[Neurologic ultrasound education according to the DEGUM and DGKN guidelines].
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Curriculum↗
Biomedical subjects
M Kaps
Publications and source records attributed to M Kaps.
Cell surface bound and soluble adhesion molecules in CSF and blood in multiple sclerosis: correlation with MRI-measures of subclinical disease severity and activity.
BACKGROUND: The expression of soluble cell adhesion molecules (AM) in cerebrospinal fluid (CSF) and blood and their significance as measures of disease activity has been extensively studied in patients with multiple sclerosis (MS). In previous studies, we found that cell surface bound AM on mononuclear cells (MNC) in CSF and blood might be useful markers of clinical disease activity in MS patients. OBJECTIVE: To analyze the correlation of cell surface bound and soluble AM in CSF and blood with magnetic resonance imaging (MRI) markers of subclinical disease severity and activity in patients with MS. METHODS: Expression levels of cell surface bound AM on peripheral blood and CSF MNC were determined by flow cytometry analysis in 77 (CSF: 33) MS patients. Concentration levels of the soluble forms of AM were measured by enzyme-linked immunosorbent assay (ELISA). In corresponding cerebral gadolinium (Gd)-enhanced MRI scans, we determined both measures of subclinical disease severity and subclinical disease activity. RESULTS: The expression levels of cell surface bound AM in peripheral blood correlated inversely with parameters for subclinical disease severity and activity on cerebral MRI scans as well as with the disease duration. Furthermore, we found significant correlations between serum levels of soluble AM and patient age but not with disease duration. CONCLUSIONS: Our results suggest that subclinical disease progression may be associated with a decrease of the expression of cell surface bound AM on peripheral blood MNC. This might be a result of activated MNC migration into the CNS.
Adult↗
Serum cytokine levels do not correlate with disease activity and severity assessed by brain MRI in multiple sclerosis.
OBJECTIVE: Chronic and acute dysregulation of the cytokine network has been described in multiple sclerosis (MS). Inflammatory lesions in the central nervous system of MS patients can be assessed by brain magnetic resonance imaging (MRI). This study has been performed to investigate whether changes of cytokines correlate with morphological changes as determined by MRI. MATERIALS AND METHODS: We included 46 patients with relapsing-remitting MS in the study. The serum concentrations of tumor necrosis factor-beta (TNF-beta), TNF receptor-1 (TNFR-1; 55 kDa) and TNFR-2 (75 kDa), interleukin-4 (IL-4), interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) were measured by enzyme linked immunosorbent assay in all patients. Each parameter was correlated with clinical findings and brain MRI parameters. We measured both the number (lesion load) and cumulated area (disease burden) of all lesions on brain MRI. In addition, the number and cumulated area of those lesions showing signs of activity [Gadolinium (Gd)-enhancement, perifocal edema] were determined. RESULTS: A non-significant trend (P < 0.05) was found only for the correlation of serum IFN-gamma levels and the number of active MRI lesions showing both Gd-enhancement and perifocal edema in the subgroup of patients (n=21) with active lesions. When corrected for multiple comparisons, this correlation was not significant anymore, as it was above the corrected P-value of 0.001. We could not observe any further correlation of cytokine levels and MRI parameters. However, TNF-beta serum levels were significantly (P < 0.05) elevated in the patient subgroups with higher number of lesions and disease burden, respectively. CONCLUSION: Our data show that the determination of serum levels of the investigated cytokines and cytokine receptors is not useful as a tool to determine subclinical disease activity and severity as assessed by brain MRI.
Adult↗
Disturbance in the serum IgG subclass distribution in patients with anti-Hu positive paraneoplastic neurological syndromes.
Autoantibodies in patients with paraneoplastic neurological syndromes (PNS) have been reported to be predominantly IgG1 and IgG3 isotypes. However, no data are available about the IgG subclass distribution of the total serum IgG in these patients. Therefore, we investigated the IgG subclass distribution (given as percentage of total IgG) in 15 anti-Hu positive PNS patients, 15 patients with small cell lung cancer (SCLC) without PNS and 23 healthy controls using a commercial enzyme-linked immunosorbant assay test. Although IgG1 (and to a lower extent IgG3) are the predominant subclasses of the anti-Hu antibodies, PNS and SCLC showed a significant decrease in IgG1 and a concomitant increase in IgG2 compared with healthy controls (P < 0.05, respectively). In contrast, only SCLC patients, but not PNS patients, had higher IgG3 and IgG4 values compared with controls (P < 0.05, respectively). There was no correlation between IgG subclass levels and the titre or the predominant isotype of the antineuronal antibodies. PNS patients with autonomic disturbances had lower IgG4 levels than PNS patients without autonomic disturbances (P < 0.05). Our study demonstrates a disturbance in the IgG subclass distribution in PNS patients which is partly different from SCLC patients. The isotype regulation of the anti-Hu antibody seems to be independent from this phenomenon.
Autoantibodies↗
Circulating microemboli after composite replacement or valve-sparing aortic root surgery.
BACKGROUND: The purpose of this study was to determine whether microembolic signals (MES) occur after valve-sparing operations on the aortic root. One of the advantages of these procedures relates to the freedom of macroemboli without anticoagulation. Whether this holds true for circulating microemboli has not yet been verified. METHODS: For comparison, 8 male patients (mean age: 51.8 +/- 12.8 years) were investigated 20.5 +/- 8.4 months after implantation of a mechanical composite graft (group I) and 9 female and 7 male patients (mean age 55.0 +/- 13.4 years) 23.5 +/- 20.0 months after valve-sparing replacement of the aortic root (group II). The middle cerebral artery was insonated for 2 periods of 30 min, breathing room air or O 2 at 9 l/min. RESULT: Breathing room air, the amount of MES was considerably smaller in group II (0.94 +/- 1.95 vs. 56.1 +/- 58.9 per 30 min, p = 0.006). The difference was less pronounced (0.5 +/- 1.3 vs. 28.9 +/- 42.6 per 30 min, p = 0.009) breathing oxygen. Breathing oxygen reduced MES significantly in group I (p < 0.05) but not in group II (p > 0.05). CONCLUSIONS: Aortic valve-sparing operations induce MES at a significantly lower rate than composite aortic valve replacement using a mechanical valve.
Aorta↗
Feasibility and validity of transcranial duplex sonography in patients with acute stroke.
OBJECTIVES: To evaluate in a prospective multicentre setting the feasibility of transcranial colour coded duplex sonography (TCCS) for examination of the middle cerebral artery (MCA) in patients with acute hemispheric stroke, and to assess the validity of sonographic findings in a subgroup of patients who also had a correlative angiographic examination. METHODS: TCCS was performed in 58 consecutive patients within six hours of the onset of a moderate to severe hemispheric stroke. Ultrasound contrast agent (Levovist) was applied if necessary. Thirty two patients also had computed tomography angiography (n=13), magnetic resonance angiography (n=18), or digital subtraction angiography (n=1). In 14 of these patients, both the sonographic and corresponding angiographic examination were performed within six hours of stroke onset (mean time difference between TCCS and angiography 0.8 hours). Eighteen patients, in whom angiography was carried out more than 24 hours after stroke onset, had a follow up TCCS for method comparison (mean time difference 6.1 hours). RESULTS: Initial unenhanced TCCS performed 3.4 (SD 1.2) hours after the onset of symptoms depicted the symptomatic MCA mainstem in 32 patients (55%) (13 occlusions, one stenosis, 18 patent arteries). After signal enhancement, MCA status could be determined in 54 patients (93%) (p<0.05), showing an occlusion in 25, a stenosis in two, and a patent artery in 27 patients. In 31 of the 32 patients who had correlative angiography, TCCS and angiography produced the same diagnosis of the symptomatic MCA (10 occlusions, three stenoses, 18 patent arteries); TCCS was inconclusive in the remaining one. CONCLUSION: TCCS is a feasible, fast, and valid non-invasive bedside method for evaluating the MCA in an acute stroke setting, particularly when contrast enhancement is applied. It may be a valuable and cost effective alternative to computed tomography and magnetic resonance angiography in future stroke trials.
Acute Disease↗
Cerebral autoregulation in middle cerebral artery territory precedes that of posterior cerebral artery in human cortex.
OBJECTIVE: Cerebral autoregulation tends to compensate changes in arterial blood pressure. This mechanism of cerebral blood flow regulation appears to be insufficient in orthostatic dysregulation in which mainly vertebrobasilar symptoms occur. To investigate this hypothesis, we compared cerebral autoregulation in the vascular territory of the carotic and vertebrobasilar vessel system using a leg cuff test to induce a drop in cerebral perfusion pressure. METHODS: We measured blood flow velocity in 10 healthy young volunteers (aged 26.7 +/- 0.3 years, 7 male) simultaneously in the middle and posterior cerebral artery with transcranial Doppler sonography. A leg cuff test was used to induce a sudden decrease in arterial blood pressure. Arterial blood pressure was measured with a non-invasive photoplethysmographic method. The averaged relative blood flow velocity changes due to the pressure step were compared between both vessel territories. RESULTS: After cuff release systolic (diastolic) blood flow velocity increased with a latency of 1.1 +/- 0.3 s (1.8 +/- 0.4 s). Due to a smaller decrease and identical time courses cerebral blood flow velocity recovery in the posterior cerebral artery precedes blood flow recovery in the middle cerebral artery by 0.9 +/- 0.3 s. DISCUSSION: Cerebral autoregulation in the carotid and vertebrobasilar system does not differ in the time course of the blood flow velocity recovery. Due to a smaller decrease in blood flow velocity recovery in the posterior cerebral artery precedes recovery in the middle cerebral artery by nearly 1 s.
Adult↗
Peak systolic velocity Doppler index reflects most appropriately the dynamic time course of intact cerebral autoregulation.
BACKGROUND: Transcranial Doppler sonography measures blood flow velocity in basal cerebral vessels with high accuracy and time resolution. Dynamic blood flow tests were used to investigate functional integrity of the cerebral autoregulation (CA) mechanism. It is known from cortical activation studies that velocity indices differ in their appropriateness to measure changes in blood flow velocity. We aimed to compare the peak systolic, end diastolic and time-averaged mean flow velocity indices for their use in measuring the effectiveness of the CA mechanism. METHODS: We performed the leg cuff test to induce in 15 healthy volunteers (aged 24.8 +/- 0.4 years, 9 males) CA due to a sudden arterial blood pressure decrease. Data from the middle and posterior cerebral arteries were measured continuously with transcranial Doppler ultrasound, and the arterial blood pressure with a noninvasive photoplethysmographic method. After transforming all variables to relative changes, velocity-pressure diagrams were calculated for each velocity-pressure index. Additionally, we calculated the autoregulation index. RESULTS: The step decrease in arterial blood pressure resulted in an initial drop, which is followed by a rapid recovery of cerebral blood flow velocity. The autoregulation index was 5.5 +/- 1. Efficacy of CA is illustrated more accurately by peak systolic velocity-pressure curves, which lie continuously above a passive velocity-pressure relationship assuming CA to be absent. CONCLUSIONS: Our data show peak systolic blood flow velocity index to be most accurate for measuring effectiveness of the dynamic CA mechanism. No differences in the CA were found between the vascular territory of the middle and posterior cerebral arteries.
Adult↗
Neurovascular coupling remains unaffected by glyceryl trinitrate.
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Adult↗
[Evaluation of stroke units as medical technology].
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Emergency Medical Services↗
Neurovascular coupling and cerebral autoregulation can be described in terms of a control system.
Neurovascular coupling and cerebral autoregulation are important and fast mechanisms for maintaining an adequate blood supply to the brain. It was suggested that both mechanisms follow a common control system. The aim of our study was to describe neurovascular coupling and cerebral autoregulation in mathematical terms of a control system and to test the aforementioned hypothesis. We analyzed the input-output dynamics of neurovascular coupling (flicker light test) and cerebral autoregulation (leg cuff test) in terms of a control system, and compared both systems. A transcranial Doppler device was used to measure continuously the blood flow velocity changes in young healthy volunteers who lacked vascular risk factors. For both tests, a control system model with only four parameters was sufficient to allow the vascular reaction to be described in all (rate time, undamped natural angular frequency, attenuation, gain). All parameters were identical for both control systems, except for gain, which is not directly comparable because, in the flicker light test, input function was not measured but assumed as a unit step function in each volunteer. This new method permits description of the regulation of cerebral blood flow using a control loop with four parameters. For the first time, these parameters allowed a demonstration that cerebral autoregulation and neurovascular coupling could be governed by the same control system.
Adult↗
Neurovascular coupling in terms of a control system: validation of a second-order linear system model.
Neurovascular coupling (NC) adapts cerebral blood flow to cortical activity. Functional transcranial Doppler (f-TCD) investigations revealed a typical time course of evoked blood flow responses with an initial overshoot and a stabilization at a lower, but stable, level. This blood flow reaction can be described in terms of a control-system model. We tested reliability and validity of this new approach using different stimulation paradigms. The P2 segment of the posterior cerebral artery was insonated in 14 healthy volunteers and, subsequently, NC was stimulated using two tests, a checkerboard stimulus of 1 s with different repetition rates and a reading test. Data were analyzed according to algorithms of control-system theory. The reading test was used to measure test reliability and side differences. A second-order linear system can describe blood flow regulation of NC. Different stimulation protocols of the checkerboard test and the related evoked blood flow curves could be described by the same control-system model. Further, there were no differences between the checkerboard and reading test nor between right and left side or test and retest of the reading test. NC can be described in a much more detailed manner using control-system analysis. We were able to show that blood flow response due to different visual stimuli follow one common control-system model. Unlike quantification of NC using overshoot, parameters of the control system have smaller SDs, increasing the statistical power and, thereby, usefulness of f-TCD as a diagnostic instrument.
Adult↗
Comparison of visually evoked peak systolic and end diastolic blood flow velocity using a control system approach.
Transcranial Doppler sonography measures blood flow velocity in basal cerebral vessels with high accuracy. For quantification, time averaged mean blood flow velocities are used most because the peak systolic and end diastolic blood flow velocities mark the velocity extremes of one heart cycle. It is known, from hemodynamic measurements of the neurovascular coupling mechanism, that the end diastolic velocity is more sensitive for change in hemodynamics than the peak systolic velocity. Thus, we used a recently introduced control system approach to compare both indices for their use in functional transcranial Doppler tests focusing on hemodynamics of blood flow velocity change. We enrolled 65 healthy young volunteers without a medical history of cardiovascular risk factors, and performed a visual stimulation test. Peak systolic and end diastolic maximal blood flow velocities were used after transformation to relative data for control-system analysis. Due to Doppler artefacts, 95% of peak systolic and 86% of end diastolic data sets were analyzed. Results showed statistically significant differences for resting blood flow velocity and the control system parameter gain, attenuation and rate time, whereas the parameters' natural frequency and time delay were equal. Increase in relative blood flow velocity in the posterior cerebral artery due to visual-cortical stimulation was higher in end diastolic values than peak systolic data. Using a complex visual stimulation paradigm, the higher sensitivity of the end diastolic index is of no practical use. Being less influenced by Doppler artefacts, the peak systolic velocity index is more feasible for control-system analysis of dynamic blood flow regulation.
Adult↗
Induction of sTNF-R1 and sTNF-R2 by interferon beta-1b in correlation with clinical and MRI activity.
OBJECTIVES: To investigate the influence of interferon (IFN) beta-1b on the serum levels of sTNF-R1, sTNF-R2 and TNF-beta in patients with multiple sclerosis (MS) in correlation with clinical and MRI activity. MATERIALS AND METHODS: Serum samples were obtained every 3 months from 24 patients treated with 8 x 10(6) U of IFN beta-lb every other day (treatment group) and from 21 patients without any immunomodulatory therapy (control group) over a 15-month observation period. The cytokine levels were measured by ELISA. Cranial MRI was performed every 6 months to determine the burden of disease of every patient. RESULTS: In the treatment group we found an obvious increase of sTNFR1 and sTNF-R2 (P < 0.001) and relatively stable serum levels of TNFbeta with no statistical significance (P = 0.56). In the control group, sTNF-R1 showed a significant decrease (P < 0.001) during the same observation period of 15 months. During the 15-month observation period, the MRI-responders group had significant larger mean AUC (area under the concentration-time curve) values of sTNF-R1 (P = 0.04) and sTNF-R2 (P = 0.01) when compared to the group of MRInonresponders. CONCLUSION: The present data suggest that IFN beta-1b induces the expression and shedding of TNF-R1 and TNF-R2. The magnitude of an increase of sTNF-Rs may be a marker for the effectiveness of treatment with IFN beta-1b.
Adjuvants, Immunologic↗
SonoVue in transcranial Doppler investigations of the cerebral arteries.
BACKGROUND AND PURPOSE: The authors investigated the safety and diagnostic potential of a new ultrasound contrast agent (SonoVue) using transcranial color-coded duplex sonography (TCCS). METHODS: Forty patients were enrolled in a multicenter, open-label (on-site), blind (off-site), randomized, dose-ranging crossover study. SonoVue was administered as an intravenous bolus injection of 4 different dosages (0.3, 0.6, 1.2, and 2.4 mL). Efficacy was evaluated as (1) off-site assessment of global quality of the Doppler investigation (based on color or power Doppler images and spectral analysis) at baseline and following each dose of SonoVue according to a 4-point scale (from very poor to excellent imaging of blood flow) and (2) duration of clinically useful signal enhancement and color or power Doppler visualization of blood flow. Additional on-site efficacy assessments performed following each dose of SonoVue included confidence in diagnosis and global consequences of contrast enhancement on diagnosis. Safety evaluations included clinical laboratory tests, neurological examination, injection site tolerability, and incidence of adverse events and their relationship to the study agent. RESULTS: All doses of SonoVue significantly improved the global quality of Doppler examinations (P < .05). The median duration of clinically useful enhancement was dose related (P < .001) and ranged from 2 to 6 minutes at the highest dose. The administration of the contrast agent changed a nondiagnostic study to a diagnostic one in 66% of patients and increased the confidence in diagnosis in 74% of cases. No serious adverse events were recorded following SonoVue administration. The observed adverse reactions were all transient and mild in intensity. CONCLUSIONS: The results obtained from this multicenter study demonstrate that the administration of SonoVue to patients with ischemic cerebrovascular disease who undergo TCCS examination of cerebral vessels improves the visualization of intracranial arteries, providing a dose-dependent contrast enhancement and a clinically useful duration of signal enhancement related to the dose. During this multicenter study, SonoVue proved to be a safe and well-tolerated compound.
Analysis of Variance↗
Pharmacokinetics of echocontrast agent infusion in a dog model.
Ultrasound contrast agents (UCAs) have a distinct diagnostic impact on transcranial Doppler (TCD) and duplex sonography. In addition to the properties of the UCA and ultrasound imaging modes, the duration of contrast enhancement depends on the administration mode. Infusion of UCAs may be appropriate for prolonging the diagnostically useful time of elevated Doppler intensity. Five sedated dogs were investigated by TCD during infusion with SonoVue, a new UCA consisting of sulfur hexafluoride microbubbles. The infusion rate was varied, and the time-intensity curves were analyzed. Infusion rate of 70 ml/h provided a stable mean level of increased Doppler intensity up to 24 to 26 dB over baseline, whereas a rate of 35 ml/h did not result in a stable plateau (range 8-19 dB over baseline [5 minutes after starting time]). The maximum increases in Doppler mean intensity (18.2 dB [35 ml/h] and 25.6 dB [70 ml/h]) were significantly different (P = .025). Pharmacokinetic analysis of SonoVue during inflow (by exponential functional fitting of the time-mean intensity curves) and elimination (by linear regression analysis) revealed no dose-related differences. This study demonstrated a dose-dependent level of increased Doppler mean intensity within the brain circulation during infusion of SonoVue. Unlike the bell-shaped course of Doppler signal enhancement seen after bolus injection, infusion generates a stable plateau, which is an important prerequisite for more advanced contrast applications.
Analysis of Variance↗
Interobserver and intraobserver reliability of venous transcranial color-coded flow velocity measurements.
BACKGROUND AND PURPOSE: Venous transcranial color-coded duplex sonography is a new technique for noninvasive evaluation of the intracranial venous system. However, the interobserver and intraobserver reliability of this method is unclear. METHODS: In 23 healthy volunteers (30 +/- 7.3 years of age), the deep middle cerebral vein (dMCV), basal vein (BV), vein of Galen (VG), and straight (SRS), transverse (TS), and superior sagittal (SSS) sinuses in addition to the arterial segments of the circle of Willis were insonated through the temporal bone window on 2 consecutive days by 2 experienced examiners. The examiners were blinded to each other's results. The interobserver and intraobserver reliability was calculated using a method described by Bland and Altman, resulting in 2-SD confidence intervals. RESULTS: Non-angle-corrected and angle-corrected systolic and end diastolic venous flow velocities (FV) were in good accordance with published normal values, ranging between 8.6 and 19.2 cm/s. The interobserver reliabilities for non-angle-corrected systolic FVs in the dMCV, BV, VG, SRS, and TS were +/- 1.8, 2.4, 2.6, 3.3, and 4.6 cm/s; for angle-corrected systolic FVs, the interobserver reliabilities were +/- 2.5, 3.1, 13.9, 11.6, and 7.7 cm/s. The intraobserver reliabilities for non-angle-corrected systolic FVs in the dMCV, BV, VG, SRS, and TS were +/- 2.9, 3.2, 2.6, 3.2, and 6.1 cm/s; for angle-corrected systolic FVs, the intraobserver reliabilities were 3.2, 3.7, 13.9, 11.6, and 7.5 cm/s. Angle correction was not attempted for the SSS. The interobserver and intraobserver reliabilities for systolic FVs in the SSS were +/- 3.3 and +/- 3.3 cm/s, respectively. CONCLUSIONS: Intracranial venous FVs can be measured with a high interobserver and intraobserver reliability in healthy human subjects. Intraobserver reliability was higher for cerebral veins than for dural sinuses, predisposing them for follow-up examinations; however, angle correction for venous FVs in the VG and the SRS is not advisable.
Adult↗
Prognostic value of soluble tumor necrosis factor receptors 1 and 2 in multiple sclerosis patients treated with interferon beta-1b.
The objective of this study was to investigate the effect of interferon (IFN) beta-1b on the serum levels of soluble tumor necrosis factor receptor 1 (sTNF-R1) and sTNF-R2 in patients with multiple sclerosis (MS) in correlation with clinical and magnetic resonance image (MRI) activity. Serum samples were obtained every 3 months from 24 patients treated with 8 x 10(6) U of IFN beta-1b every other day (treatment group) and from 21 patients without any immunomodulatory therapy (control group) over a 15-month observation period. The cytokine receptor levels were assessed by ELISA. Cranial MRI was performed every 6 months to determine the burden of disease. In the treatment group, the MRI responders had significantly larger mean values for the area under the concentration-time curve of sTNF-R1 (p = 0.04) and sTNF-R2 (p = 0.01) when compared to the MRI nonresponders during the 15-month observation period. With regard to an increase in sTNF-R1 and -2 of more than 20% during the first 3 months of treatment, we observed a sensitivity of 33 and 58%, respectively, a specificity of 90 and 60%, respectively, and a positive predictive value of 80 and 64%, respectively, for MRI response during the 15-month observation period. A decrease in sTNF-R1 and -2 of more than 20% during the first 3 months of treatment had a sensitivity of 40 and 20%, respectively, a specificity of 100 and 100%, respectively, and a positive predictive value of 100 and 100%, respectively, for further MRI nonresponse (during the 15-month observation period). The present data suggest that assessment of sTNF-Rs may contribute to the identification of subgroups of patients who are likely to respond better than others to treatment with IFN beta-1b. This could help to establish a cost-effective prescription pattern for this expensive treatment, which is of importance for the future management of patients with MS.
Adult↗