How much oxidative stress exists without the liver?

BACKGROUND: Oxidative stress (OS) represents an important pathogenetic factor of acute liver failure and chronic liver diseases. To elucidate whether the liver itself is a major source of OS, the present study was performed to assess OS and antioxidant status in an anhepatic porcine model. METHODS: Six pigs underwent a total hepatectomy, five pigs were sham operated. OS and antioxidant status were evaluated by measuring plasma concentrations of malondialdehyde (MDA), xanthine oxidase (XO), superoxide dismutase (SOD) and the ferric reducing ability of plasma (FRAP). They were sampled at the start of the experiment, immediately after surgery, and then at 8 and 16 hours post hepatectomy. RESULTS: Increased concentrations of MDA were observed in anhepatic pigs postoperatively (p < 0.02) and 8 hours after hepatectomy (p < 0.003) compared to controls. XO activity increased soon after hepatectomy (22.6 ±â€Š5.4 mU/L versus 3.3 ±â€Š2.1 mU/L in sham animals, p < 0.03) but returned to normal values in the further course. SOD levels did not change during the observational period in both groups. FRAP values rose significantly in the anhepatic animals compared to control (p < 0.015). A significant positive correlation was observed between MDA levels and FRAP levels (Spearman's ρ = 0.62; p < 0.0001). CONCLUSIONS: These findings show that hepatectomy does not completely prevent the occurrence of OS because the production and regulation of OS are also located outside the liver.

Long-term outcome prediction after a traumatic brain injury using early somatosensory and acoustic evoked potentials: analysis of the predictive value of the different single components of the potentials.

PURPOSE: The prediction of the long-term outcome of comatose patients after severe traumatic brain injury (TBI) using early somatosensory and acoustic evoked potentials is controversial. It was our aim to examine the different single components of the evoked potentials regarding their predictive capacity in comatose patients. METHODS: We examined the amplitude and latency of the wave N20, the amplitude differences between right and left hemisphere, the central conduction time (CCT), the amplitude ratio N20 left/N20 right, the amplitude and latency of peak V, the inter-peak latency I-V and the amplitude ratio V/I. The long-term clinical outcome of the patients was re-evaluated 3 years after their discharge and correlated with the different components. RESULTS: Only the central conduction time (CCT) and the latency of the wave N20 indicated a statistical correlation with the later outcome (p = 0.0366). The amplitude ratio of wave V/I of the EAEP did not reveal a significant statistical difference between the various outcome groups. CONCLUSIONS: In this study, the use of single components of the SSEP and EAEP per se could not predict the long-term clinical outcome after TBI. Combined systems such as the Riffel Score are necessary in order to achieve this goal.

A reproducible porcine model of acute liver failure induced by intrajejunal acetaminophen administration.

BACKGROUND AND AIMS: Severe intoxication following acetaminophen overdose is the most common cause of acute liver failure (ALF) in many Western European and North American countries. A reproducible large animal model of acetaminophen intoxication has not been successfully evaluated previously. METHODS: Eight male pigs underwent acetaminophen intoxication receiving an initial enteric bolus of 250 mg/kg body weight acetaminophen followed by an acetaminophen plasma level (300-450 mg/l) adapted enteric maintenance dose of 1,000-3,000 mg/h to the onset of ALF (prothrombin time value <30%). Vital and ventilation parameters were continuously recorded until death. Saline, hydroxyethyl starch, fresh frozen plasma and erythrocyte units were used for volume substitution, and norepinephrine to prevent severe hypotension. RESULTS: All animals developed ALF after 25 ± 3 h, which was confirmed by laboratory values, the clinical course and histological examinations. All animals died due to ALF after a further 21 ± 5 h, precipitated by cerebral edema. CONCLUSIONS: Using an initial enteric acetaminophen bolus, followed by body weight-adapted acetaminophen plasma level intoxication, it was possible to establish a reproducible, clinically relevant porcine model which may be used for the investigation of novel therapeutic approaches in this life-threatening condition.

A new surgical model for hepatectomy in pigs.

BACKGROUND: Anhepatic animal models are suitable for simulating acute liver failure. Hepatectomy in pigs includes en bloc resection of the vena cava, and therefore, a temporary extracorporeal bypass and total clamping of the inferior vena cava are needed. These steps cause severe depression of circulation with impaired survival. METHODS: Previous to en bloc hepatectomy including retrohepatic vena cava in 20 female pigs, a Y-shaped bypass was implanted starting with end-to-side anastomosis between the vena cava and the portal vein, followed by anastomosis to the intrathoracic vena cava. RESULTS: Blood flow was constant during and after hepatectomy because vessels were only partially clamped. No venous stasis of intestinal organs was observed. Hemodynamic parameters like heart rate, mean arterial pressure, central venous pressure, pulse oximetry and intracranial pressure remained extremely stabile during and after hepatectomy. Postoperative survival time was 100% after 12 h. Maximum survival time was 84.9 h and mean survival time 51.2 +/- 18.7 h. All animals died from multiple organ failure. Intracranial pressure remained stable during the surgical procedure and rose continuously until death. The autopsy showed massive brain edema. CONCLUSIONS: This new surgical technique is safe and easy to perform and permits total hepatectomy with minimal blood loss under stable circulation without requiring an extracorporeal bypass.

[Coma. The prognostic value of evoked potentials in patients after traumatic brain injury]. / Koma. Prognostische Wertigkeit evozierter Potentiale bei Patienten nach schwerem Schädel-Hirn-Trauma.

BACKGROUND: The prognosis after traumatic coma is often unclear. We investigated the prognostic value of somatosensory (SSEP) and early acoustic (EAEP) evoked potentials on comatose patients in the intensive care unit regarding long-term outcome. Different evaluation systems were investigated. METHODS: This was a retrospective analysis of 100 patients. SSEP and EAEP were examined at different times and analysed according to the Riffel score. Combinations of the different types of potentials were evaluated regarding possible improvement of outcome prediction. RESULTS: The positive predictive value of at least one missing peak V of the EAEP regarding a fatal prognosis was 83%. The negative predictive value of the EAEP was 96%. A good outcome (GOS 4+5) could be predicted by bilateral normal SSEP and EAEP with a positive predictive value of 98%. CONCLUSIONS: Early evaluation of SSEP and EAEP allows reliable prognostic predictions regarding a later outcome in patients with severe traumatic brain injury and should therefore be used more often for intensive care patients.

[Direct CT-arthrography versus direct MR-arthrography in chronic shoulder instability: comparison of modalities after the introduction of multidetector-CT technology]. / Direkte CT-Arthrographie versus direkte MR-Arthrographie bei chronischer Schulterinstabilität: Ein Methodenvergleich nach Einführung der Multidetektor-CT-Technik.

PURPOSE: To evaluate the diagnostic accuracy of direct multidetector CT arthrography (CTA) and direct MR arthrography (MRA) in patients suffering from chronic shoulder instability. MATERIALS AND METHODS: Twenty-nine patients suffering from chronic shoulder instability were included into a prospective study. In all cases, the indication for direct CTA and arthroscopy was set by the orthopedic surgeon. Prior to the imaging procedures, 10 to 20 ml of a special combination of contrast media (including saline, Isovist(R) and Magnevist(R) in a relation of 125 : 125 : 1) was injected into the joint under sterile conditions. First, CTA was performed with a multidetector CT, with images reconstructed in the axial, semi-coronal and semi-sagittal planes. Thereafter, MRA was performed. Axial images were obtained using a T1-weighted, fat-saturated spin echo sequence and semi-coronal images using a T1-weighted FLASH-3D GRE sequence. The results of CTA and MTA were compared with results obtained from arthroscopy or arthrotomy. RESULTS: MRA was superior to CTA in the detection of labral lesions. The sensitivity of MRA was 96 % and the specificity 96 %, compared to a sensitivity of 76 % (p < 0.05) and specificity of 92 % for CTA. Both methods showed the same effectiveness concerning the assessment of capsule distension (sensitivity for both techniques: 91 %). CONCLUSIONS: MRA seems to be superior to CTA in the diagnostic workup of chronic shoulder instability even when using a multidetector CT technique.

[MRI of intraosseous fistulous systems and sequesters in chronic osteomyelitis with standard spin echo sequences, highly selective chemical-shift imaging, diffusion weighted imaging, and magnetization-transfer]. / MRT-Darstellung intraossärer Sequester und Fistelsysteme bei chronischer Osteomyelitis durch Standardsequenzen, hochselektive Chemical-Shift-Bildgebung, Diffusionsgewichtung und Magnetisierungstransfer.

PURPOSE: To study and test the impact of modern MRI techniques in diagnostic imaging in the evaluation of intra-osseous fistulous systems and sequesters. MATERIALS AND METHODS: In a prospective study, nine patients with chronic osteomyelitis of the legs were examined by MRI. Patients with clinical signs of osteomyelitis requiring surgery were included in the study. T1-weighted spin echo (SE) sequences, proton density (PD) and T2-weighted fast spin echo (FSE) sequences, water- and fat-selective FSE sequences, and diffusion weighted (DW) PSIF sequences were used preoperatively. Furthermore, magnetizing transfer (MT) with gradient echo (GRE) sequences was evaluated. RESULTS: Water selective sequences revealed the highest sensitivity for the detection of fistulas (100%), providing the best delineation of the extent of the entire fistulous systems. Fat-selective sequences (sensitivity 55.6%) and T1-weighted sequences (sensitivity 77.8%) displayed fistulas as hypointense bands, which, however, cannot be well differentiated from cortical bone in the transcortical areas. PD and T2-weighted images were found to have a poor sensitivity (55.6% and 66.7%) for fistulas in any location. The sensitivity of water-selective sequences to demonstrate intraosseous sequesters was 100%. The sensitivity was low for the other sequences. In 4 of 5 patients with surgically proven infection, DW and MT revealed an abnormal spatial distribution, with high diffusion in the central parts of the fistulas and high MT effect peripherally surrounding a weak MT effect centrally. CONCLUSION: Water-selective sequences are superior when demonstrating fistulous systems and intraosseous sequesters. The combined use of MT and DW sequences seems to allow a differentiation between solid granulation tissue and liquid pus.

Alterations in diffusion and perfusion in the pathogenesis of peritumoral brain edema in meningiomas.

Magnetic resonance perfusion and diffusion studies were undertaken to clarify the significance of ischemia in the pathogenesis of peritumoral brain edema in patients with meningiomas. Included in this study were 26 patients with 27 meningiomas and 5 gliomas. Perfusion-weighted imaging (PWI) was performed using a gradient-echo, echo-planar-imaging (EPI) sequence for calculation of the relative regional cerebral blood volume (rrCBV) and the relative regional cerebral blood flow index (rrCBFi). Furthermore, multi-slice spin-echo EPI sequences were applied in order to obtain anisotropic and isotropic diffusion-weighted imaging (DWI). Apparent diffusion coefficient (ADC) values were then calculated for peritumoral brain parenchyma from tumors, with and without edema, using various diffusion sensitivities. Meningiomas without edema demonstrated a minimal increase of perfusion parameters in the peritumoral brain tissue. In contrast, cases with brain edema had highly significant ( p<0.0005) lower rrCBV and rrCBFi. The edema index (EI) correlated strongly with the rrCBV. A fitting procedure resulted into the following mathematical relation: EI=0.1/rrCBV(2). The DWI showed a significantly larger ADC value within areas of brain edema, compared with the normal white matter (0.74 x 10(-3) vs 1.55 x 10(-3) mm(2)/s; p<0.0001). Increases in EI correlated with increases in ADC values. In 31% of the meningiomas associated with edema, areas with increased signal, probable ischemia, demonstrated significantly lower ADC values, in comparison with the rest of the edematous areas. These areas were confined to tissue immediately adjacent to the tumor. In general, the decrease in rrCBV in brain edema represents a consequence from, rather than a cause of, vasogenic edema. Ischemic alterations can be regarded as secondary, facultative phenomena in the pathogenesis of meningioma-related brain edema.

The problem of long-term ICP drift assessment: improvement by use of the ICP drift index.

BACKGROUND: Intracranial pressure (ICP) monitoring is dependent on the precise measurement of absolute pressures and low drifts of the different transducers in use. Our investigations have shown that probes sometimes appear to reveal positive and negative drifts consecutively. There is no regard for any of these important pressure changes by the mere result of the traditional drift. Therefore, we have developed a more precise way of assessing the behavior of the ICP drift. METHOD: A special laboratory set up for the simulation of constant pressures, at definite temperatures, was designed. We examined the Camino-110-4B, Gaeltec ICT/B, HanniSet and Spiegelberg transducers. Drift index is a new term that has been developed by our group to provide a better description of the actual pressure changes over long-term measurement. The drift index consists of three parameters: the percentage of measurements which show a pressure change during the 10 days of measurement; the maximum absolute pressure deviation that occurred during a ten day measurement; and the mean absolute pressure deviation during a 10 day measurement. FINDINGS: The median proportion of pressure changes during ten days were: Camino: 1.59%; Gaeltec: 0.71%; HanniSet: 0.08%; Spiegelberg: 4.00%; The median maximum absolute pressure changes were 6; 9.5; 1; and 11 mmHg for the four types and the median mean absolute pressure changes were 2.9; 5.1; 0; and 2.4 mmHg, respectively. The median 10 day classical drift in each type of transducer was 4; 9; 0; and 2 mmHg, respectively. INTERPRETATION: We recommend the use of the drift index to be used by manufacturers. This is an additional vital parameter in order to improve ICP measurement accuracy and the proficiency of ICP monitoring.

Methods of experimental and clinical assessment of the relative measurement accuracy of an intracranial pressure transducer. Technical note.

The assessment of the actual measurement accuracy of an intracranial pressure (ICP) transducer is imperative but still very difficult in practice. The authors tested the Codman MicroSensor ICP transducer experimentally. Additionally, a bedside test for assessment of measurement accuracy was used before and after clinical monitoring. For laboratory testing, seven new transducers were examined for measurement accuracy at increasing pressures ranging from 0 to 75 mm Hg. Drift was evaluated for 10 days at six different pressure levels ranging from 0 to 50 mm Hg. Temperature drift was assessed over a temperature range from 20 to 45 degrees C. The percentage absolute difference was used in the assessment of measurement accuracy. For clinical testing, measurement accuracy was assessed intraoperatively just before the insertion of the transducer and in an open water bath after its explantation, at 10 cm H2O both times. The maximum percentage absolute difference was 9% at a pressure of 10 mm Hg, and declined toward 2.3% at a pressure of 75 mm Hg. The maximum drift over 10 days was -4 mm Hg. Within the range of 30 to 40 degrees C, temperature drift was negligible. Over a period of 2 years, between June 1997 and June 1999, 40 ICP transducers were implanted in 35 patients by one surgeon. Of these devices, a malfunction was detected in two of them by testing them in a water bath before insertion. Experimental and clinical results indicate that this miniature strain-gauge transducer measures accurately; however, control readings for the probe by means of measurement in an open water bath just before insertion are strongly recommended.

Cyclooxygenase (COX)-1 expressing macrophages/microglial cells and COX-2 expressing astrocytes accumulate during oligodendroglioma progression.

Cyclooxygenases (COX, prostaglandin endoperoxide synthases, PGG/H synthases) are potent mediators of edema, impeding blood flow and immunomodulation in the pathologically altered brain. Two COX iso-enzymes have been associated with brain disease, the constitutively expressed COX-1 and the cytokine-inducible COX-2. We have used single and double labeling immunohistochemistry to analyse COX-1 and COX-2 expression in twenty-six primary WHO grade II oligodendrogliomas, sixteen primary WHO grade III anaplastic oligodendrogliomas, twenty-seven matched recurrences and ten neuropathologically unaltered brains. COX-1 immunoreactivity was predominantly observed in macrophages/microglial cells. The number of COX-1 expressing macrophages/microglial cells was significantly lower in primary oligodendrogliomas than in primary anaplastic oligodendrogliomas (P<0.0001) and in anaplastic oligodendroglioma relapses (P=0.011). Patients with low COX-1 labeling scores in the primary tumors had significantly longer time to progression and overall survival (P=0.0285) than those with high COX-1 labeling scores. COX-2 immunoreactivity was predominantly observed in disseminated neurons and astrocytes. In glioblastoma multiforme relapses, accumulation of COX-2 expressing astrocytes was observed surrounding areas of focal necrosis. The number of COX-2 expressing astrocytes was significantly (P=0.0471) lower in primary oligodendrogliomas than in high grade oligodendroglioma relapses. These data provide convincing evidence for the differential accumulation of cyclooxygenase isoforms during oligodendroglioma progression in vivo.

Role of hydrodynamic processes in the pathogenesis of peritumoral brain edema in meningiomas.

OBJECT: In a prospective study, 28 patients with 32 intracranial meningiomas were examined to determine the role of hydrodynamic interaction between tumor and surrounding brain tissue in the pathogenesis of peritumoral brain edema. METHODS: Gadolinium-diethylenetriamine pentaacetic acid (Gd-DPTA), an extracellular contrast agent used for routine clinical imaging, remains strictly extracellular without crossing an intact blood-brain barrier. Therefore, it is well suited for investigations of hydrodynamic extracellular mechanisms in the development of brain edema. Spin-echo T1-weighted magnetic resonance images were acquired before and after intravenous administration of 0.2 mmol/kg Gd-DPTA. Additional T1-weighted imaging was performed 0.6, 3.5, and 6.5 hours later. No significant Gd-DPTA diffused from tumor into peritumoral brain tissue in 12 meningiomas without surrounding brain edema. In contrast, in 17 of 20 meningiomas with surrounding edema, contrast agent in peritumoral brain tissue was detectable after 3.5 hours and 6.5 hours. In three of 20 meningiomas with minimum surrounding edema (<5 cm3), contrast agent effusion was absent. After 3.5 hours and 6.5 hours strong correlations of edema volume and the maximum distance of contrast spread from the tumor margin into adjacent brain parenchyma (r = 0.84 and r = 0.87, respectively, p < 0.0001) indicated faster effusion in larger areas of edema. CONCLUSIONS: The results of this study show that significant contrast agent effusion from the extracellular space of the tumor into the interstitium of the peritumoral brain tissue is only found in meningiomas with surrounding edema. This supports the hypothesis that hydrodynamic processes play an essential role in the pathogenesis of peritumoral brain edema in meningiomas.

Thin and thick filament regulation of contractility in experimental cerebral vasospasm.

OBJECTIVE: Cerebral vasospasm is a potentially fatal consequence of aneurysmal subarachnoid hemorrhage and influences the prognosis of the patient. The purpose of this study was to evaluate the status of thin (actin) and thick (myosin) filament regulation of smooth muscle contraction in the double-subarachnoid hemorrhage canine model of cerebral vasospasm and to determine the effects of a kinase inhibitor reported to be effective in vasospasm, HA1077, on thin and thick filament regulation. METHODS: Cerebral vasospasm was assessed by vertebral angiography. Myosin regulatory light chain phosphorylation was measured using glycerol-urea gels, whereas protein levels of the thin filament-associated protein calponin were measured by Western blot. RESULTS: The basilar arteries of dogs in which subarachnoid hemorrhage was induced narrowed to 36% +/- 2.0% of their size on the first day (n = 12). The phosphorylation of the regulatory light chain tended to increase, but the change did not reach statistical significance (35% +/- 5.9% [n = 12] versus 25% +/- 4.8% [n = 10] in control arteries). In contrast to this increase, significant degradation of calponin was observed in the samples from vasospastic dogs (85.4% +/- 5.45% [n = 5] versus 15.2% +/- 6.21% [n = 5]; P < 0.01). Prophylactic treatment with intravenous injections of HA1077 at 0.67 mg/kg b.i.d. significantly inhibited vasospasm (diameters, 65% +/- 10.2% of Day 1 diameters [n = 5]; P < 0.05), and calponin degradation (57.8% +/- 13.9% [n = 4]) was substantially reduced. CONCLUSION: These data suggest that degradation of the thin filament-associated protein calponin plays a role in cerebral vasospasm and that the antivasospastic action of HA1077 is, at least in part, due to prevention of calponin degradation.

ICP measurement control: laboratory test of 7 types of intracranial pressure transducers.

Intracranial pressure (ICP) monitoring has become an important parameter in the assessment of comatose patients, with raised intracranial pressure. The transducers in use have to fulfill the criteria of measurement accuracy, practicability and cost-effectiveness. However, these requirements are not always met in clinical practice. The need for ongoing quality control through independent laboratories remains. We have developed a laboratory set-up for the evaluation of intracranial pressure probes. Seven different types of currently used transducers have been tested for measurement accuracy. Under in vitro conditions 3 parameters were assessed: measurement accuracy, a 24 h drift and 10 day drifts. Tests for measurement accuracy were performed at increasing pressure levels of up to 80 mmHg. They were repeated 10 times per probe. This test allowed the simultaneous assessment of 5 different ICP probes. Drift was evaluated for 24 h and 10 days, at 6 pressure levels between 0 and 50 mmHg. Seven different types of ICP probes were tested (HanniSet, Camino, Codman, Spiegelberg, Medex, Epidyn and Gaeltec). Measurement accuracy was best with HanniSet probes. The maximum errors with this transducer were 3 mmHg. Camino and Codman showed similar results. Spiegelberg had slightly larger deviations. With Epidyn and Gaeltec the highest error were noted, up to 10 mmHg in the high pressure range. The 24 h drift was lowest with HanniSet (0.2 mmHg) and Camino (0.8 mmHg). The largest drifts were seen with Medex, Spiegelberg and Gaeltec (1.8 mmHg). Ten day drift was lowest with HanniSet (0.1 mmHg/day) and Codman (0.2 mmHg/day). The highest long-term drifts were found with Epidyn and Gaeltec (1.5 mmHg/day). Drift did not exhibit a linear pattern. After an initial rise in drift during the first 24-72 h, it decreased slowly during the next 7 days. Most ICP probes revealed measurement inaccuracy and drift. These results emphasize the necessity for ongoing evaluations of ICP probes. Therefore, tests for quality assurance are essential to establish a consistent standard of proficiency of ICP transducers.

A computer-based method for continuous single pulse analysis of intracranial pressure waves.

INTRODUCTION: The single pulse analysis of intracranial pressure waves provides valuable information about the autoregulative processes after head injury. This method has not been used for routine clinical assessment as yet. Current methods for evaluation of intracranial pressure waves are based on spectral analysis or related techniques. This imposes restrictions on the wave sequences available for the investigation of ICP attributes. Therefore, we have developed a computer-based method, which enables continuous analysis of each pulse of the ICP wave, in any clinical setting. METHOD: Firstly, the raw data of the ICP wave is continuously recorded by the Multifunctional Anaesthetic Record System (MARS, Hewlett Packard). The recorded data is then subjected to single pulse wave analysis by our software. Each single pulse is identified by the algorithm. The maximum, minimum and mean value, as well as amplitude and gradient are calculated in each pulse pressure. All conceivable correlations of the listed parameters can be examined. RESULTS: We applied our software in 9 cases with head injury and evaluated the measurements over 59 days (1400 h). More than 7 million single pulse pressures have been analyzed off-line. The software proved to be accurate and easy to apply. It was possible to calculate correlations between the different wave attributes on a broad basis of data. Parameters of special clinical interest were the amplitude of the single pulse pressure and the gradient. CONCLUSION: This method is an improvement on ICP single pulse pressure analysis and facilitates its clinical application. It creates the possibility for continuous long-term analysis of the ICP wave attributes under any clinical condition without loss of data. There are indications that the amplitude and the gradient of the ICP pulse pressure could provide valuable additional information for clinical assessment. However, further evaluation is required.

[Measurement technique. Systems and methods for intracranial pressure monitoring]. / Messtechnik. Systematik und Methoden der intrakraniellen Druckmessung.

GOAL: Intracranial pressure (ICP) monitoring has a key role within the neuromonitoring, although ICP does not monitor processes of the central neuron directly and only with delay. One of the important factors in ICP monitoring is measurement accuracy. For a better understanding of ICP probes and their differences, the function and principles of intracranial pressure transducers should be evaluated from a technical point of view. METHOD: The principles of ICP measurement were analyzed and compared. Practical applications of these principles were examined and examples of different ICP probes were discussed regarding their mode of pressure transformation. The technical advances of ICP monitoring were analyzed. RESULTS: Since LUNDBERG, a variety of different types of transducers has been developed. Ventricular ICP monitoring has been supplemented by extradural and intraparenchymatous probes. An increasing miniaturization of the transducers has emerged. Additionally, fiberoptic systems have been developed. Latest developments include multifunctional ICP probes. So far, the main problem of most types of transducers consists in the inability to assess measurement accuracy of a probe during the period of patient monitoring. CONCLUSION: ICP probes should be tested better for correct function by the manufacturer prior to sale. External controls of the measurement accuracy should be performed more frequently to ensure constant quality. Future ICP transducers have still to be more cost-effective.

ICP measurement accuracy: the effect of temperature drift. Design of a laboratory test for assessment of ICP transducers.

Intracranial pressure (ICP) monitoring has become the mainstay of multimodal neuromonitoring of comatous patients after head injury. In the presence of rising ICP and faced with pressures, difficult to control, aggressive measures, such as hypothermia may be used. The ICP readings should not be influenced by temperature changes. A laboratory test was designed to simulate temperature variations between 20 degrees C and 45 degrees C at different pressure levels under physiological conditions. Five types of transducers were examined: Epidyn Braun Melsungen, ICT/B-Titan Gaeltec, Camino-OLM-110-4B, Codman MicroSensor ICP-Transducer, Neurovent ICP transducer Rehau Ag+Co. Tests were performed at 6 different pressure levels between 0 mmHg and 50 mmHg. The results show very low drifts of less than 0.15 mmHg degree C-1 for Codman, Epidyn and Neurovent. Gaeltec and Camino exhibited higher drifts of 0.18 mmHg and 0.2 mmHg degree C-1 respectively. Within the temperature range from 35 degrees C to 42 degrees C all probes tested show insignificant temperature drift. Whether these results also apply to other types of transducers needs further evaluation. Problems and requirements related to the design of a laboratory test for the in vitro assessment of ICP transducers are discussed in detail.

Angiogenesis and brain oedema in intracranial meningiomas: influence of vascular endothelial growth factor.

The correlation between angiographic neovascularization, peritumoural brain oedema (PTBOe) and the expression of vascular endothelial growth factor (VEGF), was analysed in 30 patients with intracranial meningiomas. Pre-operative angiograms were examined for the existence of either an exclusively dural tumour blush or an additionally pial tumour supply from cerebral arteries. Furthermore the presence of macroscopic tumour-neovascularization and dysplastic changes of tumour-draining cerebral veins was evaluated. VEGF expression was investigated on histological tissue samples, using immunohistochemical techniques. VEGF immunohistochemistry and neuroradiological evaluations were performed in double blind fashion. Tumour volume and the amount of oedema were calculated by computerized tomography (CT) or magnetic resonance imaging (MRI). The oedema-tumour volume ratio was defined as oedema index (OeI). Compared to VEGF-negative meningiomas, tumours with striking VEGF staining revealed a significant higher mean oedema index (OeI = 4.2 vs. OeI = 1.5; p < 0.018), and a higher oedema incidence (91.7% vs. 44.4%; p < 0.046). Equally, meningiomas with additionally tumour supply from cerebral arteries were associated with a significant higher mean OeI (OeI = 4.1 vs. OeI = 1.2; p < 0.01) and oedema incidence (94.7% vs. 20.0%; p < 0.0023) than meningiomas with exclusively tumour supply from dural arteries. All meningiomas with striking VEGF-expression were associated with vascular tumour supply from cerebral arteries, but VEGF-negative tumours only in 50% (p < 0.029). These data suggest a link between VEGF-expression, arterial tumour supply and peritumoural brain oedema. The development of tumour supply from cerebral arteries may be important for formation of meningioma-related oedema. Therefore, VEGF may represent a potent mediator in the evolution of this type of vascularization in meningiomas.

Tumor-related venous obstruction and development of peritumoral brain edema in meningiomas.

OBJECTIVE: The exact pathogenesis of peritumoral brain edema (PTBE) in meningiomas is still unknown. A number of different pathophysiological hypotheses have been considered. A detrimental effect of tumor-related venous obstruction has been suggested as one pathogenetic mechanism. We sought to characterize the significance of venous stasis in the development of PTBE in meningiomas. METHODS: Angiograms for 134 patients with 136 intracranial meningiomas were analyzed. Pathological changes affecting cortical veins, sylvian veins, bridging veins, deep veins, transmedullary veins, and dural sinuses were evaluated. From preoperative computed tomographic scans, the total tumor volume, the tumor/PTBE volume ratio (edema index [EI]), and the location of the edema were determined. For statistical evaluation, meningiomas associated with pathological venous drainage were compared with size-matched controls. RESULTS: The edema incidence and the mean EI were not different for meningiomas with unselected signs of obstructed venous drainage, compared with controls. In particular, lesions with involvement of cortical veins, bridging veins, and dural sinuses showed no higher edema incidence. However, meningiomas associated with venous changes in sylvian veins (EI = 4.9 versus EI = 2.7; P < 0.004) and with dysplastic transmedullary veins (EI = 3.3 versus EI = 1.7; P < 0.04) showed significantly higher mean EI values, compared with meningiomas without involvement of these vessels. CONCLUSION: Our data suggest that tumor-related venous obstruction does not play an essential role in the development of PTBE for the majority of meningiomas. For a small subgroup of meningiomas with involvement of sylvian veins or development of dysplastic transmedullary veins, changes in venous drainage may aggravate preexisting PTBE.

ICP monitoring with a re-usable transducer: experimental and clinical evaluation of the Gaeltec ICT/b pressure probe.

Intracranial pressure monitoring requires reliable transducers at a justifiable price. At present, transducers for single or repeated use are available. We examined the Gaeltec model ITC/b solid state miniature transducer experimentally and clinically. Measurement accuracy was assessed in vitro at increasing steps of 5 mmHg from 0 to 80 mmHg. While new and recently serviced probes revealed minimal deviations from the preset values, frequently used transducers differed up to 7 mmHg. This occurred especially in the high pressure range above 50 mmHg. Additionally the drift was investigated at different pressure levels. After 24 hours we already found drifts of 2 mmHg with new and serviced probes and up to 4 mmHg with used ones. In clinical practice we implanted 150 transducers in 121 patients from 1983 until 1995. The probes were re-used up to twelve times, the average time being 7 times. 32.7% of all measurements were regarded as not reliable. Dislocation (16.7%), inability to calibrate (3.3%) and defect pressure probes (3.3%) were the most common complications. Repeated use of the Gaeltec ICT/b probe also seemed to result in an additional decay of measurement quality. The strain of frequent cleaning and sterilizing may have caused changes of the physical properties of the probes with time. Whether these results also apply to other types of ICP probes for repeated use needs further evaluation.