Time Trends in Intracerebral Hemorrhage Associated with Oral Anticoagulation and Its Risks Factors in Spain from 2008 to 2015.

BACKGROUND: Intracerebral hemorrhage (ICH) is 7- to 10-fold higher in anticoagulated patients. Given the more extended use of oral anticoagulants, an increase in the prevalence of ICH associated with oral anticoagulation (ICH-OAC) could be expected. However, there is no previous study that assesses the time trends of ICH-OAC in Spain. METHODS: We conducted a combined data analysis after creating a joint database of the 3 most important epidemiological studies on ICH-OAC of our country: the EPICES study (2008-2009), the TAC Registry (TR) study (2012-2013) and the TAC Registry 2 (TR2) study (2015). We finally included 65, 235, and 366 patients from the EPICES, TR, and TR2 studies, respectively. RESULTS: We have observed a 3.73-fold increase in the crude annual incidence of ICH-OAC throughout the period of study, with proportion of ICH-OAC out of total ICH increasing from 8.4% in 2008 to 18.2% in 2015. Age, dyslipidemia, and prior antiplatelet treatment increased during the study, but we found no statistically significant differences in other risk factors for ICH-OAC. CONCLUSIONS: The incidence of ICH-OAC is increasing in our country. It might at least be partly explained by aging of the population, with mean age at presentation being higher in the last years.

Circulating MicroRNAs as Novel Biomarkers of Stenosis Progression in Asymptomatic Carotid Stenosis.

BACKGROUND AND PURPOSE: Progression of asymptomatic carotid artery stenosis (ACAS) in patients with >50% luminal narrowing is considered a potential risk factor for ischemic stroke; however, subclinical molecular biomarkers of ACAS progression are lacking. Recent studies suggest a regulatory function for several microRNAs (miRNAs) on the evolution of carotid plaque, but its role in ACAS progression is mostly unknown. The aim of our study was to investigate a wide miRNA panel in peripheral blood exosomes from patients with ACAS to associate circulating miRNA expression profiles with stenosis progression. METHODS: The study included 60 patients with ACAS carrying >50% luminal narrowing. First, miRNA expression profiles of circulating exosomes were determined by Affymetrix microarrays from plasma samples of 16 patients from the cohort. Second, those miRNAs among the most differentially expressed in patients with ACAS progression were quantified by real-time polymerase chain reaction in a separate replication cohort of 39 subjects within the patient sample. RESULTS: Our results showed that ACAS progression was associated with development of stroke. MiR-199b-3p, miR-27b-3p, miR-130a-3p, miR-221-3p, and miR-24-3p presented significant higher expression in those patients with ACAS progression. CONCLUSIONS: In conclusion, our study supports that specific circulating miRNA expression profiles could provide a new tool that complements the monitoring of ACAS progression, improving therapeutic approaches to prevent ischemic stroke.

Combination of Thrombolysis and Statins in Acute Stroke Is Safe: Results of the STARS Randomized Trial (Stroke Treatment With Acute Reperfusion and Simvastatin).

BACKGROUND AND PURPOSE: The STARS trial (Stroke Treatment With Acute Reperfusion and Simvastatin) was conducted to demonstrate the efficacy and safety of simvastatin treatment in acute stroke. METHODS: STARS07 was a multicentre, phase IV, prospective, randomized, double-blind, placebo-controlled trial. Patients with Acute ischemic stroke recruited within 12 hours from symptom onset were randomized to oral simvastatin 40 mg or placebo, once daily for 90 days. Primary outcome was proportion of independent patients (modified Rankin Scale score of ≤2) at 90 days. Safety end points were hemorrhagic transformation, hemorrhagic events, death, infections, and serious adverse events. RESULTS: From April 2009 to March 2014, 104 patients were included. Fifty-five patients received intravenous tissue-type plasminogen activator. No differences were found between treatment arms regarding the primary outcome (adjusted odds ratio, 0.99 [0.35-2.78]; P=0.98). Concerning safety, no significant differences were found in the rate of hemorrhagic transformation of any type, nor symptomatic hemorrhagic transformation. There were no differences in other predefined safety outcomes. In post hoc analyses, for patients receiving tissue-type plasminogen activator, a favorable effect for simvastatin treatment was noted with higher proportion of patients experiencing major neurological recovery (adjusted odds ratio, 4.14 [1.18-14.4]; P=0.02). CONCLUSIONS: Simvastatin plus tissue-type plasminogen activator combination seems safe in acute stroke, with low rates of bleeding complications. Because of the low recruitment, the STARS trial was underpowered to detect differences in simvastatin efficacy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01073007.

Downstream Migration and Fragmentation of a Spontaneous Calcific Embolus after Thrombolysis in a Patient with Ischemic Stroke.

We report a successful treatment experience with systemic thrombolysis in a patient with acute ischemic stroked caused by spontaneous calcific embolus, which resulted in clinical improvement and embolus fragmentation.

Volumetric assessment of the carotid bifurcation: an alternative concept to stenosis grading.

BACKGROUND: To design a volumetric method for the assessment of carotid atheromatosis (CA) based on computed tomography (CT) angiography and three-dimensional (3D) reconstructions; to analyze the accuracy and optimal threshold values to differentiate between equivalent degrees of severity by duplex scanning and CT angiography (two-dimensional maximum intensity projection [2D MIP]; internal carotid artery stenosis [ICS] <50%; ICS >50%); and to assess the method's suitability to detect progression of CA. DESIGN: suitability and accuracy of a new diagnostic method. POPULATION: 90 carotid bifurcations (45 patients) were assessed with duplex scanning and CT angiography, and reevaluated after 12 ± 2 months follow-up. Determinations: Assessment of internal carotid artery (ICA) stenosis degree with duplex scanning and 2D MIP CT angiography projections. Volumetric assessment of carotid bifurcation by CT angiography (contrast volume [mm(3)] and density [Hounsfield units, H.U.] between 2-cm below and 1-cm above the anatomic bifurcation of the carotid artery [BifV], and its ratio with 1-cm segment of the common carotid artery [CCV]). STATISTICAL ANALYSIS: descriptive statistics; intraobserver and interobserver agreement (Bland-Altman plot and intraclass correlation coefficient [ICC], accuracy of 3D volumetry and duplex scanning as referred to MIP 2D CT angiography as gold standard: sensitivity (Sens), specificity (Sp), kappa index, and receiver operating characteristic curves (ROCs). RESULTS: Estimation of MIP 2D images (CT angiography) confirmed the findings of duplex scanning in 23 of 30 ICS <50% and 48 of 53 ICS >50% (Sens, 0.91; Sp, 0.77% kappa = 0.68). Three-dimensional volumetric assessment of carotid bifurcation showed an intraobserver and interobserver agreement with an ICC of 0.96 (95% confidence interval [CI], 0.904-0.985) and 0.94 (95% CI, 0.822-0.977), respectively. The BifV-to-CCV ratio was 5.2 ± 1.8 in the ICS <50% group versus 3.8 ± 1.3 in the ICS >50% group (P = 0.001). The optimal cutoff point of the BifV-to-CCV relationship was identified from the ROC curve in 4.1 (Sens, 0.75; Sp, 0.75; kappa, 0.46). At 12 months, a decrease of the average BifV with regard to the baseline value (475.45 [155.6] mm(3) × H.U. vs. 501.3 [171.9] mm(3) × H.U.; P = 0.04) was observed. CA progression was detected in 32 bifurcations (14 ICS <50%; 18 ICS> 50%), with a reduced bifurcation volume of 137.8 (71.4) mm(3) × H.U.; P < 0.001. CONCLUSIONS: Volumetric assessment of carotid bifurcation is a new concept based on assessing plaque burden rather than its hemodynamic effect or maximum stenosis; thus, justifying its moderate accuracy with regard to ICS conventional ICA grading based on biplanar images. This method can be especially useful in plaque progression studies given its accuracy to detect minor changes in the arterial lumen.

Assessment of platelet function in acute ischemic stroke patients previously treated with aspirin.

BACKGROUND: Platelet inhibition measured by platelet function tests could be critical to understand the reasons for early recurrence and to guide therapeutic recommendations. We assess the platelet function during the acute phase of ischemic stroke in patients pretreated with aspirin who continue their treatment with aspirin only, are started on clopidogrel only, or add clopidogrel to aspirin. METHODS: Sixty-four patients were taking aspirin before the stroke. Depending on the administered antiplatelet, 3 groups were defined: ASA: patients who continued on aspirin orally or intravenous acetylsalicylate of lysine, n = 30; CLO: patients who discontinued aspirin and were started on clopidogrel, n = 16; and ASA + CLO: patients who were prescribed both aspirin and clopidogrel, n = 10. Collagen-induced thromboxane A2 (TXA2) synthesis, ADP (adenosine diphosphate)-induced aggregation, and occlusion time (PF-100) were measured. RESULTS: CLO group only had a marked elevation of TXA2 (17.44 ± 15.62 ng/mL, P = .000) and a shortening of the platelet function analyzer (PFA)-100 closure time (157.13 ± 88 seconds, P = .047) compared with the other 2 groups (ASA: TXA2, .62 ± 1.59 ng/mL; ASA + CLO: TXA2 1.79 ± 4.59 ng/mL). They achieved a small (13%) but significant reduction of ADP-induced aggregation (87.00 ± 23.06 mm, P = .008) compared with the ASA group (102.82 ± 22.38 seconds). CONCLUSIONS: Stopping aspirin intake within the first 72 hours of the acute stroke drastically increases TXA2 synthesis. During the same time window, the freshly prescribed clopidogrel manages to reduce the ADP-induced aggregation only slightly (13%). This study offers analytic proof that the common practice of replacing aspirin with clopidogrel does not leave stroke patients fully protected during the first days after an ischemic stroke. Possible solutions could be to preserve aspirin during a few days or to use loading doses of clopidogrel at hospital admission.

Late clinical and radiological complications of stereotactical radiosurgery of arteriovenous malformations of the brain.

INTRODUCTION: Post-radiation injury of patients with brain arteriovenous malformations (AVM) include blood-brain barrier breakdown (BBBB), edema, and necrosis. Prevalence, clinical relevance, and response to treatment are poorly known. We present a series of consecutive brain AVM treated with stereotactic radiosurgery describing the appearance of radiation injury and clinical complications. METHODS: Consecutive patients with annual clinical and radiological follow-up (median length 63 months). Edema and BBBB were classified in four groups (minimal, perilesional, moderate, or severe), and noted together with necrosis. Clinical symptoms of interest were intracranial hypertension, new neurological deficits, new seizures, and brain hemorrhages. RESULTS: One hundred two cases, median age 34 years, 52% male. Median irradiated volume 3.8 cc, dose to the margin of the nidus 18.5 Gy. Nineteen patients underwent a second radiosurgery. Only 42.2% patients remained free from radiation injury. Edema was found in 43.1%, blood-brain barrier breakdown in 20.6%, necrosis in 6.9%. Major injury (moderate or severe edema, moderate or severe BBBB, or necrosis) was found in 20 of 102 patients (19.6%). AVM diameter >3 cm and second radiosurgery were independent predictors. Time to the worst imaging was 60 months. Patients with major radiation injury had a hazard ratio for appearance of focal deficits of 7.042 (p = 0.04), of intracranial hypertension 2.857 (p = 0.025), hemorrhage into occluded nidus 9.009 (p = 0.079), appearance of new seizures not significant. CONCLUSIONS: Major radiation injury is frequent and increases the risk of neurological complications. Its late appearance implies that current follow-up protocols need to be extended in time.

Diabetes does not affect outcome of symptomatic carotid stenosis treated with endovascular techniques.

BACKGROUND: The influence of diabetes on carotid revascularization techniques is controversial, with few data regarding angioplasty and stenting (CAS). Our purpose was to analyze whether its presence constitutes a risk factor for poor outcome of patients with carotid stenosis treated with CAS. METHODS: We compared 30-day and long term morbidity and mortality, as well as restenosis rates, of non diabetic and diabetic patients with symptomatic carotid stenosis treated with endovascular techniques. RESULTS: 318 consecutive patients, 116 (36.5%) of them diabetics, were followed for a median of 56 months. Cumulative 30-day stroke, ischemic cardiopathy and death rate was 4% for non diabetics and 5.2% for diabetics (non significant). Long term stroke and mortality rate was 26.4% for the first group and 34.3% for the second (non significant). The most frequent causes of death were myocardial infarction (17.5% non diabetics, 44% diabetics, p = 0.04), ischemic stroke (12.5% non diabetics, 4% diabetics, non significant) and cancer (30% non diabetics, 16% diabetics, non significant). Twelve patients (6.4%) had restenosis ≥ 50%, 5.9% non diabetic, 7.4% diabetic, also without statistical significance. CONCLUSIONS: In our series, endovascular treatment is both efficient and safe in diabetic patients with symptomatic carotid stenosis; therefore, the presence of diabetes mellitus did not increase the risks linked to CAS procedure.

Postradiosurgery hemorrhage rates of arteriovenous malformations of the brain: influencing factors and evolution with time.

BACKGROUND AND PURPOSE: The long-term benefit of radiosurgery of brain arteriovenous malformations (AVM), especially nonhemorrhagic cases, is controversial. We calculated hemorrhage rates pre- and posttreatment and analyzed the risk factors for bleeding based on cases followed at our site. METHODS: One hundred eight patients, age 36 ± 17 years, 56 men. The mean follow-up was 65 ± 44 months (median, 54; interquartile range, 33-94). Most AVMs were small (74.1% <3 cm in diameter); 48.1% were located in an eloquent area, 27.8% had deep drainage, and 39.8% presented with hemorrhage. RESULTS: The annual hemorrhage rate for any undiagnosed AVM was 1.2%, and 3.3% for AVMs with hemorrhagic presentation. Older patients, cortical or subcortical AVMs, and cases with multiple draining veins were less likely to present with bleeding. During the first 36 months postradiosurgery, hemorrhagic AVMs had a rebleeding rate of 2.1%, and a rate of 1.1% from 3 years onwards. Nonhemorrhagic AVMs had a hemorrhage rate of 1.4% during the first 3 years and 0.3% afterward. Arterial hypertension and nidus volume were independent predictors of bleeding after treatment. Mean nidus obliteration time was 37 ± 18 months (median, 32; interquartile range, 25-40), with hemorrhage rate of 1.3% before and 0.6% after obliteration, and 1.9% for AVMs that were not closed at the end of follow-up. CONCLUSIONS: Both hemorrhagic and nonhemorrhagic AVMs benefit from radiosurgical therapy, with gradual decrease in their bleeding rates over the years. Albeit small, the risk of hemorrhage persists during the entirety of follow-up, being higher for cases with hemorrhagic presentation and nonobliterated AVM.

Long-term outcome in patients with carotid artery stenting and contralateral carotid occlusion: a single neurovascular center prospective analysis.

INTRODUCTION: The aim of this study was to analyze the clinical features and early and late outcome of patients treated with carotid artery stenting for carotid stenosis with occlusion of the contralateral vessel (CAS-CCO), and compare them to patients without occlusion (CAS-NO). METHODS: From 1999 through 2010, 426 patients with 479 procedures were prospectively recorded, 61 patients (14.3%) CAS-CCO, and 365 patients CAS-NO. Immediate CAS complications, complications within the first 30 days and long-term complications were documented through annual clinical and ultrasonological follow-up visits. Stenosis rate was recorded. RESULTS: Patients with mean age of 68.4 years, 80% men had: (1) periprocedural stroke in three cases (0.7%), (2) cumulative 30-day stroke, ischemic cardiopathy, and death in 4.2%, without differences between groups (CAS-CCO 3.3%, CAS-NO 4.4%). Mean follow-up period was 55 ± 32.78 months, median 56 months. (3) Stroke during the follow-up in 8%, without differences between CAS-CCO and CAS-NO groups (3.7% and 8.8%). (4) Myocardial infarction in 11.2% and (5) global mortality in 24.3%, without statistical differences between groups. Of the 254 cases enrolled in the restenosis analysis, 44 patients (17.3%) had restenosis of any grade during a mean follow-up period of 52 months, without statistical differences between CAS-CCO and CAS-NO groups. Only 7.5% presented restenosis ≥ 50%. Its occurrence was statistically associated with previous neck radiation. CONCLUSIONS: Periprocedural risks and long-term outcomes of patients treated with CAS and presenting a contralateral carotid occlusion does not differ from regular patients treated with CAS. Based on the low stenosis rate of our study, our results do not give credit to extra surveillance measures in patients with contralateral carotid occlusion.

Influence of COX-inhibiting analgesics on the platelet function of patients with subarachnoid hemorrhage.

BACKGROUND: Platelet function of patients with subarachnoid hemorrhage (SAH) may play an important part in both rebleeding and delayed cerebral ischemia, but little is known about aggregation pathways during the acute phase of stroke. Analgesics are used regularly in the first days after bleeding, and some can potentially inhibit the cyclooxygenase (COX) enzyme. We examined the platelet function of patients with SAH in order to describe their basal situation and determine whether the administration of intravenous nonsteroidal antiinflammatory drugs (NSAIDs) affected platelet aggregation. METHODS: Arachidonic acid (AA)-induced aggregation and the platelet function analyzer (PFA)-100 test with collagen/epinephrine cartridges were used to study a group of SAH patients that was treated with dexketoprofen and dipyrone and to compare them to patients that had received no analgesia. RESULTS: Ninety-six consecutive SAH patients prospectively enrolled in platelet studies. Twenty-seven patients were taking NSAIDs (10 on dexketoprofen and 17 on dipyrone), and there were 15 cases in the control group. AA-induced aggregation was 10% ± 3.2% for NSAIDs (mean ± standard error), specifically 17.2% ± 7% for dexketoprofen and 5.7% ± 1% for dipyrone. Aggregation in the control group was 72.4% ± 6% (P = .001). Both analgesics slowed the platelet plug formation during the PFA-100 test, with closure times of 237.2 ± 25 seconds for dexketoprofen and 198.4 ± 22 seconds for dipyrone and 138.1 ± 21 seconds in controls (P = .02). CONCLUSIONS: The administration of COX-inhibiting analgesics leads to an hypoaggregability state in the first days of SAH. Further insight into their impact on complications such as rebleeding and delayed cerebral ischemia is needed in order to optimize the headache treatment of SAH.

Intraplaque calcium and its relation with the progression of carotid atheromatous disease.

BACKGROUND: Calcification and progression of atheromatous disease (AD) both have been independently related with the risk of stroke. However, the link between the two phenomena is still unclear. The main objective of this study was to analyze the temporal evolution of Ca content of carotid atheromatous plaques and its relation with the progression of carotid AD using quantitative CT Angiography (CTA). METHODS: Forty-three asymptomatic patients with stenosis of the internal carotid artery (ICA)>50% completed the study. Contrast mold volume and calcium (Ca) content by quantitative CTA and Modified Agatston Score (Ca volume × radiological density) were assessed at baseline and after 12±2 months. Biochemical parameters, including main markers of Ca/Phosphorus (P) metabolism, were determined. RESULTS: CTA measurement showed an increase of volumetric stenosis (volume decrease of the contrast mold), compared to baseline (475.45 [155.6] mm3 × U.H vs. 501.3 [171.9] mm3 × U.H; P=0.04) as well as an increase of intraplaque Ca (64.58 [57.8] mm3 × U.H. vs. 56.8 [52.3] P=0.002). An inverse correlation between baseline Ca content and volumetric stenosis progression (r=-0.481; P<0.001), as well as between the increase of carotid Ca and plasma levels of vitamin D (r=0.4; P=0.025) were also found. Multiple regression analysis found a model with baseline intraplaque Ca, adjusted by Body Mass Index (BMI) as most predictive of carotid AD progression. CONCLUSIONS: These results suggest that a higher content of Ca confers greater stability against the progression of carotid AD and, eventually, its ability to generate symptomatology.

Association of High Serum Levels of Growth Factors with Good Outcome in Ischemic Stroke: a Multicenter Study.

The main objective of this research work was to study the association of serum levels of growth factors (GF) and SDF-1α with the functional outcome and reduction of lesion volume in ischemic stroke patients. In this multicenter study, 552 patients with non-lacunar stroke (male, 62.1%; mean age, 68.2 ± 11.4) were included within 24 h from symptom onset. The main outcome variable was good functional outcome (modified Rankin Scale [mRS] ≤ 2) at 12 months. Secondary outcome variable was infarct volume (in mL) after 6 ± 3 months. Serum levels of VEGF, Ang-1, G-CSF, BDNF, and SDF-1α were measured by ELISA at admission, 7 ± 1 days, at 3 ± 1 months, and 12 ± 3 months. Except for BDNF, all GF and SDF-1α serum levels showed a peak value at day 7 and remained elevated during the first 3 months (all p < 0.01). High serum levels at day 7 of VEGF (OR, 19.3), Ang-1 (OR, 14.7), G-CSF (OR, 9.6), and SDF-1α (OR, 28.5) were independently associated with good outcome at 12 months (all p < 0.0001). On the other hand, serum levels of VEGF (B, - 21.4), G-CSF (B, - 14.0), Ang-1 (B, - 13.3), and SDF-1α (B, - 44.6) measured at day 7 were independently associated with lesion volume at 6 months (p < 0.01). In summary, high serum levels of VEGF, Ang-1, G-CSF, and SDF-1α at day 7 and 3 months after ischemic stroke are associated with good functional outcome and smaller residual lesion at 1 year of follow-up.

Progression of carotid near-occlusion to complete occlusion: related factors and clinical implications.

BACKGROUND: The clinical consequences and factors related to the progression from a carotid near-occlusion (CNO) to a complete occlusion are not well established. Our aim is to describe the rate, predictive factors and clinical implications of the progression to complete carotid occlusion (PCCO) in a population of patients with symptomatic CNO. METHODS: We conducted a multicenter, nationwide, prospective study from January 2010 to May 2016. Patients with angiography-confirmed CNO were included. We collected information on demographic data, clinical manifestations, radiological and hemodynamic findings, and treatment modalities. A 24 month carotid-imaging follow-up of the CNO was performed. RESULTS: 141 patients were included in the study, and carotid-imaging follow-up was performed in 122 patients. PCCO occurred in 40 patients (32.8%), and was more frequent in medically-treated patients (34 out of 61; 55.7%) compared with patients treated with revascularization (6 out of 61; 9.8%) (p<0.001). 7 of the 40 patients with PCCO (17.5%) suffered ipsilateral symptoms. Factors independently related with PCCO in the multivariate analysis were: age ≥75 years (OR 2.93, 95% CI 1.05 to 8.13), revascularization (OR 0.07, 95% CI 0.02 to 0.20), and collateral circulation through the ipsilateral ophthalmic artery (OR 3.25, 95% CI 1.01 to 10.48). CONCLUSIONS: PCCO occurred within 24 months in more than half of the patients under medical treatment. Most episodes of PCCO were not associated with ipsilateral symptoms. Revascularization reduces the risk of PCCO.

MRI predicts intracranial hemorrhage in patients who receive long-term oral anticoagulation.

OBJECTIVE: We tested the hypothesis that the risk of intracranial hemorrhage (ICH) in patients with cardioembolic ischemic stroke who are treated with oral anticoagulants (OAs) can be predicted by evaluating surrogate markers of hemorrhagic-prone cerebral angiopathies using a baseline MRI. METHODS: Patients were participants in a multicenter and prospective observational study. They were older than 64 years, had a recent cardioembolic ischemic stroke, and were new users of OAs. They underwent a baseline MRI analysis to evaluate microbleeds, white matter hyperintensities, and cortical superficial siderosis. We collected demographic variables, clinical characteristics, risk scores, and therapeutic data. The primary endpoint was ICH that occurred during follow-up. We performed bivariate and multivariate Cox regression analyses. RESULTS: We recruited 937 patients (aged 77.6 ± 6.5 years; 47.9% were men). Microbleeds were detected in 207 patients (22.5%), moderate/severe white matter hyperintensities in 419 (45.1%), and superficial siderosis in 28 patients (3%). After a mean follow-up of 23.1 ± 6.8 months, 18 patients (1.9%) experienced an ICH. In multivariable analysis, microbleeds (hazard ratio 2.7, 95% confidence interval [CI] 1.1-7, p = 0.034) and moderate/severe white matter hyperintensities (hazard ratio 5.7, 95% CI 1.6-20, p = 0.006) were associated with ICH (C index 0.76, 95% CI 0.66-0.85). Rate of ICH was highest in patients with both microbleed and moderate/severe WMH (3.76 per 100 patient-years, 95% CI 1.62-7.4). CONCLUSION: Patients taking OAs who have advanced cerebral small vessel disease, evidenced by microbleeds and moderate to severe white matter hyperintensities, had an increased risk of ICH. Our results should help to determine the risk of prescribing OA for a patient with cardioembolic stroke. CLINICALTRIALSGOV IDENTIFIER: NCT02238470.

Neutrophil extracellular traps are increased in patients with acute ischemic stroke: prognostic significance.

Neutrophil extracellular traps (NETs) are networks of DNA, histones, and proteolytic enzymes produced by activated neutrophils through different mechanisms. NET formation is promoted by activated platelets and can in turn activate platelets, thus favoring thrombotic processes. NETs have been detected in venous and arterial thrombosis, but data in stroke are scarce. The aim of this study was to evaluate NETs in the plasma of patients with acute ischemic stroke and their potential association with baseline clinical characteristics, stroke severity, and one-year clinical outcomes. The study included 243 patients with acute ischemic stroke. Clinical and demographic data and scores of stroke severity (NIHSS and mRs) at onset and discharge were recorded. Markers of NETs (cell-free DNA, nucleosomes, and citrullinated histone 3 (citH3)), were determined in plasma. Patients were followed-up for 12 months after the ischemic event. NETs were significantly elevated in the plasma of patients with acute ischemic stroke when compared to healthy subjects. NETs were increased in patients who were over 65 years of age and in those with a history of atrial fibrillation (AF), cardioembolic stroke, high glucose levels, and severe stroke scores at admission and discharge. In multivariate analysis, elevated levels of citH3, the most specific marker of NETs, at onset were independently associated with AF and all-cause mortality at one-year follow-up. NETs play a role in the pathophysiology of stroke and are associated with severity and mortality. In conclusion, citH3 may constitute a useful prognostic marker and therapeutic target in patients with acute stroke.

Short- and long-term outcomes in non-aneurysmal non-perimesencephalic subarachnoid hemorrhage.

OBJECTIVE: Our aim was to assess the short- and long-term prognosis in patients suffering from non-aneurysmal non-perimesencephalic SAH (Na-NPM-SAH). METHODS: Based on admission CT-scan, SAH was categorized as perimesencephalic (PM) or non-perimesencephalic (NPM). Based on digital subtraction angiography (DSA) results, patients were classified as normal DSA (Na-SAH) or aneurysmal SAH (aSAH). Between 1997 and 2010, 67 of 571 patients with non-traumatic SAH (11.7%) suffered from non-aneurysmal non-perimesencephalic SAH. Retrospective analyses of the 67 patients were undertaken, and compared with the aneurysmal SAH group. Long-term follow-up was assessed. RESULTS: The cohort consisted of 67 Na-NPM-SAH patients, mean age 54.8 years (range: 21-84), 56.7% male. Acute phase: 10.4% mortality and 3% rebleeding (two patients) during the acute phase. Long-term: extensive follow-up was possible in all except one of the survivors at discharge. Mortality was 6.6% during the 510 patient-years follow-up period (median follow-up time per patient, 8.95 years); rebleeding rate was 0-1.6%. An aneurysmal source was found in 13% of patients who underwent a second angiography. Aneurysmal SAH: 312 patients, with confirmed aneurysm by angiography. The mortality rate for Na-NPM-SAH during the acute phase was 10.4%, vs. 20% for aneurysmal SAH in the general database, p = 0.049. DISCUSSION: Na-NPM-SAH patients without an identifiable bleeding source on initial angiography might have a more benign short- and long-term prognosis than aneurysmal SAH patients. Our study confirms an important diagnostic advantage of a second arteriography. Still, despite the major concern of an undetected aneurysm, the long-term rebleeding rate was low in this subgroup of patients.

Red blood cell distribution width in patients with cryptogenic stroke.

BACKGROUND: There is no information about a possible association of red blood cell distribution width (RDW) with cryptogenic stroke (CS). We aimed to analyze the association of RDW with CS. PATIENTS AND METHODS: One hundred and sixty-three patients with CS were included along with 186 healthy controls. Fibrinogen, leukocytes, hemoglobin, and erythrocyte indices were evaluated. RESULTS: Patients showed higher RDW, leukocyte count, and body mass index (BMI) than controls (P < .05). No differences were observed in the erythrocyte indices or in glucose, cholesterol, and triglycerides levels (P > .05). When patients with anemia were excluded from the study (6 controls and 5 cases), the differences between cases and controls persisted (P = .005). Multivariate logistic regression revealed that, after adjusting for potential confounders (anemia, age > 40 years, gender, and fibrinogen >382 mg/dL, total cholesterol >240 mg/dL, and BMI > 28.7 kg/m(2)), RDW >14% was the only parameter that independently increased the risk of CS. CONCLUSION: The RDW >14% increased the risk of CS by 2.5-fold, irrespectively of anemia, inflammation, and lipidic profile.

Characterisation of DWI-MRI confirmed cerebral infarcts in patients with subarachnoid haemorrhage and their association with MMP-9 levels.

OBJECTIVES: It has been suggested that metalloproteinase-9 (MMP-9) could predict the onset of cerebral vasospasm after subarachnoidal haemorrhage (SAH). The aim of this study was to analyse, in patients with SAH, the difference between patients with MRI ischaemic infarcts and patients without, and to investigate the role of metalloproteases as a prognostic factor for ischaemic infarcts. METHODS: Sixty eight consecutive patients with SAH and diffusion-weighted magnetic resonance imaging (DWI-MRI) done 3 weeks after SAH. We define two groups, with and without DWI-MRI infarcts. Blood samples were taken at entry, 3 days and 1 week MMP-9 was determined through ELISA method. RESULTS: Forty per cent were male, with a mean age of 54 ± 14 years. Twenty five patients, 36.8%, had DWI-MRI infarcts; in patients with MRI infarcts, SAH was more severe (Fisher = 4 52 vs 25.6%, P = 0.037), with more morbi-mortality (Rankin>3 48 vs 18.6%, P = 0.014), and more symptomatic vasospasm (28 vs 7%, P = 0.031). Levels of MMP-9 were higher than controls, but there were no significant differences between patients with and without infarcts (first determination no infarcts 39.40 ng/ml ± 35.40 vs infarcts 49.75 ng/ml ± 34.54, P > 0.005, 3 days no infarcts 72.10 ng/ml ± 70.95 vs infarcts 62.28 ± 33.84, P > 0.005, 1 week no infarcts 148.48 ng/ml ± 142.73 vs infarcts 91.5 ng/ml ± 1.20, P > 0.005). CONCLUSION: Thirty eight percent in a well-studied series of patients with SAH have DWI-MRI infarcts; the infarcts were associated to SAH severity, SAH outcome and symptomatic vasospasm. Metalloproteinase-9 was higher in SAH patients than in controls, but it could not discriminate the infarct patients.