[Survey regarding the treatment of malignant middle cerebral artery infarction in German hospitals]. / Umfragestudie zur Behandlung des malignen Mediainfarkts an deutschen Kliniken.

BACKGROUND: There are a variety of intensive care therapies in the treatment of malignant middle cerebral artery infarction (MMI) besides hemicraniectomy (HC), the only treatment with proven efficacy. It is, however, not known how HC and conservative treatments are utilized in German hospitals, Furthermore, data on the care-situation of patients with MMI in Germany is scarce. METHODS: An anonymous questionnaire was sent to 297 neurological and 133 neurosurgical hospitals in Germany. RESULTS: The Response rate was 24,7%. Most respondents indicated personal experience in the treatment of MMI (83,3%). HC is usually performed early on site (83,3%). Indication to HC is confirmed on a high level of hierarchy and profession using clinical and radiological criteria in 78,2% of hospitals. Inherent standardized treatment protocols are established in 70,8% of hospitals. Patients are treated on an intensive care unit in 74,5% of hospitals after DHC and in 42,5% of hospitals under non-surgical treatment. Intracranial pressure monitoring is not performed on a regular basis. Differing opinions were observed concerning diagnosis and treatment of MMI without recognizable consensus. CONCLUSION: Basically, structural requirements for the treatment of MMI exist in the participating hospitals. Heterogeneity in the treatment of MMI is striking. The implementation of treatment protocols and adherence to guidelines are desirable steps to optimize treatment.

Intensivtherapie des raumfordernden ischämischen Hemisphäreninfarkts: Zusammenfassung der NCS/DGNI-Leitlinie / Intensive care therapy of space-occupying large hemispheric infarction: summary of the NCS/DGNI guidelines

Der grobe ischämische Hemisphäreninfarkt ("large hemispheric infarction", LHI, Synonym maligner Mediainfarkt, MMI) ist eine schwerwiegende neurologische Erkrankung mit hoher Mortalität und Morbidität. Sowohl behandelnde Ärzte als auch Angehörige sehen sich insbesondere hinsichtlich konservativer Therapiemaßnahmen mit einer schwachen Datenlange konfrontiert. Aktuelle Leitlinien zur allgemeinen Schlaganfallbehandlung legen den Hauptfokus auf Risikofaktoren, Prävention und das akute Rekanalisierungsmanagement, beinhalten aber nur sehr limitierte Empfehlungen zur ggf. folgenden spezifischen intensivmedizinischen Behandlung. Um diese Lücke zu füllen, wurde kürzlich eine interdisziplinäre Konsensus-Konferenz der Neurocritical Care Society (NCS) und der Deutschen Gesellschaft für NeuroIntensiv- und Notfallmedizin (DGNI) zum intensivmedizinischen Management des MMI organisiert. Experten aus Neurologie, Neurointensivmedizin, Neurochirurgie, Neuroradiologie und Neuroanästhesie aus Europa und Nordamerika wurden auf Basis ihrer Expertise und ihrer Forschungsschwerpunkte ausgewählt. Arbeitsgruppen zu einzelnen Schwerpunktthemen erarbeiteten eine Reihe zentraler klinischer Fragestellungen zu diesem Thema und erstellten auf dem Boden der aktuellen Datenlage nach dem System Grading of Recommendation Assessment, Development and Evaluation (GRADE) Empfehlungen. Dies ist eine kommentierte Kurzfassung derselben.(AU)

Large hemispheric infarction (LHI), synonymously called malignant middle cerebral artery (MCA) infarction, is a severe neurological disease with a high mortality and morbidity. Treating physicians as well as relatives are often faced with few and low quality data when attempting to apply optimal treatment to these patients and make decisions. While current stroke treatment guidelines focus on risk factors, prevention and acute management, they include only limited recommendations concerning intensive care management of LHI. The Neurocritical Care Society (NCS) and the German Society for Neurocritical and Emergency Medicine (DGNI) organized an interdisciplinary consensus conference on intensive care management of LHI to meet this demand. European and American experts in neurology, neurocritical care, neurosurgery, neuroradiology and neuroanesthesiology were selected based on their expertise and research focus. Subgroups for several main topics elaborated a number of central clinical questions concerning this topic and evaluated the quality of the currently available data according to the grading of recommendation assessment, development and evaluation (GRADE) guideline system. Subsequently, evidence-based recommendations were compiled after weighing the advantages against the disadvantages of certain management options. This is a commented abridged version of the results of the consensus conference.(AU)

[Intensive care therapy of space-occupying large hemispheric infarction. Summary of the NCS/DGNI guidelines]. / Intensivtherapie des raumfordernden ischämischen Hemisphäreninfarkts. Zusammenfassung der NCS/DGNI-Leitlinie.

Large hemispheric infarction (LHI), synonymously called malignant middle cerebral artery (MCA) infarction, is a severe neurological disease with a high mortality and morbidity. Treating physicians as well as relatives are often faced with few and low quality data when attempting to apply optimal treatment to these patients and make decisions. While current stroke treatment guidelines focus on risk factors, prevention and acute management, they include only limited recommendations concerning intensive care management of LHI. The Neurocritical Care Society (NCS) and the German Society for Neurocritical and Emergency Medicine (DGNI) organized an interdisciplinary consensus conference on intensive care management of LHI to meet this demand. European and American experts in neurology, neurocritical care, neurosurgery, neuroradiology and neuroanesthesiology were selected based on their expertise and research focus. Subgroups for several main topics elaborated a number of central clinical questions concerning this topic and evaluated the quality of the currently available data according to the grading of recommendation assessment, development and evaluation (GRADE) guideline system. Subsequently, evidence-based recommendations were compiled after weighing the advantages against the disadvantages of certain management options. This is a commented abridged version of the results of the consensus conference.

Long-term outcome in patients with Guillain-Barré syndrome requiring mechanical ventilation.

We aimed to determine long-term disability and quality of life in patients with Guillain-Barré syndrome (GBS) who required mechanical ventilation (MV) in the acute phase. Our retrospective cohort study included 110 GBS patients admitted to an intensive care unit and requiring MV (01/1999-08/2010) in nine German tertiary academic medical centers. Outcome was determined 1 year or longer after hospital admission using the GBS disability scale, Barthel index (BI), EuroQuol-5D (EQ-5D) and Fatigue Severity Scale. Linear/multivariate regression analysis was used to analyze predicting factors for outcome. Mean time to follow up was 52.6 months. Hospital mortality was 5.5 % and long-term mortality 13.6 %. Overall 53.8 % had a favorable outcome (GBS disability score 0-1) and 73.7 % of survivors had no or mild disability (BI 90-100). In the five dimensions of the EQ-5D "mobility", "self-care", "usual activities", "pain" and "anxiety/depression" no impairments were stated by 50.6, 58.4, 36.4, 36.4 and 50.6 % of patients, respectively. A severe fatigue syndrome was present in 30.4 % of patients. Outcome was statistically significantly correlated with age, type of therapy and number of immunoglobulin courses. In GBS-patients requiring MV in the acute phase in-hospital, and long-term mortality are lower than that in previous studies, while long-term quality of life is compromised in a large fraction of patients, foremost by immobility and chronic pain. Efforts towards improved treatment approaches should address autonomic dysfunction to further reduce hospital mortality while improved rehabilitation concepts might ameliorate long-term disability.

[Current registry studies of acute ischemic stroke]. / Aktuelle Registerstudien beim akuten ischämischen Schlaganfall.

Study registries offer the opportunity to evaluate the effects of new therapies or to observe the consequences of new treatments in clinical practice. The SITS-MOST registry confirmed the validity of findings from randomized trials on intravenous thrombolysis concerning safety and efficacy in the clinical routine. Current study registries concerning new interventional thrombectomy techniques suggest a high recanalization rate; however, the clinical benefit can only be evaluated in randomized, controlled trials. Similarly, the experiences of the BASICS registry on basilar artery occlusion have led to the initiation of a controlled trial. The benefit of hemicraniectomy in malignant middle cerebral artery infarction has been demonstrated by the pooled analysis of three randomized trials. Numerous relevant aspects are currently documented in the DESTINY-R registry. Finally, the recently started RASUNOA registry examines diagnostic and therapeutic aspects of ischemic and hemorrhagic stroke occurring during therapy with new oral anticoagulants.

Common disorders in the neurological emergency room--experience at a tertiary care hospital.

BACKGROUND: The profile of patients with neurological diseases referred to specialized emergency rooms (ER) has not been reported and it is unknown whether a setting of decentralized ERs is associated with a high number of referrals because of inappropriate admissions. METHODS: In this prospective study, consecutive patients of a specialized neurological ER were enrolled. Data encompassed time from symptom onset to admission, discharge diagnoses, data on hospitalization and on transfers to and from other ERs. RESULTS: Thousand seven hundred and forty-three patients were enrolled. Most common diagnoses were cerebrovascular events (26.5%), headache disorders (13%) and seizures (12.7%). Time since onset of symptoms depended on who referred the patient (P<0.001); seizure patients presented earlier than other patients (P<0.001) and 30.5% of patients with cerebrovascular events presented within 3 h after symptom onset but did not present sooner than patients with other diagnoses. In 18%, diagnoses did not match neurological disorders, 4.5% of patients suffered from cardiovascular events. Referrals to and from other ERs rarely occurred (10.3% vs. 5.9%). Only 20 patients with acute cerebrovascular events were referred via other ERs (1.1%). CONCLUSION: A system of a specialized neurological ER can quickly clear up uncertainties in interpreting neurological symptoms. Owing to the rising number of neurological patients in ERs, more studies are urgently needed comparing the different organizational forms for emergency services.

Patient outcomes in historical comparators compared with randomised-controlled trials.

BACKGROUND: Decompressive hemicraniectomy for malignant middle cerebral artery infarction has long been controversial. Recently, data from randomised-controlled trials have shown that the procedure is life-saving and improves outcome. However, these randomised-controlled trials were difficult to conduct, because of ethical considerations due to high mortality in control groups. While the use of historical comparators may not be ideal for phase III efficacy trials, these data may be useful to inform the selection of trial populations. We sought to replicate the findings of the DESTINY trial of decompressive surgery in malignant middle cerebral artery infarction using the Virtual International Stroke Trials Archive, to determine whether historical comparators could be used as an alternative to control groups in situations where randomised-controlled trials are infeasible or regarded as unethical due to the high mortality under conservative treatment. METHODS: We extracted data on patients from Virtual International Stroke Trials Archive who displayed signs of malignant middle cerebral artery infarction (baseline National Institutes of Health Stroke Scale> or =20, LOC1A score of > or =1 on the National Institutes of Health Stroke Scale at baseline, lesion volume > or =145 cm(3)). We used a chi(2)-test and logistic regression (adjusting for baseline National Institutes of Health Stroke Scale) to compare the functional outcomes (modified Rankin scores and Barthel index) at the last available follow-up assessment between the DESTINY surgical and the Virtual International Stroke Trials Archive comparator groups. We assessed 90-day survival rates using a Kaplan-Meier analysis and Cox proportional hazards modelling (adjusting for the baseline National Institutes of Health Stroke Scale score). RESULTS: Fewer patients in the Virtual International Stroke Trials Archive comparator group (n=6/32, 19% with a 90-day follow-up) achieved a good functional outcome by mRS at the final follow-up, when compared with the DESTINY surgical group (n=8/17, 47% with a 6-month follow-up; chi(2)-test, P=0.04). This difference persisted after adjusting for baseline National Institutes of Health Stroke Scale (logistic regression, P=0.04), but not when accounting for patient age (P=0.66). Analysis of Barthel index at the final follow-up revealed no significant difference between the two groups (chi(2)-test, P=0.07), although a trend towards a better outcome in the DESTINY group was observed. In contrast with the findings of the DESTINY trial, we found no significant difference in 90-day survival rates between the surgical (88%) and the Virtual International Stroke Trials Archive (72%) comparator groups (Cox proportional hazards model, P=0.24). CONCLUSION: The beneficial effects of decompressive hemicraniectomy on survival were not confirmed using a historical comparator dataset. Our observations might be due to the fact that patients with malignant middle cerebral artery infarction are usually excluded from clinical trials of drug efficacy, and patients identified from Virtual International Stroke Trials Archive may not have been truly representative of patients with malignant middle cerebral artery infarction. This mismatch could be rectified through recruitment of population-based studies and stroke registries to Virtual International Stroke Trials Archive to increase the number of patients eligible for entry into the comparator patient data pool.

Evolution of stroke diagnosis in the emergency room--a prospective observational study.

BACKGROUND: Access to acute neurological care is limited. Especially in nonurban areas, and owing to uncertainties in diagnosing stroke, non-neurologists often misinterpret stroke symptoms. We evaluated the profile of patients with suspected stroke and the accuracy of the admission diagnosis 'stroke' in the setting of a specialized neurological emergency department in a nonurban region. METHODS: In this prospective observational study, (1) data from all 4,174 patients with the discharge diagnosis 'stroke' and (2) data from 1,800 consecutive patients (3 cohorts per year over 3 years) with the admission diagnosis 'stroke' were included over a 3-year period. RESULTS: The positive predictive value of the admission diagnosis 'stroke' was 0.34; the negative predictive value was 0.97. The rate of misdiagnosis significantly correlated with age and time from symptom onset to presentation. During the study period, the proportion of patients with the admission diagnosis 'stroke' admitted early after symptom onset increased from 19.9 to 27.8% within 3 h and from 26.4 to 32.7% within 4.5 h, respectively. Thrombolysis rates increased (from 9.4 to 15.4%). CONCLUSION: The uncertainties in interpreting stroke symptoms and the lack of facilities for treating emergency stroke in nonurban areas may be outweighed by offering access to a specialized neurological emergency room, thus rectifying any misinterpretation of stroke symptoms and shortening in-hospital time windows for treatment. Still, the rate of misdiagnosis is high, requiring expensive resources, despite the constant flow of information to the public. Therefore, more prospective data comparing different emergency room settings are needed which focus in particular on patients with the admission diagnosis 'stroke'.

Intensive care management of acute stroke: general management.

For a long time, patients with severe stroke were facing therapeutic nihilism of the attending physicians. Implementation of do-not-resuscitate-orders may have lead to self-fulfilling prophecies and to a pessimistic overestimation of prognosis of severe stroke syndromes. However, there have been great advances in intensive care management of acute stroke patients and it has been shown that treatment on a specialised neurological intensive care unit improves outcome. In this review, we will present a summary of the current state-of-the-art intensive care management of acute stroke patients. After presenting an overview on general management of stroke intensive care patients, special aspects of neurological intensive care of acute large middle cerebral artery stroke, intracerebral haemorrhage and subarachnoid haemorrhage will be discussed. In part II of the review, surgical management options for acute stroke will be discussed in detail.

Prospective combined brain and spinal cord MRI in clinically isolated syndromes and possible early multiple sclerosis: impact on dissemination in space and time.

BACKGROUND: The diagnosis of multiple sclerosis (MS) is based on dissemination in space (DIS) and time (DIT). The aim of the study was to assess the impact of spinal cord (SC) imaging on the evidence of DIS and DIT. METHODS: Thirty-five treatment-naive patients with a first clinical symptom suggestive of MS were examined in a 2-year prospective longitudinal follow-up assessment. Brain and SC magnetic resonance imaging (MRI), Expanded Disability Status Scale and multiple sclerosis functional composite were analysed at baseline and after 1 and 2 years. RESULTS: At study entry, 21 patients were classified as clinically isolated syndrome suggestive of MS (CIS) and 14 patients as possible early MS. SC lesions were detected at baseline in 14 CIS patients (67%, median: 1.0, enhancing 29%) and in 11 patients with possible early MS (79%, median: 2.0, enhancing 29%). DIS as depicted by additive SC imaging was detected in two additional individuals according to the revised versus the 2001 McDonald criteria. All patients with emerging cord lesions showed new brain lesions. Five individuals developed clinically asymptomatic cord lesions. CONCLUSIONS: Spinal cord abnormalities are frequent in CIS patients and in patients with possible early MS. SC imaging slightly improved the establishment of DIS, but had no impact on the evidence of DIT.

Influence of intraventricular fibrinolytic therapy with rt-PA on the long-term outcome of treated patients with spontaneous basal ganglia hemorrhage: a case-control study.

Over the recent years, fibrinolytic agents have been tested for intraventricular clot fibrinolysis (IVF). Compared with patients who did not receive IVF, administration of rt-PA induces rapid resorption of intraventricular blood and normalization of cerebrospinal fluid (CSF) circulation resulting in a reduced 30-day mortality and beneficial short-term outcome after 3 months. Our objective was to analyze possible influences of IVF on the long-term outcome after 12 months. Based on a prospective data base, patients with ganglionic supratentorial hematoma with additional intraventricular hemorrhage and occlusive hydrocephalus (n = 135) were isolated. Twenty-seven patients received IVF. To design a case-control study, we carefully matched 22 controls without IVF with regard to hematoma volume, Graeb score, Glasgow Coma Scale on admission and age (five patients remained unmatchable). We determined clinical and imaging parameters by reviewing the medical records and CT scans of all included patients. Outcome after 12 months was evaluated using the modified Rankin scale (mRS). One multivariate regression analysis was performed to determine predisposing factors for outcome. IVF significantly reduced Graeb score during treatment (eight on admission, three after IVF, one prior to discharge in the treated group versus 8/6/2 in patients without IVF). In patients with IVF requirement, a second external ventricular drainage (EVD) and a ventriculoperitoneal (VP) shunt were reduced (P = 0.08) and the incidence of a lumbar drainage was significantly higher (P < 0.01), whilst the overall time of extra-corporal CSF drainage was comparable. EVD associated complications were equal in both groups. Overall long-term outcome was poor but no significant differences were found between patients with and without IVF (mRS 4-6: 12/22 (54%) in patients with and 13/22 (59%) in patients without IVF; P = 0.81). The five excluded patients with IVF were similar to the 22 included ones with respect to imaging findings and outcome. The multivariate analysis revealed age and baseline hematoma volume, but not IVF to significantly impact the outcome. In accordance with previous studies, IVF hastened clot lysis and reduced the need for repeated EVD exchanges and permanent shunting. However, despite these advantages, IVF did not influence long-term outcome after 12 months. The results of the prospective randomized trial (Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage) need to be awaited.

Factor XII C46T gene polymorphism and the risk of cerebral venous thrombosis.

BACKGROUND: The TT genotype of a functional factor XII (FXII) C46T gene polymorphism was shown to be a risk factor for peripheral venous thrombosis. We tested whether this genetic variant also increases the risk for cerebral venous thrombosis (CVT). METHODS: We performed a case-control study including 78 consecutive patients with proven CVT and 201 healthy population controls from South Germany. The FXII C46T genotype was assessed using a PCR technique. RESULTS: The TT genotype of the FXII C46T polymorphism was more common in patients (16.7%) than in controls (5.5%). A strong association of the TT genotype with CVT was found, which was independent of covariables (adjusted odds ratio 4.57; 95% CI 1.55 to 13.41; p = 0.006). CONCLUSION: The TT genotype of the functional factor XII C46T gene polymorphism may be a new independent risk factor for cerebral venous thrombosis (CVT). Our finding warrants confirmation in an independent study before this genetic variant should be added to the panel of established risk factors for CVT.

[Acute stroke therapy. Current developments]. / Akuttherapie des Schlaganfalls. Was gibt es Neues?

This article covers three major topics of acute stroke therapy: extension of the time window for thrombolysis with desmoteplase, decompressive surgery after malignant middle cerebral artery infarction, and the effect of hemostatic therapy with recombinant activated factor VII (rFVIIa) in patients with spontaneous primary intracerebral hemorrhage. Thrombolytic therapy with recombinant tissue or tissue-type plasminogen activator is still the only approved acute stroke therapy within a 3-h time window. Imaging-based patient selection seems to help extending this time window. After promising results of two phase II trials with the thrombolytic agent desmoteplase in an extended time window after acute ischemic stroke, the DIAS-II study was reconducted in Europe, North America, and Australia as a phase III trial. First results of the included 186 patients are shown. Surprisingly, patients treated with desmoteplase had no better outcome than placebo-treated patients, and there was increased mortality in the high-dose group. Among all stroke subtypes, space-occupying malignant middle cerebral artery is one with the poorest prognosis. Most patients die within a few days due to the development of massive brain edema, despite maximum intensive care. Decompressive hemicraniectomy represents a much more effective therapy for the treatment of local brain swelling. However, until recently this method was highly controversial. Here we present the results of the randomized trials published in 2007 and discuss their relevance for acute therapy. Hematoma growth occurs within 4 h in one third of patients who suffer from intracerebral hemorrhage. Prospective, placebo-controlled, multicenter trials have shown that intravenous application of rFVIIa reduces volume increase. We present preliminary results of the latest phase III trial (FAST: recombinant factor VIIa in acute hemorrhagic stroke), which tried to find whether the hemostatic effect will translate into clinical effect.

[Thrombolysis for ischemic stroke: an update]. / Thrombolyse bei ischämischem Schlaganfall: Ein Update.

Even 10 years after the approval of thrombolysis this life-saving and disability reducing therapy is still underused. Important reasons for that are very strict inclusion criteria such as the early and narrow time-window, fear of bleeding complications and doubts regarding the effectiveness. An intensive and constant effort is required to educate the public that stroke is a treatable emergency. In addition to the medical reasons, economic considerations in a context of decreasing resources emphasize the importance of effective stroke treatment. The results of numerous recent studies such as the European register SITS-MOST help to strengthen the confidence in thrombolysis. In addition the development and advancement of new imaging tools such as multiparametric MRI and advanced CT-techniques will improve patient selection and may enable us to extend the time-window for treatment. Intraarterial thrombolysis, "bridging" methods and new devices for intravascular intervention are the subjects of intensive ongoing research. Even though no randomized trials are available intraarterial thrombolysis is the treatment of choice for acute basilar occlusion, but if this intervention is not available an intravenous approach may be an equal alternative.

Thrombolytic therapy for acute ischaemic stroke in octogenarians: selection by magnetic resonance imaging improves safety but does not improve outcome.

BACKGROUND: Owing to the fear of an increased bleeding risk, thrombolytic therapy is withheld from many patients with acute stroke > 80 years of age. OBJECTIVE: To analyse the risk for symptomatic intracranial haemorrhage (sICH), morbidity and mortality after thrombolytic therapy in octogenarians focusing, in particular, on whether patients selected using magnetic resonance imaging (MRI) had a better risk:benefit ratio. METHODS: The prospectively collected single-centre data of all patients treated with systemic thrombolytic therapy for acute ischaemic stroke since 1998 (n = 468) were reviewed, and patients > or = 80 years (n = 90) were compared with those aged < 80 years (n = 378). In addition, the group of octogenarians was analysed with respect to initial imaging modality. RESULTS: The overall rate of sICH in the octogenarians was 6.9%, compared with 5.3% in younger patients (p = 0.61). In older patients selected by computed tomography, the rate of sICH was 9.4%; no patient selected by MRI had sICH (p = 0.10). Mortality in the octogenarians selected by computed tomography was 29.7% after 3 months as compared with 26.9% in the patients selected by MRI (p = 1.0). 20.3% of the octogenarians selected by computed tomography and 15.4% of those selected by MRI had a favourable outcome (modified Rankin scale < or = 1) after 3 months (p = 0.77). CONCLUSION: Compared with younger patients, octogenarians do not have an increased risk of sICH. The use of MRI to select octogenarians for thrombolytic therapy seemed to decrease the risk of sICH, but did not influence the overall outcome after 3 months.

Diagnostic performance of spectroscopic and perfusion MRI for distinction of brain tumors.

OBJECTIVE: To assess the value of spectroscopic and perfusion MRI for glioma grading and for distinguishing glioblastomas from metastases and from CNS lymphomas. METHODS: The authors examined 79 consecutive patients with first detection of a brain neoplasm on nonenhanced CT scans and no therapy prior to evaluation. Spectroscopic MRI; arterial spin-labeling MRI for measuring cerebral blood flow (CBF); first-pass dynamic, susceptibility-weighted, contrast-enhanced MRI for measuring cerebral blood volume; and T1-weighted dynamic contrast-enhanced MRI were performed. Receiver operating characteristic analysis was performed, and optimum thresholds for tumor classification and glioma grading were determined. RESULTS: Perfusion MRI had a higher diagnostic performance than spectroscopic MRI. Because of a significantly higher tumor blood flow in glioblastomas compared with CNS lymphomas, a threshold value of 1.2 for CBF provided sensitivity of 97%, specificity of 80%, positive predictive value (PPV) of 94%, and negative predictive value (NPV) of 89%. Because CBF was significantly higher in peritumoral nonenhancing T2-hyperintense regions of glioblastomas compared with metastases, a threshold value of 0.5 for CBF provided sensitivity, specificity, PPV, and NPV of 100%, 71%, 94%, and 100%. Glioblastomas had the highest tumor blood flow values among all other glioma grades. For discrimination of glioblastomas from grade 3 gliomas, sensitivity was 97%, specificity was 50%, PPV was 84%, and NPV was 86% (CBF threshold value of 1.4), and for discrimination of glioblastomas from grade 2 gliomas, sensitivity was 94%, specificity was 78%, PPV was 94%, and NPV was 78% (CBF threshold value of 1.6). CONCLUSION: Perfusion MRI is predictive in distinguishing glioblastomas from metastases, CNS lymphomas and other gliomas vs MRI and magnetic resonance spectroscopy.

[Intracerebral hemorrhage related to anticoagulant therapy]. / Antikoagulanzienassoziierte Hirnblutungen.

Intracerebral hemorrhage (ICH) is the most serious complication of oral anticoagulant therapy (OAT). The growing use of OAT has resulted in an increase of fatal ICH. The mortality rate is about 65%, and most of the surviving patients remain disabled. While improvements in the treatment of spontaneous ICH have recently been described, there are no internationally accepted guidelines for managing patients with OAT-ICH. Therefore, identifying effective treatments is essential for improving clinical outcome. This article reviews the epidemiology of OAT-ICH, its pathophysiology, and current treatment options and discusses open questions with particular respect to more recent pharmacological therapies.

[The value of platelet inhibitors in the secondary prophylaxis of stroke -- a review]. / Stellenwert von Thrombozyten-Aggregationshemmern in der Sekundärprävention des ischämischen Schlaganfalls.

INTRODUCTION: The goal of secondary prophylaxis following cerebral ischemia is a long lasting inhibition of thrombogenesis to prevent recurrent stroke or other vascular events. Platelet inhibitors (PI) according to meta-analyses lead to a relative risk reduction (RRR) of 22 % for vascular events after stroke. The aim of this article is a summary and critical review of all relevant studies and meta-analyses for secondary prevention of stroke and to give a differentiated therapeutic recommendation. METHODS: We performed a careful and extensive review of the present literature for PI in the secondary prevention of stroke. Next to the classic meta-analyses such as the Antiplatelet Trialists' analysis, the relevant single trials (e. g. CATS, TASS, ESPS 2, CURE, CAPRIE) as well as meta-analyses and post hoc analyses of these studies are summarized and interpreted. Therapeutic recommendations are in consistence with the recommendations and guidelines of national (DGN), European (EUSI) and international (AHA/ASA) Groups/Associations. Also, the present literature was searched for new information with regard to side effects and pharmacological interactions and introduced into the review. CONCLUSIONS: ASA reduces the RR after TIA/stroke by approximately 13 % and has the same efficacy with less side effects in lower dosages (50 - 325 mg/Tag). Ticlopidine is a reserve drug due to its unfavorable side effect profile (neutropenia, TTP). Clopidogrel is better than ASA (RRR 8.7 %) for vascular patients in preventing another vascular event (stroke, MI, vascular death). This effect is pronounced in patients at high risk for atherothrombotic events such as previous MI, cardiac surgery, or diabetes. Dipyridamole+ASA is better than ASA in patients with TIA/stroke (in indirect comparison also than Clopidogrel) for the secondary prevention of recurrent stroke (RRR 23 %), but not for the prevention of other vascular events. Therefore, Clopidogrel should be primarily given to patients with a high vascular risk (one or more cardiovascular risk factors) or to patients with ASA intolerance. Dipyridamole/ASA should be primarily given to TIA/stroke patients with a lower cardiovascular comorbidity. Studies for the combination of Clopidogrel/ASA (MATCH, CHARISMA) and for the comparison of both combinations (PRoFESS) are underway. At present, the combination of clopidogrel and ASA for cerebrovascular prevention should only be given within controlled studies or as an individual treatment with an accordingly acquired informed consent.

CT and diffusion-weighted MR imaging in randomized order: diffusion-weighted imaging results in higher accuracy and lower interrater variability in the diagnosis of hyperacute ischemic stroke.

BACKGROUND AND PURPOSE: Diffusion-weighted MRI (DWI) has become a commonly used imaging modality in stroke centers. The value of this method as a routine procedure is still being discussed. In previous studies, CT was always performed before DWI. Therefore, infarct progression could be a reason for the better result in DWI. METHODS: All hyperacute (<6 hours) stroke patients admitted to our emergency department with a National Institutes of Health Stroke Scale (NIHSS) score >3 were prospectively randomized for the order in which CT and MRI were performed. Five stroke experts and 4 residents blinded to clinical data judged stroke signs and lesion size on the images. To determine the interrater variability, we calculated kappa values for both rating groups. RESULTS: A total of 50 patients with ischemic stroke and 4 patients with transient symptoms of acute stroke (median NIHSS score, 11; range, 3 to 27) were analyzed. Of the 50 patients, 55% were examined with DWI first. The mean delay from symptom onset until CT was 180 minutes; that from symptom onset until DWI was 189 minutes. The mean delay between DWI and CT was 30 minutes. The sensitivity of infarct detection by the experts was significantly better when based on DWI (CT/DWI, 61/91%). Accuracy was 91% when based on DWI (CT, 61%). Interrater variability of lesion detection was also significantly better for DWI (CT/DWI, kappa=0.51/0.84). The assessment of lesion extent was less homogeneous on CT (CT/DWI, kappa=0.38/0.62). The differences between the 2 modalities were stronger in the residents' ratings (CT/DWI: sensitivity, 46/81%; kappa=0.38/0.76). CONCLUSIONS: CT and DWI performed with the same delay after onset of ischemic stroke resulted in significant differences in diagnostic accuracy. DWI gives good interrater homogeneity and has a substantially better sensitivity and accuracy than CT even if the raters have limited experience.