Iris Q. Grunwald

Diagnosis and treatment of patients with stroke in a mobile stroke unit versus in hospital: a randomised controlled trial.

BACKGROUND Only 2-5% of patients who have a stroke receive thrombolytic treatment, mainly because of delay in reaching the hospital. We aimed to assess the efficacy of a new approach of diagnosis and treatment starting at the emergency site, rather than after hospital arrival, in reducing delay in stroke therapy. METHODS We did a randomised single-centre controlled trial to compare the time from alarm (emergency call) to therapy decision between mobile stroke unit (MSU) and hospital intervention. For inclusion in our study patients needed to be aged 18-80 years and have one or more stroke symptoms that started within the previous 2·5 h. In accordance with our week-wise randomisation plan, patients received either prehospital stroke treatment in a specialised ambulance (equipped with a CT scanner, point-of-care laboratory, and telemedicine connection) or optimised conventional hospital-based stroke treatment (control group) with a 7 day follow-up. Allocation was not masked from patients and investigators. Our primary endpoint was time from alarm to therapy decision, which was analysed with the Mann-Whitney U test. Our secondary endpoints included times from alarm to end of CT and to end of laboratory analysis, number of patients receiving intravenous thrombolysis, time from alarm to intravenous thrombolysis, and neurological outcome. We also assessed safety endpoints. This study is registered with ClinicalTrials.gov, number NCT00153036. FINDINGS We stopped the trial after our planned interim analysis at 100 of 200 planned patients (53 in the prehospital stroke treatment group, 47 in the control group), because we had met our prespecified criteria for study termination. Prehospital stroke treatment reduced the median time from alarm to therapy decision substantially: 35 min (IQR 31-39) versus 76 min (63-94), p<0·0001; median difference 41 min (95% CI 36-48 min). We also detected similar gains regarding times from alarm to end of CT, and alarm to end of laboratory analysis, and to intravenous thrombolysis for eligible ischaemic stroke patients, although there was no substantial difference in number of patients who received intravenous thrombolysis or in neurological outcome. Safety endpoints seemed similar across the groups. INTERPRETATION For patients with suspected stroke, treatment by the MSU substantially reduced median time from alarm to therapy decision. The MSU strategy offers a potential solution to the medical problem of the arrival of most stroke patients at the hospital too late for treatment. FUNDING Ministry of Health of the Saarland, Germany, the Werner-Jackstädt Foundation, the Else-Kröner-Fresenius Foundation, and the Rettungsstiftung Saar.

The POST trial: initial post-market experience of the Penumbra system: revascularization of large vessel occlusion in acute ischemic stroke in the United States and Europe

Background and purpose The purpose of this study was to assess the initial post-market experience of the device and how it is compared with the Penumbra Pivotal trial used to support the 510k application. Methods A retrospective case review of 157 consecutive patients treated with the Penumbra system at seven international centers was performed. Primary endpoints were revascularization of the target vessel (TIMI score of 2 or 3), good functional outcome as defined by a modified Rankin scale (mRS) score of ≤2 and incidence of procedural serious adverse events. Results were compared with those of the Penumbra pivotal trial. Results A total of 157 vessels were treated. Mean baseline values at enrollment were: age 65 years, NIHSS score 16. After use of the Penumbra system, 87% of the treated vessels were revascularized to TIMI 2 (54%) or 3 (33%) as compared with 82% reported in the Pivotal trial. Nine procedural serious adverse events were reported in 157 patients (5.7%). All-cause mortality was 20% (32/157), and 41% had a mRS of ≤2 at 90-day follow-up as compared with only 25% in the Pivotal trial. Patients who were successfully revascularized by the Penumbra system had significantly better outcomes than those who were not. Conclusion Initial post-market experience of the Penumbra system revealed that the revascularization rate and safety profile of the device are comparable to those reported in the Pivotal trial. However, the proportion of patients who had good functional outcome was higher than expected.

Neurological complications of acute ischaemic stroke

Complications after ischaemic stroke, including both neurological and medical complications, are a major cause of morbidity and mortality. Neurological complications, such as brain oedema or haemorrhagic transformation, occur earlier than do medical complications and can affect outcomes with potential serious short-term and long-term consequences. Some of these complications could be prevented or, when this is not possible, early detection and proper management could be effective in reducing the adverse effects. However, there is little evidence-based data to guide the management of these neurological complications. There is a clear need for improved surveillance and specific interventions for the prevention, early diagnosis, and proper management of neurological complications during the acute phase of stroke to reduce stroke morbidity and mortality.

Carotid Artery Stenting in Acute Stroke

OBJECTIVES The purpose of this study is to demonstrate the technical success of carotid artery stenting in acute extracranial internal carotid artery (ICA) occlusion as well as the benefit in clinical outcome. BACKGROUND Stroke caused by acute occlusion of the ICA is associated with a significant level of morbidity and mortality. For this type of lesion, treatment with standard intravenous thrombolysis alone leads to a good clinical outcome in only 17% of the cases, with a death rate as high as 55%. Recanalization of the occluded ICA can lead to an improvement in acute symptoms of stroke, prevent possible deterioration, and reduce long-term stroke risk. At present, there is no consensus treatment for patients with acute ischemic stroke presenting with severe clinical symptoms due to atherosclerotic occlusion of the extracranial ICA. METHODS Carotid artery stenting was performed in 22 patients with acute atherosclerotic extracranial ICA occlusion within 6 h of stroke symptom onset. In 18 patients, there was an additional intracranial occlusion at the level of the terminal segment of the ICA (n = 4) and at the level of the middle cerebral artery (n = 14). Intracranial occlusions were either treated with the Penumbra system or the Solitaire stent-based recanalization system, or a combination of mechanical recanalization and intra-arterial thrombolysis. Recanalization results were assessed by angiography immediately after the procedure. The neurologic status was evaluated before and after the treatment with a follow-up as long as 90 days using the National Institutes of Health Stroke Scale and the modified Rankin Scale. RESULTS Successful revascularization of extracranial ICA with acute stent implantation was achieved in 21 patients (95%). There was no acute stent thrombosis. After successful recanalization of the origin of the ICA, the intracranial recanalization with Thrombolysis In Myocardial Infarction flow grade 2/3 was achieved in 11 of the 18 patients (61%). The overall recanalization rate (extracranial and intracranial) was 14 of 22 patients (63%). Nine patients (41%) had a modified Rankin Scale score of ≤2 at 90 days. The mortality rate was 13.6% at 90 days. CONCLUSIONS Carotid artery stenting in acute atherosclerotic extracranial ICA occlusion with severe stroke symptoms is feasible, safe, and useful within the first 6 h after symptom onset.

Carotid artery stenting versus surgery: adequate comparisons?

A moratorium on carotid artery stenting (CAS) has been recently proposed. Current randomised evidence supports the notion that carotid endarterectomy (CEA) is better than CAS. A meta-analysis of the randomised trials compared the two strategies and included data from the recent International Carotid Stenting Study (ICSS). This meta-analysis indicated that patients who received CAS had a signifi cant increased risk of 30-day death or stroke compared with patients who received CEA (odds ratio 1·60; 95% CI 1·26–2·02). As randomised clinical trials are the gold standard of clinical investigation, it seems unwise to challenge them. However, for the comparison of CAS versus CEA, most of the randomised trials should be considered not only scientifi cally but also ethically questionable because the endovascular experience required for interventionalists to be eligible for the studies was minimal (table). As a consequence, patients allocated to CAS might have been exposed to unnecessary risk and the assessment of safety and effi cacy of the endovascular approach confounded. In the French Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) study, a lifetime experience of at least 12 CAS interventions was required. Alternatively, a minimum of fi ve CAS procedures was deemed to be suffi cient if the interventionalist had a lifetime experience of at least 30 stenting procedures in supraaortic vessels. The rationale for this adjustment is diffi cult to understand given that subclavian and carotid interventions diff er substantially. For investigators who did not comply with these minimum requirements, the EVA-3S protocol allowed the procedure “under the supervision of an experienced tutor”, defi ned in the protocol as “a clinician who qualifi ed to perform stenting in this study”. In later correspondence, the investigators acknowledged that only 16% of the 265 patients treated with stenting were managed by operators who had done more than 50 CAS procedures in their lifetime and that 39% of patients were treated by physicians in training. Although such a track record can hardly be defi ned as good clinical practice or trial conduct, the information was not thought to be suffi ciently relevant to be reported in any of the EVA-3S publications. Concerns about CAS safety in the EVA-3S trial were raised after the enrolment of 80 patients in the endovascular arm. The safety committee recommended stopping the performance of CAS without the use of embolic protection devices, because the 30-day rate of stroke among patients undergoing un protected CAS was 26·7%, which was 3·9 times higher than that of patients treated with embolic protection (8·6%). However, in the clinical alert published by the EVA-3S investigators, the experience of the interventionalists was not questioned because “a learning eff ect is also unlikely to explain the diff erent complications rates, since protected CAS is a more complex technique than unprotected CAS”. This quote reveals a fundamental gap in understanding of the CAS procedure. In real-life practice, the use of embolic protection devices is widely embraced by experienced CAS interventionalists, whereas those with less expertise might be reluctant to use these devices. Additional evidence of the little endovascular experience among the investigators of EVA-3S is derived from the high rate of emergent conversion from CAS to CEA (5%). The fact that CAS was never reimbursed in France did not help the investigators to gain exposure to the procedure. According to the Stent-Protected Angioplasty versus Carotid Endarterectomy (SPACE) study, a minimum of 25 successful consecutive CAS procedures was needed to participate as an investigator. However, a subsequent report revealed that, during the course of the trial, the protocol was amended to allow for tutoring of physicians who had only undertaken ten CAS procedures. Finally, in ICSS, a minimum of 50 total stenting procedures was required as long as at least ten of these involved the carotid artery. Tutor-assisted procedures were allowed for investigators with insuffi cient experience, again raising the concern of adequacy of training. The inexperience of the EVA-3S, SPACE, and ICSS investigators might have exposed the endovascular patients to an increased risk, not only because of insuffi cient operator skills, but also (and equally important) owing to inappropriate selection of patients. Interventions in patients with complex anatomy at the level of the aortic arch and supra-aortic vessels require more catheter manipulation than in patients with less tortuous or diseased vessels and place patients at increased risk of periprocedural stroke.

Revascularization in acute ischaemic stroke using the penumbra system: the first single center experience

Background and purpose:  This is the first single center experience illustrating the effectiveness of the penumbra system (PS) in the treatment of large vessel occlusive disease in the arena of acute ischaemic stroke. The PS is an innovative mechanical thrombectomy device, employed in the revascularization of large cerebral vessel occlusions in patients via the utilization of an aspiration platform.

Point‐of‐care laboratory halves door‐to‐therapy‐decision time in acute stroke

Currently, stroke laboratory examinations are usually performed in the centralized hospital laboratory, but often planned thrombolysis is given before all results are available, to minimize delay. In this study, we examined the feasibility of gaining valuable time by transferring the complete stroke laboratory workup required by stroke guidelines to a point‐of‐care laboratory system, that is, placed at a stroke treatment room contiguous to the computed tomography, where the patients are admitted and where they obtain neurological, laboratory, and imaging examinations and treatment by the same dedicated team. Our results showed that reconfiguration of the entire stroke laboratory analysis to a point‐of‐care system was feasible for 200 consecutively admitted patients. This strategy reduced the door‐to‐therapy‐decision times from 84 ± 26 to 40 ± 24 min (p < 0.001). Results of most laboratory tests (except activated partial thromboplastin time and international normalized ratio) revealed close agreement with results from a standard centralized hospital laboratory. These findings may offer a new solution for the integration of laboratory workup into routine hyperacute stroke management. Ann Neurol 2011;

Endovascular treatment of unruptured intracranial aneurysms: occurrence of thromboembolic events.

OBJECTIVE:The purpose of this study was to evaluate the frequency and causes of thromboembolic events associated with endovascular embolization of asymptomatic aneurysms. Correlations between radiological findings (aneurysm size, localization, embolization time, number of coils used, as well as patient age) were evaluated with the occurrence of thromboembolic events and clinical findings. METHODS:Sixty-eight patients treated for unruptured intracranial aneurysms (mean age, 49 yr) were evaluated. Hyperintense lesions on diffusion weighted imaging were analyzed in 50 patients. Aneurysm size was 3 to 15 mm. RESULTS:Complete occlusion of the aneurysms was achieved in 55 of 68 (82%). One patient had a transient paresis. There was one infarction and one aneurysm rupture during the procedure with no consecutive neurological symptoms. We found new hyperintense lesions in 21 of 50 (42%) diffusion weighted imaging studies. In 43% of these, there was only one lesion smaller than 2 mm. In 33%, there was more than one lesion less than 2 mm; in 19%, we found a lesion of 2 to 10 mm in size. In one case, a lesion greater than 10 mm occurred. There was no correlation between aneurysm location and the occurrence of lesions or among the number of coils used, the size of the aneurysm, patient age, or embolization time. Mortality rate was 0%, morbidity 4.0%. If the 18 aneurysms where no diffusion weighted imaging was obtained are included, morbidity is 2.9%. CONCLUSION:The high rate of thromboembolic events suggests that heparin is not sufficient to prevent ischemic lesions. An antiplatelet therapy, started before or during intervention, might diminish thrombus formation.

Assessment of angiographic outcomes after flow diversion treatment of intracranial aneurysms: a new grading schema

IntroductionFlow diverter (FD) devices have emerged as an alternative treatment for a subgroup of intracranial aneurysms. The principle of endovascular flow diversion is inherently different from endosaccular coil embolisation. To monitor the angiographic outcomes for FDs, a sensitive and reliable new measure is required. Oxford Neurovascular and Neuroradiology Research Unit developed a grading schema while conducting a registry to audit outcomes of patients treated using a particular FD (SILK flow diverter; Balt Extrusion, Montmorency, France). The aim of this study is to assess the applicability and reproducibility of the new schema.MethodsThe proposed grading schema is designed for saccular- or fusiform-shaped aneurysms. For both, it documents the degree of aneurysm occlusion using a five-point scale and the parent artery patency on a three-point scale. Two neuroradiologists used the schema to independently rate 55 angiograms showing comparable treatment and follow-up angiograms of patients treated with a FD. Inter-observer agreement was estimated using the weighted kappa co-efficient.ResultsBoth readers found the schema easy to apply. Overall, there were ten discordant readings for degrees of aneurysm occlusion and two for parent artery patency. Inter-observer agreement was excellent for both the assessment of aneurysm occlusion (k=0.89; C.I.=0.81–0.99) and parent artery patency (k=0.90; C.I.=0.76–1.0).ConclusionThe proposed schema is sufficiently sensitive to register gradual aneurysm occlusion and parent artery patency on interval angiograms. It is reproducible and is applicable to both saccular and fusiform aneurysms. More data on follow-up of FD-treated aneurysms is needed to prove its efficacy in predicting the long-term behaviour of treated aneurysms.

Hyperperfusion syndrome after carotid stent angioplasty.

IntroductionThis study assesses the incidence and causes of hyperperfusion syndrome occurring after carotid artery stenting (CAS).Materials and methodsWe retrospectively reviewed the clinical database of 417 consecutive patients who were treated with CAS in our department to identify patients who developed hyperperfusion syndrome and/or intracranial hemorrhage. Magnetic resonance imaging (MRI) including fluid-attenuated inversion recovery and diffusion-weighted imaging was performed before and after CAS in 269 cases. A Spearman’s rho nonparametric correlation was performed to determine whether there was a correlation between the occurrence/development of hyperperfusion syndrome and the patient’s age, degree of stenosis on the stented and contralateral side, risk factors such as diabetes, smoking, hypertension, adiposity, gender and fluoroscopy time, and mean area of postprocedural lesions as well as preexisting lesions. Significance was established at p < 0.05.ResultsOf the 417 carotid arteries stented and where MRI was also completed, we found hyperperfusion syndrome in 2.4% (ten cases). Patients who had preexisting brain lesions (previous or acute stroke) were at a higher risk of developing hyperperfusion syndrome (p = 0.022; Spearman’s rho test). We could not validate any correlation with the other patient characteristics.ConclusionExtensive microvascular disease may be a predictor of hyperperfusion syndrome after carotid stent placement. We believe that further studies are warranted to predict more accurately which patients are at greater risk of developing this often fatal complication.