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Abstract Background Guidelines recommend an early initiation of aspirin treatment in patients with acute cerebral ischemia. Comparative studies on the best starting dose for initiating aspirin therapy to achieve a rapid antiplatelet effect do not exist. This study evaluated the platelet inhibitory effect in healthy volunteers by using three different aspirin loading doses to gain a model for initiating antiplatelet treatment in acute strokes patients. Methods Using whole blood aggregometry, this study with a prospective, uncontrolled, open, crossover design examined 12 healthy volunteers treated with three different aspirin loading doses: intravenous 500 mg aspirin, oral 500 mg aspirin, and a course of 200 mg aspirin on two subsequent days followed by a five-day course of 100 mg aspirin. Aspirin low response was defined as change of impedance exceeding 0 Ω after stimulation with arachidonic acid. Results Sufficient antiplatelet effectiveness was gained within 30 seconds when intravenous 500 mg aspirin was used. The mean time until antiplatelet effect was 74 minutes for 500 mg aspirin taken orally and 662 minutes (11.2 hours) for the dose scheme with 200 mg aspirin with a high inter- and intraindividual variability in those two regimes. Platelet aggregation returned to the baseline range during the wash-out phase within 4 days. Conclusion Our study reveals that the antiplatelet effect differs significantly between the three different aspirin starting dosages with a high inter- and intraindividual variability of antiplatelet response in our healthy volunteers. To ensure an early platelet inhibitory effect in acute stroke patients, it could be advantageous to initiate the therapy with an intravenous loading dose of 500 mg aspirin. However, clinical outcome studies must still define the best way to initiate antiplatelet treatment with aspirin.

Introduction: Activated prothrombin time (aPTT) and thrombin time (TT) can serve as indicators for anticoagulation effect of dabigatran etexilate (Pradaxa), the new oral reversible, competitive inhibitor of thrombin. Further, a significant elevation of these coagulation parameters might demonstrate an increased risk of bleeding probably due to an accumulation of dabigatran., Case Reports: We present 2 cases of patients with atrial fibrillation as well as mild and moderate renal impairment, which were treated with dabigatran. The patient with the mild renal impairment [creatinine clearance in 24-hour urine collection (CrCl) 50.2 mL/min] had a comorbid slightly disturbed liver synthesis and prolongation of aPTT. Increased risk of bleeding could be identified by significant elevated coagulation parameters (TT and aPTT) during dabigatran treatment. Further speculative in this case increased risk of bleeding might be due to an accumulation of dabigatran possibly caused by comorbid kidney and liver impairment and an effective gain of dabigatran caused by reduced hepatic synthesis of coagulation factors., Conclusions: Especially in multimorbid elderly patients with comorbid liver and kidney dysfunction, a measurement of coagulation parameters not only before but also soon after initiation of treatment might provide additional information about the risk of bleeding.

There is convergent evidence that basal ganglia structures are involved in the pathogenesis of obsessive-compulsive disorder (OCD). It has been also assumed that OCD is caused by a central serotonergic dysfunction. Transcranial sonography (TCS) has become a reliable, sensitive and non-invasive diagnostic tool concerning the evaluation of extrapyramidal movement disorders. This study used TCS to examine the alterations in different parenchymal regions, especially concerning serotonergic brainstem raphe nuclei as well as basal ganglia in OCD. Thirty-one OCD patients were compared with 31 matched healthy controls. Echogenecities were investigated according to the examination protocol for extrapyramidal disorders using a Siemens Sonoline(®) Elegra system. Obsessive-compulsive disorder patients showed reduced echogenity of the serotonergic brainstem raphe nuclei (32.3%) compared with healthy controls (16.1%). In nine OCD-patients (31%), but only in 2 control subjects (6.2%), a hyperechogenicity of the caudate nucleus was found. Patients with OCD significantly more often reveal a hypoechogenic brainstem raphe possibly reflecting altered serotonergic neurons there and a hyperechogenicity of caudate nucleus indicating structural or molecular cell changes. Further research is warranted to examine, whether TCS is useful in order to classify OCD and its subtypes., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Severe internal carotid artery stenosis can cause constriction of cerebral perfusion. Different techniques of measuring brain perfusion are currently available. Ultrasound perfusion imaging (UPI) can differentiate hypoperfused and nonperfused cerebral tissue. Aim of this study was to compare the value of UPI and perfusion-weighted magnetic resonance imaging (pw-MRI) in the evaluation of cerebral perfusion in patients with severe internal carotid artery stenosis. Ten patients with severe internal carotid artery stenosis were included. UPI was performed with phase-inversion-harmonic-imaging and bolus application of contrast media for semiquantitative analysis of time-intensity curves. Time-to-peak intensity (TPI) values were compared with time-to-peak maps of pw-MRI examinations in predefined regions-of-interest (ROI). Further, a comparison of pre- and postoperative UPI data was performed in selected cases. Seven of 10 patients could be evaluated. Eighty ROIs were used for the comparison of UPI and pw-MRI, 37 ROIs were used for pre- and 36 ROIs for postoperative comparison of UPI data. There was no delay in any MRI ROI. In UPI, there were relevant delays in seven of 37 ROIs (18.9%) before and in nine of 36 ROIs (25.0%) after surgery. Eleven of these 16 ROIs (68.8%) were in the inner border zone. Compared with the established pw-MRI technique, UPI described possible subtle perfusion delays mainly of the inner border zone. These preliminary results suggest a possible diagnostic power of UPI as a noninvasive tool for the detection of hemodynamic relevance in severe internal carotid artery disease., (Copyright © 2010 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

The use of antiplatelet medications, such as acetylsalicylic acid (ASA), a combination of dipyridamol with ASA and also clopidogrel, is of great importance for the secondary prevention of ischemic stroke or transient ischemic attacks. In addition to the known form of clopidogrel hydrogen sulfate (CHS) a further clopidogrel salt, clopidogrel besylate (CB), has also been available since May 2008. The presented case illustrates that in patients with a history of cerebrovascular disease the antiplatelet response of CB can be diminished in comparison to CHS. Therefore we recommend testing the antiplatelet effectiveness when changing patient medication from CHS to CB.

Ultrasonic perfusion imaging predicts size and localization of acute stroke. It is unclear whether irreversibly damaged tissue can be differentiated from tissue at risk. Thirty-four patients (ischemic stroke <12 h) were included (Phase Inversion Harmonic Perfusion Imaging; bolus kinetic; fitted model function). Three patterns of perfusion were defined in 14 prespecified regions of interest (ROI): 'normal', 'hypoperfusion', and 'no perfusion'. Clinical status was assessed using the National Institutes of Health Stroke Scale (NIHSS) (at baseline and at days 2 to 4). Cranial Computed Tomography (CCT) (days 2 to 4) displayed final infarction. The pattern 'hypoperfusion' (ROIs presumably representing tissue at risk) was tested twofold: (i) Functional impairment by correlating their number with baseline NIHSS. (ii) Viability by correlating their recruitment rate to infarction with clinical course (DeltaNIHSS days 2 to 4). In addition, various predictive values were assessed. Twenty-seven patients were eligible for analysis. The sum of ROIs with 'no perfusion' and 'hypoperfusion' correlated highest with baseline NIHSS (rho=0.78, P<0.001). Recruitment of hypoperfused ROIs to infarction highly correlated with clinical course (rho=0.79, P<0.001). Clinical course dichotomized the patients into subgroups A ('stable', DeltaNIHSS>or=-3) and B ('improved', DeltaNIHSS

The bolus kinetic in ultrasonic cerebral perfusion imaging is the most favored data acquisition and processing technique. However, there has not yet been convincing evidence for the potential to (semi-) quantitatively describe perfusion. Aim of this study was to determine the intraindividual range of relevant perfusion parameters to describe individual physiological cutoff scores. In 20 healthy volunteers, cerebral perfusion was evaluated using the bilateral approach with phase inversion harmonic imaging and the bolus kinetic. Relevant parameters (time-to-peak intensity, TPI; peak width, PW) were derived in 14 regions-of-interest in both hemispheres. The median and quartile deviation (QD) of these values were individually calculated. Within the 20 individuals, the mean QD of TPI was 0.68 s, and there was no case in which any TPI exceeded the mean more than 2 s. With PW, the mean QD was 1.2 s, and the mean was not exceeded by more than 6 s. Intraindividual perfusion parameters, especially TPI, show a considerable small range. Thus, the bolus kinetic derives reliable semiquantitative information once intraindividual comparison can be accomplished. We therefore propose that bilateral examination with the unaffected hemisphere as referential region should be performed in acute stroke. Future studies have to evaluate the potential of this approach of discriminating ischemia and hypoperfusion in the affected hemisphere.

Objective: To validate the potential of ultrasonographic depletion imaging for semiquantitatively visualizing cerebral parenchymal perfusion with contrast burst depletion imaging (CODIM) in comparison with phase inversion harmonic depletion imaging (PIDIM) in healthy volunteers., Methods: Thirteen healthy adults were examined with both CODIM and PIDIM in accordance with previously described criteria. In addition to the perfusion coefficient, the time to decrease image intensity to 10% above equilibrium intensity from the initial value and the relative error (deviation of measured data from the fitted model) were evaluated to compare the reliability of both techniques in 3 different regions of interest., Results: Perfusion coefficient values did not show significantly differing values in both groups (1.57-1.64 * 10(-2) s(-1) for CODIM and 1.42-1.58 * 10(-2) s(-1) for PIDIM). The relative error was significantly smaller in the PIDIM group (0.38-0.53 for CODIM and 0.18-0.25 for PIDIM; P < .002)., Conclusions: Phase inversion harmonic depletion imaging proved to be more reliable than CODIM because values of the relative error were significantly lower in PIDIM even in this relatively small cohort. This is of interest because the underlying technique, phase inversion harmonic imaging, is more widely available than contrast burst imaging.

Background and Purpose: Contrast burst depletion imaging (CODIM) visualizes cerebral perfusion by destruction of microbubbles and observation of image intensity course. Because of its complexity, artifacts occur. Criteria of reliability to improve diagnostic significance were created and validated., Methods and Results: Eighteen healthy volunteers were examined with 2 echo contrast agents (ECAs) and 3 frame rates in 3 regions of interest (ROIs). Perfusion coefficient (PC), Tmin (time to decrease intensity to 10% of its max), and relative error (RE) (deviation of measured data from fitted model) were determined. PC differed significantly neither between CA nor between frame rates (overall mean = 1.60 +/- 0.21 x 10(-2) s-1). Tmin differed significantly between frame rate groups (P < .001, 33.4 +/- 11.2 s/0.5 Hz; 3.6 +/- 2.5 s/5 Hz) since it is related to destruction of microbubbles that occurs with each frame and to the perfusion rate. RE was higher in the Optison group and tended to decrease in ROIs closer to the probe., Conclusions: PC was independent of frame rate and ECA. Tmin was shorter with higher frame rates. Due to a very rapid decay at 5 Hz, the ideal frame rate should be about 1 Hz, that is, because the number of frames acquired within Tmin and therefore signal-to-noise ratio is higher at 1 Hz. Since the algorithm is complex (high RE) and more artifacts should occur in patients (insufficient bone window, etc), a triggering of the insonations by, for example, heart rate could decrease artifacts and increase diagnostic power of CODIM.

The aim was to evaluate phase-inversion harmonic imaging (PIHI) with respect to brain perfusion imaging using a novel "bilateral approach" (depth of examination: 150 mm) and established unilateral approach (100 mm). After bolus injection of two contrast agents (CA, Optison and SonoVue), perfusion-related parameters (time-to-peak intensity, Itpk, peak intensity, Ipk, and peak width, Wpk) were extracted by fitting a model function to time-intensity curves for different regions-of-interest (ROI) in 14 volunteers. In 207 (92%) of 224 ipsilateral ROIs and in 165 (98%) of 168 contralateral ROIs (372 or 95% of 392 altogether), parameters could be derived. Itpk and Wpk of gray matter ROIs did not vary in or between both CA groups (18.1-21.9 s and 7.9-14.2 s). ROIs within arteries showed significantly shorter Itpk (16.1-16.7 s) and longer Wpk (12.8-28.3 s). Level of significance was 0.05 (two-sided). Newer CAs are usable for nonlinear imaging over a wider range of acoustic intensities, so that sensitivity of PIHI is sufficient to image the brain bilaterally. This approach proves to be reliable in patients with adequate bone windows. For acute stroke patients, this implies that both hemispheres can be compared in one instead of two examinations, reducing time of examination by 50%. Furthermore, evaluation of regions close to the probe becomes possible. Thus, the "bilateral approach" should be considered as a new standard approach of acute ultrasonic perfusion imaging.

Syringomyelia classically presents with slowly progressing dissociated sensory and upper and lower motor deficits. Atypical and acute manifestations have rarely been described. We report here on 3 patients with syringomyelia, who had acute and atypical brainstem symptoms with regard to the underlying disease. These symptoms occurred after acute elevation of the intrathoracic and intra-abdominal pressure, respectively, and remitted subsequently. Vertebrobasilar ischemia was initially suspected., (Copyright 2000 S. Karger AG, Basel)

Aim of the study was the translation of three frequently used stroke scales ("National Institutes of Health Stroke Scale" NIHSS, "European Stroke Scale" ESS and "Rankin Scale") into German and the analysis of the interrater reliability of the respective German versions. The translation process followed the protocol of the Medical Outcomes Trust (Boston) and included two independent forward, one backward translation and a consensus conference for the German versions. Interrater reliability was assessed using the weighted kappa statistic. For this study 43 patients with an ischemic stroke determined by computed tomography or magnetic resonance imaging were recruited from two university hospitals. Excluded were patients with an intracerebral hemorrhage or TIA. The interrater reliability of the three German versions was substantial to excellent. Mean Kappa for the NIHSS was 0.80, for the ESS 0.79 and 0.76 for the Rankin Scale using simple weights in the analysis. Additional analysis revealed the influence of preselected weights on the results of the kappa statistic. The use of German versions of frequently used stroke scales can reduce bias that is introduced by different levels of knowledge of the English language and thus improve the standardised assessment of neurological deficits in stroke.

Power-based transcranial duplex sonography (p-TDS) is a new promising ultrasound technique that generates intravascular color signals from the amplitude of the echo signal. The present investigation was undertaken to determine the advantages and limitations of power Doppler in the assessment of the basal cerebral circulation compared with transcranial color-coded real-time sonography (TCCS) and contrast-enhanced transcranial color-coded real-time sonography (CE-TCCS). Thirty-eight patients without cerebrovascular diseases were examined with p-TDS and TCCS, and in 11 patients CE-TCCS studies were performed. The M1 segment could be identified in 100% by both ultrasound techniques. p-TDS visualized M2 (67/70 vs 46/70, p < 0.0001), A2 (63/70 vs 46/70, p < 0.001), and P2 (67/70 vs 44/70, p < 0.0001) segments significantly more frequently and accurately compared to TCCS. The posterior communicating artery (25/70) and P3 segments (32/70) were only detectable by p-TDS and not by conventional TCCS. In comparison with CE-TCCS, p-TDS had no important advantages in the detection of intracranial vessels. In conclusion, p-TDS and CE-TCCS were superior to TCCS with regard to identification of the basal arterial circulation. Both methods permit noninvasive and reliable identification of the basal cerebral circulation.