Marek Sykora

Safety of Intravenous Thrombolysis for Acute Ischemic Stroke in Patients Receiving Antiplatelet Therapy at Stroke Onset

Background and Purpose— Antiplatelets (APs) may increase the risk of symptomatic intracerebral hemorrhage (ICH) following intravenous thrombolysis after ischemic stroke. Methods— We assessed the safety of thrombolysis under APs in 11 865 patients compliant with the European license criteria and recorded between 2002 and 2007 in the Safe Implementation of Treatments in Stroke (SITS) International Stroke Thrombolysis Register (SITS-ISTR). Outcome measures of univariable and multivariable analyses included symptomatic ICH (SICH) per SITS Monitoring Study (SITS-MOST [deterioration in National Institutes of Health Stroke Scale ≥4 plus ICH type 2 within 24 hours]), per European Cooperative Acute Stroke Study II (ECASS II [deterioration in National Institutes of Health Stroke Scale ≥4 plus any ICH]), functional outcome at 3 months and mortality. Results— A total of 3782 (31.9%) patients had received 1 or 2 AP drugs at baseline: 3016 (25.4%) acetylsalicylic acid (ASA), 243 (2.0%) clopidogrel, 175 (1.5%) ASA and dipyridamole, 151 (1.3%) ASA and clopidogrel, and 197 (1.7%) others. Patients receiving APs were 5 years older and had more risk factors than AP naïve patients. Incidences of SICH per SITS-MOST (ECASS II respectively) were as follows: 1.1% (4.1%) AP naïve, 2.5% (6.2%) any AP, 2.5% (5.9%) ASA, 1.7% (4.2%) clopidogrel, 2.3% (5.9%) ASA and dipyridamole, and 4.1% (13.4%) ASA and clopidogrel. In multivariable analyses, the combination of ASA and clopidogrel was associated with increased risk for SICH per ECASS II (odds ratio, 2.11; 95% CI, 1.29 to 3.45; P=0.003). However, we found no significant increase in the risk for mortality or poor functional outcome, irrespective of the AP subgroup or SICH definition. Conclusion— The absolute excess of SICH of 1.4% (2.1%) in the pooled AP group is small compared with the benefit of thrombolysis seen in randomized trials. Although caution is warranted in patients receiving the combination of ASA and clopidogrel, AP treatment should not be considered a contraindication to thrombolysis.

Impaired baroreflex sensitivity predicts outcome of acute intracerebral hemorrhage

Objective:Impaired blood pressure regulation in the acute phase of stroke has been associated with less favorable outcome. Mechanisms and effects of blood pressure dysregulation in stroke are not well understood; however, central autonomic impairment with sympathetic overactivity and baroreflex involvement are discussed. Baroreflex sensitivity (BRS) in spontaneous intracerebral hemorrhage has not been investigated. We sought to examine BRS in patients with intracerebral hemorrhage and evaluate the relationship between BRS and short-term outcome measures. Design:An open, prospective study. Setting:Neurocritical care unit and stroke unit in a university hospital. Patients and Measurements:We studied 45 patients with acute intracerebral hemorrhage within 72 hrs from onset of symptoms and 38 control subjects. BRS was measured noninvasively using a hemodynamic monitoring device. Beat-to-beat blood pressure variability was derived. The effects of the BRS, hemorrhage volume, intraventricular blood, and admission scores on outcome at 10 days were studied using a multivariate regression model. Main Results:Compared with the control group, patients with intracerebral hemorrhage had significantly decreased BRS (p = 0.002) and significantly increased systolic, diastolic, and mean beat-to-beat blood pressure variability (p < 0.0001, p = 0.007, p = 0.015). After adjusting for age, National Institute of Heath Stroke Scale at admission, volume of intracerebral hemorrhage and presence of intraventricular blood in a multivariate regression model, BRS gain was an independent predictor of outcome at 10 days. Conclusions:We found that BRS was decreased in patients with acute intracerebral hemorrhage and correlated with increased beat-to-beat blood pressure variability. BRS independently predicted outcome at 10 days. Modulation of baroreceptor reflex sensitivity may represent a new therapeutic target in acute stroke and warrants future studies.

Impaired Cerebral Vasomotor Activity in Spontaneous Intracerebral Hemorrhage

Background and Purpose— Impairment of cerebrovascular autoregulation may promote secondary brain injury in acute brain insults. Until now, only limited data are available on autoregulation in patients with spontaneous intracerebral hemorrhage. In the current study, we aimed to investigate cerebrovascular reactivity and its significance for outcome in spontaneous intracerebral hemorrhage. Methods— We continuously recorded mean arterial pressure, intracranial pressure, and cerebral perfusion pressure for mean 95 hours in 20 patients with spontaneous intracerebral hemorrhage. The moving correlation coefficient between mean arterial pressure and intracranial pressure (pressure reactivity index), an index of cerebral vasoreactivity, was calculated from the available artifact-free monitoring time (mean, 50.4 hours). Results— In the univariate analysis pressure reactivity index (r=0.66; P=0.002), hemorrhage volume (r=0.62; P=0.007), cerebral perfusion pressure (r=−0.71; P=0.001), mean arterial pressure (r=−0.61; P=0.005), and hematoma growth (r=0.53; P=0.02) significantly correlated with National Institutes of Health Stroke Scale Score at discharge. In a multivariate stepwise linear regression model, pressure reactivity index remained the only independent predictor of outcome (&bgr;=0.659; P=0.004). In the subgroup of patients with pressure reactivity index greater than a functional threshold of >0.2, the correlation between mean cerebral perfusion pressure and outcome remained significant (r=−0.73; P=0.0102), whereas National Institutes of Health Stroke Scale Score at discharge did not correlate with cerebral perfusion pressure in patients with pressure reactivity index <0.2 (r=−0.05; P=0.9078). Conclusions— We found evidence for impaired cerebral vasomotor activity as measured by pressure reactivity index in patients with spontaneous intracerebral hemorrhage. We suggest that impaired cerebrovascular reactivity contributes to poor outcome in intracerebral hemorrhage patients. This effect may be mediated by fluctuations in cerebral perfusion.

Baroreflex: A New Therapeutic Target in Human Stroke?

Background and Purpose— Autonomic dysfunction, including increased sympathetic drive and blunted baroreflex, has repeatedly been observed in acute stroke. Of clinical importance is that the stroke-related autonomic imbalance seems to be linked to worse outcome after stroke. Here, we discuss the role of baroreflex impairment in acute stroke and its possible pathophysiological and therapeutic relevance. Summary of Review— Possible mechanisms linking baroreflex impairment with unfavorable outcome in stroke may include increased cardiovascular morbidity and mortality, promotion of secondary brain injury due to local inflammation, hyperglycemia, or altered cerebral perfusion. Conclusions— We suggest therefore that the modifying of autonomic functions may have important therapeutic implications in acute ischemic as well as in hemorrhagic stroke.

Impaired Baroreceptor Reflex Sensitivity in Acute Stroke Is Associated With Insular Involvement, But Not With Carotid Atherosclerosis

Background and Purpose— Impaired baroreflex sensitivity (BRS) has been previously shown to be of prognostic value in patients with cardiovascular disease and stroke. Because baroreflex seems to be blunted by both carotid atherosclerosis and by lesions affecting central processing, controversy exists regarding the etiology of stroke-related baroreflex changes. The insula may play a central role in baroreflex modulation. The aim of the study was therefore to examine BRS in patients with acute stroke with regard to carotid atherosclerosis and insular involvement. Methods— We evaluated spontaneous BRS in 96 patients with acute stroke within 72 hours of ictus and 41 control subjects using a sequential crosscorrelation method. Results— Fifty-two patients with ischemic stroke and 44 patients with intracerebral hemorrhage, mean age 58.4 years, were included. With comparable carotid atherosclerosis profiles, patients with stroke had significantly lower BRS than control subjects (3.3 versus 5.3, P<0.001). Carotid atherosclerosis had no influence on variance of the BRS values in the acute stroke group. Patients with insular involvement had significantly lower BRS than patients with no insular involvement (2.55 versus 4.35, P=0.001) or control subjects (2.55 versus 5.3, P<0.001). Furthermore, patients with left insular involvement had significantly lower BRS than patients with right insular involvement (2.3 versus 3.5, P=0.049). There was no significant difference between patients with no insular lesions and control subjects (P=0.263). Conclusions— We demonstrated that baroreflex impairment in acute stroke is not associated with carotid atherosclerosis but with insular involvement. Both insulae seem to participate in processing the baroreceptor information with the left insula being more dominant.

Cerebral Oxygen Transport Failure?: Decreasing Hemoglobin and Hematocrit Levels After Ischemic Stroke Predict Poor Outcome and Mortality: STroke: RelevAnt Impact of hemoGlobin, Hematocrit and Transfusion (STRAIGHT)—an Observational Study

Background and Purpose— Although conceivably relevant for penumbra oxygenation, the optimal levels of hemoglobin (Hb) and hematocrit (Hct) in patients with acute ischemic stroke are unknown. Methods— We identified patients from our prospective local stroke database who received intravenous thrombolysis based on multimodal magnet resonance imaging during the years 1998 to 2009. A favorable outcome at 3 months was defined as a modified Rankin Scale score ⩽2 and a poor outcome as a modified Rankin Scale score ≥3. The dynamics of Hemoglobin (Hb), Hematocrit (Hct), and other relevant laboratory parameters as well as cardiovascular risk factors were retrospectively assessed and analyzed between these 2 groups. Results— Of 217 patients, 114 had a favorable and 103 a poor outcome. In a multivariable regression model, anemia until day 5 after admission (odds ratio [OR]=2.61; 95% CI, 1.33 to 5.11; P=0.005), Hb nadir (OR=0.81; 95% CI, 0.67 to 0.99; P=0.038), and Hct nadir (OR=0.93; 95% CI, 0.87 to 0.99; P=0.038) remained independent predictors for poor outcome at 3 months. Mortality after 3 months was independently associated with Hb nadir (OR=0.80; 95% CI, 0.65 to 0.98; P=0.028) and Hb decrease (OR=1.34; 95% CI, 1.01 to 1.76; P=0.04) as well as Hct decrease (OR=1.12; 95% CI, 1.01 to 1.23; P=0.027). Conclusions— Poor outcome and mortality after ischemic stroke are strongly associated with low and further decreasing Hb and Hct levels. This decrease of Hb and Hct levels after admission might be more relevant and accessible to treatment than are baseline levels.

Low hemoglobin is associated with poor functional outcome after non-traumatic, supratentorial intracerebral hemorrhage

IntroductionThe impact of anemia on functional outcome and mortality in patients suffering from non-traumatic intracerebral hemorrhage (ICH) has not been investigated. Here, we assessed the relationship between hemoglobin (HB) levels and clinical outcome after ICH.MethodsOne hundred and ninety six patients suffering from supratentorial, non-traumatic ICH were extracted from our local stroke database (June 2004 to June 2006). Clinical and radiologic computed tomography data, HB levels on admission, mean HB values and nadir during hospital stay were recorded. Outcome was assessed at discharge and 3 months using the modified Rankin score (mRS).ResultsForty six (23.5%) patients achieved a favorable functional outcome (mRS ≤ 3) and 150 (76.5%) had poor outcome (mRS 4 - 6) at discharge. Patients with poor functional outcome had a lower mean HB (12.3 versus 13.7 g/dl, P < 0.001) and nadir HB (11.5 versus 13.0 g/dl, P < 0.001). Ten patients (5.1%) received red blood cell (RBC) transfusions. In a multivariate logistic regression model, the mean HB was an independent predictor for poor functional outcome at three months (odds ratio (OR) 0.73, 95% confidence interval (CI) 0.58-0.92, P = 0.007), along with National Institute of Health Stroke Scale (NIHSS) at admission (OR 1.17, 95% CI 1.11 - 1.24, P < 0.001), and age (OR 1.08, 95% CI 1.04 - 1.12, P < 0.001).ConclusionsWe report an association between low HB and poor outcome in patients with non-traumatic, supratentorial ICH. While a causal relationship could not be proven, previous experimental studies and studies in brain injured patients provide evidence for detrimental effects of anemia on brain metabolism. However, the potential risk of anemia must be balanced against the risk of harm from red blood cell infusion.

Autonomic Shift and Increased Susceptibility to Infections After Acute Intracerebral Hemorrhage

Background and Purpose— High infection rate after severe stroke may partly relate to brain-induced immunodepression syndrome. However, the underlying pathophysiology remains unclear. The aim of the current study was to investigate the role of autonomic shift in increased susceptibility to infection after acute intracerebral hemorrhage (ICH). Methods— We retrospectively analyzed 62 selected patients with acute ICH from our prospective database. Autonomic shift was assessed using the cross-correlational baroreflex sensitivity (BRS). The occurrence and cause of in-hospital infections were assessed based on the clinical and laboratory courses. Demographic and clinical data including initial stroke severity, hemorrhage volume, intraventricular blood extension, history of aspiration, and invasive procedures such as mechanical ventilation, surgical hematoma evacuation, external ventricular drainage, central venous and urinary catheters, and nasogastric feeding were recorded and included in the analysis. Results— We identified 36 (58%) patients with infection during the first 5 days of hospital stay. Patients with infections had significantly lower BRS, higher initial NIHSS scores, larger hemorrhages, and more frequently had intraventricular blood extension and underwent invasive procedures. In the multivariate regression model, decreased BRS (OR, 0.54; 95% CI, 0.32–0.91; P=0.02) and invasive procedures (OR, 2.32; 95% CI, 1.5–3.6; P<0.001) remained independent predictors for an infection after ICH. Conclusions— Decreased BRS was independently associated with infections after ICH. Autonomic shift may play an important role in increased susceptibility to infections after acute brain injury including ICH. The possible therapeutic relevance of autonomic modulation warrants further studies.

Blood Pressure Variability after Intravenous Thrombolysis in Acute Stroke Does Not Predict Intracerebral Hemorrhage but Poor Outcome

Background: The relevance of blood pressure variability (BPV) in the development of intracerebral hemorrhage (ICH) after intravenous thrombolysis (IVT) in acute stroke still remains uncertain. Methods: 427 consecutive patients treated with IVT in the years 2007–2009 were studied. Blood pressure (BP) values were analyzed from admission to follow-up imaging scan and described as mean, maximum, minimum, standard deviation (SD), difference between maximum and minimum, successive variation (SV) and maximum SV. ICH was categorized based on radiologic criteria and symptomatic ICH (sICH) was defined as ICH plus worsening of the National Institute of Health Stroke Scale by ≧4 points or leading to death. Three-month outcome was described by means of the modified Rankin Scale. Results: We observed any ICH in 51 (11.9%) and sICH in 10 (2.3%) patients. Systolic and diastolic BP profiles, including mean, maximum, minimum, SD, difference between maximum and minimum, SV and maximum SV, did not differ between ICH-negative, ICH-positive and sICH patients. In univariate analysis, high systolic BPV was associated with sICH (p = 0.03). A logistic regression model to predict ICH only found early CT findings (OR = 2.74, 95% CI = 1.47–5.11, p < 0.01) as independently associated with ICH. Poor 3-month outcome was independently predicted by age (OR = 0.96, 95% CI = 0.94–0.97, p < 0.001), NIHSS on admission (OR = 0.84, 95% CI = 0.80–0.87, p < 0.001), ICH (OR = 0.29, 95% CI = 0.13–0.66, p < 0.01) and high systolic BPV (OR = 1.68, 95% CI = 1.05–2.69, p < 0.05). Conclusions: We demonstrate that high BPV in patients receiving IVT leads to poor outcome but does not increase the risk of ICH/sICH.

C-Reactive-Protein Levels Associated with Infection Predict Short- and Long-Term Outcome after Supratentorial Intracerebral Hemorrhage

Background: The aim of the current study was to assess the occurrence of infection and its impact on the short- and long-term outcome of patients with supratentorial intracerebral hemorrhage (ICH). Methods: 247 patients suffering from supratentorial ICH were extracted from our local stroke database. Complete data sets including long-term functional outcome measured by the modified Rankin Scale (mRS), and baseline computed tomography data could be obtained in 113. The charts of these patients were screened for the presence and cause of infection, and baseline and maximal C-reactive protein (CRP) levels were recorded. Results: We identified 52 patients (50.5%) with infection during their hospital stay. Patients with infection, had significantly larger hemorrhages (28.7 vs. 11.9 ml; p = 0.002), a poorer admission status (National Institutes of Health Stroke Scale, NIHSS, score 14 vs. 6; p = 0.002) and more frequently intraventricular hemorrhage extension (46.2 vs. 23.5%; p = 0.016) than those without infection. In a multivariate logistic regression model, baseline NIHSS score (odds ratio, OR, 1.2, 95% confidence interval, CI, 1.1–1.31, p < 0.001), age (OR 1.1, 95% CI 1.03–1.16, p = 0.002) and maximal CRP levels (OR 1.72, 95% CI 1.12–2.64, p = 0.013) were independent predictors of poor long-term functional outcome (mRS >2). Conclusion: Infections were frequent complications in our cohort of ICH patients and occurred significantly more often in patients with poor functional outcome. Maximal CRP levels were an independent predictor of poor outcome in a multivariate model.