.80 ± 23.97 mIU/ml; p = 0.707) and IL-6 levels were lower in severe preeclamptic group (68.79 ± 29.89 vs. 37.30 ± 6.46 pg/ml; p = 0.372). AUC value for S100-B was calculated as 0.712. When cutoff level for serum S100-B for predicting severe preeclampsia was regarded as 0.0975 µg/L, sensitivity and specificity were found to be 81.4 % and 58.3 %, respectively. Pregnancies with ≥0.0975 µg/L S100-B levels had 12.75-fold increased risk for having CNS symptoms (OR 12.75; 95 % CI 2.69-60.28) and 3.27-fold increased risk for having HELLP syndrome (OR 3.27; 95 % CI 0.62-17.36). Our results suggest that serum S100B levels may be a potential marker in severe preeclampsia for the severity of hypoperfusion both in placenta and brain pointing at subsequent risk of organ failure.

Predictors of mortality and prehospital monitoring limitations in blunt trauma patients.

This study aimed at determining predictors of in-hospital mortality and prehospital monitoring limitations in severely injured intubated blunt trauma patients. We retrospectively reviewed patients' charts. Prehospital vital signs, Injury Severity Score (ISS), initial Glasgow Coma Scale (GCS), Revised Trauma Score (RTS), arterial blood gases, and lactate were compared in two study groups: survivors (n = 40) and nonsurvivors (n = 30). There were no significant differences in prehospital vital signs between compared groups. Nonsurvivors were older (P = 0.006), with lower initial GCS (P < 0.001) and higher ISS (P < 0.001), along with higher lactate (P < 0.001) and larger base deficit (BD; P = 0.006), whereas RTS (P = 0.001) was lower in nonsurvivors. For predicting mortality, area under the curve (AUC) was calculated: for lactate 0.82 (P < 0.001), for ISS 0.82 (P < 0.001), and for BD 0.69 (P = 0.006). Lactate level of 3.4 mmol/L or more was 82% sensitive and 75% specific for predicting in-hospital death. In a multivariate logistic regression model, ISS (P = 0.037), GCS (P = 0.033), and age (P = 0.002) were found to be independent predictors of in-hospital mortality. The AUC for regression model was 0.93 (P < 0.001). Increased levels of lactate and BD on admission indicate more severe occult hypoperfusion in nonsurvivors whereas vital signs did not differ between the groups.

Reduced cerebral blood flow in genetic prion disease with PRNP D178N–129M mutation: An arterial spin labeling MRI study

The D178N mutation in the PRNP gene is associated with fatal familial insomnia and Creutzfeldt–Jakob disease (CJD). Typically, the D178N mutation associated with the 129M genotype is related to fatal familial insomnia while the same mutation associated with the 129V genotype is linked to familial CJD. We describe a D178N-129M haplotype in a patient with early, severe dementia and late-onset minor insomnia, mainly presenting as the CJD phenotype. Cerebrospinal fluid 14-3-3 protein was positive. Diffusion weighted imaging demonstrated widespread cortical ribbon-like high signal intensity, which was also seen in the basal ganglia bilaterally. Arterial spin labeling (ASL) MRI showed severe hypoperfusion in the cerebral cortex, basal ganglia and thalami but this was least marked in the thalami. Neuroimaging abnormalities were more prominent in the cerebral cortex than the thalamus, which was in line with the clinical picture of severe dementia rather than insomnia. ASL-MRI seems to be a useful tool for the detection and follow-up of perfusion changes in patients and asymptomatic carriers harboring the PRNP mutation.

ABSTRACT 381

Background and aims: Watershed strokes (WS) affect preferentially cardiac surgery patients and can increase mortality up to ten times. Aims: We aim to describe a clinical case to call attention on this uncommon but potentially lethal complication. Methods: Chart review and literature search. IRB waived the need of informed consent. Results: Clinical case: a 4 year old boy admitted after ventriculoseptoplasty and a technically difficult RV infundibular hypertrophy repair. Time on CEC 150 minutes. MAP during de first 40 minutes on CEC was 30–40 mmHg, 10 mmHg lower than DAP before CEC, and the remaining time 45 to 50. A complete AV block after CEC rapidly convert to sinus rhythm, but the patient required epinephrine and milrinone to improve the blood pressure. At admission the patient showed clinical and laboratory signs of severe hypoperfusion: metabolic acidosis, hyperlactacidemia (7.2 mmol/L), gross hematuria, oliguria, abnormal liver test, and coagulopathy. Unconsciousness was related initially with sedoanalgesia for mechanical ventilation, but 46 hours after admission the patient presented acute arterial hypertension and pupillary changes. A CT scan revealed multiple hypodensity areas in both cerebral hemispheres and cerebellum. Despite aggressive supportive treatment for intracranial hypertension and hemodynamic stabilization, the patient presented brain death 10 days after admission. Conclusions: Postcardiac WS probably involves a combination of hypoperfusion and microembolization. Global systemic hypoperfusion caused by severe intraoperative hypotension is associated with poor outcomes. More research is needed toward improvements in intraoperative and postoperative management aimed at preventing neurologic morbidity in these patients.

Abstract T P37: Cerebral Blood Volume Does Not Differentiate Regions With Persistent Cerebral Hypoperfusion That Infarct From Those That Survive: A DEFUSE 2 Substudy

Background: The optimal Tmax threshold for predicting critically hypoperfused tissue is a delay of &gt;6 seconds. However, persistent Tmax &gt;6s lesions do not invariably progress to infarction. Differences in cerebral blood volume (CBV) may explain why some regions of persistent cerebral hypoperfusion (PCHP) infarct whereas others survive. We hypothesized that CBV is higher in areas of PCHP that survive versus those that infarct. Methods: We included patients that had: 1) a Tmax &gt;6s lesion on baseline and early follow-up MRI perfusion scans, and 2) a FLAIR lesion on the day 5 MRI scan. Regions of PCHP had to meet two criteria: 1) Tmax &gt;6s positive on both baseline and co-registered early follow-up MRI perfusion scans, and 2) DWI negative on the baseline MRI scan. PCHP regions were classified as PCHP-infarct if there was a corresponding lesion on the co-registered 5 day FLAIR and as PCHP-survival if there was no corresponding lesion. Patients with no region of either PCHP-infarct or PCHP-survival were excluded. The study had two parts. In part 1, the paired t-test was used to compare lesion volume, CBV, cerebral blood flow (CBF), mean transit time (MTT), and Tmax between PCHP-infarct and PCHP-survival regions within each patient. In part 2, the 2-sample t-test was used to compare mean volume, CBV, CBF, MTT, and Tmax in PCHP-infarct and PCHP-survival regions for all patients together as a group. Results: 61 patients were included in the analysis. Mean total PCHP volume was 26cc (16cc infarct, 10cc survival) and median total PCHP volume was 15cc (9cc infarct, 6cc survival). For part 1, CBV was not different in PCHP-infarct versus PCHP-survival (P=0.16). CBF was higher (P=0.05) in regions of PCHP-survival, and MTT and Tmax were less prolonged (P=0.03 and P &lt; 0.01). For part 2, mean CBV and MTT did not differ between PCHP-infarct and PCHP-survival (P=0.23 and P=0.40). Mean CBF trended higher (P=0.07) and mean Tmax delays were milder (P= 0.04) in PCHP-survival. Conclusion: CBV does not differ between regions of PCHP-infarct versus PCHP-survival and does not explain why some areas of persistent, severe hypoperfusion survive. Tmax was less severely delayed and CBF values were higher in regions of PCHP-survival, which warrant further study.

Abstract 4: Excellent Collaterals in STAR: Minimal Infarct Core Trumps the Degree of Hypoperfusion

Background: Collateral grade on DSA before acute endovascular therapy of stroke predicts revascularization. Excellent collaterals were a potent predictor of good clinical outcomes at 90 days after treatment in Solitaire Flow Restoration Thrombectomy for Acute Revascularization (STAR). We studied whether excellent collaterals could be detected with either CT or MR perfusion imaging acquired immediately before treatment. Methods: Independent angio and CT/MRI core labs analyzed baseline DSA ASITN/SIR collateral grade and CT/MR perfusion imaging volumes (equivalent definitions of infarct core and Tmax &gt; 4, 6, 8, 10, 12, 14 s). Hypoperfusion was defined as Tmax &gt; 6s, with Tmax hypoperfusion intensity ratios of 10/6 and 14/6, and target and malignant profiles based on DEFUSE-2. Excellent collateral grade (3-4) was analyzed by pretreatment CT/MRI patterns. Results: 64 of 202 cases in STAR (mean age 67.9 ± 13.1 years; 53% women; median baseline NIHSS 15 (8-25)) had CT/MR perfusion volumes and ASITN/SIR collateral grade analyzed. Distribution of collateral grade (0, n=2; 1, n=31; 2, n=14; 3, n=15; 4, n=2) was similar to the entire STAR population. Excellent collaterals were unrelated to age and gender, with a trend towards lower NIHSS (OR 0.9, p=0.12). Excellent collaterals in 17/64 (27%) demonstrated very small core volumes (0 cc, n=8; 1-25 cc, n=8; &gt; 25 cc, n=1) compared to other cases. Similarly, clinical-core mismatch (defined as baseline NIHSS ≥8-16 and core ≤ 25 cc; baseline NIHSS ≥17 and ≤ 50 cc) was noted in 16/17 (94%). The extent of hypoperfusion (Tmax &gt; 6s) and degrees of hypoperfusion (Tmax 4-14, 10/6, and 14/6) were not related to the presence of excellent collaterals. Target mismatch (n=53/64, 83%) showed an OR 4.32 (p=0.18) for excellent collaterals and no malignant profiles were associated with grade 3-4. Conclusions: CT/MR perfusion patterns prior to endovascular therapy are associated with excellent collaterals, evident as very small infarct core, target mismatch, and clinical-core mismatch. The degree of Tmax hypoperfusion severity alone cannot be used to identify presence of excellent collaterals.

Impact of atrial fibrillation on clinical outcome in patients with acute ischemic stroke undergoing thrombolytic therapy

To investigate the impact of atrial fibrillation (AF) on clinical outcomes in patients with acute ischemic stroke undergoing thrombolytic therapy. The clinical data of 330 patients with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator (rt-PA) therapy in the Second Affiliated Hospital, Zhejiang University School of Medicine between June 2009 and August 2013 were reviewed. Clinical outcomes in AF and non-AF groups were evaluated by univariate and multivariate analysis. Favorable outcome was defined as a modified Rankin Scale (mRS) 0-2 on day 90. Hemorrhagic transformation (HT) was classified as hemorrhagic infarction (HI) and parenchymal hematoma (PH) within the first 24h according to ECASS II criteria. Hypoperfusion and severe hypoperfusion were defined as Tmax >6 s and >8 s, respectively. The rate of reperfusion was compared between AF and non-AF groups. Among 330 patients, 137(41.5%) had AF. Compared with non-AF patients, patients with AF were older [(71.7±11.5)y vs (63.4±13.2)y, P<0.001], had higher baseline National Institutes of Health Stroke Scale [IQR, 13(8-16) vs 9(5-15), P<0.001], higher rate of HT(HI: 28.5% vs 17.1%, P=0.015; PH: 13.9% vs 4.1%, P=0.002), and lower rate of favorable outcome (41.5% vs 58.0%, P=0.005) at d 90. After adjustment, AF was not a risk factor for favorable outcome (OR=0.920, 95%CI:0.533-1.586; P=0.763) and mortality (OR=1.381, 95%CI:1.096-1.242; P=0.466) on day 90. AF was also not associated with HI (OR=1.676, 95%CI: 0.972-3.031; P=0.088), but it increased the rate of PH (OR=3.621, 95%CI: 1.403-9.344; P=0.008). Among 94 patients with pre- and post-thrombolytic perfusion-weighted image, AF was not associated with increased rate of reperfusion for hypoperfusion (Tmax >6 s, OR=1.12, 95%CI: 0.35-3.63, P=0.849), but was correlated with increased rate of reperfusion for severe hypoperfusion (Tmax>8 s, OR=10.57, 95%CI:1.16-96.50, P=0.037). The presence of AF has no independent impact on neurological outcome in thrombolytic patients with acute ischemic stroke. It is associated with increased reperfusion rate of more severe hypoperfusion area and higher frequency of PH.