Grupo de Estudio de Enfermedades Cerebrovasculares de la SEN

Lipoprotein-Associated Phospholipase A(2) Activity Is Associated with Large-Artery Atherosclerotic Etiology and Recurrent Stroke in TIA Patients.

Cerebrovasc Dis. 2011 Dec 14;33(2):150-158

Authors: Delgado P, Chacón P, Penalba A, Pelegri D, García-Berrocoso T, Giralt D, Santamarina E, Ribó M, Maisterra O, Alvarez-Sabín J, Rosell A, Montaner J

Abstract
Background: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) has emerged as a novel biomarker in cardiovascular diseases due to its ability to predict stroke in population-based studies. We aimed to investigate Lp-PLA(2) levels in transient ischemic attack (TIA) patients and to study their relationship with stroke recurrence. Methods: Lp-PLA(2) mass and activity were measured by means of the PLAC test with an automated Olympus analyzer and by a colorimetric activity method (diaDexus) in 166 TIA patients and 144 healthy controls. Vascular risk factors and stroke etiology were assessed. Outcome was defined as the presence of recurrent stroke/TIA within 7 and 30 days after the index TIA. Multivariate analyses were performed to identify potential predictors of recurrence. Results: Both Lp-PLA(2) mass and activity (p < 0.05) were higher in TIA than in controls. Several risk factors or previous treatments were associated with Lp-PLA(2) mass and activity level. During follow-up, 20 strokes/TIA (12%) occurred within the first 30 days and the presence of a large-artery atherosclerosis etiology of stroke (HR 3.28, p = 0.011), together with the past medical history of hyperlipidemia (HR 3.68, p = 0.008) and Lp-PLA(2) activity of >207 nmol/ml/min (HR 2.7, p = 0.042) were all significant predictors for recurrent stroke/TIA. Conclusions: Lp-PLA(2) activity might add significant prognostic information in the early evaluation of TIA patients.

PMID: 22178747 [PubMed - as supplied by publisher]

Quantification of Thrombus Hounsfield Units on Noncontrast CT Predicts Stroke Subtype and Early Recanalization after Intravenous Recombinant Tissue Plasminogen Activator.

AJNR Am J Neuroradiol. 2011 Dec 8;

Authors: Puig J, Pedraza S, Demchuk A, Daunis-I-Estadella J, Termes H, Blasco G, Soria G, Boada I, Remollo S, Baños J, Serena J, Castellanos M

Abstract
BACKGROUND AND PURPOSE:Little is known about the factors that determine recanalization after intravenous thrombolysis. We assessed the value of thrombus Hounsfield unit quantification as a predictive marker of stroke subtype and MCA recanalization after intravenous rtPA treatment.MATERIALS AND METHODS:NCCT scans and CTA were performed on patients with MCA acute stroke within 4.5 hours of symptom onset. Demographics, stroke severity, vessel hyperattenuation, occlusion site, thrombus length, and time to thrombolysis were recorded. Stroke origin was categorized as LAA, cardioembolic, or indeterminate according to TOAST criteria. Two blinded neuroradiologists calculated the Hounsfield unit values for the thrombus and contralateral MCA segment. We used ROC curves to determine the rHU cutoff point to discriminate patients with successful recanalization from those without. We assessed the accuracy (sensitivity, specificity, and positive and negative predictive values) of rHU in the prediction of recanalization.RESULTS:Of 87 consecutive patients, 45 received intravenous rtPA and only 15 (33.3%) patients had acute recanalization. rHU values and stroke mechanism were the highest predictive factors of recanalization. The Matthews correlation coefficient was highest for rHU (0.901). The sensitivity, specificity, and positive and negative predictive values for lack of recanalization after intravenous rtPA for rHU ≤ 1.382 were 100%, 86.67%, 93.75%, and 100%, respectively. LAA thrombi had lower rHU than cardioembolic and indeterminate stroke thrombi (P = .004).CONCLUSIONS:The Hounsfield unit thrombus measurement ratio can predict recanalization with intravenous rtPA and may have clinical utility for endovascular treatment decision making.

PMID: 22158924 [PubMed - as supplied by publisher]

Association of innate immune activation with latent Epstein-Barr virus in active MS lesions.

Neurology. 2011 Dec 7;

Authors: Tzartos JS, Khan G, Vossenkamper A, Cruz-Sadaba M, Lonardi S, Sefia E, Meager A, Elia A, Middeldorp JM, Clemens M, Farrell PJ, Giovannoni G, Meier UC

Abstract
OBJECTIVE:To determine whether the activation of innate immune responses, which can be elicited by pathogenic and endogenous triggers, is associated with the presence of Epstein-Barr virus (EBV) infection in the multiple sclerosis (MS) brain. METHODS:White matter postmortem MS (n = 10) and control tissue (n = 11) was analyzed for the expression of the proinflammatory cytokine interferon α (IFNα) by immunohistochemistry and for EBV by using the highly sensitive method of EBV-encoded RNA (EBER) in situ hybridization. RESULTS:We detected overexpression of IFNα in active areas of white matter MS lesions but not in inactive MS lesions, normal-appearing white matter, or normal brains. The presence of IFNα in macrophages and microglia (expressing human leukocyte antigen class II) is suggestive of local production as part of an acute inflammatory process. Interestingly, EBERs were also specifically detected in areas where IFNα was overexpressed in these preselected active MS lesions. EBER+ cells were also found in CNS lymphoma and stroke cases, but were absent in other control brains. We next addressed a potential mechanism, e.g., the role of EBERs in eliciting IFNα production, and transfected EBERs into human embryonic kidney (HEK) cells. We used HEK cells that stably expressed Toll-like receptor-3, which recognizes double-stranded RNAs, associated with many viral infections. EBERs elicited IFNα production in vitro. CONCLUSION:These findings suggest that latent EBV infection may contribute to the inflammatory milieu in active MS lesions by activating innate immune responses, e.g., IFNα production. Unraveling the underlying mechanisms may help in uncovering causal pathways and developing better treatment strategies for MS and other neuroinflammatory diseases.

PMID: 22156987 [PubMed - as supplied by publisher]

Variations in Quality Indicators of Acute Stroke Care in 6 European Countries: The European Implementation Score (EIS) Collaboration.

Stroke. 2011 Dec 8;

Authors: Wiedmann S, Norrving B, Nowe T, Abilleira S, Asplund K, Dennis M, Hermanek P, Rudd A, Thijs V, Wolfe CD, Heuschmann PU

Abstract
BACKGROUND AND PURPOSE: Quality indicators serve as standards of care by which performance of individual hospitals is measured. Although several audits for monitoring quality of stroke care have been established in Europe, there is currently no consensus on quality indicators for acute stroke care or for methodology for collecting information on these measures. METHODS: An up-to-date inventory on European stroke audits in place in 2006 was performed in the course of a project funded by the European Union (European Implementation Score Collaboration [EIS]). Two regional (Flanders, Belgium; Catalonia, Spain) and 4 national (Germany, Scotland, Sweden, England/Wales/Northern Ireland) stroke audits took part. Between November 2009 and July 2010, 2 standardized surveys and a series of interviews were performed to determine characteristics, methods, and content of these quality initiatives. For quality purposes, all summarized information was validated by representatives of the respective audits. RESULTS: Overall, 123 quality indicators (91 process, 24 outcome, and 8 structural indicators) were identified. Anticoagulants in patients with atrial fibrillation and brain imaging were the only quality indicators used in all, whereas another 13 indicators were used in at least 2 of the quality initiatives. Substantial variations were found across the audits in terms of the development process of quality indicators, inclusion criteria, participation, population coverage, data documentation, follow-ups, benchmarking, and feedback of results to participants. CONCLUSIONS: There is a huge variety in measuring performance of acute stroke care in Europe, hampering valid comparisons of acute stroke care. Common standards for defining quality indicators and collecting information required for these measures should be defined in Europe.

PMID: 22156695 [PubMed - as supplied by publisher]

Temporal profile and prognostic value of Lp-PLA2 mass and activity in the acute stroke setting.

Atherosclerosis. 2011 Nov 19;

Authors: Delgado P, Chacón P, Penalba A, Pelegrí D, Merino C, Ribó M, Rubiera M, Alvarez-Sabin J, Montaner J

Abstract
BACKGROUND: Lp-PLA2 is a novel biomarker in cardiovascular diseases due to its ability to predict first-ever and recurrent stroke. Little information is known regarding its influence on early outcome after stroke. OBJECTIVES: We aimed to investigate Lp-PLA2 in t-PA-treated stroke patients and to study its relationship with early outcome. METHODS: Lp-PLA2 mass and activity were measured in 135 healthy controls and also in stroke patients treated with t-PA at baseline (n=99) and serially thereafter (n=34) by means of the PLAC test at an automated Olympus analyzer and by a colorimetric activity method (diaDexus). NIHSS scores and TCD recordings were also obtained serially. Outcome was defined according to early neurological status, the presence of arterial recanalization and functional outcome at third month. RESULTS: Lp-PLA2 mass was increased as compared to controls, whereas Lp-PLA2 activity was significantly decreased at baseline as compared with controls and with 1 and 24h determinations. Lp-PLA2 mass and activity were not related with early (48h) neurological status. Regarding recanalization, higher mass and activity were found among patients who did not achieve complete recanalization by the end of t-PA treatment (p=0.029 for mass, p=0.044 for activity). Lp-PLA2 mass and the existence of a proximal occlusion at baseline were the most powerful predictors for persistent occlusions (OR for proximal occlusion 6.8. p=0.036, OR for Lp-PLA2 mass 7.2 per standard deviation increase, p=0.008). CONCLUSIONS: Significant changes in Lp-PLA2 concentrations occur early after stroke onset. Lp-PLA2 mass may add relevant information regarding early arterial recanalization in intravenous t-PA-treated stroke patients.

PMID: 22153151 [PubMed - as supplied by publisher]

Clinical Outcomes, Resource Use, and Costs at 1 Year in Patients with Acute Coronary Syndrome Undergoing PCI:: Results from the Multinational APTOR Registry.

J Interv Cardiol. 2011 Dec 8;

Authors: Bakhai A, Ferrieres J, Iñiguez A, Sartral M, Belger M, Schmitt C, Zeymer U

Abstract
Background: Limited prospectively collected data are available on the total outcomes, cost estimates, and quality of life associated with treatment of acute coronary syndrome (ACS) through 1 year in a nonclinical-trial setting, or on the impact of new clinical events by 1 year on resource utilization and costs. Methods: The Antiplatelet Therapy Observational Registry (APTOR) 12-month study followed 1,335 concurrently recruited ACS patients undergoing percutaneous coronary intervention (PCI) and treated with antiplatelet therapy from France, Spain, and the United Kingdom in a "real world" clinical setting. Data were collected on clinical events, resource utilization, quality of life, and cost estimates through 1-year follow-up. Results: By 1 year, 14.4% (95% CI 12.7-16.4%) of patients experienced a clinical event of death, MI, stroke, unstable angina, urgent target vessel revascularization, or acute heart failure. Costs by 1 year were higher among those who had a new clinical event (£8,988, 95% CI £7,848, £10,395) as compared with those with no events (£5,809, 95% CI £5,486, £6,161). This increased cost was due to higher postdischarge resource use costs. Using the EQ-5D assessment at 1 year, quality of life was directionally lower in those patients who had experienced a new clinical event. Conclusions: The risk of experiencing a new clinical event during the year following an ACS, which was treated with PCI, remains high among European patients, with one-seventh of patients having a new event. These additional clinical outcomes reduce quality of life and increase health care expenditures, expanding the already high cost of treatment for ACS. (J Interven Cardiol 2011;**:1-9).

PMID: 22150757 [PubMed - as supplied by publisher]

Central sleep apnea is associated with increased risk of ischemic stroke in the elderly.

Acta Neurol Scand. 2011 Dec 9;

Authors: Muñoz R, Durán-Cantolla J, Martinez-Vila E, Gállego J, Rubio R, Aizpuru F, De La Torre G, Barbé F

Abstract
Muñoz R, Durán-Cantolla J, Martinez-Vila E, Gállego J, Rubio R, Aizpuru F, De La Torre G, Barbé F. Central sleep apnea and risk of stroke in the elderly. Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2011.01625.x. © 2011 John Wiley & Sons A/S. Objectives -  Sleep apnea/hypopnea syndrome is a well-recognized independent risk factor for stroke in middle-aged population, but controversy remains in older subjects. We examined the possible association between different respiratory parameters and risk of stroke in a prospective population-based cohort of 394 stroke-free elderly subjects. Material and Methods -  Fully overnight polysomnography was performed at baseline. Over the 6 year follow-up period, 20 ischemic strokes occurred. Differences in stroke-free survival between subjects according to central apnea index (CAI) were assessed. Results -  We just observed association with incident ischemic stroke on central sleep apnea (CSA) episodes. Obstructive sleep apnea, time passed under 90% oxygen saturation, or arousal index were not associated. The event-free survival was lowest in the highest CAI group. This association was independent of any other vascular risk factors. Conclusions -  CSA is the specific respiratory event associated with stroke in the elderly. Additionally, CSA could be a marker of silent brain ischemia, as a sign of disturbed regulation of central respiratory mechanisms, tentatively of ischemic origin.

PMID: 22150745 [PubMed - as supplied by publisher]

Prognostic Value of Exercise Echocardiography in Patients with Hypertrophic Cardiomyopathy.

J Am Soc Echocardiogr. 2011 Dec 1;

Authors: Peteiro J, Bouzas-Mosquera A, Fernandez X, Monserrat L, Pazos P, Estevez-Loureiro R, Castro-Beiras A

Abstract
BACKGROUND: Although exercise echocardiography may assess left ventricular (LV) function and LV outflow tract (LVOT) gradients during exercise in patients with hypertrophic cardiomyopathy (HCM), its value for predicting outcomes has not been studied. The aim of this study was to determine whether exercise echocardiography predicts outcomes in patients with HCM. METHODS: LV function and LVOT gradients were evaluated during exercise echocardiography in 239 patients with HCM. RESULTS: Sixty patients (25.1%) had LVOT obstruction at rest, and 43 (18%) developed exercise-induced LVOT obstruction. The mean resting LV ejection fraction was 69 ± 9%, and the mean resting wall motion score index was 1.00 ± 0.06. Wall motion abnormalities during exercise were seen in 19 patients (7.9%). During follow-up of 4.1 ± 2.6 years, 19 patients had hard events (cardiac death, cardiac transplantation, appropriate discharge of a defibrillator, stroke, myocardial infarction, or hospitalization for heart failure), and 41 patients had composite end points of hard or soft events (including atrial fibrillation and syncope). Exercise wall motion abnormalities occurred in 31.5% of patients with hard events compared with 5.9% of patients without hard events (P < .001). After adjustment, LV wall thickness (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.05-1.21; P = .002), resting wall motion score index (HR, 21.59; 95% CI, 2.38-196.1, P = .006), and metabolic equivalents (HR, 0.74; 95% CI, 0.63-0.88; P = .001) remained independent predictors of hard events. Change in wall motion score index was also independently associated with hard events (HR, 52.30; 95% CI, 3.81-718.5; P = .003) and with the composite end point (HR, 39.51; 95% CI, 3.79-412.4; P = .002). LVOT obstruction was not associated with either end point. CONCLUSIONS: Assessment of exercise capacity and LV systolic function during exercise echocardiography may have a role in risk stratification of patients with HCM.

PMID: 22137254 [PubMed - as supplied by publisher]

Serum cholesterol levels and survival after rtPA treatment in acute stroke.

Eur J Neurol. 2011 Dec 5;

Authors: Roquer J, Cuadrado-Godia E, Rodríguez-Campello A, Jiménez-Conde J, Martínez-Rodríguez JE, Giralt E, Ois A

Abstract
Background:  According to the reverse epidemiology hypothesis, high cholesterol levels might be protective and associated with greater survival rates under certain conditions. In stroke patients, a clear correlation between lipid levels and mortality after ischaemic and hemorrhagic strokes has been demonstrated. The aim of this study was to analyze the impact of lipid levels on 3-month mortality in patients with ischaemic stroke (IS) homogeneously treated with intravenous rtPA and admitted to a monitored acute stroke unit. Methods:  Retrospective analysis of a prospective cohort of 220 patients with an IS treated with rtPA within the first 4.5 h in a single tertiary hospital from January 2005 to August 2010. Results:  Mortality at 3 months was 15.0%. Univariate analysis showed that age, NIHSS at admission, heart failure, and atrial fibrillation were directly related to 3-month mortality; cholesterol, triglycerides, and low density lipoprotein were inversely associated. The death rate by cholesterol level was 5.5% for the highest tertile (>192 mg/dl), 13.7% for the middle (192-155 mg/dl), and 25.7% for the lowest (<155 mg/dl), P = 0.003. Multivariate analysis showed that amongst the lipid determinations, only cholesterol [OR: 0.985 (95% CI: 0.972-0.998), P = 0.021] was inversely associated with 3-month mortality. The 'protective' effect of cholesterol was independent of stroke severity and remained significant in non-lacunar strokes. Conclusions:  Survival of stroke patients receiving current, most effective medical treatment is related to blood cholesterol levels, with an inverse relationship between cholesterol and mortality. The mechanism of this apparently paradoxical situation remains unexplained but merits further research.

PMID: 22136724 [PubMed - as supplied by publisher]

Predictors of Tissue-Type Plasminogen Activator Nonresponders According to Location of Vessel Occlusion.

Stroke. 2011 Dec 1;

Authors: Mendonça N, Rodriguez-Luna D, Rubiera M, Boned-Riera S, Ribo M, Pagola J, Piñeiro S, Meler P, Alvarez-Sabin J, Montaner J, Molina CA

Abstract
BACKGROUND AND PURPOSE: Information on the clinical and hemodynamic profile of intravenous tissue-type plasminogen activator nonresponders, at different locations of arterial occlusion, may improve the selection of candidates for rescue reperfusion therapies. Therefore, we aim to investigate predictors of failing intravenous tissue-type plasminogen activator therapy according to occluded vessel and location of the clot. METHODS: We prospectively evaluated consecutive patients with an acute ischemic stroke admitted within the first 6 hours of onset. Five hundred forty-eight patients with documented intracranial occlusion were included. Patients were categorized according to site of vessel occlusion into 4 distinct groups: proximal middle cerebral artery occlusion (n=251), distal middle cerebral artery occlusion (n=194), internal carotid artery bifurcation occlusion (n=61), and basilar artery occlusion (n=42). Recanalization was assessed on transcranial Doppler at 1 hour of tissue-type plasminogen activator bolus. RESULTS: Among patients with proximal middle cerebral artery occlusion, the presence of severe extracranial internal carotid artery stenosis or occlusion (OR, 2.36; 95% CI, 1.15-4.84; P=0.02) and age >74 years (OR, 1.84; 95% CI, 1.02-3.31; P=0.04) independently predicted no recanalization. No independent predictors of no recanalization were identified in patients with distal middle cerebral artery occlusion. In patients with internal carotid artery bifurcation occlusion, a previous diagnosis of hypertension (OR, 12.77; 95% CI, 2.12-76.88; P=0.05), and absence of atrial fibrillation (OR, 8.15; 95% CI, 1.40-47.44; P=0.02) emerged as independent predictors of no recanalization. Similarly, among patients with basilar artery occlusion, absence of atrial fibrillation was as an independent predictor of no recanalization (OR, 7.50; 95% CI, 1.40-40.35; P=0.02). CONCLUSIONS: The use of relevant predictors of no recanalization and a rapid neurovascular evaluation may improve the selection of patients for more aggressive rescue strategies.

PMID: 22135072 [PubMed - as supplied by publisher]

VAP-1/SSAO Plasma Activity and Brain Expression in Human Hemorrhagic Stroke.

Cerebrovasc Dis. 2011 Dec 1;33(1):55-63

Authors: Hernandez-Guillamon M, Solé M, Delgado P, García-Bonilla L, Giralt D, Boada C, Penalba A, García S, Flores A, Ribó M, Alvarez-Sabin J, Ortega-Aznar A, Unzeta M, Montaner J

Abstract
Background: Vascular adhesion protein-1 (VAP-1) is a cell surface and circulating enzyme that belongs to the semicarbazide-sensitive amine oxidase (SSAO) family, which oxidatively deaminates primary amines and is implicated in leukocyte extravasation. Our aim was to investigate the alteration of soluble VAP-1/SSAO activity in plasma samples after acute intracerebral hemorrhage (ICH) and its presence in human ICH brain tissue. Methods: VAP-1/SSAO activity was determined in plasma of 66 ICH patients and 58 healthy controls. In addition, we assessed the expression of VAP-1/SSAO in postmortem brain tissue from hemorrhagic stroke patients by Western blot and immunohistochemistry. Results: We observed significantly higher levels of plasma VAP-1/SSAO activity in patients with ICH compared to matched elderly controls (p = 0.001). Plasma VAP-1/SSAO activity <2.7 pmol/min·mg and baseline ICH volume <17 ml were independent predictors of neurological improvement after 48 h (OR 6.8, 95% CI 1.14-41.67, p = 0.035, and OR 10.64, 95% CI 1.1-100, p = 0.041, respectively), after adjustment for baseline stroke severity. We also found that membrane-bound VAP-1/SSAO levels were lower in the perihematoma region than in the corresponding contralateral brain areas of patients deceased due to ICH (p = 0.024). Conclusions: Our data demonstrate that plasma VAP-1/SSAO activity is increased in ICH and predicts neurological outcome, suggesting a possible contribution of the soluble protein in secondary brain damage. Furthermore, anti-VAP-1/SSAO strategies might be a promising approach to prevent neurological worsening following ICH.

PMID: 22133888 [PubMed - as supplied by publisher]

Fatal Intracerebral Hemorrhage Associated with Administration of Recombinant Tissue Plasminogen Activator in a Stroke Patient on Treatment with Dabigatran.

Cerebrovasc Dis. 2011;32(6):614-615

Authors: Casado Naranjo I, Portilla-Cuenca JC, Jiménez Caballero PE, Calle Escobar ML, Romero Sevilla RM

Abstract
No abstract available.

PMID: 22133608 [PubMed - as supplied by publisher]

Migraine and hypercoagulable states in ischemic stroke.

Cephalalgia. 2011 Dec;31(16):1609-17

Authors: Martínez-Sánchez P, Martínez-Martínez M, Fuentes B, Cuesta M, Cuéllar-Gamboa L, Idrovo-Freire L, Fernández-Dominguez J, Díez-Tejedor E

Abstract
Background: Whether migraine is associated with a higher prevalence of hypercoagulable states (HS) in ischemic stroke patients is unknown. Methods: This was a prospective study of patients under 55 years of age with brain ischemia. A systematic questionnaire addressed the antecedent of migraine with aura (MA) or without aura (MO). We investigated the presence of HS by an extensive battery of haematological tests. The presence of patent foramen ovale (PFO) was assessed by trans-oesophageal echocardiography. Results: A total of 154 patients (95 men; mean ± SD age, 44.12 ± 8.4 years) were included; 44 had migraine, 15 had MA. HS were more frequent in the migraine than non-migraine group (38.6% vs. 16.4%, p < 0.01). The multivariate analysis showed that MO was associated with a 2.88-fold (95% CI, 1.14 to 7.28) increased risk of HS diagnosis. However, in the group of patients with brain infarction under 50 years old, MA, but not MO, was independently associated with HS (OR 6.81; 95% CI, 1.01 to 45.79). Conclusion: In young patients with ischemic stroke, migraine may be associated with a higher frequency of HS.

PMID: 22110165 [PubMed - in process]

Transient floating thrombus of the internal carotid artery associated with the JAK2(V617F) mutation.

J Neurol. 2011 Nov 23;

Authors: Martinez-Sanchez P, Cazorla-García R, Medina-Báez J, Fuentes B, Morado M, Díez-Tejedor E

PMID: 22109638 [PubMed - as supplied by publisher]

Brain ischemia and hypometabolism treated by ozone therapy.

Forsch Komplementmed. 2011;18(5):283-7

Authors: Clavo B, Suarez G, Aguilar Y, Gutierrez D, Ponce P, Cubero A, Robaina F, Carreras JL

Abstract
Background: Radiation-induced brain injury (RBI) and low-perfusion brain syndromes are mediated by ischemia and hypometabolism and have limited treatment options. Ozone therapy as treatment in vascular diseases has been described, but the effects on brain tissue have not been well documented. Case Report: We describe a 75-year-old patient with vascular risk factors and meningioma who was treated with stereotactic radiosurgery. 14 months later the patient presented with progressive clinical impairment despite the use of acetylsalicylic acid and corticosteroids. Clinical and imaging evaluations before/after ozone therapy were done by magnetic resonance imaging (MRI), computed tomography (CT), single photon emission computed tomography (SPECT), and positron emission tomography (PET); performance status assessment was done using Barthel Index and World Health Organization/Eastern Cooperative Oncology Group Scale (WHO/ECOG Scale). Ozone therapy was performed by autohemotransfusion. Results: Basal images showed brain areas with ischemia and hypometabolism compatible with ischemic processes and/or RBI. There were no changes in MRI or CT scan images following ozone therapy. However, improvements in brain perfusion and metabolism were demonstrable with SPECT and PET; they correlated with clinical development and performance status scales. Conclusion: This report supports our previous works about the effect of ozone therapy in cerebral blood flow, and it suggests the use of ozone therapy in ischemic and hypometabolic brain syndromes such as stroke or RBI.

PMID: 22105041 [PubMed - in process]

Matrix Metalloproteinase-10 Effectively Reduces Infarct Size in Experimental Stroke by Enhancing Fibrinolysis via a Thrombin-Activatable Fibrinolysis Inhibitor-Mediated Mechanism.

Circulation. 2011 Nov 21;

Authors: Orbe J, Barrenetxe J, Rodriguez JA, Vivien D, Orset C, Parks WC, Birkland TP, Serrano R, Purroy A, Martinez de Lizarrondo S, Angles-Cano E, Páramo JA

Abstract
BACKGROUND: The fibrinolytic and matrix metalloproteinase (MMP) systems cooperate in thrombus dissolution and extracellular matrix proteolysis. The plasminogen/plasmin system activates MMPs, and some MMPs have been involved in the dissolution of fibrin by targeting fibrin(ogen) directly or by collaborating with plasmin. MMP-10 has been implicated in inflammatory/thrombotic processes and vascular integrity, but whether MMP-10 could have a profibrinolytic effect and represent a promising thrombolytic agent is unknown. METHODS AND RESULTS: The effect of MMP-10 on fibrinolysis was studied in vitro and in vivo, in MMP-10-null mice (Mmp10(-/-)), with the use of 2 different murine models of arterial thrombosis: laser-induced carotid injury and ischemic stroke. In vitro, we showed that MMP-10 was capable of enhancing tissue plasminogen activator-induced fibrinolysis via a thrombin-activatable fibrinolysis inhibitor inactivation-mediated mechanism. In vivo, delayed fibrinolysis observed after photochemical carotid injury in Mmp10(-/-) mice was reversed by active recombinant human MMP-10. In a thrombin-induced stroke model, the reperfusion and the infarct size in sham or tissue plasminogen activator-treated animals were severely impaired in Mmp10(-/-) mice. In this model, administration of active MMP-10 to wild-type animals significantly reduced blood reperfusion time and infarct size to the same extent as tissue plasminogen activator and was associated with shorter bleeding time and no intracranial hemorrhage. This effect was not observed in thrombin-activatable fibrinolysis inhibitor-deficient mice, suggesting thrombin-activatable fibrinolysis inhibitor inactivation as one of the mechanisms involved in the MMP-10 profibrinolytic effect. CONCLUSIONS: A novel profibrinolytic role for MMP-10 in experimental ischemic stroke is described, opening new pathways for innovative fibrinolytic strategies in arterial thrombosis.

PMID: 22104553 [PubMed - as supplied by publisher]

Utility of the assessment of echogenicity in the identification of symptomatic carotid artery atheroma plaques in ischemic stroke patients.

Cerebrovasc Dis. 2011;32(6):535-41

Authors: Ruiz-Ares G, Fuentes B, Martínez-Sánchez P, Martínez-Martínez M, Díez-Tejedor E

Abstract
Background and Purpose: Echogenicity of atheroma carotid plaques is related to a higher risk of stroke. Clinical and subjective ultrasound criteria are used to identify symptomatic plaques, but the standardized grayscale median (GSM) value may be an objective tool for this diagnosis. Our aim was to analyze the utility of assessing the echogenicity of atheroma carotid plaques in the identification of symptomatic plaques. Methods: Observational prospective study with inclusion of acute noncardioembolic anterior cerebral circulation ischemic stroke patients. Only patients with bilateral atheroma plaques were included. Echogenicity of plaques was measured by a digital and standardized grayscale system in carotid ultrasound B-mode (longitudinal projection) conducted within the first week after admission. Results: Sixty-six patients were included and 132 plaques were examined. Symptomatic atheroma plaques were less echogenic than asymptomatic ones (GSM 20.0 vs. 29.0; p = 0.002). A ROC curve analysis showed the predictive value of GSM with an AUC of 0.707 (95% CI 0.592-0.823; p = 0.002) and pointed to a value of 24.4 as the optimal cut-off level to identify a plaque as symptomatic (74% sensitivity; 67% specificity). This GSM cut-off point remained significantly associated with a high probability of symptomatic plaque even after the inclusion of the degree of carotid stenosis (either >70% or >50%) in the multivariate logistic regression models. Conclusions: The assessment of echogenicity of atheroma carotid plaques by the GSM value combined with clinical characteristics and stenosis degree may be useful in the identification of symptomatic plaques.

PMID: 22104509 [PubMed - in process]

Neuroprotective efficacy of quinazoline type phosphodiesterase 7 inhibitors in cellular cultures and experimental stroke model.

Eur J Med Chem. 2011 Nov 4;

Authors: Redondo M, Zarruk JG, Ceballos P, Pérez DI, Pérez C, Perez-Castillo A, Moro MA, Brea J, Val C, Cadavid MI, Loza MI, Campillo NE, Martínez A, Gil C

Abstract
A simple and efficient synthetic method for the preparation of quinazoline type phosphodiesterase 7 (PDE7) inhibitors, based on microwave irradiation, has been developed. The use of this methodology improved yields and reaction times, providing a scalable procedure. These compounds are pharmacologically interesting because of their in vivo efficacy both in spinal cord injury and Parkinson's disease models, as shown in previous studies from our group. Herein we describe for the first time that administration of one of the PDE7 inhibitors here optimized, 3-phenyl-2,4-dithioxo-1,2,3,4-tetrahydroquinazoline (compound 5), ameliorated brain damage and improved behavioral outcome in a permanent middle cerebral artery occlusion (pMCAO) stroke model. Furthermore, we demonstrate that these PDE7 inhibitors are potent anti-inflammatory as well as neuroprotective agents in primary cultures of neural cells. These results led us to propose PDE7 inhibitors as a new class of therapeutic agents for neuroprotection.

PMID: 22100138 [PubMed - as supplied by publisher]

Thrombolytic therapy for acute ischemic stroke after recent transient ischemic attack.

Int J Stroke. 2011 Nov 9;

Authors: de Leciñana MA, Fuentes B, Masjuan J, Simal P, Díaz-Otero F, Reig G, Díez-Tejedor E, Gil-Nuñez A, Vivancos J, Egido JA

Abstract
BACKGROUND AND AIM: Safety and efficacy of intravenous thrombolysis in stroke patients with recent transient ischemic attack are hotly debated. Patients suffering transient ischemic attack may present with diffusion-weighted imaging lesions, and although normal computed tomography would not preclude thrombolysis, the concern is that they may be at higher risk for hemorrhage post-thrombolysis treatment. Prior ipsilateral transient ischemic attack might provide protection due to ischemic preconditioning. We assessed post-thrombolysis outcomes in stroke patients who had prior transient ischemic attack. METHODS: Multicentered prospective study of consecutive acute stroke patients treated with intravenous tissue plasminogen activator (tPA). Ipsilateral transient ischemic attack, baseline characteristics, risk factors, etiology, and time-lapse to treatment were recorded. National Institutes of Health Stroke Scale at seven-days and modified Rankin Scale at three-months, symptomatic intracranial hemorrhage, and mortality were compared in patients with and without transient ischemic attack. RESULTS: There were 877 patients included, 60 (6·84%) had previous ipsilateral transient ischemic attack within one-month prior to the current stroke (65% in the previous 24 h). Transient ischemic attack patients were more frequently men (70% vs. 53%; P = 0·011), younger (63 vs. 71 years of age; P = 0·011), smokers (37% vs. 25%; P = 0·043), and with large vessel disease (40% vs. 25%; P = 0·011). Severity of stroke at onset was similar to those with and without prior transient ischemic attack (median National Institutes of Health Stroke Scale score 12 vs. 14 P = 0·134). Those with previous transient ischemic attack were treated earlier (117 ± 52 vs. 144 ± 38 mins; P < 0·005). After adjustment for confounding variables, regression analysis showed that previous transient ischemic attack was not associated with differences in stroke outcome such as independence (modified Rankin Scale 0-2) (odds ratios: 1·035 (0·57-1·93) P = 0·91), mortality (odds ratios: 0·99 (0·37-2·67) P = 0·99), or symptomatic intracranial hemorrhage (odds ratios: 2·04 (0·45-9·32) P = 0·36). CONCLUSIONS: Transient ischemic attack preceding ischemic stroke does not appear to have a major influence on outcomes following thrombolysis. Patients with prior ipsilateral transient ischemic attack appear not to be at higher risk of bleeding complications.

PMID: 22098785 [PubMed - as supplied by publisher]

Medical, environmental and personal factors of disability in the elderly in Spain: a screening survey based on the International Classification of Functioning.

Gac Sanit. 2011 Nov 14;

Authors: Virués-Ortega J, de Pedro-Cuesta J, Del Barrio JL, Almazan-Isla J, Bergareche A, Bermejo-Pareja F, Fernández-Mayoralas G, García FJ, Garre-Olmo J, Gascon-Bayarri J, Mahillo I, Martínez-Martín P, Mateos R, Rodríguez F, Rojo-Pérez F, Avellanal F, Saz P, Seijo-Martínez M,

Abstract
OBJECTIVES: The International Classification of Functioning, Disability and Health (ICF) advocates a multifactorial and multifaceted conceptualization of disability. The objective of this study was to ascertain major medical, environmental and personal determinants of severe/extreme disability among the elderly population in Spain. The assessment scheme was consistent with the ICF model of disability. METHODS: Nine populations contributed probabilistic or geographically-defined samples following a two-phase screening design. The Mini-Mental State Examination and the 12-item version of the World Health Organization-Disability Assessment Schedule, 2(nd) ed. (WHO-DAS II), were used as cognitive and disability screening tools, respectively. Positively screened individuals underwent clinical work-up for dementia and were administered the 36-item version of the WHO-DAS II to estimate ICF disability levels. We used logistic regression for the purposes of data combination, adjusted for age and sex in all analyses. RESULTS: The sample was composed of 503 participants aged ≥ 75 years. Alzheimeŕs disease and depression were highly predictive of severe/extreme disability (OR: 17.40, 3.71). Good access to social services was strongly associated with a low level or absence of disability (OR: 0.05 to 0.18). Very difficult access to services and having dementia or another psychiatric disorder were associated with an increase in disability (OR: 66.06). There was also a significant interaction effect between access to services and neurological disorders (OR: 12.74). CONCLUSIONS: Disability is highly prevalent among the Spanish elderly and is influenced by medical, social and personal factors. Disability could potentially be reduced by ensuring access to social services, preventing dementia and stroke, and treating depression.

PMID: 22088902 [PubMed - as supplied by publisher]