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The optimal treatment for patients with asymptomatic carotid artery stenosis is under debate. Since best medical treatment (BMT) has improved over time, the benefit of carotid endarterectomy (CEA) or carotid artery stenting (CAS) is unclear. Randomised data comparing the effect of CEA and CAS versus BMT alone are absent. We aimed to directly compare CEA plus BMT with CAS plus BMT and both with BMT only.SPACE-2 was a multicentre, randomised, controlled trial at 36 study centres in Austria, Germany, and Switzerland. We enrolled participants aged 50-85 years with asymptomatic carotid artery stenosis at the distal common carotid artery or the extracranial internal carotid artery of at least 70%, according to European Carotid Surgery Trial criteria. Initially designed as a three-arm trial including one group for BMT alone (with a randomised allocation ratio of 2·9:2·9:1), the SPACE-2 study design was amended (due to slow recruitment) to become two substudies with two arms each comparing CEA plus BMT with BMT alone (SPACE-2a) and CAS plus BMT with BMT alone (SPACE-2b); in each case in a 1:1 randomisation. Participants and clinicians were not masked to allocation. The primary efficacy endpoint was the cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischaemic stroke within 5 years. The primary safety endpoint was any stroke or death from any cause within 30 days after CEA or CAS. The primary analysis was by intention-to treat, which included all randomly assigned patients in SPACE-2, SPACE-2a, and SPACE-2b, analysed using meta-analysis of individual patient data. We did two-step hierarchical testing to first show superiority of CEA and CAS to BMT alone then to assess non-inferiority of CAS to CEA. Originally, we planned to recruit 3640 patients; however, the study had to be stopped prematurely due to insufficient recruitment. This report presents the primary analysis at 5-year follow-up. This trial is registered with ISRCTN, number ISRCTN78592017.513 patients across SPACE-2, SPACE-2a, and SPACE-2b were recruited and surveyed between July 9, 2009, and Dec 12, 2019, of whom 203 (40%) were allocated to CEA plus BMT, 197 (38%) to CAS plus BMT, and 113 (22%) to BMT alone. Median follow-up was 59·9 months (IQR 46·6-60·0). The cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischaemic stroke within 5 years (primary efficacy endpoint) was 2·5% (95% CI 1·0-5·8) with CEA plus BMT, 4·4% (2·2-8·6) with CAS plus BMT, and 3·1% (1·0-9·4) with BMT alone. Cox proportional-hazard testing showed no difference in risk for the primary efficacy endpoint for CEA plus BMT versus BMT alone (hazard ratio [HR] 0·93, 95% CI 0·22-3·91; p=0·93) or for CAS plus BMT versus BMT alone (1·55, 0·41-5·85; p=0·52). Superiority of CEA or CAS to BMT was not shown, therefore non-inferiority testing was not done. In both the CEA group and the CAS group, five strokes and no deaths occurred in the 30-day period after the procedure. During the 5-year follow-up period, three ipsilateral strokes occurred in both the CAS plus BMT and BMT alone group, with none in the CEA plus BMT group.CEA plus BMT or CAS plus BMT were not found to be superior to BMT alone regarding risk of any stroke or death within 30 days or ipsilateral stroke during the 5-year observation period. Because of the small sample size, results should be interpreted with caution.German Federal Ministry of Education and Research (BMBF) and German Research Foundation (DFG).

Background In patients with acute ischemic stroke, little is known regarding the frequency of abnormal ECG findings other than atrial fibrillation and their association with cardiovascular outcomes. We aim to analyze the frequency and type of abnormal ECG findings, subsequent changes in medical treatment, and their association with cardiovascular outcomes in patients with acute ischemic stroke. Methods and Results In the investigator‐initiated multicenter MonDAFIS (impact of standardized monitoring for detection of atrial fibrillation in ischemic stroke) study, 3465 patients with acute ischemic stroke or transient ischemic attack and without known atrial fibrillation were randomized 1:1 to receive Holter‐ECG for up to 7 days in‐hospital with systematic evaluation in a core cardiology laboratory (intervention group) or standard diagnostic care (control group). Outcomes included predefined abnormal ECG findings (eg, pauses, atrial fibrillation, brady‐/tachycardias), medical management in the intervention group, and combined vascular end point (recurrent stroke, myocardial infarction, major bleeds, or all‐cause death) and mortality at 24 months in both randomization groups. Predefined abnormal ECG findings were detected in 326 of 1693 (19.3%) patients in the intervention group. Twenty of these 326 patients (6.1%) received a pacemaker, and 62 of 326 (19.0%) patients had newly initiated or discontinued β‐blocker medication. Discontinuation of β‐blockers was associated with a higher death rate in the control group than in the intervention group during 24 months after enrollment (adjusted hazard ratio, 11.0 [95% CI, 2.4–50.4]; P =0.025 for interaction). Conclusions Systematic in‐hospital Holter ECG reveals abnormal findings in 1 of 5 patients with acute stroke, and mortality was lower at 24 months in patients with systematic ECG recording in the hospital. Further studies are needed to determine the potential impact of medical management of abnormal ECG findings. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02204267.

We sought to determine the diagnostic agreement between the revised ultrasonography approach by the German Society of Ultrasound in Medicine (DEGUM) and the established Society of Radiologists in Ultrasound (SRU) consensus criteria for the grading of carotid artery disease. Post-hoc analysis of a prospective multicenter study, in which patients underwent ultrasonography and digital subtraction angiography (DSA) of carotid arteries for validation of the DEGUM approach. According to DEGUM and SRU ultrasonography criteria, carotid arteries were independently categorized into clinically relevant NASCET strata (normal, mild [1-49 %], moderate [50-69 %], severe [70-99 %], occlusion). On DSA, carotid artery findings according to NASCET were considered the reference standard. We analyzed 158 ultrasonography and DSA carotid artery pairs. There was substantial agreement between both ultrasonography approaches for severe (κw 0.76, CI95 %: 0.66-0.86), but only fair agreement for moderate (κw 0.38, CI95 %: 0.19-0.58) disease categories. Compared with DSA, both ultrasonography approaches were of equal sensitivity (79.7 % versus 79.7 %; p = 1.0) regarding the identification of severe stenosis, yet the DEGUM approach was more specific than the SRU approach (70.2 % versus 56.4 %, p = 0.0002). There was equality of accuracy parameters (p 0.05) among both ultrasonography approaches for the other ranges of carotid artery disease. While the sensitivity was equivalent, false-positive identification of severe carotid artery stenosis appears to be more frequent when using the SRU ultrasonography approach than the revised multiparametric DEGUM approach.ZIEL: Bestimmung der diagnostischen Übereinstimmung zwischen den multiparametrischen Ultraschallkriterien der Deutschen Gesellschaft für Ultraschall in der Medizin (DEGUM) und den Konsenskriterien der Society of Radiologists in Ultrasound (SRU) hinsichtlich der Graduierung von Karotisstenosen. Post-hoc-Analyse einer prospektiven multizentrischen Studie, welche die multiparametrischen DEGUM-Ultraschallkriterien mit der digitalen Subtraktionsangiografie validierte. Die Graduierung von Karotisstenosen in klinisch relevante NASCET-Kategorien (normal, leichtgradig (1–49 %), mittelgradig (50–69 %), hochgradig (70–99 %), Verschluss) erfolgte verblindet gemäß der DEGUM- und SRU-Ultraschallkriterien. Als Referenz wurde der nach NASCET bestimmte angiografische Stenosegrad verwendet. Wir analysierten 158 konsekutive Untersuchungen aus Ultraschall und Angiografie. Zwischen beiden sonografischen Graduierungsansätzen fand sich eine gute Übereinstimmung für hochgradige (κw 0,76; 95 %-KI 0,66–0,86) und eine mäßige Übereinstimmung für mittelgradige Stenosen (κw 0,38; 95 %-KI 0,19–0,58). Verglichen mit der Referenzangiografie fand sich kein Unterschied hinsichtlich Sensitivität für hochgradige Stenosen (79,7 % versus 79,7 %; p = 1,0), jedoch eine höhere Spezifität der DEGUM-Kriterien (70,2 % versus 56,4 %; p = 0,0002). In den sonstigen Stenosekategorien bestanden keine Unterschiede der Güteparameter (p 0,05). Verglichen mit den SRU-Kriterien weist die Graduierung nach DEGUM eine höhere Spezifität bei der Detektion hochgradiger Stenosen auf. Die Integration von mehr hämodynamischen Parametern scheint somit die Anzahl falsch positiver Diagnosen zu verringern.

Neurologic manifestations are increasingly reported in patients with coronavirus disease 2019 (COVID-19). Yet, data on prevalence, predictors and relevance for outcome of neurological manifestations in patients requiring intensive care are scarce. We aimed to characterize prevalence, risk factors and impact on outcome of neurologic manifestations in critically ill COVID-19 patients.In the prospective, multicenter, observational registry study PANDEMIC (Pooled Analysis of Neurologic DisordErs Manifesting in Intensive care of COVID-19), we enrolled COVID-19 patients with neurologic manifestations admitted to 19 German intensive care units (ICU) between April 2020 and September 2021. We performed descriptive and explorative statistical analyses. Multivariable models were used to investigate factors associated with disorder categories and their underlying diagnoses as well as to identify predictors of outcome.Of the 392 patients included in the analysis, 70.7% (277/392) were male and the mean age was 65.3 (SD ± 3.1) years. During the study period, a total of 2681 patients with COVID-19 were treated at the ICUs of 15 participating centers. New neurologic disorders were identified in 350 patients, reported by these centers, suggesting a prevalence of COVID-19-associated neurologic disorders of 12.7% among COVID-19 ICU patients. Encephalopathy (46.2%; 181/392), cerebrovascular (41.0%; 161/392) and neuromuscular disorders (20.4%; 80/392) were the most frequent categories identified. Out of 35 cerebrospinal fluid analyses with reverse transcriptase PCR for SARS-COV-2, only 3 were positive. In-hospital mortality was 36.0% (140/389), and functional outcome (mRS 3 to 5) of surviving patients was poor at hospital discharge in 70.9% (161/227). Intracerebral hemorrhage (OR 6.2, 95% CI 2.5-14.9, p 0.001) and acute ischemic stroke (OR 3.9, 95% CI 1.9-8.2, p 0.001) were the strongest predictors of poor outcome among the included patients.Based on this well-characterized COVID-19 ICU cohort, that comprised 12.7% of all severe ill COVID-19 patients, neurologic manifestations increase mortality and morbidity. Since no reliable evidence of direct viral affection of the nervous system by COVID-19 could be found, these neurologic manifestations may for a great part be indirect para- or postinfectious sequelae of the infection or severe critical illness. Neurologic ICU complications should be actively searched for and treated.

The proportion of elderly, frail, and multimorbid people has increased dramatically in recent decades resulting from demographic changes and will further increase, which will impact acute medical care. Prospective, randomized studies on geriatric intensive care are still lacking. There are also no international or national recommendations regarding the management of critically ill elderly patients. Based on an expert opinion, this consensus paper provides 16 statements that should be considered when dealing with geriatric critical care patients.

Summary Background Systematic electrocardiogram (ECG) monitoring improves detection of covert atrial fibrillation in stroke survivors but the effect on secondary prevention is unknown. We aimed to assess the effect of systematic ECG monitoring of patients in hospital on the rate of oral anticoagulant use after 12 months. Methods In this investigator-initiated, randomised, open-label, parallel-group multicentre study with masked endpoint adjudication, we recruited patients aged at least 18 years with acute ischaemic stroke or transient ischaemic attack without known atrial fibrillation in 38 certified stroke units in Germany. Patients were randomly assigned (1:1) to usual diagnostic procedures for atrial fibrillation detection (control group) or additional Holter-ECG recording for up to 7 days in hospital (intervention group). Patients were stratified by centre using a random permuted block design. The primary outcome was the proportion of patients on oral anticoagulants at 12 months after the index event in the intention-to-treat population. Secondary outcomes included the number of patients with newly diagnosed atrial fibrillation in hospital and the composite of recurrent stroke, major bleeding, myocardial infarction, or death after 6 months, 12 months, and 24 months. This trial was registered with ClinicalTrials.gov , NCT02204267 , and is completed and closed for participants. Findings Between Dec 9, 2014, and Sept 11, 2017, 3465 patients were randomly assigned, 1735 (50·1%) to the intervention group and 1730 (49·9%) to the control group. Oral anticoagulation status was available in 2920 (84·3%) patients at 12 months (1484 [50·8%] in the intervention group and 1436 [49·2%] in the control group). For the primary outcome, at 12 months, 203 (13·7%) of 1484 patients in the intervention group versus 169 (11·8%) of 1436 in the control group were on oral anticoagulants (odds ratio [OR] 1·2 [95% CI 0·9–1·5]; p=0·13). Atrial fibrillation was newly detected in patients in hospital in 97 (5·8%) of 1714 in the intervention group versus 68 (4·0%) of 1717 in the control group (hazard ratio [HR] 1·4 [95% CI 1·0–2·0]; p=0·024). The composite of cardiovascular outcomes and death did not differ between patients randomly assigned to the intervention group versus the control group at 24 months (232 [13·5%] of 1714 vs 249 [14·5%] of 1717; HR 0·9 [0·8–1·1]; p=0·43). Skin reactions due to study ECG electrodes were reported in 56 (3·3%) patients in the intervention group. All-cause death occured in 73 (4·3%) patients in the intervention group and in 103 (6·0%) patients in the control group (OR 0·7 [0·5–0·9]). Interpretation Systematic core centrally reviewed ECG monitoring is feasible and increases the detection rate of atrial fibrillation in unselected patients hospitalised with acute ischaemic stroke or transient ischaemic attack, if added to usual diagnostic care in certified German stroke units. However, we found no effect of systematic ECG monitoring on the rate of oral anticoagulant use after 12 months and further efforts are needed to improve secondary stroke prevention. Funding Bayer Vital. Translation For the German translation of the abstract see Supplementary Materials section.

Infection with the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to a previously unknown clinical picture, which is known as COVID-19 (COrona VIrus Disease-2019) and was first described in the Hubei region of China. The SARS-CoV-2 pandemic has implications for all areas of medicine. It directly and indirectly affects the care of neurological diseases. SARS-CoV-2 infection may be associated with an increased incidence of neurological manifestations such as encephalopathy and encephalomyelitis, ischemic stroke and intracerebral hemorrhage, anosmia and neuromuscular diseases.In October 2020, the German Society of Neurology (DGN, Deutsche Gesellschaft für Neurologie) published the first guideline on the neurological manifestations of the new infection. This S1 guideline provides guidance for the care of patients with SARS-CoV-2 infection regarding neurological manifestations, patients with neurological disease with and without SARS-CoV-2 infection, and for the protection of healthcare workers.This is an abbreviated version of the guideline issued by the German Neurological society and published in the Guideline repository of the AWMF (Working Group of Scientific Medical Societies; Arbeitsgemeinschaft wissenschaftlicher Medizinischer Fachgesellschaften).

The German Society of Ultrasound in Medicine (DEGUM) recently revised its multiparametric criteria for duplex ultrasonography (DUS) grading of internal carotid artery (ICA) disease. We determined the diagnostic accuracy of the revised DEGUM criteria for ultrasonography grading of ICA disease in a prospective multicenter study. We evaluated consecutive patients who underwent digital subtraction angiography of the extracranial carotid arteries at four tertiary care hospitals. Blinded investigators graded ICA disease according to DEGUM-recommended ultrasonography criteria and calculated NASCET-type percent stenosis from angiography images. Endpoints included overall classification accuracy, prediction of clinically relevant disease categories and between-test agreement in the continuous range of percent stenosis. A total of 121 patients (median age: 69 [IQR, 16] years; 74 % men; median time between DUS and angiography: 1 day [IQR, 2]) provided 163 DUS-angiography carotid artery pairs. The classification accuracy of the DEGUM criteria to predict stenosis within 10 % increments as compared to angiography was 34.9 % (95 % CI, 28.0 - 42.6). The sensitivity of DUS for the detection of moderate (50 - 69 %) and severe (70 - 99 %) stenosis was 35 % and 81 %, with an overall accuracy of 73 % and 74 %, respectively. The specificity was 89 % and 69 %, respectively. Considering the continuous spectrum of the disease (0 - 100 %), the Bland-Altman interval limit of agreement was 51 %. At laboratories experienced with ultrasound grading of the extracranial ICA, the revised DEGUM multiparametric ultrasonography criteria do not eliminate the need for a confirmatory test for the identification of clinically relevant grades of the disease.ZIEL: Die multiparametrischen Ultraschallkriterien zur Graduierung von Karotisstenosen der Deutschen Gesellschaft für Ultraschall in der Medizin (DEGUM) wurden revidiert, bislang aber nicht mit dem Goldstandard Angiografie validiert. Ziel dieser prospektiven multizentrischen Validierungsstudie war es, die diagnostische Güte der DEGUM Ultraschallkriterien zu bestimmen. An vier Zentren wurden konsekutive Patienten eingeschlossen, bei denen routinemäßig eine digitale Subtraktionsangiografie (DSA) der extrakraniellen Arteria carotis interna (ACI) durchgeführt wurde. Die Graduierung des Stenosegrades der ACI erfolgte verblindet gemäß der multiparametrischen DEGUM Ultraschallkriterien. Angiografisch erfolgte die verblindete Stenosegraduierung entsprechend der NASCET Definition. Endpunkte umfassten die Gesamttrefferquote zur Vorhersage von Stenosen in vorgegebenen DEGUM Stenoseintervallen, Vorhersage von klinisch relevanten Stenosekategorien und diagnostische Übereinstimmung beider Methoden im kontinuierlichen Stenosebereich. Von insgesamt 121 rekrutierten Patienten (mittleres Alter, 69 [IQR, 16] Jahre, 74 % Männer, mediane Zeit zwischen Duplexsonografie und DSA, 1 Tag [IQR, 2]) ergaben sich 163 Duplex-DSA Gefäßpaare für die Validierung. Die Gesamttrefferquote der DEGUM-Ultraschallkriterien zur Vorhersage des Stenosegrades innerhalb von 10 % -Schritten im Vergleich zur DSA betrug 34,9 % (95 % CI, 28,0 – 42,6). Die Sensitivität der Ultraschallkriterien für den Nachweis von mittelgradigen (50 – 69 %) und hochgradigen (70 – 99 %) Stenosen betrug 35 % und 81 % mit einer Gesamtgenauigkeit von 73 % und 74 %. Die Spezifität betrug 89 % und 69 %. Der Bland-Altman-Übereinstimmungsbereich zwischen beiden Methoden betrug 51 %. In der Identifikation von klinisch relevanten Stenosekategorien der ACI beseitigen die multiparametrischen DEGUM Ultraschallkriterien nicht die Notwendigkeit eines vaskulären Bestätigungstestes.

The proportion of elderly, frail, and multimorbid people has increased dramatically in recent decades resulting from demographic changes and will further increase, which will impact acute medical care. Prospective, randomized studies on geriatric intensive care are still lacking. There are also no international or national recommendations regarding the management of critically ill elderly patients. Based on an expert opinion, this consensus paper provides 16 statements that should be considered when dealing with geriatric critical care patients.

Rationale Optimal secondary prevention of embolic stroke of undetermined source is not established. The current standard in these patients is acetylsalicylic acid, despite high prevalence of yet undetected paroxysmal atrial fibrillation. Aim The ATTICUS randomized trial is designed to determine whether the factor Xa inhibitor apixaban administered within 7 days after embolic stroke of undetermined source, is superior to acetylsalicylic acid for prevention of new ischemic lesions documented by brain magnetic resonance imaging within 12 months after index stroke. Design Prospective, randomized, blinded, parallel-group, open-label, German multicenter phase III trial in approximately 500 patients with embolic stroke of undetermined source. A key inclusion criterion is the presence or the planned implantation of an insertable cardiac monitor. Patients are 1:1 randomized to apixaban or acetylsalicylic acid and treated for a 12-month period. It is an event-driven trial aiming for core-lab adjudicated primary outcome events. Study outcomes The primary outcome is the occurrence of at least one new ischemic lesion identified by axial T2-weighted FLAIR magnetic resonance imaging and/or axial DWI magnetic resonance imaging at 12 months when compared with the baseline magnetic resonance imaging. Key secondary outcomes are the combination of recurrent ischemic strokes, hemorrhagic strokes, systemic embolism; combination of MACE including recurrent stroke, myocardial infarction, and cardiovascular death and combination of major and clinically relevant non-major bleeding defined according to ISTH, and change of cognitive function and quality of life (EQ-5D, Stroke Impact Scale). Discussion Embolic stroke of undetermined source is caused by embolic disease and associated with a high risk of recurrent ischemic strokes and clinically silent cerebral ischemic lesions. ATTICUS will investigate the impact of atrial fibrillation detected by insertable cardiac monitor and the effects of early anticoagulation with apixaban compared with antiplatelet therapy with acetylsalicylic acid on the incidence of new ischemic lesion after embolic stroke of undetermined source.

Die Erkennung einer intrakraniellen Druckerhohung und die Abschatzung des Ausmases anhand von Veranderungen der Pulsatilitat und der Stromungsgeschwindigkeit in den Hirnbasisarterien war eine der ersten klinischen Anwendungen der transkraniellen Dopplersonographie. Hohe Bedeutung hat diese Bestimmung zwischenzeitlich bei der Diagnose eines zerebralen Kreislaufstillstands im Rahmen der Hirntoddiagnostik erlangt. Daruber hinaus lassen sich intrakranielle Druckerhohungen auch anhand von Veranderungen des Durchmessers der Sehnervenscheide erkennen (Abschn. 26.2).

Background: Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)–defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH). Methods: An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population. Results: A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52–1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor. Conclusions: Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01994720.

Introduction: Novel multi-parametric criteria for duplex ultrasonography (DUS) grading of extracranial internal carotid artery (ICA) steno-occlusive disease have been recently introduced by the German ultrasound expert panel (DEGUM). We sought to determine diagnostic accuracy of the DEGUM criteria against the gold standard catheter angiography. Methods: We prospectively enrolled consecutive patients who routinely underwent diagnostic or therapeutic catheter angiography of the extracranial carotid arteries at four German study sites. Internal carotid artery disease was graded according to the DEGUM multi-parametric criteria for DUS. On angiography, extracranial ICA disease was graded using the NASCET approach. Ultrasonography and endovascular raters were blinded to clinical data and any other imaging modalities. To correspond to clinically relevant NASCET groups, all stenosis measurements were stratified into ranges: normal, mild (1-49%), moderate (50-69%), severe (70-99%) and occlusion. Results: A total of 120 patients (median age, 69 [IQR, 16] years; 74% men; median time between DUS and angiography, 1 day [IQR, 2.5]) provided 162 DUS/angiography carotid artery pairs for final analysis. On angiography, moderate stenosis was found in 48 (30%) and severe stenosis in 63 (39%) arteries. Sensitivity of DUS for detection of moderate and severe stenosis was 35% (95%CI, 22-51%) and 81% (69-90%), with a NPV of 77% (68-84%) and 85% (75-92%), respectively. Specificity was 89% (81-94%) and 97% (94-99%), with a PPV of 57% (37-75%) and 62% (51-73%), respectively. Considering the entire spectrum of the disease (0-100%), the Bland-Altman interval limit of agreement was 51% (Figure). Conclusions: At laboratories experienced with ultrasound grading of the extracranial ICA, the novel DEGUM multi-parametric ultrasonography criteria do not eliminate the need for a confirmatory test for identification of clinically relevant grades of the disease.

Introduction: The novel multi-parametric ‘DEGUM’ duplex ultrasonography (DUS) criteria may improve accuracy of extracranial carotid artery grading but have not been compared with the established Society of Radiologists in Ultrasound (SRU) consensus criteria yet. We sought to investigate the diagnostic agreement between these two widely used DUS approaches for grading of carotid artery steno-occlusive disease. Methods: This was a sub-analysis of the complete dataset from a prospective multicenter study, where a total of 120 patients underwent both DUS and catheter angiography for validation of the multi-parametric DEGUM ultrasound approach. In this analysis, two ultrasonography experts independently interpreted documented B-image, color-flow and Doppler spectra findings utilizing DEGUM and SRU criteria. Carotid arteries were categorized into clinically relevant NASCET strata: moderate (50-69%), severe (70-99%) and occlusion. On angiography, ICA was graded using the NASCET approach. Inter-rater and between-methods reliability was assessed through weighted Cohen’s kappa. Overall accuracy for both ultrasound approaches was computed using catheter angiography as the gold standard. Results: We analyzed a total of 162 carotid artery pairs on catheter angiography and DUS. There was almost perfect agreement between both ultrasonography diagnostic approaches in describing all clinically relevant grades of the disease (k w 0.91, CI95%: 0.89-0.94). Inter-rater reliability was found to be comparably high for both the DEGUM (k w 0.97, CI95%: 0.94-0.98) and the SRU (k w 0.98, CI95%: 0.97-0.99) ultrasonography approaches. Compared with catheter angiography, overall accuracy for moderate and severe stenosis ranges did not differ between the DEGUM (73% and 73%, respectively) and the SRU (73% and 70%, respectively) approaches. There was also no difference for detection of carotid artery occlusion (96% and 96%, respectively). Conclusions: Our analysis showed almost perfect diagnostic agreement between the DEGUM and the SRU approaches for ultrasonography grading of carotid artery steno-occlusive disease. Therefore, our data do not support superiority of one approach over the other in the evaluation of clinically relevant grades of the disease.

Aims Variability in responsiveness to clopidogrel is a clinical problem in secondary prevention after cerebral ischaemia which has been suggested to be linked to competitive metabolization of clopidogrel and cytochrome P450 (CYP) 3A4-oxidated statins such as simvastatin. We assessed the hypothesis that simvastatin, in contrast to CYP 2C9-metabolized fluvastatin, reduces clopidogrel-mediated platelet inhibition. Methods We performed a randomized, double-blind, double-dummy, two period crossover study in 13 patients with cerebral ischaemia (8F, 5 M), aged 64.1 ± 8.0 years (mean ± SD). After a 14 day period in which all patients received 75 mg clopidogrel day−1, patients additionally received either 20 mg simvastatin day−1 or 80 mg fluvastatin day−1 for 14 days. Regimens were crossed over after a 14 day wash-out period and switched regimens were continued for another 14 days. Platelet aggregation, clopidogrel active metabolite (CAM) plasma concentrations and routine laboratory parameters including prothrombin time (PT) Quick percent value were assessed at baseline and following each treatment phase. Results Clopidogrel reduced platelet aggregation in all patients as expected. Platelet aggregation and CAM plasma concentrations were unaltered when simvastatin or fluvastatin was added to clopidogrel. Simvastatin decreased PT Quick percent value (decrease from 109 ± 10.5% to 103 ± 11%, P < 0.05) when combined with clopidogrel but there was no such change following treatment with fluvastatin and clopidogrel. Conclusions Our data indicate that treatment with CYP 3A4-metabolized simvastatin does not jeopardize clopidogrel-mediated inhibition of platelet aggregation. After co-administration of simvastatin and clopidogrel we observed a decrease in the PT Quick percent value which could be due to simvastatin-induced reduction of activity of prothrombin fragment 1 + 2.

Die vaskulare Demenz (VaD) ist nach der Alzheimer Demenz die haufigste Ursache einer Demenz. Die vaskular bedingten Demenzen werden heute eher mit dem Begriff der vaskularen kognitiven Storung (engl. vascular cognitive impairment – VCI) bezeichnet und umfassen verschiedene nosologische Veranderungen, die sich sowohl klinisch als auch pathophysiologisch voneinander unterscheiden. Allen gemeinsam ist aber als Ursache die zerebrovaskulare Erkrankung. Unklar ist das Verhaltnis zwischen Alzheimer Demenz und vaskularer Demenz, auch wenn es sicher Uberschneidungen gibt. Daher betrachtet man diese Formen der Demenz eher als einander gegenuberstehende Enden eines gemeinsamen Spektrums dementieller Erkrankungen. Die verschiedenen Risikofaktoren fur einen Schlaganfall wie Hypertonus, Diabetes und Fettstoffwechselstorungen sind sowohl mit einem erhohten Risiko fur die Entwicklung einer Alzheimer Demenz als auch mit dem einer vaskularen kognitiven Storung verbunden. Diese Ubersicht soll die wichtigsten Formen der vaskularen Demenz erlautern.

Die Umstrukturierungen im Gesundheitssystem im Rahmen des GMG und die Umstellung des Entgeltsystems auf DRGs (vgl. Bundesministerium fur Gesundheit und Soziales 2005) haben zu einem zunehmenden Wettbewerb zwischen den Krankenhausern gefuhrt.

Introduction: Novel multi-parametric criteria for duplex ultrasonography (DUS) grading of extracranial internal carotid artery (ICA) steno-occlusive disease have been recently introduced by the German ultrasound expert panel (DEGUM). We sought to determine diagnostic accuracy of the DEGUM criteria against the gold standard catheter angiography. Methods: We prospectively enrolled consecutive patients who routinely underwent diagnostic or therapeutic catheter angiography of the extracranial carotid arteries in four German study sites. Internal carotid artery disease was graded according to the DEGUM multi-parametric criteria for DUS. On angiography, extracranial ICA disease was graded using the NASCET approach. Ultrasonography and endovascular raters were blinded to clinical data and any other imaging modalities. To correspond to clinically relevant NASCET groups, all stenosis measurements were stratified into ranges: normal, mild (1-49%), moderate (50-69%), severe (70-99%) and occlusion. Results: We studied 130 patients who underwent both DUS and catheter angiography for assessment of carotid arteries (mean age, 64±11 years; 67% men; median time between DUS and angiography, 1 day [interquartile range, 2.5]). To date, fifty-two carotid artery pairs were independently rated and available for comparative analysis. Compared with catheter angiography, DUS had the following positive (PPV) and negative predictive values (NPV): PPV 50% and NPV 72% (3 true positive, 3 false positive, 33 true negative, 13 false negative) for detection of moderate, and PPV 57% and NPV 77% (20 true positive, 15 false positive, 13 true negative, 4 false negative) for detection of severe stenosis. Conclusions: Our preliminary data indicate that the novel DEGUM multi-parametric ultrasonography criteria do not eliminate the need for a confirmatory test for identification of clinically relevant grades of extracranial ICA disease.

BACKGROUND The best therapeutic approach in patients with acute basilar artery occlusion (BAO) remains unclear. We report the results of a combined treatment approach with intravenous (IV) abciximab and intraarterial (IA) tissue plasminogen activator (tPA) in these patients. METHODS We prospectively studied patients with acute BAO on CT-angiography or MR-angiography. We treated patients with IV abciximab followed by IA thrombolysis with tPA. Primary outcome was partial or complete recanalization according to thrombolysis in myocardial infarction 2 to 3 flow grades on catheter angiography. Secondary outcomes were favorable functional outcome (mRS score ≤3) and mortality at 90 days. RESULTS Of 20 patients, mean age was 62 ± 13 years, median baseline National Institutes of Health Stroke Scale (NIHSS) score 25.5 (IQR 12-28), and median Glasgow Coma Scale score 7 (IQR 6-11). Mean time to IA treatment was 7 ± 2.8 hours. We achieved partial or complete recanalization in 17/20 patients (85%). At 3 months, 3/20 patients (15%) had a favorable functional outcome and 9/20 patients (45%) were deceased. CONCLUSIONS Combined treatment with IV abciximab and IA tPA yielded a high recanalization rate in patients with BAO. However, functional outcomes were poor, potentially due to late initiation of treatment. Early treatment might improve functional outcome. J Neuroimaging 2012;22:167–171.

Background – In patients with acute middle cerebral artery (MCA) occlusion, recanalization rates with intravenous (IV) recombinant tissue plasminogen activator (rtPA) are limited. Aim– We evaluated the feasibility and safety of combined IV thrombolysis with abciximab and reduced dose rtPA in a 3- to 6-h time window. Methods – We prospectively (March 2002 to February 2005) studied patients with symptomatic MCA occlusion on computed tomography (CT) angiography and absence of major early ischemic changes (EIC) on non-contrast CT (NCCT) within 3–6 h from symptom onset. Patients were treated with IV abciximab and half-standard dose rtPA. Outcome parameters were symptomatic intracerebral hemorrhage (sICH), early clinical improvement and functional independence at discharge (modified Rankin Scale score ≤ 2). Results – Of 13 patients, mean age was 62 ± 11 years, onset-to-treatment time 4.8 ± 0.9 h and median baseline National Institutes of Health Stroke Scale score 11 (interquartile range 6.5–13.5). sICH occurred in one patient (8%). We observed early clinical improvement in four patients (31%). Six patients (46%) were functionally independent at discharge. Conclusions – In patients with acute symptomatic MCA occlusion and absence of major EIC on NCCT, combined IV thrombolysis with abciximab and half-standard dose rtPA was feasible and seemed to be safe if applied within 3–6 h from symptom onset.

BACKGROUND AND PURPOSE: The posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) is a 10-point grading system to quantify ischemic changes in the posterior circulation. We analyzed whether pc-ASPECTS on CT angiography (CTA) source images (CTASI) predicted the final infarct extent and hemorrhagic transformation (HT) rate in patients with basilar artery occlusion. MATERIALS AND METHODS: A pc-ASPECTS score of 10 indicates absence of visible ischemic changes in the posterior circulation, and pc-ASPECTS score of 0 indicates ischemic changes in the midbrain, pons, and bilateral thalami, posterior circulation territories, and cerebellar hemispheres. We retrospectively studied patients with basilar artery occlusion on CTA within 24 hours from symptom onset. We applied pc-ASPECTS to noncontrast CT (NCCT), CTASI, and follow-up images by 3-reader-consensus and assessed HT on follow-up images. We calculated Spearman correlation coefficients and performed linear regression analysis. Final infarct extent and HT rates were compared across dichotomized CTASI pc-ASPECTS groups (≥ 8 vs < 8). RESULTS: Among 43 patients, median (range) onset to CTA time was 5.0 hours (range, 0.7–24 hours). Pc-ASPECTS on CTASI (r = 0.75; P < .001) but not NCCT (r = 0.29; P = .063) correlated with pc-ASPECTS on follow-up scans. Linear regression demonstrated a significant positive relationship between pc-ASPECTS on CTASI and follow-up scans (R(2) = 0.58; P < 01). Median follow-up pc-ASPECTS was lower in patients with a CTASI pc-ASPECTS < 8 compared with patients with a CTASI pc-ASPECTS of 8 or more, respectively (P < .001). HT rates were 27.3% vs 9.5%, respectively (P = .24). None of 8 patients without thrombolysis had HT on follow-up scans. CONCLUSIONS: The extent of hypoattenuation on CTASI predicts the final infarct extent in patients with basilar artery occlusion.

While incidence of stroke in patients 55 to 64 years of age is 2-3 per 1 000 people and per year, this rate is 10fold higher in patients 85 years of age or above. Concomitant cardiovascular diseases, e. g. arterial hypertension, diabetes mellitus and hypercholesterinaemia, increase the risk for stroke. Both prevalence and incidence increase with age. Early treatment and continuous optimisation of these risk factors can prevent stroke. Prevention of cerebro-vascular complications reduces the development and progression of vascular dementia. It is one of the most frequent subtypes of dementia along with Alzheimer's disease. After recent stroke, one out of ten patients is likely to suffer from another event within the first year. Besides treatment of risk factors, secondary prevention mainly consists of platelet aggregation inhibitors after atherosclerotic stroke, and oral anticoagulation after cardio-embolic stroke. For acute therapy of stroke the fibrinolytic drug rtPA (Actilyse®) can be applied. Age above 80 years has been an exclusion criterion so far. However, recent investigations clearly indicate that the protective effect of rtPA may outweigh the bleeding risk. The same can be stated for the secondary stroke prevention with oral anticoagulants. Hemorrhagic stroke will not be discussed in this article.

Background and Purpose— Quantification of early ischemic changes (EIC) may predict functional outcome in patients with basilar artery occlusion (BAO). We tested the validity of a novel CT score, the posterior circulation Acute Stroke Prognosis Early CT score (pc-ASPECTS). Methods— Pc-ASPECTS allots the posterior circulation 10 points. Two points each are subtracted for EIC in midbrain or pons and 1 point each for EIC in left or right thalamus, cerebellum or PCA-territory, respectively. We studied 2 different populations: (1) patients with suspected vertebrobasilar ischemia and (2) patients with BAO. We applied pc-ASPECTS to noncontrast CT (NCCT), CT angiography source images (CTASI), and follow-up image by 3-reader consensus. We calculated sensitivity for ischemic changes and analyzed the predictivity of pc-ASPECTS for independent (modified Rankin Scale [mRS] score ≤2) and favorable (mRS score ≤3) outcome. Results— Of 130 patients with suspected vertebrobasilar ischemia, 72% (94) had posterior circulation stroke, 8% (10) transient ischemic attack, and 20% (26) nonischemic etiology. Sensitivity for ischemic changes was improved with CTASI compared to NCCT (65% [95% CI, 57% to 73%] versus 46% [95% CI, 37% to 55%], respectively). Pc-ASPECTS score on CTASI but not NCCT predicted functional independence (OR 1.58; P =0.005 versus 1.22; P =0.42, respectively). Of 46 patients with BAO, 52% (12/23) with CTASI pc-ASPECTS score ≥8 but only 4% (1/23) with a score Conclusion— The CTASI pc-ASPECTS score may identify BAO patients unlikely to have a favorable outcome despite recanalization.

Population-based studies indicate that the prevalence of carotid stenosis is 0.5 % in the sixth decade of life but increases up to 10 % by the age of 80 years. Ipsilateral carotid stenosis, with > 50 % of the artery occluded, is found in about 10 % of carotid territory ischemic strokes and in about 15 % of transient ischemic attacks (TIA), and is associated with a high-risk of recurrent stroke. Treatment of carotid artery disease plays a major role in stroke prevention. In this article we focus on the role of carotid artery angioplasty and stenting as compared with carotid endarterectomy. We summarize the current positions of the Calgary Stroke Program and the Dresden University Stroke Centre in the treatment of patients with extracranial carotid stenosis as examples for a North American and a German Stroke Centre.

The treatment of patients with cerebral infarction due to vascular stenosis/occlusion includes a range of therapeutic options such as intravenous recombinant tissue plasminogen activator (rtPA) application, thrombocyte aggregation inhibition, anticoagulation, intraarterial thrombolytic medication as well as carotid endarterectomy and endovascular procedures (angioplasty or stenting of extra- and intracranial vessels). Both the drug therapies and endovascular techniques are expected to expand significantly over the next few years. The challenge consists in achieving optimal patient selection for specific therapeutic options. This position paper is a review and expert consensus document in neuromedicine, concerning the bridging concept in neurovascular diseases. It is the authors' approach to propose guidelines designed to ensure that patients with acute stroke who may be candidates for rapid revascularization have a chance to receive this type of treatment. In this ongoing multidisciplinary discussion all organizational, technical and personnel resources provided by stroke centers and cooperating hospitals should be harmonized and optimized. To ensure that no valuable time is lost and that the available time is used optimally, it may make sense to start systemic application of rtPA for thrombolysis following a diagnosis of nonhemorrhagic brain infarct and confirmation of suitability by means of teleneuromedical systems (TNS) until interventional therapy options or intraarterial local treatment can be initiated. This so-called bridging technique can further increase the success rate of treatment compared to exclusive intraarterial procedures. Endovascular therapeutic options are still considered difficult, expensive, and risky, and should be reserved for specialized centers with experienced staff. Therefore, the selection process must be extensive, thorough and precise and patients must be allocated to centers without delay. Through the diffusion of certain techniques, in particular CT- or MRI-guided techniques (CTA, CTP, MRA, DWI, PWI), specific endovascular therapy protocols can be customized to select certain subtypes of stroke. Optimal pathways for specific infarct subtypes, where combined therapy strategies (bridging concepts) are perhaps most attractive, but fairly difficult to establish, should be developed in the near future.

Ultrasound is widely used in the assessment of neurovascular diseases. In spite of its effectiveness there are considerable limitations such as low flow detection in carotid disease or limited bony windows in transcranial Doppler. One approach to overcome these limitations is the use of ultrasound contrast enhancing agents. The usefulness of ultrasound contrast enhancing agents Levovist, EchoGen and BY 963 in neurovascular applications has been evaluated. Contrast enhanced colourflow Doppler for the diagnosis of carotid disease has been investigated in three small trials and might be effective for improving the diagnostic yield in severe disease. Contrast enhanced transcranial colourflow Doppler has been relatively more widely explored also with promising results. Based on the combined findings out of these preliminary investigational trials, it appears to be reasonable to undertake larger trials for assessment of usefulness of ultrasound contrast agents for a variety of neurovascular applications.

Background: We aimed to analyse the course of early recanalization and corresponding functional outcome in patients with an acute occlusion of the carotid T who were treated conservatively or underwent intravenous thrombolysis. Methods: Forty-two patients with an acute occlusion of the carotid T within 6 h were recruited from consecutive admissions to a neurological department participating in the Duplex Sonography in Acute Stroke study. All patients underwent a standardized admission and follow-up procedure. Colour-coded duplex sonography was performed on admission, 30 min after thrombolysis, and at 6 and 24 h after onset of symptoms. Recanalization of the carotid T was classified as complete, partial and absent. Functional outcome was rated with the modified Rankin scale (mRS) at 3 months as favourable (mRS 0–2) or poor (mRS 3–6). Results: Within 6 h, complete or partial recanalization occurred in 1 of 27 patients treated conservatively and in 6 of 15 thrombolysed patients. Intravenous thrombolysis predicted early recanalization also after adjustment for age, sex, cardioembolic stroke aetiology and time to treatment (adjusted odds ratio, OR, 39.7; 95% confidence interval, CI, 2.0–801.7; p = 0.016). An early recanalization was the only selected predictor of a favourable outcome (OR, 13.6; 95% CI, 1.0–179.0; p = 0.047) at regression analysis, and was achieved in 3 thrombolysed patients but in none with conservative medical treatment. Conclusions: In patients treated conservatively, functional outcome is poor and early recanalization rarely occurs. The latter can be achieved by intravenous thrombolysis with a rate comparable to that found at an intra-arterial approach without major intracranial bleeding complications. Early recanalization is associated with a better functional outcome.

We report on a 74-year-old man with bilateral internal carotid artery (ICA) disease who suffered a stroke with hemianopia, global aphasia, and right hemiparesis while asleep. Because of the absence of ischemic edema on initial cranial computed tomography (CT) despite a tight stenosis of the proximal left ICA on CT angiogram, we considered angiography and intervention. The digital subtraction angiography (DSA) confirmed a long and tight stenosis of the left proximal ICA containing a thrombus at its distal outflow (Figure 2). Because of further progression of symptoms, we recanalized the left ICA by deployment of a stent and subsequent angioplasty under the protection of abciximab and heparin. The patient improved from an NIH stroke score (NIHSS) of 12 at the time of admission to an NIHSS of 2 within 3 days.

Variability in responsiveness to clopidogrel is a clinical problem in secondary prevention after cerebral ischaemia which has been suggested to be linked to competitive metabolization of clopidogrel and cytochrome P450 (CYP) 3A4-oxidated statins such as simvastatin. We assessed the hypothesis that simvastatin, in contrast to CYP 2C9-metabolized fluvastatin, reduces clopidogrel-mediated platelet inhibition.We performed a randomized, double-blind, double-dummy, two period crossover study in 13 patients with cerebral ischaemia (8F, 5 M), aged 64.1 ± 8.0 years (mean ± SD). After a 14 day period in which all patients received 75 mg clopidogrel day(-1) , patients additionally received either 20 mg simvastatin day(-1) or 80 mg fluvastatin day(-1) for 14 days. Regimens were crossed over after a 14 day wash-out period and switched regimens were continued for another 14 days. Platelet aggregation, clopidogrel active metabolite (CAM) plasma concentrations and routine laboratory parameters including prothrombin time (PT) Quick percent value were assessed at baseline and following each treatment phase.Clopidogrel reduced platelet aggregation in all patients as expected. Platelet aggregation and CAM plasma concentrations were unaltered when simvastatin or fluvastatin was added to clopidogrel. Simvastatin decreased PT Quick percent value (decrease from 109 ± 10.5% to 103 ± 11%, P0.05) when combined with clopidogrel but there was no such change following treatment with fluvastatin and clopidogrel.Our data indicate that treatment with CYP 3A4-metabolized simvastatin does not jeopardize clopidogrel-mediated inhibition of platelet aggregation. After co-administration of simvastatin and clopidogrel we observed a decrease in the PT Quick percent value which could be due to simvastatin-induced reduction of activity of prothrombin fragment 1 + 2.

BACKGROUND: In secondary prevention after ischemic stroke variability in individual responsiveness to clopidogrel is a clinically relevant problem. Among possible mechanisms that may contribute to this phenomenon, clopidogrel-statin interactions are discussed. Particularly, competitive metabolization of lipohilic statins (i.e. simvastatin) and clopidogrel by cytochrome P450 (CYP) 3A4 was suggested to reduce the inhibitory effect of clopidogrel on platelet aggregation. In contrast, hydrophilic fluvastatin is predominantly metabolized by CYP 2C9 and is therefore assumed not to alter clopidogrel efficacy. We assessed the hypothesis that simvastatin, in contrast to fluvastatin, reduces clopidogrel-mediated platelet inhibition. METHODS: We performed a randomized double blind placebo controlled crossover study in 13 patients with acute ischemic stroke. After an initial 13 day period in which all patients received 75 mg clopidogrel/day, one group (n=6) was randomized to additionally receive 20 mg simvastatin/day and placebo for 13 days. During this period the other group (n=7) received 80 mg fluvastatin and placebo in addition to clopidogrel. Regimens were crossed over after a 13 day wash-out period during which patients received clopidogrel only. Switched regimens were then continued for another 13 days. Assessment of ADP-induced platelet aggregation, plasma levels of clopidogrel active metabolite and coagulation was performed at baseline, at each regimen change and at study completion. RESULTS: We studied 7 female and 6 male patients, ages 63.9±3 years (mean±SD). Plasma levels of clopidogrel active metabolite and platelet aggregation were unaltered when simvastatin or fluvastatin were added to treatment with clopidogrel. Simvastatin decreased prothrombin ratio (decrease from 109±10,5% to 103±11%, p CONCLUSIONS: This study indicates that neither fluvastatin nor simvastatin alter clopidogrel-mediated platelet inhibition. In co-administration of simvastatin and clopidogrel we observed decrease in prothrombin ratio which could be due to simvastatin-induced reduction of prothrombin fragment 1 and 2 activity.

Background and Purpose — A 1997 report suggests that the posterior circulation of the normal brain has diminished vasoreactivity compared with the anterior circulation. To further study this, we quantified and compared the vasodilatory capacities of the middle cerebral (MCA) and basilar artery (BA) territories in response to changes in Pa co 2 , as indices of respective cerebrovascular reserve (CVR). If posterior circulation CVR is indeed physiologically lower than that of the MCA, it might indicate a greater risk of low-flow ischemia distal to basilar obstructive cerebrovascular lesions and provide a rationale for earlier treatment of such lesions with interventional techniques. We also wished to establish normal baseline CVR values for the posterior circulation. Methods — Twelve patients with signs and/or symptoms suggestive of posterior circulation disease but without flow-limiting obstructive changes and 11 normal controls were entered into the study. With the use of transcranial Doppler techniques, alterations in blood flow velocity in response to sequential breath-holding trials of varying duration were simultaneously monitored in both MCAs and the BA. CVR was measured as the percent velocity increase (during breath-holding) from resting baseline values. Results — No significant differences were found in CVR between the MCA and BA territories in or between patients and controls. Conclusions — Our study suggests that the anterior and posterior circulations have similar reserve capacities in individuals without flow-limiting cerebrovascular obstructive lesions and that the BA territory, relative to the MCA territory, is not at increased risk for low-flow stroke on the basis of limited reserve potential.

Ultrasound is widely used for assessment of neurovascular disease, mainly during the subacute or chronic phases of cerebral ischaemia. The availability of aggressive and potentially harmful treatments for acute ischaemic stroke demands fast, and noninvasive examination of the intracranial vasculature. Current ultrasound techniques have the potential to provide essential information about the intracranial arteries in acute stroke. Application of echo-enhancing agents promises to effectively extend current techniques. The clinical significance of sonography in acute stroke needs to be evaluated prospectively and compared with other radiological techniques.

We prospectively evaluated 30 consecutive patients with echo-enhanced transcranial color-coded duplexsonography (TCCD) and correlative transfemoral digital subtraction angiography to assess the diagnostic efficacy of echo-enhanced TCCD for evaluation of collateral pathways through the circle of Willis in patients with limited acoustic bone windows and critical symptomatic carotid disease. Echo-enhanced TCCD detected collateral blood flow through the anterior communicating artery in 16 of 18 patients (sensitivity 89%, 95% CI 65–99%) and was false positive in one out of 12 patients without collateral flow (specificity 92%, 95% CI 59–100%). For the posterior communicating artery, sensitivity was 11/14 (79%, 95% CI 49–95%) and specificity was 15/16 (94%, 95% CI 70–100%). Echo-enhanced TCCD enables to study collateral blood flow through the communicating arteries of the circle of Willis with high sensitivity and specificity in patients with obstructions of the internal carotid artery and limited acoustic bone windows. Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Background and purpose To date, pre-treatment with anti-platelet agents does not constitute a contraindication for thrombolysis in acute ischemic stroke. We tested the hypothesis that combined pre-treatment with aspirin and clopidogrel is a risk factor for thrombolysis-related symptomatic intracerebral hemorrhage (sICH). Methods We retrospectively studied patients with acute ischemic stroke receiving standard IV thrombolytic therapy with rt-PA in our institution. Exclusion criteria were thrombolysis initiated later than 3 h from symptom onset or with non-tPA-agents, no follow-up imaging was performed and data on prior medication was missing. We recorded clinical baseline variables including known risk factors for ICH. Our outcome measure was the incidence of ICH defined as parenchymal hematoma type 2 with ≥ 4 points deterioration on the National Institute of Health Stroke Scale score. We performed univariate analysis to determine risk factors for sICH. Results We identified 102 patients receiving any thrombolysis of which 63 fulfilled the inclusion criteria. Mean age was 69 years, onset-to-treatment-time 138 min, 56% male, median NIHSS score was 10, and 3 patients received additional intra-arterial interventions. A total of 3 patients had received combined aspirin and clopidogrel treatment before thrombolysis. SICH occurred in 3/63 (4.7%) of patients. Out of these, 2 patients had received the combined anti-platelet treatment. In univariate analysis, only combined pre-treatment with aspirin and clopidogrel treatment were associated with the occurrence of sICH. Conclusion In our retrospective study, only pre-treatment with aspirin and clopidogrel was associated with thrombolysis-related intracerebral hemorrhage. This finding should be further validated in large prospective databases like the SITS-MOST registry.

Introduction Early hemicraniectomy reduces mortality in malignant middle cerebral artery (MCA) infarctions to 16%, although the benefit on functional outcome is still unclear. We treat patients with malignant MCA infarction younger than 60 years. Epidural or subgaleal hemorrhages are relatively common complications. Only 1 trial described parenchymal hemorrhage as a complication of hemicraniectomy. Case report A 55-year-old man was admitted to our stroke unit with right-sided hemiparesis and aphasia. NIHSS was 18; GCS, 3. The initial CT showed hypoattenuation in the basal ganglia and the insular ribbon on the left side. CT-angiography showed M1 occlusion. Despite thrombolysis with rtPA in the 3-hour time window, no recanalization was achieved. We performed early hemicraniectomy. Additionally, we started mild hypothermia and deep sedation to prevent increasing cerebral edema. Control CT on day 2 showed intracerebral hemorrhage and an obstructive hydrocephalus because of intraventricular blood. To avoid herniation, the patient received an extraventricular drainage (EVD). Thereafter, the intracerebral pressure remained stable. The patient was discharged, with a NIHSS of 18 and GCS of 10. Conclusion The reported patient is the first in the literature that suffered from deep hemorrhage after hemicraniectomy. Hemorrhagic transformation might be a risk factor for clinically relevant hemorrhage after hemicraniectomy.

Departments of a Neurology, b Internal Medicine, and c Institute of Neuroradiology, Technical University Dresden, Dresden , Germany Case Report A 62-year-old woman was admitted to our hospital with acute onset of left-sided hemiparesis. On admission, she had left-sided hemiplegia and facial palsy with minor dysarthria – National Institutes of Health Stroke Scale (NIHSS) 11. Cerebral computed tomography (CCT) and CT angiography demonstrated right MCA mainstem occlusion but no early ischemic changes. We initiated thrombolysis with rt-PA (0.9 mg/kg) 165 min after symptom onset. With this therapy, the patient improved to NIHSS 5. However, 1 h after termination of thrombolysis, she developed a sudden decline of consciousness. Since a repeat CCT ruled out intracranial hemorrhage (ICH), we suspected non-convulsive status epilepticus and gave intravenous lorazepam (6 mg) and valproic acid (bolus administration 900 mg, followed by 6-hour infusion 100 mg h –1 ). Electroencephalographic (EEG) monitoring was technically not feasible. The patient remained stuporous requiring intubation and mechanical ventilation the next morning. MRI demonstrated a new occlusion of the left MCA and the left internal carotid artery (ICA), as confi rmed by duplex ultrasound. The right MCA appeared recanalized ( fi g. 1 ). In the presence of only small DWI lesions, PI showed a perfusion defi cit of the complete left MCA territory resulting in a large PI/DWI mismatch. Therefore, we initiated treatment with intravenous abciximab (bolus administration 0.25 mg/kg, followed by 12-hour infusion therapy 0.125 g kg –1 min –1 ) 17.5 h after onset of new symptoms. Duplex sonography performed after the abciximab infusion demonstrated persistent occlusion of the left ICA but recanalization of the left MCA. The patient initially remained comatous. Repeated CCTs on days 1, 3 and 5 after thrombolysis ruled out ICH or major ischemia. EEG ruled out seizure activity, and there was no evidence for metabolic coma. She subsequently regained consciousness and was extubated after 11 days. Further workup revealed a stalked thrombus in the left atrial ear (transesophageal echocardiography) and intermittent atrial fi Introduction Intravenous thrombolysis with alteplase (rt-PA) is the treatment of choice for ischemic stroke within 3 h of symptom onset [1] . Metaanalysis of the major thrombolytic stroke trials suggest a small, but still signifi cant, benefi t if given within 3–6 h [2–4] . Based on the results of a recent trial, the glycoprotein IIb/IIIa receptor antagonist abciximab may be a treatment option for this time window [5] . Potentially viable penumbral tissue may be present well beyond 6 h, in isolated cases even up to 48 h [6] . Modern imaging techniques like magnetic resonance imaging (MRI) using diffusionweighted (DWI) and perfusion imaging (PI) may identify the penumbra and permit improved patient selection [7, 8] . Nevertheless, the best treatment for these patients has not yet been defi ned. This particularly applies to patients with recurrent or new symptoms after an initially successful thrombolysis where an early second thrombolytic therapy is debatable. We report on a patient with acute left middle cerebral artery (MCA) occlusion occurring after thrombolysis with rt-PA for right MCA occlusion, whom we successfully treated with intravenous abciximab 17.5 h after onset of new symptoms.

BackgroundTelemedicine may facilitate the selection of stroke patients who require emergency transfer to a comprehensive stroke center to receive additional therapies other than intravenous tissue plasminogen activator.Aims and/or hypothesisWe sought to analyze frequency, patient characteristics, and specific therapies among emergently transferred patients within the telemedical Stroke East Saxony Network.MethodsWe reviewed consecutive patients who were transferred emergently from remote spoke sites to hub sites. Certified stroke neurologists performed teleconsultations 24/7, with access to high-speed videoconferencing and transfer of brain images. Emergent transfers were initiated when considered necessary by the stroke neurologist.ResultsIn 2009 and 2010, we conducted 1413 teleconsultations and subsequently recommended transfer in 339 (24%) patients [mean age 64 ± 14 years, 54% males, median National Institutes of Health Stroke Scale score 5 (interquartile range, IQR 12). The mean teleconsultation-to-arrival time was 1·7 ± 0·8 h (median 1·6 h). Sixty-eight (20%) transferred patients had a nonstroke diagnosis. The remaining 271 (80%) patients had stroke diagnoses [ischemic stroke, 114 (34%); transient ischemic attack, 8 (2%); and intracranial haemorrhage, 149 (44%)]. Forty (35%) ischemic stroke patients received tissue plasminogen activator at spoke sites (‘drip and ship’). Of the 240 stroke patients emergently transferred to the main hub site, 119 (49·6%) received at least one specific stroke therapy.ConclusionA remarkable number of stroke patients can be transferred within a telemedical network to enable the delivery of specific stroke therapies that require advanced multispecialty expertise. Whether associated logistic efforts and costs have an impact on patients' clinical outcomes needs to be evaluated.

Objective: To determine the reliability and therapeutic impact of standardized cerebral CT evaluation and quantification of early ischemic changes (EIC) with the Alberta Stroke Program Early CT Score (ASPECTS) by stroke neurologists in the Stroke Eastern Saxony Network (SOS-NET), which provides telemedical consultations for patients with acute ischemic stroke. Methods: Two neuroradiologists re-evaluated all CT scans of consecutive SOS-NET patients in 2009 blinded to clinical information providing reference standard. We defined discrepant CT findings as all false-positive or false-negative EIC and brain pathology findings and ASPECTS deviations >1 point. We subsequently discussed the clinical impact of discrepant CT findings unblinded to clinical information. Weighted kappa (κ w ) statistic was used to determine the interobserver agreement for ASPECTS. Results: Of 582 patients, complete imaging data were available for 536 patients (351 cerebral ischemic events, 105 primary intracranial hemorrhages, and 80 stroke mimics). The neuroradiologists detected discrepant CT findings in 43 patients (8.0%) that were rated as clinically relevant in 9 patients (1.7%). Stroke neurologists recommended IV thrombolysis in 8 patients despite extensive EIC (ASPECTS ≤5). One of these patients had symptomatic intracranial hemorrhage. In 1 nonthrombolyzed patient, the stroke neurologist missed subdural hematoma. The interobserver agreement on ASPECTS between stroke neurologists and expert readers was substantial (κ w = 0.62; 95% confidence interval 0.54–0.71). Conclusions: Clinically relevant misinterpretation of the CT scans was rare in our acute telestroke service. ASPECTS is a reliable tool to assess the extent of EIC by stroke neurologists in telemedicine in real time.

Background: Carotid endarterectomy (CEA) is the first-line treatment in severe carotid stenosis to prevent stroke. Because of methodological limitations, the acute impact of CEA on baroreflex function and cerebral autoregulation is not well defined and was therefore investigated by applying a novel algorithm. Methods and Results: Systemic arterial blood pressure, ECG and respiration during metronomic breathing and Valsalva maneuver were continuously recorded in 18 patients with carotid stenosis before and after CEA, and in 10 healthy controls. Baroreflex sensitivity, frequency spectra of RR intervals and indices for cerebral autoregulation were evaluated by trigonometric regressive spectral analysis. Compared with the controls, patients had impaired baroreflex sensitivity. Baroreflex sensitivity and frequency spectra were not changed by CEA. Cerebral autoregulation of patients with carotid stenosis as calculated by phase shift was reduced compared with controls but it improved significantly after CEA. Improvement of cerebral autoregulation was independent of changes in cerebral blood flow velocity. Conclusions: Baroreflex sensitivity and cerebral autoregulation are impaired in patients with carotid stenosis, conferring a high stroke risk. CEA improves cerebral autoregulation, but does not affect baroreflex sensitivity. For further risk reduction, interventional approaches targeting baroreflex function need to be considered. (Circ J 2010; 74: 2139-2145)