[Integration of primary and secondary data in the Study of Health in Pomerania and description of clinical outcomes using stroke as an example]. / Die Integration von Primär- und Sekundärdaten in der Study of Health in Pomerania und die Beschreibung von klinischen Endpunkten am Beispiel Schlaganfall.

OBJECTIVE: This study describes (i) the procedure of obtaining patients' consent for secondary data usage, (ii) the complexity of integrating data from multiple sources, and (iii) the correspondence among patients' self-reports, physician reports, routine data, hospital discharge diagnosis, and cause-of-death coding regarding stroke. METHODS: Data from the first follow-up (N=3 186) of the population-based Study of Health in Pomerania (SHIP) were used. These data were combined with secondary data from the Greifswald University Hospital, the association of statutory health insurance physicians Mecklenburg-Western Pomerania, physician reports, and death certificates. RESULTS: Consent for using health-related information from all data sources in question was obtained from more than 90% of the SHIP participants. Follow-up data from at least one source were available for 2 747 (86%) participants. For 92 participants information about the occurrence of stroke was found in at least one data source. In 59 cases the event appeared in only one data source, in 24 cases the event was found in 2 sources, and for 9 participants 3 data sources reported on the event. CONCLUSION: Participants of a population-based cohort are highly willing to give consent for using their health-related information from secondary data sources. Yet, data integration is challenging due to considerable differences in data type, structure and coverage.

Mannheim carotid intima-media thickness and plaque consensus (2004-2006-2011). An update on behalf of the advisory board of the 3rd, 4th and 5th watching the risk symposia, at the 13th, 15th and 20th European Stroke Conferences, Mannheim, Germany, 2004, Brussels, Belgium, 2006, and Hamburg, Germany, 2011.

Intima-media thickness (IMT) provides a surrogate end point of cardiovascular outcomes in clinical trials evaluating the efficacy of cardiovascular risk factor modification. Carotid artery plaque further adds to the cardiovascular risk assessment. It is defined as a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrates a thickness >1.5 mm as measured from the media-adventitia interface to the intima-lumen interface. The scientific basis for use of IMT in clinical trials and practice includes ultrasound physics, technical and disease-related principles as well as best practice on the performance, interpretation and documentation of study results. Comparison of IMT results obtained from epidemiological and interventional studies around the world relies on harmonization on approaches to carotid image acquisition and analysis. This updated consensus document delineates further criteria to distinguish early atherosclerotic plaque formation from thickening of IMT. Standardized methods will foster homogenous data collection and analysis, improve the power of randomized clinical trials incorporating IMT and plaque measurements and facilitate the merging of large databases for meta-analyses. IMT results are applied to individual patients as an integrated assessment of cardiovascular risk factors. However, this document recommends against serial monitoring in individual patients.

Pre-hospital delays and intravenous thrombolysis in urban and rural areas.

INTRODUCTION: It is crucial to understand the reasons behind pre- and in-hospital delays to improve nationwide access to effective treatment for acute stroke. AIMS: To evaluate the pre- and in-hospital delays and to compare the intravenous (IV) thrombolysis rates in the urban and rural areas of the Province of Pomerania, Poland. MATERIALS & METHODS: We evaluated the medical records of 2134 patients treated in the stroke units (SUs) and consecutively reported to the Pomeranian Stroke Register from June 2006-December 2007. RESULTS: The time of ischaemic stroke onset was known in 488 (59%) of the 834 urban patients and in 744 (70%) of the 1063 rural patients (P < 0.001). The proportion of patients who called the emergency medical services with a delay of >45 min was similar in both locations: urban, 314/488 (64.3%) vs rural, 490/744 (65.8%). Although the proportion of patients who reached the emergency room within 3 h was higher in the rural areas (29.0% vs 24.3%; P = 0.02), only 4.2% of these patients received IV thrombolysis compared with 23.1% in the urban areas (P < 0.001). The proportion of patients who did not seek any kind of professional medical help prior to admission was lower in the rural areas (29/744 (3.9%) vs urban 50/488 (10.2%)) (P < 0.001). CONCLUSIONS: Pre-hospital delays reduced the number of patients eligible for IV thrombolysis in both rural and urban areas. The low proportion of patients treated with IV thrombolysis in rural SUs may be attributed to ineffective in-hospital procedures.

The potential of neurosonography in neurological emergency and intensive care medicine: monitoring of increased intracranial pressure, brain death diagnostics, and cerebral autoregulation­ part 2.

Transcranial B-mode sonography is an easy to use bedside imaging modality to monitor significant changes of the brain parenchyma such as in malignant middle cerebral infarction or intracerebral hemorrhage. The elevation of intracranial pressure can be followed with various neurosonographical techniques: Measurements of the ventricular width, midline shift, arterial resistance, and optic nerve sheath diameter. They should be viewed as complementary to each other and to other imaging modalities. Repeated cCT and MRI may be avoided in unstable patients by bedside neurosonography in the hands of an experienced physician. Monitoring of evolving hydrocephalus using serial measurements of the third and lateral ventricles can be used to guide therapeutic decisions such as the removal of a ventricular drainage. The cessation of cerebral blood flow in the case of intracranial pressure exceeding systemic arterial pressure is an important part of brain death diagnostics. Early demonstration of a sufficient temporal bone window is needed in patients in whom brain death may be expected. Cerebrovascular autoregulation is an integer component of the brain's blood supply and is compromised in a variety of neurological diseases. In neurological/neurosurgical patients in the intensive care unit, its assessment allows for extended neuromonitoring and control of therapeutic procedures.

Current management and risk of recurrent stroke in cerebrovascular patients with right-to-left cardiac shunt.

BACKGROUND: Right-to-left cardiac shunt (RLS) is considered a risk factor for stroke, especially in patients aged <55 years. We aimed to investigate the current management and prognosis in consecutive patients with RLS and otherwise cryptogenic cerebrovascular events. METHODS: In total, 1,126 patients with cryptogenic stroke or TIA were included from 17 German neurology departments. During a mean follow-up of 28.4 months, we assessed current antithrombotic medication, percutaneous device closure (PDC) and recurrent cerebrovascular events in 899 patients (79.8%). Stroke recurrence was compared between 548 patients without RLS and 351 patients with RLS under various prevention regimens. RESULTS: RLS was detected in 35.9% of cryptogenic cerebrovascular patients, but could not be evaluated as an independent predictor for recurrent stroke (adjusted HR 1.6, 95% CI: 0.9-2.7). In RLS-positive patients, the Kaplan-Meier estimate for stroke during the first year was 4.1% (95% CI: 1.9-6.3%) and 1.7% (95% CI: 0.9-2.4%) per year thereafter. At the last follow-up before recurrent stroke or end of study, 117 RLS-positive patients (33.3%) had received a PDC, 154 (43.9%) were receiving antiplatelets, 63 (17.9%) received anticoagulation, and 17 (4.8%) received none of the above. No association with recurrent stroke was found for the secondary preventive regime. CONCLUSION: Our multicenter hospital-based cohort study confirmed low recurrent event rates in RLS patients with otherwise cryptogenic stroke or TIA, as well as a great heterogeneity of current management. Despite the lack of scientific evidence, a substantial number of RLS-positive patients underwent PDC for secondary stroke prevention.

Factors associated with gender difference in the intima-media thickness of the common carotid artery.

AIM: To investigate the gender differences associated with a thinner intima-media thickness (IMT) of the common carotid artery (CCA) in women. MATERIALS AND METHODS: In a sample of 218 consecutive healthy volunteers comprising 110 men and 108 women, the IMT of the CCA was measured using B-mode ultrasonography. Blood pressure, fasting blood sugar, body mass index (BMI), blood lipid profile, homocysteine, folic acid, uric acid, high sensitive C-reactive protein, and thiobarbituric acid reactive substances (TBARS) levels were measured and compared with each other in both genders. RESULTS: The IMT of the CCA was significantly thinner in women than in men (p=0.012). Blood pressure, fasting plasma glucose, BMI, low-density lipoprotein cholesterol, triglycerides, homocysteine, uric acid, and TBARS were significantly (p<0.05) lower, folic acid and high-density lipoprotein cholesterol (HDL-C) were significantly (p<0.0001) higher in women compared with men. Multivariable logistic regression analysis revealed that higher serum levels of homocysteine, uric acid, and TBARS, and lower serum levels of HDL-C were significantly (p<0.05) associated with male sex. Multiple linear regression analysis further revealed that age, sex, and BMI were independently associated with CCA IMT. CONCLUSIONS: The IMT of the CCA was thinner in women than in men. Traditional vascular risk factors explain only a small amount of variance in multivariate regression models supporting the hypothesis that other behavioural, sex hormone-related or genetic factors, which have not been sufficiently explored so far, may play a role in the gender differences of IMT.

The Association between Bone Quality and Atherosclerosis: Results from Two Large Population-Based Studies.

OBJECTIVE: It is highly debated whether associations between osteoporosis and atherosclerosis are independent of cardiovascular risk factors. We aimed to explore the associations between quantitative ultrasound (QUS) parameters at the heel with the carotid artery intima-media thickness (IMT), the presence of carotid artery plaques, and the ankle-brachial index (ABI). METHODS: The study population comprised 5680 men and women aged 20-93 years from two population-based cohort studies: Study of Health in Pomerania (SHIP) and SHIP-Trend. QUS measurements were performed at the heel. The extracranial carotid arteries were examined with B-mode ultrasonography. ABI was measured in a subgroup of 3853 participants. Analyses of variance and linear and logistic regression models were calculated and adjusted for major cardiovascular risk factors. RESULTS: Men but not women had significantly increased odds for carotid artery plaques with decreasing QUS parameters independent of diabetes mellitus, dyslipidemia, and hypertension. Beyond this, the QUS parameters were not significantly associated with IMT or ABI in fully adjusted models. CONCLUSIONS: Our data argue against an independent role of bone metabolism in atherosclerotic changes in women. Yet, in men, associations with advanced atherosclerosis, exist. Thus, men presenting with clinical signs of osteoporosis may be at increased risk for atherosclerotic disease.

Endothelial-derived adhesion molecules in bacterial meningitis: association to cytokine release and intrathecal leukocyte-recruitment.

The release of circulating isoforms of selectin- (L-selectin, ELAM-1) and immunoglobulin-type- (ICAM-1) adhesion molecules, responsible for accumulation of leukocytes at sites of tissue injury was studied in CSF and serum of 21 patients with bacterial meningitis and in healthy subjects. Their concentrations were compared with the intrathecal leukocyte recruitment and release of inflammatory cytokines. In contrast to serum concentrations of the leukocyte-derived adhesion molecule, sL-selectin, serum concentrations of endothelial-derived adhesion molecules, sELAM-1 and sICAM-1, were significantly increased in meningitis. No intrathecal synthesis of these adhesion molecules was observed. Serum levels of sELAM-1 were associated with extent of CSF pleocytosis and with concentrations of proinflammatory cytokines IL-1beta and TNF alpha in CSF, but not in serum. Therefore, expression of endothelial adhesion molecules i.e. ELAM-1 may be responsible for the massive intrathecal recruitment of potentially harmful leukocytes in patients with bacterial meningitis. Intrathecally released proinflammatory cytokines may represent the inducing signals for their endothelial upregulation.

Three-dimensional power-mode ultrasound for quantification of the progression of carotid artery atherosclerosis.

Elucidation of the dynamic nature of plaque progression has important implications for clinicians. The present study sought to establish an in vivo method for visualizing structural changes in carotid plaques. Three-dimensional reconstruction of parallel two-dimensional gray-scale B-mode ultrasound combined with power-mode examination of 38 carotid artery plaques was performed in a prospective study of 32 patients (18 men, 14 women; mean age 67.5 +/- 7.6 years). Initial mean plaque volume was 391 microl. After a mean of 18.9 months carotid artery plaque progression had occurred in 15% of carotid artery plaques, with plaque volume increasing 59% in these cases. Plaque volume remained constant, within a range of +/- 20% in 85% of cases. Progressive plaques were predominantly hypoechoic (3/5 cases) or had an ulcerated surface in cases of a hyperechoic echogenicity (2/5 cases). Risk factors and drug therapy were unrelated to plaque progression. This study illustrates that the combination of three-dimensional ultrasound with power-mode imaging improves the separation of the intraluminal plaque surface from the vessel lumen. Three-dimensional reconstruction of atherosclerotic carotid artery plaques enables the reproducible quantification of plaque volume and is therefore an excellent technique for longitudinal trials assessing progression or regression of carotid artery disease.

Cerebrovascular involvement in the acute phase of bacterial meningitis.

Cerebral ischaemia is a common complication of bacterial meningitis. Although cerebrovascular involvement in the acute phase of inflammation may be particularly important for the still unacceptably high morbidity and mortality, only, a few studies have investigated cerebrovascular changes in bacterial meningitis. We prospectively investigated changes of intracranial cerebral blood flow velocities (CBFV) in 22 patients (12 men, 10 women, mean age 48 years, 19 years, SD) with bacterial meningitis, by means of transcranial Doppler sonography (TCD). According to previously published criteria the degree of arterial narrowing was assessed and related to the patients' outcome. Elevated CBFVs in the middle cerebral artery were documented in 18/22 patients with markedly increased systolic peak velocities (CBFV of > 210 cm/s) in 7 patients. Serial examinations performed in 11 patients showed elevated CBFV as early as day 1, reaching peak CBFV between day 3 and day 6 after onset of symptoms in most cases. Furthermore, cerebrovascular involvement was also documented by disturbances of physiological slow spontaneous oscillations of blood flow velocities in 5/10 patients examined with TCD. Low Glasgow Coma Scales (< 7) on admission (29% vs 0%), focal cerebral ischaemic deficits (29% vs 7%) and, seizures (43% vs 7%) were more frequent in patients with CBFV of > 210 cm/s. Finally, a poor clinical outcome was significantly related to severe vascular involvement (P < 0.05). In conclusion, cerebrovascular complications are frequently found in patients with bacterial meningitis. TCD is an easily applicable technique for revealing vascular changes non-invasively, even in severely ill patients. Since our data suggest an unfavourable course of the disease in association with increased CBFV in intracranial arteries, probably indicating vasospasm, TCD could potentially be used to identify high-risk patients who could benefit from adjuvant therapeutic interventions.

Three-dimensional transcranial color-coded sonography for the examination of the arteries of the circle of Willis.

Because examinations of the intracranial vessels using conventional transcranial color-coded sonography (TCCS) lack spatial orientation and reproducibility, development of a three-dimensional (3-D) imaging technique is required. Three patients with middle cerebral artery (MCA) stenosis, three with suspected intracranial aneurysm, two with vascular malformation, and one healthy volunteer were investigated by 3-D TCCS using a magnetic spatial positioning sensor mounted on the transducer for simultaneous recording of the probe coordinates to create a volumetric data set. Three-dimensional transcranial color-coded sonography enabled good visualization of intracranial aneurysms and MCA stenoses. However, it failed to detect morphological details in vascular malformations. In conclusion, 3-D TCCS is a promising technique that opens new perspectives in depicting intracranial vessels and provides volume measurement of intracranial aneurysms.

Three-dimensional ultrasound angiography (power mode) for the quantification of carotid artery atherosclerosis.

Three-dimensional (3D) ultrasound angiography was performed to diagnose carotid artery atherosclerosis. Thirty-five patients (15 women, 20 men) with a history of cerebrovascular disease were examined using conventional color-coded Doppler ultrasound and 3D ultrasound angiography. Carotid stenosis was initially diagnosed using continuous-wave Doppler ultrasound. To determine intraobserver and interobserver reliabilities, 21 patients were evaluated using 3D ultrasound on three occasions. Sixty-five percent of patients were diagnosed with stenosis of more than 50%. Twenty-two percent of plaques had a smooth surface, 72.9% were ulcerated, and 5.1% were indeterminate. Data collection for 3D imaging required 5 minutes per patient, whereas image processing and plaque volume quantification required 30 minutes. Plaque volume ranged from 0.053 to 0.685 ml. The intraobserver and interobserver variabilities were 4.16 and 5.87%, respectively (r = 0.96, p < 0.0001; r = 0.89, p < 0.0001). 3D Color Doppler and 3D ultrasound angiography assessments of plaque volume differed by 8.5%. Plaques were more precisely differentiated using 3D ultrasound, and plaque volume quantification was less affected by echo shadowing after 3D reconstruction. In comparison to other techniques for the quantification of atherosclerotic lesions. 3D ultrasound angiography offers a more precise quantitative method for prospective, clinical studies of atherosclerosis.

Volumetric assessment of plaque progression with 3-dimensional ultrasonography under statin therapy.

BACKGROUND AND PURPOSE: Lowering of serum cholesterol levels with HMG-CoA reductase inhibitors (statins) slowed the progression of atherosclerosis in the carotid arteries in several clinical trials using carotid artery intima media thickness as primary outcome measure. Whereas conventional ultrasonography is limited to thin 2-dimensional image planes, 3-dimensional (3D) ultrasonography provides quantitative measurement of the entire carotid artery plaque volume. This study aims to assess the feasibility of 3D ultrasonography to monitor plaque progression in hypercholesterolemic patients. METHODS: The authors prospectively assessed the progression of 31 carotid artery plaques over 15.1 +/- 4.5 months in a study of 23 patients (6 women, 17 men; mean age = 61.7 +/- 7.5 years) with hypercholesterolemia under therapy with HMG-CoA reductase inhibitors. All patients were maintained on a lipid-lowering diet. Sixteen patients were additionally treated with statins. Quantitative measurements of carotid artery plaque volumes were performed after 3D reconstruction of exactly parallel transverse duplex ultrasound scans (slice distance = 0.1 mm) into volumetric 3D data sets and segmentation of voxels representing the carotid artery plaque. RESULTS: Within the treatment group, plaques were significantly less frequently progressive if they had a hypoechoic echogenicity (11%, n = 9 vs 64%, n = 14; P = .016) or if baseline serum cholesterol levels were above 8.0 mmol/L (9%, n = 11 vs 75%, n = 12; P = .002). CONCLUSION: Three-dimensional ultrasonography extends the measurement of the arterial wall thickness to the 3D volume of an entire atherosclerotic plaque including analysis of its morphology and configuration. However, further clinical trials with an adequate sample size to achieve sufficient statistical power are necessary to assess the effect of statin therapy on plaque progression.

Transcranial power mode Doppler duplex sonography of intracranial aneurysms.

The application of different color-coding techniques in transcranial color-coded duplex sonography (TCCD) was assessed for detection and measurement of the size of intracranial aneurysms. Thirty-two consecutively examined patients with 36 angiographically verified cerebral aneurysms underwent TCCD with color Doppler flow imaging (CDFI), power Doppler imaging (PDI), and both methods with contrast enhancement. The diameters of the aneurysms were measured in comparable planes by means of angiography and TCCD-PD with and without 400 mg/ml of the monosaccharide microparticle contrast agent Levovist. TCCD with CFD enabled detection of 27 of 36 aneurysms (75%), and PD depicted 29 aneurysms (80%). After administration of Levovist, an additional two aneurysms were detected with CFD and three with PD color coding. Measurements of aneurysm size obtained by means of PD with contrast enhancement corresponded more highly with angiographic findings than did measurements obtained with PD alone. Use of alternative color-coding techniques with the addition of contrast agents increases the number of intracranial nonthrombosed aneurysms detectable with TCCD.

Bilateral cerebellar infarctions caused by a stenosis of a congenitally unpaired posterior inferior cerebellar artery.

Bilateral symmetrical cerebellar infarcts in the territory supplied by the medial posterior inferior cerebellar artery (PICA) branches are extremely rare. In the few cases published, it has not been possible to clearly pinpoint the cause of this infarct pattern. The authors present the case history of a 58-year-old man who had acute headaches accompanied by pronounced rotatory vertigo with nausea and vomiting. The neurological examination revealed bilateral cerebellar signs. Cranial magnetic resonance imaging showed bilateral, nearly symmetrical infarcts in the territory of the medial branches of both PICAs. These bilateral PICA infarctions were caused by a stenosis of an unpaired PICA originating from the left vertebral artery supplying both cerebellar hemispheres.

High intensity transient signals (HITS) in patients with carotid artery disease.

Interest in the Doppler ultrasound phenomenon of "High Intensity Transient Signals" (HITS) is based on the, thus far, unproven hypothesis, that these signals may to some extent represent silent cerebral microembolism ahead of a TIA/stroke and hence identify patients at risk for stroke. We prospectively investigated 80 patients with 102 moderate/severe internal carotid artery lesions. Patients with additional potential sources of cerebral ischemia were excluded. Bilateral transcranial Doppler monitorings of the middle cerebral arteries (MCA) were performed for =>30 min. HITS occurred more often in patients with completed stroke (21.9%) than in patients with transient ischemic deficits (12.5%), but significantly less in asymptomatic subjects (4.3%) (p<0.05). The incidence was maximal in patients examined within the first week after the onset of stroke. HITS were significantly more often associated with severe (> 70%) (23.5%) than with moderate (50 - 70%) internal carotid artery stenosis (3.4%) (p<0.05). These figures are closely related to annual stroke risk estimates recently reported about patients evaluated in multi-centre trials for carotid endarterectomy, and support the concept that HITS associated with carotid disease represent an important individual risk predictor.

[Sonographic diagnostics in neurological emergency and intensive care medicine]. / Sonographische Diagnostik in der neurologischen Notfall- und Intensivmedizin.

BACKGROUND: This article gives an up-to-date overview of neurosonographic emergency and intensive care diagnostics. METHODS: Selective literature research from 1984 with critical appraisal and including national and international guidelines. RESULTS: Fast and valid diagnostics in acute stroke is the main field of application of neurosonography. Specific monitoring methods bear great advantages for intensive care patients, especially "as-often-as-wanted" repetitive imaging under real-time conditions. A number of new developments make neurosonography an interesting area of research. CONCLUSIONS: Neurosonography has played a key role in neurological emergency and intensive care medicine for many years. It remains important to continuously support dissemination of the method.

Long-term health-related quality of life after decompressive hemicraniectomy in stroke patients with life-threatening space-occupying brain edema.

BACKGROUND: Although randomized clinical trials have reported significant improvement in mortality and functional outcome as measured with modified Rankin Scale (mRS) or Barthel index (BI) in stroke patients with space-occupying anterior circulation infarctions treated with hemicraniectomy, many clinicians are still concerned about the long-term health-related quality of life (HRQoL). AIM: Assessment of HRQoL after hemicraniectomy to holistically reevaluate clinical outcome. METHODS: Eleven patients (6 men, 5 women; mean age 48 (SD 5.8) years) were examined at 9-51 months after hemicraniectomy. Test batteries comprised NIH stroke scale, BI, mRS, neuropsychological tests (Visual Object and Space Perception Battery and clock test), and HRQoL-scales (Short Form 36 Health Survey (SF-36), Nottingham Health Profile (NHP), Questions on Life Satisfaction, Hospital Anxiety and Depression Scale and EQ-5D). RESULTS: Median values for NIHSS, BI and mRS were 11.5, 55 and 3.5. In HRQoL-scales, subscales related to physical mobility and functioning were consistently severely impaired, while subscales related to psychological well-being were impaired to a lesser extent. Mean scores for physical functioning and physical role were 10.5 and 12.5 in the SF-36, and 61.3 and 43.3 for physical mobility and energy in the NHP; emotional role and mental health scored 63.3 and 66.4 (SF-36), scores for emotional reaction and social isolation were 18.9 and 16.0 (NHP), respectively. CONCLUSION: Although, physical components of HRQoL are highly impaired, these stroke patients achieved a satisfying level of psychological well-being which was endorsed by a nearly unanimous retrospective appraisal of life-saving hemicraniectomy.