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Showing papers by "Werner Hacke published in 2001"


Journal ArticleDOI
01 Nov 2001-Stroke
TL;DR: The results foster the concept of ischemic stroke as a polyetiologic disease with marked differences between subtypes regarding risk factors and outcome, and studies involving risk factors of isChemic stroke should differentiate between etiologic stroke subtypes.
Abstract: 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 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...

932 citations


Journal ArticleDOI
01 Jun 2001-Stroke
TL;DR: Only parenchymal hematoma type 2 independently causes clinical deterioration and impairs prognosis, and has a distinct radiological feature: it is a dense homogeneous hematomas >30% of the ischemic lesion volume with significant space-occupying effect.
Abstract: 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...

527 citations


Journal ArticleDOI
TL;DR: Compared with aspirin, clopidogrel therapy results in a striking reduction in the elevated risk for recurrent ischemic events seen in patients with a history of prior cardiac surgery, along with a decreased risk of bleeding.
Abstract: Background—After coronary artery bypass surgery, patients have a high cumulative rate of graft closure and recurrent ischemic events. We sought to determine whether antiplatelet therapy with clopidogrel would be more effective than aspirin, the accepted standard, in these patients. Methods and Results—The event rates for all-cause mortality, vascular death, myocardial infarction, stroke, and rehospitalization were determined for the 1480 patients with a history of cardiac surgery randomized to either clopidogrel or aspirin in a trial of 19 185 patients. The event rate per year of vascular death, myocardial infarction, stroke, or rehospitalization was 22.3% in the 705 patients randomized to aspirin and 15.9% in the 775 patients randomized to clopidogrel (P=0.001). A risk reduction was also seen in each of the individual end points examined, including a 42.8% relative risk reduction in vascular death in patients on clopidogrel versus aspirin (P=0.030). In a multivariate model incorporating baseline clinical...

257 citations


Journal ArticleDOI
TL;DR: Stimulation of the GPi reduces medication side effects, which leads to a better drug tolerance, and the STN is the target of choice for treating patients with severe Parkinson's disease who have side effects from drugs.
Abstract: OBJECTIVES—Deep brain stimulation of the basal ganglia has become a promising treatment option for patients with Parkinson's disease who have side effects from drugs. Which is the best target—globus pallidus internus (GPi) or subthalamic nucleus (STN)—is still a matter of discussion. The aim of this prospective study is to compare the long term effects of GPi and STN stimulation in patients with severe Parkinson's disease. PATIENTS AND METHODS—Bilateral deep brain stimulators were implanted in the GPi in six patients and in the STN in 12 patients with severe Parkinson's disease. Presurgery and 3, 6, and 12 months postsurgery patients were scored according to the CAPIT protocol. RESULTS—Stimulation of the STN increased best Schwab and England scale score significantly from 62 before surgery to 81 at 12 months after surgery; GPi stimulation did not have an effect on the Schwab and England scale. Stimulation of the GPi reduced dyskinesias directly whereas STN stimulation seemed to reduce dyskinesias by a reduction of medication. Whereas STN stimulation increased the unified Parkinson's disease rating scale (UPDRS) motor score, GPi stimulation did not have a significant effect. Fluctuations were reduced only by STN stimulation and STN stimulation suppressed tremor very effectively. CONCLUSION—Stimulation of the GPi reduces medication side effects, which leads to a better drug tolerance. There was no direct improvement of bradykinesia or tremor by GPi stimulation. Stimulation of the STN ameliorated all parkinsonian symptoms. Daily drug intake was reduced by STN stimulation. The STN is the target of choice for treating patients with severe Parkinson's disease who have side effects from drugs.

237 citations


Journal ArticleDOI
TL;DR: It is 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.
Abstract: 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. Ann Neurol 2001;49:460–469

215 citations


Journal ArticleDOI
TL;DR: In the Heidelberg decompression surgery trial, mortality in surgically treated patients was significantly lower than in non-treated patients despite conventional treatment, and of the surviving treated patients, 66% were rated independent with only mild to moderate disability.
Abstract: 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%).

143 citations


Journal ArticleDOI
01 Dec 2001-Stroke
TL;DR: Slow, controlled rewarming is feasible and may be used for ICP and CPP control after moderate hypothermia for space-occupying infarction.
Abstract: Background and Purpose — Moderate hypothermia has been found to reduce intracranial pressure (ICP) significantly in patients who have severe middle cerebral artery infarction However, during passive rewarming, ICP continuously rises and some patients suffer transtentorial herniation Methods — We investigated the question of whether slower rewarming leads to slower increase in ICP and slower decrease in cerebral perfusion pressure (CPP) Furthermore, we studied feasibility of slow, controlled rewarming ICP, CPP, and core body temperature were monitored continuously Achievement of rewarming protocol was assessed by hit rate of temperature target intervals Side effects of hypothermia were assessed Results — Rates of change of both ICP and CPP were correlated significantly with increase in temperature (ICP r =062, P =0002; CPP r =−050, P =0017) In feasibility analysis of 13 controlled rewarmed patients, hit rate of temperature target intervals was 63% (median; range 48% to 81%); hit rate within the target interval or below was 79% (median; range 62% to 94%) Conclusions — Slow, controlled rewarming is feasible and may be used for ICP and CPP control after moderate hypothermia for space-occupying infarction

136 citations


Journal ArticleDOI
TL;DR: DWI was much more reliable than CT in the detection of early ischaemic lesions and it is believed that it should be used in acute ischaemia stroke before aggressive therapeutic intervention.
Abstract: Tissue changes in ischaemic stroke are detectable by diffusion-weighted MRI (DWI) within minutes of the onset of symptoms. However, in daily routine CT is still the preferred imaging modality for patients with acute stroke. Our purpose of this study was to determine how early and reliably ischaemic brain infarcts can be identified by CT and DWI. Three neuroradiologists, blinded to clinical signs but aware that they were dealing with stroke, analysed the CT and DWI of 31 patients with an acute ischaemic stroke. We calculated k-values to analyse inter-rater variability. The ratings were compared with follow-up studies showing the extent of the infarct. The combined assessment of all observers gave positive findings in 77.4 % of all CT examinations, with k = 0.58. Areas of high signal were seen on all DWI studies by all observers (k = 1). Estimation of the extent of the infarct based on DWI yielded k = 0.70 and that based on CT k = 0.39. DWI was much more reliable than CT in the detection of early ischaemic lesions and we believe that it should be used in acute ischaemic stroke before aggressive therapeutic intervention.

93 citations


Journal ArticleDOI
TL;DR: An overview of all hitherto completed trials of intra-arterial thrombolytic therapy for carotid and vertebrobasilar artery stroke is presented including recommendations for therapy and a meta-analysis, and new imaging techniques such as diffusion- and perfusion-weighted magnetic resonance imaging and their impact on patient selection are discussed.
Abstract: Objective: Intra-arterial thrombolytic therapy for carotid and vertebrobasilar stroke may result in a more rapid clot lysis and higher recanalization rates than can be achieved with intravenous thrombolysis and thus may warrant the more invasive and timeconsuming therapeutic approach. We present an overview of all hitherto completed trials of intra-arterial thrombolytic therapy for carotid and vertebrobasilar artery stroke including recommendations for therapy and a meta-analysis. Furthermore, new imaging techniques such as diffusion- and perfusion-weighted magnetic resonance imaging and their impact on patient selection are discussed. Finally, phase IV trials of thrombolysis in general and cost efficacy analyses are presented. Data Sources: We performed an extensive literature search not only to identify the larger and well-known randomized trials but also to identify smaller pilot studies and case series. Trials included in this review, among others, are the PROACT I and PROACT II studies and the Cochrane Library report. Conclusion: Intra-arterial thrombolytic therapy of acute M1 and M2 occlusions with 9 mg/2 hrs pro-urokinase significantly improves outcome if administered within 6 hrs after stroke onset. Seven patients need to be treated to prevent one patient from death or dependence. Vertebrobasilar occlusion has a grim prognosis and intra-arterial thrombolytic therapy to date is the only life-saving therapy that has demonstrated benefit with regard to mortality and outcome, albeit not in a randomized trial. New magnetic resonance imaging techniques may facilitate and improve the selection of patients for thrombolytic therapy. Presently, thrombolytic therapy is still underutilized because of problems with clinical and time criteria, and lack of public and professional education to regard stroke as a treatable emergency. If applied more widely, thrombolytic therapy may result in profound cost savings in health care and reduction of long-term disability of stroke patients. (Crit Care Med 2001; 29:1819 ‐1825)

87 citations


Journal ArticleDOI
TL;DR: An overview of all hitherto completed trials of intravenous thrombolytic therapy for carotid artery stroke including recommendations for therapy and diagnostic procedures and their impact on patient selection and meta-analyses is presented.
Abstract: ObjectiveThrombolytic therapy for acute ischemic stroke was implemented into clinical routine 4 yrs ago. Unfortunately, at present <2% of eligible patients receive thrombolytic therapy. We present an overview of all hitherto completed trials of intravenous thrombolytic therapy for carotid artery str

77 citations


Journal ArticleDOI
TL;DR: The development of reversible noncovalent DTIs has resulted in safer, more specific and predictable anticoagulant treatment, and Oral DTIs, such as ximelagatran, are set to provide a further breakthrough in the prophylaxis and treatment of thrombosis.
Abstract: 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.

Journal ArticleDOI
01 Feb 2001-Spine
TL;DR: Four patients with severe trauma to the cervical spine, defined as luxation, subluxation, or fracture, in whom symptoms of vertebral artery dissection developed after a delay ranging from several hours to weeks are presented.
Abstract: Study Design. A prospective case study was performed. Objectives. To illustrate the association of cervical trauma with vertebral artery dissection, and to propose a diagnostic and therapeutic algorithm for suspected traumatic vertebral artery dissection. Summary of Background Data. Vertebral artery dissection is a recognized but underdiagnosed complication of trauma to the cervical spine. Symptoms of spinal cord injury, however, may obscure those of vertebral artery dissection, presumably causing gross underdiagnosis of this complication. Methods. All patients with vertebral artery dissection admitted to the authors’ facility between 1992 and 1997 were screened for cervical trauma. Results. This article presents four patients with severe trauma to the cervical spine, defined as luxation, subluxation, or fracture, in whom symptoms of vertebral artery dissection developed after a delay ranging from several hours to weeks. The traumatic vertebral artery dissection typically was located at the site of vertebral injury or cranial to it. One patient with fracture of the odontoid process survived symptom free without ischemic brain infarctions. Another patient survived with traumatic quadriplegia in addition to large cerebellar and posterior cerebral artery infarctions. Two patients died as a result of fulminant vertebrobasilar infarctions, both with only moderate impairment from the primary spinal cord injury. Conclusions. Early signs of vertebral artery dissection include head and neck pain, often localized to the site of intimal disruption, which may be disguised by the signs of the spinal injury. Early Doppler ultrasound and duplex sonography as a noninvasive screening method should be performed for patients with severe trauma to the cervical spine. In cases of vertebral artery dissection, immediate anticoagulation should be initiated. Traumatologists should be aware of this complication in evaluating patients with severe trauma of the cervical spine, and also for a variety of forensic reasons.

Journal ArticleDOI
01 Nov 2001-Stroke
TL;DR: The data suggest that with multimodal monitoring, pathophysiological changes could be predicted considerably in advance, and this method might help to optimize the timing of invasive therapy in space-occupying infarction.
Abstract: 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 (Pbro2) 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 Pbro2 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...

Journal ArticleDOI
TL;DR: This post hoc analysis of ECASS II data was designed to make the least number of a priori assumptions by a bootstrap-based hypothesis test on a non-parametric test statistic and rejected the null hypothesis.
Abstract: 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.



Journal ArticleDOI
TL;DR: In this article, a review illustrates all completed trials of intravenous and intra-arterial thrombolytic therapy for carotid artery and vertebrobasilar artery stroke and includes recommendations for therapy, diagnostic procedures and their effect on patient selection, meta-analyses, phase IV trials and cost efficacy analyses.
Abstract: Thrombolytic therapy for acute ischemic stroke within the 3-h time window has been approved. In the US, where FDA approval has existed for about 4 years, less than 2% of stroke patients presently receive thrombolytic therapy. This review illustrates all completed trials of intravenous and intra-arterial thrombolytic therapy for carotid artery and vertebrobasilar artery stroke and includes recommendations for therapy, diagnostic procedures and their effect on patient selection, meta-analyses, phase IV trials, and cost efficacy analyses.


Journal ArticleDOI
TL;DR: Preliminary data, however, suggest that the sensitivity of modern stroke MRI protocols is sufficiently high for hyperacute ICH and SAH and may render additional information with regard to the etiology of ICH or SAH.
Abstract: Intracranial hemorrhage (ICH) accounts for 15% of all strokes. In hyperacute emergency assessment, CT is the diagnostic standard for differentiating between hyperacute ICH and ischemic stroke. At this stage, MRI is considered to be of little value for the diagnosis of ICH or subarachnoidal hemorrhage (SAH). We review the current literature and characterize the role of MRI in the diagnosis of ICH and SAH as well as hyperacute stroke in general: While MRI is considered superior to CT in the diagnosis of subacute and chronic ICH/SAH, in hyperacute ICH this is still a matter of debate. MRI signal characteristics of ICH depend on hemoglobin degradation. Deoxyhemoglobin is the MRI substrate for demonstration of blood due to its paramagnetic properties causing signal loss on susceptibility weighted images (T2*-WI). Preliminary data, however, suggest that the sensitivity of modern stroke MRI protocols is sufficiently high for hyperacute ICH and SAH and may render additional information with regard to the etiology of ICH or SAH. Further interest is focused on perihemorrhagic pathophysiologic processes, which may help to improve therapeutic decision making in patients with ICH.


Book ChapterDOI
01 Jan 2001
TL;DR: In this article, a postinfektiose Bewegungsstorung, das enzephalitische Parkinson-Syndrom, and die daran gekoppelte Verlangsamung aller motorischen and expressiven psychischen Ablaufe durch eine medikamentose Behandlung with einem Vorlaufer der defizienten Transmittersubstanz gebessert werden kann.
Abstract: Jeder angehende Neurologe, eigentlich auch jeder Medizinstudent sollte den Oscar-gekronten Film »Awakenings« (»Zeit des Erwachens« ) gesehen haben. In ihm wurde eindrucksvoll gezeigt, wie eine postinfektiose Bewegungsstorung, das enzephalitische Parkinson-Syndrom, und die daran gekoppelte Verlangsamung aller motorischen und expressiven psychischen Ablaufe durch eine medikamentose Behandlung mit einem Vorlaufer der defizienten Transmittersubstanz gebessert werden kann. Der Film endet tragisch: die wiedergewonnene geistige und korperliche Aktivitat verschwindet wieder, und der stuporose, akinetische Zustand kehrt, jetzt unwiderruflich, zuruck. Weitaus positiver ist die Entwicklung von Diagnose und Therapie des M. Parkinson und anderer Bewegungsstorungen in der Folgezeit gewesen: Parallel zur Aufklarung der Funktion der Basalganglien in der Regulation der Motorik (▸ Kap. 1.7) sind Genetik, Pathophysiologie und Therapie auch anderer Bewegungsstorungen intensiv erforscht worden. Den Patienten konnen heute differenzierte Behandlungsprogramme angeboten werden, die die Prognose gegenuber der jungeren Vergangenheit erheblich verbessern. Dies schlie.t sogar die elektrische Stimulation von extrapyramidalen Kernen (z.B. Ncl. subthalamicus) ein.