Rüdiger Gerlach

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

OBJECTIVEWe 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. METHODSFourteen 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 (&lgr; = 780 nm) illuminated the operating field. The intravascular fluorescence of ICG (maximal &lgr; = 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. RESULTSA 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. CONCLUSIONICG 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.

Increased Risk for Postoperative Hemorrhage After Intracranial Surgery in Patients With Decreased Factor XIII Activity: Implications of a Prospective Study

Background and Purpose— The functional integrity of the hemostatic system is a prerequisite for the safe performance of neurosurgical procedures. To monitor the individual coagulation capacity of each patient, standard tests are effective to detect deficiencies involving the generation of fibrin. However, fibrin clot strength depends primarily on coagulation factor XIII, which cross-links fibrin monomers and enhances clot resistance against fibrinolysis. Therefore, factor XIII is functionally involved in both the hemostatic and fibrinolytic systems. The objective of this prospective study was to determine the incidence and clinical relevance of perioperative decreased factor XIII with respect to standard coagulation parameters and the occurrence of postoperative hematoma. Methods— In 876 patients, 910 neurosurgical procedures were performed. Prothrombin time (PT), partial thromboplastin time (PTT), platelet count, fibrinogen, and factor XIII were tested in each patient preoperatively and postoperatively. Results— Postoperative intracranial hematoma (defined as requiring surgical evacuation) occurred after 39 (4.3%) of 910 surgical procedures. Patients with postoperative hematoma had significantly lower factor XIII and fibrinogen levels preoperatively and postoperatively than patients without hematoma. In patients with postoperative hematoma, PT and platelets differed significantly only postoperatively, whereas PTT was different neither preoperatively nor postoperatively. Of the 39 patients with a postoperative hematoma, 13 (33.3%) had a postoperative factor XIII <60% compared with 61 (7%) of 867 patients without hematoma (P <0.01, Fisher’s exact test). The relative risk of developing a postoperative hematoma is therefore increased 6.4-fold in patients with postoperative factor XIII <60%. The risk is increased 12-fold in patients who additionally have postoperative decreased fibrinogen levels (<1.5 g/L) and 9-fold in patients with platelet count <150×109/L and factor XIII <60%. Conclusions— This is the first prospective study that demonstrates the association of decreased perioperative factor XIII with an increased risk of postoperative hematoma in neurosurgical patients. The risk is further increased in those patients with low factor XIII and additional abnormalities of fibrinogen, PT, platelets, and PTT. Factor XIII testing and specific replacement, as accepted for other clotting factors, may reduce the risk of postoperative hematoma.

Risk of shunt-dependent hydrocephalus after occlusion of ruptured intracranial aneurysms by surgical clipping or endovascular coiling: a single-institution series and meta-analysis.

OBJECTIVETo compare the risk of shunt-dependent hydrocephalus after treatment of ruptured intracranial aneurysms by clipping versus coiling. METHODSWe analyzed 596 patients prospectively added to our database from July of 1999 to November of 2005 concerning the risk of shunt dependency after clipping versus coiling. Factors analyzed included age; sex; Hunt and Hess grade; Fisher grade; acute hydrocephalus; intraventricular hemorrhage; angiographic vasospasm; and number, size, and location of aneurysms. In addition, a meta-analysis of available data from the literature was performed identifying four studies with quantitative data on the frequency of clip, coil, and shunt dependency. RESULTSThe institutional series revealed Hunt and Hess grade, Fisher grade, acute hydrocephalus, intraventricular hemorrhage, and angiographic vasospasm as significant (P < 0.05) risk factors for shunt dependency after a univariate analysis. In a multivariate logistic regression analysis, we isolated intraventricular hemorrhage, acute hydrocephalus, and angiographic vasospasm as independent, significant risk factors for shunt dependency. The meta-analysis, including the current data, revealed a significantly higher risk for shunt dependency after coiling than after clipping (P = 0.01). CONCLUSIONClipping of a ruptured aneurysm may be associated with a lower risk for developing shunt dependency, possibly by clot removal. This might influence long-term outcome and surgical decision making.

Factor XIII deficiency and postoperative hemorrhage after neurosurgical procedures

BACKGROUND Factor XIII is of physiological importance for hemostasis, especially in patients undergoing surgery. It catalyzes the enzymatic cross-linking of fibrin monomers into stable polymers and protects polymers from plasmatic and nonspecific degradation. Postoperative hemorrhage in patients with congenital and acquired Factor XIII deficiencies has been described in various surgical fields. However, there are no data about the incidence and clinical relevance of decreased Factor XIII after neurosurgical procedures. The objective of our study was to investigate the association between Factor XIII deficiency and postoperative hemorrhage after intracranial surgery. METHODS A total of 1264 patients who underwent intracranial operations were reviewed retrospectively. Standard coagulation parameters were monitored during the perioperative course in all patients. Factor XIII testing was performed postoperatively in 34 patients in whom coagulopathies were suspected despite normal platelets, fibrinogen, prothrombin, and partial thromboplastin time. Data were analyzed to evaluate the association of Factor XIII deficiency and major postoperative hemorrhage. RESULTS In this series of 1264 patients, a total of 20 patients (1. 6%) suffered from a major postoperative hemorrhage. Of the 34 patients with suspected coagulopathies and postoperative Factor XIII testing, 11 had a major postoperative hemorrhage. Normal levels of Factor XIII, defined as more than 60%, were found in 26 of the 34 patients. Factor XIII deficiency, defined as less than 60%, was found in eight patients. All patients with Factor XIII deficiency (n = 8) had a major postoperative hemorrhage. Of the remaining 26 patients with normal Factor XIII levels only three had a postoperative hemorrhage (p < 0.00001, Fishers exact test). CONCLUSIONS Decreased Factor XIII activity may be associated with an increased risk of postoperative hemorrhage after intracranial surgery.

Subarachnoid hemorrhage and intracerebral hematoma: incidence, prognostic factors, and outcome.

OBJECTIVE To analyze the incidence and impact of an intracerebral hematoma (ICH) on treatment and outcome in patients with aneurysmal subarachnoid hemorrhage. METHODS Data of 585 consecutive patients with subarachnoid hemorrhage from June 1999 to December 2005 were prospectively entered in a database. ICH was diagnosed and size was measured by computed tomographic scan before aneurysm occlusion. Fifty patients (8.5%) presented with an ICH larger than 50 cm3. The treatment decision (coil, clip, or hematoma evacuation) was based on an interdisciplinary approach. Patients were stratified into good (Hunt and Hess Grades I–III) versus poor (Hunt and Hess Grades IV and V) grade, and outcome was assessed according to the modified Rankin Scale at 6 months. RESULTS Overall, 358 patients presented in good grade, with 4 of them having ICH (1.1%); and 227 patients presented in poor grade, with 46 of them having ICH (20.3%, P < 0.01). In good-grade patients with an ICH (n = 4), a favorable outcome (modified Rankin Scale score of 0–2) was achieved in 1 patient (25%), and in 246 patients (75%) without an ICH (P = 0.053; odds ratio, 0.11). A favorable outcome was achieved in 5 poor-grade patients (12.8%) with an ICH and in 40 patients (23.7%) without an ICH (P = 0.19; odds ratio, 0.47). Time to treatment was significantly shorter in patients with an ICH than without an ICH (median, 7 versus 26 h; P < 0.001) and shortest in patients with favorable outcome (3.5 hours; P < 0.01). CONCLUSION The current data confirm that the presence of an ICH is a predictor of unfavorable outcome. However, despite large ICHs, a significant number of patients have a good outcome. To achieve a favorable outcome, ultra-early treatment with hematoma evacuation and aneurysm obliteration seems to be mandatory.

Treatment related morbidity of unruptured intracranial aneurysms: results of a prospective single centre series with an interdisciplinary approach over a 6 year period (1999–2005)

Objectives: To review the angiographic and clinical outcome of patients with unruptured intracranial aneurysm(s) (UIA) with regard to complications and successful obliteration by surgical clipping or endovascular coiling. Methods: Data were derived from a prospective database of intracranial aneurysms from June 1999 to May 2005. All patients were followed-up for 6 months using the modified Rankin Scale (mRS). Favourable outcome was classified as mRS 0–2. From a total of 691 patients included in the database, 173 harboured 206 UIA of whom 118 patients (133 UIA) were treated. Results: Primary treatment assignment was surgical repair in 91 UIA and endovascular treatment in 42. In 3 UIA (7.1%), endovascular treatment was not feasible and had to be abandoned. Definite treatment was surgery in 94 UIA (81 patients) and endovascular obliteration in 39 UIA (37 patients). There were no deaths related to any treatment. Immediately after treatment, 6.4% of the surgical and 7.7% of the endovascular patients showed new neurological deficits, mainly related to cerebral ischaemia. After 6 months, 3 (2.3%) patients had a treatment related unfavourable outcome, defined as mRS >2, 2 patients after surgical and 1 patient after endovascular aneurysm repair (not statistically different, p = 0.3; Fisher’s exact test). This led to an overall satisfactory outcome in 97.9% of surgically and 97.4% of endovasculary treated UIA. After surgical clipping, complete occlusion of the aneurysm was achieved in 88 (93.6%) and near complete (small residual neck) in 4 (4.3%) of 94 UIA. Two small posterior communicating artery aneurysms with a fetal type posterior communicating artery were wrapped. After endovascular treatment, obliteration was complete in 26 (66.7%). Small residual neck was seen in 13 (33.3%), but none of the UIA showed residual aneurysm filling. Five patients in the endovascular group (13.9%) underwent repeated endovascular treatment after aneurysm recanalisation. Conclusions: If patients are carefully selected and individually assigned to their optimum treatment modality, UIA can be obliterated by surgery or endovascular treatment in the majority of patients, with a low percentage of unfavourable outcomes. In this series, the outcome was not dependent on treatment. However, the rate of recanalisation of UIA is higher after endovascular obliteration. After diagnosis of an UIA, an individual interdisciplinary decision is essential for each patient to provide the optimum management.

Inhibition of tissue factor/protease-activated receptor-2 signaling limits proliferation, migration and invasion of malignant glioma cells

Tissue factor (TF) is upregulated in several malignant diseases, including gliomas. Here, we demonstrate pronounced differences in the expression of TF and its interactors factor VII and protease-activated receptor 2 (PAR-2) in nine human glioma cell lines (U87, U251, U343, U373, MZ-18, MZ-54, MZ-256, MZ-304, Hs 683) as detected by RT-PCR and Western blot analysis. Inhibition of TF signaling by a neutralizing monoclonal antibody (mAb TF9-10H10) led to significantly reduced proliferation in high-grade astroglial (MZ-18 and MZ-304) and oligodendroglial (Hs 683) cell lines abundantly expressing TF, but not in U373 cells expressing low amounts of TF. Scratch migration assays and Boyden chamber assays indicated that mAb TF9-10H10 and lentiviral knockdown of TF significantly reduced cell migration and invasion of MZ-18, MZ-304 and Hs 683 cells, both under normoxic and hypoxic conditions. Of note, all three cell lines displayed increased cell migration and invasion under hypoxic conditions (1% O(2)), which was associated with enhanced expression of TF and increased phosphorylation of p44/42 mitogen-activated protein kinase (ERK1/2). Silencing of TF blocked activation of the ERK pathway, induction of TF expression and the potentiating effect of hypoxia on cell migration and invasion. RNA interference against PAR-2 abrogated the autocrine effects of TF on cell proliferation, migration and invasion, indicating that TF signals via PAR-2 in glioma cells. Our results suggest an important role for the TF/FVIIa/PAR-2/ERK axis in tumor growth and invasion of glioma and suggest that TF may be a suitable target for the development of novel therapies against high-grade glioma.

The influence of preoperative anticoagulation on outcome and quality of life after surgical treatment of chronic subdural hematoma

The main aim of this study was to investigate the influence of perioperative anticoagulation on the clinical course and outcome of 144 patients who underwent surgery for chronic subdural hematoma (CSDH). The outcome was categorized according to the modified Rankin Scale (mRS), Barthel Index and postoperative quality of life (QoL) scale. There was a significant correlation between preoperative aspirin medication and reoperation (Mann-Whitney U-test, p<0.05). Moreover, dosage and duration of postoperative low-molecular-weight heparin (LMWH) administration were associated with a higher risk of reoperation (Mann-Whitney U-test, p<0.01) and a worse outcome on the mRS (Mann-Whitney U-test, p<0.05). Intraoperative treatment with prothrombin complex concentrate led to a poor outcome on the mRS (Craddock-Flood test, p<0.05). Reoperation is the strongest predictive factor of a poor QoL after surgical treatment of CSDH. Both preoperative and postoperative anticoagulation treatment may affect reoperation rate and, thus, postoperative QoL.

Cold storage of citrated whole blood induces drastic time- dependent losses in factor VIII and von willebrand factor : potential for misdiagnosis of haemophilia and von willebrand disease

This study investigates the effect of pre-analytic storage conditions on the laboratory evaluation of von Willebrand disease (VWD) and haemophilia. Samples from healthy controls and patients with VWD were stored as whole blood and as separated plasma, both at room temperature and on crushed ice, for two different time periods (3 or 6 h). In samples from healthy individuals (n = 10) and in patients with suspected type 1 VWD (n = 10), storage of whole blood on ice caused a drastic time-dependent decrease in von Willebrand factor (VWF):ristocetin cofactor activity, in VWF:antigen activity and factor VIII activity (mean ± SD) to 35 ± 18, 55 ± 23 and 53 ± 15% of baseline levels after 6 h storage, respectively. Patients with type 2 VWD and non-detectable VWF:ristocetin cofactor activity did not demonstrate such drastic cold-induced losses in VWF and factor VIII levels. Storage of plasma caused only minor changes in VWF levels. The cold-induced loss in VWF might thus depend on the presence of platelets and of high molecular weight VWF. Chilling of platelets induces a clustering of the glycoprotein Ib subunit. We therefore hypothesize that cold-induced loss in VWF might be due to a cold-promoted binding of VWF to glycoprotein VWF receptor Ib alpha. These results suggest a serious potential for misdiagnosis of haemophilia or VWD due to inappropriate pre-analytical handling of blood.

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

Abstract 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 μg/l, standard deviation 2.61 μg/l, range 0.31–9.66 μg/l). Twenty-eight of these patients (85%) showed S-100B increases >0.5 μg/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.