Piero Verro

Publications (23)125.67 Total impact

• Article: RNA in blood is altered prior to hemorrhagic transformation in ischemic stroke.

  Glen C Jickling, Bradley P Ander, Boryana Stamova, Xinhua Zhan, Dazhi Liu, Lena Rothstein Bsc, Piero Verro, Jane Khoury, Edward C Jauch, Arthur Pancioli, Joseph P Broderick, Frank R Sharp
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  ABSTRACT: OBJECTIVE: Hemorrhagic transformation (HT) is a major complication of ischemic stroke that worsens outcomes and increases mortality. Disruption of the blood brain barrier is a central feature to HT pathogenesis, and leukocytes may contribute to this process. We sought to determine whether ischemic strokes that develop HT have differences in RNA expression in blood within 3 hours of stroke onset prior to treatment with thrombolytic therapy. METHODS: Stroke patient blood samples were obtained prior to treatment with thrombolysis, and leukocyte RNA assessed by microarray analysis. Strokes that developed HT (n=11) were compared to strokes without HT (n=33) and controls (n=14). Genes were identified (corrected p-value <0.05, fold change ≥|1.2|) and functional analysis performed. RNA prediction of HT in stroke was evaluated using cross-validation, and in a second stroke cohort (n=52). RESULTS: Ischemic strokes that developed HT had differential expression of 29 genes in circulating leukocytes prior to treatment with thrombolytic therapy. A panel of 6 genes could predict strokes that later developed HT with 80% sensitivity and 70.2% specificity. Key pathways involved in HT of human stroke are described, including amphiregulin, a growth factor that regulates matrix metalloproteinase-9; a shift in transforming growth factor-beta signaling involving SMAD4, INPP5D and IRAK3; and a disruption of coagulation factors V and VIII. INTERPRETATION: Identified genes correspond to differences in inflammation and coagulation that may predispose to HT in ischemic stroke. Given the adverse impact of HT on stroke outcomes, further evaluation of the identified genes and pathways is warranted to determine their potential as therapeutic targets to reduce HT and as markers of HT risk. ANN NEUROL 2010.
  Annals of Neurology 03/2013; · 11.09 Impact Factor
• Article: Prediction of cardioembolic, arterial, and lacunar causes of cryptogenic stroke by gene expression and infarct location.

  Glen C Jickling, Boryana Stamova, Bradley P Ander, Xinhua Zhan, Dazhi Liu, Shara-Mae Sison, Piero Verro, Frank R Sharp
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  ABSTRACT: The cause of ischemic stroke remains unclear, or cryptogenic, in as many as 35% of patients with stroke. Not knowing the cause of stroke restricts optimal implementation of prevention therapy and limits stroke research. We demonstrate how gene expression profiles in blood can be used in conjunction with a measure of infarct location on neuroimaging to predict a probable cause in cryptogenic stroke. The cause of cryptogenic stroke was predicted using previously described profiles of differentially expressed genes characteristic of patients with cardioembolic, arterial, and lacunar stroke. RNA was isolated from peripheral blood of 131 cryptogenic strokes and compared with profiles derived from 149 strokes of known cause. Each sample was run on Affymetrix U133 Plus 2.0 microarrays. Cause of cryptogenic stroke was predicted using gene expression in blood and infarct location. Cryptogenic strokes were predicted to be 58% cardioembolic, 18% arterial, 12% lacunar, and 12% unclear etiology. Cryptogenic stroke of predicted cardioembolic etiology had more prior myocardial infarction and higher CHA(2)DS(2)-VASc scores compared with stroke of predicted arterial etiology. Predicted lacunar strokes had higher systolic and diastolic blood pressures and lower National Institutes of Health Stroke Scale compared with predicted arterial and cardioembolic strokes. Cryptogenic strokes of unclear predicted etiology were less likely to have a prior transient ischemic attack or ischemic stroke. Gene expression in conjunction with a measure of infarct location can predict a probable cause in cryptogenic strokes. Predicted groups require further evaluation to determine whether relevant clinical, imaging, or therapeutic differences exist for each group.
  Stroke 05/2012; 43(8):2036-41. · 5.73 Impact Factor
• Article: Y chromosome gene expression in the blood of male patients with ischemic stroke compared with male controls.

  Yingfang Tian, Boryana Stamova, Glen C Jickling, Huichun Xu, Dazhi Liu, Bradley P Ander, Cheryl Bushnell, Xinhua Zhan, Renee J Turner, Ryan R Davis, Piero Verro, William C Pevec, Nasim Hedayati, David L Dawson, Jane Khoury, Edward C Jauch, Arthur Pancioli, Joseph P Broderick, Frank R Sharp
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  ABSTRACT: Sex is suggested to be an important determinant of ischemic stroke risk factors, etiology, and outcome. However, the basis for this remains unclear. The Y chromosome is unique in males. Genes expressed in males on the Y chromosome that are associated with stroke may be important genetic contributors to the unique features of males with ischemic stroke, which would be helpful for explaining sex differences observed between men and women. We compared Y chromosome gene expression in males with ischemic stroke and male controls. Blood samples were obtained from 40 male patients ≤3, 5, and 24 hours after ischemic stroke and from 41 male controls (July 2003-April 2007). RNA was isolated from blood and was processed using Affymetrix Human U133 Plus 2.0 expression arrays (Affymetrix Inc., Santa Clara, California). Y chromosome genes differentially expressed between male patients with stroke and male control subjects were identified using an ANCOVA adjusted for age and batch. A P < 0.05 and a fold change >1.2 were considered significant. Seven genes on the Y chromosome were differentially expressed in males with ischemic stroke compared with controls. Five of these genes (VAMP7, CSF2RA, SPRY3, DHRSX, and PLCXD1) are located on pseudoautosomal regions of the human Y chromosome. The other 2 genes (EIF1AY and DDX3Y) are located on the nonrecombining region of the human Y chromosome. The identified genes were associated with immunology, RNA metabolism, vesicle fusion, and angiogenesis. Specific genes on the Y chromosome are differentially expressed in blood after ischemic stroke. These genes provide insight into potential molecular contributors to sex differences in ischemic stroke.
  Gender Medicine 02/2012; 9(2):68-75.e3. · 2.10 Impact Factor
• Article: Ischemic transient neurological events identified by immune response to cerebral ischemia.

  Glen C Jickling, Xinhua Zhan, Boryana Stamova, Bradley P Ander, Yingfang Tian, Dazhi Liu, Shara-Mae Sison, Piero Verro, S Claiborne Johnston, Frank R Sharp
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  ABSTRACT: Deciphering whether a transient neurological event (TNE) is of ischemic or nonischemic etiology can be challenging. Ischemia of cerebral tissue elicits an immune response in stroke and transient ischemic attack (TIA). This response, as detected by RNA expressed in immune cells, could potentially distinguish ischemic from nonischemic TNE. Analysis of 208 TIAs, ischemic strokes, controls, and TNE was performed. RNA from blood was processed on microarrays. TIAs (n=26) and ischemic strokes (n=94) were compared with controls (n=44) to identify differentially expressed genes (false discovery rate <0.05, fold change ≥1.2). Genes common to TIA and stroke were used predict ischemia in TIA diffusion-weighted imaging-positive/minor stroke (n=17), nonischemic TNE (n=13), and TNE of unclear etiology (n=14). Seventy-four genes expressed in TIA were common to those in ischemic stroke. Functional pathways common to TIA and stroke related to activation of innate and adaptive immune systems, involving granulocytes and B cells. A prediction model using 26 of the 74 ischemia genes distinguished TIA and stroke subjects from control subjects with 89% sensitivity and specificity. In the validation cohort, 17 of 17 TIA diffusion-weighted imaging-positive/minor strokes were predicted to be ischemic, and 10 of 13 nonischemic TNE were predicted to be nonischemic. In TNE of unclear etiology, 71% were predicted to be ischemic. These subjects had higher ABCD(2) scores. A common molecular response to ischemia in TIA and stroke was identified, relating to activation of innate and adaptive immune systems. TNE of ischemic etiology was identified based on gene profiles that may be of clinical use once validated.
  Stroke 02/2012; 43(4):1006-12. · 5.73 Impact Factor
• Article: Effects of gender on gene expression in the blood of ischemic stroke patients.

  Yingfang Tian, Boryana Stamova, Glen C Jickling, Dazhi Liu, Bradley P Ander, Cheryl Bushnell, Xinhua Zhan, Ryan R Davis, Piero Verro, William C Pevec, Nasim Hedayati, David L Dawson, Jane Khoury, Edward C Jauch, Arthur Pancioli, Joseph P Broderick, Frank R Sharp
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  ABSTRACT: This study examined the effects of gender on RNA expression after ischemic stroke (IS). RNA obtained from blood of IS patients (n=51; 153 samples at < or =3, 5, and 24 hours) and from matched controls (n=52) were processed on Affymetrix microarrays. Analyses of covariance for stroke versus control samples were performed separately for both genders and the regulated genes for females compared with males. In all, 242, 227, and 338 male-specific genes were regulated at < or =3, 5, and 24 hours after IS, respectively, of which 59 were regulated at all time points. Overall, 774, 3,437, and 571 female-specific stroke genes were regulated at < or =3, 5, and 24 hours, respectively, of which 152 were regulated at all time points. Male-specific stroke genes were associated with integrin, integrin-liked kinase, actin, tight junction, Wnt/β-catenin, RhoA, fibroblast growth factors (FGF), granzyme, and tumor necrosis factor receptor (TNFR)2 signaling. Female-specific stroke genes were associated with p53, high-mobility group box-1, hypoxia inducible factor (HIF)1α, interleukin (IL)1, IL6, IL12, IL18, acute-phase response, T-helper, macrophage, and estrogen signaling. Cell death signaling was overrepresented in both genders, although the molecules and pathways differed. Gender affects gene expression in the blood of IS patients, which likely implies gender differences in immune, inflammatory, and cell death responses to stroke.
  Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 12/2011; 32(5):780-91. · 5.46 Impact Factor
• Article: The X-chromosome has a different pattern of gene expression in women compared with men with ischemic stroke.

  Boryana Stamova, Yingfang Tian, Glen Jickling, Cheryl Bushnell, Xinhua Zhan, Dazhi Liu, Bradley P Ander, Piero Verro, Vihar Patel, William C Pevec, Nasim Hedayati, David L Dawson, Edward C Jauch, Arthur Pancioli, Joseph P Broderick, Frank R Sharp
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  ABSTRACT: Differences in ischemic stroke between men and women have been mainly attributed to hormonal effects. However, sex differences in immune response to ischemia may exist. We hypothesized that differential expression of X-chromosome genes in blood immune cells contribute to differences between men and women with ischemic stroke. RNA levels of 683 X-chromosome genes were measured on Affymetrix U133 Plus2.0 microarrays. Blood samples from patients with ischemic stroke were obtained at ≤ 3 hours, 5 hours, and 24 hours (n=61; 183 samples) after onset and compared with control subjects without symptomatic vascular diseases (n=109). Sex difference in X-chromosome gene expression was determined using analysis of covariance (false discovery rate ≤ 0.05, fold change ≥ 1.2). At ≤ 3, 5, and 24 hours after stroke, there were 37, 140, and 61 X-chromosome genes, respectively, that changed in women; and 23, 18, and 31 X-chromosome genes that changed in men. Female-specific genes were associated with post-translational modification, small-molecule biochemistry, and cell-cell signaling. Male-specific genes were associated with cellular movement, development, cell-trafficking, and cell death. Altered sex specific X-chromosome gene expression occurred in 2 genes known to be associated with human stroke, including galactosidase A and IDS, mutations of which result in Fabry disease and Hunter syndrome, respectively. There are differences in X-chromosome gene expression between men and women with ischemic stroke. Future studies are needed to decipher whether these differences are associated with sexually dimorphic immune response, repair or other mechanisms after stroke, or whether some of them represent risk determinants.
  Stroke 11/2011; 43(2):326-34. · 5.73 Impact Factor
• Article: Profiles of lacunar and nonlacunar stroke.

  Glen C Jickling, Boryana Stamova, Bradley P Ander, Xinhua Zhan, Yingfang Tian, Dazhi Liu, Huichun Xu, S Claiborne Johnston, Piero Verro, Frank R Sharp
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  ABSTRACT: Determining which small deep infarcts (SDIs) are of lacunar, arterial, or cardioembolic etiology is challenging, but important in delivering optimal stroke prevention therapy. We sought to distinguish lacunar from nonlacunar causes of SDIs using a gene expression profile. A total of 184 ischemic strokes were analyzed. Lacunar stroke was defined as a lacunar syndrome with infarction <15mm in a region supplied by penetrating arteries. RNA from blood was processed on whole genome microarrays. Genes differentially expressed between lacunar (n = 30) and nonlacunar strokes (n = 86) were identified (false discovery rate ≤ 0.05, fold change >|1.5|) and used to develop a prediction model. The model was evaluated by cross-validation and in a second test cohort (n = 36). The etiology of SDIs of unclear cause (SDIs ≥ 15mm or SDIs with potential embolic source) (n = 32) was predicted using the derived model. A 41-gene profile discriminated lacunar from nonlacunar stroke with >90% sensitivity and specificity. Of the 32 SDIs of unclear cause, 15 were predicted to be lacunar, and 17 were predicted to be nonlacunar. The identified profile represents differences in immune response between lacunar and nonlacunar stroke. Profiles of differentially expressed genes can distinguish lacunar from nonlacunar stroke. SDIs of unclear cause were frequently predicted to be of nonlacunar etiology, suggesting that comprehensive workup of SDIs is important to identify potential cardioembolic and arterial causes. Further study is required to evaluate the gene profile in an independent cohort and determine the clinical and treatment implications of SDIs of predicted nonlacunar etiology.
  Annals of Neurology 06/2011; 70(3):477-85. · 11.09 Impact Factor
• Article: Posterior reversible encephalopathy syndrome in the context of phentermine use resulting in intracranial hemorrhage.

  Victoria S S Wong, Harpreet Singh, Piero Verro
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  ABSTRACT: Posterior reversible encephalopathy syndrome (PRES) is a brain disorder characterized by clinical symptoms of headache, visual changes, altered mentation, and seizures. On neuroimaging, focal regions of symmetrical hemispheric edema are most commonly seen in the occipital lobes. It has been suggested that associated intracranial hemorrhage is present in approximately 5% to 17% of cases. We report a case of PRES with large bilateral parieto-occipital hemorrhages in the context of phentermine use. To our knowledge, this is the first reported case of phentermine use associated with PRES. A 35-year-old woman taking phentermine for weight loss presented with altered mental status and 2 witnessed generalized seizures. She was found to have large bilateral parieto-occipital hemorrhages. The radiographic imaging was consistent with PRES with hemorrhagic conversion. After treatment with anti-epileptic medication, normalization of blood pressure, and discontinuation of phentermine, the patient improved clinically. Five months after the event, the patient had a repeat brain magnetic resonance imaging that showed resolution of the diffuse edema and hemorrhage. This case of PRES with hemorrhagic conversation is distinctive in the bilateral and extensive nature of the hemorrhage, and, to our knowledge, is the first reported case of phentermine use likely resulting in PRES. Physicians should be aware of the cerebrovascular risks associated with phentermine use.
  The Neurologist 03/2011; 17(2):111-3. · 1.26 Impact Factor
• Article: Teaching NeuroImages: Brain air embolism due to YAG laser bronchoscopy.

  Piero Verro
  Neurology 11/2010; 75(18):e73. · 8.31 Impact Factor
• Source

  Available from: Renee J Turner

  Article: Signatures of cardioembolic and large-vessel ischemic stroke.

  Glen C Jickling, Huichun Xu, Boryana Stamova, Bradley P Ander, Xinhua Zhan, Yingfang Tian, Dazhi Liu, Renée J Turner, Matthew Mesias, Piero Verro, Jane Khoury, Edward C Jauch, Arthur Pancioli, Joseph P Broderick, Frank R Sharp
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  ABSTRACT: The cause of stroke remains unknown or cryptogenic in many patients. We sought to determine whether gene expression signatures in blood can distinguish between cardioembolic and large-vessel causes of stroke, and whether these profiles can predict stroke etiology in the cryptogenic group. A total of 194 samples from 76 acute ischemic stroke patients were analyzed. RNA was isolated from blood and run on Affymetrix U133 Plus2.0 microarrays. Genes that distinguish large-vessel from cardioembolic stroke were determined at 3, 5, and 24 hours following stroke onset. Predictors were evaluated using cross-validation and a separate set of patients with known stroke subtype. The cause of cryptogenic stroke was predicted based on a model developed from strokes of known cause and identified predictors. A 40-gene profile differentiated cardioembolic stroke from large-vessel stroke with >95% sensitivity and specificity. A separate 37-gene profile differentiated cardioembolic stroke due to atrial fibrillation from nonatrial fibrillation causes with >90% sensitivity and specificity. The identified genes elucidate differences in inflammation between stroke subtypes. When applied to patients with cryptogenic stroke, 17% are predicted to be large-vessel and 41% to be cardioembolic stroke. Of the cryptogenic strokes predicted to be cardioembolic, 27% were predicted to have atrial fibrillation. Gene expression signatures distinguish cardioembolic from large-vessel causes of ischemic stroke. These gene profiles may add valuable diagnostic information in the management of patients with stroke of unknown etiology though they need to be validated in future independent, large studies.
  Annals of Neurology 11/2010; 68(5):681-92. · 11.09 Impact Factor
• Source

  Available from: Renee J Turner

  Article: Distinctive RNA expression profiles in blood associated with white matter hyperintensities in brain.

  Huichun Xu, Boryana Stamova, Glen Jickling, Yingfang Tian, Xinhua Zhan, Bradley P Ander, Dazhi Liu, Renée Turner, Jonathan Rosand, Larry B Goldstein, Karen L Furie, Piero Verro, S Claiborne Johnston, Frank R Sharp, Charles S Decarli
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  ABSTRACT: White matter hyperintensities (WMH) are areas of high signal detected by T2 and fluid-attenuated inversion recovery sequences on brain MRI. Although associated with aging, cerebrovascular risk factors, and cognitive impairment, the pathogenesis of WMH remains unclear. Thus, RNA expression was assessed in the blood of individuals with and without extensive WMH to search for evidence of oxidative stress, inflammation, and other abnormalities described in WMH lesions in brain. Subjects included 20 with extensive WMH (WMH+), 45% of whom had Alzheimer disease, and 18 with minimal WMH (WMH-), 44% of whom had Alzheimer disease. All subjects were clinically evaluated and underwent quantitative MRI. Total RNA from whole blood was processed on human whole genome Affymetrix HU133 Plus 2.0 microarrays. RNA expression was analyzed using an analysis of covariance. Two hundred forty-one genes were differentially regulated at ± 1.2-fold difference (P < 0.005) in subjects with WMH+ as compared to WMH-, regardless of cognitive status and 50 genes were differentially regulated with ± 1.5-fold difference (P < 0.005). Cluster and principal components analyses showed that the expression profiles for these genes distinguished WMH+ from WMH- subjects. Function analyses suggested that WMH-specific genes were associated with oxidative stress, inflammation, detoxification, and hormone signaling, and included genes associated with oligodendrocyte proliferation, axon repair, long-term potentiation, and neurotransmission. The unique RNA expression profile in blood associated with WMH is consistent with roles of systemic oxidative stress and inflammation, as well as other potential processes in the pathogenesis or consequences of WMH.
  Stroke 10/2010; 41(12):2744-9. · 5.73 Impact Factor
• Article: Prolonged dependence of ischemic penumbra on induced hypertension.

  Piero Verro, Matthew Chow
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  ABSTRACT: Pharmacological elevation of blood pressure in acute stroke due to large artery occlusion may enhance collateral blood flow and salvage penumbral tissue. The duration of viability of human penumbral tissue under such circumstances is unclear. To describe a patient presenting with acute middle cerebral artery occlusion treated with induced hypertension who had prolonged survival of penumbral tissue with subsequent infarct extension after pressor agents were withdrawn. Enhanced collateral flow by elevation of blood pressure may result in prolonged survival of the ischemic penumbra which remains dependent on persistent use of pressor agents.
  The Neurologist 10/2009; 15(5):296-7. · 1.26 Impact Factor
• Article: IV vs. IA TPA in acute ischemic stroke with CT angiographic evidence of major vessel occlusion: a feasibility study.

  Souvik Sen, David Y Huang, Omid Akhavan, Susan Wilson, Piero Verro, Sten Solander
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  ABSTRACT: Studies suggest that stroke patients with thrombus in a major cerebral vessel respond less favorably to intravenous (IV) thrombolysis. The purpose of this study was to test the feasibility of a protocol comparing IV versus intra-arterial (IA) recombinant tissue plasminogen activator (TPA) in an acute ischemic stroke with major vessel occlusion. Consecutive ischemic stroke patients presenting <3 h from symptom onset with major vessel occlusion on CT angiogram (CTA) were randomly assigned to IV TPA (per NINDS protocol) or IA TPA (22 mg over 2 h). Demographics, times to presentation and thrombolysis, presenting NIH stroke scale (NIHSS) and 90-day NIHSS, Barthel Index, and modified Rankin Scale were recorded. CT-scans at 24-h were reviewed for presence of hemorrhage. Recanalization was determined by post-procedure MR angiograms, which are obtained the day after thrombolytic therapy. Seven patients (median NIHSS = 16) were randomized to IV (N = 4) or IA (N = 3) TPA. There were no significant differences in the presentation NIHSS, time to presentation, or time to treatment between the two groups. Hemorrhage was noted in one patient in the IA group (asymptomatic) and one patient in the IV group (symptomatic). Recanalization was seen in all patients treated with IA TPA and none treated with IV TPA (P = 0.03, Fisher's Exact test). We found that it is feasible to conduct a trial comparing IV vs. IA TPA in ischemic stroke patients with major vessel occlusion presenting <3 h from onset. Patients treated with IA TPA showed a trend toward higher rate of recanalization. A larger trial may be designed to test safety and effectiveness of IA TPA in this specific group of stroke patients.
  Neurocritical Care 03/2009; 11(1):76-81. · 2.47 Impact Factor
• Source

  Available from: Joseph P Broderick

  Article: Gene expression in peripheral blood differs after cardioembolic compared with large-vessel atherosclerotic stroke: biomarkers for the etiology of ischemic stroke.

  Huichun Xu, Yang Tang, Da-Zhi Liu, Ruiqiong Ran, Bradley P Ander, Michelle Apperson, Xin She Liu, Jane C Khoury, Jeffrey P Gregg, Arthur Pancioli, Edward C Jauch, Kenneth R Wagner, Piero Verro, Joseph P Broderick, Frank R Sharp
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  ABSTRACT: There are no biomarkers that differentiate cardioembolic from large-vessel atherosclerotic stroke, although the treatments differ for each and approximately 30% of strokes and transient ischemic attacks have undetermined etiologies using current clinical criteria. We aimed to define gene expression profiles in blood that differentiate cardioembolic from large-vessel atherosclerotic stroke. Peripheral blood samples were obtained from healthy controls and acute ischemic stroke patients (<3, 5, and 24 h). RNA was purified, labeled, and applied to Affymetrix Human U133 Plus 2.0 Arrays. Expression profiles in the blood of cardioembolic stroke patients are distinctive from those of large-vessel atherosclerotic stroke patients. Seventy-seven genes differ at least 1.5-fold between them, and a minimum number of 23 genes differentiate the two types of stroke with at least 95.2% specificity and 95.2% sensitivity for each. Genes regulated in large-vessel atherosclerotic stroke are expressed in platelets and monocytes and modulate hemostasis. Genes regulated in cardioembolic stroke are expressed in neutrophils and modulate immune responses to infectious stimuli. This new method can be used to predict whether a stroke of unknown etiology was because of cardioembolism or large-vessel atherosclerosis that would lead to different therapy. These results have wide ranging implications for similar disorders.
  Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 08/2008; 28(7):1320-8. · 5.46 Impact Factor
• Source

  Available from: ciape.org.br

  Article: Aspirin plus dipyridamole versus aspirin for prevention of vascular events after stroke or TIA: a meta-analysis.

  Piero Verro, Phillip B Gorelick, Danh Nguyen
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  ABSTRACT: This meta-analysis systematically reviewed randomized controlled trials comparing aspirin plus dipyridamole with aspirin alone in patients with stroke and TIA to determine the efficacy of these agents in preventing recurrent cerebral and systemic vascular events. We performed separate analyses of the incidences of stroke alone and composite outcome of stroke, myocardial infarction, or vascular death. We also performed two subset analyses, planned a priori, to examine effect size based on trials using (1) exclusively immediate-release and (2) predominantly extended-release dipyridamole. The summary results indicate a significant reduction in the overall risk ratio in favor of aspirin plus dipyridamole for stroke alone with relative risk 0.77 (0.67 to 0.89) and the composite end point with relative risk 0.85 (0.76 to 0.94). Studies using immediate-release dipyridamole showed a nonstatistically significant trend in favor of the combination for stroke alone with relative risk 0.83 (0.59 to 1.15) and for the composite outcome with relative risk 0.95 (0.75 to 1.19). Studies using predominantly extended-release dipyridamole showed a statistically significant difference in favor of the combination for stroke alone with relative risk 0.76 (0.65 to 0.89) and for the composite outcome with relative risk 0.82 (0.73 to 0.92). The combination of aspirin plus dipyridamole is more effective than aspirin alone in preventing stroke and other serious vascular events in patients with minor stroke and TIAs. The risk reduction was greater and statistically significant for studies using primarily extended release dipyridamole, which may reflect a true pharmacological effect or lack of statistical power in studies using immediate release dipyridamole.
  Stroke 05/2008; 39(4):1358-63. · 5.73 Impact Factor
• Article: Genomic profiles of stroke in blood.

  Frank R Sharp, Huichun Xu, Lisa Lit, Wynn Walker, Joseph Pinter, Michelle Apperson, Piero Verro
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  ABSTRACT: These studies show that gene expression changes in most patients by 2 to 3 hours after ischemic stroke, and in all patients studied by 24 hours.
  Stroke 03/2007; 38(2 Suppl):691-3. · 5.73 Impact Factor
• Article: Clinical application of CT angiography in acute ischemic stroke.

  Piero Verro, Lawrence N Tanenbaum, Neil Borden, Noam Eshkar, Souvik Sen
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  ABSTRACT: To evaluate the contribution of CT angiography (CTA) in predicting clinical outcome in a broad spectrum of patients presenting with acute neurological deficits suggestive of brain ischemia, to assess its strengths and limitations in this setting, and examine its influence on selection of patients for thrombolytic treatment. Prospective, observational outcome study of 54 consecutive patients with acute neurological deficits suggestive of brain ischemia who received immediate CTA. Clinical outcome was compared for patients presenting with and without arterial occlusion on CTA. Treatment decisions made by a vascular neurologist blinded to CTA results were compared to CTA cognizant treatment. For patients presenting with slight to moderate neurological deficits, the sensitivity and specificity for predicting good clinical outcome was 0.62 and 0.79, respectively, using the initial NIH Stroke Scale (NIHSS) score alone, and 0.38 and 0.92 if additionally, CTA showed no occlusion. For patients presenting with more severe deficits, the sensitivity and specificity for predicting poor clinical outcome using the NIHSS score alone was 0.79 and 0.60, compared to 0.67 and 0.92 if CTA showed vessel obstruction. CTA correctly identified six stroke mimickers. Selection of patients for thrombolysis made with knowledge of CTA results were more often conservative, and corresponded to CTA blinded decisions in 42/50 cases (84%, r=0.72). Combining CTA results with the neurological exam allows increased specificity for predicting clinical outcome as compared to predictions based on admission NIH Stroke Scale score alone. Awareness of CTA results was occasionally associated with less aggressive treatment and testing decisions.
  Clinical Neurology and Neurosurgery 03/2007; 109(2):138-45. · 1.58 Impact Factor
• Source

  Available from: Janice Carrozzella

  Article: Gene expression in blood changes rapidly in neutrophils and monocytes after ischemic stroke in humans: a microarray study.

  Yang Tang, Huichun Xu, XinLi Du, Lisa Lit, Wynn Walker, Aigang Lu, Ruiqiong Ran, Jeffrey P Gregg, Melinda Reilly, Art Pancioli, [......], Laura R Sauerbeck, Janice A Carrozzella, Judith Spilker, Joseph Clark, Kenneth R Wagner, Edward C Jauch, Dongwoo J Chang, Piero Verro, Joseph P Broderick, Frank R Sharp
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  ABSTRACT: Ischemic brain and peripheral white blood cells release cytokines, chemokines and other molecules that activate the peripheral white blood cells after stroke. To assess gene expression in these peripheral white blood cells, whole blood was examined using oligonucleotide microarrays in 15 patients at 2.4+/-0.5, 5 and 24 h after onset of ischemic stroke and compared with control blood samples. The 2.4-h blood samples were drawn before patients were treated either with tissue-type plasminogen activator (tPA) alone or with tPA plus Eptifibatide (the Combination approach to Lysis utilizing Eptifibatide And Recombinant tPA trial). Most genes induced in whole blood at 2 to 3 h were also induced at 5 and 24 h. Separate studies showed that the genes induced at 2 to 24 h after stroke were expressed mainly by polymorphonuclear leukocytes and to a lesser degree by monocytes. These genes included: matrix metalloproteinase 9; S100 calcium-binding proteins P, A12 and A9; coagulation factor V; arginase I; carbonic anhydrase IV; lymphocyte antigen 96 (cluster of differentiation (CD)96); monocarboxylic acid transporter (6); ets-2 (erythroblastosis virus E26 oncogene homolog 2); homeobox gene Hox 1.11; cytoskeleton-associated protein 4; N-formylpeptide receptor; ribonuclease-2; N-acetylneuraminate pyruvate lyase; BCL6; glycogen phosphorylase. The fold change of these genes varied from 1.6 to 6.8 and these 18 genes correctly classified 10/15 patients at 2.4 h, 13/15 patients at 5 h and 15/15 patients at 24 h after stroke. These data provide insights into the inflammatory responses after stroke in humans, and should be helpful in diagnosis, understanding etiology and pathogenesis, and guiding acute treatment and development of new treatments for stroke.
  Journal of Cerebral Blood Flow &#38 Metabolism 09/2006; 26(8):1089-102. · 5.01 Impact Factor
• Article: Early risk of stroke after transient ischemic attack: back to the future.

  Piero Verro
  Canadian Medical Association Journal 04/2004; 170(7):1113-4. · 8.22 Impact Factor
• Article: Hyperdense middle cerebral artery sign: can it be used to select intra-arterial versus intravenous thrombolysis in acute ischemic stroke?

  Pinky Agarwal, Sanjeev Kumar, Subramanian Hariharan, Noam Eshkar, Piero Verro, Barry Cohen, Souvik Sen
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  ABSTRACT: Stroke patients with a hyperdense middle cerebral artery sign (HMCAS) may respond less favorably to intravenous (IV) thrombolysis. To compare outcomes of patients with and without early CT findings treated with IV versus intra-arterial (IA) recombinant tissue plasminogen activator (rtPA). Initial and 24-hour CT scans of the head were evaluated in 83 consecutive stroke patients (66 on IV rtPA, 17 on IA rtPA). Time permitting, a CT angiogram was performed immediately after the initial CT scan to ascertain major cerebral artery occlusion. Demographics and etiological stroke subtype, times to thrombolysis and CT scan, baseline (prethrombolysis) and 24-hour National Institutes of Health stroke scale (NIHSS) score, discharge NIHSS score and 90-day modified Rankin scale (mRS) were recorded. The initial CT of these patients was examined for early signs of stroke. The 24-hour scan was reviewed for the presence of infarct, hemorrhage and persistence of HCMAS. A favorable outcome, indicated by a significant improvement in the discharge NIHSS score, was noted with IA rtPA, irrespective of the presence (p = 0.001) or absence (p = 0.01) of HCMAS. A less favorable outcome in discharge NIHSS score was noted with IV rtPA in patients with HCMAS (p = not significant) than those without the sign (p < 0.001). A similar proportion of patients with HCMAS exhibited a neurological improvement at 24 h as those without the sign in the IA rtPA group (p = 0.9). However, a smaller proportion of patients with HCMAS exhibited a neurological improvement at 24 h than those without the sign in the IV rtPA group (p = 0.005). The results were similar using 90-day mRS </=1 as an indicator of significant persistent improvement (p = 1.0 for IA rtPA and 0.04 for IV rtPA group). In a small sample, patients with HMCAS appeared to respond better to IA than IV rtPA.
  Cerebrovascular Diseases 02/2004; 17(2-3):182-90. · 2.72 Impact Factor