Rogelio Leira

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 of SBP, the risk of early neurological deterioration, poor outcome, and mortality increased by 6%, 25%, and 7%, respectively, whereas 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 cm3 for every 10 mm Hg ≤180 and >180 mm Hg. A similar pattern was found in patients with DBP ≤100 or >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.

Early neurologic deterioration in intracerebral hemorrhage Predictors and associated factors

Objective: To identify potential predictors of and factors associated with early neurologic deterioration (END) in primary intracerebral hemorrhage (ICH). Methods: Two hundred sixty-six patients with spontaneous supratentorial ICH admitted within 12 hours of stroke onset were investigated in a multicenter, prospective study. Sixty-one clinical, biochemical, and neuroimaging variables were registered on admission, and 37 clinical and neuroimaging variables were registered at 48 hours. The volumes of the ICH and peripheral edema on admission and at 48 hours were measured on CT scan. Stroke severity and functional outcome were evaluated with the Canadian Stroke Scale (CSS) and modified Rankin Scale. END was diagnosed when the CSS score decreased ≥1 points between admission and 48 hours. With use of logistic regression analyses, baseline variables that predicted END and factors measured after the early acute phase and associated with END were investigated. Results: END occurred in 61 (22.9%) patients. Body temperature of >37.5 °C (odds ratio [OR] 24.5; 95% CI 4.8 to 125), neutrophil count (by 1,000-unit increase; OR 2.1; 95% CI 1.6 to 2.6), and serum fibrinogen levels of >523 mg/dL (OR 5.6; 95% CI 1.9 to 16.2) on admission were independent predictors of END. Among the factors recorded at 48 hours, early ICH growth (OR 4.3; 95% CI 1.3 to 14.5), intraventricular bleeding (OR 2.6; 95% CI 1.4 to 5.0), and highest systolic blood pressure (by 10-unit increase; OR 1.17; 95% CI 1.02 to 1.32) were associated with END in multivariate analyses. Conclusions: Clinical and biologic markers of the inflammatory reaction on admission are predictors of subsequent END, whereas early ICH growth, intraventricular bleeding, and high systolic blood pressure within 48 hours are factors associated with END in patients with spontaneous ICH.

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 cm3 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 ≥140 ng/mL had a positive and negative predictive value of HT of 61% and 97%, respectively. MMP-9 ≥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.

Statin treatment withdrawal in ischemic stroke A controlled randomized study

Background: Pretreatment with statins has been shown to reduce brain injury in cerebral ischemia. In this controlled randomized study, we investigated the influence of statin pretreatment and its withdrawal on the outcome of acute ischemic stroke patients. Methods: From 215 patients admitted within 24 hours of a hemispheric ischemic stroke, 89 patients on chronic statin treatment were randomly assigned either to statin withdrawal for the first 3 days after admission (n = 46) or to immediately receive atorvastatin 20 mg/day (n = 43). The primary outcome event was death or dependency (modified Rankin Scale [mRS] score > 2) at 3 months. Early neurologic deterioration (END) and infarct volume at days 4 to 7 were secondary outcome variables. In a secondary analysis, outcome variables were compared with the nonrandomized patients without previous statin therapy (n = 126). Results: Patients with statin withdrawal showed a higher frequency of mRS score > 2 at the end of follow-up (60.0% vs 39.0%; p = 0.043), END (65.2% vs 20.9%; p < 0.0001), and greater infarct volume (74 [45, 126] vs 26 [12, 70] mL; p = 0.002) compared with the non–statin-withdrawal group. Statin withdrawal was associated with a 4.66 (1.46 to 14.91)–fold increase in the risk of death or dependency, a 8.67 (3.05 to 24.63)–fold increase in the risk of END, and an increase in mean infarct volume of 37.63 mL (SE 10.01; p < 0.001) after adjusting for age and baseline stroke severity. Compared with patients without previous treatment with statins, statin withdrawal was associated with a 19.01 (1.96 to 184.09)–fold increase in the risk of END and an increase in mean infarct volume of 43.51 mL (SE 21.91; p = 0.048). Conclusion: Statin withdrawal is associated with increased risk of death or dependency at 90 days. Hence, this treatment should be continued in the acute phase of ischemic stroke.

Molecular signatures of brain injury after intracerebral hemorrhage.

BackgroundThe mechanisms of cellular death in the tissue surrounding an intracerebral hemorrhage (ICH) are not defined. ObjectiveTo investigate the relationship of markers of excitotoxicity and inflammation to brain injury after ICH. MethodsA total of 124 consecutive patients with spontaneous ICH admitted within 24 hours of stroke onset were prospectively investigated. The volumes of the initial ICH, peripheral edema on days 3 to 4, and the residual cavity at 3 months were measured on CT scan. Glutamate, cytokines, and adhesion molecules were measured in blood samples obtained on admission. Stroke severity and neurologic outcome were evaluated with the Canadian Stroke Scale. ResultsPoor neurologic outcome at 3 months (Canadian Stroke Scale < 7) was observed in 53 patients (43%). Stroke severity and glutamate concentrations (by each increment of 10 &mgr;mol/L, odds ratio 1.23; 95% CI 1.09 to 1.41), but not the initial volume of ICH, were independent predictors of poor outcome. In the multiple linear regression analyses, tumor necrosis factor-&agr; concentration was correlated (r = 0.83, p < 0.0001) with the volume of perihematoma edema, and glutamate concentrations were correlated (r = 0.78, p < 0.0001) with the volume of the residual cavity. These same results were observed when lobar (n = 58) and deep (n = 66) ICH were analyzed separately. ConclusionsHigh plasma levels of proinflammatory molecules within 24 hours of intracerebral hemorrhage onset are correlated with the magnitude of the subsequent perihematoma brain edema, whereas poor neurologic outcome and the volume of the residual cavity are related to increased plasma glutamate concentrations.

The Increase of Circulating Endothelial Progenitor Cells After Acute Ischemic Stroke Is Associated With Good Outcome

Background and Purpose— Increased circulating endothelial progenitor cells (EPC) have been associated with a low cardiovascular risk and may be involved in endothelial cell regeneration. The present study was designed to evaluate the prognostic value of EPC in acute ischemic stroke. Methods— Forty-eight patients with a first-ever nonlacunar ischemic stroke were prospectively included in the study within 12 hours of symptoms onset. Stroke severity was evaluated by the National Institutes of Health Stroke Scale, and functional outcome was assessed at 3 months by the modified Rankin Scale (mRS). Infarct volume growth between admission and days 4 to 7 was measured on multiparametric MRI. EPC colonies were defined as early outgrowth colony-forming unit-endothelial cell (CFU-EC). The increment of CFU-EC was quantified during the first week and defined as the absolute difference between the number of CFU-EC at day 7 and admission. The influence of CFU-EC increase on good functional outcome (mRS ≤2) and infarct growth was analyzed by logistic regression and linear models. Results— Patients with good outcome (n=25) showed a higher CFU-EC increment during the first week (median [quartiles], 23 [11, 36] versus −3 [−7, 1], P<0.0001) compared with patients with poor outcome. CFU-EC increment ≥4 during the first week was associated with good functional outcome at 3 months (odds ratio, 30.7; 95% CI, 2.4 to 375.7; P=0.004) after adjustment for baseline stroke severity, ischemic volume and thrombolytic treatment. For each unit increase in the CFU-EC the mean reduction in the growth of infarct volume was 0.39 (0.03 to 0.76) mL (P=0.033). Conclusions— The increase of circulating EPC after acute ischemic stroke is associated with good functional outcome and reduced infarct growth. These findings suggest that EPC might participate in neurorepair after ischemic stroke.

The clinical-DWI mismatch: a new diagnostic approach to the brain tissue at risk of infarction.

Objective: To evaluate the usefulness of a mismatch between the severity of acute clinical manifestations and the diffusion-weighted imaging (DWI) lesion in predicting early stroke outcome and infarct volume. Methods: One hundred sixty-six patients with a hemispheric ischemic stroke of <12 hours’ duration were studied. The NIH Stroke Scale (NIHSS) score and the volume of DWI lesion were measured on admission and at 72 ± 12 hours. Infarct volume was measured on T2-weighted or fluid-attenuated inversion recovery images at day 30. Early neurologic deterioration (END) was defined as an increase of ≥4 points between the two NIHSS evaluations. Thirty-eight patients received IV thrombolysis or abciximab. Clinical–DWI mismatch (CDM) was defined as NIHSS score of ≥8 and ischemic volume on DWI of ≤25 mL on admission. The adjusted influence of CDM on END, DWI lesion enlargement at 72 hours, and infarct growth at day 30 was evaluated by logistic regression analysis and generalized linear models. Results: CDM was found in 87 patients (52.4%). Patients with CDM had a higher risk of END than patients without CDM because NIHSS < 8 (odds ratio [OR], 9.0; 95% CI,1.9 to 42) or DWI lesion > 25 mL (OR, 2.0; 95% CI, 0.8 to 4.9). CDM was associated with an increase of 46 to 68 mL in the mean volume of DWI lesion enlargement and infarct growth in comparison with non-CDM. All the effects were even greater and significant in patients not treated with reperfusion therapies. Conclusions: Acute stroke patients with an NIHSS score of ≥8 and DWI volume of ≤25 mL have a higher probability of infarct growth and early neurologic deterioration. The new concept of CDM may identify patients with tissue at risk of infarction for thrombolytic or neuroprotective drugs.

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-&agr; (TNF-&agr;), 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 ≥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-&agr; (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] &mgr;g/mL) were significantly higher in patients with early growth of ICH (all P<0.001). C-Fn levels >6 &mgr;g/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.

The Prognostic Value of Capillary Glucose Levels in Acute Stroke The GLycemia in Acute Stroke (GLIAS) Study

Background and Purpose— Evidence is accumulating regarding the prognostic influence of hyperglycemia in patients with acute ischemic stroke. However, the level associated with poor outcome is unknown. Our objectives were to establish the capillary glucose threshold with the highest predictive accuracy of poor outcome and to evaluate its hypothetical value in influencing functional outcome by adjusting for other well-known prognostic factors in acute stroke. Methods— The authors conducted a multicenter, prospective, and observational cohort study of 476 patients with ischemic stroke within less than 24 hours from stroke onset. Capillary finger-prick glucose and stroke severity were determined on admission and 3 times a day during the first 48 hours. Poor outcome (modified Rankin Scale >2) was evaluated at 3 months. Results— The receiver operating characteristic curves showed the predictive value of maximum capillary glucose at any time within the first 48 hours with an area under the curve of 0.656 (95% CI, 0.592 to 0.720; P<0.01) and pointed to 155 mg/dL as the optimal cutoff level for poor outcome at 3 months (53% sensitivity; 73% specificity). This point was associated with a 2.7-fold increase (95% CI, 1.42 to 5.24) in the odds of poor outcome after adjustment for age, diabetes, capillary glucose on admission, infarct volume, and baseline stroke severity and with a 3-fold increase in the risk of death at 3 months (hazard ratio, 3.80; 95% CI, 1.79 to 8.10). Conclusions— Hyperglycemia ≥155 mg/dL at any time within the first 48 hours from stroke onset, and not only the isolated value of admission glycemia, is associated with poor outcome independently of stroke severity, infarct volume, diabetes, or age.

Mortality and Morbidity of Acute Cerebral Infarction Related to Temperature and Basal Analytic Parameters

We evaluated the mortality and morbidity of acute cerebral infarction as related to modifiable factors: glucose level, temperature, hematocrit, hemoglobin and platelet count. We studied 177 patients with acute cerebral infarction in the territory of the middle cerebral artery, admitted within 24 h of stroke onset. Blood was drawn on admission and temperature was recorded every 2 h, selecting the highest during the 1st day. Patient follow-up lasted 6 months. Barthel Index and Neurological Score of patients were evaluated at admission and on days 1, 4, 7, 14, 21 and at 3 and 6 months. A Glasgow Scale was administered at 6 months. Forty-five of 177 patients died within this period. These patients reached a temperature of 38.3 ± 0.76 °C, while temperature in those surviving was 36.9 ± 0.46°C ( p