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Biomedical subjects

Andreas Raabe

Publications and source records attributed to Andreas Raabe.

At least 37 records · Page 2Linked to original sources

Clazosentan (AXV-034343), a selective endothelin A receptor antagonist, in the prevention of cerebral vasospasm following severe aneurysmal subarachnoid hemorrhage: results of a randomized, double-blind, placebo-controlled, multicenter phase IIa study.

OBJECTIVE: The goal of this study was to investigate the safety and tolerability of the novel endothelin A (ETA) receptor antagonist clazosentan in patients with subarachnoid hemorrhage (SAH) and its potential to reduce the incidence and severity of cerebral vasospasm following surgical clipping of the aneurysm. METHODS: This Phase IIa multicenter study had two parts: a double-blind, randomized Part A (some patients given clazosentan [0.2 mg/kg/hr] and others given placebo), in which statistical inference was performed, and an open-label Part B (patients with established vasospasm given clazosentan [0.4 mg/kg/hr for 12 hours followed by 0.2 mg/kg/hr]) for exploratory purposes only. Primary end points were the incidence and severity of angiographic vasospasm on Day 8 after SAH and the safety and tolerability of the drug. Thirty-four patients (Hunt and Hess Grades III and IV and Fisher Grade > or = 3) were recruited and 32 (15 in the clazosentan group and 17 in the placebo group) were retained in the intent-to-treat population; 19 patients entered Part B. In Part A, treatment with clazosentan resulted in a reduced incidence of angiographically evident cerebral vasospasm (40% compared with 88% of patients, p = 0.008). In addition, the severity of vasospasm was reduced in the clazosentan group (p = 0.012). In Part B of the study, in 50% of assessable patients who were initially treated with placebo reversal of vasospasm was observed following the initiation of clazosentan therapy. The incidence of new infarctions was 15% in the clazosentan group and 44% in the placebo group (p = 0.130). There was no adverse event pattern indicating a specific organ toxicity of clazosentan. CONCLUSIONS: This study indicates that clazosentan reduces the frequency and severity of cerebral vasospasm following severe aneurysmal SAH with the incidence and severity of adverse events comparable to that of placebo.

Adult↗

Relative importance of hypertension compared with hypervolemia for increasing cerebral oxygenation in patients with cerebral vasospasm after subarachnoid hemorrhage.

OBJECT: Hypervolemia and hypertension therapy is routinely used for prophylaxis and treatment of symptomatic cerebral vasospasm at many institutions. Nevertheless, there is an ongoing debate about the preferred modality (hypervolemia, hypertension, or both), the degree of therapy (moderate or aggressive), and the risk or benefit of hypervolemia, moderate hypertension, and aggressive hypertension in patients following subarachnoid hemorrhage. METHODS: Monitoring data and patient charts for 45 patients were retrospectively searched to identify periods of hypervolemia, moderate hypertension, or aggressive hypertension. Measurements of central venous pressure, fluid input, urine output, arterial blood pressure, intracranial pressure, and oxygen partial pressure (PO2) in the brain tissue were extracted from periods ranging from 1 hour to 24 hours. For these periods, the change in brain tissue PO2 and the incidence of complications were analyzed. During the 55 periods of moderate hypertension, an increase in brain tissue PO2 was found in 50 cases (90%), with complications occurring in three patients (8%). During the 25 periods of hypervolemia, an increase in brain oxygenation was found during three intervals (12%), with complications occurring in nine patients (53%). During the 10 periods of aggressive hypervolemic hypertension, an increase in brain oxygenation was found during six of the intervals (60%), with complications in five patients (50%). CONCLUSIONS: When hypervolemia treatment is applied as in this study, it may be associated with increased risks. Note, however, that further studies are needed to determine the role of this therapeutic modality in the care of patients with cerebral vasospasm. In poor-grade patients, moderate hypertension (cerebral perfusion pressure 80-120 mm Hg) in a normovolemic, hemodiluted patient is an effective method of improving cerebral oxygenation and is associated with a lower complication rate compared with hypervolemia or aggressive hypertension therapy.

Adult↗

Prospective evaluation of surgical microscope-integrated intraoperative near-infrared indocyanine green videoangiography during aneurysm surgery.

OBJECT: The authors prospectively compared a new technique of surgical microscope-based indocyanine green (ICG) videoangiography with intraoperative or postoperative digital subtraction (DS) angiography. METHOD: The technique was performed during 187 surgical procedures in which 124 aneurysms in 114 patients were clipped. Using a newly developed setup, the ICG technique has been integrated into an operating microscope (Carl Zeiss Co., Oberkochen, Germany). A microscope-integrated light source containing infrared excitation light illuminates the operating field. The dye is injected intravenously into the patient, and intravascular fluorescence from within the blood vessels is imaged using a video camera attached to the microscope. The patency of parent, branching, and perforating arteries and documentation of clip occlusion of the aneurysm as shown by ICG videoangiography were compared with intraoperative or postoperative findings on DS angiography. The results of ICG videoangiography corresponded with intra- or postoperative DS angiography in 90% of cases. The ICG technique missed mild but hemodynamically irrelevant stenosis that was evident on DS angiography in 7.3% of cases. The ICG technique missed angiographically relevant findings in three cases (one hemodynamically relevant stenosis and two residual aneurysm necks [2.7% of cases]). In two cases the missed findings were clinically and surgically inconsequential; in the third case, a 4-mm residual neck may require a second procedure. Indocyanine green videoangiography provided significant information for the surgeon in 9% of cases, most of which led to clip correction. CONCLUSIONS: Microscope-based ICG videoangiography is simple and provides real-time information about the patency of vessels of all sizes and about the aneurysm sac. This technique may be useful during routine aneurysm surgery as an independent form of angiography or as an adjunct to intra- or postoperative DS angiography.

Adult↗

Mutations in the lysyl oxidase gene not associated with intracranial aneurysm in central European families.

BACKGROUND: Lysyl oxidase is a promising candidate gene for a mutation search in intracranial aneurysm families because (a) it controls the processing, cross-linking and maturation of collagen and elastin fibers in the blood vessel wall, (b) its expression levels and activity are altered in different animal models of aneurysm pathogenesis, and (c) it is encoded within the chromosome 5q22-31 region of suggestive linkage to intracranial aneurysms. METHODS: We have performed genomic sequencing of all 7 exons including the intron-exon splice sites and of the putative promoter region for lysyl oxidase in 25 patients from intracranial aneurysm multiplex families resident in Central Europe. RESULTS: We observed 4 genetic variants including 2 novel polymorphisms, 1 in the noncoding sequence of exon 7 and the other upstream from the lysyl oxidase promoter. None of these single nucleotide polymorphisms showed an allelic association or cosegregation with intracranial aneurysm in the families. CONCLUSIONS: Genetic variants in the lysyl oxidase gene do not appear to be a major factor in the etiology of intracranial aneurysms in Central Europe.

Adenine↗

GFAP versus S100B in serum after traumatic brain injury: relationship to brain damage and outcome.

Research indicates that glial fibrillary acidic protein (GFAP), part of the astroglial skeleton, could be a marker of traumatic brain injury (TBI). S100B, an astroglial protein, is an acknowledged marker of TBI. Our goal was to analyze the relationship of GFAP/S100B to brain damage and outcome, and to compare the accuracy of GFAP/S100B for prediction of mortality after TBI. Our prospective study included 92 patients admitted <12 h after TBI (median injury severity score 25, median Glasgow Coma Scale 6). TBI was verfied by computerized tomography. GFAP/S100B were measured immunoluminometrically at admission and daily in the intensive care unit (average 10 days, range 1-21 days). We compared GFAP/S100B in non-survivors versus survivors, accuracy for mortality prediction according to receiver operated characteristic curve analysis, correlation between GFAP and S100B, relationship of GFAP/S100B to computerized tomography, cerebral perfusion pressure (CPP), mean arterial pressure (MAP) and 3-month Glasgow Outcome Score (GOS). GFAP (p < 0.005) and S100B (p < 0.0005) were higher in non-survivors than survivors. Both GFAP and S100B were accurate for mortality prediction (area under curve 0.84 versus 0.78 at <12 h after TBI). GFAP and S100B release correlated better later than 36 h after TBI (r = 0.75) than earlier (r = 0.58). GFAP was lower in focal lesions of <25 mL than in shifts of >0.5 cm (p < 0.0005) and non-evacuated mass lesions of >25 mL (p < 0.005). S100B was lower in focal lesions of <25 mL than in non-evacuated mass lesions (p < 0.0005) and lower in swelling than in shifts of >0.5 cm (p < 0.005). GFAP and S100B were lower in ICP < 25 than ICP > or = 25 (p < 0.0005), in CPP > or = 60 than CPP < 60 (p < 0.0005), in MAP > 70 than MAP < or = 70 mm Hg, and in GOS 4-5 than GOS 1 (p < 0.0005). Both measurement of GFAP and S100B is a useful non-invasive means of identifying brain damage with some differences based on the pattern of TBI and accompanying multiple trauma and/or shock.

Adult↗

Glial fibrillary acidic protein in serum after traumatic brain injury and multiple trauma.

BACKGROUND: This study aimed to determine whether glial fibrillary acidic protein (GFAP) is released after traumatic brain injury (TBI), whether GFAP is related to brain injury severity and outcome after TBI, and whether GFAP is released after multiple trauma without TBI. METHODS: This prospective study enrolled 114 patients who had TBI with or without multiple trauma (n = 101) or multiple trauma without TBI (n = 13), as verified by computerized tomography. Daily GFAP measurement began at admission (<12 hours after trauma) and continued for the duration of intensive care (1-22 days). Documentation included categorization of computerized tomography according to Marshall classification, based on daily highest intracranial pressure (ICP), lowest cerebral perfusion pressure (CPP), lowest mean arterial pressure (MAP), and 3-month Glasgow Outcome Score (GOS). RESULTS: The GFAP concentration was lower for diffuse injury 2 than for diffuse injury 4 (p < 0.0005) or nonevacuated mass lesions larger than than 25 mL (p < 0.005), lower for a ICP less than 25 mm Hg than for a ICP of 25 mm Hg or more, lower for a CPP of 60 mm Hg or more than for a CPP of 60 mm Hg or less, lower for a MAP of 60 mm Hg or more than for a MAP less than 60 mm Hg (all p < 0.0005), and lower for a GOS of 1 or 2 than for a GOS of 3, 4 (p < 0.05), or 5 (p < 0.0005). After TBI, GFAP was higher in nonsurvivors (n = 39) than in survivors (n = 62) (p < 0.005). After multiple trauma without TBI, GFAP remained normal. CONCLUSIONS: The findings showed that GFAP is released after TBI, that GFAP is related to brain injury severity and outcome after TBI, and that GFAP is not released after multiple trauma without brain injury.

Adult↗

S-100B protein as a serum marker of secondary neurological complications in neurocritical care patients.

There is growing evidence that S-100B protein measured by a simple blood test can be used as a novel biochemical marker of brain cell damage. The objective of our study was to investigate the potential of S-100B measurements to diagnose an acute neurological complication in the analgo-sedated and intubated intensive care patient and the impact on patient management. Serum S-100B levels were serially investigated in 246 neurocritical care patients. Venous blood samples for S-100B determination were obtained as soon as possible after admission and every 24 hours thereafter, for the duration of the stay at the neurocritical care unit. Blood samples were taken every morning as part of the routine laboratory investigation for analysis of S-100B using the immunoluminometric assay (AB Sangtec Medical, Bromma, Sweden) and a fully automated LIAISON system (Byk-Sangtec-Diagnostica, Dietzenbach, Germany) with a short time to result. The primary endpoint of our study was the occurrence of a severe neurological complication. Patients were admitted to the neurosurgical intensive care unit after routine major intracranial surgery in 116 cases (47%) and after a neurological or neurosurgical emergency in 130 cases (53%). Of the latter group, 79 patients (32%) underwent emergency surgery for evacuation or decompression of a space-occupying lesion before ICU admission. A severe neurological complication was defined as a new infarction, new hemorrhage or a newly developed progressive disease despite maximum therapy with a radiologically confirmed increase of mass lesion and midline shift. In 33 patients (13%) a complication with neurological deterioration occurred. All patients showed pathologically increased serum S-100B values (mean 2.00 microg/l, standard deviation 2.61 microg/l, range 0.31-9.66 microg/l). Twenty-eight of these patients (85%) showed S-100B increases >0.5 microg/l. In five cases (16%), the increase in S-100B was the first sign of neurological complication and prompted emergency computed tomography scanning. In another two cases, increasing S-100B values changed management decision towards a surgical intervention. The major finding of our study was the influence of serial S-100B measurement on actual management of the patient in 21% of cases with neurological complications.

Adolescent↗

Characterization of the potent combined endothelin(A/B)-antagonist PD 142893 on cerebral vessels.

A disturbed balance between endothelin (ET)-1 and nitric oxide (NO) seems to play a key role in the development of delayed cerebral vasospasm following subarachnoidal hemorrhage. Therefore, the effect of PD 142893 one of the first potent ET(A)- and ET(B)-receptor antagonists was characterized on the contraction and relaxation induced by ET-1 and bigET-1 on rat basilar artery (BA). Concentration-effect curves (CECs) were constructed by cumulative application of ET-1 or big ET-1 on BA ring segments with (E+) and without (E-) functionally intact endothelium. The effect of PD 142893 was determined by the modified pK(b) value and the shift between the CECs. PD 142893 inhibited the contraction by ET-1 and bigET-1. The pK(b)-values were for ET-1: 5.17 (E+) and 5.15 (E-) and for big ET-1: 5.34 (E+) and 5.57 (E-), respectively. A significant relaxation of pre-contracted segments by ET-1 or big ET-1 was neither observed in the presence nor in the absence of the receptor antagonist. The present data suggest a competitive inhibition of the ET(A)-receptor mediated contraction of cerebral arteries by PD 142893. The ET(B)-dependent relaxation of the cerebrovasculature is inhibited by PD 142893 at least in a comparable amount of contraction.

Animals↗

Post-operative hematoma after surgery for intracranial meningiomas: causes, avoidable risk factors and clinical outcome.

Intracranial meningiomas are mainly benign lesions amenable for surgical resection. However, removal of an intracranial meningioma carries a higher risk of post-operative hemorrhage compared to surgery for other intracranial neoplasms. Because avoidance of post-operative hematoma is of vital interest for neurosurgical patients, the aim of this retrospective study was to analyze risk factors of post-operative hematoma associated with meningioma surgery. Two hundred and ninety six patients with intracranial meningiomas, operated between June 1998 and June 2002, were included in this study. Patients who developed a space-occupying post-operative intracranial hemorrhage and were treated surgically were identified. Data of patients with and without hematoma were retrospectively analyzed to identify risk factors associated with post-operative hematoma. Variables analyzed included patients' age, invasion of venous sinus by the meningioma, tumor vascularization, arachnoidal infiltration, pre-operative prophylaxis of thromboembolic events, peri-operative coagulation abnormalities, residual tumor, location and histology of the tumor. Outcome of patients with post-operative hematoma was assessed according to the Glasgow Outcome Scale (GOS) at discharge and at three months. 21 patients (7.1 %) of 296 patients developed a post-operative intracranial hematoma requiring surgical evacuation. Age was significantly higher in the hematoma group 62.4 +/- 14.0 years compared to patients without post-operative hematoma 56.1 +/- 12.0 (p < 0.05; t-test). Patients older than 70 years had a six-fold increased risk to develop a post-operative hematoma (Chi2 test, 95% CI 1.949-13.224). Patients with post-operative hemorrhage had significant lower post-operative prothrombin time, fibrinogen and platelets immediately after surgery and lower platelets at day 1. None of the other parameters, including pre-operative routine coagulation values, differed significantly between patients with and without post-operative hemorrhage. Three patients with post-operative hematoma showed platelet dysfunction and three patients showed decreased FXIII activity. Of those patients with post-operative hemorrhage at three months follow up three patients (13%) succumbed from reasons not directly related to hemorrhage, one patient remained GOS 2 (4.3%), four patients (17.4%) were GOS 3 and 15 (65.4%) patients had favorable outcome (GOS 4 [one patient] and GOS5 [14 patients]). Meningioma surgery carries a higher risk for post-operative hematoma in the elderly. Thrombocytopenia and other hemostatic disorders were frequently associated with post-operative hemorrhage after meningioma surgery, while no surgical factors could be defined. Extending coagulation tests and specific replacement therapy may prevent hematoma formation and improve the patients outcome.

Adult↗

Functional magnetic resonance imaging-integrated neuronavigation: correlation between lesion-to-motor cortex distance and outcome.

OBJECTIVE: The integration of functional magnetic resonance imaging (fMRI) data into neuronavigation is a new concept for surgery adjacent to the motor cortex. However, the clinical value remains to be defined. In this study, we investigated the correlation between the lesion-to-fMRI activation distance and the occurrence of a new postoperative deficit. METHODS: fMRI-integrated "functional" neuronavigation was used for surgery around the motor strip in 54 patients. During standardized paradigms for hand, foot, and tongue movements, echo-planar imaging T2* blood oxygen level-dependent sequences were acquired and processed with BrainVoyager 2000 software (Brain Innovation, Maastricht, The Netherlands). Neuronavigation was performed with the VectorVision(2) system (BrainLAB, Heimstetten, Germany). For outcome analysis, patient age, histological findings, size of lesion, distance to the fMRI areas, preoperative and postoperative Karnofsky index, postoperative motor deficit, and type of resection were analyzed. RESULTS: In 45 patients, a gross total resection (>95%) was performed, and for 9 lesions (low-grade glioma, 4; glioblastoma, 5), a subtotal resection (80-95%) was achieved. The neurological outcome improved in 16 patients (29.6%), was unchanged in 29 patients (53.7%), and deteriorated in 9 patients (16.7%). Significant predictors of a new neurological deficit were a lesion-to-activation distance of less than 5 mm (P < 0.01) and incomplete resection (P < 0.05). CONCLUSION: fMRI-integrated neuronavigation is a useful concept to assess the risk of a new motor deficit after surgery. Our data suggest that a lesion-to-activation distance of less than 5 mm is associated with a higher risk of neurological deterioration. Within a 10-mm range, cortical stimulation should be performed. For a lesion-to-activation distance of more than 10 mm, a complete resection can be achieved safely. The visualization of fiber tracks is desirable to complete the representation of the motor system.

Adult↗

Functional impairment, disability, and quality of life outcome after decompressive hemicraniectomy in malignant middle cerebral artery infarction.

OBJECT: Whether decompressive hemicraniectomy is an appropriate treatment for space-occupying middle cerebral artery (MCA) infarction is still a controversial issue. Previous studies are in agreement on a reduction of the mortality rate, but the reported functional outcome was highly variable. The authors sought to determine functional impairment, disability, and health-related quality of life (QOL) outcome in long-term survivors who had undergone this procedure, and tried to identify factors related to functional outcome. METHODS: The study included 36 consecutive patients (mean age 58.8 +/- 12.7 years, 20 men and 16 women) who underwent decompressive hemicraniectomy for treatment of malignant MCA infarction (29 on the right and seven on the left side; mean time to surgery 37.8 +/- 20 hours). The survival rate was determined at 6 months: 13.7 +/- 6.7 months after the stroke, a cross-sectional personal investigation of survivors was performed to assess functional impairment, disability, and health-related QOL. Survival rates were 78% at 6 months and 64% at the time of the follow-up investigation; one patient was lost to follow up. Sixteen of 22 long-term survivors lived at home. The median Barthel Index (BI) was 45 (25th and 75th percentile 19 and 71) and the BI correlated negatively with patient age (r = -0.58, p = 0.005). Three patients reached a BI of at least 90. Older age, more severe neurological deficit on admission, and longer duration of intensive care treatment and mechanical ventilation were significantly associated with worse disability (BI < 50). The health-related QOL was considerably impaired in the subscales of mobility, household management, and body care. CONCLUSIONS: Decompressive hemicraniectomy improves survival in patients with malignant MCA infarction when compared with earlier reports of conservative treatment alone. Functional outcome and QOL remain markedly impaired, especially among elderly patients and in those with a severe neurological deficit at admission.

Adult↗

Postoperative nadroparin administration for prophylaxis of thromboembolic events is not associated with an increased risk of hemorrhage after spinal surgery.

AIM: To determine the risk of postoperative hemorrhage during a 3-year period of early postoperative administration of nadroparin (Fraxiparin) plus compression stockings in a large cohort of patients who underwent spinal surgery. METHODS: A total of 1,954 spinal procedures at different levels (503 cervical, 152 thoracic and 1,299 lumbar), performed between June 1999 and 2002 at the Department of Neurosurgery, Johann-Wolfgang-Goethe University Frankfurt, were included in this study. To prevent venous thromboembolic events (VTE), all patients were routinely treated subcutaneously with 0.3 ml of early (less than 24 h) postoperative nadroparin calcium (Fraxiparin) (2850 IU anti-Xa, Sanofi Winthrop Industrie, France) plus intra- and postoperative compression stockings until discharge. The occurrence of a postoperative hematoma (defined as a hematoma requiring surgical evacuation because of space occupation and/or neurological deterioration) and a deep venous thrombosis (DVT) were recorded in a database and analyzed retrospectively. RESULTS: 13 (0.7%) of the 1,954 spinal operations were complicated by major postoperative hemorrhages. In 5 of the 13 patients (38.5%) the hemorrhage occurred on the day of surgery before the administration of nadroparin. Thus, the hemorrhage rate of patients receiving nadroparin was 0.4% (8/1,949). Ten (77%) of the 13 patients with major postoperative hematoma showed a progressive neurological deficit, which resolved in 6 patients and resulted in a hematoma-related morbidity of 31% (4/13). Only 1 patient (0.05%) in this series developed a clinically evident DVT, and none of the patients suffered from pulmonary embolus during the hospital stay. CONCLUSION: Although retrospective, this is to date the largest study providing information about the hemorrhage rate associated with early postoperative anticoagulation following spinal surgery. The results confirm that early postoperative pharmacological thromboembolic prophylaxis using nadroparin in patients with spinal surgery is not associated with an increased risk of postoperative hemorrhage.

Adult↗

Elastin polymorphism haplotype and intracranial aneurysms are not associated in Central Europe.

BACKGROUND AND PURPOSE: The occurrence of intracranial aneurysms and of aneurysmal subarachnoid hemorrhage are influenced by genetic factors. Recent genomic studies in Japan have defined 3 chromosomal loci and 1 haplotype of elastin polymorphisms as important risk factors, both for affected sib pairs and sporadic patients. METHODS: We have genotyped 2 single nucleotide polymorphisms in the elastin gene and evaluated their allelic association with intracranial aneurysm in a Central European sample of 30 familial and 175 sporadic patients and 235 population controls. RESULTS: We found no allelic association between this elastin polymorphism haplotype and intracranial aneurysm. CONCLUSIONS: Our data probably reflect increased genetic heterogeneity of intracranial aneurysm in Europe compared with Japan.

Adult↗

Near-infrared indocyanine green video angiography: a new method for intraoperative assessment of vascular flow.

OBJECTIVE: We report our initial clinical experience with a new method for intraoperative blood flow assessment. The purposes of the study were to assess the use of indocyanine green (ICG) video angiography in neurovascular cases, to assess the handling and image quality, to compare the findings with postoperative angiographic results, and to evaluate the clinical value of the method in a preliminary feasibility study. METHODS: Fourteen patients with aneurysms (n = 12) or spinal (n = 1) or intracranial (n = 1) dural fistulae were included. Before and/or after aneurysm or dural fistula occlusion, ICG (25 mg) was injected intravenously. A near-infrared laser excitation light source (lambda = 780 nm) illuminated the operating field. The intravascular fluorescence of ICG (maximal lambda = 835 nm) was recorded by a nonintensified video camera, with optical filtering to block ambient and laser light for collection of only ICG-induced fluorescence. RESULTS: A total of 21 investigations were performed for 14 patients. For the 17 successful ICG video angiographic investigations, image quality and resolution were excellent, allowing intraoperative real-time assessment of the cerebral circulation. ICG angiographic results could be divided into arterial, capillary, and venous phases, comparable to those observed with digital subtraction angiography. In all cases, the postoperative angiographic results corresponded to the intraoperative ICG video angiographic findings. In three cases, the information provided by intraoperative ICG angiography significantly changed the surgical procedure. CONCLUSION: ICG video angiography is simple and provides real-time information on the patency of arterial and venous vessels of all relevant diameters, including small and perforating arteries (<0.5 mm), and the visible aneurysm sac. It may be a useful adjunct to improve the quality of neurovascular procedures and to document the intraoperative vascular flow.

Adolescent↗

Adaptive noninvasive assessment of intracranial pressure and cerebral autoregulation.

BACKGROUND AND PURPOSE: A mathematical model has previously been introduced to estimate noninvasively intracranial pressure (nICP). In the present multicenter study, we investigated the ability of model to adapt to the state of cerebral autoregulation (SCA). This modification was intended to improve the quality of nICP estimation and noninvasive assessment of pressure reactivity of the cerebrovascular system. METHODS: We studied 145 patients after severe head injuries or stroke. All patients had direct ICP, arterial blood pressure (ABP), and transcranial Doppler middle cerebral artery blood flow velocity (FV) monitored. The SCA was assessed by moving correlation (Mx index) of cerebral perfusion pressure (CPP=ABP-ICP) and cerebral blood flow velocity and correlation of ABP and ICP (PRx index). nICP was calculated from ABP and FV waveforms. When nICP was used instead of ICP, the SCA was continuously estimated, and the model was dynamically adapted to the SCA. RESULTS: High and moderate correlations between invasively (Mx, PRx) and noninvasively (nMx, nPRx) estimated autoregulation indexes were observed (Mx: R=0.90, P<0.001; PRx: R=0.62, P<0.001). Values of Mx and nMx indicated contradictory SCA in 4 of 167 evaluated recordings; values of PRx and nPRx were contradictory in 27 recordings. When the model was adapted to the SCA, the mean error of ICP estimation decreased significantly (P<0.005). CONCLUSIONS: Continuous adaptation of the model to SCA improves the accuracy of noninvasive estimation of ICP and ICP dynamics. The same model provides a noninvasive and continuous assessment of SCA.

Adolescent↗

Increased levels of plasma tissue factor pathway inhibitor in patients with glioblastoma and intracerebral metastases.

Tissue Factor Pathway Inhibitor (TFPI) prevents further participation of Tissue Factor (TF) in the coagulation process by forming a stable quaternary complex of TF-FVIIa-FXa-TFPI. Recently, plasma TFPI level were found to be elevated in patients with malignant disease outside the brain. Therefore the aim of this study was to investigate the TFPI plasma level in patients with primary brain tumors and intracerebral metastases. From May 2000 to December 2001 the total tissue factor pathway inhibitor antigen (TFPI) was preoperatively determined in blood samples of 225 patients with primary or metastatic brain tumors. Tumor histology classified as benign (WHO grade I and II) and malignant (WHO grade III and IV, intracerebral metastases) was correlated to plasma TFPI-levels. Plasma TFPI was significantly higher in patients with malignant tumors including intracerebral metastasis compared to benign tumors (80.1 +/- 34.31 versus 64.3 +/- 25.8 ng ml-1 [p < 0.01; t-test]). To exclude the influence of primary systemic neoplasms with secondary brain metastasis on plasma TFPI-level a subgroup of patients with primary brain tumors (meningioma, astrocytoma, oligodendroglioma and glioblastoma) was separated. In this group TFPI-level was also significantly elevated in patients with malignant (n = 66) (78.6 +/- 29.9) compared to benign brain tumors (n = 127) (64.3 +/- 25.8 ng ml-1 [p < 0.01; t-test]). To the authors' knowledge this is the first study describing the correlation of increased plasma TFPI and malignancy in patient with brain tumors. Further studies are needed to clarify the pathogenic mechanism and the clinical relevance of this phenomenon.

Adult↗

Increased incidence of thrombophilic abnormalities in patients with cranial dural arteriovenous fistulae.

Cranial dural arteriovenous fistulae (DAVF) may occur post-traumatic or sporadic. The physiopathologic mechanisms of sporadic DAVF are still unclear. A dural sinus thrombosis followed by an increase in venous pressure and/or an increased procoagulatory activity of the coagulation system are associated at least with some DAVF. The objective of this study was to investigate the coagulation profile in patients with DAVF. Thus the association of thrombophilic abnormalities, sinus thrombosis and DAVF should be analyzed. A total of 15 patients with cranial DAVF were included in this study. Blood samples were analyzed for 20210A mutation of the prothrombin gene, resistance to activated protein C and factor V Leiden mutation. Fibrinogen (Fib), Textarin time (TT), antithrombin (AT), protein C and protein S activity, von Willebrand factor antigen (vWF:Ag), Ristocetin cofactor activity (vWF:RCo), D-Dimer (DD) and coagulation factor VIII-activity (F VIII) were determined in all patients. Blood was screened for the occurrence of lupus antiphospholipid antibodies and cardiolipin antibodies. Thrombophilic risk factors were found in 5 (33%) of the 15 patients with cranial DAVF. Four patients had a heterozygote 20210A mutation of the prothrombin gene and one patient had a heterozygote FV Leiden mutation. Sinus thrombosis was detected in two patients with grade 2b DAVF and was associated with a 20210A mutation of the prothrombin gene in both patients. Additionally, one patient had deficient protein C activity and screening for cardiolipin antibodies was positive in three patients. In the current series the frequency of prothrombin Gene 20210A mutation was higher in patients with DAVF compared to the general population, whereas the incidence of Factor V Leiden mutation was not. Therefore in patients with cranial DAVF thrombophilic abnormalities should be considered in the post-operative/post-interventional management.

Adult↗

Clinical evaluation of intraparenchymal Spiegelberg pressure sensor.

OBJECTIVE: The Spiegelberg 3-PN intraparenchymal pressure sensor was clinically evaluated. DESCRIPTION OF INSTRUMENTATION: The Spiegelberg intraparenchymal pressure sensor is a low-cost device that uniquely performs regular automatic zeroing in situ throughout the measurement period. OPERATIVE TECHNIQUE: The Spiegelberg sensor was inserted in 87 patients who required intracranial pressure monitoring as part of their routine management. Complications were assessed by postoperative computed tomographic scanning and clinical investigation. The automated zeroing procedure was assessed after implantation of the sensor and during long-term measurement. In five patients, the "gold standard' of intraventricular pressure was measured simultaneously and compared with the intraparenchymal or subdural Spiegelberg 3-PN pressure. EXPERIENCE AND RESULTS: No complications associated with the Spiegelberg sensor were observed. The duration of monitoring ranged from 3 to 28 days (mean, 10 d). In 3 patients, technical problems occurred, and in 84 patients, the pressure measurement was successful, including the automatic zeroing procedures performed by the monitor after insertion and hourly thereafter. The absolute difference between the Spiegelberg reading and the intraventricular pressure was less than +/-3 mm Hg in 99.6% and less than +/-2 mm Hg in 91.3% of readings. An Altman-Bland bias plot revealed good agreement between the two methods, with an average bias of 0.5 mm Hg, but revealed a significant trend toward 10% lower Spiegelberg readings with increasing intracranial pressure of >25 mm Hg. There was no difference between intraparenchymal and subdural locations. CONCLUSION: The Spiegelberg 3-PN sensor was reliable and simple to use. It can be recommended for routine intraparenchymal and subdural pressure measurement at a considerably lower price compared with other tip transducers and has the unique advantage of automated zeroing in vivo.

Brain Neoplasms↗