Karsten Alfke

Aggressive Therapy With Intravenous Abciximab and Intra-Arterial rtPA and Additional PTA/Stenting Improves Clinical Outcome in Acute Vertebrobasilar Occlusion Combined Local Fibrinolysis and Intravenous Abciximab in Acute Vertebrobasilar Stroke Treatment (FAST): Results of a Multicenter Study

Background and Purpose— A combined therapy of local recombinant tissue plasminogen activator (rtPA) fibrinolysis and intravenous Abciximab platelet inhibition with additional percutaneous transluminal angioplasty (PTA)/stenting may improve recanalization and neurological outcome in patients with acute vertebrobasilar occlusion. Methods Combined FAST therapy consisted on intravenous bolus of Abciximab (0.25 mg/kg) followed by a 12-hour infusion therapy (0.125 &mgr;g/kg per minute) and low-dose intra-arterial rtPA (median dosage: 20 mg, FAST cohort: N=47). The results were compared with a retrospective cohort, treated by intraarterial rtPA monotherapy (median dosage: 40 mg, rtPA cohort, N=41). Additional PTA/stenting was performed in case of severe residual stenosis. Recanalization success was classified according to the Trials in Myocardial Infarction (TIMI) criteria: TIMI0/1, failed recanalization; TIMI2/3, successful recanalization. Bleeding complications were evaluated according to severe extracerebral hemorrhage (ECH), asymptomatic intracerebral hemorrhage (AIH), and symptomatic intracerebral hemorrhage (SIH). Results— Overall bleeding rate was higher under the combined therapy, but the SIH rate did not differ (FAST versus rtPA: ECH, 3% versus 0%; AIH, 32% versus 22%; SIH 13% versus 12%). Additional PTA/stenting was performed in 14 (FAST) versus 5 (rtPA) patients. TIMI2/3 recanalization rate was similar (FAST, 72%; rtPA, 68%), but TIMI3 rate was remarkably higher under combined therapy (FAST, 45%; rtPA, N=22%). Neurologic outcome appeared better under combined therapy (FAST versus rtPA: favorable outcome rate: 34% versus 17%) with a significantly lower mortality rate (FAST versus rtPA: 38% versus 68%; P=0.006). These results were consistent for embolic and atherothrombotic occlusions. Conclusion Combined therapy of intravenous Abciximab and half dose intra-arterial rtPA with additional PTA/stenting appears to improve neurologic outcome in acute vertebrobasilar occlusion despite an increase of overall bleeding complications.

Clinical and angiographic risk factors for stroke and death within 30 days after carotid endarterectomy and stent- protected angioplasty: a subanalysis of the SPACE study

BACKGROUND Carotid endarterectomy (CEA) and carotid artery stenting (CAS) are used to prevent ischaemic stroke in patients with stenosis of the internal carotid artery. Better knowledge of risk factors could improve assignment of patients to these procedures and reduce overall risk. We aimed to assess the risk of stroke or death associated with CEA and CAS in patients with different risk factors. METHODS We analysed data from 1196 patients randomised to CAS or CEA in the Stent-Protected Angioplasty versus Carotid Endarterectomy in Symptomatic Patients (SPACE) trial. The primary outcome event was death or ipsilateral stroke (ischaemic or haemorrhagic) with symptoms that lasted more than 24 h between randomisation and 30 days after therapy. Six predefined variables were assessed as potential risk factors for this outcome: age, sex, type of qualifying event, side of intervention, degree of stenosis, and presence of high-grade contralateral stenosis or occlusion. The SPACE trial is registered at Current Controlled Trials, with the international standard randomised controlled trial number ISRCTN57874028. FINDINGS Risk of ipsilateral stroke or death increased significantly with age in the CAS group (p=0.001) but not in the CEA group (p=0.534). Classification and regression tree analysis showed that the age that gave the greatest separation between high-risk and low-risk populations who had CAS was 68 years: the rate of primary outcome events was 2.7% (8/293) in patients who were 68 years old or younger and 10.8% (34/314) in older patients. Other variables did not differ between the CEA and CAS groups. INTERPRETATION Of the predefined covariates, only age was significantly associated with the risk of stroke and death. The lower risk after CAS versus CEA in patients up to 68 years of age was not detectable in older patients. This finding should be interpreted with caution because of the drawbacks of post-hoc analyses.

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.

Assessment of thrombus in acute middle cerebral artery occlusion using thin-slice nonenhanced Computed Tomography reconstructions.

Background and Purpose— We sought to evaluate how accurately length and volume of thrombotic clots occluding cerebral arteries of patients with acute ischemic stroke can be assessed from nonenhanced CT (NECT) scans reconstructed with different slice widths. Methods— NECT image data of 58 patients with acute ischemic stroke with vascular occlusion proven by CT angiography were reconstructed with slice widths of 1.25 mm, 2.5 mm, 3.75 mm, and 5 mm. Thrombus lengths and volumes were quantified based on these NECT images by detecting and segmenting intra-arterial hyperdensities. The results were compared with reference values of thrombus length and volume obtained from CT angiography images using Bland-Altman analysis and predefined levels or tolerance to find NECT slice thicknesses that allow for sufficiently accurate thrombus quantification. Results— Thrombus length can be measured with high accuracy using the hyperdense middle cerebral artery sign detected in NECT images with slice thicknesses of 1.25 mm and 2.5 mm. We found mean deviations from the reference values and limits of agreement of −0.1 mm±0.6 mm with slice widths of 1.25 mm and 0.1 mm±0.7 mm for slice widths of 2.5 mm. Thrombus length measurements in NECT images with higher slice width and all evaluated thrombus volume measurements exhibited severe dependence on the level and did not match the accuracy criteria. Conclusion— The length of the hyperdense middle cerebral artery sign as detected on thin-slice NECT reconstructions in patients with acute ischemic stroke can be used to quantify thrombotic burden accurately. Thus, it might qualify as a new diagnostic parameter in acute stroke management that indicates and quantifies the extent of vascular obliteration.

Four patients with speech delay, seizures and variable corpus callosum thickness sharing a 0.440 Mb deletion in region 1q44 containing the HNRPU gene.

Structural genome aberrations are frequently associated with highly variable congenital phenotypes involving mental retardation and developmental delay. Although some of these aberrations may result in recognizable phenotypes, a high degree of phenotypic variability often complicates a comprehensive clinical and genetic diagnosis. We describe four patients with overlapping deletions in chromosomal region 1q44, who show developmental delay, in particular of expressive speech, seizures, hypotonia, CNS anomalies, including variable thickness of the abnormal corpus callosum in three of them. High resolution oligonucleotide and SNP array-based segmental aneuploidy profiling showed that these three patients share a 0.440 Mb interstitial deletion, which does not overlap with previously published consensus regions of 1q44 deletions. Two copies of AKT3 and ZNF238, two previously proposed dosage sensitive candidate genes for microcephaly and agenesis of the corpus callosum, were retained in two of our patients. The deletion shared by our patients encompassed the FAM36A, HNRPU, EFCAB2 and KIF26B genes. Since HNRPU is involved in the regulation of embryonic brain development, this represents a novel plausible candidate gene for the combination of developmental delay, speech delay, hypotonia, hypo- or agenesis of the corpus callosum, and seizures in patients with 1q44 deletions. Since only one of the two patients with deletions including the ZNF124 gene showed a vermis hypoplasia, mere hemizygosity for this gene is not sufficient to cause this anomaly. Moreover, to reconcile the variability in the corpus callosum thickness, additional mechanisms, such as unmasking of hemizygous mutations, position effects and possible interactions with other loci need consideration.

Continuous artery‐selective spin labeling (CASSL)

A new technique for selective spin labeling of individual arteries is presented. It is based on continuous arterial spin labeling (CASL) with an amplitude‐modulated control experiment. Precessionary motion of the labeling gradient about the axis of the artery, combined with an appropriate frequency modulation of the labeling RF pulse, restricts the adiabatic inversion to the desired artery. In phantom studies, it was found that the level of selectivity could be controlled by the sequence parameters, and that the achievable labeling efficiency was at a level of ∼80% compared to a regular, nonselective CASL experiment. In a volunteer study we acquired high‐quality images of the perfusion territories of the internal carotid artery (ICA), the basilar artery (BA), the middle cerebral artery (MCA), and both anterior cerebral arteries (ACAs). The results show the methods flexibility for different geometries and flow velocities. Potential applications include perfusion territory imaging of smaller cerebral arteries, and selective angiography techniques. Magn Reson Med 53:1006–1012, 2005.

Evolution of hippocampal CA‐1 diffusion lesions in transient global amnesia

Selective focal MR‐Signal (diffusion‐) changes in the CA‐1 sector of the hippocampus have been described in transient global amnesia (TGA), but the pathophysiological substrate of these lesions is largely unknown. As several imaging and epidemiological findings point to a vascular origin an analysis of the temporal evolution of the hippocampal apparent diffusion coefficient (ADC) changes may offer new understanding of the pathomechanisms of TGA.

Superselective pseudocontinuous arterial spin labeling.

A new technique for the imaging of flow territories of individual extra‐ and intracranial arteries is presented. The method is based on balanced pseudocontinuous arterial spin labeling but employs additional time‐varying gradients in between the radiofrequency pulses of the long labeling train. The direction of the additional gradient vector is perpendicular to the selected artery and its azimuthal angle is switched after every radiofrequency pulse. The phases of the radiofrequency pulses are adopted to cancel out the phase accrual of the spins at the center of the target vessel due to the extra applied gradients. This results in efficient inversion at the targeted position, whereas elsewhere time‐varying phase changes will result in marginal inversion efficiency. By changing the moment of the added gradients, the size of the labeling focus can be adjusted. Influence of the temporal order of the additional gradients on the labeling efficiency and on the selectivity was investigated by simulations and experimental measurements. In a volunteer study, the acquisition of high signal‐to‐noise ratio flow territory images of small branches of the anterior cerebral artery distal to the circle of Willis was demonstrated. This shows the methods flexibility for dealing with complicated arterial geometries and its ability to superselectively label small intracranial arteries. Magn Reson Med, 2010.

Neuropsychological consequences of endarterectomy and endovascular angioplasty with stent placement for treatment of symptomatic carotid stenosis : A prospective randomised study

Background and purposePrevious studies compared carotid endarterectomy (CEA) and carotid artery stent placement (CAS) for treatment of symptomatic carotid artery stenosis. Whereas most previous studies showed both treatment modalities to be associated with a comparable risk of periprocedural cerebrovascular complications, these previous studies have shown significantly more microemboli and significantly more lesions in diffusion-weighted MR imaging after CAS compared to CEA. The clinical relevance of these differences remains unknown.We therefore compared the neuropsychological consequences of CAS and CEA and additionally measured the S100β protein, a marker of cerebral damage.MethodsA total of 48 patients with symptomatic carotid artery stenosis greater than 70 % (according to ECST criteria) were enrolled and 45 patients participated in the follow-up. The patients were randomly assigned for CEA (24 patients) or CAS (21 patients). S100β protein values were evaluated 2 hours before the procedure, as well as one and two hours thereafter. Patients were assessed before treatment, and again 6 and 30 days after treatment using a comprehensive neuropsychological test battery.ResultsPatients of the CAS and the CEA groups did not significantly differ in terms of age, gender, education, degree of carotid artery stenosis, cerebrovascular symptoms and vascular risk factors. Following previously used criteria, a cognitive change in patients was assumed to have occurred when there was a decline of more than one standard deviation in two or more tests assessing various cognitive domains. Six days and 30 days after the treatment both groups showed a comparable number of patients with cognitive changes compared to baseline. There were no significant differences in S100β protein values.ConclusionThese results provide some reassurance that CAS is not associated with greater cognitive deterioration than CEA is.

Brain perfusion territory imaging applying oblique-plane arterial spin labeling with a standard send/receive head coil.

A new method for the selective spin labeling of left‐ or right‐sided supplying arteries of the brain without the need for additional RF coils is demonstrated. A clinical 1.5 T scanner was used. The spatial selectivity of the labeling process is based on the limited coverage of the excitation field of a standard send/receive head coil together with an oblique positioning of the labeling plane. A computer simulation was used to optimize key labeling parameters under the condition of laminar flow. The validity of the computer model results was confirmed by MRI measurements with a flow model. For human studies, a double‐inversion continuous arterial spin labeling (CASL) sequence was modified to allow for arbitrary positioning of the labeling plane. The obtained perfusion‐weighted images showed a clear delineation of the perfusion territories of the selected arteries in the anterior circulation of the brain and good gray/white matter contrast. Magn Reson Med 52:1443–1447, 2004.