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Biomedical subjects

Rogelio Leira

Publications and source records attributed to Rogelio Leira.

At least 19 recordsLinked to original sources
PubMed2006

High blood pressure and inflammation are associated with poor prognosis in lacunar infarctions.

UNLABELLED: Lacunar infarction has long been considered to be associated with good prognosis, however a significant percentage of these patients remain functionally dependent. In this study we sought to investigate the factors associated with poor outcome in patients with lacunar infarction. SUBJECTS AND METHODS: We have performed a secondary study in 113 patients with lacunar infarctions admitted within the first 24 h of symptom onset (mean age 70 years, 57.5% men). Blood pressure, body temperature, serum glucose levels, neurotransmitters and pro-inflammatory markers were measured at admission and during the first 72 h. Stroke severity was assessed by the Canadian Stroke Scale (CSS). Neuroimaging evaluation was performed at admission and between days 4 and 7. Poor functional outcome was considered as a Barthel index <85 at 3 months. RESULTS: 36 patients (31.9%) had poor outcome. Older age (p = 0.009), history of hypertension (p = 0.005), higher body temperature (p < 0.0001), systolic blood pressure (SBP) (p = 0.010), serum glucose (p = 0.002) and interleukin-6 (IL-6) (p < 0.0001) levels, as well as lower CSS score at admission (p < 0.0001) were all predictive factors of poor outcome in bivariate analyses. SBP at admission (OR 2.07, CI 95% 1.04-3.28, p = 0.015) was the only clinical predictor on multivariate analysis. When the logistic model was further adjusted for biomarkers of inflammation and excitotoxicity, IL-6 levels (OR 1.09, CI 95% 1.01-1.26, p = 0.003), but not SBP, was independently associated with poor outcome. This association persisted even after adjusting for potential predictors recorded during the first 72 h of hospitalization. CONCLUSION: High SBP and IL-6 levels on admission may predict poor outcome in patients with lacunar infarction.

Aged↗
PubMed2006

Non-pharmacological neuroprotection: role of emergency stroke management.

Acute stroke should be considered a medical emergency, where actions taken in the first hours are fundamental for achieving recovery of the damaged cerebral tissue and a better prognosis for the patient. Recanalization and neuroprotective treatment has been used with mixed results. The effectiveness observed in the first hours with thrombolytic drug treatment is only applicable to a small percentage of patients, and attempts to widen this treatment window have not yet proved fruitful. Pharmacological neuroprotective treatment has not yet demonstrated the clinical effectiveness observed in experimental models. The concept of neuroprotection in cerebral ischemia also involves a series of mechanisms that take place at the cerebral level following vascular occlusion. In this context, it should be borne in mind that a series of physiological functions usually involved in the cerebral metabolism (control of blood pressure, of temperature, of glycemia and of arterial oxygen saturation) play a key role in modulation of the ischemic process. Changes in the control of these mechanisms may aggravate the process of cerebral damage in the first hours of ischemic stroke. In this work we review the prognostic importance of the main mechanisms that may influence the acute phase of cerebral ischemic stroke, as well as their therapeutic management and control in the clinical situation.

Antihypertensive Agents↗
PubMed2006

Efficacy of therapeutic intervention in headache units in patients with frequent headaches: the EFUNCE study.

Data confirming that therapeutic intervention in headache units is superior to care received by patients in other levels of the health system are scant. This is a pilot study that includes patients seen in 4 headache units for at least 1 year, who had a headache frequency of more than 15 days per month. The results of the first 30 patients showed a significant improvement in different headache parameters and a high degree of satisfaction with the treatment received.

Adult↗
PubMed2005

Platelets, inflammation, and atherothrombotic neurovascular disease: the role of endothelial dysfunction.

The vascular endothelium is an indispensable organ in the regulation of tonicity and vascular homeostasis. Endothelial dysfunction is a marker of atherosclerosis and contributes to the atherogenic process and the development of atherothrombotic complications. Endothelial dysfunction is the common meeting point among factors for vascular risk and launches complex cellular and biochemical interactions that are characterized by oxidative stress and an intense inflammatory response. The strategic importance of the concept of endothelial dysfunction arises from the following facts: its diagnosis is simple, it allows the identification of asymptomatic arteriosclerotic subjects with a high risk of developing atherothrombotic complications, it is reversible, and it responds to various therapeutic strategies.

Animals↗
PubMed2005

The prediction of malignant cerebral infarction by molecular brain barrier disruption markers.

BACKGROUND AND PURPOSE: Space-occupying brain edema is a life-threatening complication in patients with large hemispheric stroke. The aim of the study was to determine whether molecular markers of endothelial damage may help to predict secondary brain edema and, secondly, to identify patients who could benefit from aggressive therapies such as decompressive hemicraniectomy or hypothermia. METHODS: We studied 40 consecutive patients with malignant middle cerebral artery (MCA) infarction and 35 controls with massive MCA infarctions <70 years of age and matched by stroke severity on admission. Cranial computed tomography (CT) was performed at entry and repeated between days 4 and 7, or earlier if there was neurological worsening. Malignant MCA (m-MCA) infarction was diagnosed when follow-up CT detected a more than two-thirds space-occupying MCA infarction with midline shift, compression of the basal cisterns, and neurological deterioration. Plasma concentrations of glutamate, glycine, gamma-aminobutyric acid, interleukin-6 (IL-6), IL-10, tumor necrosis factor-alpha, matrix metalloproteinase-9 (MMP-9), and cellular-fibronectin (c-Fn) were determined in blood samples obtained at admission. RESULTS: Mean time from stroke onset to blood sampling was 6.3+/-4.8 in m-MCA and 7.7+/-6.0 hours in the control group (P=0.63). Baseline characteristics were comparable in both groups. c-Fn and MMP-9 levels were significantly higher in patients with m-MCA than in controls (all P<0.001). c-Fn >16.6 microg/mL had the highest sensitivity (90%), specificity (100%), and negative and positive predictive values (89% and 100%, respectively) for the prediction of m-MCA infarction. CONCLUSIONS: A plasma c-Fn concentration >16.6 microg/mL at admission is associated with the development of m-MCA infarction with high sensitivity and specificity, suggesting that c-Fn might be useful in therapeutic decision making.

Aged↗
PubMed2005

Increased plasma levels of 15-deoxyDelta prostaglandin J2 are associated with good outcome in acute atherothrombotic ischemic stroke.

BACKGROUND AND PURPOSE: The 15-deoxyDelta prostaglandin J2 (15-dPGJ2) is an anti-inflammatory prostaglandin that has been proposed to be the endogenous ligand of peroxisome proliferator-activated receptor-gamma (PPARgamma), a nuclear receptor that can exert potent anti-inflammatory actions by repressing inflammatory genes when activated. It has been suggested that 15-dPGJ2 could be beneficial in neurological disorders in which inflammation contributes to cell death such as stroke. METHODS: We investigated the relationship between plasma levels of 15-dPGJ2 and early neurological deterioration (END), infarct volume, and neurologic outcome in 552 patients with an acute stroke admitted within 24 hours after symptoms onset. RESULTS: Median [quartiles] plasma 15-dPGJ2 levels on admission were significantly higher in patients than in controls (60.5 [11.2 to 109.4] versus 5.0 [3.8 to 7.2] pg/mL; P<0.0001). Levels of this prostaglandin were also significantly higher in patients with vascular risk factors (history of hypertension or diabetes) and with atherothrombotic infarcts (113.9 [81.6 to 139.7] pg/mL), than in those with lacunar (58.7 [32.7 to 86.2] pg/mL), cardioembolic (12.1 [6.5 to 39.2] pg/mL), or undetermined origin infarcts (11.4 [5.6 to 24.3] pg/mL) (P<0.0001). In the subgroup of patients with atherothrombotic infarcts, the adjusted odds ratio of END and poor outcome for 1 pg/mL increase in 15-dPGJ2 were 0.95 (95% CI, 0.94 to 0.97) and 0.97 (95% CI, 0.96 to 0.98), respectively. In a generalized linear model, by 1 U increase in 15-dPGJ2, there was a reduction of 0.47 mL (95% CI, 0.32 to 0.63) in the mean estimated infarct volume. CONCLUSIONS: Increased plasma 15-dPGJ2 concentration is associated with good early and late neurological outcome and smaller infarct volume. These findings suggest a neuroprotective effect of 15-dPGJ2 in atherothrombotic ischemic stroke.

Acute Disease↗
PubMed2005

Headache in cerebral hemorrhage is associated with inflammatory markers and higher residual cavity.

BACKGROUND AND PURPOSE: The mechanisms responsible for headache in patients with intracerebral hemorrhage (ICH) are not completely understood. The present study was undertaken to analyze the headache-associated factors, the possible related biochemical mechanisms, and the headache potential predictors of outcome in spontaneous ICH. METHODS: We prospectively studied 189 patients from a large cohort of 266 consecutive patients with supratentorial ICH admitted within the first 12 hours of symptoms onset. The presence of headache at stroke onset was evaluated in these patients. The volumes of the initial ICH, peripheral edema at 48 hours, and the residual cavity at 3 months were measured on CT scan. Glutamate, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha levels were measured in blood samples obtained on admission. The Canadian Stroke Scale (CSS) and the modified Rankin Scale were used to evaluate stroke severity and neurological outcome, respectively. RESULTS: Headache at onset of stroke was observed in 65 patients (34.4%). Patients who experienced headache had a significantly higher frequency of history of infection (P= .009) or inflammation (P= .045), as well as higher body temperature (P= .021), leukocyte count (P= .038), ESR (P= .011), and mass effect (P= .017) on admission. Plasma concentrations of IL-6 and TNF-alpha were significantly higher in patients with headache than in those without. Headache was an independent predictor of the residual cavity volume in patients with spontaneous ICH (odds ratio 6.49; 95% CI 2.51 to 16.78; P= .0001). CONCLUSIONS: Headache at ICH onset is associated with clinical and biochemical markers of inflammation and is an independent predictor of higher residual cavity volume after spontaneous ICH.

Aged↗
PubMed2005

The impact of migraine on psychological well-being of young women and their communication with physicians about migraine: a multinational study.

OBJECTIVE: To describe the impact of migraine on psychological well-being of young women and to evaluate their communication with physicians about migraine. RESEARCH DESIGN AND METHODS: This cross-sectional telephone survey was conducted in Israel and eight European countries (Finland, Germany, Greece, Italy, Norway, Spain, Sweden, and The Netherlands). Random-digit dialing was used to identify eligible study participants: women 18-35 years of age with migraine, who used medication to treat their migraine, and who were employed or full-time students. RESULTS: Of 1810 participants, 42% self-reported having a physician diagnosis of migraine. Eighty-six per cent believed that their life would be better if they did not suffer from migraines; and 58% of participants felt frustrated, 46% felt angry, and 44% felt depressed because of their migraines. Negative feelings related to migraine varied substantially from country to country. For example, feelings of frustration caused by migraine ranged from 32% in Italy to 84% in Finland; feelings of anxiety ranged from 21% in Norway to 57% in Italy; and feelings of confusion ranged from 13% in Greece to 61% in Italy. Overall, 81% of participants had visited a physician in the past year but only 50% of them had discussed their severe headaches or migraines with their physician within the year. While 68% of those who had visited a physician stated that they were comfortable speaking with their physician about migraine, 71% reported being the one who initiated the conversation about severe headaches or migraines. Of all participants, 39% did not feel that their physician understood how much severe headaches or migraines interfered with their life. CONCLUSIONS: Migraines and severe headaches impose a substantial burden on the psychological well-being of young women with migraine in Europe and Israel. In general, communication between these women and their physicians about migraine is incomplete.

Adolescent↗
PubMed2004

Molecular signatures of vascular injury are associated with early growth of intracerebral hemorrhage.

BACKGROUND AND PURPOSE: To investigate whether molecular markers of inflammation and endothelial injury are associated with early growth of intracerebral hemorrhage (ICH). METHODS: In a multicenter prospective study, we determined concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), matrix metalloproteinase-9 (MMP-9), and cellular fibronectin (c-Fn) in blood samples obtained on admission from 183 patients with primary hemispheric ICH of <12 hours' duration. Patients had a neurological evaluation and a computed tomography (CT) scan performed at baseline and at 48+/-6 hours. Early growth of the ICH was defined as a volume increase >33% between the 2 CT examinations for ICH with a baseline volume <20 mL and >10% for ICH > or =20 mL. Clinical, radiological, and biochemical predictive factors of ICH enlargement were analyzed by logistic regression analysis. RESULTS: Fifty-four (29.5%) patients showed a relevant early growth of ICH. High leukocyte count and fibrinogen levels, low platelet count, and intraventricular bleeding were associated with early ICH growth in bivariate analyses. Plasma concentrations of IL-6 (median [quartiles]: 19.6 [13.6; 29.9] versus 15.9 [11.5; 19.8] pg/mL), TNF-alpha (13.5 [8.4; 30.5] versus 8.7 [4.7; 13.5] pg/mL), MMP-9 (153.3 [117.7; 204.7] versus 70.6 [47.8; 103.8] ng/mL), and c-Fn (8.8 [6.2; 12.5] versus 2.8 [1.6; 4.2] microg/mL) were significantly higher in patients with early growth of ICH (all P<0.001). C-Fn levels >6 microg/mL (OR, 92; 95%CI, 22 to 381; P<0.0001) and IL-6>24 pg/mL (OR, 16; 95%CI, 2.3 to 119; P=0.005) were independently associated with ICH enlargement in the logistic regression analysis. CONCLUSIONS: Molecular signatures of vascular injury and inflammatory markers in the early acute phase of ICH are associated with subsequent enlargement of the hematoma.

Aged↗
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↗
PubMed2004

Cerebral hemodynamic reserve and early neurologic deterioration in acute ischemic stroke.

Early neurological deterioration (END) is associated with increased mortality and morbidity. Although several predictive factors have been reported, there are little data about the hemodynamic factors. Our aim was to determine the capacity of cerebral hemodynamic reserve (CHR) to predict END. We studied 100 hospitalized patients with a first ever ischemic stroke of the middle cerebral artery (MCA) within the first 24 hours of symptoms onset. END was defined as a drop of at least one point in the Canadian Stroke Scale between admission and 72 hours. The mean flow velocity (mV) in the MCA and the CHR were measured by means of transcranial Doppler within the first 24 hours of admission. The CHR was expressed as the percentage increase in the MCA mV divided by the absolute increase in the end-tidal CO2 pressure in mm Hg after carbogen inhalation. END was observed in 23 patients. Reduced values of the mV in the symptomatic MCA (P = 0.043) and of the CHR in the symptomatic hemisphere (P < 0.001) were significantly associated with END. A CHR of less than 2%/1 mm Hg was independently associated with END (OR 8.45, 95% CI 1.82-39.2) after adjusting for potential confounders. CHR impairment within the first 24 hours of acute ischemic stroke is associated with a higher risk of END. This technique may be useful in selecting patients requiring a more intensive management.

Aged↗
PubMed2004

The impact of migraine on work, family, and leisure among young women -- a multinational study.

OBJECTIVE: To assess the impact of migraine on work, family, and leisure among young women who were employed full or part time, or as a full-time student. RESEARCH DESIGN AND METHODS: This cross-sectional telephone survey with 6-month recall was conducted in Israel and eight European countries (Finland, Germany, Greece, Italy, Norway, Spain, Sweden, and The Netherlands). Random-digit dialing was used to identify study participants: women 18-35 years of age with migraine, who used medication to treat their migraine, and who were employed or full-time students. RESULTS: Of 1810 participants, 42% self-reported having a physician diagnosis of migraine. During the prior 6 months, 46% of participants missed at least 1 day of work or school and 74% were prevented from functioning fully at work or school because of migraine. Mean work/school absenteeism due to migraine was 1.9 days over 6 months (range, 0.8 days in Sweden to 2.8 days in Norway). Over half of participants reported one or more occurrences of being unable to spend time with family or friends (62%) or being unable to enjoy recreational or leisure activities (67%) because of migraine. The percentage of study participants using triptans was lowest in southern Europe and highest in the Nordic countries, ranging from 1% in Greece to 50% in Sweden. Country, age, marital status, physician diagnosis of migraine, and number of migraines or severe headaches in the prior year were independent predictors of the mean number of days of migraine-related work loss. Migraine-related work loss was lowest in Sweden and greatest in Greece, Israel, and The Netherlands. Higher work loss was recorded for those 18-24 years of age; those who were separated, widowed, or divorced; those with migraine diagnosed by a physician; and those with more frequent migraines or severe headaches (> or =24/year). The 6-month recall period used when estimating patient-reported work loss, and identifying participants with migraine based on self-reported migraine or severe headache, were the most important limitations of the study. CONCLUSIONS: We found substantial migraine-related impairment of productivity at work and school as well as of family and leisure time among young women in Israel and eight European countries.

Adolescent↗
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

The release of tumor necrosis factor-alpha is associated with ischemic tolerance in human stroke.

Tumor necrosis factor (TNF)-alpha overexpression has been related to experimental ischemic tolerance when transient ischemia precedes cerebral infarction. We investigated TNF-alpha and interleukin (IL)-6 plasma concentrations in 283 patients with an acute stroke within 24 hours after symptom onset. An ipsilateral transient ischemic attack (TIA) within 72 hours before stroke was recorded in 38 patients. The infarct volume measured on computed tomography on days 4 to 7 and the frequency of poor outcome (Barthel Index score < 85) at 3 months were significantly lower in patients with prior TIA. Plasma concentrations of TNF-alpha were higher (42.5 +/- 9.9 vs 13.1 +/- 6.4pg/ml, p < 0.0001) and IL-6 levels were lower (10.1 +/- 6.2 vs 28.3 +/- 17.3pg/ml, p < 0.0001) in patients with prior TIA. A new variable termed TNF-alpha/IL-6 index was considered positive when TNF-alpha was greater than 30pg/ml and IL-6 was less than 30pg/ml. Positive TNF-alpha/IL-6 index was found in 92% of patients with prior TIA and in 1% of those without. TNF-alpha/IL-6 index (p = 0.0003) and TIA (p = 0.0001) were associated with good outcome in logistic regression analysis after adjusting for potential confounding factors. Ischemic tolerance in acute stroke is associated with increased plasma levels of TNF-alpha in the presence of reduced concentrations of IL-6.

Aged↗
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

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↗