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N Vila

Publications and source records attributed to N Vila.

At least 19 recordsLinked to original sources

[Diffusion-weighted magnetic resonance in deep cerebral venous thrombosis].

Changes in the apparent diffusion coefficient (ADC) are well established in acute ischemic stroke of arterial origin. However, ADC behaviour and its prognostic significance in cerebral venous thrombosis (CVT) are not fully understood. Diffusion-weighted imaging (DWI) findings in a 34-year old woman with deep cerebral venous thrombosis are described. Recent literature concerning DWI and cerebral venous thrombosis is also reviewed. A MRI performed within 7 hours from onset revealed hyperintensities in deep grey matter bilaterally (FLAIR/T2), without changes in ADC maps, suggesting vasogenic edema. After anticoagulation a new MRA disclosed complete recanalization of venous thrombosis. Despite her good clinical outcome the MRI showed hemorrhagic lesions suggesting venous infarct. Lesions detected in acute CVT with DWI may have normal ADC values. There is no good correlation between the acute ADC values and clinical and radiological evolution. The prognostic value of ADC in the acute phase of CVT remains unsettled.

Adult↗

alpha(1)-antichymotrypsin polymorphism: a risk factor for hemorrhagic stroke in normotensive subjects.

BACKGROUND AND PURPOSE: Although genetic factors may be important in the pathogenesis of ischemic stroke (IS), little is known on the potential role of genes in most cases of hemorrhagic stroke (HS). Preliminary data showed that the TT genotype of the alpha(1)-antichymotrypsin (ACT) gene polymorphism was associated with HS, although it remained unsettled whether prevalence of this polymorphism might differ between hypertensive and normotensive HS. METHODS: Ninety-nine patients with HS, 182 patients with IS (symptomatic control subjects), and 80 asymptomatic control subjects were genotyped for the ACT polymorphism using polymerase chain reaction amplification. Chronic hypertension was recorded in 66 patients with HS. RESULTS: The ACT-TT genotype was more prevalent in patients than in asymptomatic or symptomatic control subjects: 26%, 15%, and 16%, respectively. The ACT-TT genotype was obtained in 33% of HS who lacked arterial hypertension (P<0.05). After adjustment for age, gender, and vascular risk factors, the ACT-TT genotype remained independently associated with HS (OR 2.80, 95% CI 1.19 to 6.58, compared with asymptomatic control subjects; OR 1.79, 95% CI 0.95 to 3.40, compared with symptomatic control subjects). In analyses restricted to HS in normotensive patients, the ORs were 3.10 (95% CI 1.10 to 8.68) and 2.53 (95% CI 1.04 to 6.18), respectively. CONCLUSIONS: These findings confirm in a larger series of patients the association between the ACT-TT genotype and HS. This polymorphism is more prevalent in normotensive bleedings. Pathological studies will be required to establish whether the ACT-TT genotype facilitates proteolytic rupture of vessels that harbor amyloidotic changes or another form of nonhypertensive cerebral angiopathy.

Aged↗

Comparison of the acute-phase response in patients with ischemic stroke treated with high-dose heparin or aspirin.

Experimental studies have suggested that unfractionated heparin (UH) has antiinflammatory properties. It is unknown whether UH also has these properties in patients with acute ischemic stroke. Within 12-24 h of treatment onset we measured the acute-phase response as reflected by the erythrocyte sedimentation rate (ESR) and total number of leukocytes (x10(9)/l) in 706 consecutive patients with acute ischemic stroke treated with full-dose UH (n=450), or 300 mg/day aspirin (n=256). Clinical outcome (Mathew scale) at hospital discharge and the effect of factors such as treatment (UH and aspirin), and acute phase response were assessed using multivariate analyses adjusted for baseline confounders and incident complications. Separate models were created for patients with lacunar and nonlacunar stroke. Whereas there were not differences at baseline between the two treatment groups, total leukocyte counts (8. 0+/-4.1 vs. 8.6+/-3.2, P<0.01) and ESR (21.7+/-20.9 vs. 25.2+/-22.9, P<0.05) were statistically significantly lower in patients treated with UH. This effect of UH was more accentuated in patients with nonlacunar stroke. Overall, leukocytes (7.2+/-2.3 vs. 8.4+/-4.0, P<0. 01), and ESR (15.7+/-17.2 vs. 24.3+/-22.2, P=0.0001) were lower in patients with complete early recovery and this effect was restricted to patients with nonlacunar stroke. Whereas baseline impairment, symptomatic bleeding and stroke recurrence were independent negative outcome predictors, the use of UH was positively associated with early recovery in all patients. This study shows that full-dose UH reduces the acute-phase reaction that follows ischemic stroke more effectively than aspirin. The prognostic implications of such effect seem more notable in patients with nonlacunar stroke.

Acute-Phase Reaction↗

Meningitis caused by Pseudallescheria boydii treated with voriconazole.

Meningitis caused by Pseudallescheria boydii is an uncommon infection of the CNS that usually has a poor prognosis and a difficult treatment. We describe a case of chronic meningitis caused by P. boydii in an immunocompetent host that was successfully treated with voriconazole, a new antifungal agent.

Adult↗

Interaction between interleukin-6 and the natural anticoagulant system in acute stroke.

Inflammatory reactions mediated by cytokines are involved in the pathogenesis of acute stroke. Decrease in circulating levels of protein C (PC) and protein S (PS) induced by inflammatory cytokines has been postulated as a potential mechanism for a procoagulant tendency during acute stroke. The procoagulant state associated with impairments in natural anticoagulants may induce microvascular obstruction leading to a tissue perfusion reduction that worsens cerebral ischemia. Interleukin-6 (IL-6) regulate the synthesis of C4b-binding protein (C4BP), an acute-phase protein that also regulates PS plasma levels. We measured IL-6, C4BP, erythrocyte sedimentation rate (ESR), total and free PS and PC in 44 patients with acute ischemic stroke to determine if IL-6 decreases circulating levels of natural anticoagulants through the C4BP pathway and if these acute changes in natural anticoagulants may have clinical implications. Patients with higher levels of IL-6 had more severe neurologic deficits on admission, greater infarct size, higher levels of acute-phase reactants, and lower levels of free PS. IL-6 was significantly correlated with C4BP, ESR, and free PS levels. PC levels were also lower in the group of patients with greater IL-6, but differences were not statistically significant. No correlations were found between C4BP and natural anticoagulants. Severe neurologic deficit, greater infarct volume, atrial fibrillation, increased levels of inflammatory parameters (ESR and IL-6), and reduced levels of free PS were associated with disabling stroke at 3 months, but only neurologic severity and ESR remained as independent predictors of stroke disability on multiple regression analysis. Inflammatory reactions mediated by IL-6 during the acute phase of stroke influence the modulation of free PS. However, variations in free PS levels do not have implications for clinical outcome in stroke patients. The link between proinflammatory cytokines and free PS in the acute phase of stroke is not related to the C4BP pathway.

Blood Coagulation↗

Proinflammatory cytokines and early neurological worsening in ischemic stroke.

BACKGROUND AND PURPOSE: The mechanisms for clinical deterioration in patients with ischemic stroke are not completely understood. Several proinflammatory cytokines are released early after the onset of brain ischemia, but it is unknown whether inflammation predisposes to neurological deterioration. We assessed the implication of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha in early neurological worsening in ischemic stroke. METHODS: Two hundred thirty-one patients consecutively admitted with first-ever ischemic cerebral infarction within the first 24 hours from onset were included. Neurological worsening was defined when the Canadian Stroke Scale (CSS) score fell at least 1 point during the first 48 hours after admission. IL-6 and TNF-alpha were determined in plasma and cerebrospinal fluid (CSF; n=81) obtained on admission. RESULTS: Eighty-three patients (35.9%) deteriorated within the first 48 hours. IL-6 in plasma (>21.5 pg/mL; OR 37.7, CI 11.9 to 118.8) or in CSF (>6.3 pg/mL; OR 13.1, CI 2.2 to 77.3) were independent factors for early clinical worsening, with multiple logistic regression. The association was statistically significant in all ischemic stroke subtypes as well as in subjects with cortical or subcortical infarctions. IL-6 in plasma was highly correlated with body temperature, glucose, fibrinogen, and infarct volume. CSF and plasma concentrations of TNF-alpha were also higher in patients who deteriorated, but the differences observed did not remain significant on multivariate analysis. CONCLUSIONS: In addition to participating in the acute-phase response that follows focal cerebral ischemia, IL-6 levels on admission are associated with early clinical deterioration. The association between IL-6 and early neurological worsening prevails without regard to the initial size, topography, or mechanism of the ischemic infarction.

Aged↗

Alpha(1)-antichymotrypsin gene polymorphism in patients with stroke.

BACKGROUND AND PURPOSE: A role for proteolytic enzymes has been suggested in the pathogenesis of stroke. In a search for new genetic factors, we investigated the gene polymorphism of the serine protease inhibitor alpha(1)-antichymotrypsin (ACT) in patients with stroke. METHODS: Two hundred twenty patients with acute ischemic stroke (n=182) and primary intracerebral hemorrhage (n=38) and 70 control subjects without clinical cerebrovascular disease were genotyped for the ACT polymorphism. RESULTS: The ACT-TT genotype was more frequent in patients with primary intracerebral hemorrhage than in patients with ischemic stroke (31.6% versus 16.4%, P:<0.05) or in control subjects (21.4%, P:=0.1). After adjusting for age, gender, and vascular risk factors, the ACT-TT genotype was associated with primary intracerebral hemorrhage, with an OR of 2.3 (95% CI 1.0 to 5. 2) compared with ischemic stroke and an OR of 1.8 (95% CI 0.85 to 9. 65) compared with controls. CONCLUSIONS: Pending confirmation in a larger study, our results suggest that the ACT-TT genotype might be a risk factor for primary cerebral hemorrhage.

Acute Disease↗

Ex vivo response to aspirin differs in stroke patients with single or recurrent events: a pilot study.

The dose of aspirin for secondary stroke prevention and the clinical meaning of ex vivo platelet abnormalities are debated. We assessed prospectively 39 noncardioembolic stroke patients in which 300 mg/day aspirin had proved effective (n=24) or ineffective (n=15) to prevent recurrent ischemic events. We evaluated platelet aggregation induced by arachidonic acid, adenosine diphosphate and epinephrine, and the sensitivity of platelets to increasing concentrations of the synthetic thromboxane mimetic U46619. Aggregation studies were repeated while subjects received 300 (study phase 1), and 600 (study phase 2) mg/day aspirin, respectively. Overall, arachidonic acid-induced platelet aggregation was less effectively inhibited during study phase 1 compared to phase 2. Arachidonic acid and epinephrine promoted a stronger platelet aggregation in aspirin nonresponders than in aspirin responders while taking 300 mg/day aspirin. On the other hand, 600 mg/day effectively inhibited platelet function in both clinical groups. A lower sensitivity to thromboxane receptors was also found during phase 1 of the study, although the response was similar between aspirin responders and nonresponders. This pilot study suggests that 300 mg/day aspirin is less effective than 600 mg/day to block the cyclooxygenase pathway in noncardioembolic stroke and, incomplete cyclooxygenase inhibition is associated with recurrent thromboembolic events despite adequate aspirin compliance. It is likely that patients could receive a more efficacious stroke prevention if the dose of aspirin is tailored to individual needs as reflected by laboratory findings.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Cytokine-induced inflammation and long-term stroke functional outcome.

Inflammatory reactions are involved in the pathogenesis of cerebral ischemia. Cytokines exacerbate brain ischemic injury by several mechanisms and they activate the synthesis of acute-phase reactants. We evaluated the association between cytokine-induced inflammation and functional outcome in 41 patients with acute ischemic stroke. Blood samples for interleukin-1 receptor antagonist (IL-1ra), erythrocyte sedimentation rate (ESR), c-reactive protein (CRP) and polymorphonuclear leukocyte (PMNL) count were taken within 48 h from stroke onset. Functional outcome was assessed at six months with the Modified Rankin Scale. Patients with a Rankin score > or = 3 were classified as dependent outcome. The effect of inflammatory variables on outcome was analyzed by logistic regression. Mathew score <75 on admission, atrial fibrillation, non-lacunar infarct size, ESR>13 mm/h in men or >20 mm/h in women, PMNL count >8 x 10(9)/l, CRP>0.8 mg/dl and IL-1ra>500 pg/ml were associated with dependent outcome. On multiple logistic regression, severe stroke on admission, non-lacunar infarct size and ESR remain in the predictive model of outcome with a sensitivity and specificity of 76 and 80%, respectively. This study suggests that in addition to clinical evaluation and neuroimaging, measurement of ESR may be useful for the early detection of stroke patients with poor long-term functional outcome.

Aged↗

Heparin in acute stroke with atrial fibrillation: clinical relevance of very early treatment.

BACKGROUND: The risk-benefit ratio of early vs late heparinization for acute stroke with nonvalvular atrial fibrillation remains unsettled. OBJECTIVE: To clarify the relationship between timing to heparinization and functional outcome in acute cardioembolic stroke. DESIGN: Consecutive case series. SETTING: Referral center. PATIENTS: In 231 patients with stroke and nonvalvular atrial fibrillation, intravenous or subcutaneous heparin administered with the goal of achieving an activated partial thromboplastin time (APTT) 1.5 to 2.0 times control values. Delay to the initiation of heparin therapy was less than 6 hours from the onset of symptoms in 74 patients and between 6 and 48 hours in 157 patients. Functional outcome (Rankin scale) was assessed 9 +/- 3 (mean +/- SD) days from stroke onset using multivariate analysis and including in the model treatment delay, risk factors (eg, age, hypertension, diabetes, hypercholesterolemia, previous stroke, and heart disease), initial neurological severity, and baseline computed tomographic findings (eg, early signs of infarction and white matter abnormalities). Clinical symptoms on admission (Mathew score) and baseline radiological findings were evaluated in all subjects. The bleeding rate was assessed on subsequent computed tomographic (CT) scans (obtained 7 +/- 2 days after stroke). The relationship between APTT ratios and stroke recurrence or hemorrhagic worsening was also tested. MAIN OUTCOME MEASURES: Functional outcome at hospital discharge and incidence of early recurrent strokes and bleeding complications. RESULTS: Mortality (9%), hemorrhagic worsening (3.4%), and early stroke recurrence (2.1%) occurred in the hospital. Complete recovery was associated with age younger than 70 years (odds ratio [OR], 0.21; 95% confidence interval [CI], 0.05-0.70), a baseline Mathew score higher than 74 (OR, 11.5; 95% CI, 4.95-26.70), normal baseline CT findings (OR, 8.86; CI, 3.99-19.60), and early heparinization (OR, 1.7; 95% CI, 1.10-2.50). Targeted APTT ratios were achieved at 24 hours in fewer than 50% of patients. Whereas stroke recurrence was associated with lower mean APTT ratios, higher mean APTT ratios were observed in patients with symptomatic bleeding, especially on the day of bleeding. Age, admission stroke severity, blood pressure, and baseline CT findings did not predict hemorrhagic worsening. CONCLUSIONS: Delaying anticoagulation in alert patients with stroke and nonvalvular atrial fibrillation is not endorsed by the initial severity of symptoms or the early signs of infarction on CT scan. Functional recovery is improved the sooner heparin is administered. These findings suggest that heparin also has therapeutic properties. However, close APTT monitoring is warranted to lessen the incidence of untoward complications.

Acute Disease↗

Polymorphonuclear leukocyte elastase in patients with stroke.

INTRODUCTION/OBJECTIVES: Polymorphonuclear leukocytes (PMNL) are involved in the pathogenesis of acute cerebral ischemia and atherosclerosis. Elastase is one of the proteolytic enzymes released by activated PMNL. We evaluated whether plasma levels of elastase-inhibitor complexes (EIC) are related to acute cerebral damage or with extension of carotid atherosclerosis in patients with stroke. METHODS: Plasma levels of EIC were determined in 44 patients during acute and chronic phases of stroke. We recorded in all patients vascular risk factors, clinical severity on admission, infarct volume, and extension of carotid atherosclerosis using B-mode ultrasound exam. RESULTS: EIC levels were not different between acute and chronic phases of stroke. Eleven patients (25%) had increased values of EIC. On multiple regression analysis diabetes, dislipemia, and coronary disease were predictors of abnormal EIC levels. EIC levels were not related to neurological severity on admission, infarct volume, or carotid atherosclerosis. CONCLUSION: EIC levels in stroke patients are associated to the presence of vascular risk factors and may reflect cellular inflammatory aspects of chronic vessel disease. However, whether elastase contributes to the development of carotid atherosclerosis in patients with stroke remains unknown.

Acute Disease↗

[Heparin in acute cerebral ischemia].

Non fractionated heparin is used in neurovascular disease because of its antithrombolytic action. Therefore, the design of the clinical studies performed to date has emphasized these actions. However, the results obtained in the most recent clinical studies have been discouraging, not only because they have demonstrated its lack of efficacy, but also because the use of this heparin has been followed by an excessive number of complications. This article provides critical comments on the possible causes of these results and underlines the most recent advances obtained in the knowledge of the mechanism of action of this drug. Particularly, its potential antiinflammatory role is emphasized as are the experimental requisites required for this antiinflammatory action to be fully expressed. Based on the results shown it is concluded that it is necessary to prospectively evaluate the role of heparin in acute ischemic ictus.

Acute Disease↗

[Plasma homocysteine levels in patients with ischemic cerebral infarction].

BACKGROUND: Moderate hyperhomocysteinemia is an independent risk factor for stroke. The relationship between homocysteinemia and stroke and its related factors are unknown in Spain. PATIENTS AND METHODS: We determined plasma homocysteine concentrations in 80 stroke patients and in 48 control subjects without vascular risk factors. Folate, vitamin B12 and creatinine concentrations were also measured in stroke patients. RESULTS: Total plasma homocysteine concentrations were higher in stroke patients compared to controls (11.2 [SD 3.2] mumol/l versus 8.1 [2.6] mumol/l; p < 0.001). Hyperhomocysteinemia was present in 20% of patients and in 2.2% of controls (odds ratio [OR] = 5.75; 95% CI = 1.24-53.4; p < 0.01). Homocysteine values were related to vitamin B12 (r = 0.28; p < 0.05) and creatinine concentrations (r = 0.24; p < 0.05). Multiple regression analysis showed that about 15% of the variation in plasma homocysteine concentrations could be predicted by the values of vitamin B12 (p < 0.001) and creatinine (p < 0.05). Homocysteine values were unrelated to age, sex, folate concentrations, atherosclerotic subtype or to the presence of vascular risk factors. CONCLUSIONS: Moderate hyperhomocysteinemia was present in about 20% of stroke patients in our series. Homocysteine plasma level was not related with other stroke risk factors or with the atherosclerotic subtype of stroke, but it was partially related with the renal function parameters and the serum levels of vitamin B12.

Brain Ischemia↗

Sympathetic skin response in patients with lateral medullary syndrome.

We have carried out a prospective study of the sympathetic skin response (SSR) in 21 patients with lateral medullary syndrome (LMS), with the aim of identifying the most common pattern of SSR abnormalities and its possible correlation with clinical and radiological findings. The amplitude of the SSR recorded in the ipsilateral hand to the infarct was abnormally reduced in the patients as a group. However, using different stimulation and recording sites, and considering only the presence or absence of the response, we identified 5 different patterns of SSR abnormalities: 1. Normal responses; 2. Bilaterally absent responses to stimulation of the ipsilateral supraorbital nerve but not to other stimulation sites; 3. Absent responses in the side ipsilateral to the stroke, with normal responses in the contralateral side; 4. A combination of patterns 2 and 3; and 5. Absent responses to all stimuli. All patients with ipsilateral facial sensory loss had absent SSR to ipsilateral supraorbital nerve stimulation, while there was only a positive correlation between abnormal contralateral facial sensation and preservation of the SSR (Fisher's exact test P=0.003). No correlation was found between the pattern of SSR abnormalities and the infarct topography, assessed with the MRI. Our findings suggest that the damage to the SSR circuits of patients with LMS is not uniform, and follows an heterogeneous distribution independent from the MRI findings, and poorly related to the clinical sensory manifestations.

Adult↗