Search PubMed⌕ Search

Biomedical subjects

W Hacke

Publications and source records attributed to W Hacke.

At least 55 records · Page 3Linked to original sources
PubMed2001

Early prediction of irreversible brain damage after ischemic stroke at CT.

PURPOSE: To assess the capability of computed tomography (CT) in the prediction of irreversible ischemic brain damage and its association with the clinical course within 6 hours of stroke onset. MATERIALS AND METHODS: Serial CT scans obtained within 6 hours of stroke onset, at 22-96 hours (median, 1 day), and at 2-36 days (median, 7 days) after symptom onset in 786 patients with ischemic stroke were prospectively studied, and follow-up CT scans were used as the reference. Clinical variables were assessed prospectively and independently of CT evaluation. RESULTS: The specificity and positive predictive value of ischemic edema at baseline CT for brain infarcts were 85% (95% CI: 77%, 91%) and 96% (95% CI: 94%, 98%), respectively. Sensitivity and negative predictive values were 64% (95% CI: 60%, 67%) and 27% (95% CI: 23%, 32%), respectively. Patients without early CT findings were less severely affected (P<.001), developed smaller infarcts (P<.001), had fewer intracranial bleeding events (P<.001), and had a better clinical outcome at 90 days (P<.001) compared with patients with hypoattenuating brain tissue at early CT. CONCLUSION: After ischemic stroke, x-ray hypoattenuation at CT is highly specific for irreversible ischemic brain damage if detection occurs within the first 6 hours. Patients without hypoattenuating brain tissue have a more favorable clinical course.

Adolescent↗
PubMed2001

Bootstrap statistics of ECASS II data: just another post hoc analysis of a negative stroke trial?

UNLABELLED: The results of the Second European-Australasian Acute Stroke Study (ECASS II) were negative with respect to the primary endpoint. This post hoc analysis of ECASS II data was designed to make the least number of a priori assumptions. This is accomplished by a bootstrap-based hypothesis test on a non-parametric test statistic. No assumptions are made on shape or variance of population distributions and the method does not suffer from the disadvantages of dichotomization. By reducing the number of a priori assumptions, the possibilities to modify the test result by adjusting the test procedure are minimized. RESULTS: If rt-PA does not improve the outcome (null hypothesis), the probability of observing a difference of modified ranking scale equal or larger than the one observed in ECASS II is 0.047. We therefore rejected the null hypothesis.

Controlled Clinical Trials as Topic↗
PubMed2001

Hemorrhagic transformation of ischemic brain tissue: asymptomatic or symptomatic?

BACKGROUND AND PURPOSE: The term symptomatic hemorrhage secondary to ischemic stroke implies a clear causal relationship between clinical deterioration and hemorrhagic transformation (HT) regardless of the type of HT. The aim of this study was to assess which type of HT independently affects clinical outcome. METHODS: We used the data set of the European Cooperative Acute Stroke Study (ECASS) II for a post hoc analysis. All patients had a control CT scan after 24 to 96 hours or earlier in case of rapid and severe clinical deterioration. HT was categorized according to radiological criteria: hemorrhagic infarction type 1 and type 2 and parenchymal hematoma type 1 and type 2. The clinical course was prospectively documented with the National Institutes of Health Stroke Scale and the modified Rankin Scale: The independent risk of each type of HT was calculated for clinical deterioration at 24 hours and disability and death at 3 months after stroke onset and adjusted for possible confounding factors such as age, severity of stroke syndrome at baseline, and extent of the ischemic lesion on the initial CT. RESULTS: Compared with absence of HT, only parenchymal hematoma type 2 was associated with an increased risk for deterioration at 24 hours after stroke onset (adjusted odds ratio, 18; 95% CI, 6 to 56) and for death at 3 months (adjusted odds ratio, 11; 95% CI, 3.7 to 36). All other types of HT did not independently increase the risk of late deterioration. CONCLUSIONS: Only parenchymal hematoma type 2 independently causes clinical deterioration and impairs prognosis. It has a distinct radiological feature: it is a dense homogeneous hematoma >30% of the ischemic lesion volume with significant space-occupying effect.

Age Factors↗
PubMed2001

Multimodal online monitoring in middle cerebral artery territory stroke.

BACKGROUND AND PURPOSE: Patients with large middle cerebral artery infarction and elevated intracranial pressure (ICP) who are undergoing invasive intensive care therapy require technical monitoring. However, the effectiveness of the current gold standard, measurement of ICP, is limited. Furthermore, the effects of what is considered to be standard antiedema medical treatment are not fully understood. We studied whether multimodal monitoring can help to overcome this problem. METHODS: ICP, cerebral perfusion pressure (CPP), and partial brain tissue oxygen pressure (PbrO(2)) were continuously measured within the white matter of the frontal lobe unilaterally or bilaterally. We analyzed the effects of antiedema drugs and looked for pattern changes in the PbrO(2) before transtentorial herniation in patients in whom this could not be prevented. Furthermore, complications were registered. RESULTS: We performed 27 measurements in 21 patients. A total of 297 antiedema drug administrations were analyzed in 11 patients. Hyper-HAES and mannitol were most often associated with an increase in CPP and PbrO(2), whereas the use of thiopental and tromethamine led to negative or contrary effects, although ICP was decreased in every case. Pattern changes in the PbrO(2) curve could be observed between 6 to 18 hours before transtentorial herniation. No bleeding complication or infections were observed. CONCLUSIONS: Multimodal monitoring can be used to monitor antiedema drug effects. Our data suggest that with multimodal monitoring, pathophysiological changes could be predicted considerably in advance. ICP alone is of questionable use. Furthermore, this method might help to optimize the timing of invasive therapy in space-occupying infarction.

Brain Edema↗
PubMed2001

Risk factors, outcome, and treatment in subtypes of ischemic stroke: the German stroke data bank.

BACKGROUND AND PURPOSE: Data on risk factors for etiologic subtypes of ischemic stroke are still scant. The aim of this study was to characterize stroke subtypes regarding risk factor profile, outcome, and current treatment strategies. METHODS: We analyzed data from 5017 patients with acute ischemic stroke (42.4% women, aged 65.9+/-14.1 years) who were enrolled in a large multicenter hospital-based stroke data bank. Standardized data assessment and stroke subtype classification were used by all centers. RESULTS: Sex and age distribution, major risk factors and comorbidities, recurrent stroke, treatment strategies, and outcome were all unevenly distributed among stroke subtypes (P<0.001, respectively). Cardioembolism, the most frequent etiology of stroke (25.6%), was particularly common in the elderly (those aged >70 years) and associated with an adverse outcome, a low rate of early stroke recurrence, and frequent use of thrombolytic therapy and intravenous anticoagulation. Large-artery atherosclerosis (20.9%), the most common cause of stroke in middle-aged patients (those aged 45 to 70 years), showed the highest male preponderance, highest rate of early stroke recurrence, and highest prevalence of previous transient ischemic attack, current smoking, and daily alcohol consumption among all subtypes. The highest prevalence of hypertension, diabetes mellitus, hypercholesterolemia, and obesity was found in small-vessel disease (20.5%), which, in turn, was associated with the lowest stroke severity and mortality. CONCLUSIONS: Our results foster the concept of ischemic stroke as a polyetiologic disease with marked differences between subtypes regarding risk factors and outcome. Therefore, studies involving risk factors of ischemic stroke should differentiate between etiologic stroke subtypes.

Adult↗
PubMed2001

Anticoagulation: the present and future.

Thrombin is a central bioregulator of coagulation and is therefore a key target in the therapeutic prevention and treatment of thromboembolic disorders, including deep vein thrombosis and pulmonary embolism. The current mainstays of anticoagulation treatment are heparins, which are indirect thrombin inhibitors, and coumarins, such as warfarin, which modulate the synthesis of vitamin K-dependent proteins. Although efficacious and widely used, heparins and coumarins have limitations because their pharmacokinetics and anticoagulant effects are unpredictable, with the risk of bleeding and other complications resulting in the need for close monitoring with their use. Low-molecular-weight heparins (LMWHs) provide a more predictable anticoagulant response, but their use is limited by the need for subcutaneous administration. In addition, discontinuation of heparin treatment can result in a thrombotic rebound due to the inability of these compounds to inhibit clot-bound thrombin. Direct thrombin inhibitors (DTI) are able to target both free and clot-bound thrombin. The first to be used was hirudin, but DTIs with lower molecular weights, such as DuP 714, PPACK, and efegatran, have subsequently been developed, and these agents are better able to inhibit clot-bound thrombin and the thrombotic processes that take place at sites of arterial damage. Such compounds inhibit thrombin by covalently binding to it, but this can result in toxicity and nonspecific binding. The development of reversible noncovalent DTIs, such as inogatran and melagatran, has resulted in safer, more specific and predictable anticoagulant treatment. Oral DTIs, such as ximelagatran, are set to provide a further breakthrough in the prophylaxis and treatment of thrombosis.

Administration, Oral↗
PubMed2001

Treatment options for large hemispheric stroke.

Some stroke patients suffering acute middle cerebral artery (MCA) infarction develop massive brain edema and herniation, a condition known as malignant MCA infarction. Severe swelling increases intracranial pressure (ICP) and leads to progressive brainstem dysfunction. Once ICP reaches critical values (>30 mm Hg) herniation occurs, usually within 2 to 5 days. Patients rarely survive (80% mortality) with standard treatment, and those who do are often severely disabled. Malignant MCA infarction is often missed by neurologists, despite well-defined clinical and neuroimaging (CT scan) diagnostic criteria. After diagnosis, conventional treatments such as osmotherapy, barbiturates, buffers, and hyperventilation center on reducing ICP. The goal of hyperosmolar therapy is to increase the serum osmolarity to approximately 315-320 mOsm/L. Enteric glycerol is used routinely to reduce ICP. In more severe cases and when glycerol fails, mannitol may be administered. Other therapies are also available, including hypertonic saline solution, THAM (Tris-hydroxy-methyl-aminomethane) buffer, and high-dose barbiturates. Hyperventilation also helps reduce ICP. All measures work effectively for a short time only. Other approaches to control elevated ICP, including decompression surgery and hypothermia, have shown promising results. In the Heidelberg decompression surgery trial, mortality in surgically treated patients was significantly lower (32%) than in non-treated patients (76%) despite conventional treatment. Importantly, of the surviving treated patients, 66% were rated independent with only mild to moderate disability. Moderate hypothermia (33-36 degrees C) has recently been shown to be effective in severe MCA infarction. Hypothermia induction within 14 hours of ischemic injury and maintained for 72 hours significantly reduced ICP and mortality (44%).

Brain Edema↗
PubMed2001

Stroke magnetic resonance imaging within 6 hours after onset of hyperacute cerebral ischemia.

We studied the diagnostic and prognostic value of diffusion- and perfusion-weighted magnetic resonancce imaging (DWI and PWI) for the initial evaluation and follow-up monitoring of patients with stroke that had ensued less than 6 hours previously. Further, we examined the role of vessel patency or occlusion and subsequent recanalization or persistent occlusion for further clinical and morphological stroke progression so as to define categories of patients and facilitate treatment decisions. Fifty-one patients underwent stroke magnetic resonance imaging (DWI, PWI, magnetic resonance angiography, and T2-weighted imaging) within 3.3 +/- 1.29 hours, and, of those, 41 underwent follow-up magnetic resonance imaging on day 2 and 28 on day 5. In addition, we assessed clinical scores (on the National Institutes of Health Stroke Scale, Scandinavian Stroke Scale, Barthel Index, and Modified Rankin Scale) on days 1, 2, 5, 30, and 90 and performed volumetric analysis of lesion volumes. In all, 25 patients had a proximal, 18 a distal, and 8 no vessel occlusion. Furthermore, 15 of 43 patients exhibited recanalization on day 2. Vessel occlusion was associated with a PWI-DWI mismatch on the initial magnetic resonance imaging, vessel patency with a PWI-DWI match (p < 0.0001). Outcome scores and lesion volumes differed significantly between patients experiencing recanalization and those who did not (all p < 0.0001). Acute DWI and PWI lesion volumes correlated poorly with acute clinical scores and only modestly with outcome scores. We have concluded on the basis of this study that early recanalization saves tissue at risk of ischemic infarction and results in significantly smaller infarcts and a significantly better clinical outcome. Patients with proximal vessel occlusions have a larger amount of tissue at risk, a lower recanalization rate, and a worse outcome. Urgent recanalization seems to be of utmost importance for these patients.

Aged↗
PubMed2000

Changes in cerebral blood flow and oxygen metabolism during moderate hypothermia in patients with severe middle cerebral artery infarction.

OBJECT: Moderate hypothermia has been reported to be effective in the treatment of postischemic brain edema. The effect of hypothermia on cerebral hemodynamics is a matter of controversial discussion in literature. Clinical studies have yet to be performed in patients with ischemic stroke after induction of hypothermia. METHODS: Measurements during mild hypothermia (33-34 degrees C) were made in six patients with severe ischemic stroke involving the middle cerebral artery territory. Hypothermia was induced as soon as possible and maintained for 48 to 72 hours. Cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were estimated by a new double-indicator dilution method. Measurements of CBF were made during normothermia, immediately after induction of hypothermia, at the end of hypothermia, and after rewarming. A total of 19 measurements of CBF and jugular bulb O2 saturation were made. Immediately after induction of hypothermia, CBF decreased in all patients. During late hypothermia, CBF improved in patients who survived but remained diminished in the two patients who died. Reduced CMRO2 levels were observed during all phases of hypothermia in all but one case. CONCLUSIONS: Preliminary oberservations indicate that moderate hypothermia seems to reduce CMRO2. Immediately after induction of hypothermia, CBF may decrease in all patients. During late hypothermia CBF seems to recover in patients with good outcome but remains diminished in patients who die. Serial bedside CBF measurements with the new double-indicator dilution technique may be useful to describe cerebral hemodynamic characteristics in patients with severe ischemic stroke during hypothermia.

Adult↗
PubMed2000

Effect of propentofylline (HWA 285) on focal ischemia in rats: effect of treatment and posttreatment duration on infarct size.

UNLABELLED: BACKGROUND AND PUROSEe: in this study we tested the potentially neuroprotective properties of propentofylline in a model of focal ischemia with long-term, repeated treatment. METHODS: 37 male Wistar rats (280-300 g) underwent permanent occlusion of the middle cerebral artery (MCA). Infusion was started 30 min after occlusion of the MCA over a period of 2 h with a dosage of 0.01 mg/kg body weight. Immediately after the termination of infusion repetitive intraperitoneal injections were started. Animals were assigned to four groups: continuous treatment for a period of 12 h with 24-h survival (group A, n=9) or 48-h survival (group B, n=10), continuous treatment for a period of 48 h with 48-h survival (group C, n=9) and placebo (group D, n=9). Infarct size was calculated from brain slices stained with 2,3,5-triphenyltetrazolium chloride. RESULTS: the infarct size was significantly reduced in group C (treatment for 48 h) (163.9+/-30.5 mm(3)) compared to the placebo group (297.4+/-17. 7 mm(3)). No effect on infarct size was observed in group A (196. 8+/-37.3 mm(3)) and group B (239.6+/-42.9 mm(3)) compared to placebo. CONCLUSION: continuous i.p. injections of propentofylline over a period of 48 h significantly reduces infarct size in an animal model of focal cerebral ischemia. With shorter periods of continuous administration of the drug and delayed postmortem analysis, reductions in the infarct size did not reach a level of significance. These data show the importance of continuous long-term administration after ischemic stroke in clinical trials to achieve the beneficial effects of neuroprotection by propentofylline.

Animals↗
PubMed2000

Thrombolytic properties of leukocytes from peripheral blood in healthy subjects and in patients with acute cerebral ischemia.

Polymorphonuclear leukocytes are activated in acute ischemic stroke. Activated polymorphonuclear leukocytes may contribute to thrombolysis by proteolytic degradation of fibrin and by modification of the plasminogen system. We used an in vitro thrombolysis model to investigate (1) thrombolytic properties of leukocytes in young and healthy subjects, (2) to test the hypothesis of increased polymorphonuclear leukocyte-associated thrombolysis in patients with acute cerebral ischemia, and (3) to assess plasminogen-dependent and -independent thrombolytic properties of polymorphonuclear leukocyte elastase. Coincubation of polymorphonuclear leukocytes with fibrin clots led to increased thrombolysis, a process reaching statistical significance after 8 hours [1x10(7) polymorphonuclear leukocytes/mL; 12.8+/-1.9% (mean+/-SEM), spontaneous clot lysis: 7.3+/-0.7%]. Polymorphonuclear leukocytes inside clots caused more efficient thrombolysis than polymorphonuclear leukocytes in the incubation medium. Spontaneous and polymorphonuclear leukocyte-associated lysis tended to be lower in patients with acute cerebral ischemia (n=9, 24 hours, 9.5+/-1.8% and 12.9+/-2.2%) than in age- and sex-matched control subjects (n=8; 12.2+/-2.0% and 17.4+/-1.9%). In the presence of alpha(2)-antiplasmin, thrombolysis tended to be faster with elastase-digested plasminogen (miniplasminogen) than with native plasminogen. Purified polymorphonuclear leukocyte elastase itself had no thrombolytic effect. We conclude that the thrombolytic capacity of polymorphonuclear leukocytes from peripheral blood is small and slow and may have been overestimated in previous reports. Polymorphonuclear leukocyte thrombolytic activity may not be increased in acute cerebral ischemia. Miniplasminogen may be an interesting adjunct to plasminogen activators in acute stroke models.

Aged↗
PubMed2000

Magnetic evoked potentials in neurocritical care patients with acute brainstem lesions.

OBJECTIVES: Motor evoked potentials (MEPs) are widely used in various neurological diseases, but have not been systematically employed in neurocritical care patients. We evaluated the clinical and predictive value of MEPs by magnetic transcranial stimulation in intensive care patients with acute brainstem lesions of predominantly vascular origin. METHODS: In a prospective trial, a total of 30 patients with acute brainstem lesions were studied. Diagnoses were brainstem infarction (n=15), brainstem hemorrhage (n=3), encephalitis (n=1), basilar artery aneurysm (n=1), and space-occupying cerebellar infarct (n=5), cerebellar hemorrhage (n=3), and brainstem contusion (n=2). We performed MEP tests by transcranial stimulation to the abductor pollicis brevis bilaterally, bilateral somatosensory (SEPs) and auditory evoked (BAEPs) potentials. We determined motor function at the time of electrophysiological testing and after 3 months, the presence of radiologically confirmed lesions, and clinical outcome after 3 months. At the time of MEP recordings, ten patients were comatose, twelve stuporous, seven somnolent and one awake. RESULTS: MEPs were present bilaterally in seventeen, absent unilaterally in eight and bilateral absent in five patients. Absent MEP highly correlated with the presence of persisting motor deficit 3 months later (P<0.0001). Absent MEPs predicted motor deficit after 3 months with a high specificity and more precisely than the clinical examination at the time of MEP testing. MEP findings correlated with the presence of radiologically confirmed lesions within the brainstem (P<0.0001). Combined with SEP and BAEP data, MEPs predicted the presence of unilateral brainstem lesions with high accuracy. CONCLUSIONS: MEP recordings can be safely performed in neurointensive care patients and yield utilizable results. In patients with brainstem lesions, MEPs correlate with radiological findings and predict final motor function more accurately than clinical findings. MEPs are a reliable diagnostic tool for assessing motor function in otherwise unresponsive patients.

Adolescent↗
PubMed2000

[Treatment of acute clinical stroke].

Stroke is an emergency. Treatment must begin as soon as possible because significant sustained neurological improvement has been demonstrated when thrombolytic treatment, mainly with recombined tissue plasminogen activator (rtPA) is initiated within the first hours of stroke onset. On the other hand in the acute phase of stroke it is critical that patients get adequate management for the prevention of early complications. Management of the acute phase of stroke is the target of this article. Preclinically started treatment must be continued in the neurological emergency unit. Clinical examination is followed by technical investigations: cerebral computer tomography (CCT) is the most useful radiological investigation in the acute phase. It allows to distinguish between ischemia and hemorrhagic lesions and also to rule out nonstroke brain conditions. Multimodal magnetic resonance imaging (mMRI) may provide data on viable versus irreversibly damaged tissue. Sufficient stroke treatment is based on well managed in-hospital infrastructure. Thrombolysis is the only causative treatment of stroke in selected patients. Complications of acute stroke comprise changes of blood pressure with hemodynamically relevant effects on cerebral perfusion pressure, acute post- ischemic brain edema, and intracerebral bleedings.

Brain↗