Biomedical subjects

Antoni Dávalos

Publications and source records attributed to Antoni Dávalos.

12 recordsLinked to original sources

PubMed2004

Comparison of preperfusion and postperfusion magnetic resonance angiography in acute stroke.

BACKGROUND AND PURPOSE: The multimodal magnetic resonance imaging study in acute stroke includes perfusion-weighted imaging (PWI) after administration of contrast and magnetic resonance angiography (MRA). However, MRA may overestimate the degree of vessel obstruction caused by limitations to detect low flow states. Our aim was to determine the usefulness of a new fast imaging protocol combining classical MRA, PWI, and postperfusion MRA to improve the diagnostic management in acute ischemic stroke. METHODS: We studied 31 patients with a middle cerebral artery (MCA) infarction within the first 12 hours from the onset of symptoms. All patients had an MCA stenosis or occlusion. The study protocol included a preperfusion MRA and a postperfusion MRA. Modified thrombolysis in myocardial infarction (TIMI) classification was used to assess the patency of vessels. RESULTS: In 17 patients (group A, 55%), preperfusion MRA and postperfusion MRA accorded in the estimation of vascular status, whereas in 14 patients (group B, 45%) postperfusion MRA showed a better vascular flow than preperfusion MRA. The improvement in the depiction of flow was from a complete occlusion (TIMI I) to a partial occlusion (TIMI II) in 9 patients and from TIMI II to normal patency (TIMI III) in 5 patients. Thirty-six percent of the patients with suspected internal carotid artery occlusion in the preperfusion MRA showed flow in the intracranial internal carotid artery in the postperfusion MRA. CONCLUSIONS: Postperfusion contrast-enhanced MRA can demonstrate arterial segments with low flow and avoid overestimation of vascular obstruction.

Acute Disease↗

PubMed2004

Plasma cellular-fibronectin concentration predicts hemorrhagic transformation after thrombolytic therapy in acute ischemic stroke.

BACKGROUND AND PURPOSE: Elevated plasma levels of cellular fibronectin (c-Fn) reflect vascular damage, so c-Fn might be a marker of secondary bleeding risk in cerebral ischemia. We investigated whether high plasma levels of c-Fn were associated with hemorrhagic transformation (HT) after treatment with tissue plasminogen activator (tPA) in patients with acute stroke. METHODS: Eighty-seven patients (mean age: 67+/-12) received tPA after the ECASS II criteria (mean time to infusion: 160+/-46 minutes; median NIHSS: 12). HT and hypodensity volume were studied on computed tomography (CT) performed 24 to 36 hours after treatment. HT was classified according to the ECASS II definitions. c-Fn and matrix metalloproteinase 9 (MMP-9) levels were determined by ELISA in blood samples obtained before treatment and in 30 healthy subjects. RESULTS: HT was found in 26 patients (30%); 15 patients had hemorrhagic infarction type 1 (HI-1), 7 had HI-2, and 4 had parenchymal hemorrhage (PH). Median c-Fn concentrations were 1.3, 1.7, 4.2, 5.4, and 7.3 microg/mL in controls, non-HT, HI-1, HI-2, and PH groups, respectively (P<0.001); median MMP-9 values were 54, 87, 154, 176, and 225 ng/mL (P<0.001). Logistic regression analysis showed that only c-Fn plasma levels remained independently associated with HT after adjusting for potential confounders (OR, 2.1; 95% CI, 1.3 to 3.4; P=0.002). Similar results were obtained in the 71 patients treated within 3 hours. CONCLUSIONS: High plasma c-Fn levels are significantly associated with subsequent HT in stroke patients treated with tPA, so plasma c-Fn determinations might be useful in clinical practice to improve the risk/benefit ratio of thrombolytic treatment.

Aged↗

PubMed2004

Blood pressure decrease during the acute phase of ischemic stroke is associated with brain injury and poor stroke outcome.

BACKGROUND AND PURPOSE: Studies on the relation between blood pressure (BP) and stroke outcome have shown contradictory results. We explored the association of systolic (SBP) and diastolic (DBP) BP during acute stroke with early neurological deterioration, infarct volume, neurological outcome, and mortality at 3 months. METHODS: We included 304 patients with acute ischemic stroke. SBP and DBP on admission and on the first day were the average values of all readings obtained in the emergency department and during a 24-hour period after patient allocation in the stroke unit. RESULTS: A U-shaped effect was observed: for every 10 mm Hg 180 mm Hg, the risk of early neurological deterioration increased by 40% and the risk of poor outcome increased by 23%, with no effect on mortality. Mean infarct volume increased 7.3 and 5.5 cm(3) for every 10 mm Hg 180 mm Hg. A similar pattern was found in patients with DBP 100 mm Hg. These effects disappeared after adjustment for the use of antihypertensive drugs and BP drop >20 mm Hg within the first day, with the latter being the more important prognostic factor of poor outcome. CONCLUSIONS: High and low SBP and DBP, as well as a relevant drop in BP, are associated with poor prognosis in patients with ischemic stroke.

Acute Disease↗

PubMed2003

Neuroprotective effects of aspirin in patients with acute cerebral infarction.

Aspirin may reduce ischemic brain injury. The aim of this study was to explore the effect of aspirin on glutamate release after acute stroke. We studied 238 patients with a first episode of hemispheric ischemic stroke of less than 24 h duration. Early neurological deterioration was diagnosed when the Canadian Stroke Scale dropped 1 or more points between admission and 48 h. Glutamate was determined on cerebrospinal fluid (CSF) samples obtained at admission. Sixty-three patients were undergoing treatment with 75-500 mg/day of aspirin at the time of stroke onset. CSF glutamate concentrations were higher in the group of patients not taking aspirin (8.9+/-5.2 vs. 4.9+/-3.1 microM/l, P< 0.0001). Aspirin treatment at stroke onset had a 97% risk reduction of early neurological deterioration, and this effect remained unchanged after a further adjustment for glutamate concentrations. These findings suggest that low doses of aspirin may be useful in the management of patients with cerebral ischemia, not only for its antithrombotic properties, but also by direct neuroprotective effects.

Acute Disease↗

PubMed2003

[Intravenous tissue-type plasminogen activator for the treatment of acute cerebral ischemia].

BACKGROUND AND OBJECTIVE: Whether the risk of symptomatic hemorrhagic transformation (SHT) of cerebral infarction associated with the use of tissue plasminogen activator (t-PA) is higher in clinical practice than in clinical trials is unknown. The aim of this study was to analyze the safety profile and clinical outcome of patients with acute cerebral ischemia who received open treatment with t-PA in Spanish hospitals. PATIENTS AND METHOD: This prospective and observational study included 155 consecutive patients with an ischemic stroke treated within 3 hours from the onset of symptoms, or within 6 hours in the absence of early signs of large cerebral infarction on CT. Intravenous t-PA was administered at 0.9 mg/kg (10% as bolus) during a 60 minutes infusion. Neurological worsening within 24-36 hours was evaluated by the NIH stroke scale (NIHSS). Primary safety and outcome variables were SHT on CT performed at 24-36 hours, mortality and independence at 90 days. Patients were treated by neurologists with expertise in acute stroke, and stroke monitoring was performed in acute stroke units. RESULTS: Baseline median NIHSS was 16, and mean time from stroke onset to treatment was 163 minutes. SHT was found in 12 patients (7.7%; 95% CI, 4.0-13.1), and it was fatal in 7 (4.5%, 95% CI, 1.8-9.1). Overall mortality at 90 days was 16.8% (95% CI, 11.2-23.6). At 24 hours, 48% (95% CI, 39.7-55.9) of patients had improved >= 4 points in the NIHSS, and 29% (95 % CI, 22.0-36.8) showed a >= 10 points improvement or total recovery. At 3 months, 56% (95% CI, 47.9-64.1) of patients were independent. CONCLUSIONS: In Spanish hospitals with stroke units or stroke teams, the use in the clinical practice of intravenous t-PA by experienced neurologists is safe, and it is associated with a favourable outcome similar to that observed in clinical trials.

Acute Disease↗

PubMed2003

L-arginine levels in blood as a marker of nitric oxide-mediated brain damage in acute stroke: a clinical and experimental study.

There are no useful markers in blood of nitric oxide (NO)-mediated brain damage. Because l-arginine (l-arg) is the only known substrate for NO generation, the authors investigated the plasma profile of l-arg after cerebral ischemia, and the relationship of L-arg concentrations in blood with stroke outcome and infarct volume in a clinical and experimental study. l-Arg levels were determined with high-performance liquid chromatography in blood and CSF samples obtained on admission, and in blood 48 hours after inclusion, in 268 patients admitted with a hemispheric ischemic stroke lasting 8.2 +/- 5.9 hours. Infarct volume was measured by days 4 to 7 using computed tomography. Plasma l-arg profiles were analyzed in a separate group of 29 patients seen within 8 hours of onset (median, 4.5 hours) and in 24 male Fischer rats treated with subcutaneous vehicle or 20-mg/kg 1400W (a specific inducible NO synthase inhibitor) every 8 hours for 3 days after performing sham or permanent middle cerebral artery occlusion. Plasma l-arg concentrations decreased after the ischemic event, both in patients and rats, and peaked between 6 and 24 hours. In patients, there was a highly correlation between l-arg levels in CSF and plasma at 48 hours (r = 0.85, P<0.001). CSF and plasma l-arg concentrations negatively correlated with infarct volume (r = -0.40 and r = -0.35, respectively, P<0.001), and were significantly lower in patients with early neurologic deterioration and in those with poor outcome (Barthel index <85) at 90 days (P<0.001). In rats, the administration of 1400W resulted in a 55% significant reduction of infarct volume measured 72 hours after permanent middle cerebral artery occlusion, an effect that correlated with the inhibition caused by 1400W on the ischemia-induced decrease of plasma l-arg concentrations at 6 to 24 hours after the onset of the ischemia. Taken together, these data indicate that determination of l-arg levels in blood might be useful to evaluate the neurotoxic effects of NO generation. These findings might be helpful to guide future neuroprotective strategies in patients with ischemic stroke.

Acute Disease↗

PubMed2003

Stroke on awakening: looking for a more rational management.

BACKGROUND AND PURPOSE: Stroke on awakening (SOA) is denied the benefits of thrombolytic therapy and is typically excluded from acute clinical trials on the grounds that the time of onset is unknown. In this study we compared the clinical characteristics of SOA and of stroke while awake (SWA), particularly in the subgroup of patients seen within a time frame of 6 h after stroke awareness. MATERIAL AND METHODS: Patients were included consecutively in the Stroke Data Bank of the Spanish Neurological Society (BADISEN) that records 365 different items, including vascular risk factors, neurological findings, stroke severity, aetiopathogenic diagnosis and neuroimaging data. RESULTS: A total of 1,248 patients with acute cerebral infarction were included in the study, 301 (24.1%) with SOA and 947 (75.9%) with SWA. The peak time for stroke occurrence was between 6:01 a.m. and 12 noon, both in the whole stroke group and in each aetiopathogenic stroke subtype. Age, sex, stroke risk factors, stroke severity at admission, vital signs and stroke subtypes were not significantly different between SOA and SWA, neither in the group as a whole nor in the group of patients seen within 6 h of stroke recognition. Six hundred and fifty-four patients were seen within the potential 6-hour therapeutic window. In this group, the CT scan on admission was normal in 39.4% of SOA but the ultimate CT/MRI scan showed that 46.2% of these had a territorial infarction (in SWA these same figures were 60.8 and 67.7%, respectively). CONCLUSION: There are no relevant differences in the clinical, neuroimaging and aetiopathogenic characteristics of SOA and SWA. We should rely on new techniques such as DWI/PWI to indicate the most appropriate treatment in a more rational manner as nearly half of the patients with SOA seen early may benefit from them.

Aged↗

PubMed2003

Plasma metalloproteinase-9 concentration predicts hemorrhagic transformation in acute ischemic stroke.

BACKGROUND AND PURPOSE: Matrix metalloproteinase-9 (MMP-9) activity has been associated with hemorrhagic transformation (HT) in experimental models of cerebral ischemia. Our aim was to investigate the relationship between MMP-9 concentrations in blood within 24 hours of stroke onset and subsequent HT of cerebral infarction. METHODS: We studied 250 patients with a hemispheric ischemic stroke of 7.8+/-4.5 hours' duration. Early CT signs of cerebral infarction were evaluated on admission. The HT and infarct volume were analyzed from the CT performed on days 4 through 7. MMP-9 levels were determined by enzyme-linked immunosorbent assay in blood samples obtained on admission. RESULTS: HT was observed in 38 patients (15.2%): 24 (63.2%) had a hemorrhagic infarction, and 14 (36.8%) had a parenchymal hematoma. A total of 108 patients (43%) received anticoagulants before the second CT scan. Systolic and diastolic blood pressures, body temperature, frequency of early CT signs of ischemia (92% versus 22%), and treatment with anticoagulants (79% versus 37%) were significantly higher in the group with HT (P<0.001). Mean infarct volume was 126+/-60 cm(3) in the HT group and 90+/-68 cm3 in the group without HT (P=0.003). Median (quartiles) plasma MMP-9 concentrations were higher in the HT group (193 [163, 213] versus 62 [40, 93] ng/mL, P<0.001), even in the 24 patients seen within 3 hours of symptom onset (P=0.014). MMP-9 levels > or =140 ng/mL had a positive and negative predictive value of HT of 61% and 97%, respectively. MMP-9 > or =140 ng/mL was associated with HT (odds ratio, 12; 95% confidence interval, 3 to 51; P<0.001) after adjustment for potential confounders and final infarct volume. CONCLUSIONS: High plasma MMP-9 concentration in the acute phase of a cerebral infarct is an independent biochemical predictor of HT in all stroke subtypes.

Biomarkers↗

PubMed2002

Iron intake increases infarct volume after permanent middle cerebral artery occlusion in rats.

Experimental and clinical data suggest an important role of iron in cerebral ischaemia. We measured infarct volume and analysed the oxidative stress, and also the excitatory and inflammatory responses to brain injury in a rat stroke model after an increased oral iron intake. Permanent middle cerebral artery occlusion (MCAO) was performed in ten male Wistar rats fed with a diet containing 2.5% carbonyl iron for 9 weeks, and in ten control animals. Glutamate, interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) were determined in blood samples before and at 2, 4, 6, 8, 24 and 48 h after MCAO, and thiobarbituric acid reaction substances (TBARS) were analysed at 48 h. Infarct volume was measured at 48 h by image analysis on brain slices stained with 1% TTC. Tissue iron was measured by atomic absorption spectrophotometry. Infarct volume was 66% greater in the iron fed rats than in the control group (178+/-49 mm(3) versus 107+/-53 mm(3), P<0.01). Significant higher levels of glutamate, IL-6 and TNF-alpha were observed in the group with iron intake (peak values were obtained at 6, 8 and 4 h, respectively). Iron-fed animals also showed significantly higher levels of TBARS than those receiving a normal diet (6.52+/-0.59 vs. 5.62+/-0.86 micro mol/l, P=0.033) Liver iron stores (3500+/-199 vs. 352+/-28 micro g Fe/g, P<0.0001), but not brain iron stores (131 vs. 139 micro g Fe/g, P=0.617), were significantly higher in the iron fed rats group. These results suggest that iron intake is associated with larger infarct volumes after MCAO in the rat. This effect seems to be associated with higher oxidative stress, excitotoxicity and inflammatory responses.

Administration, Oral↗

PubMed2002

Upregulation of TACE/ADAM17 after ischemic preconditioning is involved in brain tolerance.

A short ischemic event (ischemic preconditioning [IPC]) can result in a subsequent resistance to severe ischemic injury (ischemic tolerance [IT]). Although tumor necrosis factor-alpha (TNF-alpha) contributes to the brain damage, its expression and neuroprotective role in models of IPC have also been described. However, the role of TNF-alpha convertase (TACE) in IPC and IT is not known. Using in vitro models, the authors previously demonstrated that TACE is upregulated after ischemic brain damage. In the present study, the authors used a rat model of transient middle cerebral artery occlusion as IPC to investigate TACE expression, its involvement in TNF-alpha release, and its role in IT. Western blot analysis showed that TACE expression is increased after IPC. Ischemic preconditioning caused TNF-alpha release, an effect that was blocked by the selective TACE inhibitor BB-1101 (10 mg. kg(-1). day(-1); SHAM, 1,050 +/- 180; IPC, 1,870 +/- 290; IPC + BB, 1,320 +/- 260 ng/mg; n = 4, < 0.05). Finally, IPC produced a reduction in infarct volume, which was inhibited by treatment with BB-1101 and with anti-TNF-alpha (10 microg/5 doses; SHAM + permanent middle cerebral artery occlusion [pMCAO], 335 +/- 20; IPC + pMCAO, 244 +/- 14; IPC + BB + pMCAO, 300 +/- 6; IPC + anti-TNF + pMCAO, 348 +/- 22 mm3; n = 6-10, < 0.05). Taken together, these data demonstrate that TACE is upregulated after IPC, plays a major role in TNF-alpha shedding in IPC, and has a neuroprotective role in IT.

ADAM Proteins↗

PubMed2002

Oral citicoline in acute ischemic stroke: an individual patient data pooling analysis of clinical trials.

BACKGROUND AND PURPOSE: No single neuroprotective agent has been shown to influence outcome after acute stroke. Citicoline has been studied worldwide in many clinical trials with positive findings, but only 1 trial has obtained significant results in the primary efficacy variables. Our objective was to evaluate the effects of oral citicoline in patients with acute ischemic stroke by a data pooling analysis of clinical trials. The primary efficacy end point chosen was the common evaluation of recovery, combining National Institutes of Health Stroke Scale </=1, modified Rankin Scale score </=1, and Barthel Index >/=95 at 3 months using the generalized estimating equations analysis. METHODS: A systematic search of all prospective, randomized, placebo-controlled, double-blind clinical trials with oral citicoline (MEDLINE, Cochrane, and Ferrer Group bibliographic databases) was undertaken. Individual patient data were extracted from each study and pooled in a single data file. The main inclusion criteria included compatible neuroimaging with ischemic stroke, National Institutes of Health Stroke Scale >/=8, and prior modified Rankin Scale score </=1. Four clinical trials using various doses of oral citicoline (500, 1000, and 2000 mg) were identified. RESULTS: Of 1652 randomized patients, 1372 fulfilled the inclusion criteria (583 received placebo, 789 received citicoline). Recovery at 3 months was 25.2% in citicoline-treated patients and 20.2% in placebo-treated patients (odds ratio [OR], 1.33; 95% CI, 1.10 to 1.62; P=0.0034). The dose showing the largest difference with placebo was 2000 mg, with 27.9% of patients achieving recovery (OR, 1.38; 95% CI, 1.10 to 1.72; P=0.0043). The overall safety of citicoline was similar to placebo. CONCLUSIONS: Treatment with oral citicoline within the first 24 hours after onset in patients with moderate to severe stroke increases the probability of complete recovery at 3 months.

Acute Disease↗

PubMed2002

Inflammation-mediated damage in progressing lacunar infarctions: a potential therapeutic target.

BACKGROUND AND PURPOSE: The mechanisms underlying neurological deterioration in patients with lacunar infarction are not completely understood. In this study, we sought to investigate the role of proinflammatory molecules in the early worsening and outcome of acute lacunar stroke. METHODS: We performed a secondary analysis of 113 consecutive patients with lacunar infarction included within the first 24 hours of the onset of symptoms in a previous study aimed at investigating clinical and biochemical factors of early neurological deterioration (END). END was defined as a fall of > or =1 points in the motor items of Canadian Stroke Scale between inclusion and 48 hours. Poor outcome at 3 months was considered death or Barthel Index <85. Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and intercellular adhesion molecule-1 (ICAM-1) were determined by enzyme-linked immunoabsorbent assay in blood samples obtained on admission. RESULTS: END was recorded in 27 patients (23.9%); poor outcome was noted in 26 (23%). Median (quartiles) concentrations in plasma of TNF-alpha [16.5 pg/mL (13.7 and 21.2 pg/mL) versus 7.5 pg/mL (6.2 and 9.0 pg/mL)], IL-6 [28.8 pg/mL (22.5 and 35.7 pg/mL) versus 11.5 pg/mL (8.5 and 16.2 pg/mL)], and ICAM-1 [285 pg/mL (219 and 315 pg/mL) versus 158 pg/mL (137 and 187 pg/mL)] were significantly higher in patients who had END than in those with nonprogressing strokes (P< 0.001). Significant differences were also observed between patients with poor and good outcome at 3 months. Logistic regression analysis after adjustment for potential confounders showed that TNF-alpha >14 pg/mL and ICAM-1 >208 pg/mL were independently associated with both END (OR, 511; 95% CI, 17 to 4937; P<0.001; and OR, 315; 95% CI, 17 to 5748; P< 0.001, respectively) and poor outcome at 3 months (OR, 3.0; 95% CI, 1.0 to 8.5; P=0.042; and OR, 4.2; 95% CI, 1.3 to 13.6; P<0.015, respectively). CONCLUSIONS: High concentrations of inflammatory markers in blood are associated with END and poor functional outcome in lacunar infarctions. These findings suggest that inflammation contributes to brain injury in lacunar stroke.

Aged↗