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Biomedical subjects

Manfred Kaps

Publications and source records attributed to Manfred Kaps.

At least 37 records · Page 2Linked to original sources
PubMed2005

A new model of reversible sinus sagittalis superior thrombosis in the rat: magnetic resonance imaging changes.

OBJECTIVE: The causes of cerebral sinus and vein occlusion and the accompanying parenchymal changes remain largely unexplained. The clinical variability and low incidence of the disease complicate systematic clinical investigations. Animal studies are indispensable; however, existing animal models of sinus thrombosis do not allow for long-term follow-up studies and are not suitable for pharmacological recanalization because sinus thrombosis is induced by ligation and injection of thrombogenic substances and does not resemble sinus thrombosis in humans. METHODS: We induced thrombosis of the superior sagittal sinus (SSS) by careful topical application of ferric chloride onto the SSS of rats, leading to highly reproducible occlusions. Magnetic resonance imaging was performed immediately after initiation of thrombosis and on postoperative Days 1, 2, and 7. Diffusion- and T2-weighted images allowed for calculation of the apparent diffusion coefficient and T2 relaxation time. Vascular status was assessed by venous magnetic resonance angiography. Neurological deficits were assessed with the rotarod test. RESULTS: Seven days after induction of thrombosis, partial recanalization (50.7% of the SSS remaining occluded) was accompanied by a resolution of early generalized changes of the apparent diffusion coefficient and of T2 relaxation time, indicating edema of the entire brain parenchyma. Compared with sham-treated animals, clinical skills in the experimental group improved over time, which was statistically independent from the degree of recanalization. Histopathological analysis revealed no signs of cerebral infarction. CONCLUSION: This is the first animal model of SSS thrombosis that offers the possibility to investigate pathophysiological aspects of the disease as well as the influence of therapy on the nature of disease progression.

Animals↗
PubMed2005

Reversible MR imaging abnormalities following cerebral venous thrombosis.

BACKGROUND AND PURPOSE: Although rare, cerebral venous thrombosis (CVT) is being diagnosed more frequently owing to improved imaging techniques. The venous infarcts caused by CVT in 50% of patients are largely reversible and differ from arterial stroke. Our purpose was to study the time-dependent changes of venous infarcts on MR images and to define the variables that influence lesion volume in humans. METHODS: MR images and venous angiograms were evaluated in 15 consecutive patients with venous infarcts due to CVT of sinus, cortical, or internal veins. All patients were treated with intravenous dose-adjusted heparin followed by oral anticoagulation for 12 months. Reduction of signal intensity changes on T1- and T2-weighted images was correlated to the degree of recanalization, age, initial absolute lesion size, and hemorrhage. RESULTS: Within the first 30 days, we found a significant correlation between the volume of the lesion on T1-weighted images and recanalization. However, early recanalization did not influence the final lesion volume after 12 months. Eleven patients showed complete resolution of changes on T1- and T2-weighted images. Age of the patients influenced initial absolute volume of brain damage. CONCLUSION: In venous stroke, even large parenchymal changes can resolve completely independent from recanalization of the thrombosed veins and sinuses. A plausible hypothesis is that venous infarcts largely consist of a persistent edema and that the lesion volume is influenced by the development of collateral veins. However, further investigations are necessary to understand the underlying abnormal mechanisms.

Administration, Oral↗
PubMed2004

Complications and pitfalls in rat stroke models for middle cerebral artery occlusion: a comparison between the suture and the macrosphere model using magnetic resonance angiography.

BACKGROUND AND PURPOSE: Investigating focal cerebral ischemia requires animal models that are relevant to human stroke. Complications and side effects are common among these models. The present study describes potential pitfalls in 3 techniques for middle cerebral artery occlusion (MCAO) in rats using magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). METHODS: Rats were subjected to temporary MCAO for 90 minutes using the suture technique (group I; n=10) or to permanent MCAO using the suture technique (group II; n=10) or the macrosphere technique (group III; n=10). Clinical evaluation was performed after 3 hours and 24 hours. After 24 hours, animals underwent MRI and MRA to determine lesion size and the intracranial vascular status. RESULTS: Hemispheric lesion volume was significantly smaller in group I (14.6%) compared with groups II (35.2%; P<0.01) and III (21.3%; P<0.05). Two animals (1 each in group II and III) did not demonstrate neurological deficits and had no lesion on MRI and a patent MCA main stem on MRA. Subarachnoid hemorrhage was detected in 2 animals (1 each in group I and II). MRA indicated a patent MCA main stem in 2 animals (group II), although both rats displayed neurological deficits. Hypothalamic infarction with subsequent pathological hyperthermia was detected in all animals in group II and in 1 rat in group III. CONCLUSIONS: Model failures occurred frequently in all groups. MRI and MRA helps to identify animals that need to be excluded from experimental stroke studies.

Animals↗
PubMed2004

Diffusion-weighted magnetic resonance imaging and neurobiochemical markers after aortic valve replacement: implications for future neuroprotective trials?

BACKGROUND AND PURPOSE: Cardiac surgery carries a high risk of neurological complications; therefore, these patients would be an appropriate target population for neuroprotective strategies. In this study, we evaluated postoperative diffusion-weighted imaging (DWI) as a potential surrogate marker for brain embolism and its relationship to neurobiochemical markers of brain injury. METHODS: Of a total of 45 consecutive patients undergoing aortic valve replacement, 37 completed preoperative and postoperative MRI. At the time of the MRI studies, serum S100beta and neuron-specific enolase concentrations were determined. Preexisting T2 and postoperative DWI lesion volumes were quantified. All patients had a blinded neurological examination before and after operation. RESULTS: New perioperative DWI lesions were present in 14 patients (38%), of whom only 3 developed focal neurological deficits. Eighteen small lesions were found in the white matter or vascular border zones in all but 2 patients with territorial stroke. The appearance of new DWI lesions correlated with age, pre-existing T2 lesion volume, and postoperative S100beta concentrations on days 2 to 4 after surgery. In a forward stepwise canonical discrimination model, only T2 lesion volume was selected as a relevant variable. CONCLUSIONS: The incidence of postoperative DWI lesions in aortic valve replacement is high, and a suitable marker for neuroprotective trials would be a reduction in the number of such lesions. The volume of preexisting T2 lesions is related to the development of perioperative DWI lesions.

Aged↗
PubMed2004

Influence of recanalization on outcome in dural sinus thrombosis: a prospective study.

BACKGROUND AND PURPOSE: Recanalization in dural sinus thrombosis (DST) has been observed previously; however, systematic prospective data are lacking. The influence of recanalization on DST outcome has not yet been thoroughly evaluated. METHODS: Thirty-seven consecutive patients with DST were prospectively examined. Neurological deficits were graded with the National Institutes of Health Stroke Scale (NIHSS) on hospital admission and discharge. Functional outcome was assessed with the modified Rankin Scale (mRS) on hospital discharge and after 12 months. All patients were treated with intravenous heparin in the acute stage of illness, followed by oral anticoagulation for 12 months. Imaging follow-up with MR angiography and, in a few cases, with CT or conventional angiography was performed on hospital discharge and after 6 and 12 months. RESULTS: Twelve-month functional outcome was excellent in 89% of patients with an mRS of 0 or 1. A recanalization rate of 60% was already observed on hospital discharge (22+/-6 days); thereafter, recanalization rates increased insignificantly. Early recanalization was not related to NIHSS score on hospital discharge or an mRS of 0 on discharge or after 12 months. CONCLUSIONS: We found a high frequency of early recanalization but without influence on clinical outcome parameters. Frequent imaging follow-ups in DST are not useful because they provide no information on patient outcome.

Adult↗
PubMed2004

Strategies for the reduction of cerebral microembolism during transmyocardial laser revascularization.

BACKGROUND AND OBJECTIVES: During transmyocardial laser revascularization (TMLR), multiple microembolic signals (MES) can be detected in cerebral arteries. We sought to characterize composition and clinical relevance of these MES and to evaluate strategies to reduce cerebral microembolization during TMLR. STUDY DESIGN/MATERIALS AND METHODS: TMLR was performed in pigs. Laser energy was set to 4-10 J (group A) or 80 J (group B). Oxygen concentration was varied between 21 and 100%. MES were recorded in the ophthalmic artery. Brain and spinal cord were investigated histologically after 10 days. RESULTS: More MES could be detected during high- compared to low-energy laser procedures. Ventilation with 100% oxygen reduced the number of MES. No lesions were found on histology. CONCLUSIONS: The number of MES depends on the laser energy. Laser-induces cavitation-effects lead to an additional release of nitrogen bubbles. Thus, the microembolic load can be reduced by ventilation with 100% oxygen and by decreasing the laser energy.

Animals↗
PubMed2004

Interferon-beta 1b leads to a short-term increase of soluble but long-term stabilisation of cell surface bound adhesion molecules in multiple sclerosis.

Adhesion molecules (AMs) are believed to regulate the transmigration of blood leukocytes across the blood-brain barrier (BBB), which is an essential step in the pathogenesis of multiple sclerosis (MS). Previous studies have investigated changes of the soluble forms of AM during interferon-beta1b (IFN-beta1b) treatment in MS patients. In this study, we analysed the influence of IFN-beta1b treatment on the cell surface bound forms of the AMs cICAM-1 and cICAM-3 on blood mononuclear cells (MNC). Sixty-eight patients with relapsing-remitting MS were enrolled in this open study; thirty of them were treated with IFN-beta1b. Blood samples were collected every three months over a period of 18 months. The expression levels of cell surface bound forms of AM on blood MNC were measured by two colour flow cytometry analysis. sVCAM-1, sICAM-1 and sICAM-3 were determined by ELISA. We found a short-term induction effect on the serum concentrations of sICAM-1 and sVCAM-1 after three months of IFN-beta1b treatment. The expression levels of cell surface bound AMs on blood MNC remained stable during treatment. Untreated MS patients, however, showed a continuous decrease in the expression of cell surface bound AM expression over 18 months. Stabilisation of the expression of cell surface bound AMs on blood MNC may indicate the beneficial effects of IFN-beta1b therapy in MS patients.

Adult↗
PubMed2004

Middle cerebral artery occlusion during MR-imaging: investigation of the hyperacute phase of stroke using a new in-bore occlusion model in rats.

Magnetic resonance imaging (MRI) provides insights into the dynamics of focal cerebral ischemia. Usually, experimental stroke is induced outside the magnet bore, preventing investigators from acquiring pre-ischemic images for later pixel-by-pixel comparisons and from studying the earliest changes in the hyperacute phase of ischemia. Herein, we introduce a new and easy to apply in-bore occlusion protocol based on the intraarterial embolization of ceramic macrospheres. PE-50 tubing, filled with saline and six macrospheres (0.315-0.355 mm in diameter), was placed into the internal carotid artery (ICA) of anesthetized Sprague-Dawley rats. The animals were transferred into an MRI scanner (7.0 T) and baseline diffusion-weighted imaging (DWI) and T2-imaging was performed. Then the macrospheres were injected into the internal artery to occlude the MCA. Post-ischemic DWI and T2-imaging was started immediately thereafter. The apparent diffusion coefficient (ADC) (a marker for cytotoxic brain edema) and T2-relaxation time (a marker for vasogenic brain edema) were determined in the ischemic lesions and compared to the unaffected hemisphere. ADC significantly declined within the first 5-10 min after stroke onset. T2-relaxation time increased as early as at the first T2-imaging time-point (20-35 min after embolization). After 150 min of ischemia, the lesions covered 18.0 +/- 7.4% of the hemispheres. The model failed in one out of nine animals (11%). This model allows MR-imaging from the initial minutes after permanent middle cerebral artery (MCA) occlusion. It does not permit reperfusion. This technique might provide information about the pathophysiological processes in the hyperacute phase of stroke.

Acute Disease↗
PubMed2004

Sinus thrombosis after a jump from a small rock and a sneezing attack: minor endothelial trauma as a precipitating factor for cerebral venous thrombosis?

Cerebral venous thrombosis (CVT) associated with minor or trivial head trauma has only been described in a few cases so far. We report two patients who developed CVT after a sudden intracranial pressure increase and head acceleration. A 49-year-old woman jumped from a small rock, 1 m in height, and developed instantaneous occipital headaches. Magnetic resonance imaging (MRI) confirmed confluens sinuum thrombosis. Risk factors consisted of smoking and oral contraceptives. Our second patient, an 18-year-old woman, experienced instantaneous headaches after a sneezing attack. Superior sagittal and right-sided transverse sinus thrombosis were confirmed by venous computed tomography angiography. She took oral contraceptives as an additional risk factor. In about 20% of CVT cases the cause remains unclear. As minor head trauma may not have been recognized during history taking, this may represent a so far under-recognized precipitating factor for CVT.

Adolescent↗
PubMed2003

Control system analysis of visually evoked blood flow regulation in humans under normocapnia and hypercapnia.

OBJECTIVE: Among other factors, the cerebral blood flow (CBF) is regulated in accordance to the arterial CO(2) tension and the cortical activity. The CO(2) test is commonly used to measure the vascular reserve capacity. Most functional imaging studies rely on the activity-flow coupling (AFC). We aimed to combine both challenges in order to increase the insight into mechanisms of CBF regulation. METHODS: Fifteen healthy students underwent a functional transcranial Doppler test using a visual stimulation paradigm: firstly under normocapnia and secondly under conditions of hypercapnia. Hypercapnia was induced by breathing a carbogene gas mixture of 5% CO(2) and 95% O(2). The entire time course of flow velocity adaptation in the posterior cerebral artery (PCA) was analyzed mathematically using a control system approach. RESULTS: Resting CBF velocities increased by nearly 26% under conditions of hypercapnia, whereas the slight increase in arterial blood pressure (ABP) and the decrease in the Pourcelot-Pulsatility index (PI) were statistically not significant. From the control system parameters which were time delay, rate time, gain, attenuation and natural frequency, only the parameter rate time, indicative for the initial steepness of flow velocity increase, showed a statistically significant decrease, consistently for the peak systolic and enddiastolic flow velocity data. As concluded from the unchanged gain parameter the absolute amount of blood flow evoked by the same visual stimulus increased also by 26%. CONCLUSION: Evaluated by Doppler measurements hypercapnia seems to influence the AFC in two ways: It decreases the steepness of the initial increase in blood flow velocity and enhances the absolute amount of blood flow evoked by the same stimulus.

Adult↗
PubMed2003

Cerebrovascular reactivity in adolescents with migraine and tension-type headache during headache-free interval and attack.

BACKGROUND: Migraine is a common cause of headache in adolescents. Assuming that the cerebral vasculature is involved in the pathophysiology of migraine, we compared cerebral vasoreactivity in adolescents both during a migraine attack and a headache-free interval. METHODS: A functional transcranial Doppler test utilizing a visual stimulation paradigm was undertaken to measure the evoked flow velocity in the posterior cerebral artery of adolescents suffering from a migraine without aura or a tension-type headache. To serve as a control, data previously obtained from age-matched adolescents with no primary headache disorder were used. The flow curves were evaluated by determining the maximal flow velocity increase and by modeling their time course according to a control system analysis. In that analysis, the main dynamic features of the flow response were described mathematically in terms of a control system model of low order. The parameters were time delay, gain, attenuation, rate time, and natural frequency. RESULTS: The attenuation parameter (P<.005), indicative of an increased tone of the vessel, and the resting absolute flow velocity (P<.01) both showed a significant increase during an attack in the adolescents with migraine; the gain parameter showed a trend towards similar increase (P =.07). The maximal flow velocity did not increase significantly during an attack. CONCLUSIONS: The control system approach utilized here appears to be more sensitive for detecting migraine-associated changes in cerebral vasoreactivity than examination of the maximal flow velocities alone.

Adolescent↗
PubMed2003

Association between right-to-left shunts and brain lesions in sport divers.

BACKGROUND: Recent studies suggest that healthy sport divers may develop clinically silent brain damage, based on the association between a finding of multiple brain lesions on MRI and the presence of right-to-left shunt, a pathway for venous gas bubbles to enter the arterial system. METHODS: We performed echocontrast transcranial Doppler sonography in 42 sport divers to determine the presence of a right-to-left shunt. Cranial MRI was carried out using a 1.5 T magnet. A lesion was counted if it was hyperintense on both T2-weighted and T2-weighted fluid attenuated inversion recovery sequences. To test the hypothesis that the occurrence of postdive arterial gas emboli is related to brain lesions on MRI, we measured postdive intravascular bubbles in a subset of 15 divers 30 min after open water scuba dives. RESULTS: Echocontrast transcranial Doppler sonography revealed a right-to-left shunt in 16 of the divers (38%). Only one hyperintensive lesion of the central white matter was found and that was in a diver with no evidence of a right-to-left shunt. Postdive arterial gas emboli were detected in 3 out of 15 divers; they had a right-to-left shunt, but no pathologic findings on cranial magnetic resonance imaging. CONCLUSIONS: Our data support the theory that right-to-left shunts can serve as a pathway for venous gas bubbles into the arterial circulation. However, we could not confirm an association between brain lesions and the presence of a right-to-left shunt in sport divers.

Adult↗
PubMed2002

Assessment of intracranial collateral flow by transcranial color-coded duplex sonography using a temporal and frontal axial insonation plane.

BACKGROUND AND PURPOSE: The insonation of the posterior communicating artery (PcomA) is often hampered by the unfavorable insonation angle when the temporal acoustic bone window (TBW) is used. This problem may be ameliorated by a lateral frontal bone window (LFBW). This study evaluated the TBW and LFBW for the assessment of collateral intracranial flow conditions and aimed at defining diagnostic transcranial color-coded duplex sonography (TCCS) criteria that do not need compression maneuvers. METHODS: The A1 segment of the anterior cerebral artery (ACA), the PcomA, and the P1 segment of the posterior cerebral artery (PCA) were insonated by TCCS in 40 controls and 20 patients (16 internal carotid artery [ICA] occlusions or high grade stenoses, 3 middle cerebral artery stenoses or occlusions, 1 PCA stenosis). RESULTS: Detection rates for the A1 ACA and P1 PCA were higher for the TBW (94%, 98%) compared to the LFBW (86%, 81%) in controls. The PcomA was identified more frequently through the LFBW (86%) compared to the TBW (80%). Through the LFBW angle, corrected flow velocity (FV) measurements were possible for the PcomA with an average correction of 6.5 degrees. In controls, in > 80% of identified PcomAs, flow was directed towards the ICA. Side to side differences were below 7% for peak systolic FVs. In the patients with ICA disease, a flow reversal in the ipsilateral A1 ACA and a FV difference of > 30% seemed feasible for diagnosis of anterior communicating artery crossflow. Criteria for PcomA crossflow were side differences of FVs in the PcomA of > or = 30% and in the P1 PCA of > or = 20%. CONCLUSIONS: The LFBW proved useful as a complementary insonation plane to assess intracranial crossflow conditions, especially via the PcomA. We were able to define TCCS criteria for functional relevant collateralization without the need of compression maneuvers.

Adult↗
PubMed2002

SonoVue (BR1), a new long-acting echocontrast agent, improves transcranial colour-coded duplex ultrasonic imaging.

BACKGROUND AND PURPOSE: Visualization of normal or pathological flow in the intracranial arteries using transcranial colour-coded duplex sonography (TCCS) is occasionally obstructed by insufficient temporal bone windows, unfavourable insonation angles, or low flow velocities or volumes. SonoVue (BR1) is a new, long-acting echocontrast agent, which could be helpful in these instances. METHODS: SonoVue was studied in two separate multicentre investigations of patients with insufficient bone windows (BR1-014 with 73 patients and BR1-017 with 40 patients) using an identical protocol. The agent was given intravenously as a bolus in four different doses (0.3, 0.6, 1.2 and 2.4 ml). Evaluation was performed on-site and off-site with video clips. RESULTS: The contrast agent was well tolerated. As compared to the precontrast scans, SonoVue facilitated the visualization of vessel patency, stenosis, occlusion, and collateral flow, decreased the need for additional tests, and had an impact on the patient's treatment. In 66-74%, a non-diagnostic investigation was converted into a diagnostic investigation. The highest dose (2.4 ml) allowed for a clinically useful signal enhancement of a median 1.9-6.3 min. CONCLUSIONS: SonoVue at a single dose of 1.2 or 2.4 ml is effective in increasing the detection of normal or pathological flow in the intracerebral arteries in patients who do not have a fully diagnostic unenhanced TCCS examination.

Aged↗
PubMed2002

Intracranial venous hemodynamics is a factor related to a favorable outcome in cerebral venous thrombosis.

BACKGROUND: In recent studies, coma, cerebral hemorrhage, older age, and infectious origin have been identified as prognostic factors in cerebral venous thrombosis (CVT). However, no studies of the prognosis of CVT have evaluated hemodynamic factors. However, it is conceivable that the presence or absence and the efficiency of venous collaterals, as well as recanalization, may have an impact on brain tissue damage and hence on the prognosis of acute CVT. METHODS: Twenty-six patients with acute CVT (mean age, 40+/-15 years) were recruited prospectively. All patients were treated with intravenous heparin, followed by oral anticoagulation for 12 months, except for 2 patients who were lost to follow-up after hospital discharge. Neurological deficits were graded on the National Institute of Health Stroke Scale on admission, at hospital discharge, and at 90+/-14 days after admission. The functional clinical outcome was graded on the modified Rankin Scale on day 90 after admission. All patients received a venous transcranial duplex sonography (TCCS) on admission and were followed up in case of a pathological result until normalization was recorded (mean follow-up, 316+/-395 days; range, 13 to 1180 days). RESULTS: Initial TCCS was pathological in 18 of 26 patients (69%). Four distinct venous drainage types were identified: increased drainage to the cavernous sinus and to the deep cerebral veins, flow reversal in the basal veins, and either compensatory increased or reversed flow in the transverse sinus. Initially normal venous TCCS or normalized TCCS within 90 days was significantly related to favorable outcome. CONCLUSIONS: TCCS can be used to evaluate venous drainage patterns in acute CVT. Furthermore, initially normal and normalization of initially pathological venous TCCS within 90 days is related to a favorable outcome in this disease.

Administration, Oral↗
PubMed2002

Intracranial venous hemodynamics in patients with midline dislocation due to postischemic brain edema.

BACKGROUND AND PURPOSE: Cerebral venous pressure is governed by intracranial pressure, cerebral perfusion pressure, and venous outflow resistance. Therefore, changes in venous flow velocities are to be expected because of changes in intracranial pressure and brain tissue dislocation in patients with ischemic stroke and space-occupying brain edema. METHODS: In 21 prospectively recruited patients with middle cerebral artery stroke and postischemic edema, flow velocities in the basal veins, the vein of Galen, the straight sinus, and the P2 segment of the posterior cerebral artery were recorded every 0.9+/-0.5 days during the first 5 days after symptom onset with the use of transcranial color-coded duplex sonography. The midline shift of the third ventricle was determined by B-mode imaging. RESULTS: We observed an initial increase of flow velocity in the basal vein ipsilateral to the lesion, followed by a significant decrease within 5 days after symptom onset and with increasing midline shift in patients with brain herniation. In the straight sinus, flow velocity showed a biphasic U-shaped response to increasing dislocation of the third ventricle, with an initial decrease followed by an increase in the course of mass movement (midline shift 1 to 1.5 cm). A steep increase of flow velocity in the vein of Galen took place with a midline shift >1.5 cm. In the survivors these changes could not be observed. Flow velocity in the P2 segment of the posterior cerebral artery followed a typical course in neither the fatal cases nor the survivors. CONCLUSIONS: Monitoring of flow velocities in the basal cerebral veins and in the straight sinus can provide additional pathophysiological information in patients with space-occupying brain edema after acute stroke.

Aged↗