Philippe Lyrer

Background: Data on endovascular therapy (EVT) in patients with stroke attributable to CeAD is scarce. We performed a systematic review and meta-analysis of all studies comparing EVT to intravenous thrombolysis (IVT) in CeAD-patients and compared EVT to IVT with regard to 3-month outcome and complications. Additionally, we included data of IVT-/EVT-treated CeAD-patients from a Swiss multicenter IVT-/EVT registry based cohort study. Methods: We systematically searched the pubmed® database to identify all existing studies comparing IVT to EVT in CeAD-patients. Studies were eligible if IVT-treated CeAD- patients were compared to EVT-treated patients, and 3-month outcomes were reported as modified Rankin Scale (mRS) score. Outcome measures in this study were favorable 3-month outcome (i.e. mRS 0-2), excellent 3-month outcome (i.e. mRS 0-1), symptomatic intracranial hemorrhage (sICH) and death. Additionally, in a Swiss multicenter IVT-/EVT registry based cohort-study (SWISS) we identified all consecutive patients with ischemic stroke attributable to CeAD and included outcome data of these patients in our analyses. In a meta-analysis across all studies, we compared EVT to IVT with regard to primary and secondary outcome measures using a fixed-effect Mantel-Haenszel model. Results: The literature search yielded 388 results. We identified 7 eligible studies for a systematic comparison of EVT versus IVT. Data on 62 patients from the SWISS cohort were included as an additional study. In total, we compared EVT (n=102) versus IVT (n=110) in 212 CeAD-patients. With regard to the occurrence of mRS 0-2, there was no significant difference between both treatment groups (OR 1.04 (95% CI 0.57-1.88)). Separate Data on mRS 0-1 was available in 5 studies (OR 0.88 (95% CI 0.39-2.00)). There was no difference between groups with regard to death at 3 months (OR 0.66 (0.22-1.94)) which was separately reported in 6 studies. For sICH there were too few data (n=5 patients) available for meta-analysis. Conclusion: In this systematic review and meta-analysis of all existing studies comparing EVT to IVT in CeAD patients there was no clear signal of superiority of EVT. Further investigation of EVT with up-to-date devices is warranted.

Extracranial internal carotid artery dissection (eICAD) is a leading cause of stroke in younger patients. 1. To determine whether, in patients with eICAD, treatment with anticoagulants, antiplatelet agents or control was associated with a better functional outcome. 2. To compare, among patients treated with either anticoagulants or antiplatelet agents, the risk of ischaemic strokes and major bleeding episodes. We searched the Cochrane Stroke Group Trials Register (last searched 3 October 2009). In addition, we performed comprehensive searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2009), MEDLINE (January 1966 to November 2009) and EMBASE (January 1980 to November 2009), checked all relevant papers for additional eligible studies and contacted authors and researchers in the field. Randomised controlled trials, controlled clinical trials and non‐randomised studies (if they reported on outcome stratified by antithrombotic treatment and included at least four patients) of anticoagulants or antiplatelet agents for the treatment of extracranial internal carotid artery dissection. Two review authors independently extracted data. Primary outcomes were death (all causes) and death or disability. Secondary outcomes were ischaemic stroke, symptomatic intracranial haemorrhage, and major extracranial haemorrhage during the reported follow‐up period. The first choice treatment was taken for analyses. We did not find any completed randomised trials. Comparing antiplatelets with anticoagulants across 36 observational studies (1285 patients), there were no significant differences in the odds of death (Peto odds ratio (Peto OR) 2.02, 95% CI 0.62 to 6.60), or the occurrence of ischaemic stroke (OR 0.63, 95% CI 0.21 to 1.86) (34 studies, 1262 patients). For the outcome of death or disability, there was a non‐significant trend in favour of anticoagulants (OR 1.77, 95% CI 0.98 to 3.22; P = 0.06) (26 studies, 463 patients). Symptomatic intracranial haemorrhages (5/627; 0.8%) and major extracranial haemorrhages (7/425; 1.6%) occurred only in the anticoagulation group; however, for both these outcomes, the estimates were imprecise and indicated no significant difference between the two treatment modalities. There were no randomised trials comparing either anticoagulants or antiplatelet drugs with control, thus there is no evidence to support their routine use for the treatment of extracranial internal carotid artery dissection. There were also no randomised trials that directly compared anticoagulants with antiplatelet drugs and the reported non‐randomised studies did not show any evidence of a significant difference between the two. Fármacos antitrombóticos para la disección carotídea La disección de la arteria carótida interna extracraneal (DACIe) es una de las causas principales de accidente cerebrovascular en los pacientes más jóvenes. 1. Determinar si el tratamiento con anticoagulantes, antiagregantes plaquetarios o control se asoció con un mejor resultado funcional en los pacientes con DACIe. 2. Comparar el riesgo de accidentes cerebrovasculares isquémicos y episodios de hemorragia graves entre los pacientes que recibieron anticoagulantes o antiagregantes plaquetarios. Se hicieron búsquedas en el Registro de Ensayos del Grupo Cochrane de Accidentes Cerebrovasculares (Cochrane Stroke Group) (última búsqueda 3 octubre 2009). Además, se realizaron búsquedas exhaustivas en el Registro Cochrane Central de Ensayos Controlados (Cochrane Central Register of Controlled Trials, CENTRAL) (The Cochrane Library número 2, 2009), MEDLINE (enero 1966 hasta noviembre 2009) y en EMBASE (enero 1980 hasta noviembre 2009), se verificaron todos los artículos relevantes para obtener estudios adicionales elegibles y se contactó con autores e investigadores en el área. Ensayos controlados aleatorios, ensayos clínicos controlados y estudios no aleatorios (si informaron resultados estratificados por tratamiento antitrombótico y si incluyeron al menos cuatro pacientes) de anticoagulantes o antiagregantes plaquetarios para el tratamiento de la disección de la arteria carótida interna extracraneal. Dos autores de la revisión extrajeron los datos de forma independiente. Los resultados primarios fueron muerte (por todas las causas), muerte o discapacidad. Los resultados secundarios fueron accidente cerebrovascular isquémico, hemorragia intracraneal sintomática y hemorragia extracraneal grave durante el período de seguimiento informado. Se consideró al tratamiento de primera elección para los análisis. No se encontró ningún ensayo aleatorio finalizado. Al comparar los antiagregantes plaquetarios con los anticoagulantes a través de 36 estudios observacionales (1285 pacientes) no hubo diferencias significativas en el odds de muerte (odds ratio de Peto [OR de Peto] 2,02; IC del 95%: 0,62 a 6,60) ni en la presencia de accidente cerebrovascular isquémico (OR 0,63; IC del 95%: 0,21 a 1,86) (34 estudios, 1262 pacientes). Para la medida de resultado de muerte o discapacidad no hubo una tendencia significativa a favor de los anticoagulantes (OR 1,77; IC del 95%: 0,98 a 3,22; P = 0,06) (26 estudios, 463 pacientes). Las hemorragias intracraneales sintomáticas (5/627; 0,8%) y las hemorragias extracraneales graves (7/425; 1,6%) ocurrieron sólo en el grupo con anticoagulación; sin embargo, para ambos resultados las estimaciones fueron imprecisas y no indicaron diferencias significativas entre las dos formas de tratamiento. No se identificaron ensayos aleatorios que compararan anticoagulantes o antiagregantes plaquetarios con control, por lo que no hubo pruebas para apoyar el uso sistemático de estos fármacos para el tratamiento de la disección de la arteria carótida interna extracraneal. Tampoco hubo ensayos aleatorios que compararan directamente los fármacos anticoagulantes con antiplaquetarios y los estudios no aleatorios informados no mostraron una diferencia significativa entre ambos. Traducción realizada por el Centro Cochrane Iberoamericano Médicaments antithrombotiques pour la dissection de l'artère carotide La dissection de l'artère carotide interne extracrânienne (DACIE) est une cause majeure d'AVC chez les patients plus jeunes. 1. Déterminer si, chez les patients souffrant de DACIE, le traitement par anticoagulants, les antiagrégants plaquettaires ou un groupe témoin était associée à un meilleur résultat fonctionnel. 2. Comparer, parmi les patients traités par anticoagulants ou antiagrégants plaquettaires, le risque d'AVC ischémique aigu et de saignements majeurs. Nous avons effectué des recherches dans le groupe Cochrane sur les accidents vasculaires cérébraux (dernière recherche le 3 octobre 2009). En outre, nous avons effectué des recherches exhaustives dans le registre Cochrane des essais contrôlés (CENTRAL) ( La Bibliothèque Cochrane Numéro 2, 2009), MEDLINE (de janvier 1966 à novembre 2009) et EMBASE (de janvier 1980 à novembre 2009), examiné tous les articles pertinents afin d'identifier des études éligibles et contacté les auteurs et des chercheurs dans le domaine. Les essais contrôlés randomisés, essais cliniques comparatifs et études non randomisées (si elles avaient rendu des résultats stratifiés par traitement antithrombotique et incluaient au moins quatre patients) sur les anticoagulants ou antiagrégants plaquettaires pour le traitement de la dissection de l'artère carotide interne extracrânienne. Deux auteurs de la revue ont extrait les données de manière indépendante. Les critères de jugement primaire étaient la mortalité (toutes causes confondues) et le décès ou lincapacité. Les critères de jugement secondaires étaient un AVC ischémique aigu, une hémorragie intracrânienne symptomatique, et l'hémorragie extracrânienne majeure rapportés pendant la période de suivi. La première option de traitement était utilisée pour les analyses. Nous n'avons trouvé aucun essai randomisé terminé. En comparant lutilisation des antiagrégants plaquettaires avec celle des anticoagulants dans 36 études observationnelles (1 285 patients), il n'y avait aucune différence significative au niveau des risques de décès (rapport des cotes de Peto (RC de Peto) 2,02, IC à 95 % 0,62 à 6,60), ou de la survenue d'un accident vasculaire cérébral (AVC) ischémique aigu (rapport des cotes de 0,63, IC à 95 % 0,21 à 1,86) (34 études, 1262 patients). Pour le critère de jugement de mortalité ou dincapacité, il y avait une tendance non significative en faveur des anticoagulants (RC 1,77, IC à 95 % 0,98 à 3,22 ; P =0,06) (26 études, 463 patients). Des hémorragies intracrâniennes symptomatiques (5/627 ; 0,8 %) et des hémorragies extracrâniennes majeures (7/425 ; 1,6%) sont survenues uniquement dans le groupe des anticoagulants ; cependant, pour ces deux critères de jugement, les estimations étaient imprécises et n'indiquaient aucune différence significative entre les deux modalités de traitement. Il n'y avait aucun essai randomisé comparant les anticoagulants ou antiagrégants plaquettaires avec un groupe témoin, par conséquent, il n'existe aucune preuve permettant de recommander leur utilisation systématique pour le traitement de la dissection de l'artère carotide interne extracrânienne. Il n'y avait également aucun essai randomisé qui comparait directement les anticoagulants avec des médicaments antiplaquettaires et les études non randomisées identifiées n'ont pas mis en évidence une différence significative entre les deux.

The EC/IC Bypass Study Group found no benefit of extracranial to intracranial (EC/IC) bypass surgery over medical therapy in patients with symptomatic carotid artery occlusion (sCAO). However, the study was criticised for many reasons and the real effect of this treatment is still not known conclusively. To determine whether bypass surgery plus medical care is superior to medical care alone in patients with sCAO. We searched the Cochrane Stroke Group Trials Register (last searched June 2009). In addition, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2006), MEDLINE (1966 to June 2009) and EMBASE (1980 to June 2009). We also searched ongoing trials and research registers, checked reference lists of relevant articles, and contacted colleagues, trial authors and researchers. Randomised controlled trials (RCT) and non-random studies of EC/IC bypass surgery plus best medical treatment compared with best medical treatment alone to prevent subsequent stroke, improve cerebral haemodynamics and reduce dependency after stroke. Two review authors independently selected studies for inclusion, and extracted data items on the number of outcome events onto a data extraction form. We only analysed secondary outcomes if the study provided information on at least one primary outcome. We also used intention-to-treat analysis where possible. We included 21 trials, including two RCTs, involving 2591 patients. For all endpoints, no benefit of EC/IC bypass surgery was shown either in the RCTs (any death: odds ratio (OR) 0.81, 95% confidence interval (CI) 0.62 to 1.05, P = 0.11; stroke: OR 0.99, 95% CI 0.79 to 1.23, P = 0.91; death and dependency: OR 0.94, 95% CI 0.74 to 1.21, P = 0.64), or in the non-RCTs (any death: OR 1.00, 95% CI 0.62 to 1.62, P = 0.99; stroke: OR 0.80, 95% CI 0.54 to 1.18, P = 0.25; death and dependency: OR 0.80, 95% CI 0.50 to 1.29, P = 0.37). EC/IC bypass surgery in patients with sCAO disease was neither superior nor inferior to medical care alone. However, most studies included patients irrespective of their cerebral haemodynamics. Participation in an ongoing RCT, which is restricted to patients with impaired haemodynamics, is recommended as these patients might benefit from bypass surgery.

Objective: Data about the distribution of stroke severity and its correlates are sparse. In a population-based approach, we determined the NIH Stroke Scale Score (NIHSSS) and studied associations with demographic variables, stroke unit care, etiology, the onset assessment interval (OAI), and the rate of thrombolysis. Methods: We performed a databank-based post-hoc analysis of data ascertained during the prospective, population-based stroke study among the 188,015 permanent residents of Basel City, Switzerland. Results: In 246/269 (91.4%) patients, NIHSSS was available. The median NIHSSS was 5.0 ± 6.0. NIHSSS 0–6, 7–15, and >15 were present in 156 (63%), 56 (23%), and 34 (14%) patients. Higher NIHSSS were associated with advancing age (p = 0.038), female gender (p = 0.04), stroke unit treatment (p = 0.003), cardioembolism (p < 0.001), shorter OAI (p = 0.009), and thrombolytic therapy (p < 0.001). In multivariate regression analyses, age, OAI, and thrombolysis correlated independently with higher NIHSSS. Stroke unit patients differed from non-stroke unit patients in shorter OAI, younger age, and higher NIHSSS. Conclusion: In a geographically defined stroke population, 1/3 patients had moderate-to-severe stroke. Patients with less severe strokes were younger, sought medical attention later and were less likely to receive thrombolysis. Thus, public stroke awareness programs might consider targeting also younger individuals and stress that also mild-to-moderate strokes benefit from emergency medical care.

Diffusion-weighted magnetic resonance imaging (DWI) is an advanced imaging technique that allows non-invasive evaluation of water diffusibility in brain tissue. The following report focuses on the clinical significance of DWI in stroke and TIA patients (1) TIA patients demonstrate DWI lesions at a rate of 1 in 6 to 2 in 3. Symptom duration, speech or motor symptoms and aetiology seem to correlate with the rate of DWI positivity. (2) In stroke patients, the DWI detection rate of ischaemic lesions is >95%. Small lesion size and location in the brainstem increase the risk of false-negative DW-images. A negative DW-image in a patient with stroke-like symptoms should stimulate the search for an alternative diagnosis. However, one half of such patients can be expected to have ischaemic stroke as the best final diagnosis. (3) Infarct age determination based on DWI characteristics is not possible in the first few hours. However, the combined interpretation of DWI-images and apparent diffusion coefficient (ADC) maps enables the distinction of infarcts ?5 day old from infarcts >10 days old. On average in DW-images alone, the hyperintense signal disappears after two months. Normalisation can occur as early as one month and as late as four and a half months. (4) DWI lesion size is a prognostic marker of stroke outcome. However, in a mixed stroke population, outcome prediction by DWI cannot replace clinical outcome scores. (5) The mismatch concept hypothesises that DWI lesions reflect irreversibly infarcted tissue that is surrounded by an area of reduced perfusion. The larger the perfusion-diffusion mismatch the more tissue is potentially salvageable, e.g., by early reperfusion. Although this concept is appealing, more recent data have shown that DWI lesions are not necessarily irreversibly damaged tissue and that perfusion abnormalities tend to overestimate the ischaemic penumbra. More recently, the mismatch between clinical stroke severity as measured with the NIH-stroke Scale Score (NIHSSS) and the volume of DWI lesions has been introduced. (6) In posterior circulation stroke, DWI lesion detection rate is significantly lower than in anterior circulation stroke. (7) DWI features provide important information about stroke aetiology. Multiple DWI lesions in more than one circulation suggest cardioembolism. However, this assignment should be restricted to DWI lesions showing the same appearance on ADC-maps. In patients with lacunar syndromes, every fourth to sixth patient can be expected to have >1 DWI lesion, indicating an embolic mechanism. Thus, DWI findings may be clinically useful to tailor the aetiological work-up, which may result in early implementation of specific treatment for secondary stroke prevention. (8) DWI may detect clinically silent ischaemic lesions after carotid interventions. A systematic review reported the rate of new DWI lesions as being significantly higher in carotid stenting patients (37%) compared to carotid endarterectomy patients (10%). As caveats, all studies included were non randomized trials. In addition, the clinical significance of these lesions is unclear. Studies, comparing the risk of silent ischaemia in carotid stenting versus endarterectomy patients and evaluating the value of DWI as surrogate marker in a randomised, prospective setting are currently under way. DWI provides clinically useful information and has the means to improve the quality of diagnosis, treatment, and outcome prediction in stroke and TIA patients.

Ntiplatelet drugs are effective and safe in a wide variety of patients at high risk for vascular ischemic events. Among patients undergoing vascular surgical procedures, these agents significantly reduce the risk of graft or native vessel occlusion. In this context, we examined their effects in patients after carotid endarterectomy (CEA).