[Evaluation of treatment adaptation for low response to ASA in vascular surgery]. / Evaluation einer Therapieanpassung bei ASS-Low-Response in der Gefäßchirurgie.

BACKGROUND: A decreased antiplatelet prophylaxis (low response, LR/high on-treatment platelet reactivity, HPR) with acetylsalicylic acid (ASA) is associated with an increased risk of thromboembolic events. The prevalence of a LR is frequent with about 20% and a therapeutic regimen is not yet established. The aim of this prospective study was to evaluate the effectiveness of a therapeutic regimen for treatment adaptation when LR/HPR is detected in vascular surgery patients. METHODS: Overall, 36 patients under long-term antiplatelet treatment with 100 mg/day ASA and a detected ASA low response (ALR) were included in the study. In this patient group a modification of the prophylactic medication was carried out according to the established treatment plan and a control aggregometry was performed. The therapeutic regimen followed the test and treat principle. To evaluate the effect of ASA impedance, aggregometry with multiple electrodes was used (multiplate). RESULTS: All 36 patients were successfully transferred to response status with the treatment scheme. In 32 (88.89%) patients an increased dose of 300 mg/day ASA was carried out and in 2 (5.56%) patients the medication was changed from ASA to clopidogrel. A further 2 (5.56%) patients were switched to oral anticoagulation with phenprocoumon, due to other indications. Bleeding complications or other side effects did not occur. CONCLUSION: The chosen treatment regime for a low response proved to be effective and safe in vascular surgery patients. A guideline-compliant increase of the ASA dose from 100 mg to 300 mg/day predominantly led to an effective inhibition of platelet aggregation in the aggregometry.

[Prevalence of acetylsalicylic acid (ASA) - low response in vascular surgery]. / Prävalenz der ASS-Low-Response in der Gefäßchirurgie.

BACKGROUND: Research has revealed that a decreased antiplatelet effect (low response [LR]/high on-treatment platelet reactivity [HPR]) of acetylsalicylic acid (ASA) and clopidogrel is associated with an increased risk of thromboembolic events. There are extensive ASA low response (ALR) and clopidogrel low response (CLR) prevalence data in the literature, but there are only a few studies concerning vascular surgical patients. The aim of this study was to examine the prevalence and risk factors of ALR and CLR in vascular surgical patients. MATERIALS AND METHODS: We examined n = 154 patients with an antiplatelet long-term therapy, who were treated due to peripheral artery occlusive disease (PAD) and/or arteria carotis interna stenosis (CVD). To detect an ALR or CLR, we examined full blood probes with impedance aggregometry (ChronoLog® Aggregometer model 590). Risk factors were examined by acquisition of concomitant disease, severity of vascular disease, laboratory test results and medication. RESULTS: We found a prevalence of 19.3 % in the ALR group and of 21.1 % in the CLR group. Risk factors for ALR were an increased platelet and leucocyte count and co-medication with pantoprazole. We found no significant risk factors for a decreased antiplatelet effect of clopidogrel treatment. CONCLUSION: The investigated prevalence for ALR and CLR are in the range of other studies, particularly based on cardiological patients. More investigations are needed to gain a better evaluation of the risk factors for HPR and to develop an effective antiplatelet therapy regime to prevent cardiovascular complications.

Safety of early endarterectomy in patients with symptomatic carotid artery stenosis: an international multicenter study.

BACKGROUND AND PURPOSE: Although the latest recommendations suggest that carotid endarterectomy (CEA) should be performed in symptomatic carotid artery stenosis (sCAS) patients within 2 weeks of the index event, only a minority of patients undergo surgery within the recommended time-frame. The aim of this international multicenter study was to prospectively evaluate the safety of early CEA in patients with sCAS in everyday clinical practice settings. METHODS: Consecutive patients with non-disabling acute ischaemic stroke (AIS) or transient ischaemic attack (TIA) due to sCAS (≥ 70%) underwent early (≤ 14 days) CEA at five tertiary-care stroke centers during a 2-year period. Primary outcome events included stroke, myocardial infarction (MI) or death occurring during the 30-day follow-up period and were defined according to the International Carotid Stenting Study criteria. RESULTS: A total of 165 patients with sCAS [mean age 69 ± 10 years; 69% men; 70% AIS; 6% crescendo TIA; 8% with contralateral internal carotid artery (ICA) occlusion] underwent early CEA (median elapsed time from symptom onset 8 days). Urgent CEA (≤ 2 days) was performed in 20 cases (12%). The primary outcomes of stroke and MI were 4.8% [95% confidence interval (CI) 1.5%-8.1%] and 0.6% (95% CI 0%-1.8%). The combined outcome event of non-fatal stroke, non-fatal MI or death was 5.5% (95% CI 2.0%-9.0%). Crescendo TIA, contralateral ICA occlusion and urgent CEA were not associated (P > 0.2) with a higher 30-day stroke rate. CONCLUSIONS: Our findings indicate that the risk of early CEA in consecutive unselected patients with non-disabling AIS or TIA due to sCAS is acceptable when the procedure is performed within 2 weeks (or even within 2 days) from symptom onset.

[Switching from clopidogrel hydrogen sulfate to clopidogrel besylate. Impaired antiplatelet effect in patients with ischemic stroke]. / Umstellung von Clopidogrel-Hydrogensulfat auf Clopidogrel-Besilat. Unzureichende plättchenhemmende Wirkung bei Patienten mit Hirninfarkt.

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.

Recanalization of acute symptomatic occlusions of the internal carotid artery.

BACKGROUND: Little is known about the natural course of internal carotid artery (ICA) occlusion and its possible recanalization. The present study was designed to evaluate recanalization rates of extracranial ICA occlusions in acute stroke patients by means of color-coded duplex sonography (CCDS). METHODS: 305 patients with acute ischemia in the territory of the middle cerebral artery were included in this study. All patients had a neurological examination on admission and on discharge and were rated by means of the European Stroke Scale (ESS). Extracranial color-coded duplexsonography, transcranial Doppler sonography and cranial computed tomography were immediately performed after admission and within 7 days. RESULTS: 254 patients showed no sign of hemodynamic relevant stenosis greater than 70% of the ICA. 21 patients had symptomatic high grade ICA stenosis. 20 patients had an acute occlusion and 10 patients an old ICA occlusion as judged by duplex sonographic criteria. Six patients (5 male, 1 female; age range 57 to 77 years) with an acute atherothrombotic or cardioembolic occlusion showed a recanalization of the ICA in the follow-up ultrasonography. Two patients with cardiogenic embolic occlusion of the ICA had the most favorable outcome and these patients showed no residual stenosis. 4 patients who had ultrasound findings consistent with atherosclerosis on follow-up examination (2 high-grade stenosis, 2 with carotid plaques) did not show a notable improvement of their ESS-score. Patients with carotid plaques developed complete MCA infarctions; the other 4 patients had partial anterior circulation infarction on follow-up CT. CONCLUSIONS: The present study showed that recanalization of the occluded ICA in acute stroke patients is more frequent than generally presumed. CCDS should be routinely performed in the follow-up of stroke patients as spontaneous recanalization may influence clinical outcome.

Distribution of artificially-produced microembolic signals into the cerebral circulation.

According to clinical observations, cardiogenic embolism occurs more often in the anterior than in the posterior cerebral circulation. An ultrasound (US) contrast agent was used to artificially produce microembolic signals (MES) to imitate the intracranial distribution of systemic emboli. Systemic microemboli were simulated by IV administered US agent (Levovist(R) 300 mg/mL as bolus). A total of 20 patients were monitored by means of transcranial Doppler sonography (TCD), 3 min after the injection, with a 2-MHz transducer simultaneously at 50 mm (middle cerebral artery, MCA, on one side) and 90 mm (basilar artery, BA). Four 3-min recordings were done (two of the right MCA, two of the left MCA, with the BA, respectively). Three observers and an automatic detection system independently performed an off-line analysis. A total of 160 recordings were analyzed. The mean numbers of detected high-intensity transient signals (HITS) were 34.5 +/- 28.2 in the right MCA (simultaneously registered HITS in the BA: 9.4 +/- 16.8) and 39.1 +/- 34.2 in the left MCA (simultaneously registered HITS in the BA: 12.2 +/- 14.5). Only 21.4 to 23.7% of all HITS were recorded in the BA. Microembolic signals artificially produced by means of US contrast agent made it possible to mimic the physiologic distribution of small embolic particles. In future, these might help to investigate the distribution of systemic emboli in different vascular territories in various pathologic conditions of the cerebral blood flow.

Ultrasonic evaluation of pathological brain perfusion in acute stroke using second harmonic imaging.

OBJECTIVE: To evaluate the use of transient response second harmonic imaging (HI) by means of ultrasound to assess abnormalities of cerebral echo contrast agent enhancement in patients with acute stroke. METHODS: The study comprised 25 patients with acute onset of hemispheric stroke (<24 h) with sufficient insonation conditions and 14 control subjects without cerebrovascular disease. All stroke patients had HI, extracranial and transcranial colour coded duplex examinations of the arteries supplying the brain, and clinical examinations (European stroke scale) performed in the acute phase, on day 2, and within 1 week. Acute CT was repeated within 1 week and facultatively accompanied by angiography. Examinations using HI were performed in an axial diencephalic plane of section using the transtemporal acoustic bone window. After bolus application of galactose based microbubbles, 61 ultrasound images with a cardiac cycling triggering frequency of once every 2 seconds were recorded and evaluated off line. Focal perfusion deficit was identified if no contrast enhancement was visualised in a circumscribed region of interest and insufficient temporal bone window was excluded. In cases of reappearance of contrast enhancement reperfusion was assessed. RESULTS: Adequate cerebral contrast enhancement could be seen in 21 subjects. In seven, a large hemispheric deficit of contrast enhancement affecting the entire middle cerebral artery (MCA) territory was detectable; the lentiform nucleus was affected in three subjects. Assessment of cerebral contrast abnormalities was possible in two patients with superficial MCA infarctions but in none of the patients with lacunar ischaemias. None of the control persons had focal deficits of cerebral echo contrast enhancement. In all patients with complete MCA infarction and striatocapsular infarction, presumed ischaemic areas in HI examinations correlated with final CT findings. Overall sensitivity and specifity of HI examinations for predicting size and localisation of the infarction were 75 and 100%, respectively. During follow up, reappearance of contrast enhancement was determined in three patients, in two patients circulatory arrest due to malignant brain oedema with missing contrast enhancement in the entire cerebral hemisphere could be seen. Extent of contrast enhancement deficits significantly correlated with the clinical status on admission and after 1 week (p<0.01). CONCLUSIONS: Second harmonic imaging is the first ultrasonic technique that enables visualisation of pathological cerebral echo contrast enhancement. Because this method identifies deficits of focal contrast enhancement in patients with acute stroke and allows estimation of the final infarct size and clinical prognosis, it may help to select and monitor patients for invasive therapies.

Glutathione S-transferase polymorphism in Parkinson's disease.

Glutathione S-transferases (GSTs) are involved in the detoxification of endogenous or exogenous toxins, which may play a role in the pathogenesis of Parkinson's disease. We genotyped the Glutathione-S-Transferase isoenzymes GSTM1 and GSTT1 by polymerase chain reaction in order to evaluate different gene polymorphisms of these isoenzymes in 149 parkinsonian and 99 control subjects. No differences appeared between both groups regarding the frequencies of the homozygous deletion of GSTM1 (odds ratio 1.021; 95% CI [0.613; 1.699], p < 0.521 Fisher's exact test) and GSTT1 (odds ratio 1.514; 95% CI [0.811; 2.824], p < 0.127). Age of onset of PD did not correlate to GSTM1 and GSTT1 polymorphisms. These results do not support the hypothesis of a possible impact of GSTM1 and GSTT1 detoxification activities in the pathogenesis of Parkinson's disease.

Acute brainstem symptoms associated with cervical syringomyelia.

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.

Contrast-enhanced transcranial color-coded sonography in acute hemispheric brain infarction.

PURPOSE: The aim of the present study was to investigate the diagnostic potential of contrast-enhanced transcranial color-coded real-time sonography (CE-TCCS) in otherwise ultrasound-refractory acute stroke patients with an ischemia in the territory of the middle cerebral artery (MCA). Furthermore, correlations of CE-TCCS findings with clinical, angiographic, and CT results were investigated. METHODS: In 90 acute stroke patients with inadequate insonation conditions in unenhanced transcranial color-coded real-time sonography (TCCS) examinations, CE-TCCS, clinical, angiographic, and CT examinations were performed within 12 hours, 36 hours (CE-TCCS only), and 1 week after onset of clinical symptoms. A CT angiography (CTA) as reference method was available in 39 individuals. After application of a galactose-based echo-enhancing agent, the portion of conclusive ultrasound examinations of the MCA, as manifested by an MCA occlusion, decreased or increased flow velocity (FV), and symmetrical MCA FV, was evaluated. CE-TCCS findings on admission and during follow-up were correlated with infarction size as demonstrated on follow-up CT, and clinical findings were assessed by use of the European Stroke Scale. RESULTS: Adequate diagnosis was achieved in 74 of 90 patients (82%) by the use of echo contrast agents. MCA occlusion or reduction of MCA FV was found in 20 and 27 patients, respectively. MCA occlusion was confirmed by CTA in 17 cases. In one individual, false-positive diagnosis of MCA occlusion was made according to ultrasound criteria. In 5 patients with MCA occlusion, vessel recanalization was observed during follow-up; 15 of 27 patients with decreased flow velocities showed normalization after the third examination that was associated with a significantly better clinical outcome (P<0.0001). Furthermore, MCA occlusion or decreased FV in the first 12 hours were associated with significantly larger infarctions in the MCA territory compared with normal CE-TCCS findings (P<0.0001). CONCLUSIONS: CE-TCCS enables adequate diagnosis in approximately 80% of acute hemispheric stroke patients with insufficient unenhanced TCCS examinations. It is a reliable diagnostic tool regarding MCA mainstem and branch occlusions. Because this method conveys useful information concerning cerebral tissue and clinical prognosis, it may be useful to identify those patients who benefit most from local or intra-arterial thrombolytic therapy.

[The reliability of stroke scales. The german version of NIHSS, ESS and Rankin scales]. / Untersuchung zur Reliabilität von Schlanganfallskalen. Die deutschen Versionen von NIHSS, ESS und Rankin Scale.

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.

Echo contrast-enhanced three-dimensional power Doppler of intracranial arteries.

The purpose of this study was to evaluate the potential of contrast-enhanced three-dimensional (3-D) power Doppler (CE3DPD) in the assessment of intracranial vascular structures, and to compare the results with unenhanced 3-D power Doppler (3DPD) and magnetic resonance angiography (MRA) findings. We insonated 25 patients without cerebrovascular diseases through the temporal bone window using 3DPD and CE3DPD; for comparison, 13 patients underwent MRA. Identification rates of vascular segments and of small branches of intracranial vessels were evaluated by two independent investigators blinded to MRA results. In 21 patients with adequate insonation conditions, CE3DPD significantly improved identification rates compared to 3DPD for the complete visualization of the P1 segment (80.9 vs. 19.0%, p < 0.005, P2 segment (80.9 vs. 42.8%, p < 0.05 and A1 segment (85.7 vs. 38.1%, p < 0.005). Furthermore, CE3DPD depicted, in significantly more examinations, branches of the middle (MCA) and posterior cerebral artery (PCA). Interobserver agreement was higher than 95% for the main intracranial segments and branches of the MCA, but relatively low (80.1-85.7%) for branches of the PCA. In comparison to CE3DPD, MRA identified only parieto-occipital branches of the PCA, temporal branches of the MCA, frontal branches of the anterior cerebral artery and the MCA bifurcation more frequently and accurately. In 4 patients with inadequate acoustic temporal bone windows, the application of a galactose-based microbubble suspension allowed clear 3-D visualization of almost all major intracranial vascular segments and some branches of the large arteries. In conclusion, CE3DPD is a more sensitive ultrasonic tool compared to unenhanced 3-D reconstructions. It makes 3-D ultrasound imaging of the basal cerebral circulation easier to perform and interpret, by providing an improved spatially oriented display of image position. As such, this method may increase operator diagnostic confidence level under pathologic conditions.

Transient response harmonic imaging: an ultrasound technique related to brain perfusion.

BACKGROUND AND PURPOSE: Gray-scale harmonic imaging is the first method to visualize blood perfusion and capillary blood flow with ultrasound after intravenous contrast agent application. The purpose of the present study was to evaluate the potential of transient response second harmonic imaging (TRsHI) to assess normal echo contrast characteristics in different brain areas by transcranial ultrasound. METHODS: In 18 patients without cerebrovascular diseases, TRsHI examinations were performed bilaterally with the use of the transtemporal approach after application of 6.5 mL of a galactose-based microbubble suspension (400 mg/mL). The transmission rate was once every 4 cardiac cycles. Regional cerebral contrast was visually assessed and then quantified off-line with the use of time-intensity curves. In 4 different regions of interest (ROI) (posterior part of the thalamus [ROIa], anterior part of the thalamus [ROIb], lentiform nucleus [ROIc], and white matter [ROId]), the following parameters were evaluated: peak intensity, area under the curve (AUC), and time to peak intensity. AUC ratios for ROIc/a, d/a, c/b, and d/b were calculated. RESULTS: In all patients parenchymal contrast enhancement was visually detectable. One hundred thirty-one characteristic time-intensity curves (baseline phase, peak contrast intensity, slow washout phase) were demonstrable in 144 ROIs. In ROIc and ROId, characteristic contrast curves could be observed most frequently (68/72 examinations), whereas time-intensity curves in ROIa and ROIb could not be evaluated because of inadequate contrast enhancement in 9 of 72 examinations. Time to peak intensity varied between 20 and 52 cardiac cycles; in 1 patient it was 88 cardiac cycles. In all individuals AUCs and in 16 of 18 subjects peak intensity in ROIc and ROId showed a 2- to 10-fold increase compared with ROIa and ROIb. In no examination did AUC ratios show a >2-fold side difference irrespective of the ROI. CONCLUSIONS: The present study demonstrates for the first time that TRsHI produces accurate contrast in different brain areas and represents an ultrasonic tool related to brain perfusion. Absolute values of quantitative parameters show high variations caused by different temporal bone thicknesses and a complex relationship between echo contrast concentrations and measurements of optic intensities. Ratios between different ROIs help to compare contrast enhancement in different brain areas. Furthermore, because of the fact that attenuation of contrast enhancement in TRsHI depends strictly on the insonation depth, harmonic imaging studies of brain perfusion cannot be compared directly with other imaging techniques such as positron emission tomography.

High prevalence of parkinsonism after occupational exposure to lead-sulfate batteries.

Seven of nine postal workers exposed to lead-sulfate batteries over a period of up to 30 years developed parkinsonian symptoms. One of the remaining two showed left-hand bradykinesia and one was not available for examination. The high prevalence and cause of parkinsonism in these patients remains unexplained. Lead intoxication may play a role in the occurrence of parkinsonian symptoms, but involvement of sulfate and other sulfur compounds must also be considered.

Power Doppler compared to color-coded duplex sonography in the assessment of the basal cerebral circulation.

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.

Spinocerebellar ataxia type 2. Genotype and phenotype in German kindreds.

BACKGROUND: Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant cerebellar ataxia (ADCA) for which the disease-causing mutation has recently been characterized as an expanded CAG trinucleotide repeat. We investigated 64 families of German ancestry with ADCA and 55 patients with sporadic ataxia for the SCA2 mutation. RESULTS: Expanded alleles were found in 6 of the 64 families and in 1 patient with sporadic ataxia. This patient had a de novo mutation from an intermediate paternal allele. Length of repeats in 21 patients with SCA2 ranged from 36 to 52 CAG motifs and was inversely correlated with age at onset and progression of the disease. Expanded alleles were unstable during meiosis; paternal transmission especially caused significant anticipation of onset up to 26 years earlier. The SCA2 phenotype differed from those of SCA1 and SCA3 with higher frequencies of slowed ocular movements, postural and action tremor, myoclonus, and hyporeflexia. However, no single feature was sufficient to permit a specific clinical diagnosis. CONCLUSIONS: Spinocerebellar ataxia type 2 accounts for about 10% of German families with ADCA but may also be present in sporadic ataxia due to de novo mutations. Clinical features are highly variable among and even within families. However, the size of the expanded repeat influences the phenotype and is relevant for course and prognosis of the disease.

Reversible urinary retention as the main symptom in the first manifestation of a syringomyelia.

A neurogenic bladder is seldom described as the first manifestation of syringomyelia. A patient is reported with an extensive syrinx along the entire spinal cord and a Chiari type I malformation, who experienced dysaesthesia and weakness during shooting practice and presented with urinary retention.