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Surgical management of sphenoorbital meningiomas ranges among the most complex of intracranial tumors. We report on our experience of surgical technique, outcome, and tumor recurrence in sphenoorbital meningiomas.Between 2003 and 2013, surgical resections for sphenoorbital meningioma were performed in 18 patients (aged 49·6±9·8 years, only women), with two patients operated anew due to tumor recurrence.Main symptom was proptosis (83·3%), followed by diminished visual acuity (38·9%), and dizziness (11·1%). In all patients the lateral orbital wall was resected, whereas the orbital roof and the zygoma were removed according to the extent of their tumorous infiltration. Unroofing of the optic canal was performed in 10 cases (55·6%) and unroofing of the optic foramen in two (11·1%). For reconstruction split calvarian bone and titanium mesh were used in six (33·3%) and seven patients (38·9%), respectively; in one patient both techniques were applied. In five patients (27·8%), no reconstruction was necessary. Complete tumor resection (Simpson grade 1 and 2) was achieved in 14 cases (77·7%). Postoperatively, proptosis improved in all patients. Median follow-up was 39·5±33·3 months (range 1-105) in 16 patients; 2 patients were lost to follow-up. No tumor recurrence was noted in five (27·8%) patients, whereas in nine (50%) patients tumor remnants proved stable over time. Two (11·1%) patients experienced progression of residual tumor, resulting in reoperation after 27 and 109 months, respectively.Despite their delicate anatomical relations, surgery of sphenoorbital meningiomas is safe when combining modern techniques.

Monomethylated L-arginine (L-NMMA) has been proven to be a strong inhibitor of nitric oxide synthase (NOS) and has been used as an exogenous tool in experimental evaluation of cerebrovascular reactivity leading to vasoconstriction. However, L-NMMA is also produced endogenously and belongs, as does asymmetric dimethylated L-arginine (ADMA), to a family of endogenous NOS inhibitors. While ADMA has been associated with cerebral vasospasm (CVS) but not with delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH), no results are available concerning endogenous L-NMMA and SAH. We therefore decided to investigate the role of endogenous L-NMMA with regard to CVS and DCI after SAH.Retrospective analysis of cerebro-spinal fluid (CSF) and serum of SAH patients and controls was performed by high performance liquid chromatography (HPLC) and chemiluminescence. Delayed CVS was detected by arteriography and cerebral ischemic events by follow-up computed tomography (CT) scans.Cerebro-spinal fluid and serum L-NMMA concentrations neither correlated with CVS nor with NO2(-) levels (P0·05, in both cases). However, endogenous L-NMMA concentrations correlated with cerebral ischemic events and with the size of infarction (cc = 0·459, P = 0·032, 95% CI: 0·046-0·738).This study shows that endogenous L-NMMA is associated with the occurrence of cerebral ischemic events, but seems not to be involved in CVS after SAH. Therefore, endogenous L-NMMA after SAH features intriguing differences compared with previous reports on exogenous L-NMMA and ADMA after SAH.

Recurrence rate, time to progression, and facial nerve function were analysed by comparing patients with complete and near total tumor removal after suboccipital craniotomy for vestibular schwannoma surgery.From 1996 to 2004, 118 patients with vestibular schwannoma were operated with an interdisciplinary approach. Fifty patients fulfilled the inclusion criteria and were included in the study. Progression was defined as an increase of ⩾2 mm in the largest diameter in the magnetic resonance imaging. Preoperative tumor size, facial nerve function estimated using the House-Brackmann score (HBS), time to progression, and recurrence rate were analysed and related to the extent of resection.In 28 cases (group I), a capsular remnant was left. In 22 cases (group II), tumor removal was complete. In group I, nine patients (32·1%) showed progression. In group II, two patients (9·1%) developed a recurrent tumor, no significance (P = 0·085). In groups I and II, 53·6 and 59·6% had a good function of the facial nerve (HBS I+II), 28·6% in group I and 13·5% in group II had a moderate disturbance (HBS III+IV), and 17·9% in group I and 27·7% in group II had a poor function (HBS V+VI). There was no significant difference between median preoperative tumor size and facial nerve function within patients with HBS III and IV.Complete tumor removal may be associated with a risk of functional loss, whereas near total tumor removal may be associated with a higher risk of progression.

Acute subdural hematomas (aSDHs) are found in up to one-third of patients with severe traumatic brain injury and are associated with an unfavorable outcome in the majority of cases. Mortality ranges between 40 and 60%, but was reported to be even higher in patients undergoing oral anticoagulation therapy (OAT) at the time of injury. The objective of this study is to specifically report on the peri-operative management and outcome of patients with aSDH and pre-injury OAT.From June 2002 to June 2006, all patients with OAT who underwent surgical treatment of aSDH were retrospectively analysed. Results of pre-operative blood tests, the peri-operative and surgical management and the clinical courses were assessed. Patient outcome is reported according to the Glasgow Outcome Scale (GOS) at 6 months.Eleven (10.3%) out of 107 patients with aSDH were on OAT. Patients with OAT were significantly older than patients without OAT (72.4 +/- 9.3 versus 59.9 +/- 17.5 years; p0.05, Mann-Whitney U-test). Intensity of head trauma was moderate in four and severe in seven patients with a median pre-operative Glasgow Coma Scale (GCS) of 8. Median pre-treatment prothrombin time and international normalized ratio were 23% (range: 10-65%) and 3.3 (range: 1.5-10.6), respectively. Replacement therapy consisted of administration of prothrombin complex concentrates, vitamin K and FFP (fresh frozen plasma). In four patients, antithrombin was additionally given to prevent disseminated intravascular coagulation. Surgical treatment consisted of craniotomy (n=10) or craniectomy (n=1) and hematoma evacuation with intracranial pressure probe placement. Low molecular weight heparin was administered as pharmacological prophylaxis of thrombembolic events in an increasing dose post-operatively. At 6 months, six out of 11 patients survived with a median GOS of 4. All-cause mortality was 45.5%. A pre-operative GCS ofor = 8 was not associated with an increased risk of mortality (p0.5, Fisher's exact test). No relevant rebleedings or thrombembolic complications were observed. The mortality rate of patients who did not undergo OAT was 50%.A large number of patients with aSDH are on pre-injury OAT. Specific replacement therapy facilitates successful clot evacuation without bleeding complications. The overall outcome of these patients does not seem to differ from historical cohorts with aSDH without OAT, but a large prospective multicenter study is warranted to answer that question.

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.

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.

Cellular homeostatic adaptation to cerebral ischemia is complex and contains changes in receptor mediated gene expression and signaling pathways. The proteins of the immediate early genes c-Fos and c-Jun are thought to be involved in coupling neuronal excitation to target gene expression, due to formation of heterodimers and binding to the AP1 promotor region. We used an in vitro model to compare ischemia induced c-Fos and c-Jun expression in rat neuronal cell cultures and nerve growth factor (NGF) differentiated PC 12 cells. Since activation of glutamate receptors is known to mediate ischemic injury we determined the effect of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist MK 801 on c-Fos and c-Jun expression in both cell culture systems during ischemia. Neuron rich cultures and NGF differentiated PC 12 cells were exposed to sublethal in vitro ischemia using an hypoxic chamber flushed with argon/CO2 (95 %/5%). C-Fos and c-Jun mRNA expression was analyzed by competitive reverse transcription-polymerase chain reaction using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as internal standard. One hour of in vitro ischemia significantly increased c-Fos and c-Jun mRNA levels in both cell culture systems. In neuron rich cultures a 10-fold (c-Fos) and 7-fold (c-Jun) mRNA increase was observed. The mRNA rise was less pronounced in PC 12 cells (5.5-fold and 2-fold) for c-Fos and c-Jun, respectively. The addition of MK 801 significantly reduced the expression of c-Fos and c-Jun mRNA in neuronal cultures, whereas no effect was detectable in PC 12 cells. Since MK 801 failed to reduce the c-Fos and c-Jun expression in NGF differentiated PC 12 cells different signaling pathways may initiate c-Fos and c-Jun expression in both cell culture systems.

The object of the study was to evaluate brain tissue oxygenation (p(ti)O2) for intra-operative monitoring of critical ischemic events during early cerebral aneurysm surgery of the anterior circulation supplementary to somatosensory evoked potentials (SEPs). P(ti)O2 was continuously evaluated during surgery for an intracranial aneurysm in 28 patients. Standard cortical SEP monitoring was simultaneously performed. The two monitoring methods were compared by evaluating their respective responses to intra-operative events (particularly temporary vessel occlusion), clinical and neuroradiological outcome. P(ti)O2 and SEPs were reliably used for monitoring in 16 patients. Seven patients were excluded due to too high or too low p(ti)O2 readings or initial absence of SEPs (six patients). Of 64 intra-operative events 19 events (eight patients) were associated with a significant decrease in p(ti)O2 (below 10 mmHg), 22 events (13 patients) were associated with a significant change in SEP amplitude (< 50% decrease related to baseline). Temporary vessel occlusion (six SEP andp(ti)O2 changes each in eightpatients) and surgical dissection were most likely to be followed by significant changes in a monitoring method. Intra-operative p(ti)O2 was found to be a safe, rapid method for documenting ischemic events. P(ti)O2 was found to supplement SEP monitoring. The use of p(ti)O2 measurement as a routine monitoring method in aneurysm surgery is limited by its focal spatial resolution. Nevertheless, it might be helpful as an adjunct in situations when SEPs are absent at baseline, in aneurysms when parent vessel anatomy is complex or if temporary vessel occlusion is planned.

To correlate serial measurements of serum S100B and neuron-specific enolase (NSE) with histopathological changes of the spinal cord and to assess their prognostic significance in a set-up of experimental spinal cord compression.The thoracic cords of 22 rabbits were increasingly compressed and decompressed once paresis had developed. After decompression, outcome was rated as favorable or unfavorable. Following sacrifice of the animals, the cord was analyzed microscopically and morphometrically. Serum S100B and NSE were measured daily, and levels were correlated with initial degree of paresis, outcome after decompression, and histopathological changes of the cord.Regardless of the initial degree of paresis, animals with favorable outcome had significantly higher cell counts than animals with unfavorable outcome. The time course of S100B values following decompression was correlated with outcome. Animals with favorable outcome had either always normal levels or levels that were initially increased but normalized within 2 days. The values of animals with unfavorable outcome were elevated throughout (P0.0001). No correlation was found between NSE levels and outcome.The initial degree of paresis is not a prognostic factor to predict outcome. Despite timely decompression, pronounced structural lesions of the cord may develop, resulting in an unfavorable outcome. In cases with favorable outcome, sufficient tissue is preserved to maintain function regardless of the initial extent of paresis. This different reaction of the cord may be followed indirectly with serial measurements of S100B serum levels. Thus, S100B is a reliable biochemical marker allowing for prediction of outcome. NSE does not have this prognostic significance.

To assess the potential prognostic relevance of serial serum measurements of S100B and NSE in patients with spinal intradural lesions.Forty-four patients with spinal intradural lesions were included in this prospective study. S100b and NSE serum levels were measured on admission and daily after operative treatment. The pre-operative values of both markers were correlated with degree of paresis and duration of symptoms, the post-operative levels with functional outcome. Outcome was dichotomized into favorable and unfavorable. Neurological recovery with retrieval or preservation of gait function was regarded as favorable, whereas non-improvement without restoration of gait function was considered as unfavorable.No correlation was found between S100b or NSE serum levels and degree of paresis or duration of symptoms before surgery. The post-operative time course of S100b and NSE serum concentrations was not correlated with functional outcome.Serial serum measurements of neither S100b nor NSE allow for an individual prediction of neurological outcome in patients with spinal intradural lesions. Despite their limited validity for the individual patient, 'classical' predictors as degree and duration of paresis before therapy are still the most important prognostic parameters in these patients with chronic spinal lesions.

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.

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.

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.

Cerebral vasospasm and delayed ischaemic neurological deficits (DIND) remain the leading cause of death and major disability after aneurysmal subarachnoid haemorrhage (SAH). Experimental and clinico-radiological studies have clearly demonstrated the relationship between the volume of blood accumulated in the basal cisterns after aneurysm rupture and SAH, and the incidence and severity of vasospasm and DIND. Recently intrathecal thrombolysis using recombinant tissue plasminogen activator (rTPA) has been introduced as an innovative pharmacological method for the removal of subarachnoid blood accumulations, in order to prevent the development of cerebral vasospasm. In this survey a number of experimental and clinical studies which have been performed recently by the neurovascular research group of the author on the possible use of rTPA during SAH will be presented and discussed in the light of other experimental investigations as well as other recently performed pilot studies on the use of rTPA. [Neu...