Hermann Zeumer

30 day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomised non-inferiority trial.

BACKGROUND Carotid endarterectomy is effective in stroke prevention for patients with severe symptomatic carotid-artery stenosis, and carotid-artery stenting has been widely used as alternative treatment. Since equivalence or superiority has not been convincingly shown for either treatment, we aimed to compare the two. METHODS 1200 patients with symptomatic carotid-artery stenosis were randomly assigned within 180 days of transient ischaemic attack or moderate stroke (modified Rankin scale score of < or =3) carotid-artery stenting (n=605) or carotid endarterectomy (n=595). The primary endpoint of this hospital-based study was ipsilateral ischaemic stroke or death from time of randomisation to 30 days after the procedure. The non-inferiority margin was defined as less than 2.5% on the basis of an expected event rate of 5%. Analyses were on an intention-to-treat basis. This trial is registered at Current Controlled Trials with the international standard randomised controlled trial number ISRCTN57874028. FINDINGS 1183 patients were included in the analysis. The rate of death or ipsilateral ischaemic stroke from randomisation to 30 days after the procedure was 6.84% with carotid-artery stenting and 6.34% with carotid endarterectomy (absolute difference 0.51%, 90% CI -1.89% to 2.91%). The one-sided p value for non-inferiority is 0.09. INTERPRETATION SPACE failed to prove non-inferiority of carotid-artery stenting compared with carotid endarterectomy for the periprocedural complication rate. The results of this trial do not justify the widespread use in the short-term of carotid-artery stenting for treatment of carotid-artery stenoses. Results at 6-24 months are awaited.

Local intra-arterial fibrinolytic therapy in patients with stroke : urokinase versus recombinant tissue plasminogen activator (r-TPA)

SummaryA group of 59 patients with stroke due to acute vertebrobasilar or carotid territory occlusion have been treated by local intra-arterial fibrinolysis (LIF). A high recanalisation rate was accomplished with either urokinase or recombinant tissue plasminogen activator (r-TPA). However, with either substance, even if a high dose was used, recanalisation was a time-consuming process which usually took 120 min. A reasonable explanation for the lack of effectiveness of these plasminogen-activating substances might be a deficit of substrate, e.g. plasminogen, in aged thrombus. LIF was capable of improving clinical outcome in acute vertebrobasilar artery occlusion, reducing mortality to 50% in patients fulfilling inclusion criteria. In the carotid territory multiple occlusions had a poor prognosis while good clinical results could be achieved in occlusions of the proximal middle cerebral artery or single branches.

Short-term outcome after stenting versus endarterectomy for symptomatic carotid stenosis: a preplanned meta-analysis of individual patient data.

BACKGROUND Results from randomised controlled trials have shown a higher short-term risk of stroke associated with carotid stenting than with carotid endarterectomy for the treatment of symptomatic carotid stenosis. However, these trials were underpowered for investigation of whether carotid artery stenting might be a safe alternative to endarterectomy in specific patient subgroups. We therefore did a preplanned meta-analysis of individual patient data from three randomised controlled trials. METHODS Data from all 3433 patients with symptomatic carotid stenosis who were randomly assigned and analysed in the Endarterectomy versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial, the Stent-Protected Angioplasty versus Carotid Endarterectomy (SPACE) trial, and the International Carotid Stenting Study (ICSS) were pooled and analysed with fixed-effect binomial regression models adjusted for source trial. The primary outcome event was any stroke or death. The intention-to-treat (ITT) analysis included all patients and outcome events occurring between randomisation and 120 days thereafter. The per-protocol (PP) analysis was restricted to patients receiving the allocated treatment and events occurring within 30 days after treatment. FINDINGS In the first 120 days after randomisation (ITT analysis), any stroke or death occurred significantly more often in the carotid stenting group (153 [8·9%] of 1725) than in the carotid endarterectomy group (99 [5·8%] of 1708, risk ratio [RR] 1·53, [95% CI 1·20-1·95], p=0·0006; absolute risk difference 3·2 [1·4-4·9]). Of all subgroup variables assessed, only age significantly modified the treatment effect: in patients younger than 70 years (median age), the estimated 120-day risk of stroke or death was 50 (5·8%) of 869 patients in the carotid stenting group and 48 (5·7%) of 843 in the carotid endarterectomy group (RR 1·00 [0·68-1·47]); in patients 70 years or older, the estimated risk with carotid stenting was twice that with carotid endarterectomy (103 [12·0%] of 856 vs 51 [5·9%] of 865, 2·04 [1·48-2·82], interaction p=0·0053, p=0·0014 for trend). In the PP analysis, risk estimates of stroke or death within 30 days of treatment among patients younger than 70 years were 43 (5·1%) of 851 patients in the stenting group and 37 (4·5%) of 821 in the endarterectomy group (1·11 [0·73-1·71]); in patients 70 years or older, the estimates were 87 (10·5%) of 828 patients and 36 (4·4%) of 824, respectively (2·41 [1·65-3·51]; categorical interaction p=0·0078, trend interaction p=0·0013]. INTERPRETATION Stenting for symptomatic carotid stenosis should be avoided in older patients (age ≥70 years), but might be as safe as endarterectomy in younger patients. FUNDING The Stroke Association.

Outcome and Symptomatic Bleeding Complications of Intravenous Thrombolysis Within 6 Hours in MRI-Selected Stroke Patients: Comparison of a German Multicenter Study With the Pooled Data of ATLANTIS, ECASS, and NINDS tPA Trials

Background and Purpose— We compared outcome and symptomatic bleeding complications of intravenous tissue plasminogen activator (IV-tPA) within 6 hours of symptom onset in MRI-selected patients with acute middle cerebral artery infarction with the pooled data of the large stroke tPA trials. Methods— Patients were examined by perfusion-weighted and diffusion-weighted imaging ≤6 hours. Within 3 hours, patients were treated according to Second European-Australasian Acute Stroke Study (ECASS II) criteria. After 3 to 6 hours, treatment with IV-tPA was performed based on MRI findings. Favorable outcome was assessed after 90 days using a dichotomized modified Rankin scale score of 0 to 1. Intracerebral bleeding complications were assessed on follow-up MRI or computed tomography. Data were compared with the pooled placebo and pooled tPA patients of the ATLANTIS, ECASS, and National Institute of Neurological Disorders and Stroke (NINDS) tPA trials. Results— From 174 MRI-selected tPA patients, 62% (n=108) were treated in ≤3 hours and 38% (n=66) after 3 to 6 hours. Favorable outcome was more frequent in MRI-selected tPA patients (48% [95% CI, 39 to 54]) compared with pooled placebo (33% [95% CI, 31 to 36]; P<0.001) and pooled tPA patients (40% [95% CI, 37 to 42]; P=0.046). Odds ratios for favorable outcome in the MRI-selected tPA group were 1.82 (1.32 to 2.51) compared with the pooled placebo and 1.39 (1.01 to 1.92) compared with the pooled tPA group. The rate of symptomatic intracerebral hemorrhage in MRI-selected tPA patients (3% [95% CI, 0 to 5]) was lower than in the pooled tPA group (8% [95% CI, 7 to 10]; P=0.012) and comparable to the pooled placebo group (2% [95% CI, 1 to 3]; P=0.392). Conclusions— This study supports that it is safe and effective to expand the time window for IV-tPA up to 6 hours in patients with tissue at risk as defined by MRI.

Predictors of Apparent Diffusion Coefficient Normalization in Stroke Patients

Background and Purpose— We sought to describe the frequency of normalization of apparent diffusion coefficient (ADC) values that are decreased in hyperacute stroke and to identify characteristics of tissue demonstrating normalization. Methods— Sixty-eight acute ischemic stroke patients underwent MRI examination (including diffusion/perfusion imaging and MR angiography) within 6 hours (mean, 2.8 hours) after symptom onset, after 24 hours, and again 4 to 7 days later. Lesion volumes with decreased ADC and delayed time to peak in perfusion imaging were determined. In patients showing ADC normalization, volumes with ADC decrease graded as <50%, 50% to 60%, 60% to 70%, and 70% to 80% of the contralateral value were determined by thresholding. Patients were categorized as normalizers (demonstrating ADC normalization in >5 mL tissue with initially decreased ADC) or nonnormalizers (demonstrating ADC normalization in <5 mL tissue). Results— Fourteen patients (19.7%) were classified as normalizers. Eleven of 31 patients (35.5%) initially imaged <3 hours after stroke onset and 3 of 37 (7.5%) of those imaged 3 to 6 hours after onset were normalizers. ADC normalization occurred predominantly in the basal ganglia and white matter after thrombolytic therapy in patients with more distal vessel occlusions. All normalizers demonstrated at least partial tissue reperfusion. Tissue with more severe initial decrease in ADC was less likely to demonstrate normalization. Conclusions— ADC normalization is not a rare event in acute stroke after tissue reperfusion. Brain tissue with initially decreased ADC, especially within 3 hours after stroke onset, may include “tissue at risk.”

Selective cerebral intraarterial DSA

SummaryIn 1095 patients 2770 brain supplying arteries have been studied by i.a.-DSA. Definitive neurological deficits occurred in 0.09%, transient deficits were observed in 0.45%. The reduced complication rate in comparison to former studies seems to be a continued effect of technical progress (DSA) and the use of new isoosmotic contrast media. In order to reduce the “training hospital effect” as to complication rate careful supervision of trainees is necessary. The average fluoroscopy time per vessel is proposed as an objective measure of the investigational skill of a neuroradiologist.

Long-term follow-up of cerebral aneurysms after endovascular therapy prediction and outcome of retreatment.

BACKGROUND AND PURPOSE: The purpose of this study was to analyze angiographic and clinical results before and after additional endovascular therapy in patients with previously coiled but reopened cerebral aneurysms and to identify possible risk factors for retreatment of an aneurysm. MATERIALS AND METHODS: Follow-up with selective digital subtraction angiography was performed in 323/596 (54.2%) patients harboring 342 aneurysms with a mean follow-up time of 28.6 months. The patients were divided into 3 groups: group A, who remained stable after initial treatment; group B, who showed minor morphologic changes; and group C, who underwent repeat treatment. Univariate and multivariate regression analyses were performed to determine possible risk factors for aneurysmal retreatment. RESULTS: Single or multiple retreatment was performed in 33 of 323 (10.2%) patients. Retreatment of small aneurysms (≤10 mm) with small necks (≤4 mm) was performed in 6 of 214 aneurysms. When summarizing all other aneurysms as a “risk group” (n = 128), the odds ratio (OR) for retreatment in the “risk group” was 3.11 (95% CI: 1.43–6.75; P = .004). In patients with residual aneurysm after the first treatment, OR for retreatment was 3.96 (95% CI: 1.48–10.65; P = .006), whereas a neck remnant, clinical presentation, and aneurysmal localization were not predictive. We observed no resulting morbidity and mortality from the 33 retreatment procedures. CONCLUSION: In our series, the retreatment of aneurysmal recurrences was a safe procedure. The best single predictors of aneurysmal recurrence were aneurysmal anatomy (neck width >4 mm and diameter >10 mm) and the presence of a residual aneurysm after initial treatment. A limitation in our study was the significant number of patients lost to follow-up (22.7%).

Local intraarterial fibrinolysis in acute vertebrobasilar occlusion

SummaryLocal intraarterial fibrinolytic therapy (LIF) in patients with acute vertebrobasilar occlusion (AVBO) is a rational and if successful a life saving treatment. The recent progress in this field is determined by the use of microcatheters for superselective basilar artery catheterisation and a “short time, highdose” regimen using 750.000 IU Urokinase in not more than two h. Two out of 7 patients died and 1 did not improve to a better than a locked-in-state. Four patients however survived with excellent outcome.

Blood Oxygen Level–Dependent MRI Allows Metabolic Description of Tissue at Risk in Acute Stroke Patients

Background and Purpose— The delineation of the “penumbra” is of particular interest in acute stroke imaging. The “mismatch concept” applying perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) appears to be an oversimplification of the underlying electrophysiological tissue status. An additional parameter reflecting the metabolic state of the threatened brain tissue would improve our ability to describe the penumbra. One candidate is deoxyhemoglobin (deoxy-Hb) as an indicator of the oxygen extraction fraction that can be visualized by T2*-based blood oxygen level–dependent (BOLD) imaging. Methods— We analyzed data from 32 patients with acute stroke in the territory of the middle cerebral artery. MRI included fluid-attenuated inversion recovery, DWI, PWI, time-of-flight angiography, and quantitative T2 and T2* (qT2, qT2*) imaging. Follow-up was performed on day 1 and days 5 to 8. We calculated 1/T2′=1/qT2*−1/qT2. Changes of T2′, representing the deoxy-Hb effect, were analyzed by 3D regions of interest (ROIs): apparent diffusion coefficient lesion day 0 (L0), time-to-peak–lesion day 0 (T0), final infarct size days 5 to 8 (F5–8), lesion growth (LG; F5–8−L0), and surviving tissue (ST; T0−F5–8). Results— We observed a clear decrease of T2′ in the infarcted hemisphere compared with the unaffected control ROIs. The mean value showed the most pronounced loss of T2′ signal intensity in L0 (−15.7%), followed by LG (−10.5%) and ST (−8.0%). Conclusions— The implementation of BOLD imaging in acute stroke MRI offers a noninvasive estimation of the O2 utilization and is able to add additional information concerning the present metabolic state of the threatened brain tissue. The changes in T2′ intensity are visually noticeable in the reconstructed T2′ images and provide a better estimation of the real penumbra.

The Stent-Supported Percutaneous Angioplasty of the Carotid Artery vs. Endarterectomy Trial

The Stent-Supported Percutaneous Angioplasty of the Carotid Artery versus Endarterectomy (SPACE) Trial is investigating if both treatment modalities are equivalent in the treatment of severe symptomatic carotid stenoses. Patients with symptomatic (transient ischaemic attack or minor stroke) stenosis (above 50% following the North American Symptomatic Endarterectomy Trial criteria) eligible for both methods can be recruited into this trial. The primary endpoint is the incidence of an ipsilateral stroke or death between randomisation and day 30 after treatment. Surgeons as well as the interventionalists have to demonstrate their expertise prior to participation in the trial. Funding is mostly by public institutions (Federal Ministry of Education and Research and German Research Foundation). An external monitoring is applied. Thirty-two centres are currently taking part in the SPACE Trial that has been running in Germany, Austria and Switzerland for 3 years, and they have been able to recruit a total of around 670 patients. The definitive results of this study cannot be expected before 3–5 years.